1 00:00:05,680 --> 00:00:08,640 >>WELCOME TO 2 00:00:08,640 --> 00:00:13,080 DAY TWO OF OUR VIRTUAL WORKSHOP. 3 00:00:13,080 --> 00:00:19,200 CURRENT AND FUTURE NEEDS IN THE 4 00:00:19,200 --> 00:00:22,560 ERA OF HIGHLY EFFECTIVE 5 00:00:22,560 --> 00:00:24,440 MODULATOR THERAPIES FOR CYSTIC 6 00:00:24,440 --> 00:00:27,840 FIBROSIS AND I'M AT NHLBI AND 7 00:00:27,840 --> 00:00:29,360 OVERSEE THE PORTFOLIO IN CYSTIC 8 00:00:29,360 --> 00:00:30,960 FIBROSIS AND OTHER DISORDERS AND 9 00:00:30,960 --> 00:00:33,080 GENE THERAPY TECHNOLOGIES. 10 00:00:33,080 --> 00:00:36,120 IT IS ALSO MY PLEASURE TO 11 00:00:36,120 --> 00:00:38,280 WELCOME TO YOU DAY TWO AND 12 00:00:38,280 --> 00:00:40,480 PROVIDE YOU WITH SOME OF OUR 13 00:00:40,480 --> 00:00:41,680 MEETING LOGISTICS AS WELL AS THE 14 00:00:41,680 --> 00:00:48,120 CHARGE FOR THE WORKSHOP AND 15 00:00:48,120 --> 00:00:53,400 RECAP OF YESTERDAY'S MEETING. 16 00:00:53,400 --> 00:00:54,960 SO YESTERDAY MORNING OUR 17 00:00:54,960 --> 00:00:56,600 DIVISION DIRECTOR DR. JIM KILEY 18 00:00:56,600 --> 00:00:59,680 SHARED THE CONCEPT CAME OUT OF A 19 00:00:59,680 --> 00:01:02,000 TRANS-NIH WORKING GROUP WITH 20 00:01:02,000 --> 00:01:05,440 REPRESENTATIVES FROM NIDDK AND 21 00:01:05,440 --> 00:01:07,800 THE CYSTIC FIBROSIS FOUNDATION 22 00:01:07,800 --> 00:01:10,120 TOGETHER WITH INPUT FROM THE 23 00:01:10,120 --> 00:01:11,160 RESEARCH COMMUNITY WE REALIZED 24 00:01:11,160 --> 00:01:15,760 THERE WAS A CHANGE AFTER THE 25 00:01:15,760 --> 00:01:18,560 APPROVAL OF TRI KAPTA AND BRING 26 00:01:18,560 --> 00:01:20,000 EXPERTS IN THE FIELD TO ADDRESS 27 00:01:20,000 --> 00:01:21,640 CRITICAL QUESTIONS AND INFORM 28 00:01:21,640 --> 00:01:23,720 FUTURE RESEARCH NEEDS IN THE ERA 29 00:01:23,720 --> 00:01:26,160 OF HIGHLY EFFECTIVE MODULATED 30 00:01:26,160 --> 00:01:27,200 THERAPIES FOR THE TREATMENT. 31 00:01:27,200 --> 00:01:28,800 TO ORGANIZE THE WORKSHOP WE 32 00:01:28,800 --> 00:01:31,040 BROUGHT TOGETHER A PANEL OF 33 00:01:31,040 --> 00:01:32,880 EXPERTS ON THE PLANNING 34 00:01:32,880 --> 00:01:35,560 COMMITTEE WITH A BREADTH OF 35 00:01:35,560 --> 00:01:36,800 EXPERTS FROM CLINICAL BACKGROUND 36 00:01:36,800 --> 00:01:38,960 TO BEGIN TO ADDRESS THESE 37 00:01:38,960 --> 00:01:39,240 QUESTIONS. 38 00:01:39,240 --> 00:01:41,120 THE GOAL OF THE WORKSHOP IS TO 39 00:01:41,120 --> 00:01:43,480 HIGHLIGHT THE CHALLENGES AND 40 00:01:43,480 --> 00:01:44,880 OPPORTUNITIES FOR RESEARCH IN 41 00:01:44,880 --> 00:01:46,520 THE CONTEXT OF TREATMENT OPTIONS 42 00:01:46,520 --> 00:01:48,360 FOR ALL PEOPLE WITH CF INCLUDING 43 00:01:48,360 --> 00:01:50,600 THOSE NOT ELIGIBLE FOR CURRENT 44 00:01:50,600 --> 00:01:51,840 MODULATED THERAPIES. 45 00:01:51,840 --> 00:01:54,000 YESTERDAY AND TODAY WE ALSO HAVE 46 00:01:54,000 --> 00:01:55,560 A CHANCE TO HEAR PERSPECTIVES 47 00:01:55,560 --> 00:01:57,240 FROM INDIVIDUALS WITH CF AND 48 00:01:57,240 --> 00:02:00,360 THEIR CAREGIVERS. 49 00:02:00,360 --> 00:02:02,880 IT'S CLEAR FROM THE SHEER NUMBER 50 00:02:02,880 --> 00:02:04,400 OF REGISTRANTS THERE'S A HIGH 51 00:02:04,400 --> 00:02:06,720 PRIORITY FOR THIS AREA FOR THE 52 00:02:06,720 --> 00:02:06,920 FIELD. 53 00:02:06,920 --> 00:02:08,400 WE'RE LOOKING TO HEAR FROM ALL 54 00:02:08,400 --> 00:02:11,680 OF YOU ABOUT YOUR EXPERIENCES, 55 00:02:11,680 --> 00:02:13,080 INSIGHTS AND KNOWLEDGE TO HELP 56 00:02:13,080 --> 00:02:15,200 MOVE THE FIELD FORWARD IN THE 57 00:02:15,200 --> 00:02:16,280 NEXT 5 TO 10 YEARS. 58 00:02:16,280 --> 00:02:18,040 I HOPE THIS GROUP WILL ALSO FORM 59 00:02:18,040 --> 00:02:20,560 NEW COLLABORATIONS AND BE BOLD 60 00:02:20,560 --> 00:02:21,720 AND INNOVATIVE WITH THE IDEAS 61 00:02:21,720 --> 00:02:25,160 YOU SHARE. 62 00:02:25,160 --> 00:02:26,880 I'D LIKE TO BRIEFLY REMIND THE 63 00:02:26,880 --> 00:02:28,360 GROUP OF MEETING LOGISTICS. 64 00:02:28,360 --> 00:02:32,240 THIS MEETING IS BEING RECORDED. 65 00:02:32,240 --> 00:02:36,000 SOME SPEAKERS MAY SHARE 66 00:02:36,000 --> 00:02:37,680 PRELIMINARY TODAY WE ASK YOU 67 00:02:37,680 --> 00:02:41,000 KEEP CONFIDENTIALITY AND WE'LL 68 00:02:41,000 --> 00:02:43,000 HAVE THE CHAT FUNCTION FOR 69 00:02:43,000 --> 00:02:44,240 QUESTIONS YOU WANT ADDRESSED BY 70 00:02:44,240 --> 00:02:46,880 THE SPEAKERS AND A DEDICATED Q&A 71 00:02:46,880 --> 00:02:48,480 AT THE END OF EACH SESSION AND 72 00:02:48,480 --> 00:02:51,160 YOU CAN ALSO USE THIS IF YOU 73 00:02:51,160 --> 00:02:53,760 NEED ANY TECHNICAL ASSISTANCE. 74 00:02:53,760 --> 00:02:55,400 FINALLY, AS WE HAVE A LOT OF 75 00:02:55,400 --> 00:02:56,800 REGISTRANTS AS YOU ENTER THE 76 00:02:56,800 --> 00:02:59,800 WORKSHOP YOU ARE MUTED AND OFF 77 00:02:59,800 --> 00:03:00,040 CAMERA. 78 00:03:00,040 --> 00:03:01,960 WE ASK YOU STAY THIS WAY TO SAVE 79 00:03:01,960 --> 00:03:03,160 BAND WIDTH. 80 00:03:03,160 --> 00:03:05,040 YOU'RE WELCOME TO SPEAK AND USE 81 00:03:05,040 --> 00:03:07,200 YOUR CAMERA FREELY IN THE 82 00:03:07,200 --> 00:03:09,080 AFTERNOON AT THE INSTRUCTION OF 83 00:03:09,080 --> 00:03:11,320 YOUR MODERATORS TO HELP 84 00:03:11,320 --> 00:03:11,960 FACILITATE OPEN DISCUSSION AND 85 00:03:11,960 --> 00:03:15,040 COLLABORATION. 86 00:03:15,040 --> 00:03:19,320 WE ALSO HAVE A PROGRAM BOOKLET 87 00:03:19,320 --> 00:03:21,280 WITH BIOS AND MEETING MATERIALS. 88 00:03:21,280 --> 00:03:23,360 TO STAY ON TIME WE ASK YOU USE 89 00:03:23,360 --> 00:03:26,000 THIS AS A RESOURCE AS THE 90 00:03:26,000 --> 00:03:27,800 MODERATORS WILL NOT BE READING 91 00:03:27,800 --> 00:03:28,440 FULL BIOS. 92 00:03:28,440 --> 00:03:30,120 FOR EACH SESSION WE'LL HAVE 93 00:03:30,120 --> 00:03:31,520 15-MINUTE PRESENTATIONS BACK TO 94 00:03:31,520 --> 00:03:34,600 BACK AND THEN WE'LL HAVE A 95 00:03:34,600 --> 00:03:35,240 DEDICATED Q&A SESSION FOR EACH 96 00:03:35,240 --> 00:03:37,720 PANEL. 97 00:03:37,720 --> 00:03:38,960 AGAIN, PLEASE USE THE CHAT TOOL 98 00:03:38,960 --> 00:03:40,200 FOR YOUR QUESTIONS THAT YOU WANT 99 00:03:40,200 --> 00:03:44,120 DIRECTED FOR THAT SESSION. 100 00:03:44,120 --> 00:03:45,600 THREE BREAKOUT SESSIONS WILL 101 00:03:45,600 --> 00:03:48,280 OCCUR TOWARDS THE END OF THE DAY 102 00:03:48,280 --> 00:03:50,320 AND WILL OCCUR SIMULTANEOUSLY. 103 00:03:50,320 --> 00:03:53,040 THEY'LL BE MODERATED BY A PANEL 104 00:03:53,040 --> 00:03:54,560 AND DESIGNED TO BE WORKING 105 00:03:54,560 --> 00:03:56,440 BREAKOUT SESSIONS WHERE WE DO 106 00:03:56,440 --> 00:03:57,080 WELCOME YOUR PARTICIPATION AND 107 00:03:57,080 --> 00:03:59,920 DISCUSSION. 108 00:03:59,920 --> 00:04:02,080 YOU CAN USE YOUR COLLABORATIVE 109 00:04:02,080 --> 00:04:03,040 TOOLS SUCH AS CHAT, HAND RAISING 110 00:04:03,040 --> 00:04:04,360 AND CAMERA DURING THE SESSIONS 111 00:04:04,360 --> 00:04:06,040 AND HOPE YOU'LL BE FULLY ENGAGED 112 00:04:06,040 --> 00:04:07,040 IN THE WORKING GROUP. 113 00:04:07,040 --> 00:04:10,960 YOU'LL BE INSTRUCTED TO ENTER 114 00:04:10,960 --> 00:04:12,480 THE BREAKOUT SESSIONS FROM THE 115 00:04:12,480 --> 00:04:14,080 MAIN ZOOM ROOM. 116 00:04:14,080 --> 00:04:17,960 IF YOU'RE WATCHING FROM THE NIH 117 00:04:17,960 --> 00:04:21,520 LIVE CAST AND WISH TO JOIN YOU 118 00:04:21,520 --> 00:04:24,120 MUST ENTER THROUGH THE ZOOM LINK 119 00:04:24,120 --> 00:04:25,800 IF YOU WANT REPLACEMENT YOU CAN 120 00:04:25,800 --> 00:04:26,880 COME BACK TO THE MAIN MEETING 121 00:04:26,880 --> 00:04:28,720 AND ASK FOR ASSISTANCE. 122 00:04:28,720 --> 00:04:31,320 AS I MENTIONED, WE'LL FREQUENTLY 123 00:04:31,320 --> 00:04:32,880 POST THE AGENDA AND PROGRAM BOOK 124 00:04:32,880 --> 00:04:35,280 IN THE CHAT AS A RESOURCE FOR 125 00:04:35,280 --> 00:04:36,160 WORKSHOP PARTICIPANTS. 126 00:04:36,160 --> 00:04:38,360 OUR STRUCTURE FOR TODAY IS 127 00:04:38,360 --> 00:04:41,160 SIMILAR AS TO YESTERDAY AND WE 128 00:04:41,160 --> 00:04:42,440 WILL HAVE THREE ADDITIONAL 129 00:04:42,440 --> 00:04:44,600 SCIENTIFIC SESSIONS. 130 00:04:44,600 --> 00:04:46,040 SESSION 3 WILL ADDRESS EARLY 131 00:04:46,040 --> 00:04:48,160 LUNG DISEASE IN CYSTIC FIBROSIS 132 00:04:48,160 --> 00:04:49,560 HOW WE CAN MONITOR DISEASE 133 00:04:49,560 --> 00:04:50,600 PROGRESSION AND IMPORTANT 134 00:04:50,600 --> 00:04:52,000 QUESTIONS REGARDING INITIATING 135 00:04:52,000 --> 00:04:53,840 OR STOPPING THERAPIES. 136 00:04:53,840 --> 00:04:56,200 SESSION 4 WILL CONSIDER THE USE 137 00:04:56,200 --> 00:04:58,440 OF HIGHLY EFFECTIVE MODULATED 138 00:04:58,440 --> 00:05:00,560 THERAPIES IN SPECIAL POPULATIONS 139 00:05:00,560 --> 00:05:03,880 INCLUDING DURING PREGNANCY, 140 00:05:03,880 --> 00:05:04,960 POST-TRANSPLANT AND ALSO DISCUSS 141 00:05:04,960 --> 00:05:08,160 THE RISK FOR AGE-RELATED 142 00:05:08,160 --> 00:05:09,840 COMORBIDITIES IN CYSTIC 143 00:05:09,840 --> 00:05:10,240 FIBROSIS. 144 00:05:10,240 --> 00:05:11,560 WE'LL ALSO DISCUSS WAYS TO 145 00:05:11,560 --> 00:05:13,400 BRIDGE THE GAP FOR THOSE 146 00:05:13,400 --> 00:05:14,760 CURRENTLY NOT ELIGIBLE FOR 147 00:05:14,760 --> 00:05:18,800 MODULATED THERAPIES. 148 00:05:18,800 --> 00:05:21,320 AND SESSION 5 WILL DISCUSS 149 00:05:21,320 --> 00:05:22,600 CLINICAL CARE THROUGH NEW TOOLS 150 00:05:22,600 --> 00:05:23,920 AND TECHNOLOGIES AND WE'LL 151 00:05:23,920 --> 00:05:25,920 CONCLUDE THE SESSION WITH 152 00:05:25,920 --> 00:05:27,640 ANOTHER COMMUNITY MEMBER 153 00:05:27,640 --> 00:05:27,960 PERSPECTIVE. 154 00:05:27,960 --> 00:05:30,560 AS WE DID YESTERDAY, WE'LL HAVE 155 00:05:30,560 --> 00:05:33,320 THREE CONCURRENT BREAKOUT 156 00:05:33,320 --> 00:05:35,440 SESSIONS WITH A GROUP REPORT OUT 157 00:05:35,440 --> 00:05:37,480 AS WELL AS A DISCUSSION OF THE 158 00:05:37,480 --> 00:05:40,680 MAJOR THEMES FROM BOTH DAYS. 159 00:05:40,680 --> 00:05:42,480 SO AS A SAID SEVERAL TIMES, WE 160 00:05:42,480 --> 00:05:43,560 WOULD LIKE TO HEAR YOU FROM. 161 00:05:43,560 --> 00:05:45,880 WE HAVE THE BREAKOUT SESSIONS 162 00:05:45,880 --> 00:05:47,240 DESIGNED FOR YOUR PARTICIPATION. 163 00:05:47,240 --> 00:05:50,560 YOU CAN ALSO SEND YOUR THOUGHTS 164 00:05:50,560 --> 00:05:53,080 VIA LIVE TWEETS USING THE 165 00:05:53,080 --> 00:05:55,200 MEETING HASH TAG OR E-MAIL US 166 00:05:55,200 --> 00:05:56,480 DIRECTLY TO SEND YOUR COMMENTS, 167 00:05:56,480 --> 00:05:57,600 IDEAS OR FEEDBACK. 168 00:05:57,600 --> 00:06:00,040 WE'LL ALSO POST THIS CONTACT 169 00:06:00,040 --> 00:06:01,440 INFORMATION IN THE CHAT 170 00:06:01,440 --> 00:06:05,080 THROUGHOUT THE WORKSHOP. 171 00:06:05,080 --> 00:06:06,560 I WANT TO TAKE THIS OPPORTUNITY 172 00:06:06,560 --> 00:06:09,160 TO SAY A HUGE THANKS TO THE 173 00:06:09,160 --> 00:06:10,200 WORKSHOP PLANNING TEAM AND 174 00:06:10,200 --> 00:06:12,680 CO-CHAIRS AND ALL OF OUR 175 00:06:12,680 --> 00:06:14,520 SPEAKERS AND BREAKOUT 176 00:06:14,520 --> 00:06:14,840 MODERATORS. 177 00:06:14,840 --> 00:06:15,880 THEY'VE PUT A LOT OF TIME AND 178 00:06:15,880 --> 00:06:20,760 EFFORT IN PLANNING THE EVENT AND 179 00:06:20,760 --> 00:06:23,480 THANK YOU ALL FOR PARTICIPATING 180 00:06:23,480 --> 00:06:25,720 AND REGISTERING FOR THE WORKSHOP 181 00:06:25,720 --> 00:06:28,000 AND THIS WOULD NOT BE POSSIBLE 182 00:06:28,000 --> 00:06:29,520 WITHOUT OUR SUPPORT MEMBERS 183 00:06:29,520 --> 00:06:33,440 WORKING BEHIND THE SCENES TO 184 00:06:33,440 --> 00:06:35,120 MAKE THIS A FANTASTIC EVENT. 185 00:06:35,120 --> 00:06:36,760 BEFORE WE BEGIN OUR FIRST 186 00:06:36,760 --> 00:06:38,920 SESSION, I WANTED TO RECAP A FEW 187 00:06:38,920 --> 00:06:41,200 OF THE THEMES FROM YESTERDAY AS 188 00:06:41,200 --> 00:06:42,480 A PRIMER FOR MOVING INTO OUR 189 00:06:42,480 --> 00:06:43,960 FINAL DAY OF THE MEETING. 190 00:06:43,960 --> 00:06:45,800 SO ONE OF THE TOPICS THAT WAS 191 00:06:45,800 --> 00:06:50,920 DISCUSSED IS WHEN WE'RE THINKING 192 00:06:50,920 --> 00:06:52,240 ABOUT IN VITRO MODELS THERE WAS 193 00:06:52,240 --> 00:06:54,760 A DISCUSSION ON THE NEED TO 194 00:06:54,760 --> 00:06:56,480 DEVELOP MORE COMPLEX AND MIXED 195 00:06:56,480 --> 00:06:59,000 CELLULAR MODELS THAT BETTER 196 00:06:59,000 --> 00:07:00,200 REFLECT THE IN VIVO SITUATION 197 00:07:00,200 --> 00:07:03,280 AND REMINDED WE NEEDED TO BE 198 00:07:03,280 --> 00:07:04,200 AWARE OF SENESCENCE AND 199 00:07:04,200 --> 00:07:06,440 EPIGENETIC PATTERNS IN THE 200 00:07:06,440 --> 00:07:07,320 SYSTEMS. 201 00:07:07,320 --> 00:07:09,240 AN OPPORTUNITY WAS IDENTIFIED TO 202 00:07:09,240 --> 00:07:11,200 FIND BETTER WAYS TO LEVERAGE THE 203 00:07:11,200 --> 00:07:13,080 MODELS FOR PRE-CLINICAL AND 204 00:07:13,080 --> 00:07:17,320 CLINICAL APPLICATAPPLICATIONS. 205 00:07:17,320 --> 00:07:20,600 THERE WERE WAYS TO USE ANIMAL 206 00:07:20,600 --> 00:07:22,920 MODELS FOR THE HUMAN CONDITION 207 00:07:22,920 --> 00:07:25,240 AND HOW TO BE USED FOR DISEASE 208 00:07:25,240 --> 00:07:26,560 PHENOTYPES AND BIOMARKERS. 209 00:07:26,560 --> 00:07:28,280 A GAP WAS IDENTIFIED HERE AS A 210 00:07:28,280 --> 00:07:30,480 POTENTIAL BARRIER TO ACCESS SOME 211 00:07:30,480 --> 00:07:32,560 OF THESE MODELS IS THE HIGH 212 00:07:32,560 --> 00:07:33,800 LEVEL OF TRAINING NEEDED TO 213 00:07:33,800 --> 00:07:35,320 BRING THEM INTO NEW LABS AND 214 00:07:35,320 --> 00:07:37,800 ALSO FOR THE COST OF MAINTAINING 215 00:07:37,800 --> 00:07:39,440 RESEARCH COLONIES. 216 00:07:39,440 --> 00:07:41,920 FINALLY, THERE WAS A LOT OF 217 00:07:41,920 --> 00:07:43,240 DISCUSSION ABOUT LATE-STAGE LUNG 218 00:07:43,240 --> 00:07:47,080 DISEASE AND HOW TO MONITOR 219 00:07:47,080 --> 00:07:47,880 INDIVIDUALS WITH CYSTIC FIBROSIS 220 00:07:47,880 --> 00:07:49,520 AND MUCH OF THE DISCUSSION WAS 221 00:07:49,520 --> 00:07:52,080 AROUND WHAT ARE THE BEST 222 00:07:52,080 --> 00:07:53,960 CLINICAL END POINTS. 223 00:07:53,960 --> 00:07:57,240 AS DISCUSSED, FEB1 IS NOT THAT 224 00:07:57,240 --> 00:07:57,720 SENSITIVE. 225 00:07:57,720 --> 00:07:59,040 SHOULD WE LOOK AT OTHER 226 00:07:59,040 --> 00:08:01,760 TECHNOLOGIES OR OMICS-BASED 227 00:08:01,760 --> 00:08:02,080 BIOMARKERS? 228 00:08:02,080 --> 00:08:03,440 THERE WAS A DISCUSSION AROUND 229 00:08:03,440 --> 00:08:06,240 THE CHANGES IN NUTRITION AND 230 00:08:06,240 --> 00:08:07,320 PANCREATIC FUNCTION IN THE ERA 231 00:08:07,320 --> 00:08:09,080 OF MODULATED THERAPIES OR 232 00:08:09,080 --> 00:08:10,640 KNOWLEDGE GAPS WERE IDENTIFIED 233 00:08:10,640 --> 00:08:14,040 AND SHARED INTEREST IN THIS AREA 234 00:08:14,040 --> 00:08:17,360 COULD MEAN A NEED FOR RESEARCH 235 00:08:17,360 --> 00:08:17,640 STIMULATION. 236 00:08:17,640 --> 00:08:19,360 AND OPPORTUNITIES TO CONTINUE 237 00:08:19,360 --> 00:08:21,080 DEVELOPING BETTER MODULATORS OR 238 00:08:21,080 --> 00:08:22,880 NEW DRUGS OR ADVANCING GENE 239 00:08:22,880 --> 00:08:24,040 THERAPY TECHNOLOGIES WAS 240 00:08:24,040 --> 00:08:26,160 DISCUSSED AS A WAY TO ADDRESS 241 00:08:26,160 --> 00:08:28,080 NEEDS FOR THOSE WITH CF NOT 242 00:08:28,080 --> 00:08:30,000 CURRENTLY ELIGIBLE OR CANNOT 243 00:08:30,000 --> 00:08:31,440 TAKE CURRENT MODULATED 244 00:08:31,440 --> 00:08:31,720 THERAPIES. 245 00:08:31,720 --> 00:08:34,320 AS WE MOVE INTO TODAY'S 246 00:08:34,320 --> 00:08:37,160 SESSIONS, I'M SURE WE WILL HEAR 247 00:08:37,160 --> 00:08:38,120 ADDITIONAL AREAS THAT NEED 248 00:08:38,120 --> 00:08:39,440 CRITICAL ATTENTION AND I LOOK 249 00:08:39,440 --> 00:08:40,960 FORWARD TO ALL OF YOUR 250 00:08:40,960 --> 00:08:41,280 CONTRIBUTIONS. 251 00:08:41,280 --> 00:08:43,240 AT THIS TIME I'LL TURN OUR 252 00:08:43,240 --> 00:08:48,200 MEETING OVER TO MODERATORS. 253 00:08:48,200 --> 00:08:56,160 I'M JENNIFER BOMBERGER AND 254 00:08:56,160 --> 00:09:05,440 DR. LAGUNA. 255 00:09:05,440 --> 00:09:06,720 WE'LL BE TALKING ABOUT THE 256 00:09:06,720 --> 00:09:08,880 CLINICAL CHALLENGES FOR THOSE ON 257 00:09:08,880 --> 00:09:11,320 MODULATOR WHO HAVE NOT YET 258 00:09:11,320 --> 00:09:14,760 DEVELOPED CHRONIC LUNG DISEASE. 259 00:09:14,760 --> 00:09:20,080 OUR SPEAKERS ARE DR. LAGUNA AND 260 00:09:20,080 --> 00:09:22,680 MYSELF, DR. CHRISTOPHER FORTNER 261 00:09:22,680 --> 00:09:24,160 AND DR. CUTTING. 262 00:09:24,160 --> 00:09:26,160 IN THE INTEREST OF TIME WE'LL 263 00:09:26,160 --> 00:09:30,240 START THE TALK WITH DR. TERI 264 00:09:30,240 --> 00:09:33,760 LAGUNA FROM NORTHWESTERN INVEST. 265 00:09:33,760 --> 00:09:36,720 I'M GOING TO TALK TO YOU GUYS 266 00:09:36,720 --> 00:09:38,400 ABOUT HIGHLY EFFECTIVE 267 00:09:38,400 --> 00:09:41,040 MODULATORS IN EARLY LUNG 268 00:09:41,040 --> 00:09:41,280 DISEASE. 269 00:09:41,280 --> 00:09:44,920 THE MAGIC 8 BALL. 270 00:09:44,920 --> 00:09:48,560 FIRST, DISCLOSURES I RECEIVE 271 00:09:48,560 --> 00:09:50,880 GRANT FROM THE NIH AND CFF AND 272 00:09:50,880 --> 00:09:53,720 REVIEW GRANTS AND I'M A PU 273 00:09:53,720 --> 00:09:55,640 PULMONOLO 274 00:09:55,640 --> 00:09:56,000 PULMONOLOGIST. 275 00:09:56,000 --> 00:09:59,200 THREE OBJECTIVES TO RUN THROUGH. 276 00:09:59,200 --> 00:10:02,720 THE FIRST IS TO GET THINKING BY 277 00:10:02,720 --> 00:10:05,800 REVIEWING PATIENT CASES 278 00:10:05,800 --> 00:10:08,920 INVOLVING HIGHLY EFFECTIVE 279 00:10:08,920 --> 00:10:10,840 MODULATORY USE AND TALK ABOUT 280 00:10:10,840 --> 00:10:13,520 THE CLINICAL CARE OF CHILDREN 281 00:10:13,520 --> 00:10:16,080 WITH CF ON HIGHLY EFFECTIVE 282 00:10:16,080 --> 00:10:17,760 MODULATORS OR WAITING FOR ONE 283 00:10:17,760 --> 00:10:19,760 AND I'LL END BY IDENTIFYING THE 284 00:10:19,760 --> 00:10:21,360 GAPS IN KNOWLEDGE I FEEL SHOULD 285 00:10:21,360 --> 00:10:22,200 BE ADDRESSED. 286 00:10:22,200 --> 00:10:24,600 LET'S START BY REVIEWING SOME 287 00:10:24,600 --> 00:10:26,680 CASES WITH CLINICAL DILEMMAS. 288 00:10:26,680 --> 00:10:28,040 SO BEFORE I JUMP TO THE CASES, I 289 00:10:28,040 --> 00:10:30,440 WANT TO HAVE A FOUNDATION THAT 290 00:10:30,440 --> 00:10:32,040 WE'RE STARTING FROM IN REGARDS 291 00:10:32,040 --> 00:10:33,680 TO MODULATOR THERAPIES. 292 00:10:33,680 --> 00:10:44,120 SO JUST TO REMIND YOU, SO 293 00:10:44,600 --> 00:10:47,960 IVACAFTOR IS FDA APPROVED FOR 294 00:10:47,960 --> 00:10:52,080 CHILDREN GREATER THAN 4 MONTHS 295 00:10:52,080 --> 00:10:56,440 OF AGE AND ORKAMBI IS APPROVED 296 00:10:56,440 --> 00:10:58,440 FOR KIDS GREATER THAN YEARS WITH 297 00:10:58,440 --> 00:11:04,280 TWO COPIES OF DELTA A508 AND THE 298 00:11:04,280 --> 00:11:06,080 LAST ONE IS APPROVED FOR 299 00:11:06,080 --> 00:11:08,120 CHILDREN GREATER THAN 6 YEARS OF 300 00:11:08,120 --> 00:11:16,520 AGE WITH TWO COPIES OF F508DEL 301 00:11:16,520 --> 00:11:21,080 AND TRIKAFTA IS CONSIDERED A 302 00:11:21,080 --> 00:11:22,560 MODULATOR AND APPROVED FOR KIDS 303 00:11:22,560 --> 00:11:28,080 GREATER THAN 6 YEARS OF AGE WITH 304 00:11:28,080 --> 00:11:31,920 AT LEAST ONE COPY WHENEVER WE 305 00:11:31,920 --> 00:11:37,800 USE THE TERM HIGHLY EFFECTIVE 306 00:11:37,800 --> 00:11:38,960 MODULATORS WE'RE REFERRING TO 307 00:11:38,960 --> 00:11:39,280 THESE. 308 00:11:39,280 --> 00:11:40,760 BASED ON THE LIST THERE'S 309 00:11:40,760 --> 00:11:46,000 CURRENTLY SOME GAPS YOU CAN SEE. 310 00:11:46,000 --> 00:11:48,320 AND THERE'S NO MODULATOR 311 00:11:48,320 --> 00:11:50,640 APPROVED FOR CHILDREN LESS THAN 312 00:11:50,640 --> 00:11:51,240 6. 313 00:11:51,240 --> 00:11:53,920 THERE'S MUTATION GAPS. 314 00:11:53,920 --> 00:11:56,240 SO PEOPLE OFTEN DON'T QUALIFY 315 00:11:56,240 --> 00:11:59,160 FOR A MODULATED THERAPY. 316 00:11:59,160 --> 00:12:01,200 THERE'S TOLERABILITY GAP. 317 00:12:01,200 --> 00:12:02,680 SOME PEOPLE WITH CF AREN'T ABLE 318 00:12:02,680 --> 00:12:05,000 TO TOLERATE THE MODULATOR GIVEN 319 00:12:05,000 --> 00:12:06,920 DRUG INTERACTIONS, ETCETERA. 320 00:12:06,920 --> 00:12:08,400 AND THEN THERE ARE STUDY DESIGN 321 00:12:08,400 --> 00:12:08,600 GAPS. 322 00:12:08,600 --> 00:12:10,960 THIS IS SOMETHING TO KEEP IN 323 00:12:10,960 --> 00:12:11,160 MIND. 324 00:12:11,160 --> 00:12:13,720 ALL MODULATOR STUDIES WERE DONE 325 00:12:13,720 --> 00:12:15,800 IN THE SETTING OF STANDARD OF 326 00:12:15,800 --> 00:12:17,800 CARE, BASELINE MEDICATIONS AN 327 00:12:17,800 --> 00:12:18,880 AIRWAY CLEARANCE REGIMENTS. 328 00:12:18,880 --> 00:12:20,920 I'LL START WITH SOME CASES. 329 00:12:20,920 --> 00:12:24,120 SOME ARE A MIX OF REAL AND 330 00:12:24,120 --> 00:12:25,320 FICTION. 331 00:12:25,320 --> 00:12:28,160 I HAVE PERMISSION FROM ALL THE 332 00:12:28,160 --> 00:12:30,720 PATIENTS TO USE THEIR PHOTOS. 333 00:12:30,720 --> 00:12:36,000 GRACIE IS A 6-YEAR-OLD GIRL WITH 334 00:12:36,000 --> 00:12:38,120 PANCREATIC INSUFFICIENT CF AND 335 00:12:38,120 --> 00:12:41,840 ON ORKAMBI AND SHE HAS ENZYMES 336 00:12:41,840 --> 00:12:46,240 AND VITAMINS AND AIRWAY 337 00:12:46,240 --> 00:12:52,760 CLEARANCE AND NEBULIZED 338 00:12:52,760 --> 00:12:56,360 ALBUTEROL AND HER F EV1 IS 339 00:12:56,360 --> 00:12:58,000 PREDICTED AND HAS NEVER BEEN 340 00:12:58,000 --> 00:12:58,720 HOSPITALIZED. 341 00:12:58,720 --> 00:13:00,720 QUESTIONS TO THINK ABOUT, WOULD 342 00:13:00,720 --> 00:13:07,960 YOU SWITCH HER CF MODULATOR FROM 343 00:13:07,960 --> 00:13:14,840 ORKAMBI TO TRIKAFTA AND HAS DONE 344 00:13:14,840 --> 00:13:18,040 WELL WITH AN FEV OVER 100% WOULD 345 00:13:18,040 --> 00:13:20,200 YOU DECREASE HER VEST, WHY OR 346 00:13:20,200 --> 00:13:20,480 WHY NOT? 347 00:13:20,480 --> 00:13:24,280 AND FINALLY WITH THE DECISION TO 348 00:13:24,280 --> 00:13:27,920 SWITCH TO TRIKAFTA DECREASE HER 349 00:13:27,920 --> 00:13:30,320 BURDEN OF CARE WITH MEDS AND 350 00:13:30,320 --> 00:13:34,040 THERAPIES? 351 00:13:34,040 --> 00:13:42,320 WHY OR WHY NOT? 352 00:13:42,320 --> 00:13:52,400 MADDIE IS A 2-YEAR-OLD INFANT 353 00:13:52,400 --> 00:13:54,720 CASE 2, THIS IS HER GENOTYPE. 354 00:13:54,720 --> 00:13:59,280 SHE WILL NOT QUALIFY FOR A CF 355 00:13:59,280 --> 00:14:00,760 MODULATOR UNTIL ONE IS DEVELOPED 356 00:14:00,760 --> 00:14:01,880 FOR HER MUTATION. 357 00:14:01,880 --> 00:14:04,880 QUESTION TO CONSIDER. 358 00:14:04,880 --> 00:14:08,080 HOW WOULD YOU APPROACH CLINICAL 359 00:14:08,080 --> 00:14:10,080 CARE KNOWING ONE WILL QUALIFY 360 00:14:10,080 --> 00:14:12,480 ONCE APPROVED FOR HER AGE AND 361 00:14:12,480 --> 00:14:13,760 ONE MAY NOT FOR MANY YEARS. 362 00:14:13,760 --> 00:14:16,360 WOULD YOU BE MORE AGGRESSIVE 363 00:14:16,360 --> 00:14:19,000 WITH NUTRITION AND/OR MORE 364 00:14:19,000 --> 00:14:20,280 VIGILANT ABOUT THE APPROACH TO 365 00:14:20,280 --> 00:14:23,600 LUNG DISEASE AND WHAT WOULD IT 366 00:14:23,600 --> 00:14:25,240 LOOK LIKE AND WOULD IT BE 367 00:14:25,240 --> 00:14:27,280 DIFFERENT IN CASE 1 VERSUS CASE 368 00:14:27,280 --> 00:14:29,040 2 AND WHAT WOULD THE 369 00:14:29,040 --> 00:14:32,680 CONVERSATION OF INFANTS SOUND 370 00:14:32,680 --> 00:14:32,880 LIKE? 371 00:14:32,880 --> 00:14:35,640 CASE 3, AUSTIN IS A 12-YEAR-OLD 372 00:14:35,640 --> 00:14:42,320 BOY WITH PANCREATIC INSUFFICIENT 373 00:14:42,320 --> 00:14:42,480 CF. 374 00:14:42,480 --> 00:14:51,080 HE WAS SWITCHED TO TRIKAFTA AND 375 00:14:51,080 --> 00:14:53,200 GETS ENZYMES AND VITAMINS AND 376 00:14:53,200 --> 00:14:59,880 VEST TWIS A DAY WITH ALBUTEROL 377 00:14:59,880 --> 00:15:03,080 AND CHRONICALLY GROWS TOBI 378 00:15:03,080 --> 00:15:05,240 CYCLES AND HE HASN'T BEEN 379 00:15:05,240 --> 00:15:06,480 HOSPITALIZED SINCE AGE 4. 380 00:15:06,480 --> 00:15:07,800 AGAIN, QUESTION TO CONSIDER. 381 00:15:07,800 --> 00:15:09,360 GIVEN HOW WELL HE'S DOING NOW 382 00:15:09,360 --> 00:15:12,040 WOULD YOU MAKE CHANGES TO HIS 383 00:15:12,040 --> 00:15:17,440 AIRWAY CLEARANCE REGIMENT, 384 00:15:17,440 --> 00:15:26,400 REMOVE THESE AND WHAT WOULD GET 385 00:15:26,400 --> 00:15:28,920 TO YOU STOP HIS VEST AND WHAT 386 00:15:28,920 --> 00:15:31,200 WOULD THAT LOOK LIKE. 387 00:15:31,200 --> 00:15:35,840 AND A HYPOTHETICAL CASE. 388 00:15:35,840 --> 00:15:39,680 EMMA IS A 6-MONTH-OLD GIRL WITH 389 00:15:39,680 --> 00:15:44,720 FORMERLY PANCRECATTIC 390 00:15:44,720 --> 00:15:49,120 INSUFFICIENT CF AND HER FECAL 391 00:15:49,120 --> 00:15:51,280 ELASTASE IS NORMAL. 392 00:15:51,280 --> 00:15:55,480 HER THROAT SWABS HAVE BEEN 393 00:15:55,480 --> 00:15:58,600 NEGATIVE FOR BACTERIA AND HER 394 00:15:58,600 --> 00:15:59,840 GROWTH IS NORMAL. 395 00:15:59,840 --> 00:16:02,040 WOULD YOU HAD START HER ON 396 00:16:02,040 --> 00:16:05,160 PANCREATIC ENZYMES, VITAMINS AND 397 00:16:05,160 --> 00:16:05,440 SALTS? 398 00:16:05,440 --> 00:16:10,920 WHY OR WHY NOT AND WOULD YOU 399 00:16:10,920 --> 00:16:19,920 START HER ON PULMOZYME. 400 00:16:19,920 --> 00:16:22,360 WOULD YOU FOLLOW CARE FOR 401 00:16:22,360 --> 00:16:23,720 INFANTS? 402 00:16:23,720 --> 00:16:25,760 WHY OR WHY NOT? 403 00:16:25,760 --> 00:16:27,560 THESE ARE PATIENT WE TAKE CARE 404 00:16:27,560 --> 00:16:29,560 OF OR THINK ABOUT IN THE ERA OF 405 00:16:29,560 --> 00:16:31,520 HIGHLY EFFECTIVE MODULATORS. 406 00:16:31,520 --> 00:16:33,120 I'LL REVIEW WHAT CURRENT 407 00:16:33,120 --> 00:16:34,600 LITERATURE EXIST THE CLINICAL 408 00:16:34,600 --> 00:16:36,600 CARE OF KIDS WITH CF ON HIGHLY 409 00:16:36,600 --> 00:16:37,800 EFFECTIVE MODULATOR OR WAITING 410 00:16:37,800 --> 00:16:39,640 FOR A MODULATOR. 411 00:16:39,640 --> 00:16:42,480 SO A FEW FACTS IN GAPS. 412 00:16:42,480 --> 00:16:44,480 FACT, MOST INFANTS AND YOUNGER 413 00:16:44,480 --> 00:16:48,320 CHILDREN WITH CF ARE NOT 414 00:16:48,320 --> 00:16:50,280 CANDIDATES FOR HIGHLY EFFECTIVE 415 00:16:50,280 --> 00:16:50,560 MODULATORS. 416 00:16:50,560 --> 00:16:52,200 WHEN I SAY YOUNGER CHILDREN I'M 417 00:16:52,200 --> 00:17:02,720 TALKING LESS THAN 6 RIGHT NOW. 418 00:17:06,000 --> 00:17:09,080 A RIGOROUS APPROACH IS WARRANTED 419 00:17:09,080 --> 00:17:12,800 AND THOSE ON CF ON A HIGHLY 420 00:17:12,800 --> 00:17:14,600 EFFECTIVE MODULATOR HAVE 421 00:17:14,600 --> 00:17:15,720 IMPROVED GROWTH AND QUALITY OF 422 00:17:15,720 --> 00:17:16,080 LIFE. 423 00:17:16,080 --> 00:17:21,920 WE KNOW THAT FROM THE ORIGINAL 424 00:17:21,920 --> 00:17:23,800 STUDIES DONE. 425 00:17:23,800 --> 00:17:25,240 PATIENTS, FAMILIES AND PROVIDERS 426 00:17:25,240 --> 00:17:27,440 ARE ASKING IF AND WHEN THE LARGE 427 00:17:27,440 --> 00:17:30,480 BURDEN OF DAILY CARE CAN BE 428 00:17:30,480 --> 00:17:30,760 DECREASED. 429 00:17:30,760 --> 00:17:34,200 HOWEVER, HOW-TO GUIDELINE 430 00:17:34,200 --> 00:17:35,000 DOESN'T YET EXIST. 431 00:17:35,000 --> 00:17:37,200 AND RARE CF MUTATIONS ARE 432 00:17:37,200 --> 00:17:38,280 CONCENTRATED IN BLACK AND BROWN 433 00:17:38,280 --> 00:17:40,720 CHILDREN WITH CF RESULTING IN A 434 00:17:40,720 --> 00:17:42,440 SIGNIFICANT DISPARITY IN CARE. 435 00:17:42,440 --> 00:17:45,480 THE GAP HERE IS IDENTIFYING AND 436 00:17:45,480 --> 00:17:47,240 CHARACTERIZING RARE MUTATIONS 437 00:17:47,240 --> 00:17:48,520 AND FOCUSSING RESEARCH ON 438 00:17:48,520 --> 00:17:49,160 SUPPORTING THESE COMMUNITIES 439 00:17:49,160 --> 00:17:52,000 SHOULD BE PRIORITIZED. 440 00:17:52,000 --> 00:17:57,240 SO THE WAY IT FEELS NOW AS A 441 00:17:57,240 --> 00:17:58,920 PEDIATRIC LUNG DOCTOR TAKING 442 00:17:58,920 --> 00:18:00,600 CARE OF THESE KIDS ON MODULATORS 443 00:18:00,600 --> 00:18:02,280 AND DOING WELL OR DON'T QUALIFY, 444 00:18:02,280 --> 00:18:04,440 IT FEELS LIKE A MAGIC 8 BALL. 445 00:18:04,440 --> 00:18:06,040 I THINK DATING MYSELF IN TERMS 446 00:18:06,040 --> 00:18:07,560 OF WHAT THIS IS. 447 00:18:07,560 --> 00:18:10,080 BUT IT'S A BALL YOU USED TO 448 00:18:10,080 --> 00:18:12,280 SHAKE AND ASK A QUESTION AND 449 00:18:12,280 --> 00:18:15,480 TURN IT OVER AND AN ANSWER WOULD 450 00:18:15,480 --> 00:18:16,960 TURN UP AN IT DOESN'T SIT WELL 451 00:18:16,960 --> 00:18:18,200 WITH THOSE OF US IN THE 452 00:18:18,200 --> 00:18:19,480 SCIENTIFIC COMMUNITY. 453 00:18:19,480 --> 00:18:22,360 WHAT ABOUT THE KIDS WAITING FOR 454 00:18:22,360 --> 00:18:25,600 A MODULATOR. 455 00:18:25,600 --> 00:18:28,160 WE KNOW THE ACHIEVEMENTS OF 456 00:18:28,160 --> 00:18:29,080 NUTRITION THROUGH METRICS 457 00:18:29,080 --> 00:18:32,040 STUDIED AND PUBLISHED IS THE KEY 458 00:18:32,040 --> 00:18:33,520 TO HIGHER LUNG FUNCTION LATER IN 459 00:18:33,520 --> 00:18:37,000 LIFE AND PREVENTING THE ONSET OF 460 00:18:37,000 --> 00:18:38,560 PROGRESSION OF CF LUNG DISEASE 461 00:18:38,560 --> 00:18:41,640 SHOULD BE PRIORITIZED. 462 00:18:41,640 --> 00:18:47,600 KIDS WAITING FOR A MODULATOR AND 463 00:18:47,600 --> 00:18:50,080 KEEPING THEM HEALTHY IS A 464 00:18:50,080 --> 00:18:51,240 STANDARD OF CARE FOR KIDS 465 00:18:51,240 --> 00:18:53,040 GREATER THAN OR EQUAL TO 6 BUT 466 00:18:53,040 --> 00:18:56,480 THIS IS HARD FOR KIDS TO PERFORM 467 00:18:56,480 --> 00:19:00,440 WHEN YOUNGER THAN 6. 468 00:19:00,440 --> 00:19:03,880 CHEST CT AND MRI ARE NOT 469 00:19:03,880 --> 00:19:10,880 ROUTINELY PERFORMED AND SWABZ -- 470 00:19:10,880 --> 00:19:12,760 SWABS ARE DONE AND THIS IS WHAT 471 00:19:12,760 --> 00:19:16,200 WE DO NOW BUT IS THAT AGGRESSIVE 472 00:19:16,200 --> 00:19:17,680 AND GOOD ENOUGH. 473 00:19:17,680 --> 00:19:18,400 QUESTIONS TO CONSIDER. 474 00:19:18,400 --> 00:19:20,680 IS THERE A ROLE FOR A MORE 475 00:19:20,680 --> 00:19:22,240 AGGRESSIVE NUTRITIONAL 476 00:19:22,240 --> 00:19:23,800 MANAGEMENT APPROACH. 477 00:19:23,800 --> 00:19:26,560 SO EARLIER GT PLACEMENT AND 478 00:19:26,560 --> 00:19:29,400 FEEDS IN PATIENTS WAIT BEING FOR 479 00:19:29,400 --> 00:19:30,400 A CF MODULATOR? 480 00:19:30,400 --> 00:19:32,720 SHOULD WE BE PUSHING FOR MORE 481 00:19:32,720 --> 00:19:34,360 WIDESPREAD IMPLEMENTATION OF 482 00:19:34,360 --> 00:19:35,760 THINGS LIKE A LUNG CLEARANCE 483 00:19:35,760 --> 00:19:39,520 INDEX AND MORE ROUTINE IMAGEING 484 00:19:39,520 --> 00:19:42,320 STUDIES LIKE CHEST CT OR MRI AND 485 00:19:42,320 --> 00:19:44,160 MY COLLEAGUE WILL TALK ABOUT 486 00:19:44,160 --> 00:19:49,560 THIS AND SHOULD WE CONSIDER 487 00:19:49,560 --> 00:19:51,040 SURVEILLANCE BRONCHOSCOPY TO 488 00:19:51,040 --> 00:19:52,760 MITIGATE THE PROGRESSION OF LUNG 489 00:19:52,760 --> 00:19:53,160 DISEASE? 490 00:19:53,160 --> 00:19:54,800 WE KNOW IT'S BEEN STUDIED IN THE 491 00:19:54,800 --> 00:19:57,280 PAST PRIOR TO HIGHLY EFFECTIVE 492 00:19:57,280 --> 00:19:58,560 MODULATOR THERAPY BUT I THINK 493 00:19:58,560 --> 00:20:00,080 THE QUESTION IS NOW IF WE'RE 494 00:20:00,080 --> 00:20:01,840 LOOKING FOR PATHOGENS WE CAN 495 00:20:01,840 --> 00:20:02,520 TREAT WHILE WAITING FOR A 496 00:20:02,520 --> 00:20:06,680 MODULATOR. 497 00:20:06,680 --> 00:20:08,080 WHAT DO WE KNOW ABOUT DECREASING 498 00:20:08,080 --> 00:20:13,880 THE BURDEN OF CARE IN THE 499 00:20:13,880 --> 00:20:21,040 MODULATOR ERA? 500 00:20:21,040 --> 00:20:23,400 AND WHAT ABOUT ADULTS STARTED ON 501 00:20:23,400 --> 00:20:27,040 A HIGHLY EFFECTIVE MODULATOR. 502 00:20:27,040 --> 00:20:28,200 WE DON'T KNOW MUCH YET. 503 00:20:28,200 --> 00:20:29,760 I WANT TO DRAW YOUR ATTENTION TO 504 00:20:29,760 --> 00:20:39,240 A STUDY MENTIONED YESTERDAY. 505 00:20:39,240 --> 00:20:42,480 THIS IS A STUDY TO EVALUATE THE 506 00:20:42,480 --> 00:20:45,840 IMPACT OF STOPPING CHRONIC 507 00:20:45,840 --> 00:20:48,280 THERAPIES AFTER A HIGHLY 508 00:20:48,280 --> 00:20:49,960 EFFECTIVE MODULATOR WAS STARTED 509 00:20:49,960 --> 00:20:51,560 AND I'LL DRAW YOUR ATTENTION TO 510 00:20:51,560 --> 00:20:53,880 A SIMILAR STUDY CALLED CF STORM 511 00:20:53,880 --> 00:20:56,080 OCCURRING IN THE U.K. 512 00:20:56,080 --> 00:20:57,520 SO BRIEFLY, THE TRIAL STUDY 513 00:20:57,520 --> 00:20:59,200 DESIGN WAS TO TEST WHETHER OR 514 00:20:59,200 --> 00:21:03,960 NOT IT IS SAFE TO STOP TAKING 515 00:21:03,960 --> 00:21:07,600 INHALED HYPERTONIC SALINE IN 516 00:21:07,600 --> 00:21:11,080 PEOPLE WITH CF TAKING HIGHLY 517 00:21:11,080 --> 00:21:13,400 EFFECTIVE MODULATOR IN THIS CASE 518 00:21:13,400 --> 00:21:23,480 DEF 519 00:21:30,840 --> 00:21:30,840 520 00:22:08,760 --> 00:22:10,360 THERE ARE THREE ARMS. 521 00:22:10,360 --> 00:22:12,400 PEOPLE WHO CAME IN ON HYPER 522 00:22:12,400 --> 00:22:14,520 TONIC SALINE AND PEOPLE WHO CAME 523 00:22:14,520 --> 00:22:19,880 IN ON BOTH HYPER TONIC SALINE 524 00:22:19,880 --> 00:22:24,520 AND PULMOZYME. 525 00:22:24,520 --> 00:22:25,880 THE KIDS WOULD STAY ON 526 00:22:25,880 --> 00:22:27,320 MEDICATIONS TWO WEEKS AND 527 00:22:27,320 --> 00:22:31,480 RANDOMIZED TO EITHER STOP IT OR 528 00:22:31,480 --> 00:22:32,600 CONTINUE IT. 529 00:22:32,600 --> 00:22:34,040 ALL WHILE CONTINUING TO TAKE 530 00:22:34,040 --> 00:22:35,640 THEIR TRIKAPTA. 531 00:22:35,640 --> 00:22:37,600 THIS WENT FOR SIX WEEKS AND HAD 532 00:22:37,600 --> 00:22:38,600 THE OPTION TO SWITCH TO THE 533 00:22:38,600 --> 00:22:40,040 OTHER ARM IF THEY WANTED. 534 00:22:40,040 --> 00:22:42,120 WHAT ARE WE GOING LEARN FROM THE 535 00:22:42,120 --> 00:22:42,320 STUDY? 536 00:22:42,320 --> 00:22:44,600 THE GOAL OF THIS AGAIN IS TO 537 00:22:44,600 --> 00:22:46,560 REDUCE THE TREATMENT BURDEN. 538 00:22:46,560 --> 00:22:48,840 WE'RE HOPING TO DO WITHOUT 539 00:22:48,840 --> 00:22:49,720 SACRIFICING THE INCREMENTAL 540 00:22:49,720 --> 00:22:51,680 HEALTH GAINS ACHIEVED THROUGH 541 00:22:51,680 --> 00:22:57,520 THE ACCUMULATIVE CONDITIONS AND 542 00:22:57,520 --> 00:22:59,560 MOST ARE ON MULTIPLE THERAPIES 543 00:22:59,560 --> 00:23:01,080 WE DON'T KNOW WHAT WILL HAPPEN 544 00:23:01,080 --> 00:23:02,360 IF WE START TO REMOVE THEM ONE 545 00:23:02,360 --> 00:23:03,000 AT A TIME. 546 00:23:03,000 --> 00:23:04,120 THAT'S THE GOAL TO TEST THAT AND 547 00:23:04,120 --> 00:23:07,760 SEE HOW THINGS GO. 548 00:23:07,760 --> 00:23:09,080 IT'S IMPORTANT TO HAVE BUY-IN 549 00:23:09,080 --> 00:23:11,280 FROM THE COMMUNITY TO COMPLETE A 550 00:23:11,280 --> 00:23:12,240 STUDY LIKE THIS. 551 00:23:12,240 --> 00:23:13,200 YESTERDAY THERE WERE COMMENTS 552 00:23:13,200 --> 00:23:14,960 HOW PATIENTS HAVE JUST STOPPED 553 00:23:14,960 --> 00:23:16,120 DOING THEIR THERAPIES. 554 00:23:16,120 --> 00:23:18,240 SOME HAVE STAYED HEALTHY AND 555 00:23:18,240 --> 00:23:21,960 SOME HAVE NOT SO HEALTHY. 556 00:23:21,960 --> 00:23:23,520 THE IMPORTANCE OF PARTNERING 557 00:23:23,520 --> 00:23:24,880 WITH A COMMUNITY AND ENCOURAGING 558 00:23:24,880 --> 00:23:26,400 THEM TO HAVE PATIENCE AS WE 559 00:23:26,400 --> 00:23:27,840 STUDY THIS TO MAKE SURE THE 560 00:23:27,840 --> 00:23:29,880 DECISIONS THEY MAKE ARE GOING TO 561 00:23:29,880 --> 00:23:31,160 KEEP THEM HEALTHY. 562 00:23:31,160 --> 00:23:33,440 THE FOCUS HERE WAS ON TWO 563 00:23:33,440 --> 00:23:34,920 MEDICATIONS ONLY AND ON THE 564 00:23:34,920 --> 00:23:36,080 SHORT TERM IMPACT. 565 00:23:36,080 --> 00:23:37,560 SIX WEEKS WAS WHAT WAS GOING TO 566 00:23:37,560 --> 00:23:39,920 BE STUDIED AND SIMPLIFIED. 567 00:23:39,920 --> 00:23:42,040 AGAIN, THE STUDY POPULATION IS 568 00:23:42,040 --> 00:23:44,480 GREATER AND EQUAL TO 12. 569 00:23:44,480 --> 00:23:46,560 THEY'RE NOT INFANTS OR YOUNG 570 00:23:46,560 --> 00:23:47,120 KIDS. 571 00:23:47,120 --> 00:23:48,200 WE SHOULD HAVE MORE INFORMATION 572 00:23:48,200 --> 00:23:49,040 COMING HOPEFULLY BY THE END OF 573 00:23:49,040 --> 00:23:51,280 THE SUMMER. 574 00:23:51,280 --> 00:23:53,360 SO WHAT ARE THE REMAINING GAPS? 575 00:23:53,360 --> 00:23:55,280 I'M GOING TO CLOSE BY TALKING 576 00:23:55,280 --> 00:23:57,880 ABOUT A FEW GAPS WE SHOULD BE 577 00:23:57,880 --> 00:23:59,680 THINKING ABOUT AS A COMMUNITY 578 00:23:59,680 --> 00:24:03,440 THAT WE SHOULD START TO ADDRESS. 579 00:24:03,440 --> 00:24:05,840 SO ONE OF THE THINGS IS WHAT 580 00:24:05,840 --> 00:24:07,920 CLINICAL PROTOCOL SHOULD WE 581 00:24:07,920 --> 00:24:10,800 FOLLOW TO BRIDGE THE GAP SO 582 00:24:10,800 --> 00:24:11,360 HIGHLY EFFECTIVE MODULATOR 583 00:24:11,360 --> 00:24:13,280 APPROVAL OR AVAILABILITY FOR AN 584 00:24:13,280 --> 00:24:14,760 INFANT WITH CF? 585 00:24:14,760 --> 00:24:16,480 I DRAW YOUR ATTENTION TO TWO 586 00:24:16,480 --> 00:24:17,560 GUIDELINES WE CURRENTLY HAVE FOR 587 00:24:17,560 --> 00:24:21,080 THE CARE OF INFANTS AND PRE 588 00:24:21,080 --> 00:24:22,400 SCHOOLERS WITH CF AS WELL AS A 589 00:24:22,400 --> 00:24:24,320 RECENT ARTICLE TALKING ABOUT 590 00:24:24,320 --> 00:24:26,280 THIS VERY CLINICAL SCENARIO. 591 00:24:26,280 --> 00:24:28,440 THE WHOLE CONCEPT SHOULD BE MORE 592 00:24:28,440 --> 00:24:30,240 AGGRESSIVE AND LOU TO MONITOR 593 00:24:30,240 --> 00:24:30,920 NUTRITION AND LUNG DISEASE 594 00:24:30,920 --> 00:24:38,520 KNOWING WE MAY NOT BE ABLE TO 595 00:24:38,520 --> 00:24:41,000 REVERSE BRONCHIEPSIS SO WHAT IS 596 00:24:41,000 --> 00:24:42,800 THE OPPORTUNITY TO TAKE CARE OF 597 00:24:42,800 --> 00:24:44,240 THE INFANTS AND KIDS TO KEEP 598 00:24:44,240 --> 00:24:47,360 THEM AS HEALTHY AS POSSIBLE? 599 00:24:47,360 --> 00:24:49,480 IN SOME SCENARIOS THIS MAY BE 600 00:24:49,480 --> 00:24:50,480 YEARS IF YOU HAVE A RARE 601 00:24:50,480 --> 00:24:53,240 MUTATION BEFORE A MODULATOR OR 602 00:24:53,240 --> 00:24:53,880 THERAPY IS AVAILABLE FOR YOUR 603 00:24:53,880 --> 00:24:56,640 CF. 604 00:24:56,640 --> 00:24:57,480 SO IF HIGHLY EFFECTIVE 605 00:24:57,480 --> 00:24:58,600 MODULATORS CAN BE STARTED AT 606 00:24:58,600 --> 00:25:04,520 BIRTH OR IF THEY'RE STARTED IN 607 00:25:04,520 --> 00:25:06,160 UTERO WILL INFANTS STILL NEED 608 00:25:06,160 --> 00:25:07,640 THE CLINICAL STANDARD OF CARE 609 00:25:07,640 --> 00:25:09,040 FOR CF? 610 00:25:09,040 --> 00:25:10,320 AGAIN, I DRAW YOUR ATTENTION TO 611 00:25:10,320 --> 00:25:11,640 THE TWO GUIDELINES WE HAVE FOR 612 00:25:11,640 --> 00:25:14,000 THE CARE OF INFANTS AND 613 00:25:14,000 --> 00:25:14,320 PRESCHOOLERS. 614 00:25:14,320 --> 00:25:15,960 DOES THIS CHANGE NOW THAT WE 615 00:25:15,960 --> 00:25:20,720 KNOW OUR KID HAS A NORMAL SWEAT 616 00:25:20,720 --> 00:25:29,640 TEST AND FECAL ELASTASE AND THE 617 00:25:29,640 --> 00:25:31,160 CF AIRWAY AND LUNG DISEASE IN 618 00:25:31,160 --> 00:25:32,240 KIDS IS WEEK AND THAT NEEDS TO 619 00:25:32,240 --> 00:25:35,880 BE STUDIED. 620 00:25:35,880 --> 00:25:38,440 THE EFFECTIVE MODULATORS IN THE 621 00:25:38,440 --> 00:25:41,200 MICROBIOME OVER TIME AND CHRONIC 622 00:25:41,200 --> 00:25:43,280 OR ACUTE INFECTION AND 623 00:25:43,280 --> 00:25:44,240 INFLAMMATION IN THE PRESENCE OF 624 00:25:44,240 --> 00:25:46,480 MODULATORS AND THE REMOVAL OF 625 00:25:46,480 --> 00:25:57,000 AIRWAY CLEARANCE AND FINALLY WE 626 00:26:14,480 --> 00:26:15,680 NEED CONTINUED WORK ON THOSE 627 00:26:15,680 --> 00:26:18,800 WITH CF WHO DO NOT QUALIFY FOR A 628 00:26:18,800 --> 00:26:19,080 MODULATOR. 629 00:26:19,080 --> 00:26:20,560 WE HEARD SOME PATIENTS AND 630 00:26:20,560 --> 00:26:22,440 FAMILY TESTIMONIALS WHAT THAT'S 631 00:26:22,440 --> 00:26:24,520 LIKE TO FEEL LIKE YOU'RE LEFT 632 00:26:24,520 --> 00:26:25,400 BEHIND AND THERE ARE SUBSTANTIAL 633 00:26:25,400 --> 00:26:27,720 NUMBER OF PEOPLE WHO EITHER 634 00:26:27,720 --> 00:26:29,640 DON'T QUALIFY OR DON'T TOLERATE 635 00:26:29,640 --> 00:26:30,640 A MODULATOR. 636 00:26:30,640 --> 00:26:32,000 THAT'S AN IMPORTANT GROUP OF 637 00:26:32,000 --> 00:26:34,080 PEOPLE WE HAVE TO CONTINUE 638 00:26:34,080 --> 00:26:37,320 WORKING FOR UNTIL THEY HAVE A 639 00:26:37,320 --> 00:26:39,040 THERAPY FOR THEMSELVES AS WELL. 640 00:26:39,040 --> 00:26:40,280 WITH THAT I'D LIKE TO THANK YOU 641 00:26:40,280 --> 00:26:40,840 FOR YOUR ATTENTION. 642 00:26:40,840 --> 00:26:43,080 I LOOK FORWARD TO QUESTIONS IN 643 00:26:43,080 --> 00:26:43,880 THE QUESTION AND ANSWER SESSION 644 00:26:43,880 --> 00:26:54,400 AND NOW I'D LIKE TO HAND IT OFF. 645 00:26:56,960 --> 00:26:59,280 >> THANK YOU, TERI AND I'D LIKE 646 00:26:59,280 --> 00:27:01,720 TO THANK THE ORGANIZERS. 647 00:27:01,720 --> 00:27:02,840 IT'S BEEN HIGH QUALITY ALREADY 648 00:27:02,840 --> 00:27:04,600 AND I'M LOOKING FORWARD TO THE 649 00:27:04,600 --> 00:27:07,360 ONGOING DISCUSSIONS TODAY. 650 00:27:07,360 --> 00:27:08,800 IT'S ALSO VERY NICE THAT 651 00:27:08,800 --> 00:27:10,320 PREVIOUS TALKS HAVE SET THE 652 00:27:10,320 --> 00:27:13,200 SCENE FOR WHAT I'M GOING TO TALK 653 00:27:13,200 --> 00:27:15,120 ABOUT EARLY DISEASE MONITORING 654 00:27:15,120 --> 00:27:17,440 IN THE ERA OF MODULATED THERAPY. 655 00:27:17,440 --> 00:27:20,720 I CAN'T TOUCH UPON ALL THE AREAS 656 00:27:20,720 --> 00:27:27,720 BECAUSE IT'S A RELATIVELY BROAD 657 00:27:27,720 --> 00:27:29,760 AREA TO COVER AND FOCUS ON LUNG 658 00:27:29,760 --> 00:27:32,440 DISEASE AND FUNCTIONAL MEASURES 659 00:27:32,440 --> 00:27:37,560 AND TOUCH A LITTLE BIT ABOUT 660 00:27:37,560 --> 00:27:48,000 MONITORING OF OTHER AREAS. 661 00:27:51,880 --> 00:27:54,360 SO WHAT ARE THE CHALLENGES IN 662 00:27:54,360 --> 00:27:56,120 EARLY DISEASE THERE'S SOME NOT 663 00:27:56,120 --> 00:27:58,480 CONSIDERED IN THE AGE GROUP WE 664 00:27:58,480 --> 00:27:59,480 USUALLY THINK ABOUT WHICH IS 665 00:27:59,480 --> 00:28:01,360 YOUNGER PEDIATRIC PATIENTS. 666 00:28:01,360 --> 00:28:03,880 WHAT WE SEE IN THESE PATIENTS IS 667 00:28:03,880 --> 00:28:06,120 SYMPTOMS ARE LIMITED OR ABSENT 668 00:28:06,120 --> 00:28:11,240 AND LUNG FUNCTION BASED ON 669 00:28:11,240 --> 00:28:16,400 TRADITIONAL MEASURES SPIROMETRY 670 00:28:16,400 --> 00:28:19,080 ARE MOSTLY NORMAL AND IN THIS 671 00:28:19,080 --> 00:28:20,560 SCENARIO WE HAVE PROGRESSION OF 672 00:28:20,560 --> 00:28:20,800 DISEASE. 673 00:28:20,800 --> 00:28:23,080 WE CAN'T SAY THEY HAVE NO 674 00:28:23,080 --> 00:28:24,240 SYMPTOMS WE DON'T HAVE TO BE 675 00:28:24,240 --> 00:28:25,320 AGGRESSIVE IN TERMS OF TREATMENT 676 00:28:25,320 --> 00:28:28,800 AND IN TERMS OF INTERVENTIONS. 677 00:28:28,800 --> 00:28:30,800 AS JP HAS POINTED OUT NICELY IN 678 00:28:30,800 --> 00:28:34,800 THE TALK YESTERDAY, THIS GROUP 679 00:28:34,800 --> 00:28:36,960 OF PATIENTS IN THIS CATEGORY 680 00:28:36,960 --> 00:28:38,760 WILL CONTINUE TO GROW AND 681 00:28:38,760 --> 00:28:41,360 CERTAINLY MORE GROW WITH THE 682 00:28:41,360 --> 00:28:42,680 INTRODUCTION AND BROADER 683 00:28:42,680 --> 00:28:43,360 INTRODUCTION OF HIGHLY EFFECTIVE 684 00:28:43,360 --> 00:28:53,560 MODULATORS. 685 00:29:07,320 --> 00:29:10,160 WE SEE THIS IN ASSESSMENT AND 686 00:29:10,160 --> 00:29:16,600 WITH SPIROMETRY WE HAVE THIS 687 00:29:16,600 --> 00:29:19,600 THIS MEASURED. 688 00:29:19,600 --> 00:29:21,120 IF WE LOOK AT INDIVIDUAL DISEASE 689 00:29:21,120 --> 00:29:23,160 PROGRESSION WHICH IS WHAT WE TRY 690 00:29:23,160 --> 00:29:24,840 TO AVOID, THAT HAS BEEN RATHER 691 00:29:24,840 --> 00:29:27,560 DIFFICULT TO PREDICT IN 692 00:29:27,560 --> 00:29:32,560 INDIVIDUAL PATIENT EVEN BEFORE 693 00:29:32,560 --> 00:29:36,680 HIGHLY EFFECTIVE MODULATED 694 00:29:36,680 --> 00:29:40,960 THERAPY AND THERE'S HOW MUCH 695 00:29:40,960 --> 00:29:51,520 DISEASE MODIFYING POTENTIAL HAS 696 00:29:51,800 --> 00:29:54,560 WITH EXPECT TO SEE IT AT A LOWER 697 00:29:54,560 --> 00:29:55,800 RATE BUT IS THAT THE CASE FOR 698 00:29:55,800 --> 00:29:59,520 THOSE WITH LIMITED OR NO LUNG 699 00:29:59,520 --> 00:29:59,880 DAMAGE? 700 00:29:59,880 --> 00:30:10,360 AND WE NEED AND LOOKING AT 701 00:30:23,280 --> 00:30:23,720 THERAPIES. 702 00:30:23,720 --> 00:30:27,640 TO HIGHLIGHT THE ISSUE WITH 703 00:30:27,640 --> 00:30:30,840 SPIROMETRY IF WE USE IT IT'S THE 704 00:30:30,840 --> 00:30:32,800 SWEET SPOT OF MODERATE DISEASE 705 00:30:32,800 --> 00:30:35,120 WHERE THIS HAS BEEN HELPFUL AND 706 00:30:35,120 --> 00:30:36,680 USEFUL. 707 00:30:36,680 --> 00:30:38,680 THAT'S USUALLY WHERE WE 708 00:30:38,680 --> 00:30:41,560 RECOMMEND THIS TO BE USED IN 709 00:30:41,560 --> 00:30:42,760 CLINICAL TRIALS AND MOST PIVOTAL 710 00:30:42,760 --> 00:30:43,800 CLINICAL TRIALS HAVE BEEN USED 711 00:30:43,800 --> 00:30:49,240 IN THIS GROUP OF PATIENTS WHO 712 00:30:49,240 --> 00:30:55,520 HAVE AN FE1 BETWEEN 30% AND 90%. 713 00:30:55,520 --> 00:30:57,440 THOSE WITH NORMAL FE 1 IS 714 00:30:57,440 --> 00:30:59,520 INCREASING AND YOU'LL SEE 715 00:30:59,520 --> 00:31:02,520 LIMITED RESPONSE AND THE TWO 716 00:31:02,520 --> 00:31:04,400 TECHNOLOGIES THAT SEEM TO BE 717 00:31:04,400 --> 00:31:06,920 PROMISING IS THE INDEX LCI AND 718 00:31:06,920 --> 00:31:07,080 MRI. 719 00:31:07,080 --> 00:31:08,160 FOCUS ON THAT. 720 00:31:08,160 --> 00:31:09,960 I'LL NOT FOCUS ON THE SEVERE 721 00:31:09,960 --> 00:31:20,280 DISEASE SPECTRUM. 722 00:31:43,800 --> 00:31:46,120 IN THE GREENISH AREAS YOU SEE 723 00:31:46,120 --> 00:31:47,880 PATIENTS WITH A NORMAL FE1 AND 724 00:31:47,880 --> 00:31:49,520 THAT'S THE CASE FOR THE MAJORITY 725 00:31:49,520 --> 00:31:51,520 OF PATIENTS THAT HAVE BEEN 726 00:31:51,520 --> 00:31:53,680 STUDIED IN THIS SETTING. 727 00:31:53,680 --> 00:31:55,200 IF WE LOOK BEFORE HIGHLY 728 00:31:55,200 --> 00:31:58,880 EFFECTIVE MODULATED THERAPY FOR 729 00:31:58,880 --> 00:32:00,280 SCHOOL AGE CHILDREN THAT WAS THE 730 00:32:00,280 --> 00:32:02,680 CASE FOR 70% OF THE PATIENTS IN 731 00:32:02,680 --> 00:32:03,240 PRESCHOOLERS IT'S HALF THE 732 00:32:03,240 --> 00:32:07,560 PATIENTS. 733 00:32:07,560 --> 00:32:09,240 THIS SLIDE SHOWS THE TECHNOLOGY 734 00:32:09,240 --> 00:32:12,440 AND HOW YOU MEASURE IT AND 735 00:32:12,440 --> 00:32:14,280 THERE'S DIFFERENT TRACES YOU CAN 736 00:32:14,280 --> 00:32:18,000 USE AND A WON'T GO IN THE 737 00:32:18,000 --> 00:32:21,200 DETAILS OF THE CONS FOR BOTH AND 738 00:32:21,200 --> 00:32:25,400 THE WASH OUT IS BEING USED WHERE 739 00:32:25,400 --> 00:32:27,920 YOU SWITCH A PATIENT FROM ROOM 740 00:32:27,920 --> 00:32:32,320 AIR TO IF YOU GO TO THE NEXT 741 00:32:32,320 --> 00:32:35,080 SLIDE AND USE 100% OXYGEN TO 742 00:32:35,080 --> 00:32:40,840 WASH OUT THE NITROGEN OF THE 743 00:32:40,840 --> 00:32:51,400 LUNG AND LCI IS THE TURN OVERS 744 00:32:58,440 --> 00:33:05,840 AND WE SAY 1/40 CONCENTRATION 745 00:33:05,840 --> 00:33:07,800 AND IN THIS OBSERVATIONAL STUY 746 00:33:07,800 --> 00:33:13,080 WITH DID A NUMBER OF YEARS AGO 747 00:33:13,080 --> 00:33:15,840 FUNDED BY NHLBI WE LOOK AT CF 748 00:33:15,840 --> 00:33:18,640 PATIENTS AND HOW TO CONTROL 749 00:33:18,640 --> 00:33:20,640 SYMPTOMS OF THE EVOLUTION OVER A 750 00:33:20,640 --> 00:33:22,720 ONE YEAR TIME PERIOD. 751 00:33:22,720 --> 00:33:27,480 WHAT WE SAW STUDY UNLESS THIS 752 00:33:27,480 --> 00:33:29,280 REMAINS RELATIVELY STABLE WE SEE 753 00:33:29,280 --> 00:33:33,040 A WORSENING IN LCI OVER THE 754 00:33:33,040 --> 00:33:36,240 ONE-YEAR PERIOD IN PRESCHOOL 755 00:33:36,240 --> 00:33:37,600 CHILDREN. 756 00:33:37,600 --> 00:33:38,640 THIS WAS NOT PICKED UP ON THE 757 00:33:38,640 --> 00:33:48,920 RIGHT-HAND SIDE. 758 00:33:50,440 --> 00:33:52,600 WHAT ABOUT THE PATIENTS BECOMING 759 00:33:52,600 --> 00:33:54,120 ASYMPTOMATIC AND I WON'T SHOW 760 00:33:54,120 --> 00:33:56,560 THE DATA THE PRESCHOOL STUDY 761 00:33:56,560 --> 00:33:58,280 BECAUSE WE HAVE RECENTLY DONE 762 00:33:58,280 --> 00:34:00,080 THIS IN ANOTHER COHORT IN THE CF 763 00:34:00,080 --> 00:34:02,880 FUNDED STUDY AT TWO CENTERS IN 764 00:34:02,880 --> 00:34:03,720 INDIANAPOLIS AND TORONTO. 765 00:34:03,720 --> 00:34:07,080 WE LOOKED AT PATIENTS WHEN THEY 766 00:34:07,080 --> 00:34:09,480 WERE SYMPTOMATIC AND HOW THE 767 00:34:09,480 --> 00:34:15,480 LUNG INDEX CHANGES AND HOW 768 00:34:15,480 --> 00:34:22,080 SYMPTOM S DID NOT SHOW CHANGE 769 00:34:22,080 --> 00:34:26,600 AND THE PREVIOUS DATA SHOWED 50% 770 00:34:26,600 --> 00:34:29,720 OF THE EVENTS ARE NOT ASSOCIATED 771 00:34:29,720 --> 00:34:36,240 WITH REDUCTION IN FE 1. 772 00:34:36,240 --> 00:34:37,920 HOWEVER YOU SEE AN INCREASE AND 773 00:34:37,920 --> 00:34:39,920 INDICATES IT MAY BE MORE 774 00:34:39,920 --> 00:34:43,040 SENSITIVE IN PICKING UP ACUTE 775 00:34:43,040 --> 00:34:46,160 WORSENING IN THIS SCENARIO WHERE 776 00:34:46,160 --> 00:34:47,560 PATIENTS ARE HERE AND WHICH 777 00:34:47,560 --> 00:34:51,480 COULD BE HELPFUL FOR THE 778 00:34:51,480 --> 00:34:52,400 CLINICAL SETTING IN DECIDING 779 00:34:52,400 --> 00:34:55,360 WHEN TO TREAT AND NOT TREAT. 780 00:34:55,360 --> 00:34:57,440 YOU MAY ARGUE I MAY NOT BE 781 00:34:57,440 --> 00:34:58,840 RELEVANT IN THE LONGER TERM 782 00:34:58,840 --> 00:35:00,360 OUTCOME AND PATIENTS COME BACK 783 00:35:00,360 --> 00:35:01,400 TO THEIR NORMAL BASELINE. 784 00:35:01,400 --> 00:35:03,400 YOU CAN SEE AT THE LOWER PART OF 785 00:35:03,400 --> 00:35:05,000 THE SLIDE THAT'S NOT THE CASE. 786 00:35:05,000 --> 00:35:09,160 IF WE LOOK AT 90% OF BASELINE 787 00:35:09,160 --> 00:35:10,880 RECOVERED AND THIS IS NOT 788 00:35:10,880 --> 00:35:12,000 NECESSARY THE BEST AIM WE HAVE 789 00:35:12,000 --> 00:35:13,920 BECAUSE IDEALLY WE WANT TO 790 00:35:13,920 --> 00:35:16,600 RECOVER 100% OF PREVIOUS LUNG 791 00:35:16,600 --> 00:35:18,680 FUNCTION. 792 00:35:18,680 --> 00:35:21,080 YOU CAN SEE FOR BOTH FE 1 AND 793 00:35:21,080 --> 00:35:26,600 THE INDEX AT THE NEXT VISIT 794 00:35:26,600 --> 00:35:31,800 THAT'S ONLY THE CASE FOR A 795 00:35:31,800 --> 00:35:33,440 PROPORTION OF THE PATIENT AND 796 00:35:33,440 --> 00:35:40,280 THAT IS LOWER FOR THE INDEX. 797 00:35:40,280 --> 00:35:44,320 IF YOU RELY ON IT ALONE IT MAY 798 00:35:44,320 --> 00:35:45,840 BE FAULTY THE PATIENT HAS 799 00:35:45,840 --> 00:35:46,240 RECOVERED. 800 00:35:46,240 --> 00:35:49,760 WHAT YOU SEE ALSO IS AS A 801 00:35:49,760 --> 00:35:54,640 MEASURE OF LCI SEEMS TO BE MORE 802 00:35:54,640 --> 00:35:56,200 VARIABLE AND WE ASK ASK THAT 803 00:35:56,200 --> 00:35:58,160 DRIVEN BY THE FACT OF WHAT WE 804 00:35:58,160 --> 00:36:02,280 SEE IN STABLE PATIENTS IS 805 00:36:02,280 --> 00:36:08,640 EVIDENCE OF WORSENING OF 806 00:36:08,640 --> 00:36:08,880 DISEASE. 807 00:36:08,880 --> 00:36:11,680 WHEN WE LOOKED AT THE DATA IT 808 00:36:11,680 --> 00:36:14,720 WAS SIMILAR IN HEALTH AND 809 00:36:14,720 --> 00:36:17,720 DISEASE WHAT WE SAW IN AND THE 810 00:36:17,720 --> 00:36:22,360 MAJORITY OF WHAT WE SAW WAS A 811 00:36:22,360 --> 00:36:23,920 SIGNAL OF CLINICAL WORSENING 812 00:36:23,920 --> 00:36:26,120 PICKED UP. 813 00:36:26,120 --> 00:36:27,960 AS A TEST IT'S NOT NECESSARILY 814 00:36:27,960 --> 00:36:28,800 MORE VARIABLE IT'S YOU PICK UP 815 00:36:28,800 --> 00:36:39,040 MORE SIGNALS. 816 00:36:44,440 --> 00:36:46,760 I WON'T GO IN THE STUDY BUT I'LL 817 00:36:46,760 --> 00:36:48,160 USE THIS SLIDE AS AN EXAMPLE OF 818 00:36:48,160 --> 00:36:49,640 WHAT WE MIGHT SEE IN THE FUTURE 819 00:36:49,640 --> 00:36:55,120 FOR PATIENTS IF WE LOOK AT 820 00:36:55,120 --> 00:36:57,560 INTERVENT 821 00:36:57,560 --> 00:36:59,520 INTERVENTIONS THAT MAY NOT BE AS 822 00:36:59,520 --> 00:37:04,200 EFFECTIVE AS HIGHLY EFFECTIVE 823 00:37:04,200 --> 00:37:06,440 MODULATORS AND THESE ARE 824 00:37:06,440 --> 00:37:16,880 PATIENTS THAT WERE INTRODUCED TO 825 00:37:16,880 --> 00:37:21,440 T 826 00:37:21,440 --> 00:37:21,720 T 827 00:37:21,720 --> 00:37:22,000 TRIKACTA. 828 00:37:22,000 --> 00:37:23,720 THERE WENT A SIGNIFICANT CHANGE 829 00:37:23,720 --> 00:37:24,920 IN THE LUNG CLEARANCE INDEX AND 830 00:37:24,920 --> 00:37:26,640 THE MAJOR THEME I WANTED TO 831 00:37:26,640 --> 00:37:29,760 POINT OUT IS THE EFFECT SIZE FOR 832 00:37:29,760 --> 00:37:33,760 LCI WAS THREE TIMES OF THAT FOR 833 00:37:33,760 --> 00:37:33,920 FE1. 834 00:37:33,920 --> 00:37:36,800 THIS IS IMPORTANT IF WE THINK OF 835 00:37:36,800 --> 00:37:41,880 PATIENTS HAVING OVERALL BETTER 836 00:37:41,880 --> 00:37:52,440 LUNG FUNCTION AND MAY NOT BE AS 837 00:37:53,680 --> 00:37:55,480 EFFECTIVE AS HIGHLY EFFECTIVE 838 00:37:55,480 --> 00:37:55,720 MODULATOR. 839 00:37:55,720 --> 00:37:57,920 SHOULD WE MOVE LCI TO THE 840 00:37:57,920 --> 00:37:58,120 CLINIC? 841 00:37:58,120 --> 00:38:02,360 THE PRO IS THE NEED IS THERE AND 842 00:38:02,360 --> 00:38:04,440 THE POPULATION OF F EV1 IS 843 00:38:04,440 --> 00:38:04,680 GROWING. 844 00:38:04,680 --> 00:38:08,160 IT'S ALSO NOT A SIMPLE TEST. 845 00:38:08,160 --> 00:38:14,000 IT'S TIME CONSUMING AND NOT 846 00:38:14,000 --> 00:38:14,760 REIMBURSED IN THE UNITED STATES. 847 00:38:14,760 --> 00:38:16,600 WE NEED TO FIND THE RIGHT 848 00:38:16,600 --> 00:38:21,600 BALANCE AND EVIDENCE TO MAKE 849 00:38:21,600 --> 00:38:32,040 SURE THIS HAS DATA AND IS 850 00:38:34,480 --> 00:38:38,080 IMPORTANT TO ENSURE THE BENEFIT 851 00:38:38,080 --> 00:38:39,400 OUTWEIGHS THE BURDEN. 852 00:38:39,400 --> 00:38:41,880 WE ARE CURRENTLY EXPLORING THAT 853 00:38:41,880 --> 00:38:44,440 IN A PLANNING STUDY SUPPORTED BY 854 00:38:44,440 --> 00:38:50,680 CFF TO SEE HOW CAN WE DO THIS 855 00:38:50,680 --> 00:38:56,080 BEST IN THE COMMUNITY AND LOOK 856 00:38:56,080 --> 00:38:58,000 AT FAMILIES AND PATIENTS AND 857 00:38:58,000 --> 00:38:59,680 CENTERS AND SEE WHAT IS FEASIBLE 858 00:38:59,680 --> 00:39:10,200 IN TERMS OF MOVING THIS FORWARD. 859 00:39:29,800 --> 00:39:32,280 THIS IS A PANEL AND THIS IS MORE 860 00:39:32,280 --> 00:39:33,400 EFFECTIVE IN FEV1. 861 00:39:33,400 --> 00:39:36,080 HOW CAN WE POTENTIALLY USE THIS 862 00:39:36,080 --> 00:39:37,200 IN THE FUTURE? 863 00:39:37,200 --> 00:39:38,800 AND ON THE NEXT SLIDE IS THE SET 864 00:39:38,800 --> 00:39:42,480 UP FOR THAT WHICH IS QUITE 865 00:39:42,480 --> 00:39:42,760 COMPLICATED. 866 00:39:42,760 --> 00:39:50,200 YOU NEED AN MRI MEASURE AND 867 00:39:50,200 --> 00:39:51,840 POLARIZER AND CURRENTLY NOT 868 00:39:51,840 --> 00:39:53,440 SOMETHING THAT CAN BE UTILIZED 869 00:39:53,440 --> 00:39:59,280 ACROSS MANY CENTERS IN NORTH 870 00:39:59,280 --> 00:40:01,000 AMERICA. 871 00:40:01,000 --> 00:40:03,280 ACCESS TO THE EQUIPMENT CHANGES 872 00:40:03,280 --> 00:40:08,160 OVER TIME AND OTHER MRI DO NOT 873 00:40:08,160 --> 00:40:10,400 REQUIRE HYPERPOLARIZED GASES AND 874 00:40:10,400 --> 00:40:11,920 MAY BE EASIER TO USE IN A 875 00:40:11,920 --> 00:40:22,200 BROADER COMMUNITY. 876 00:40:22,880 --> 00:40:26,320 THIS IS A LONGITUDINAL STUDY IN 877 00:40:26,320 --> 00:40:28,760 THE U.K. AND LOOKED AT DISEASE 878 00:40:28,760 --> 00:40:31,160 PROGRESSION IN PATIENTS WHO HAD 879 00:40:31,160 --> 00:40:33,000 RELATIVELY MILD LUNG DISEASE TO 880 00:40:33,000 --> 00:40:34,040 BEGIN WITH FOR TWO YEARS. 881 00:40:34,040 --> 00:40:38,200 THEY DID NOT FIND A CHANGE IN 882 00:40:38,200 --> 00:40:41,840 FEV1 OVER THE TIME PERIOD. 883 00:40:41,840 --> 00:40:44,400 THE SIGNAL THAT WAS THE 884 00:40:44,400 --> 00:40:46,360 STRONGEST WAS THE VENTILATION 885 00:40:46,360 --> 00:40:49,680 EFFECT PERCENTAGE WAS ONE OF THE 886 00:40:49,680 --> 00:40:51,960 OUTCOME MEASURES OF MRI THAT WAS 887 00:40:51,960 --> 00:40:55,080 SEEN ON HYPERPOLARIZED GAS MRI. 888 00:40:55,080 --> 00:40:57,480 THIS MAY POTENTIALLY BE THE MOST 889 00:40:57,480 --> 00:40:59,480 SENSITIVE TECHNIQUE AND STILL 890 00:40:59,480 --> 00:41:01,920 HAVE TO LEARN THIS TO FOLLOW 891 00:41:01,920 --> 00:41:03,280 PATIENTS OVER TIME AND THIS WILL 892 00:41:03,280 --> 00:41:04,840 BECOME IMPORTANT AS WE THINK OF 893 00:41:04,840 --> 00:41:08,680 HOW MUCH DISEASE PROGRESSION WE 894 00:41:08,680 --> 00:41:09,960 HAVE IN THE ERA OF HIGHLY 895 00:41:09,960 --> 00:41:11,840 EFFECTIVE MODULATORS. 896 00:41:11,840 --> 00:41:16,720 TO GIVE YOU A BIT OF A TEASER IN 897 00:41:16,720 --> 00:41:19,680 TERMS HOW THIS COULD BE USED IN 898 00:41:19,680 --> 00:41:22,160 AN INTERVENTIONAL STUDY IS A 899 00:41:22,160 --> 00:41:23,440 HIGH POINT STUDY WHICH IS A 900 00:41:23,440 --> 00:41:27,160 STUDY TO LOOK AT HOW THE IMAGING 901 00:41:27,160 --> 00:41:32,480 CHANGES IN PATIENTS INTRODUCED 902 00:41:32,480 --> 00:41:35,200 TO HIGHLY EFFECTIVE THERAPY. 903 00:41:35,200 --> 00:41:39,840 THEY'RE NOT COMPLETELY ABSENT WE 904 00:41:39,840 --> 00:41:43,240 HAVE TO LOOK INTO THIS MORE AND 905 00:41:43,240 --> 00:41:44,960 UNDERSTANDING THE LONG-TERM 906 00:41:44,960 --> 00:41:46,800 EFFECTS OF THESE MODULATORS ON 907 00:41:46,800 --> 00:41:57,000 VENTILATION. 908 00:42:01,560 --> 00:42:04,920 I TALKED ABOUT THE DISEASE AND 909 00:42:04,920 --> 00:42:06,960 AS DISCUSSED YESTERDAY 910 00:42:06,960 --> 00:42:08,800 INFORMATION WILL LIKELY CONTINUE 911 00:42:08,800 --> 00:42:13,560 TO BE A PROBLEM FOR PATIENTS 912 00:42:13,560 --> 00:42:15,360 WITH THE DISEASE. 913 00:42:15,360 --> 00:42:21,120 AND PATIENTS IN THE PEDIATRIC 914 00:42:21,120 --> 00:42:27,680 POPULATION I DON'T THINK 915 00:42:27,680 --> 00:42:31,960 SURVEILLANCE BRONCOSCOPIES WILL 916 00:42:31,960 --> 00:42:37,800 BE WIDELY USED IT HASN'T SHOWN 917 00:42:37,800 --> 00:42:48,200 TO BE HIGHLY EFFECTIVE 918 00:43:00,920 --> 00:43:05,080 I SUMMARIZED THE FOCUS ASPECTS 919 00:43:05,080 --> 00:43:06,800 OF MY TALK HERE. 920 00:43:06,800 --> 00:43:09,040 EARLY LUNG DISEASE IS NOT 921 00:43:09,040 --> 00:43:11,600 ADEQUATELY CAPTURED WITH ROUTINE 922 00:43:11,600 --> 00:43:13,880 MONITORING TOOLS AND CLINICAL 923 00:43:13,880 --> 00:43:15,920 MONITORING IS CHALLENGING AS 924 00:43:15,920 --> 00:43:17,600 SYMPTOMS ARE LATER RATHER THAN 925 00:43:17,600 --> 00:43:20,040 EARLY INDICATORS AND WE NEED 926 00:43:20,040 --> 00:43:23,480 TOOLS TO FIND THE RIGHT BALANCE 927 00:43:23,480 --> 00:43:28,680 OF EARLY INTERVENTION AND 928 00:43:28,680 --> 00:43:34,920 TREATMENT AND MRI MAY HAVE 929 00:43:34,920 --> 00:43:37,680 DEFINED DISEASE PROGRESSION AND 930 00:43:37,680 --> 00:43:41,040 THE LACK THEREOF WHICH IS AS 931 00:43:41,040 --> 00:43:43,920 IMPORTANT IN THE ERA OF HIGHLY 932 00:43:43,920 --> 00:43:44,840 EFFECTIVE MODULATOR AND COULD 933 00:43:44,840 --> 00:43:46,000 FACILITATE CLINICAL DECISION 934 00:43:46,000 --> 00:43:48,000 MAKING AND THE LATER I FEEL 935 00:43:48,000 --> 00:43:49,360 STILL NEEDS TO BE PROVEN. 936 00:43:49,360 --> 00:43:52,760 WE ALSO NEED TO DEFINE HOW 937 00:43:52,760 --> 00:43:54,880 FREQUENT MONITORING IS FOR A 938 00:43:54,880 --> 00:43:56,840 CURE, ROUTINELY OR ONLY AT TIMES 939 00:43:56,840 --> 00:43:57,680 OF SYMPTOMS? 940 00:43:57,680 --> 00:44:08,160 THESE ARE IMPORTANT QUESTIONS. 941 00:44:08,720 --> 00:44:13,960 AND ONE MENTION OF PANCREATIC 942 00:44:13,960 --> 00:44:16,600 AND LIVER DISEASE ONE EFFECTIVE 943 00:44:16,600 --> 00:44:19,400 WITH HIGHLY EFFECTIVE MODULATOR. 944 00:44:19,400 --> 00:44:21,120 THE KNOWLEDGE IS STILL LACKING 945 00:44:21,120 --> 00:44:27,640 WHETHER THIS IS THE CASE FOR ALL 946 00:44:27,640 --> 00:44:30,400 CFTR MUTATIONS. 947 00:44:30,400 --> 00:44:36,240 AND LOWER NUMBER OF PATIENTS 948 00:44:36,240 --> 00:44:39,720 HAVING INEFFICIENT AND WE'LL SEE 949 00:44:39,720 --> 00:44:42,600 WHETHER THIS IS ALSO ASSOCIATED 950 00:44:42,600 --> 00:44:47,480 WITH OTHER COMPLICATIONS SUCH AS 951 00:44:47,480 --> 00:44:48,280 PANCREATITIS AND TRACKING LIVER 952 00:44:48,280 --> 00:44:50,880 DISEASE HAS BEEN A CHALLENGE. 953 00:44:50,880 --> 00:44:59,000 ON ONE HAND IT COULD BE 954 00:44:59,000 --> 00:44:59,680 EFFICAC 955 00:44:59,680 --> 00:45:00,000 EFFICACIOUS. 956 00:45:00,000 --> 00:45:02,760 ON THE OTHER HAND IT CAN MAKE IT 957 00:45:02,760 --> 00:45:03,280 MORE DIFFICULT. 958 00:45:03,280 --> 00:45:04,440 HERE'S RESEARCH OPPORTUNITIES. 959 00:45:04,440 --> 00:45:14,880 I ALLUDED TO SOME ALREADY. 960 00:45:24,520 --> 00:45:30,360 WE NEED ALTERNATIVE MEASURES TO 961 00:45:30,360 --> 00:45:33,200 SPUTUM AND FOR THE OTHER ASPECTS 962 00:45:33,200 --> 00:45:36,880 OF PANCREATIC DISEASE AS WELL AS 963 00:45:36,880 --> 00:45:37,880 LIVER DISEASE THERE'S LOTS OF 964 00:45:37,880 --> 00:45:40,560 GAPS AND I'M NOTE REALLY THE 965 00:45:40,560 --> 00:45:42,840 EXPERT IN THIS FIELD BUT I CAN 966 00:45:42,840 --> 00:45:44,640 SAY IT'S BEEN QUITE CHALLENGING 967 00:45:44,640 --> 00:45:47,080 IN TERMS OF MONITORING LIVER 968 00:45:47,080 --> 00:45:49,080 DISEASE EVEN BEFORE WE HAVE THE 969 00:45:49,080 --> 00:45:53,120 ISSUE OF HIGHLY EFFECTIVE 970 00:45:53,120 --> 00:45:53,840 MODULATORS. 971 00:45:53,840 --> 00:46:04,400 SO WITH THAT TO MY FINAL SLIDE. 972 00:46:07,840 --> 00:46:09,640 AND THE MEASURES CAN HELP 973 00:46:09,640 --> 00:46:10,920 IDENTIFY SUBGROUPS OF PATIENT TO 974 00:46:10,920 --> 00:46:14,760 PREDICT IN THE FUTURE TO SAY 975 00:46:14,760 --> 00:46:18,840 SOME MAY NOT NEED MORE INTENSE 976 00:46:18,840 --> 00:46:19,640 THERAPIES OR OTHERS AND WITH 977 00:46:19,640 --> 00:46:20,600 THAT I THANK YOU FOR YOUR 978 00:46:20,600 --> 00:46:22,640 ATTENTION AND HAPPY TO TAKE 979 00:46:22,640 --> 00:46:24,160 QUESTIONS LATER ON BUT BEFORE WE 980 00:46:24,160 --> 00:46:31,800 DO QUESTIONS, I HAND IT OVER TO 981 00:46:31,800 --> 00:46:41,880 JIM. 982 00:47:11,840 --> 00:47:14,080 >> I'VE USED GRANTS BY THE NIH 983 00:47:14,080 --> 00:47:18,640 AND WE'LL START TALK ABOUT ACUTE 984 00:47:18,640 --> 00:47:20,440 RESPIRATORY VIRAL INFECTIONS IN 985 00:47:20,440 --> 00:47:20,800 CYSTIC FIBROSIS. 986 00:47:20,800 --> 00:47:23,520 THESE ARE ASSOCIATED WITH HALF. 987 00:47:23,520 --> 00:47:28,280 MOST COMMONLY ASSOCIATED WITH CF 988 00:47:28,280 --> 00:47:33,040 ARE RHINO VIRUS AND INFLUENZA A 989 00:47:33,040 --> 00:47:33,400 VIRUS. 990 00:47:33,400 --> 00:47:35,800 CYSTIC FIBROSIS WILL EXPERIENCE 991 00:47:35,800 --> 00:47:37,360 ONE TO TWO RESPIRATORY 992 00:47:37,360 --> 00:47:38,240 COMPLICATIONS PER YEAR BUT THE 993 00:47:38,240 --> 00:47:40,200 SYMPTOMS ARE OFTEN MORE SEVERE 994 00:47:40,200 --> 00:47:43,000 INCLUDING INCREASES IN 995 00:47:43,000 --> 00:47:43,880 HOSPITALIZATION, INCREASED 996 00:47:43,880 --> 00:47:47,240 RESPIRATORY SYMPTOMS, INCREASED 997 00:47:47,240 --> 00:47:49,880 USE OF ANTIBIOTICS AND 998 00:47:49,880 --> 00:47:51,040 REDUCTIONS IN PULMONARY 999 00:47:51,040 --> 00:47:51,280 FUNCTION. 1000 00:47:51,280 --> 00:47:53,840 THESE VIRUS DETECTED BY OUR 1001 00:47:53,840 --> 00:47:54,680 CELLS THROUGH PATTERN 1002 00:47:54,680 --> 00:47:58,640 RECOGNITION RECEPTORS THAT THEN 1003 00:47:58,640 --> 00:48:01,320 INDUCE INFLAMMATORY RESPONSES AS 1004 00:48:01,320 --> 00:48:03,920 WELL AS INITIATING INTERFERON 1005 00:48:03,920 --> 00:48:04,160 SIGNALING 1006 00:48:04,160 --> 00:48:07,560 THE CYTOKINES SIGNAL THROUGH THE 1007 00:48:07,560 --> 00:48:10,920 RECEPTOR AND TURN ON A SUITE OF 1008 00:48:10,920 --> 00:48:13,440 GENES THAT INITIATE THE 1009 00:48:13,440 --> 00:48:15,160 ANTIVIRAL PROGRAM TO CARRY OUT 1010 00:48:15,160 --> 00:48:16,160 THE DEFENSE AGAINST VIRUS. 1011 00:48:16,160 --> 00:48:17,960 WHAT WE KNOW IN CYSTIC FIBROSIS 1012 00:48:17,960 --> 00:48:20,520 THERE'S REDUCED INTERFERON 1013 00:48:20,520 --> 00:48:21,640 SECRETION DURING VIRAL 1014 00:48:21,640 --> 00:48:23,360 INFECTIONS AND THERE'S AN 1015 00:48:23,360 --> 00:48:25,400 ALTERATION OF INITIATION OF THE 1016 00:48:25,400 --> 00:48:27,080 PROGRAM AND DIFFERENTIAL SUITE 1017 00:48:27,080 --> 00:48:30,200 OF GENES ACTIVATED DURING CF 1018 00:48:30,200 --> 00:48:33,760 LEADING TO POOR CONTROL OF VIRAL 1019 00:48:33,760 --> 00:48:34,320 INFECTION. 1020 00:48:34,320 --> 00:48:36,080 THE GAPS MOVING FORWARD WITH 1021 00:48:36,080 --> 00:48:40,920 MODULATORS IF MODULATORS IMPROVE 1022 00:48:40,920 --> 00:48:42,760 THE ANTIVIRAL IMMUNITY DURING 1023 00:48:42,760 --> 00:48:45,680 THESE EXACERBATIONS WITH PEOPLE 1024 00:48:45,680 --> 00:48:48,000 WITH CF AND DO MODULATORS REDUCE 1025 00:48:48,000 --> 00:48:50,640 EXACERBATIONS AND REDUCE 1026 00:48:50,640 --> 00:48:52,240 SEVERITY AND HOSPITALIZATIONS OF 1027 00:48:52,240 --> 00:48:53,320 THE EVENTS? 1028 00:48:53,320 --> 00:48:55,960 THINKING OF VIRAL AND BACTERIAL 1029 00:48:55,960 --> 00:48:56,280 INTERACTIONS. 1030 00:48:56,280 --> 00:48:59,520 WHAT WE KNOW IS VIRAL INFECTION 1031 00:48:59,520 --> 00:49:01,880 ASSOCIATED WITH INCREASES IN 1032 00:49:01,880 --> 00:49:03,920 ANTIBODIES AND CYSTIC FIBROSIS 1033 00:49:03,920 --> 00:49:08,040 PATIENTS. 1034 00:49:08,040 --> 00:49:18,600 INCREASED PSEUDOMONIS INFECTIONS 1035 00:49:21,800 --> 00:49:26,160 AND IF CHANGE HAPPENING DURING 1036 00:49:26,160 --> 00:49:26,640 EXACERBATIONS. 1037 00:49:26,640 --> 00:49:27,720 IT'S BEEN A MAJOR FOCUS. 1038 00:49:27,720 --> 00:49:33,760 WE STARTED BY USING A MODEL 1039 00:49:33,760 --> 00:49:44,040 SYSTEM AND THEY'RE HARD TO CLEAR 1040 00:49:44,040 --> 00:49:45,840 BY THE IMMUNE SYSTEM AND WE 1041 00:49:45,840 --> 00:49:48,160 THINK ASSOCIATED WITH THE 1042 00:49:48,160 --> 00:49:49,120 DEVELOPMENT OF CHRONIC 1043 00:49:49,120 --> 00:49:50,280 INFECTIONS IN CF. 1044 00:49:50,280 --> 00:49:55,120 WE USE A MODEL SYSTEM WHERE WE 1045 00:49:55,120 --> 00:49:59,920 GROW HUMAN CELLS AND SIMILAR TO 1046 00:49:59,920 --> 00:50:02,640 WHAT WE SEE IN VIVO. 1047 00:50:02,640 --> 00:50:06,560 IF WE GIVE A PRECEDING VIRAL 1048 00:50:06,560 --> 00:50:08,400 INFECTION AND HOW IT MIGHT 1049 00:50:08,400 --> 00:50:11,800 IMPACT BIO GENESIS WE SEE THIS 1050 00:50:11,800 --> 00:50:14,280 AS A TOP-DOWN VIEW AND SEE GREEN 1051 00:50:14,280 --> 00:50:15,720 CLUSTERS OF BACTERIA AND 1052 00:50:15,720 --> 00:50:18,360 AGGREGATES FORMING IN OUR MODEL 1053 00:50:18,360 --> 00:50:18,680 SYSTEM. 1054 00:50:18,680 --> 00:50:21,840 IF WE GIVE A PRECEDING VIRAL 1055 00:50:21,840 --> 00:50:23,400 INFECTION WE SEE A DRAMATIC 1056 00:50:23,400 --> 00:50:25,800 ENHANCEMENT IN THE FORMATION, 1057 00:50:25,800 --> 00:50:26,600 INCREASES IN THE GREEN CLUSTERS 1058 00:50:26,600 --> 00:50:36,840 OF BACTERIA. 1059 00:50:37,280 --> 00:50:47,760 AND IT CREATES OTHER PATHOGENS. 1060 00:50:49,640 --> 00:50:52,440 AND WHAT HAS BEEN CHARACTERIZED 1061 00:50:52,440 --> 00:50:58,240 IS THAT THERE ARE INEFFECTIVE 1062 00:50:58,240 --> 00:51:01,640 ANTIMICROBIAL RESPONSES IN 1063 00:51:01,640 --> 00:51:02,040 CYSTIC FIBROSIS. 1064 00:51:02,040 --> 00:51:05,720 OUR GROUP HAS PUBLISHED 1065 00:51:05,720 --> 00:51:07,640 DYSREGULATION IN NUTRITIONAL 1066 00:51:07,640 --> 00:51:12,280 IMMUNITY ALLOWING IRON THAT'S A 1067 00:51:12,280 --> 00:51:15,240 NUTRIENT FORCE TO CREATE 1068 00:51:15,240 --> 00:51:17,080 BACTERIAL GROWTH AND THERE'S 1069 00:51:17,080 --> 00:51:19,480 METABOLIC CHANGES IN THE 1070 00:51:19,480 --> 00:51:20,360 RESPIRATORY EPITHELIAL DURING 1071 00:51:20,360 --> 00:51:21,760 VIRUS INFECTION THAT CAN SERVE 1072 00:51:21,760 --> 00:51:30,840 AS A SOURCE OF HE METABOLITES 1073 00:51:30,840 --> 00:51:41,320 THAT CAN EFFECT PSEUDOMONAS 1074 00:51:41,680 --> 00:51:41,920 MODULATORS. 1075 00:51:41,920 --> 00:51:44,640 IT'S NOT CLEAR WHICH WILL END UP 1076 00:51:44,640 --> 00:51:45,280 BEING CYSTIC FIBROSIS SPECIFIC. 1077 00:51:45,280 --> 00:51:46,960 IN OUR WORK WE SEE THE 1078 00:51:46,960 --> 00:51:49,480 MAGNITUDES OF THE DYSFUNCTIONS 1079 00:51:49,480 --> 00:51:51,480 IN NUTRITIONAL IMMUNITY OF 1080 00:51:51,480 --> 00:51:58,800 METABOLISM ARE MORE MAGNIFIED 1081 00:51:58,800 --> 00:52:00,960 AND THINK IT WILL BE IMPORTANT 1082 00:52:00,960 --> 00:52:02,920 TO THINK ABOUT ADJUNCTIVE 1083 00:52:02,920 --> 00:52:05,080 THERAPIES THAT TARGET THE 1084 00:52:05,080 --> 00:52:06,200 DISRESOLUTION LIKE NUTRITIONAL 1085 00:52:06,200 --> 00:52:08,760 IMMUNITY AND METABOLISM AS MAYBE 1086 00:52:08,760 --> 00:52:10,440 SECONDARY THERAPIES IN ADDITION 1087 00:52:10,440 --> 00:52:12,560 TO MODULATED THERAPY. 1088 00:52:12,560 --> 00:52:14,920 THE STUDIES HAVE BEEN DONE 1089 00:52:14,920 --> 00:52:16,920 PRIMARILY HOW THEY IMPACT ONE 1090 00:52:16,920 --> 00:52:18,840 MICROBE OR BACTERIA. 1091 00:52:18,840 --> 00:52:21,080 WE KNOW IN CYSTIC FIBROSIS 1092 00:52:21,080 --> 00:52:21,920 INFECTIONS IN THE RESPIRATORY 1093 00:52:21,920 --> 00:52:24,200 TRACT ARE POLY MICROBIAL. 1094 00:52:24,200 --> 00:52:25,720 MY GROUP IS INTERESTED IN TRYING 1095 00:52:25,720 --> 00:52:28,920 TO UNDERSTAND HOW VIRAL 1096 00:52:28,920 --> 00:52:30,360 INFECTIONS SHAPE THE ENTIRE 1097 00:52:30,360 --> 00:52:32,520 COMMUNITY IN THE RESPIRATORY 1098 00:52:32,520 --> 00:52:36,280 TRACT AND ARE INTERESTED IN 1099 00:52:36,280 --> 00:52:39,840 COLLABORATION WITH STELLA LEE AN 1100 00:52:39,840 --> 00:52:41,120 OTOLARYNGOLOGIST AND NOW MOVED 1101 00:52:41,120 --> 00:52:42,600 TO BRIGHAM AND HAVE LOOKED AT 1102 00:52:42,600 --> 00:52:45,200 HOW VIRAL INFECTIONS IMPACT 1103 00:52:45,200 --> 00:52:48,160 MICROBIAL COMMUNITIES IN THE 1104 00:52:48,160 --> 00:52:49,760 UPPER AND LOWER RESPIRATORY 1105 00:52:49,760 --> 00:52:49,960 TRACT. 1106 00:52:49,960 --> 00:52:51,200 PART OF THE INTEREST IS THE 1107 00:52:51,200 --> 00:52:52,680 GROWING AC ACCEPTANCE IN OUR 1108 00:52:52,680 --> 00:52:54,440 FIELD THE UPPER RESPIRATORY 1109 00:52:54,440 --> 00:52:56,920 TRACT MAY SERVE AS A RESERVOIR 1110 00:52:56,920 --> 00:52:58,160 FOR LOWER RESPIRATORY TRACT 1111 00:52:58,160 --> 00:52:59,640 INFECTIONS MOVING FORWARD. 1112 00:52:59,640 --> 00:53:01,520 WE'VE BECOME INTERESTED IN HOW 1113 00:53:01,520 --> 00:53:02,640 VIRUSES MAY CHANGE THE 1114 00:53:02,640 --> 00:53:03,960 COMMUNITIES IN BOTH COMPARTMENTS 1115 00:53:03,960 --> 00:53:07,040 AND HOW VIRUSES MAY CHANGE 1116 00:53:07,040 --> 00:53:08,960 COMMUNICATION BETWEEN THESE TWO 1117 00:53:08,960 --> 00:53:11,120 COMPARTMENTS IN A STUDY I'M 1118 00:53:11,120 --> 00:53:12,440 GOING EXPLAIN. 1119 00:53:12,440 --> 00:53:16,520 THE WORK HAS BEEN DONE BY TWO 1120 00:53:16,520 --> 00:53:18,040 POST-DOCTORAL FELLOWS IN MY LAP 1121 00:53:18,040 --> 00:53:18,720 AS WELL AS A TEAM AT THE 1122 00:53:18,720 --> 00:53:29,160 UNIVERSITY OF PITTSBURGH. 1123 00:53:42,920 --> 00:53:49,400 WE WE STUDIED A GROUP AND THEY 1124 00:53:49,400 --> 00:53:52,760 HAD SINUS AND SPUTUM SAMPLES TO 1125 00:53:52,760 --> 00:53:56,680 GET SINUS AND SPUTUM SAMPLES AND 1126 00:53:56,680 --> 00:53:59,080 HAVE SWABS FOR MICROBIOME AND 1127 00:53:59,080 --> 00:54:03,000 COLLECT SINUS WASHES AND SPUTUM 1128 00:54:03,000 --> 00:54:08,200 TO ANALYZE CYTOKINES UNDERSTAND 1129 00:54:08,200 --> 00:54:09,920 WHAT IT'S GOING ON DURING THESE 1130 00:54:09,920 --> 00:54:15,960 PERIODS OF SURVEILLANCE AND 1131 00:54:15,960 --> 00:54:16,960 CAPTURE THE PSEUDOMONAS 1132 00:54:16,960 --> 00:54:19,160 POPULATION TO LOOK AT THE 1133 00:54:19,160 --> 00:54:20,120 PSEUDOMONAS POPULATION AND HOW 1134 00:54:20,120 --> 00:54:29,440 THE POPULATIONS OF PSEUDO MOW -- 1135 00:54:29,440 --> 00:54:32,080 PSEUDOMONAS SAMPLING AND DO WE 1136 00:54:32,080 --> 00:54:35,360 SEE CHANGES IN MICROBIAL 1137 00:54:35,360 --> 00:54:38,040 COMMUNITIES AT THE PSEUDOMONAS 1138 00:54:38,040 --> 00:54:40,480 POPULATION LEVEL AND DID A 1139 00:54:40,480 --> 00:54:44,840 MODULATOR STUDY BECAUSE TRIKAFTA 1140 00:54:44,840 --> 00:54:46,640 WAS ROLLED OUT AND LOOKED AT IT 1141 00:54:46,640 --> 00:54:48,840 BEFORE AND AFTER THE INITIATION 1142 00:54:48,840 --> 00:54:50,960 OF MODULATORS IN OUR PATIENT 1143 00:54:50,960 --> 00:54:51,240 POPULATION. 1144 00:54:51,240 --> 00:54:53,240 SO WHEN WE LOOK FIRST AT 1145 00:54:53,240 --> 00:54:54,800 RESPIRATORY VIRAL DISTRIBUTION. 1146 00:54:54,800 --> 00:54:57,920 WE SEE INFECTION DETECTED MORE 1147 00:54:57,920 --> 00:54:59,040 FREQUENTLY IN THE UPPER 1148 00:54:59,040 --> 00:55:03,560 RESPIRATORY TRACT AND THE 1149 00:55:03,560 --> 00:55:08,920 DIVERSITY IS MORE DIVERSE IN THE 1150 00:55:08,920 --> 00:55:15,520 UPPER RESPIRATORY TRACT. 1151 00:55:15,520 --> 00:55:19,040 WE CAN LOOK AT 16S SEQUENCING. 1152 00:55:19,040 --> 00:55:21,320 ONE PATIENT'S LONGITUDINAL 1153 00:55:21,320 --> 00:55:24,080 SERIES IS GOING FROM LEFT TO 1154 00:55:24,080 --> 00:55:24,400 RIGHT. 1155 00:55:24,400 --> 00:55:26,400 SINUS SAMPLES ARE IN THE TOP 1156 00:55:26,400 --> 00:55:28,120 PANEL AND BOTTOM PANEL ARE 1157 00:55:28,120 --> 00:55:30,240 SPUTUM SAMPLES. 1158 00:55:30,240 --> 00:55:32,320 I'M SHOWING THE RELATIVE 1159 00:55:32,320 --> 00:55:34,280 ABUNDANCE OF THE BACTERIAL 1160 00:55:34,280 --> 00:55:35,840 COMMUNITY MEMBERS AND THE DOTS 1161 00:55:35,840 --> 00:55:38,920 ARE ASSESSMENTS OF VIRAL 1162 00:55:38,920 --> 00:55:40,080 INFECTION STATUS WITH COLORED 1163 00:55:40,080 --> 00:55:42,600 DOTS WHEN WE SEE A VIRUS 1164 00:55:42,600 --> 00:55:42,880 INFECTION. 1165 00:55:42,880 --> 00:55:47,920 FIRST YOU MIGHT NOTICE IN SOME 1166 00:55:47,920 --> 00:55:54,160 VISITS WE SEE SINUS VIRAL 1167 00:55:54,160 --> 00:55:58,520 INFECTIONS. 1168 00:55:58,520 --> 00:56:00,920 AND IN SOME CASES WE SEE 1169 00:56:00,920 --> 00:56:01,680 DRAMATIC CHANGES IN THE 1170 00:56:01,680 --> 00:56:02,600 MICROBIAL COMMUNITIES WITH THE 1171 00:56:02,600 --> 00:56:05,040 VIRAL INFECTIONS BUT IN OTHER 1172 00:56:05,040 --> 00:56:07,280 CASES MORE SUBTLE CHANGES IN THE 1173 00:56:07,280 --> 00:56:09,920 MICROBAL COMMUNITIES AND IT WILL 1174 00:56:09,920 --> 00:56:11,800 BE IMPORTANT STUDYING THE 1175 00:56:11,800 --> 00:56:13,040 LONGITUDINAL STUDIES AND 1176 00:56:13,040 --> 00:56:15,920 UNDERSTANDING HOW VIRUSES MAY BE 1177 00:56:15,920 --> 00:56:18,280 IMPACTING MICROBIAL COMMUNITY 1178 00:56:18,280 --> 00:56:18,560 CHANGES. 1179 00:56:18,560 --> 00:56:22,280 HERE'S ENTIRE PATIENT COHORT WE 1180 00:56:22,280 --> 00:56:23,840 HAVE 39 PATIENTS WE'VE NOW 1181 00:56:23,840 --> 00:56:24,120 FOLLOWED. 1182 00:56:24,120 --> 00:56:25,360 WE HAVE PAIRED SAMPLES FOR THE 1183 00:56:25,360 --> 00:56:27,280 MAJORITY OF THE PATIENTS AND THE 1184 00:56:27,280 --> 00:56:28,880 MAJORITY OF THEIR VISITS. 1185 00:56:28,880 --> 00:56:31,800 WE HAVE A NUMBER OF THE FILLED 1186 00:56:31,800 --> 00:56:33,800 IN CIRCLES IN RED DOTS IS 1187 00:56:33,800 --> 00:56:36,800 SHOWING VIRAL INFECTIONS 1188 00:56:36,800 --> 00:56:38,200 DETECTED AND THE PEACH BLOCKS 1189 00:56:38,200 --> 00:56:40,080 ARE WHEN PATIENTS WERE ENROLLED 1190 00:56:40,080 --> 00:56:42,200 IN TRIKAFTA. 1191 00:56:42,200 --> 00:56:44,520 USING THIS COHORT WE'LL BE ABLE 1192 00:56:44,520 --> 00:56:46,720 TO ASK WHEN MODULATORS WERE 1193 00:56:46,720 --> 00:56:50,040 ROLLED OUT DO WE SEE CHANGES IN 1194 00:56:50,040 --> 00:56:50,800 THE FREQUENT OF RESPIRATORY 1195 00:56:50,800 --> 00:56:52,120 VIRAL INFECTION. 1196 00:56:52,120 --> 00:56:54,080 I WANT TO CAUTION INTERPRETATION 1197 00:56:54,080 --> 00:56:55,760 OF THE DATA IN THE CURRENT 1198 00:56:55,760 --> 00:56:59,640 COHORT AS MANY FOLKS HAVE 1199 00:56:59,640 --> 00:57:01,120 ALREADY SAID THE ROLL OUT 1200 00:57:01,120 --> 00:57:02,040 CORRESPONDED BIG THE PANDEMIC 1201 00:57:02,040 --> 00:57:03,400 AND SOCIAL DISTANCING AND 1202 00:57:03,400 --> 00:57:03,640 MASKING. 1203 00:57:03,640 --> 00:57:05,600 IT'S GOING TO BE HARD FOR US TO 1204 00:57:05,600 --> 00:57:07,840 PULL APART THE CONTRIBUTIONS OF 1205 00:57:07,840 --> 00:57:13,440 THE PANDEMIC AND MODULATORS. 1206 00:57:13,440 --> 00:57:16,040 WE MAY NEED TO STUDY THESE GOING 1207 00:57:16,040 --> 00:57:17,640 FORWARD BUT WE CAN ASK QUESTION 1208 00:57:17,640 --> 00:57:18,800 ARE IMPORTANT AND WE DON'T KNOW 1209 00:57:18,800 --> 00:57:21,480 ALL THE ANSWERS BUT DO VIRAL 1210 00:57:21,480 --> 00:57:24,240 INFECTIONS SHAPE MICROBIAL 1211 00:57:24,240 --> 00:57:28,200 COMMUNITIES AND DO MODULATORS 1212 00:57:28,200 --> 00:57:30,080 IMPACT THAT DIVERSITY AND DO WE 1213 00:57:30,080 --> 00:57:32,360 SEE SHIFTS WITH ACUTE 1214 00:57:32,360 --> 00:57:34,600 RESPIRATORY VIRAL INFECTION AND 1215 00:57:34,600 --> 00:57:43,920 DO MODULATORS IMPACT THAT. 1216 00:57:43,920 --> 00:57:51,920 NOW IF WE FOCUS IN ON 1217 00:57:51,920 --> 00:57:57,800 PSEUDOMONAS FORMS AND WE WERE 1218 00:57:57,800 --> 00:57:59,320 INTERESTED IN UNDERSTANDING THE 1219 00:57:59,320 --> 00:58:04,560 COMMUNICATION OF THE MICROBIAL 1220 00:58:04,560 --> 00:58:07,920 COMMUNITIES PARTICULARLY THE 1221 00:58:07,920 --> 00:58:08,560 PSEUDOMONAS ARE THERE SHARED 1222 00:58:08,560 --> 00:58:14,880 STRAINS BETWEEN THE COMMUNITIES. 1223 00:58:14,880 --> 00:58:19,840 IF WE LOOK AT THE POPULATION OF 1224 00:58:19,840 --> 00:58:22,040 PSEUDOMONAS WE SEE THAT THE 1225 00:58:22,040 --> 00:58:25,720 POPULATIONS OF PSEUDOMONAS IF WE 1226 00:58:25,720 --> 00:58:28,640 ORIENT THEM WITH THE THREE CLADS 1227 00:58:28,640 --> 00:58:30,400 AND THE ONE PATIENT I'M SHOWING 1228 00:58:30,400 --> 00:58:31,720 IN THIS PARTICULAR FIGURE ALL 1229 00:58:31,720 --> 00:58:33,480 CLUSTER TOGETHER SUGGESTING THIS 1230 00:58:33,480 --> 00:58:36,520 IS A CLONAL LINEAGE OF 1231 00:58:36,520 --> 00:58:37,360 PSEUDOMONAS DETECTED IN THE 1232 00:58:37,360 --> 00:58:39,240 PATIENT AND BOTH IN THE UPPER 1233 00:58:39,240 --> 00:58:41,800 AND LOWER RESPIRATORY TRACT 1234 00:58:41,800 --> 00:58:42,880 SHOWING SIMILAR STRAINS. 1235 00:58:42,880 --> 00:58:45,240 IF WE THEN ASK QUESTIONS ABOUT 1236 00:58:45,240 --> 00:58:47,000 ARE THESE STRAINS MOVING BETWEEN 1237 00:58:47,000 --> 00:58:48,880 THE UPPER AND LOWER RESPIRATORY 1238 00:58:48,880 --> 00:58:54,680 TRACT BRUISE WE HAVE PSEUDOMONAS 1239 00:58:54,680 --> 00:58:55,920 POPULATIONS WE CAN LOOK AT 1240 00:58:55,920 --> 00:58:57,000 VARIANTS THAT TRACT TOGETHER 1241 00:58:57,000 --> 00:58:59,680 THAT SHOW UP IN ONE COMPARTMENT 1242 00:58:59,680 --> 00:59:05,160 AND MOVE TO BOTH COMPARTMENTS. 1243 00:59:05,160 --> 00:59:07,720 WE SEE HERE WITH ONE LINEAGE OR 1244 00:59:07,720 --> 00:59:09,120 ONE CLUSTER OF VARIANTS THAT 1245 00:59:09,120 --> 00:59:14,160 SHOWS UP FIRST IN SIGN -- 1246 00:59:14,160 --> 00:59:16,080 SINUSES THIS IS KNOWN IN THE 1247 00:59:16,080 --> 00:59:18,240 LITERATURE OF THE SINUS SEARCH 1248 00:59:18,240 --> 00:59:20,320 AS A RESERVOIR FOR LOWER 1249 00:59:20,320 --> 00:59:21,840 RESPIRATORY TRACT INFECTIONS AND 1250 00:59:21,840 --> 00:59:23,160 WE SEE IN THE PATIENT POPULATION 1251 00:59:23,160 --> 00:59:26,200 IF WE LOOK WE SEE A CLUSTER OF 1252 00:59:26,200 --> 00:59:28,680 VARIANTS THAT SHOW UP FIRST IF 1253 00:59:28,680 --> 00:59:31,240 THE SPUTUM AND SHOW LATER DATES 1254 00:59:31,240 --> 00:59:33,120 IN THE TRAJECTORY OF PATIENT 1255 00:59:33,120 --> 00:59:34,520 SAMPLES IN THE UPPER RESPIRATORY 1256 00:59:34,520 --> 00:59:43,960 TRACT AND PERSIST OVER TIME. 1257 00:59:43,960 --> 00:59:47,160 AND IT'S INTERESTING TO TRACT 1258 00:59:47,160 --> 00:59:48,480 OVER TIME AND WE CAN ASK IF 1259 00:59:48,480 --> 00:59:51,120 THEY'RE TRACTING TOGETHER AND 1260 00:59:51,120 --> 00:59:55,360 CAN LOOK AT ALLELE FREQUENCY. 1261 00:59:55,360 --> 00:59:58,160 THIS IS SHOWING IN THE ALLELE 1262 00:59:58,160 --> 00:59:59,400 FREQUENCY GRAFT SHOWING THE 1263 00:59:59,400 --> 00:59:59,680 VARIANTS. 1264 00:59:59,680 --> 01:00:04,280 YOU CAN SEE THE ALLELE FREQUENCY 1265 01:00:04,280 --> 01:00:06,240 INCREASES AND THE LINES TRAVEL 1266 01:00:06,240 --> 01:00:09,520 TOGETHER SUGGESTING ONE SUB 1267 01:00:09,520 --> 01:00:16,200 LINEAR PSEUDOMONAS AND 1268 01:00:16,200 --> 01:00:25,760 INTERESTINGLY IF WE ASK AND IT 1269 01:00:25,760 --> 01:00:27,800 CORRELATES WITH THE RESPIRATORY 1270 01:00:27,800 --> 01:00:28,800 INFECTION SUGGESTING MUCOSAL 1271 01:00:28,800 --> 01:00:31,000 CHANGES THAT ALLOW THE NEW 1272 01:00:31,000 --> 01:00:32,040 VARIANT TO BE ACQUIRED. 1273 01:00:32,040 --> 01:00:35,080 THAT VARIANT THEN IS DETECTED AT 1274 01:00:35,080 --> 01:00:37,680 LATER TIME POINTS IN THE SINUS. 1275 01:00:37,680 --> 01:00:39,480 THESE RISE TO HIGH FREQUENCY TO 1276 01:00:39,480 --> 01:00:40,440 OBSERVE IN THE POPULATION BEFORE 1277 01:00:40,440 --> 01:00:44,120 THEN BEING REPLACED BY OTHER 1278 01:00:44,120 --> 01:00:46,160 PSEUDOMONAS LINEAGES. 1279 01:00:46,160 --> 01:00:47,160 WE'RE EXCITED TO USE THE DATA 1280 01:00:47,160 --> 01:00:49,320 AND MUTATIONS TO SUGGEST WHAT 1281 01:00:49,320 --> 01:00:51,960 THE SELECTIVE PRESSURES ARE IN 1282 01:00:51,960 --> 01:00:53,320 THE DIFFERENT MUCOSAL SITES AND 1283 01:00:53,320 --> 01:00:56,080 HOW VIRUSES MAY BE CHANGING THE 1284 01:00:56,080 --> 01:00:57,280 SELECTIVE PRESSURES BY CHANGES 1285 01:00:57,280 --> 01:00:58,960 IN THE VARIANTS THAT APPEAR AND 1286 01:00:58,960 --> 01:01:00,000 HOW THE MODULATORS MAY ALSO 1287 01:01:00,000 --> 01:01:06,760 CHANGE THAT. 1288 01:01:06,760 --> 01:01:08,480 INITIALLY THERE'S REDUCTIONS IN 1289 01:01:08,480 --> 01:01:09,720 BACTERIAL BURDEN. 1290 01:01:09,720 --> 01:01:11,440 WE'D LIKE TO KNOW IN GAPS ARE 1291 01:01:11,440 --> 01:01:18,920 THE SAME STRAINS OF PSEUDOMONAS 1292 01:01:18,920 --> 01:01:20,800 PERSISTING OR IS THIS SELECTING 1293 01:01:20,800 --> 01:01:23,080 FOR NEW DOMINANT STRAINS. 1294 01:01:23,080 --> 01:01:25,280 ARE VIRUS INFECTIONS IMPACTING 1295 01:01:25,280 --> 01:01:26,000 THE MOVEMENT BETWEEN THE 1296 01:01:26,000 --> 01:01:29,080 COMPARTMENTS AND REDUCTIONS OF 1297 01:01:29,080 --> 01:01:32,240 BACTERIAL BURDEN BEING 1298 01:01:32,240 --> 01:01:33,440 MAINTAINED WITH MODULATORS. 1299 01:01:33,440 --> 01:01:35,000 I WANT TO STOP BY SAYING WE 1300 01:01:35,000 --> 01:01:35,880 THINK IT'S IMPORTANT TO CONTINUE 1301 01:01:35,880 --> 01:01:39,640 DOING THE DEEP STUDIES IN 1302 01:01:39,640 --> 01:01:47,920 PATIENTS TO UNDERSTAND MICROBIAL 1303 01:01:47,920 --> 01:01:48,680 COMMUNITY MOVEMENTS AND SUGGEST 1304 01:01:48,680 --> 01:01:50,960 NEW THERAPEUTIC TARGETS AS WE 1305 01:01:50,960 --> 01:01:52,360 THINK OF BACTERIAL INTERACTIONS 1306 01:01:52,360 --> 01:01:54,120 IN THE RESPIRATORY TRACT. 1307 01:01:54,120 --> 01:01:57,080 WE NEED TO IMPROVE OUR 1308 01:01:57,080 --> 01:02:03,120 UNDERSTANDING OF HOW THEY CHANGE 1309 01:02:03,120 --> 01:02:05,000 MICROBIAL COMMUNITYIES AND WE 1310 01:02:05,000 --> 01:02:06,760 NEED TO STUDY THE INTERACTIONS 1311 01:02:06,760 --> 01:02:08,640 IN THE NEW SETTING. 1312 01:02:08,640 --> 01:02:11,560 WE ALSO KNOW IN THIS SETTING OF 1313 01:02:11,560 --> 01:02:13,480 REDUCED SPUTUM AVAILABILITY WE 1314 01:02:13,480 --> 01:02:16,160 MAY NEED TO RELY ON SURVEILLANCE 1315 01:02:16,160 --> 01:02:17,920 OF OTHER SITES BECAUSE WE HAVE 1316 01:02:17,920 --> 01:02:19,480 PAIRED COLLECTIONS WE MAY BE 1317 01:02:19,480 --> 01:02:20,800 ABLE TO ANSWER IF THE 1318 01:02:20,800 --> 01:02:25,520 RESPIRATORY TRACT IS A NEW 1319 01:02:25,520 --> 01:02:26,880 SURVEILLANCE SITE AND ADVOCATE 1320 01:02:26,880 --> 01:02:31,400 FOR THE CONTINUED COMMITMENT TO 1321 01:02:31,400 --> 01:02:41,000 TRACKING MICRO -- MICROBIAL 1322 01:02:41,000 --> 01:02:41,440 INTERVENTIONS. 1323 01:02:41,440 --> 01:02:47,920 I'D LIKE TO THANK MY LAB MEMBERS 1324 01:02:47,920 --> 01:02:58,320 THAT HELPED DO THE WORK. 1325 01:03:06,840 --> 01:03:09,520 >> THANK YOU TO THE ORGANIZERS 1326 01:03:09,520 --> 01:03:13,320 FOR INVITE MEG TO SHARE. 1327 01:03:13,320 --> 01:03:16,240 -- INVITING ME TO SHARE. 1328 01:03:16,240 --> 01:03:18,520 I'M SHARE FACTS IN THE WAY OF 1329 01:03:18,520 --> 01:03:18,760 REPORTS. 1330 01:03:18,760 --> 01:03:20,480 I'M A CLINICIAN NOT A LAB 1331 01:03:20,480 --> 01:03:22,440 RESEARCHER SO NONE OF THESE ARE 1332 01:03:22,440 --> 01:03:26,440 EXPERIMENTS JUST OBSERVATIONS 1333 01:03:26,440 --> 01:03:28,680 MADE FOR PATIENTS WITH MODULATOR 1334 01:03:28,680 --> 01:03:32,920 EXPOSURE IN UTERO. 1335 01:03:32,920 --> 01:03:34,920 WE WILL TALK WITH THE 1336 01:03:34,920 --> 01:03:37,840 POSSIBILITIES THEY SUGGEST AND 1337 01:03:37,840 --> 01:03:40,200 MAKE INFERENCES AND GIVE 1338 01:03:40,200 --> 01:03:41,920 OPINIONS AND THEN TALK ABOUT 1339 01:03:41,920 --> 01:03:52,360 QUESTIONS FOR THE FUTURE. 1340 01:04:02,440 --> 01:04:06,520 AT LEAST FIVE INFANTS HAVE BEEN 1341 01:04:06,520 --> 01:04:07,800 BORN AFTER MOTHERS TOOK THIS 1342 01:04:07,800 --> 01:04:12,400 MODULATOR AND ALL BUT ONE HAD 1343 01:04:12,400 --> 01:04:13,880 NORMAL IRTs SO NOT DETECT 1344 01:04:13,880 --> 01:04:16,040 NEWBORN SCREENING AND ALL AT 1345 01:04:16,040 --> 01:04:22,320 SOME POINT HAD NORMAL FECAL E 1346 01:04:22,320 --> 01:04:24,240 ELASTASE AFTER BIRTH AND I'LL 1347 01:04:24,240 --> 01:04:25,760 START WITH THE FIRST ONE THAT IS 1348 01:04:25,760 --> 01:04:36,040 FROM OUR CENTER. 1349 01:04:39,880 --> 01:04:40,720 THE TRADITIONAL NEWBORN 1350 01:04:40,720 --> 01:04:42,200 SCREENING FOR IFRT DID NOT 1351 01:04:42,200 --> 01:04:43,880 DETECT ANY PROBLEMS. 1352 01:04:43,880 --> 01:04:45,280 IF WE HADN'T REQUEST THE 1353 01:04:45,280 --> 01:04:46,720 GENETICS TO BE RUN WE WOULDN'T 1354 01:04:46,720 --> 01:04:49,120 HAVE KNOWN SHE HAD CF. 1355 01:04:49,120 --> 01:04:51,360 AND IF YOU LOOK AT HER GROWTH 1356 01:04:51,360 --> 01:04:53,080 CURVE AND THINK AS A 1357 01:04:53,080 --> 01:04:55,120 PEDIATRICIAN WOULD ANYONE HAVE 1358 01:04:55,120 --> 01:04:57,440 SENT THIS CHILD FOR EVALUATION? 1359 01:04:57,440 --> 01:04:57,640 NO. 1360 01:04:57,640 --> 01:04:58,760 THIS CHILD'S THRIVING. 1361 01:04:58,760 --> 01:05:00,640 AND ALONG THE BOTTOM FOR THE 1362 01:05:00,640 --> 01:05:03,040 CASE REPORTS YOU CAN SEE I HAVE 1363 01:05:03,040 --> 01:05:07,160 DIFFERENT LEVELS OF MODULATOR 1364 01:05:07,160 --> 01:05:07,480 EXPOSURE. 1365 01:05:07,480 --> 01:05:10,080 IN UTERO WE LEAVE THE EXPOSURE 1366 01:05:10,080 --> 01:05:13,120 TO MODULATORS IS SIMILAR TO 1367 01:05:13,120 --> 01:05:18,560 THERAPEUTIC LEVELS IN MATERNAL 1368 01:05:18,560 --> 01:05:18,920 SERUM. 1369 01:05:18,920 --> 01:05:20,560 THERE'S EVIDENCE THAT THE 1370 01:05:20,560 --> 01:05:24,320 INGREDIENTS IN TRIKAPTA GO INTO 1371 01:05:24,320 --> 01:05:26,120 THE BREAST MILK BUT A LOWER 1372 01:05:26,120 --> 01:05:26,680 LEVEL THAN IS FOUND IN THE 1373 01:05:26,680 --> 01:05:31,080 SERUM. 1374 01:05:31,080 --> 01:05:32,960 MY PATIENT BREAST FED AND MOM 1375 01:05:32,960 --> 01:05:35,400 REMAINED ON TRIKAFTA FOR HER OWN 1376 01:05:35,400 --> 01:05:38,320 HEALTH WELL SHE REMAINS BUT WAS 1377 01:05:38,320 --> 01:05:40,560 ABLE TO BREAST FIELD AND THE 1378 01:05:40,560 --> 01:05:43,960 CHILD WEANED AT ABOUT 10 MONTHS 1379 01:05:43,960 --> 01:05:46,080 OLD AND MOM HAD A SUPPLY TO 1380 01:05:46,080 --> 01:05:48,360 STRETCH TO 12 MONTHS OLD BUT 1381 01:05:48,360 --> 01:05:52,560 SINCE THAT POINT SHE'S BEEN OFF 1382 01:05:52,560 --> 01:05:55,600 CF MODULATORS BECAUSE THERE'S NO 1383 01:05:55,600 --> 01:06:00,680 FDA APPROVED MODULATORS FOR THE 1384 01:06:00,680 --> 01:06:02,200 PATIENTS BELOW AGE 2. 1385 01:06:02,200 --> 01:06:06,120 WE'VE HAD NO LOOK GETTING HER 1386 01:06:06,120 --> 01:06:07,920 PRESCRIBED MODULATOR OFF LABEL 1387 01:06:07,920 --> 01:06:12,360 FOR HER AGE. 1388 01:06:12,360 --> 01:06:14,120 HER SWEAT CHLORIDE WAS 1389 01:06:14,120 --> 01:06:14,800 INTERESTING. 1390 01:06:14,800 --> 01:06:25,360 IT REMAINS CONSISTENT WITH CF 1391 01:06:26,160 --> 01:06:31,760 ABOVE 60 NANO MOLS PER LATER AND 1392 01:06:31,760 --> 01:06:39,200 IT WAS OVER 100. 1393 01:06:39,200 --> 01:06:47,280 I'VE BEEN MONITORING HER FECAL 1394 01:06:47,280 --> 01:06:47,560 ELASTASE. 1395 01:06:47,560 --> 01:06:50,200 I CAN'T SPOT A TREND IN HERE. 1396 01:06:50,200 --> 01:06:52,080 I WAS CONCERNED AROUND 6 MONTHS 1397 01:06:52,080 --> 01:06:53,920 WHERE IT SEEMED TO DROP TOWARDS 1398 01:06:53,920 --> 01:06:56,120 THE INEFFICIENCY RANGE AND 1399 01:06:56,120 --> 01:07:00,960 POPPED BACK UP. 1400 01:07:00,960 --> 01:07:04,160 SHE REMAINS CONSISTENT AND HAS 1401 01:07:04,160 --> 01:07:06,880 NOT AND I GAVE HER A WEEK'S 1402 01:07:06,880 --> 01:07:08,680 WORTH WHEN SHE WAS FIRST BORN 1403 01:07:08,680 --> 01:07:11,240 BEFORE WE GOT THE ELASTASE 1404 01:07:11,240 --> 01:07:12,040 LEVELS BACK BASED ON HER TWO 1405 01:07:12,040 --> 01:07:17,640 MUTATIONS. 1406 01:07:17,640 --> 01:07:23,920 AROUND 10 MONTHS OLD I STARTED 1407 01:07:23,920 --> 01:07:29,400 CHECKING SERUM LIPASE AND IT'S 1408 01:07:29,400 --> 01:07:30,840 BEYOND THE LOWER LIMITS THAN 1409 01:07:30,840 --> 01:07:36,880 NORMAL BECAUSE THEY DON'T HAVE A 1410 01:07:36,880 --> 01:07:45,120 WORKING EXOCRINE PANCREAS AND 1411 01:07:45,120 --> 01:07:47,840 THERE'S EVIDENCE OF PANCREATIC 1412 01:07:47,840 --> 01:07:52,320 CELLULAR LEAKAGE OR INJURY GOING 1413 01:07:52,320 --> 01:07:53,880 ON WHENEVER WE'VE CHECKED. 1414 01:07:53,880 --> 01:07:55,600 I DON'T KNOW IF THIS IS A TREND 1415 01:07:55,600 --> 01:07:57,760 EITHER WITH THE LIMITED NUMBER 1416 01:07:57,760 --> 01:07:59,840 OF DATA POINTS BUT WE'LL 1417 01:07:59,840 --> 01:08:00,920 CONTINUE TO MONITOR THAT JUST 1418 01:08:00,920 --> 01:08:03,160 MOST AS OFTEN AS WE CHECK THE 1419 01:08:03,160 --> 01:08:04,320 STOOL BECAUSE IT'S A PROCEDURE 1420 01:08:04,320 --> 01:08:13,200 TO DRAW BLOOD FROM AN INFANT. 1421 01:08:13,200 --> 01:08:15,160 CASE 2 ILLUSTRATED PART OF THIS 1422 01:08:15,160 --> 01:08:19,240 CASE HE WAS UNABLE TO BREAST 1423 01:08:19,240 --> 01:08:20,400 FEED AND MOMENT'S SUPPLY NEVER 1424 01:08:20,400 --> 01:08:23,760 CAME IN BUT THE CHILD WAS 1425 01:08:23,760 --> 01:08:25,440 THRIVING WITH WEIGHTS GREATER 1426 01:08:25,440 --> 01:08:27,600 THAN THE 50th PERCENTILE 1427 01:08:27,600 --> 01:08:29,400 INITIALLY AND BETWEEN 6 AND 8 1428 01:08:29,400 --> 01:08:33,280 WEEKS OLD HE STARTED DEVELOPING 1429 01:08:33,280 --> 01:08:35,920 SIGNIFICANT SYMPTOMS OF 1430 01:08:35,920 --> 01:08:39,560 MALABSORPTION AND HE EVEN WAS 1431 01:08:39,560 --> 01:08:42,000 FOUND TO BE PANCREATIC 1432 01:08:42,000 --> 01:08:42,360 INSUFFICIENT. 1433 01:08:42,360 --> 01:08:45,600 HE HAD TO START ON PANCREATIC 1434 01:08:45,600 --> 01:08:47,520 ENZYME REPLACEMENT THERAPY. 1435 01:08:47,520 --> 01:08:48,800 SIMILAR TO WHAT WAS REPORTED IN 1436 01:08:48,800 --> 01:08:51,520 THE ANIMAL MODELS LIKE THE 1437 01:08:51,520 --> 01:08:53,920 FERRET AT THE SAME TIME HE HAD 1438 01:08:53,920 --> 01:09:04,480 THE PANCREATIC INFLAMMATION AND 1439 01:09:05,000 --> 01:09:08,600 CASE 3 IS THE YOUNGEST. 1440 01:09:08,600 --> 01:09:10,240 HE'S CARED FOR AT OUR CENTER AND 1441 01:09:10,240 --> 01:09:15,680 HIS FACETS ARE HE ONLY HAS ONE 1442 01:09:15,680 --> 01:09:18,120 F508 MUTATION AND THE OTHER IS A 1443 01:09:18,120 --> 01:09:19,720 CLASS 1 MUTATION. 1444 01:09:19,720 --> 01:09:22,120 BUT LIKE THE OTHERS THOUGH HE 1445 01:09:22,120 --> 01:09:24,520 WASN'T ABLE TO BREAST FEED HE'S 1446 01:09:24,520 --> 01:09:27,680 BEEN THRIVING AND BASED ON 1447 01:09:27,680 --> 01:09:29,160 PATIENT'S 2s EXPERIENCE I'VE 1448 01:09:29,160 --> 01:09:32,240 BEEN CHECKING HIS FECAL ELASTASE 1449 01:09:32,240 --> 01:09:34,000 MORE FREQUENTLY AND MOM AND DAD 1450 01:09:34,000 --> 01:09:38,240 DROP IT OFF TO A LAP CLOSER TO 1451 01:09:38,240 --> 01:09:39,920 THEIR HOME EVERY WEEK BECAUSE IF 1452 01:09:39,920 --> 01:09:43,960 HE'S STARTING TO HAVE PANCREATIC 1453 01:09:43,960 --> 01:09:45,760 PROBLEMS I DON'T WANT TO MISS 1454 01:09:45,760 --> 01:09:48,160 THEM OR PROGRESS TO POOR WEIGHT 1455 01:09:48,160 --> 01:09:49,200 GAIN OR ANYTHING. 1456 01:09:49,200 --> 01:09:56,800 ALL THE KIDS HAVE BEEN EVALUATED 1457 01:09:56,800 --> 01:10:01,120 FOR MODULATOR AND MOST HAD LIVER 1458 01:10:01,120 --> 01:10:09,040 FUNCTION AND WHEN A PEDIATRIC 1459 01:10:09,040 --> 01:10:09,840 OPHTHALMOLOGIST MONITORED THEM 1460 01:10:09,840 --> 01:10:11,920 AND IT WILL BE YEARS BEFORE WE 1461 01:10:11,920 --> 01:10:16,040 KNOW IF THERE'S A FUNCTIONAL 1462 01:10:16,040 --> 01:10:18,760 INSTRUCTION BUT THE MERE 1463 01:10:18,760 --> 01:10:21,720 PRESENCE OF A VAS DEFERENCE WITH 1464 01:10:21,720 --> 01:10:22,960 A BOY WITH CF IS REMARKABLE IN 1465 01:10:22,960 --> 01:10:29,280 ITSELF. 1466 01:10:29,280 --> 01:10:36,560 AGAIN, HE'S BEEN THRIVING. 1467 01:10:36,560 --> 01:10:43,200 THEY'VE ALL BEEN WELL ABOVE THE 1468 01:10:43,200 --> 01:10:53,440 NORMAL RANGE. 1469 01:11:00,360 --> 01:11:04,200 HIS SWEAT CHLORIDE IS NOT AT THE 1470 01:11:04,200 --> 01:11:05,400 LEVEL YOU'D EXPECT FOR SOMEBODY 1471 01:11:05,400 --> 01:11:10,320 WITH THE TWO MUTATION. 1472 01:11:10,320 --> 01:11:13,000 I'D EXPECT A VALUE GREATER THAN 1473 01:11:13,000 --> 01:11:21,520 THIS AND WE DO PLAN TO REPEAT A 1474 01:11:21,520 --> 01:11:23,480 SWEAT WHEN HE'S A LITTLE OLDER. 1475 01:11:23,480 --> 01:11:26,960 CASE 4 WAS PUBLISHED WE A TEAM 1476 01:11:26,960 --> 01:11:36,200 AT SOUTH CAROLINA. 1477 01:11:36,200 --> 01:11:39,840 THE MOM IS A CARRIER AND THE 1478 01:11:39,840 --> 01:11:42,440 FAMILY KNOWS DAD'S A CARRIER AND 1479 01:11:42,440 --> 01:11:45,680 HAVE A FAMILY WITH CF AND 1480 01:11:45,680 --> 01:11:47,120 FAMILIAR WITH THE MANIFESTATIONS 1481 01:11:47,120 --> 01:11:47,720 OF THE DISEASE. 1482 01:11:47,720 --> 01:11:48,680 WHAT HAPPENED IN THIS CASE WAS 1483 01:11:48,680 --> 01:11:50,160 THE PREGNANCY SEEMED TO BE GOING 1484 01:11:50,160 --> 01:11:51,920 WELL AND THEN THERE WERE 1485 01:11:51,920 --> 01:11:54,800 FINDINGS ON ULTRASOUND THAT 1486 01:11:54,800 --> 01:12:01,640 SUGGESTED MECONIUM ILLIUS. 1487 01:12:01,640 --> 01:12:06,800 THEY WORKED WITH THE CARE TEAMS 1488 01:12:06,800 --> 01:12:17,320 AND BUT THEY STARTED TO START 1489 01:12:19,280 --> 01:12:30,120 MORNING LATE-- MODULATORS AND T 1490 01:12:30,120 --> 01:12:40,640 WAS NO CHANGE MECONIUM ILEUS AND 1491 01:12:42,400 --> 01:12:43,440 SLOWED NO FURTHER SIGNS. 1492 01:12:43,440 --> 01:12:46,240 THE BABY WAS BORN A COUPLE DAYS 1493 01:12:46,240 --> 01:12:48,240 LATER AND WHEN SHE WAS BORN 1494 01:12:48,240 --> 01:12:50,840 THERE WAS NO EVIDENCE OF 1495 01:12:50,840 --> 01:12:57,400 MECONIUM ILEUS AND HER FECAL 1496 01:12:57,400 --> 01:12:58,680 ELASTASE WAS LOW BUT IN WANTING 1497 01:12:58,680 --> 01:13:01,040 TO CONTINUE THE BENEFITS OF 1498 01:13:01,040 --> 01:13:03,760 MODULATORS THROUGH THE BREAST 1499 01:13:03,760 --> 01:13:05,480 MILK MOM CONTINUED TO TAKE 1500 01:13:05,480 --> 01:13:07,280 MODULATOR THERAPY AND BREAST 1501 01:13:07,280 --> 01:13:09,520 FEED AND WITH THAT THE FECAL 1502 01:13:09,520 --> 01:13:10,840 ELASTASE CLIMBED IN THE NORMAL 1503 01:13:10,840 --> 01:13:13,200 RANGE AND THE CHILD CONTINUED TO 1504 01:13:13,200 --> 01:13:16,440 THRIVE BUT AT ABOUT FOUR MONTHS 1505 01:13:16,440 --> 01:13:18,160 OLD MOM HAD TO DO SAFETY 1506 01:13:18,160 --> 01:13:19,880 MONITORING LABS FOR HERSELF ON 1507 01:13:19,880 --> 01:13:24,440 THE TRIKAFTA AND HER OWN HEPATIC 1508 01:13:24,440 --> 01:13:27,000 LEVELS AST AND ALT WERE THREE 1509 01:13:27,000 --> 01:13:30,320 TIMES NORMAL SO HAD TO STOP THE 1510 01:13:30,320 --> 01:13:30,560 THERAPY. 1511 01:13:30,560 --> 01:13:32,400 THOUGH SHE CONTINUED BREAST 1512 01:13:32,400 --> 01:13:34,800 FEEDING AT THIS POINT THE CHILD 1513 01:13:34,800 --> 01:13:37,400 WAS NOT GETTING ANY MODULATOR 1514 01:13:37,400 --> 01:13:40,120 THROUGH THE BREAST MILK ANY 1515 01:13:40,120 --> 01:13:46,360 LONGER AND WAS DEVELOPING 1516 01:13:46,360 --> 01:13:47,200 MALABSORPTION AND ABDOMINAL 1517 01:13:47,200 --> 01:13:48,840 ISSUES AND CRAMPING AND THE 1518 01:13:48,840 --> 01:13:50,040 PARENTS BEING FAMILIAR WITH CF 1519 01:13:50,040 --> 01:13:52,480 DIDN'T WANT TO SEE THEIR CHILD 1520 01:13:52,480 --> 01:13:54,200 GO THROUGH THIS WITHDRAWAL 1521 01:13:54,200 --> 01:13:56,040 PROFESSION AND BECAUSE THEY HAD 1522 01:13:56,040 --> 01:13:58,320 MODULATOR IN THE HOUSE SINCE MOM 1523 01:13:58,320 --> 01:14:00,600 WASN'T USING HERS ANYMORE THEY 1524 01:14:00,600 --> 01:14:02,640 CRUSHED IT UP AND GAVE A TINY 1525 01:14:02,640 --> 01:14:03,920 DOSE KIND OF IN CONSULTATION 1526 01:14:03,920 --> 01:14:05,920 WITH EXPERTS AROUND THE COUNTRY 1527 01:14:05,920 --> 01:14:10,920 AND THEY STARTED VERY LOW WITH 1528 01:14:10,920 --> 01:14:15,640 2% OF THE ADULT DOSING AND THAT 1529 01:14:15,640 --> 01:14:17,280 LED TO AN IMPROVEMENT IN 1530 01:14:17,280 --> 01:14:20,960 SYMPTOMS AND ALSO AN IMPROVEMENT 1531 01:14:20,960 --> 01:14:23,960 IN FECAL ELASTASE AND EVERYTHING 1532 01:14:23,960 --> 01:14:26,200 WAS GOING WELL AND PUSHED IT 3% 1533 01:14:26,200 --> 01:14:28,520 OF THE ADULT DOSE AND SAW 1534 01:14:28,520 --> 01:14:34,480 FURTHER IMPROVEMENT IN THE FECAL 1535 01:14:34,480 --> 01:14:37,800 ELASTASE. 1536 01:14:37,800 --> 01:14:44,120 AND STARTED OFF LABEL. 1537 01:14:44,120 --> 01:14:47,920 AND BY THE TIME SHE TURNS 2 SHE 1538 01:14:47,920 --> 01:14:57,160 WOULD BE A CANDIDATE WITH THE 1539 01:14:57,160 --> 01:15:00,640 MEDICATION. 1540 01:15:00,640 --> 01:15:02,120 THEY MADE AN ESTIMATE ON WHAT 1541 01:15:02,120 --> 01:15:04,960 HER DOSE WOULD BE AND CONSISTENT 1542 01:15:04,960 --> 01:15:08,360 WITH THE DOSING IN THE TRIAL 1543 01:15:08,360 --> 01:15:09,960 THEY'VE DONE IN UNDER FOR 1544 01:15:09,960 --> 01:15:20,280 PATIENTS AGES 1-2. 1545 01:15:29,320 --> 01:15:31,000 THIS MAY BENEFIT FROM EARLY 1546 01:15:31,000 --> 01:15:35,680 MODULATORS AND THOSE WITH 1547 01:15:35,680 --> 01:15:42,280 RESPONSE MUTATIONS YOU WILL THE 1548 01:15:42,280 --> 01:15:45,440 CASES SUGGESTED THE DEVELOPING 1549 01:15:45,440 --> 01:15:48,440 PANCREAS BENEFITS FROM MODULATOR 1550 01:15:48,440 --> 01:15:48,720 EXPOSURE. 1551 01:15:48,720 --> 01:15:54,360 I THINK CASES 2 AND 4 SHOW RISKS 1552 01:15:54,360 --> 01:15:57,840 TO THE PANCREAS IS MODULATOR 1553 01:15:57,840 --> 01:15:59,480 THERAPY IS WITHDRAWN AND THE 1554 01:15:59,480 --> 01:16:01,200 FERRET MODEL SUGGESTS IT'S TRUE. 1555 01:16:01,200 --> 01:16:02,320 I DON'T KNOW IF IT WILL REQUIRE 1556 01:16:02,320 --> 01:16:05,440 THE FULL DOSE TO HELP THE 1557 01:16:05,440 --> 01:16:05,720 PANCREAS. 1558 01:16:05,720 --> 01:16:08,840 THAT'S BECAUSE IT DOESN'T TAKE 1559 01:16:08,840 --> 01:16:15,240 MUCH CFTR FUNCTION TO BE 1560 01:16:15,240 --> 01:16:22,720 PANCREATIC SUFFICIENT. 1561 01:16:22,720 --> 01:16:26,000 AND YOU NEED A LEVEL OF RESERVE 1562 01:16:26,000 --> 01:16:29,960 TO GET INFLAMED BUT WHAT'S 1563 01:16:29,960 --> 01:16:31,760 HAPPENING WITH THESE KIDS IS 1564 01:16:31,760 --> 01:16:33,240 THEY'VE GOT THE WORKING PANCREAS 1565 01:16:33,240 --> 01:16:35,800 TO BEGIN WITH BUT THEIR 1566 01:16:35,800 --> 01:16:37,200 MUTATIONS ARE SUCH THEY'LL HAVE 1567 01:16:37,200 --> 01:16:38,720 LOW CFTR FUNCTION. 1568 01:16:38,720 --> 01:16:42,920 FROM THE BEGINNING THEY'RE AT 1569 01:16:42,920 --> 01:16:46,080 RISK FOR PANCREATITIS AS IT 1570 01:16:46,080 --> 01:16:48,280 WORSENS WITHOUT THE BENEFIT OF 1571 01:16:48,280 --> 01:16:49,560 MODULATOR THERAPY. 1572 01:16:49,560 --> 01:16:52,520 I THINK CASE 4 AT LEAST ANSWERS 1573 01:16:52,520 --> 01:16:54,320 THE QUESTION OF COULD IT BE 1574 01:16:54,320 --> 01:16:56,440 OFFERED TO MOTHERS CARRYING A 1575 01:16:56,440 --> 01:16:58,520 FETUS BUT THAT'S A DISCUSSION OF 1576 01:16:58,520 --> 01:17:04,560 SHOULD AND A LARGER DISCUSSION. 1577 01:17:04,560 --> 01:17:13,080 AND COULD IT BENEFIT FROM LOWER 1578 01:17:13,080 --> 01:17:21,720 DOSES OR IVACAFTOR HAS BEEN ABLE 1579 01:17:21,720 --> 01:17:23,320 TO BE STARTED YOUNG. 1580 01:17:23,320 --> 01:17:25,520 I'D LIKE TO LEARN ABOUT THE CELL 1581 01:17:25,520 --> 01:17:25,720 LINES. 1582 01:17:25,720 --> 01:17:28,200 THE DOSE RESPONSE CURVES HAVE 1583 01:17:28,200 --> 01:17:32,400 BEEN GENERATED IN EPITHELIAL OR 1584 01:17:32,400 --> 01:17:34,600 INTESTINAL CULTURES BUT WOULD 1585 01:17:34,600 --> 01:17:36,840 LOVE TO SEE SOME IN PANCREATIC 1586 01:17:36,840 --> 01:17:38,800 CELL LINES AND WE NEED TO KNOW 1587 01:17:38,800 --> 01:17:44,280 WHAT THE RISKS ARE OF MODULATOR 1588 01:17:44,280 --> 01:17:46,240 WITHDRAWAL AND HOW TO TREAT 1589 01:17:46,240 --> 01:17:46,520 INFANTS. 1590 01:17:46,520 --> 01:17:48,000 I'LL TURN IT OVER TO DR. CUTTING 1591 01:17:48,000 --> 01:17:48,760 FROM JOHNS HOPKINS. 1592 01:17:48,760 --> 01:17:48,840 1593 01:18:42,440 --> 01:18:46,240 >> WE HAD A BLUE JOURNAL PAPER 1594 01:18:46,240 --> 01:18:47,560 AND MANY HAVE BEEN INSTRUMENTAL 1595 01:18:47,560 --> 01:18:48,360 IN PREPARING THE SLIDES I'M 1596 01:18:48,360 --> 01:18:54,520 GOING TO SHOW YOU. 1597 01:18:54,520 --> 01:18:57,080 DISCLOSURES I HAVE A RELATIVE 1598 01:18:57,080 --> 01:18:58,600 THAT WORKS AT THE COMPANY I'LL 1599 01:18:58,600 --> 01:19:00,200 TALK ABOUT. 1600 01:19:00,200 --> 01:19:01,880 AND CLINICAL TRIALS REPORT 1601 01:19:01,880 --> 01:19:05,120 SHORT-TERM EFFECTS AND WE'RE 1602 01:19:05,120 --> 01:19:05,760 TALKING ABOUT WEEKS. 1603 01:19:05,760 --> 01:19:08,000 THESE ARE OBVIOUSLY PROFOUND 1604 01:19:08,000 --> 01:19:11,160 CHANGES IN SWEAT CHLORIDE WITH A 1605 01:19:11,160 --> 01:19:12,760 TRIPLE COMBINATION OVER 24 WEEKS 1606 01:19:12,760 --> 01:19:19,200 AND SAME WITH LUNG FUNCTION 1607 01:19:19,200 --> 01:19:26,800 IMPRESSIVE CHANGES. 1608 01:19:26,800 --> 01:19:29,040 AND HOW MUCH DO THEY TRANSLATE 1609 01:19:29,040 --> 01:19:34,840 TO LONG-TERM IMPROVEMENTS ARE 1610 01:19:34,840 --> 01:19:45,240 THERE OTHER COMPARISONS. 1611 01:19:49,600 --> 01:19:53,400 AND IN ACUTE INCREASE IN THE 1612 01:19:53,400 --> 01:19:57,800 LEVEL OF CFTR FUNCTION AND HOW 1613 01:19:57,800 --> 01:20:02,240 MUCH COMPARES TO A LIFE TIME OF 1614 01:20:02,240 --> 01:20:03,000 FUNCTION. 1615 01:20:03,000 --> 01:20:05,640 HIGH CFTR FUNCTION FROM 1616 01:20:05,640 --> 01:20:06,720 CONCEPTION. 1617 01:20:06,720 --> 01:20:08,520 DEVELOPMENT ISSUE ADDRESSED AND 1618 01:20:08,520 --> 01:20:08,800 SO FORTH. 1619 01:20:08,800 --> 01:20:19,320 I CAN POSE A QUESTION TO YOU. 1620 01:20:26,440 --> 01:20:31,000 AN THERE'S SOME FEATURES THEY 1621 01:20:31,000 --> 01:20:33,360 MANIFEST BUT THEY DON'T DEVELOP 1622 01:20:33,360 --> 01:20:37,440 LIFE TIME LUNG DISEASE. 1623 01:20:37,440 --> 01:20:46,320 IF YOU ACHIEVE 50% FUNCTION THAT 1624 01:20:46,320 --> 01:20:46,560 MATCHED? 1625 01:20:46,560 --> 01:20:48,200 IF YOU FALL SHORT OF THAT AND 1626 01:20:48,200 --> 01:20:50,520 HAVE LESSER RECOVERY OF FUNCTION 1627 01:20:50,520 --> 01:20:50,840 WHAT HAPPENS? 1628 01:20:50,840 --> 01:20:55,840 SO MOVING TO THE NEXT SLIDE, ANY 1629 01:20:55,840 --> 01:20:58,240 CONTEXT AND WE JUST SAW CONTEXT 1630 01:20:58,240 --> 01:20:59,840 AND SHOWING A GROWTH CURVE. 1631 01:20:59,840 --> 01:21:04,360 I'M GOING SHOW A GROWTH CURVE 1632 01:21:04,360 --> 01:21:04,560 FIRST. 1633 01:21:04,560 --> 01:21:15,080 HERE'S THE CHART AGAINST YEARS. 1634 01:21:18,720 --> 01:21:20,400 THERE'S CLEARLY A BIG 1635 01:21:20,400 --> 01:21:21,720 DIFFERENCE. 1636 01:21:21,720 --> 01:21:22,640 WHAT'S IT MEAN? 1637 01:21:22,640 --> 01:21:25,960 IF YOU PUT IT ON A GROWTH CURVE 1638 01:21:25,960 --> 01:21:27,600 YOU CAN NOW SEE WHAT HAPPENED. 1639 01:21:27,600 --> 01:21:30,280 IT GIVES CONTEXT AND LIFE TIME 1640 01:21:30,280 --> 01:21:31,680 CONTEXT BECAUSE NOW SHE'S 1641 01:21:31,680 --> 01:21:35,440 REACHED 50th PERCENTILE AND WHAT 1642 01:21:35,440 --> 01:21:36,560 THE EXPECTATION WOULD BE AND 1643 01:21:36,560 --> 01:21:39,240 THAT THERAPY WENT WELL AND 1644 01:21:39,240 --> 01:21:48,360 LIKELY SHE'LL CONTINUE ON THE 50 1645 01:21:48,360 --> 01:21:54,720 PERCENTILE. 1646 01:21:54,720 --> 01:21:56,000 AND WE'LL LOOK AT LUNG FUNCTION 1647 01:21:56,000 --> 01:21:57,720 AND RELATED DISEASE AND WE 1648 01:21:57,720 --> 01:21:58,840 STARTED WITH A COUPLE ELEMENTS 1649 01:21:58,840 --> 01:22:03,360 AND LOOKING AT MORE AND USE THE 1650 01:22:03,360 --> 01:22:05,120 DATA FROM THE CFTR PROJECT WITH 1651 01:22:05,120 --> 01:22:05,720 THOUSANDS OF INDIVIDUALS TO 1652 01:22:05,720 --> 01:22:08,440 STUDY. 1653 01:22:08,440 --> 01:22:11,960 AND WE NEED TO ESTABLISH THE 1654 01:22:11,960 --> 01:22:15,280 RELATIONSHIP BETWEEN CFTR AND 1655 01:22:15,280 --> 01:22:17,120 THE DIFFERENT TRAITS AND BY CFTR 1656 01:22:17,120 --> 01:22:18,680 FUNCTION I'LL DERIVE THAT BASED 1657 01:22:18,680 --> 01:22:20,280 ON THE CELL-BASED STUDIES AND 1658 01:22:20,280 --> 01:22:24,280 WE'RE LOOKING AT CHLORIDE AND 1659 01:22:24,280 --> 01:22:27,280 THERE'S OTHER PROPERTIES WE ARE 1660 01:22:27,280 --> 01:22:30,880 NOT ASSAYING AND IF YOU THINK OF 1661 01:22:30,880 --> 01:22:33,080 CHLORIDE TRANSPORT AND LOOK AT 1662 01:22:33,080 --> 01:22:36,120 THE STUDIES DONE YOU CAN 1663 01:22:36,120 --> 01:22:37,040 ESTIMATE WHAT THE CFTR FUNCTION 1664 01:22:37,040 --> 01:22:41,800 COULD BE AND WE DID IT FOR 226 1665 01:22:41,800 --> 01:22:43,080 GENOTYPES AND WE USED AN 1666 01:22:43,080 --> 01:22:48,240 ADDITIVE MODEL AND TAKE THE 1667 01:22:48,240 --> 01:22:51,240 FUNCTION OF THE VARIANT 1 AND 1668 01:22:51,240 --> 01:23:00,600 ADD IT TO VARIANT 2. 1669 01:23:00,600 --> 01:23:04,960 YOU PLOT IT OUT AND THE 226 1670 01:23:04,960 --> 01:23:05,240 GENOTYPES. 1671 01:23:05,240 --> 01:23:06,360 THERE'S A LOT OF DOTS ON THE 1672 01:23:06,360 --> 01:23:08,160 PAGE BUT THIS IS REAL DATA FROM 1673 01:23:08,160 --> 01:23:11,120 PATIENTS AND INDIVIDUALS WITH CF 1674 01:23:11,120 --> 01:23:13,760 AND SO YOU'LL HAVE EXPECTATIONS 1675 01:23:13,760 --> 01:23:14,720 WITH THIS OF DISTRIBUTION BUT 1676 01:23:14,720 --> 01:23:17,800 YOU CAN DRAW A ROBUST 1677 01:23:17,800 --> 01:23:18,880 STATISTICALLY RELEVANT BEST FIT 1678 01:23:18,880 --> 01:23:23,520 LINE AND THIS IS A NON-LINEAR 1679 01:23:23,520 --> 01:23:28,120 RELATIONSHIP BETWEEN SWEAT 1680 01:23:28,120 --> 01:23:29,480 CHLORIDE AND CFTR FUNCTION. 1681 01:23:29,480 --> 01:23:31,480 LUNG FUNCTION HAS THE SAME 1682 01:23:31,480 --> 01:23:35,040 ATTRIBUTES AND FITS A NON-LINEAR 1683 01:23:35,040 --> 01:23:36,040 RELATIONSHIP AND CAN IT BE 1684 01:23:36,040 --> 01:23:39,920 REPRESENTED IN A DIFFERENT WAY? 1685 01:23:39,920 --> 01:23:41,440 SO HERE IS NOW PUTTING ON A PLOT 1686 01:23:41,440 --> 01:23:45,560 AND YOU CAN LOOK AT THAT CFTR 1687 01:23:45,560 --> 01:23:47,400 FUNCTION INVERTED AGAINST THE 1688 01:23:47,400 --> 01:23:48,600 SWEAT CHLORIDE AND CAN YOU SEE 1689 01:23:48,600 --> 01:23:56,200 THE DATA NOW SCATTERS IN A WAY 1690 01:23:56,200 --> 01:24:00,280 TO LOOK AT THE PERCENTILE. 1691 01:24:00,280 --> 01:24:01,560 AND THAT'S WHAT THE MEANS IF YOU 1692 01:24:01,560 --> 01:24:08,280 TAKE SOME OF THE GENOTYPE S LIKE 1693 01:24:08,280 --> 01:24:13,640 THE F508 HOMO ZYGOTE AND SEE IT 1694 01:24:13,640 --> 01:24:14,480 DROP ALONG THE LINE. 1695 01:24:14,480 --> 01:24:17,200 YOU CAN DRAW THE LINE AND USE 1696 01:24:17,200 --> 01:24:18,480 THIS NOW TO PLOT OUT CLINICAL 1697 01:24:18,480 --> 01:24:20,560 RESULT DATA AGAINST IT. 1698 01:24:20,560 --> 01:24:22,400 AND ONE ISSUE IS THAT THIS END 1699 01:24:22,400 --> 01:24:24,160 OF THE SPECTRUM ONCE YOU GET 1700 01:24:24,160 --> 01:24:26,080 BEYOND 50% FUNCTION, WE DON'T 1701 01:24:26,080 --> 01:24:26,720 HAVE A LOT OF INFORMATION 1702 01:24:26,720 --> 01:24:29,400 BECAUSE MOST OF OUR DATA IS 1703 01:24:29,400 --> 01:24:31,640 DERIVED FROM CF PATIENTS AND 1704 01:24:31,640 --> 01:24:34,200 CFTR AND AS PUBLISHED IN THE 1705 01:24:34,200 --> 01:24:37,320 JOURNAL OF CYSTIC FIBROSIS AN 1706 01:24:37,320 --> 01:24:42,720 ELEGANT RE-ANALYSIS AT 100% WILD 1707 01:24:42,720 --> 01:24:43,920 TYPE YOU EXPECT IT TO BE BELOW 1708 01:24:43,920 --> 01:24:54,000 40. 1709 01:24:58,080 --> 01:24:59,520 AND IT FITS THE LUNG FUNCTION 1710 01:24:59,520 --> 01:25:02,360 AND THERE'S THE CURVE AND AT 1711 01:25:02,360 --> 01:25:06,680 100% FUNCTION YOU'RE START TO 1712 01:25:06,680 --> 01:25:12,080 REACH THE MEAN. 1713 01:25:12,080 --> 01:25:13,800 WHAT HAPPENS? 1714 01:25:13,800 --> 01:25:15,040 IF YOU START PLOTTING CLINICAL 1715 01:25:15,040 --> 01:25:20,760 TRIAL DATA THIS IS WHAT IS 1716 01:25:20,760 --> 01:25:22,200 PUBLISHED. 1717 01:25:22,200 --> 01:25:25,200 YOU SEE IT PLOT OUT IN THE OPEN 1718 01:25:25,200 --> 01:25:28,880 SYMBOLS AND THE SWEAT CHLORIDE 1719 01:25:28,880 --> 01:25:31,520 AND POST-TRIAL VALUES AND THEY 1720 01:25:31,520 --> 01:25:32,080 FOLLOW THIS NATURAL HISTORY 1721 01:25:32,080 --> 01:25:36,280 PLOT. 1722 01:25:36,280 --> 01:25:39,200 SO 65% IN FUNCTION AND A 1723 01:25:39,200 --> 01:25:40,480 DECREASE IN 58 NORMAL FOR AN 1724 01:25:40,480 --> 01:25:41,400 AVERAGE FOR THAT GROUP AND FITS 1725 01:25:41,400 --> 01:25:48,160 NICELY. 1726 01:25:48,160 --> 01:25:49,520 WHAT HAPPENS WITH LUNG FUNCTION? 1727 01:25:49,520 --> 01:25:51,600 THERE'S A DECREASE IN FUNCTION 1728 01:25:51,600 --> 01:25:55,960 BUT ONLY A 9% INCREASE IN FEV1. 1729 01:25:55,960 --> 01:25:57,320 ARE WE FALLING SHORT FOR SOME 1730 01:25:57,320 --> 01:25:59,360 REASON AND WHY? 1731 01:25:59,360 --> 01:26:02,040 PERHAPS WE ARE IF YOU COULD PLOT 1732 01:26:02,040 --> 01:26:05,720 MORE DATA OUT MAYBE WE CAN SEE 1733 01:26:05,720 --> 01:26:06,680 WHY WE'RE FALLING SHORT MAYBE 1734 01:26:06,680 --> 01:26:07,840 SOMETHING ELSE IS IMPORTANT TO 1735 01:26:07,840 --> 01:26:11,080 CONSIDER IN THE PLOT. 1736 01:26:11,080 --> 01:26:12,880 MAYBE THERE'S AN IRREVERSIBLE 1737 01:26:12,880 --> 01:26:15,080 COMPONENT WE CAN'T RECOVER. 1738 01:26:15,080 --> 01:26:16,560 LOOKS LIKE PERHAPS WE MIGHT HAVE 1739 01:26:16,560 --> 01:26:20,400 FALLEN SHORT BUT LOOKING AT MORE 1740 01:26:20,400 --> 01:26:23,360 DATA WE CAN CONSIDER THIS AND 1741 01:26:23,360 --> 01:26:24,320 THAT'S WHAT WE'VE DONE. 1742 01:26:24,320 --> 01:26:27,040 WE HAVE DATA PLOTTED OUT USING 1743 01:26:27,040 --> 01:26:29,960 MORE RECENT INFORMATION FROM 1744 01:26:29,960 --> 01:26:32,280 FIVE TRIALS WITH THE SWEAT 1745 01:26:32,280 --> 01:26:33,240 CHLORIDE SLOPE IS BETTER THAN WE 1746 01:26:33,240 --> 01:26:35,600 WOULD HAVE PREDICTED AND WE 1747 01:26:35,600 --> 01:26:38,600 CHANGED THE ASSUMPTIONS OF THE 1748 01:26:38,600 --> 01:26:40,240 FUNCTION IN THE CELL LINE BASED 1749 01:26:40,240 --> 01:26:42,640 SYMPTOMS AND EITHER WAY WE HAVE 1750 01:26:42,640 --> 01:26:45,960 QUITE A SUBSTANTIAL RESPONSE IN 1751 01:26:45,960 --> 01:26:47,800 THESE TRIALS AND NEXT ALSO SHOWS 1752 01:26:47,800 --> 01:26:49,320 A VERY NICE RESPONSE IN LUNG 1753 01:26:49,320 --> 01:26:51,920 FUNCTION BUT MATCHES WHAT WE 1754 01:26:51,920 --> 01:26:55,440 EXPECT FROM HISTORICAL DATA AND 1755 01:26:55,440 --> 01:26:56,760 GOOD INFORMATION SWEAT CHLORIDE 1756 01:26:56,760 --> 01:26:58,520 AT LEAST ASSOCIATES WITH A 1757 01:26:58,520 --> 01:27:01,000 CHANGE IN LUNG FUNCTION AND YOU 1758 01:27:01,000 --> 01:27:03,080 CAN DO THIS FOR ANY AGE IF THEY 1759 01:27:03,080 --> 01:27:04,560 HAVE A CHANGE OF SWEAT CHLORIDE 1760 01:27:04,560 --> 01:27:06,000 YOU CAN EXPECT A CHANGE IN LUNG 1761 01:27:06,000 --> 01:27:16,200 FUNCTION. 1762 01:27:17,240 --> 01:27:27,680 AND IVACAFTOR AND TESS -- TE 1763 01:27:47,360 --> 01:27:57,480 TEZACAFTOR. 1764 01:28:33,320 --> 01:28:35,240 WE HAVE F508 AND PROFOUND 1765 01:28:35,240 --> 01:28:36,400 CHANGES IN THOSE WITH ONE OR TWO 1766 01:28:36,400 --> 01:28:40,480 VARIANTS. 1767 01:28:40,480 --> 01:28:42,440 SHORT TERM RESULTS AFTER 29 DAYS 1768 01:28:42,440 --> 01:28:44,520 SHOWING HERE AND SOME LONGER 1769 01:28:44,520 --> 01:28:46,520 TERM DATA HAS NOW BEEN PUBLISHED 1770 01:28:46,520 --> 01:28:50,200 ARE PROMISING. 1771 01:28:50,200 --> 01:28:53,720 WHAT'S GOING ON LONG TERM? 1772 01:28:53,720 --> 01:28:54,840 THIS IS THE PLOT. 1773 01:28:54,840 --> 01:28:57,640 THE 508s ARE PLOTTED OUT AGAINST 1774 01:28:57,640 --> 01:28:59,080 THE EXPECTATION AND CHANGE IN 1775 01:28:59,080 --> 01:29:01,200 SWEAT CHLORIDE AND INDEED THEY 1776 01:29:01,200 --> 01:29:09,440 MATCH UP FOR THE SIX TRIALS. 1777 01:29:09,440 --> 01:29:12,240 AND LUNG FUNCTION FALLS SHORT. 1778 01:29:12,240 --> 01:29:13,560 WE KNOW DATA FALLS SHORT AND 1779 01:29:13,560 --> 01:29:15,800 THIS IS RETROSPECTIVE ANALYSIS 1780 01:29:15,800 --> 01:29:18,600 AND BELIEVE THE PLOTS COULD BE 1781 01:29:18,600 --> 01:29:20,320 USED FOR DESIGN PROSPECTIVE 1782 01:29:20,320 --> 01:29:21,720 STUDIES BUT FROM WHAT WE HAVE IN 1783 01:29:21,720 --> 01:29:23,200 HAND RIGHT NOW IT SEEMS THERE'S 1784 01:29:23,200 --> 01:29:28,040 A BIT OF A GAP FROM OUR 1785 01:29:28,040 --> 01:29:29,480 EXPECTATION MAY BE. 1786 01:29:29,480 --> 01:29:33,040 PROVEN LUNG FUNCTION ONCE YOU 1787 01:29:33,040 --> 01:29:36,480 PUSH CFTR FUNCTION TO 100% WILD 1788 01:29:36,480 --> 01:29:36,680 TYPE. 1789 01:29:36,680 --> 01:29:39,120 WHAT ABOUT SINGLE MUTATIONS? 1790 01:29:39,120 --> 01:29:41,280 WE HAVE 508 MUTATION AND SWEAT 1791 01:29:41,280 --> 01:29:43,120 CHLORIDE RESULTS LOOK PRETTY 1792 01:29:43,120 --> 01:29:43,920 GOOD. 1793 01:29:43,920 --> 01:29:46,560 THEY'RE RESPONDING VERY NICELY. 1794 01:29:46,560 --> 01:29:49,880 LUNG FUNCTION AGAIN IS NOT QUITE 1795 01:29:49,880 --> 01:29:51,000 ACHIEVING WHAT WE THINK IT 1796 01:29:51,000 --> 01:29:53,400 SHOULD HAVE. 1797 01:29:53,400 --> 01:29:55,200 AGAIN, THIS IS POPULATION DATA. 1798 01:29:55,200 --> 01:29:58,200 IT'S DIFFICULT TO THEN TRANSLATE 1799 01:29:58,200 --> 01:29:59,640 COMPLETELY TO AN INDIVIDUAL BUT 1800 01:29:59,640 --> 01:30:01,080 IT'S DIFFICULT TO DO. 1801 01:30:01,080 --> 01:30:02,360 THERE ARE SOME WAYS WE THINK YOU 1802 01:30:02,360 --> 01:30:06,160 CAN CONSIDER THEM. 1803 01:30:06,160 --> 01:30:09,640 THIS IS A PLOT THAT WE'VE 1804 01:30:09,640 --> 01:30:13,000 PRODUCED FOR THE BLUE JOURNAL 1805 01:30:13,000 --> 01:30:14,440 PAPER CITATION IS THERE. 1806 01:30:14,440 --> 01:30:17,240 WE ARE REVISITING IT NOW TO REDO 1807 01:30:17,240 --> 01:30:20,960 THIS BASED AND THE FACT WE NOW 1808 01:30:20,960 --> 01:30:26,280 HAVE 122,000 INDIVIDUALS IN 1809 01:30:26,280 --> 01:30:28,120 RECRUITMENT OF CFTR AND 1810 01:30:28,120 --> 01:30:32,680 PREDICTED A DIFFERENT AGE RANGES 1811 01:30:32,680 --> 01:30:34,440 AND DIFFERENT PREDICTED LEVELS 1812 01:30:34,440 --> 01:30:37,840 RANGE FROM LESS THAN 2% UP TO 1813 01:30:37,840 --> 01:30:40,320 25% TO 50% FUNCTION. 1814 01:30:40,320 --> 01:30:45,120 EACH BOX IS STARTING OUT 1815 01:30:45,120 --> 01:30:47,240 APPROXIMATELY 100% FEV1 IN 1816 01:30:47,240 --> 01:30:48,240 INDIVIDUALS BASICALLY CHILDREN 1817 01:30:48,240 --> 01:30:49,600 AND WE'RE SEEING HOW THEY 1818 01:30:49,600 --> 01:30:51,840 PROGRESS OVER TIME. 1819 01:30:51,840 --> 01:30:53,280 IF YOU HAVE AN INDIVIDUAL OVER 1820 01:30:53,280 --> 01:30:55,480 40 YEARS OF AGE AND ACUTELY 1821 01:30:55,480 --> 01:30:58,520 RAISE THEIR FUNCTION FROM 2% UP 1822 01:30:58,520 --> 01:31:00,920 TO 10% OR 15%, WHAT MIGHT YOU 1823 01:31:00,920 --> 01:31:01,280 EXPECT? 1824 01:31:01,280 --> 01:31:03,400 YOU MIGHT EXPECT FROM THIS PLOT 1825 01:31:03,400 --> 01:31:06,960 TO GET ABOUT A 15% TO 20% 1826 01:31:06,960 --> 01:31:08,400 IMPROVEMENT IN FEV1. 1827 01:31:08,400 --> 01:31:09,440 IF WE COMPLETELY REVERSE THE 1828 01:31:09,440 --> 01:31:12,280 DISEASE IN THAT INDIVIDUAL. 1829 01:31:12,280 --> 01:31:16,760 WHAT REALLY IS IMPORTANT THOUGH 1830 01:31:16,760 --> 01:31:18,920 IS THIS. 1831 01:31:18,920 --> 01:31:23,840 IF YOU HAVE 25% TO 50% CFTR 1832 01:31:23,840 --> 01:31:27,160 FUNCTION YOU CAN MAINTAIN 100 1833 01:31:27,160 --> 01:31:37,440 FEV1 LIFE TIME. 1834 01:31:44,480 --> 01:31:46,160 YOU HAVE TARGETS THAT WILL NEED 1835 01:31:46,160 --> 01:31:47,040 TO BE HIGHER. 1836 01:31:47,040 --> 01:31:48,280 PROBABLY 20% AND PROBABLY NEED 1837 01:31:48,280 --> 01:31:58,520 TO TARGET 50%. 1838 01:32:00,800 --> 01:32:02,440 AND THIS DATA PROVIDES EVIDENCE 1839 01:32:02,440 --> 01:32:12,800 THAT THAT IS THE CASE. 1840 01:32:14,440 --> 01:32:16,120 CAN IT BE USED TO PREDICT 1841 01:32:16,120 --> 01:32:16,760 OUTCOMES? 1842 01:32:16,760 --> 01:32:18,280 I THINK SO. 1843 01:32:18,280 --> 01:32:20,600 IF YOU SEE THEM MATCH HISTORICAL 1844 01:32:20,600 --> 01:32:21,640 EXPECTATIONS THAT'S PRETTY GOOD 1845 01:32:21,640 --> 01:32:24,400 EVIDENCE LIKELY YOU'LL HAVE 1846 01:32:24,400 --> 01:32:25,760 CHANGES IN LUNG FUNCTION THAT 1847 01:32:25,760 --> 01:32:27,960 ARE GOING TO AT LEAST IMPROVE. 1848 01:32:27,960 --> 01:32:32,960 IT'S NOT A 1:1 CORRELATION BUT 1849 01:32:32,960 --> 01:32:36,280 THERE'S A QUANTITATIVE 1850 01:32:36,280 --> 01:32:38,080 CORRELATION BUT PREDICTIVE OF 1851 01:32:38,080 --> 01:32:38,720 LUNG FUNCTION. 1852 01:32:38,720 --> 01:32:43,000 CAN THE DIFFERENCE IN PREDICTED 1853 01:32:43,000 --> 01:32:44,400 IN IMPROVEMENT OF DISEASE 1854 01:32:44,400 --> 01:32:46,160 SUGGEST IT COULD BE BUT KEEP IN 1855 01:32:46,160 --> 01:32:49,960 MIND WE'RE ONLY LOOKING AT THE 1856 01:32:49,960 --> 01:32:52,640 CHLORIDE FUNCTION OF CFTR. 1857 01:32:52,640 --> 01:32:57,240 NOT LOOKING AT REGULATION OF 1858 01:32:57,240 --> 01:32:57,440 EMAP. 1859 01:32:57,440 --> 01:32:59,440 IT'S POSSIBLE THOSE OTHER 1860 01:32:59,440 --> 01:33:00,480 FUNCTIONS WHEN ASSAYED FILL THAT 1861 01:33:00,480 --> 01:33:04,160 GAP AND CAN WE USE THE 1862 01:33:04,160 --> 01:33:07,360 PREDICTIONS THERE'S BEEN PUBLS 1863 01:33:07,360 --> 01:33:09,360 ON THIS AND I SHOWED WAYS TO 1864 01:33:09,360 --> 01:33:11,760 START THINKING ABOUT IT IN THIS 1865 01:33:11,760 --> 01:33:12,000 MANNER. 1866 01:33:12,000 --> 01:33:13,400 THANKS VERY MUCH FOR YOUR 1867 01:33:13,400 --> 01:33:13,680 ATTENTION. 1868 01:33:13,680 --> 01:33:14,120 APPRECIATE IT. 1869 01:33:14,120 --> 01:33:17,400 I'VE ENJOYED THE CONFERENCE. 1870 01:33:17,400 --> 01:33:18,400 >>ALL RIGHT, EVERYBODY. 1871 01:33:18,400 --> 01:33:18,720 WELCOME BACK. 1872 01:33:18,720 --> 01:33:22,560 I HAVE TO SAY YOU GUYS ARE GOING 1873 01:33:22,560 --> 01:33:24,520 NUTS IN THE CHAT BOX. 1874 01:33:24,520 --> 01:33:26,240 WHICH IS PHENOMENAL. 1875 01:33:26,240 --> 01:33:29,640 IT'S COOL TO SEE ALL THE THINGS 1876 01:33:29,640 --> 01:33:30,280 THE QUESTIONS AND THINGS BEING 1877 01:33:30,280 --> 01:33:40,480 SENT AROUND. 1878 01:33:50,240 --> 01:34:00,720 IN RELATION TO BRONCOSCOPY -- 1879 01:34:05,880 --> 01:34:08,800 BRONCHOSCOPY IN KIDS TO DEFINE 1880 01:34:08,800 --> 01:34:13,880 THE AIRWAY CONDITIONS AND 1881 01:34:13,880 --> 01:34:24,400 THERAPEUTIC TARGETS AND LOOKING 1882 01:34:32,440 --> 01:34:41,520 AT MODULATORS WHAT'S THE THOUGHT 1883 01:34:41,520 --> 01:34:43,480 WHETHER BRONCHOSCOPY COULD BE 1884 01:34:43,480 --> 01:34:53,600 HELPFUL. 1885 01:34:58,000 --> 01:35:02,840 >> THERE WAS A LOOK AT USING 1886 01:35:02,840 --> 01:35:05,320 THIS FOR PSEUDOMONAS AND IS IT 1887 01:35:05,320 --> 01:35:07,320 AN INTERESTING TOOL TO ASSESS 1888 01:35:07,320 --> 01:35:12,040 THE ENVIRONMENT IN THE LUNG AND 1889 01:35:12,040 --> 01:35:20,400 THE MUCUS AND DO THE STUDIES AT 1890 01:35:20,400 --> 01:35:20,880 THIS POINT. 1891 01:35:20,880 --> 01:35:21,840 THAT'S WHERE I SEE THE 1892 01:35:21,840 --> 01:35:22,160 CHALLENGE. 1893 01:35:22,160 --> 01:35:24,800 I SEE THE BENEFIT AND IN DOING 1894 01:35:24,800 --> 01:35:30,600 THE STUDIES TO BETTER UNDERSTAND 1895 01:35:30,600 --> 01:35:34,640 HOW MUCH WHAT IS GOING ON AND 1896 01:35:34,640 --> 01:35:36,880 HOW MUCH INFLAMMATION IS LEFT IN 1897 01:35:36,880 --> 01:35:47,440 THE SETTING ESPECIALLY EARLY ON. 1898 01:36:00,800 --> 01:36:02,440 >> IS THE QUESTION WE'RE ASKING 1899 01:36:02,440 --> 01:36:04,000 DIFFERENT THAN WHAT WE WERE 1900 01:36:04,000 --> 01:36:05,520 ASKING BACK THEN? 1901 01:36:05,520 --> 01:36:06,880 SPECIFICALLY, IF WE'RE WAITING 1902 01:36:06,880 --> 01:36:10,160 FOR A TIME WHEN AN INFANT OR A 1903 01:36:10,160 --> 01:36:12,040 YOUNG CHILD IS GOING TO BE 1904 01:36:12,040 --> 01:36:14,280 ELIGIBLE FOR MODULATORS SO WITH 1905 01:36:14,280 --> 01:36:15,760 A DIFFERENT QUESTION OF BEING AS 1906 01:36:15,760 --> 01:36:19,880 AGGRESSIVE AS WE CAN TO IDENTIFY 1907 01:36:19,880 --> 01:36:20,560 PSEUDOMONAS EARLY. 1908 01:36:20,560 --> 01:36:25,000 IS THE QUESTION DIFFERENT? 1909 01:36:25,000 --> 01:36:30,160 >> FOR PSEUDOMONAS I WOULD SAY 1910 01:36:30,160 --> 01:36:36,760 NO BECAUSE THAT'S THE QUESTION. 1911 01:36:36,760 --> 01:36:39,840 AND IF YOU HAVE EFFECTIVE 1912 01:36:39,840 --> 01:36:42,240 THERAPY YOU CAN HAVE THIS 1913 01:36:42,240 --> 01:36:43,200 DISCUSSION FROM DATA AND FROM 1914 01:36:43,200 --> 01:36:50,000 THE STUDY IN AUSTRALIA BUT IN 1915 01:36:50,000 --> 01:36:51,480 THE ABSENCE OF CLEAR 1916 01:36:51,480 --> 01:36:52,640 INTERVENTION IT BECOMES MORE 1917 01:36:52,640 --> 01:37:02,800 DIFFICULT. 1918 01:37:03,200 --> 01:37:05,480 >> THERE'S A NUMBER OF THINGS 1919 01:37:05,480 --> 01:37:13,600 GOING IN THE CHAT NOTING HIGHLY 1920 01:37:13,600 --> 01:37:14,240 EFFECTIVE MODULATED THERAPIES 1921 01:37:14,240 --> 01:37:16,240 LOOKING AT MICROBIOLOGY AND 1922 01:37:16,240 --> 01:37:17,080 INFLAMMATION AND THERE WERE 1923 01:37:17,080 --> 01:37:19,360 ISSUES WITH THE STUDIO THE 1924 01:37:19,360 --> 01:37:21,120 INCIDENTS OF PSEUDOMONAS IS 1925 01:37:21,120 --> 01:37:23,600 LOWER THAN EXPECTED WHICH LEFT 1926 01:37:23,600 --> 01:37:30,920 IT A BIT UNDER POWERED. 1927 01:37:30,920 --> 01:37:41,360 IT'S WORTH SOME DISCUSSION. 1928 01:37:41,840 --> 01:37:43,720 >> AS A PHYSICIAN I WOULD HAVE 1929 01:37:43,720 --> 01:37:45,920 ISSUES TRYING TO CONVINCE MY 1930 01:37:45,920 --> 01:37:51,520 PATIENTS TO GO INTO THE STUDIES. 1931 01:37:51,520 --> 01:37:54,480 >> JEN, NEXT QUESTION. 1932 01:37:54,480 --> 01:37:55,160 >> SURE. 1933 01:37:55,160 --> 01:37:58,040 I GUESS THE NEXT QUESTION I WAS 1934 01:37:58,040 --> 01:38:01,360 GOING TO ASK IS FOR THE WHOLE 1935 01:38:01,360 --> 01:38:04,040 PANEL BUT PROBABLY MORE THE 1936 01:38:04,040 --> 01:38:05,040 PULMONOLOGISTS IN THE GROUP. 1937 01:38:05,040 --> 01:38:09,640 IS IT TIME TO BRING BACK INFANT 1938 01:38:09,640 --> 01:38:10,360 PFDs. 1939 01:38:10,360 --> 01:38:12,240 IT WAS USED FOR RESEARCH YEARS 1940 01:38:12,240 --> 01:38:13,880 BACK IN THE SAME VEIN SHOULD WE 1941 01:38:13,880 --> 01:38:17,200 EXPLORE THE DEVELOPMENT OF 1942 01:38:17,200 --> 01:38:18,560 INFANTS LCI. 1943 01:38:18,560 --> 01:38:28,840 AS TALKED ABOUT. 1944 01:39:12,520 --> 01:39:13,720 >> ON THE PROVIDER SIDE THEY'RE 1945 01:39:13,720 --> 01:39:15,480 A PAIN AND VERY CHALLENGING FOR 1946 01:39:15,480 --> 01:39:16,800 MANY MANY REASONS. 1947 01:39:16,800 --> 01:39:20,400 THE SEDATION IS AN ISSUE. 1948 01:39:20,400 --> 01:39:22,480 >>I CAN'T 1949 01:39:22,480 --> 01:39:26,920 EVEN GET MRIs ON MY PATIENTS 1950 01:39:26,920 --> 01:39:27,880 BECAUSE THEY'RE PATIENTS. 1951 01:39:27,880 --> 01:39:29,120 I DON'T WANT TO EXPERIMENT ON 1952 01:39:29,120 --> 01:39:33,720 THEM OR TRY TO MAKE THEM INTO A 1953 01:39:33,720 --> 01:39:37,200 CASE STUDY. 1954 01:39:37,200 --> 01:39:38,760 >> I THINK THE CHALLENGE HAS 1955 01:39:38,760 --> 01:39:40,400 BEEN LAID OUT. 1956 01:39:40,400 --> 01:39:43,280 THE INFRASTRUCTURE FOR TESTING 1957 01:39:43,280 --> 01:39:45,280 IS DWINDLING BECAUSE IT'S HIGHLY 1958 01:39:45,280 --> 01:39:48,320 RESOURCE INTENSE AND THE 1959 01:39:48,320 --> 01:39:50,520 INFORMATION GAINED IS PROBABLY 1960 01:39:50,520 --> 01:39:52,040 NOT AT THE SAME LEVEL. 1961 01:39:52,040 --> 01:39:53,880 LCI FOR INFANTS MAY BE MORE 1962 01:39:53,880 --> 01:39:56,280 INTERESTING BECAUSE YOU CAN AT 1963 01:39:56,280 --> 01:39:57,600 LEAST EARLY ON YOU MAY BE ABLE 1964 01:39:57,600 --> 01:40:00,480 TO DO IT WITHOUT SEDATION AS A 1965 01:40:00,480 --> 01:40:02,160 GROUP IN SOUTH AFRICA THEY'VE 1966 01:40:02,160 --> 01:40:04,120 BEEN ABLE TO DO IT THROUGHOUT 1967 01:40:04,120 --> 01:40:05,520 INFANCY WITHOUT SEDATION WHICH 1968 01:40:05,520 --> 01:40:07,920 IS QUITE REMARKABLE AND THE 1969 01:40:07,920 --> 01:40:12,360 GROUP IN DENMARK IS USING MILD 1970 01:40:12,360 --> 01:40:13,560 INTRANASAL SEDATION FOR THAT. 1971 01:40:13,560 --> 01:40:16,080 THAT'S SOMETHING TO MOVE FORWARD 1972 01:40:16,080 --> 01:40:18,400 THEN IT'S MORE REALISTIC IN 1973 01:40:18,400 --> 01:40:19,920 TERMS OF THE BALANCE OF THE 1974 01:40:19,920 --> 01:40:21,160 BURDEN AND THE INFORMATION 1975 01:40:21,160 --> 01:40:23,280 GAINED FOR THE OTHER 1976 01:40:23,280 --> 01:40:24,080 METHODOLOGIES IT HAS BEEN RATHER 1977 01:40:24,080 --> 01:40:29,680 CHALLENGING. 1978 01:40:29,680 --> 01:40:32,240 >> THE MAIN POINT IS WHAT 1979 01:40:32,240 --> 01:40:33,560 OBJECTIVE DATA AND WHAT IS THE 1980 01:40:33,560 --> 01:40:37,840 RIGHT MODALITY TO USE TO OBTAIN 1981 01:40:37,840 --> 01:40:38,480 THAT. 1982 01:40:38,480 --> 01:40:44,800 PFTs ARE NOT IT BUT IS IT LCI OR 1983 01:40:44,800 --> 01:40:45,000 MRI. 1984 01:40:45,000 --> 01:40:47,320 ARE THERE OTHER THINGS WE CAN 1985 01:40:47,320 --> 01:40:51,440 DO. 1986 01:40:51,440 --> 01:41:00,880 THAT'S THE RIGHT WAY. 1987 01:41:00,880 --> 01:41:06,600 >> THERE WAS DISCUSSION 1988 01:41:06,600 --> 01:41:09,560 YESTERDAY IN THE BREAKOUT OF 1989 01:41:09,560 --> 01:41:10,240 HIGHLY EFFECTIVE MODULATORS WHO 1990 01:41:10,240 --> 01:41:14,360 GET VIRAL INFECTIONS AND MAY BE 1991 01:41:14,360 --> 01:41:17,240 ABLE TO CLEAR WITHOUT NEEDING 1992 01:41:17,240 --> 01:41:20,160 ANTIBIOTICS IS IT POSSIBLE 1993 01:41:20,160 --> 01:41:20,800 HIGHLY EFFECTIVE MODULATOR LEADS 1994 01:41:20,800 --> 01:41:23,600 TO UNCOUPLING OF INFLAMMATION 1995 01:41:23,600 --> 01:41:27,720 SINCE ONLY SOME IS TRIGGERED BY 1996 01:41:27,720 --> 01:41:28,000 THIS. 1997 01:41:28,000 --> 01:41:38,520 THAT'S A MULTI-PRONGED QUESTION. 1998 01:42:28,200 --> 01:42:30,600 >> I WOULDN'T WANT TO DO THIS 1999 01:42:30,600 --> 01:42:31,320 WITHOUT SUFFICIENT EVIDENCE 2000 01:42:31,320 --> 01:42:33,360 BECAUSE THERE'S A RISK YOU STILL 2001 01:42:33,360 --> 01:42:35,880 HAVE AN ISSUE OF LOSING FUNCTION 2002 01:42:35,880 --> 01:42:39,120 DURING EXACERBATION AND I'D HATE 2003 01:42:39,120 --> 01:42:40,440 TO SEE THAT BEFORE WE HAVE 2004 01:42:40,440 --> 01:42:41,680 ADEQUATE EVIDENCE. 2005 01:42:41,680 --> 01:42:43,640 >> I THINK SOME OF MY THOUGHTS 2006 01:42:43,640 --> 01:42:45,720 ARE THIS IS WHERE I THINK WE 2007 01:42:45,720 --> 01:42:46,600 NEED MORE INFORMATION. 2008 01:42:46,600 --> 01:42:48,880 I THINK WE DON'T KNOW WHAT'S 2009 01:42:48,880 --> 01:42:50,760 GOING ON DURING THESE VIRAL 2010 01:42:50,760 --> 01:42:51,120 EXACERBATIONS. 2011 01:42:51,120 --> 01:42:52,760 SO OUR HOPE IS WITH OUR STUDY 2012 01:42:52,760 --> 01:42:57,120 AND I KNOW THERE'S OTHER FOLKS 2013 01:42:57,120 --> 01:42:59,040 THAT IF WE CAN UNDERSTAND THE 2014 01:42:59,040 --> 01:43:01,480 MICROBIAL POPULATIONS OF THE 2015 01:43:01,480 --> 01:43:04,080 PROBLEMATIC MICROBES LIKE 2016 01:43:04,080 --> 01:43:06,160 PSEUDOMONAS OR THE GENERAL 2017 01:43:06,160 --> 01:43:07,760 BURDEN AND TAXA CHANGES. 2018 01:43:07,760 --> 01:43:08,840 IF WE UNDERSTAND WHAT'S CHANGING 2019 01:43:08,840 --> 01:43:10,880 BETTER IT MAY GIVE HOPEFULLY 2020 01:43:10,880 --> 01:43:12,480 MORE INFORMATION TO PHYSICIANS 2021 01:43:12,480 --> 01:43:14,920 TO THINK ABOUT WHETHER TO BE 2022 01:43:14,920 --> 01:43:15,840 PRESCRIBING ANTIBIOTICS OR NOT 2023 01:43:15,840 --> 01:43:26,360 AND WE STILL DON'T KNOW ENOUGH. 2024 01:43:45,720 --> 01:43:50,200 >> IF WE LEARN ABOUT MOLECULAR 2025 01:43:50,200 --> 01:43:52,360 MECHANISMS AND THINK OF IRON OR 2026 01:43:52,360 --> 01:43:54,480 MODULATORS OF METABOLISM BEING 2027 01:43:54,480 --> 01:43:56,440 TESTED IN CANCER, CAN WE USE 2028 01:43:56,440 --> 01:43:57,720 SOMETHING LIKE THAT MAYBE THE 2029 01:43:57,720 --> 01:43:59,840 ANTIBIOTIC IS THE APPROACH BUT 2030 01:43:59,840 --> 01:44:01,760 TARGETING SOME OF THOSE 2031 01:44:01,760 --> 01:44:04,520 DYSREGULATIONS IS MAYBE 2032 01:44:04,520 --> 01:44:05,120 SOMETHING TO CONSIDER. 2033 01:44:05,120 --> 01:44:10,560 >> I WAS GOING TO MAKE A COMMENT 2034 01:44:10,560 --> 01:44:16,400 ABOUT SOME DATA IN THE SETTING 2035 01:44:16,400 --> 01:44:18,640 OF HIGHLY EFFECTIVE MODULATORS 2036 01:44:18,640 --> 01:44:21,640 THE BURDEN OF CF PATHOGENS WENT 2037 01:44:21,640 --> 01:44:22,280 DOWN. 2038 01:44:22,280 --> 01:44:24,360 BEING ON MODULATORS AND 2039 01:44:24,360 --> 01:44:25,480 PSEUDOMONAS AND THINGS WE 2040 01:44:25,480 --> 01:44:29,320 CONSIDER TO BE CF PATHOGENS THAT 2041 01:44:29,320 --> 01:44:31,560 DENSITY DECREASED IF YOU HAVE A 2042 01:44:31,560 --> 01:44:33,160 KID ON HIGHLY EFFECTIVE 2043 01:44:33,160 --> 01:44:35,880 MODULATORS WHO GETS AN INFECTION 2044 01:44:35,880 --> 01:44:38,920 THE THOUGHT IT WILL CAUSE MORE 2045 01:44:38,920 --> 01:44:39,800 INFLAMMATION AND DAMAGE BUT IF 2046 01:44:39,800 --> 01:44:44,880 THE PATHOGENS THE BURDEN IS 2047 01:44:44,880 --> 01:44:46,160 DECREASED THEN MAYBE WE DON'T 2048 01:44:46,160 --> 01:44:48,080 HAVE TO USE ANTIBIOTICS IF THOSE 2049 01:44:48,080 --> 01:44:50,000 SPECIFIC PATHOGENS AREN'T GOING 2050 01:44:50,000 --> 01:44:50,840 TO FLOURISH. 2051 01:44:50,840 --> 01:44:53,440 IT WAS VERY INTRIGUING DATA I 2052 01:44:53,440 --> 01:44:55,160 DON'T THINK I'D SEEN BEFORE TO 2053 01:44:55,160 --> 01:44:56,560 THINK ABOUT WHAT ARE THE IMPACT 2054 01:44:56,560 --> 01:45:00,000 OF THE MODULATORS ON THE 2055 01:45:00,000 --> 01:45:01,080 TRADITIONAL CF PATHOGENS AND HOW 2056 01:45:01,080 --> 01:45:03,440 CAN WE USE THAT TO HELP MAKE 2057 01:45:03,440 --> 01:45:04,160 CLINICAL DECISIONS? 2058 01:45:04,160 --> 01:45:05,760 WE ARE FAR FROM THAT BUT IT WAS 2059 01:45:05,760 --> 01:45:06,440 INTERESTING TO SEE THAT WAS WHAT 2060 01:45:06,440 --> 01:45:11,520 WAS PRESENTED. 2061 01:45:11,520 --> 01:45:13,840 >> ON THE OTHER HAND THE 2062 01:45:13,840 --> 01:45:24,280 PATHOGENS DID NOT GO AWAY. 2063 01:45:25,160 --> 01:45:26,880 >> I'VE BEEN USING IT ON THE 2064 01:45:26,880 --> 01:45:28,680 OLDER KIDS AND BEEN WILLING TO 2065 01:45:28,680 --> 01:45:31,880 DO A PFG AND LET A FEW HAVE 2066 01:45:31,880 --> 01:45:34,880 COLDS WITHOUT A COURSE OF 2067 01:45:34,880 --> 01:45:40,000 ANTIBIOTICS IF THEY'RE STABLE ON 2068 01:45:40,000 --> 01:45:40,560 HIGHLY EFFECTIVE MODULATED 2069 01:45:40,560 --> 01:45:41,680 THERAPY AND BEEN ABLE TO SHORTEN 2070 01:45:41,680 --> 01:45:44,120 THE COURSES BASED ON THE LIQUID 2071 01:45:44,120 --> 01:45:46,400 ANTIBIOTICS ARE ONLY GOOD FOR 10 2072 01:45:46,400 --> 01:45:46,600 DAYS. 2073 01:45:46,600 --> 01:45:49,520 I KNOW THEY'RE WORKING ON A 2074 01:45:49,520 --> 01:45:51,880 PEDIATRIC TRIAL TO KNOW THE 2075 01:45:51,880 --> 01:45:54,960 DURATION WE NEED BUT I'VE BEEN 2076 01:45:54,960 --> 01:45:59,160 WILLING FOR THE ONES ON 2077 01:45:59,160 --> 01:46:01,080 MODULATORS SAYING WE'LL ASSET AT 2078 01:46:01,080 --> 01:46:02,680 NINE DAYS OF ANTIBIOTICS TO 2079 01:46:02,680 --> 01:46:04,360 FINISH OUT THE PRESCRIPTION OR 2080 01:46:04,360 --> 01:46:05,800 DO FOUR MORE DAYS OR ANOTHER 2081 01:46:05,800 --> 01:46:06,280 WEEK'S WORTH. 2082 01:46:06,280 --> 01:46:11,120 >> I THINK WE ALL AGREE IT'S AN 2083 01:46:11,120 --> 01:46:12,760 OPPORTUNITY TO LEARN MORE IN AN 2084 01:46:12,760 --> 01:46:14,360 AREA VERY IMPORTANT TO EXPLORE. 2085 01:46:14,360 --> 01:46:24,600 >> ABSOLUTELY. 2086 01:46:34,480 --> 01:46:36,360 >> JEN, DO YOU HAVE THE NEXT 2087 01:46:36,360 --> 01:46:36,600 ONE. 2088 01:46:36,600 --> 01:46:39,200 >> SORRY, LOOKING IN THE CHAT. 2089 01:46:39,200 --> 01:46:41,040 THERE'S A LOT GOING ON. 2090 01:46:41,040 --> 01:46:43,440 >> AS FOLKS CHAT, THEY'RE LOSING 2091 01:46:43,440 --> 01:46:44,680 THEIR QUESTIONS BECAUSE THEY 2092 01:46:44,680 --> 01:46:45,800 HAVE TO SCROLL FOR THEM. 2093 01:46:45,800 --> 01:46:48,760 THAT'S THE DELAY. 2094 01:46:48,760 --> 01:46:49,000 APOLOGIES. 2095 01:46:49,000 --> 01:46:51,360 >> STOP TALKING, GUYS. 2096 01:46:51,360 --> 01:46:54,920 [LAUGHTER] 2097 01:46:54,920 --> 01:46:57,280 >> THE ONE QUESTION RAISED IS 2098 01:46:57,280 --> 01:46:58,440 THAT GIVEN WE'RE EXPECTING 2099 01:46:58,440 --> 01:47:01,040 PATIENTS TO LIVE AT LEAST 50 2100 01:47:01,040 --> 01:47:02,560 YEARS NOW ON MODULATORS AND WE 2101 01:47:02,560 --> 01:47:06,080 WANT TO ENSURE THEY'RE IMPROVING 2102 01:47:06,080 --> 01:47:07,400 IN QUALITY OF LIFE AND GIVING 2103 01:47:07,400 --> 01:47:09,880 PEOPLE THE BEST POSSIBLE START, 2104 01:47:09,880 --> 01:47:15,120 WHAT SHOULD WE BE DOING IN TERMS 2105 01:47:15,120 --> 01:47:17,120 OF I GUESS THE QUESTION IS WHAT 2106 01:47:17,120 --> 01:47:19,200 SHOULD WE BE DOING IN TERMS OF 2107 01:47:19,200 --> 01:47:29,720 HELP KIDS HAVE THE BEST START? 2108 01:47:30,640 --> 01:47:32,080 TERI RAISED GREAT QUESTIONS IN 2109 01:47:32,080 --> 01:47:32,840 HER TALK. 2110 01:47:32,840 --> 01:47:38,440 >> I THINK FOR ME THAT'S A HUGE 2111 01:47:38,440 --> 01:47:39,000 QUESTION. 2112 01:47:39,000 --> 01:47:40,440 I THINK THAT'S WHERE MY HEAD 2113 01:47:40,440 --> 01:47:45,720 GOES IN TERMS OF THINKING ABOUT 2114 01:47:45,720 --> 01:47:48,240 BRONCHOSCOPY AND WHAT TOOLS DO 2115 01:47:48,240 --> 01:47:50,440 WE HAVE TO ENCOURAGE OUR KIDS TO 2116 01:47:50,440 --> 01:47:57,200 BE ADEQUATELY NOURISHED AND HAVE 2117 01:47:57,200 --> 01:47:58,800 AS LITTLE LUNG DISEASE UNTIL WE 2118 01:47:58,800 --> 01:47:59,960 START THEIR MODULATOR. 2119 01:47:59,960 --> 01:48:01,200 WE MONITOR AND SEE KIDS AND 2120 01:48:01,200 --> 01:48:02,560 CULTURE THEM AND TREAT THEM WHEN 2121 01:48:02,560 --> 01:48:05,760 THEY HAVE INFECTIONS OR 2122 01:48:05,760 --> 01:48:06,640 EXACERBATIONS. 2123 01:48:06,640 --> 01:48:08,840 WE DO A LOT RIGHT NOW. 2124 01:48:08,840 --> 01:48:10,200 I GUESS MY QUESTION IN MY HEAD 2125 01:48:10,200 --> 01:48:12,440 IS DO WE NEED TO PUSH DOWN ON 2126 01:48:12,440 --> 01:48:14,680 THE ACCELERATOR FURTHER KNOWING 2127 01:48:14,680 --> 01:48:16,760 THAT WE'RE PROBABLY NOT GOING TO 2128 01:48:16,760 --> 01:48:17,600 REVERSE ANY ESTABLISHED LUNG 2129 01:48:17,600 --> 01:48:20,320 DISEASE WITH THE START OF A 2130 01:48:20,320 --> 01:48:20,600 MODULATOR. 2131 01:48:20,600 --> 01:48:22,320 SO DO WE NEED TO MAKE SURE WE'RE 2132 01:48:22,320 --> 01:48:25,400 IN THE BEST PLACE POSSIBLE AND 2133 01:48:25,400 --> 01:48:26,840 ARE WE -- ARE THE PROTOCOLS WE 2134 01:48:26,840 --> 01:48:28,760 CURRENTLY FOLLOW, DO THEY PUT US 2135 01:48:28,760 --> 01:48:30,720 IN THAT POSITION. 2136 01:48:30,720 --> 01:48:31,960 IS THERE SOMETHING ELSE WE NEED 2137 01:48:31,960 --> 01:48:34,080 TO BE DOING AND THAT IS A BIG 2138 01:48:34,080 --> 01:48:36,920 GAP FOR US AS A COMMUNITY TO DO 2139 01:48:36,920 --> 01:48:38,480 THE SAME THING SO THAT OUR 2140 01:48:38,480 --> 01:48:39,040 PATIENTS ARE IN THE BEST 2141 01:48:39,040 --> 01:48:42,640 POSITION POSSIBLE. 2142 01:48:42,640 --> 01:48:44,400 >> I THINK IT'S INTERESTING HOW 2143 01:48:44,400 --> 01:48:45,440 YOU RAISE THE QUESTION. 2144 01:48:45,440 --> 01:48:48,240 IN A WAY FOR ME THAT WAS ALWAYS 2145 01:48:48,240 --> 01:48:49,720 THE STRATEGY WE WERE FOLLOWING 2146 01:48:49,720 --> 01:48:53,680 TO KEEP PATIENTS AS HEALTHY AS 2147 01:48:53,680 --> 01:48:54,440 POSSIBLE FOR THE FUTURE 2148 01:48:54,440 --> 01:48:57,520 OPPORTUNITIES COMING IN. 2149 01:48:57,520 --> 01:49:00,200 THAT'S THE WAY I SAW EARLY 2150 01:49:00,200 --> 01:49:02,160 INTERVENTION THERAPY WITH OTHER 2151 01:49:02,160 --> 01:49:06,320 INTERVENTION SAYING OKAY THIS IS 2152 01:49:06,320 --> 01:49:08,400 AN INVESTMENT AND WE CAN THEN 2153 01:49:08,400 --> 01:49:09,760 BENEFIT FROM OTHER THERAPIES 2154 01:49:09,760 --> 01:49:16,160 THAT MAY BE MORE DRAMATIC. 2155 01:49:16,160 --> 01:49:17,000 IT'S INTERESTING BUT ALSO 2156 01:49:17,000 --> 01:49:19,080 DIFFICULT FOR KNOW ENVISION HOW 2157 01:49:19,080 --> 01:49:20,680 WE WOULD BE MORE AGGRESSIVE IN A 2158 01:49:20,680 --> 01:49:22,040 WAY THAT WOULD BE BENEFICIAL 2159 01:49:22,040 --> 01:49:23,520 BECAUSE ON THE OTHER HAND WE 2160 01:49:23,520 --> 01:49:24,920 DON'T WANT TO BE IN THE 2161 01:49:24,920 --> 01:49:28,080 SITUATION WHERE WE THROW THE 2162 01:49:28,080 --> 01:49:30,120 KITCHEN THINK AT EVERYBODY AND 2163 01:49:30,120 --> 01:49:32,400 ALL DIAGNOSTIC MEASURES IF WE 2164 01:49:32,400 --> 01:49:36,440 DON'T KNOW THEY'RE OF BENEFIT. 2165 01:49:36,440 --> 01:49:38,600 I FEEL AND THINK IT HAS BEEN 2166 01:49:38,600 --> 01:49:44,360 DONE FOR BRONCHOSCOPY AND NEED 2167 01:49:44,360 --> 01:49:45,920 TO DO THIS AND BE DILIGENT IN 2168 01:49:45,920 --> 01:49:49,600 WHATEVER WE TRY TO IMPLEMENT IS 2169 01:49:49,600 --> 01:49:50,360 ACTUALLY PROVIDING BENEFIT TO 2170 01:49:50,360 --> 01:49:58,760 THE PATIENTS. 2171 01:49:58,760 --> 01:50:00,440 >> THE ONE THING THAT COMES MY 2172 01:50:00,440 --> 01:50:02,320 MIND IS NUTRITION AND PUSHING 2173 01:50:02,320 --> 01:50:03,560 FAMILIES TO MAKE THE DECISION. 2174 01:50:03,560 --> 01:50:05,840 THINKING IN MY MIND THE KIDS 2175 01:50:05,840 --> 01:50:07,560 I'VE TAKEN CARE OF OVER THE YEAR 2176 01:50:07,560 --> 01:50:08,760 WHO WILL SOMETIMES BE WE'LL GIVE 2177 01:50:08,760 --> 01:50:10,440 YOU THREE MONTHS OR SIX MONTHS 2178 01:50:10,440 --> 01:50:12,480 AND TURNS INTO A YEAR OR 18 2179 01:50:12,480 --> 01:50:15,760 MONTHS AND WE STILL HAVE A KID 2180 01:50:15,760 --> 01:50:16,200 NOT GROWING. 2181 01:50:16,200 --> 01:50:18,440 AND SPECIFICALLY FOR SITUATIONS 2182 01:50:18,440 --> 01:50:20,840 LIKE THAT WHERE WE KNOW HOW 2183 01:50:20,840 --> 01:50:22,440 IMPORTANT NUTRITION IS DO WE 2184 01:50:22,440 --> 01:50:26,920 NEED TO PULL THE TRIGGER SOONER 2185 01:50:26,920 --> 01:50:31,480 AND SAY WHEN YOU TURN 6 YOU'LL 2186 01:50:31,480 --> 01:50:32,640 HAVE THIS MODULATOR AND 2187 01:50:32,640 --> 01:50:34,880 SITUATIONS LIKE THAT WHERE I 2188 01:50:34,880 --> 01:50:36,320 AGREE, FELIX, WE'RE DOING AS 2189 01:50:36,320 --> 01:50:39,480 MUCH AS WE CAN TO KEEP OUR KIDS 2190 01:50:39,480 --> 01:50:39,720 HEALTHY. 2191 01:50:39,720 --> 01:50:42,040 I'M THINKING ABOUT THE SPECIFIC 2192 01:50:42,040 --> 01:50:46,360 SCENARIOS WHERE WE TEND TO HAVE 2193 01:50:46,360 --> 01:50:47,000 MORE PATIENCE AND MAYBE WE 2194 01:50:47,000 --> 01:50:47,720 SHOULDN'T WHEN WE KNOW WHAT'S AT 2195 01:50:47,720 --> 01:50:57,840 STAKE. 2196 01:50:59,680 --> 01:51:05,720 >> AS A GENETICISTS WE DEAL WITH 2197 01:51:05,720 --> 01:51:07,960 DISEASE AND GENETIC DISORDERS 2198 01:51:07,960 --> 01:51:11,120 AND I THINK THE DATA WAS 2199 01:51:11,120 --> 01:51:12,360 PROVOCATIVE IF YOU START 2200 01:51:12,360 --> 01:51:18,720 TREATMENT EVEN IN UTERO YOU CAN 2201 01:51:19,000 --> 01:51:19,800 AVOID A LOT OF THE PROBLEMS IN 2202 01:51:19,800 --> 01:51:23,880 THE LUNGS THAT OCCUR IN UTERO. 2203 01:51:23,880 --> 01:51:25,640 THE REAL GOAL AT THEN OF THE DAY 2204 01:51:25,640 --> 01:51:28,720 IS TO START TREATMENT AS SOON AS 2205 01:51:28,720 --> 01:51:29,400 POSSIBLE. 2206 01:51:29,400 --> 01:51:31,240 CERTAIN PKU THE SUCCESS OF 2207 01:51:31,240 --> 01:51:33,680 TREATING THAT DISEASE IS 2208 01:51:33,680 --> 01:51:35,800 STARTING FIRST WITH SCREENING 2209 01:51:35,800 --> 01:51:40,280 AND THEN STARTING AND FOLLOWING 2210 01:51:40,280 --> 01:51:50,800 AS THE KEY INDICATOR OF SUCCESS 2211 01:51:51,960 --> 01:51:57,840 AND THERE'S MANY OTHER GENETIC 2212 01:51:57,840 --> 01:52:02,640 DISEASES THAT YOU WANT LONG TERM 2213 01:52:02,640 --> 01:52:04,480 OUTCOMES YOU HAVE TO START 2214 01:52:04,480 --> 01:52:04,680 EARLY. 2215 01:52:04,680 --> 01:52:05,640 ALL THE OTHER MEASURES WE NEED 2216 01:52:05,640 --> 01:52:07,840 TO DEVELOP BUT WE NEED TO START 2217 01:52:07,840 --> 01:52:09,480 CONSIDERING HOW TO DO IT. 2218 01:52:09,480 --> 01:52:11,480 IN ORDER TO START EARLY WE NEED 2219 01:52:11,480 --> 01:52:13,200 TO CONSIDER RISK BENEFIT. 2220 01:52:13,200 --> 01:52:16,280 SO TREATING A CHILD OR A BABY 2221 01:52:16,280 --> 01:52:19,000 WITH A DRUG THAT WE DON'T KNOW 2222 01:52:19,000 --> 01:52:20,560 LONG TERM OUTCOMES HAS RISKS AND 2223 01:52:20,560 --> 01:52:23,160 WE DON'T KNOW WHAT THEY ARE 2224 01:52:23,160 --> 01:52:25,280 THOUGH WE'RE STARTING TO SEE 2225 01:52:25,280 --> 01:52:26,800 BEHAVIORAL ISSUES AND VISION AND 2226 01:52:26,800 --> 01:52:27,920 IN THE LIVER. 2227 01:52:27,920 --> 01:52:30,320 WHAT'S THE BENEFIT? 2228 01:52:30,320 --> 01:52:32,800 HOW MUCH DO WE KNOW OBJECTIVELY 2229 01:52:32,800 --> 01:52:33,760 ABOUT THE BENEFIT. 2230 01:52:33,760 --> 01:52:35,800 THAT'S WHAT WE TRY TO PRESENT. 2231 01:52:35,800 --> 01:52:37,040 THERE'S CLEAR BENEFIT. 2232 01:52:37,040 --> 01:52:39,400 YOU CAN ACHIEVE 25% TO 50% 2233 01:52:39,400 --> 01:52:41,240 FUNCTION SHORTLY AFTER BIRTH, 2234 01:52:41,240 --> 01:52:43,880 YOU'RE GOING HAVE, WE BELIEVE 2235 01:52:43,880 --> 01:52:45,680 NORMAL FUNCTION LIFE TIME. 2236 01:52:45,680 --> 01:52:47,080 I KNOW THERE'S A LOT OF CAVEATS 2237 01:52:47,080 --> 01:52:48,320 IN THIS. 2238 01:52:48,320 --> 01:52:50,040 THERE IS. 2239 01:52:50,040 --> 01:52:53,120 THIS IS A HIGH-LEVEL VIEW BUT 2240 01:52:53,120 --> 01:52:55,040 TOGETHER IF WE DEVELOP A LOT OF 2241 01:52:55,040 --> 01:52:56,800 INFORMATION THAT WE CAN PRESENT 2242 01:52:56,800 --> 01:53:00,160 TO PARENTS AND WE CAN PRESENT 2243 01:53:00,160 --> 01:53:04,280 THAT THE BENEFITS TRULY IN OUR 2244 01:53:04,280 --> 01:53:06,520 BEST ESTIMATE OUTWEIGH THE RISK 2245 01:53:06,520 --> 01:53:08,600 AND GETTING TREATMENT TO THE 2246 01:53:08,600 --> 01:53:11,680 YOUNGEST AGES OF PATIENTS WITH 2247 01:53:11,680 --> 01:53:13,080 INDIVIDUAL CF BECOME A 2248 01:53:13,080 --> 01:53:14,080 POSSIBILITY OTHERWISE IT MAY 2249 01:53:14,080 --> 01:53:16,480 TAKE A LONG TIME TO GET THERE. 2250 01:53:16,480 --> 01:53:18,480 AND MAYBE ONE OF OUR GOALS AND I 2251 01:53:18,480 --> 01:53:20,360 CERTAINLY SEE SOME OF THIS 2252 01:53:20,360 --> 01:53:22,000 EVOLVING IN THE SESSION AND ALSO 2253 01:53:22,000 --> 01:53:22,920 THROUGH THE CONFERENCE ACTUALLY 2254 01:53:22,920 --> 01:53:25,960 IS HOW DO WE GET THAT DATA TO 2255 01:53:25,960 --> 01:53:27,920 MAKE THE ARGUMENT THE BENEFIT 2256 01:53:27,920 --> 01:53:30,560 REALLY DO OUTWEIGH THE RISKS 2257 01:53:30,560 --> 01:53:33,440 WHEN WE GIVE THESE DRUGS TO A 2258 01:53:33,440 --> 01:53:33,760 2-MONTH-OLD. 2259 01:53:33,760 --> 01:53:37,720 THAT'S WHAT I'VE BEEN THINKING. 2260 01:53:37,720 --> 01:53:41,280 GREAT IF WE GET IT FROM PFTs OR 2261 01:53:41,280 --> 01:53:45,720 OTHER TOOLS FOR INFECTION. 2262 01:53:45,720 --> 01:53:46,880 >> I THINK IT'S GOOD. 2263 01:53:46,880 --> 01:53:49,120 WE'RE TALKING ABOUT THE 2264 01:53:49,120 --> 01:53:52,440 UNCERTAINTY OF LONG-TERM 2265 01:53:52,440 --> 01:53:54,280 OUTCOMES OF THE MODULATORS AND 2266 01:53:54,280 --> 01:53:56,320 I'VE HAD DISCUSSIONS WITH BOTH 2267 01:53:56,320 --> 01:53:58,400 PATIENT WE WILLING TO LET THEIR 2268 01:53:58,400 --> 01:54:01,880 PANCREAS SLOWLY OR RAPIDLY DIE 2269 01:54:01,880 --> 01:54:02,040 OFF. 2270 01:54:02,040 --> 01:54:03,440 THERE IS UNCERTAINTY BUT THERE'S 2271 01:54:03,440 --> 01:54:06,120 ALSO WE KNOW WHAT UNTREATED CF 2272 01:54:06,120 --> 01:54:06,400 LOOKS LIKE. 2273 01:54:06,400 --> 01:54:10,480 IT'S NOT GOOD. 2274 01:54:10,480 --> 01:54:12,760 >> AS I SAID, YOU KNOW WHAT A 2275 01:54:12,760 --> 01:54:15,440 CARRIER LOOKS LIKE. 2276 01:54:15,440 --> 01:54:18,840 AS ANN HARRIS POINTED OUT IT'S 2277 01:54:18,840 --> 01:54:23,960 AN IN UTERO MALDEVELOPMENT 2278 01:54:23,960 --> 01:54:25,840 PROBLEM AND SOME CHILDREN WILL 2279 01:54:25,840 --> 01:54:27,840 RAPIDLY DEVELOP IT AND NEW DATA 2280 01:54:27,840 --> 01:54:30,360 IS VERY CLEAR WHAT YOU CAN DO 2281 01:54:30,360 --> 01:54:31,880 WITH EARLY APPLICATION OF 2282 01:54:31,880 --> 01:54:32,160 MODULATORS. 2283 01:54:32,160 --> 01:54:33,560 IT SOUNDS LIKE MORE EVIDENCE 2284 01:54:33,560 --> 01:54:35,280 THAT WAY THAN IN OTHER VENUES 2285 01:54:35,280 --> 01:54:38,440 WILL HELP. 2286 01:54:38,440 --> 01:54:43,240 >> I THINK OF THE CHILD WHO HER 2287 01:54:43,240 --> 01:54:44,920 SISTER HAS TO GO TO THE SCHOOL 2288 01:54:44,920 --> 01:54:47,560 NURSE TO GET ENZYMES BEFORE 2289 01:54:47,560 --> 01:54:50,720 BIRTHDAY PARTIES OR WHATEVER AND 2290 01:54:50,720 --> 01:54:53,160 MAYBE THE YOUNGER ONE WILL NEVER 2291 01:54:53,160 --> 01:54:53,680 HAVE TO. 2292 01:54:53,680 --> 01:55:00,320 IN TERMS OF QUALITY OF LIFE, 2293 01:55:00,320 --> 01:55:03,640 IMAGINE THAT. 2294 01:55:03,640 --> 01:55:08,840 >> WANTED TO MAKE A COMMENT OF A 2295 01:55:08,840 --> 01:55:13,720 MOTHER NOT ON CF TAKING TRIK 2296 01:55:13,720 --> 01:55:14,000 TRIKAFTA. 2297 01:55:14,000 --> 01:55:16,080 I DON'T KNOW WHAT TO SAY ABOUT 2298 01:55:16,080 --> 01:55:16,320 THAT. 2299 01:55:16,320 --> 01:55:17,520 THE CONCEPT MAKES SENSE. 2300 01:55:17,520 --> 01:55:20,200 THAT'S WHAT GARY WAS SAYING. 2301 01:55:20,200 --> 01:55:21,960 IF WE'RE GOING TO -- THAT'S 2302 01:55:21,960 --> 01:55:26,400 WHAT'S GOING TO PREVENT A LOT OF 2303 01:55:26,400 --> 01:55:28,080 THE SEQUELAE WE SEE BUT WHAT ARE 2304 01:55:28,080 --> 01:55:31,600 THE RISKS OF DOING THAT? 2305 01:55:31,600 --> 01:55:35,360 I'M PRETTY AMAZED THEY WERE ABLE 2306 01:55:35,360 --> 01:55:37,320 TO GET THAT AND ADMINISTER THAT 2307 01:55:37,320 --> 01:55:43,320 AND THIS WAS THE SAME KID THAT 2308 01:55:43,320 --> 01:55:53,720 HAD THE PALPABLE VAS DEFERENS. 2309 01:55:53,720 --> 01:55:59,160 >> WE'RE WATCHING IT EVERY WEEK. 2310 01:55:59,160 --> 01:56:02,320 >> 2311 01:56:02,320 --> 01:56:04,280 >> THE DATA FROM THE FERRETS AND 2312 01:56:04,280 --> 01:56:06,320 THE PIGS THE ANIMAL MODELS 2313 01:56:06,320 --> 01:56:08,880 PROVIDE AN IDEAL WAY TO TEST IN 2314 01:56:08,880 --> 01:56:12,480 A MORE THOROUGH AND OBJECTIVE 2315 01:56:12,480 --> 01:56:22,880 WAY IN UTERO TREATMENT. 2316 01:56:28,600 --> 01:56:30,320 WE DO OTHER THINGS TO MINIMIZE 2317 01:56:30,320 --> 01:56:31,840 THE LIFE TIME EFFECTS BY WORKING 2318 01:56:31,840 --> 01:56:34,400 AS EARLY AS WE CAN WITH THESE 2319 01:56:34,400 --> 01:56:41,320 CONDITIONS. 2320 01:56:41,320 --> 01:56:45,520 THERE'S PRECEDENCE AND THE IDEA 2321 01:56:45,520 --> 01:56:47,960 OF TREATING A MOM MAY NOT BE 2322 01:56:47,960 --> 01:56:48,840 THAT SURPRISING. 2323 01:56:48,840 --> 01:56:50,520 WE MAY SIT AND PONDER ABOUT IT 2324 01:56:50,520 --> 01:56:53,120 FOR SOME TIME AND IF WE CAN FIND 2325 01:56:53,120 --> 01:56:56,440 EVIDENCE A CARRIER MOM MAY 2326 01:56:56,440 --> 01:56:59,640 BENEFIT FROM TAKING TRIKAFTA BUT 2327 01:56:59,640 --> 01:57:00,760 TO TREAT HER CHILD, THIS WOULD 2328 01:57:00,760 --> 01:57:03,040 NOT BE COMPLETELY UNHEARD OF 2329 01:57:03,040 --> 01:57:10,440 BECAUSE WE TREAT PKU THAT WAY. 2330 01:57:10,440 --> 01:57:15,720 WE ALREADY PUT HER ON A 2331 01:57:15,720 --> 01:57:23,600 RESTRICTIVE DIET TO PREVENT THE 2332 01:57:23,600 --> 01:57:33,800 FETUS AND PROTECT IT AND IT WILL 2333 01:57:33,800 --> 01:57:37,120 BE WORTH IT THE EFFECT OF 2334 01:57:37,120 --> 01:57:39,040 TRIKAFTA ON MENTAL HEALTH 2335 01:57:39,040 --> 01:57:40,920 BECAUSE THAT'S BEEN WELL 2336 01:57:40,920 --> 01:57:42,040 DESCRIBED OR TALKED ABOUT A LOT 2337 01:57:42,040 --> 01:57:45,280 IN THE ADULT POPULATION. 2338 01:57:45,280 --> 01:57:48,680 I THINK MANY OF US HAVE 2339 01:57:48,680 --> 01:57:51,160 ANECDOTAL PATIENTS THAT HAVE HAD 2340 01:57:51,160 --> 01:57:52,960 MENTAL HEALTH ISSUES RELATED TO 2341 01:57:52,960 --> 01:57:55,160 STARTING TRIKAFTA BUT THAT'S 2342 01:57:55,160 --> 01:57:55,560 IMPORTANCE. 2343 01:57:55,560 --> 01:57:57,560 THAT'S A DIRECT IMPACT 2344 01:57:57,560 --> 01:58:01,000 POTENTIALLY OF TRIKAFTA ON A 2345 01:58:01,000 --> 01:58:04,200 DEVELOPING BRAIN OR ON CHILDREN. 2346 01:58:04,200 --> 01:58:05,840 THAT IS SOMETHING WE HAVE TO 2347 01:58:05,840 --> 01:58:07,200 UNDERSTAND IF WE'RE TRYING TO 2348 01:58:07,200 --> 01:58:09,240 TALK ABOUT WHEN TO START THE 2349 01:58:09,240 --> 01:58:09,520 MODULATORS. 2350 01:58:09,520 --> 01:58:11,640 IF WE'RE GOING TO START IT AT 2351 01:58:11,640 --> 01:58:13,280 BIRTH, WE HAVE TO HAVE A BETTER 2352 01:58:13,280 --> 01:58:15,400 UNDERSTANDING OF WHAT THE IMPACT 2353 01:58:15,400 --> 01:58:18,160 IS ON A GROWING DEVELOPING BRAIN 2354 01:58:18,160 --> 01:58:20,000 AND MAYBE THE ANIMAL MODEL IS 2355 01:58:20,000 --> 01:58:21,960 THE PLACE TO START TO UNDERSTAND 2356 01:58:21,960 --> 01:58:22,360 THAT. 2357 01:58:22,360 --> 01:58:26,200 THAT'S A BIG ISSUE. 2358 01:58:26,200 --> 01:58:28,120 >> I WANT TO JUMP IN AND SAY 2359 01:58:28,120 --> 01:58:29,960 WE'RE AT TIME FOR THIS SESSION. 2360 01:58:29,960 --> 01:58:31,960 THANK YOU ALL TO SESSION 3 2361 01:58:31,960 --> 01:58:32,320 SPEAKERS. 2362 01:58:32,320 --> 01:58:33,640 IT SOUNDS LIKE THERE'S MORE TO 2363 01:58:33,640 --> 01:58:34,120 BE DISCUSSED. 2364 01:58:34,120 --> 01:58:36,240 PLEASE USE THE CHAT AND WE'LL 2365 01:58:36,240 --> 01:58:37,200 HAVE DISCUSSION OPPORTUNITY IN 2366 01:58:37,200 --> 01:58:39,360 THE BREAKOUTS THIS AFTERNOON. 2367 01:58:39,360 --> 01:58:42,240 BUT FOR NOW WE'RE GOING MOVE ON 2368 01:58:42,240 --> 01:58:44,560 TO SESSION 4. 2369 01:58:44,560 --> 01:58:45,840 WHICH IS CONSIDERATION FOR 2370 01:58:45,840 --> 01:58:48,280 MODULATOR USE IN SPECIAL 2371 01:58:48,280 --> 01:58:49,080 POPULATIONS. 2372 01:58:49,080 --> 01:58:53,920 I WOULD LIKE TO TURN THE MEETING 2373 01:58:53,920 --> 01:58:54,480 OVER TO THE SESSION 4 2374 01:58:54,480 --> 01:59:04,680 MODERATORS. 2375 01:59:15,520 --> 01:59:17,960 >> THE TALKS WERE AMAZING AND I 2376 01:59:17,960 --> 01:59:19,240 FEEL WE CAN GO HOURS ON 2377 01:59:19,240 --> 01:59:29,640 EVERYTHING PRESENTED. 2378 01:59:34,240 --> 01:59:39,480 >> WE'LL HAVE FIVE TALKS FROM A 2379 01:59:39,480 --> 01:59:43,680 PROFESSOR OF MEDICINE AND PETE 2380 01:59:43,680 --> 01:59:46,840 -- PEDIATRICS AND LOOK AT THE 2381 01:59:46,840 --> 01:59:57,280 PERINATAL PERIODS AND CF. 2382 02:00:14,360 --> 02:00:15,880 >> THANK YOU FOR THE OPPORTUNITY 2383 02:00:15,880 --> 02:00:17,000 TO SPEAK TODAY. 2384 02:00:17,000 --> 02:00:19,640 I'LL GO OVER MY DISCLOSURES 2385 02:00:19,640 --> 02:00:21,160 BECAUSE I DO CONSULTING AS WELL 2386 02:00:21,160 --> 02:00:24,640 AS ACT AS A PRIMARY INVESTIGATOR 2387 02:00:24,640 --> 02:00:26,200 FOR OUR STUDIES. 2388 02:00:26,200 --> 02:00:27,280 FOR THIS TALK I'LL QUICKLY 2389 02:00:27,280 --> 02:00:28,560 DESCRIBE WHAT WE THINK WE KNOW 2390 02:00:28,560 --> 02:00:35,320 ABOUT THE IMPACTS OF CFTR 2391 02:00:35,320 --> 02:00:37,400 MODULATORS ON SEXUAL AND 2392 02:00:37,400 --> 02:00:38,120 REPRODUCTIVE HEALTH AND TALK 2393 02:00:38,120 --> 02:00:39,160 ABOUT THE SHORT-TERM OUTCOMES 2394 02:00:39,160 --> 02:00:39,960 AND GAPS. 2395 02:00:39,960 --> 02:00:41,960 AS MOST ARE WELL AWARE, AT THIS 2396 02:00:41,960 --> 02:00:44,360 POINT THE MAJORITY OF PEOPLE 2397 02:00:44,360 --> 02:00:49,600 WITH CF ARE AT LEAST VARIANT 2398 02:00:49,600 --> 02:00:51,520 ELIGIBLE FOR HIGHLY EFFECTIVE 2399 02:00:51,520 --> 02:00:52,120 MODULATED THERAPY IMPACTING 2400 02:00:52,120 --> 02:00:55,600 EVERYONE PROFOUNDLY AND THAT 2401 02:00:55,600 --> 02:00:57,440 CORRELATES WITH SURVIVAL. 2402 02:00:57,440 --> 02:00:58,600 THE REASON IT'S AN IMPORTANT 2403 02:00:58,600 --> 02:00:59,840 POINT IS BECAUSE WE'RE EXPECTING 2404 02:00:59,840 --> 02:01:03,000 TO SEE OVER THE NEXT 20 YEARS A 2405 02:01:03,000 --> 02:01:04,320 SIGNIFICANT INCREASE IN THE 2406 02:01:04,320 --> 02:01:06,080 POPULATION OF ADULTS WITH CF. 2407 02:01:06,080 --> 02:01:08,480 PEOPLE ARE LIVING LONGER. 2408 02:01:08,480 --> 02:01:10,160 THEY'RE FEELING HEALTHIER AND 2409 02:01:10,160 --> 02:01:10,760 CONSIDERING THEIR OPTIONS FOR 2410 02:01:10,760 --> 02:01:14,920 HAVING CHILDREN. 2411 02:01:14,920 --> 02:01:17,000 WHAT DO WE KNOW ABOUT FERTILITY 2412 02:01:17,000 --> 02:01:20,280 IN PEOPLE WITH CF? 2413 02:01:20,280 --> 02:01:24,200 GENERALLY, FEMALES WITH CF HAVE 2414 02:01:24,200 --> 02:01:25,680 REPRODUCTIVE ANATOMY AND THERE 2415 02:01:25,680 --> 02:01:28,000 ARE FACTORS THAT CAN AFFECT 2416 02:01:28,000 --> 02:01:28,640 FERTILITY. 2417 02:01:28,640 --> 02:01:36,680 THICK DE HYDRATED PH IMBALANCED 2418 02:01:36,680 --> 02:01:38,680 CERVICAL MUCUS AND IN THE PAST 2419 02:01:38,680 --> 02:01:41,360 WE SAW DELAYED PUBERTY AND 2420 02:01:41,360 --> 02:01:43,440 OVULATION AND PEOPLE HAD 2421 02:01:43,440 --> 02:01:49,720 SUBOPTIMAL NUTRITIONAL STATUS. 2422 02:01:49,720 --> 02:01:51,360 MOST FEMALES CAN BECOME 2423 02:01:51,360 --> 02:01:51,640 PREGNANT. 2424 02:01:51,640 --> 02:01:52,520 COLLEAGUES LOOKED AT FACTORS 2425 02:01:52,520 --> 02:01:55,520 THAT MADE IT HARDER FOR WOMEN TO 2426 02:01:55,520 --> 02:02:00,040 GET PREGNANT AND SHOW PANCREATIC 2427 02:02:00,040 --> 02:02:01,000 INSUFFICIENT AND OVER AT FIRST 2428 02:02:01,000 --> 02:02:03,200 ATTEMPT MADE IT HARDER FOR A 2429 02:02:03,200 --> 02:02:05,760 SUBSET OF PEOPLE WITH CF 2430 02:02:05,760 --> 02:02:07,040 HOWEVER, EVEN IN THE 2431 02:02:07,040 --> 02:02:10,200 PREMODULATOR ERA 29% TO 39% OF 2432 02:02:10,200 --> 02:02:10,880 PREGNANCIES IN FEMALES WITH CF 2433 02:02:10,880 --> 02:02:12,880 WERE UNPLANNED. 2434 02:02:12,880 --> 02:02:18,160 WHAT ABOUT THE IMPACT OF 2435 02:02:18,160 --> 02:02:18,480 MODULATORS? 2436 02:02:18,480 --> 02:02:20,120 I'LL SHOW YOU SEVERAL SLIDES IN 2437 02:02:20,120 --> 02:02:21,960 WHICH THE REPRODUCTIVE HEALTH 2438 02:02:21,960 --> 02:02:25,280 IMPACT ON THE LEFT AND THE 2439 02:02:25,280 --> 02:02:26,480 INDIVIDUAL MODULATOR STUDIED IN 2440 02:02:26,480 --> 02:02:27,800 ANIMAL REPRODUCTIVE ANIMALS WERE 2441 02:02:27,800 --> 02:02:38,080 ACROSS THE TOP. 2442 02:02:55,360 --> 02:03:00,120 IF YOU LOOK AT THE IMPACT ON 2443 02:03:00,120 --> 02:03:03,280 FERTILITY, THERE WAS IMPAIRED 2444 02:03:03,280 --> 02:03:05,800 FERTILITY WITH TEZACAFTOR BUT AT 2445 02:03:05,800 --> 02:03:07,200 NORMAL HUMAN DOSES THERE WAS NO 2446 02:03:07,200 --> 02:03:17,320 IMPACT. 2447 02:03:32,760 --> 02:03:37,600 WHEN THE PH IS ACIDIC IT'S MAKES 2448 02:03:37,600 --> 02:03:40,240 IT DIFFICULT FOR THE SPERM AND 2449 02:03:40,240 --> 02:03:44,880 WHAT IS THE EVIDENCE? 2450 02:03:44,880 --> 02:03:46,440 THERE'S A LITTLE BIT AT THIS 2451 02:03:46,440 --> 02:03:56,960 POINT THIS WOMAN WAS DIAGNOSED 2452 02:03:57,680 --> 02:04:04,080 WITH CF AND HAS THICK MUCUS AND 2453 02:04:04,080 --> 02:04:07,240 AFTER STARTING IVACAFTOR IT'S 2454 02:04:07,240 --> 02:04:09,080 NOT AS THICK AND WE'RE LOOKING 2455 02:04:09,080 --> 02:04:15,440 AT WHETHER OR NOT CERVICAL MUCUS 2456 02:04:15,440 --> 02:04:17,480 CHANGES WITH THE USE OF THIS AND 2457 02:04:17,480 --> 02:04:18,960 THOUGH PEOPLE WITH CF ARE 2458 02:04:18,960 --> 02:04:21,080 SUPPOSED TO BE ON CONTRACEPTION 2459 02:04:21,080 --> 02:04:28,040 DURING THE IVACAFTOR TRIALS 2% 2460 02:04:28,040 --> 02:04:29,440 BECAME PREGNANT WE THINK BECAUSE 2461 02:04:29,440 --> 02:04:31,480 THEY DIDN'T THINK THEY COULD GET 2462 02:04:31,480 --> 02:04:32,480 PREGNANT AND WITH THE MODULATOR 2463 02:04:32,480 --> 02:04:35,560 WERE ABLE TO GET PREGNANT. 2464 02:04:35,560 --> 02:04:40,360 THERE WERE CASES OF UNINTENDED 2465 02:04:40,360 --> 02:04:43,000 PREGNANCIES WITH AND SEVEN WOMEN 2466 02:04:43,000 --> 02:04:49,880 WHO REPORTED INFERTILITY BECAME 2467 02:04:49,880 --> 02:04:52,960 PREGNANT WITH IVACAFTOR AND 2468 02:04:52,960 --> 02:04:54,320 COLLEAGUES REPORTED 14 FEMALES 2469 02:04:54,320 --> 02:04:59,160 WITH CF ACHIEVED CONCEPTION AT 2470 02:04:59,160 --> 02:05:09,640 EIGHT WEEKS AFTER STARTING 2471 02:05:17,920 --> 02:05:20,080 ELAXCAFTOR AND THE DATE IS SUPER 2472 02:05:20,080 --> 02:05:26,120 IMPOSED FOR THE TIMING OF TRIALS 2473 02:05:26,120 --> 02:05:36,680 PEOPLE WERE SUPPOSED TO NOT -- 2474 02:05:58,480 --> 02:06:00,920 AND WE'VE LOOKED AT OUTCOMES FOR 2475 02:06:00,920 --> 02:06:01,400 PREGNANCY. 2476 02:06:01,400 --> 02:06:02,440 GENERALLY THEY'VE SHOWN PEOPLE 2477 02:06:02,440 --> 02:06:04,280 WITH CF WHO HAVE LOWER LUNG 2478 02:06:04,280 --> 02:06:07,120 FUNCTION ESPECIALLY IF THE LUNG 2479 02:06:07,120 --> 02:06:08,720 FUNCTION IS BELOW 50 OR 60 ARE 2480 02:06:08,720 --> 02:06:13,600 LIKELY TO HAVE POORER OUTCOMES 2481 02:06:13,600 --> 02:06:16,160 ALONG WITH PEOPLE AND TWO 2482 02:06:16,160 --> 02:06:18,360 STUDIES LOOKED AT RETROSPECTIVE 2483 02:06:18,360 --> 02:06:20,200 STUDIES IN PREVIOUSLY DONE 2484 02:06:20,200 --> 02:06:21,000 STUDIES THAT SHOWED MAYBE THERE 2485 02:06:21,000 --> 02:06:23,600 WASN'T AN IMPACT ON SURVIVAL. 2486 02:06:23,600 --> 02:06:25,960 GOSS AND COLLEAGUES LOOKED AT 2487 02:06:25,960 --> 02:06:27,680 FEMALES WHO BECAME PREGNANT 2488 02:06:27,680 --> 02:06:30,200 ABOUT 700 AND WERE HEALTHIER AT 2489 02:06:30,200 --> 02:06:31,800 BASELINE AND HAD A BETTER 2490 02:06:31,800 --> 02:06:33,440 10-YEAR SURVIVAL COMPARED TO 2491 02:06:33,440 --> 02:06:34,960 THOSE WHO COULDN'T BECOME 2492 02:06:34,960 --> 02:06:36,560 PREGNANT AND SCHEFTER AND 2493 02:06:36,560 --> 02:06:39,760 COLLEAGUES LOOKED AT AN 2494 02:06:39,760 --> 02:06:41,800 EPIDEMIOLOGIC STUD AGREE 1994 TO 2495 02:06:41,800 --> 02:06:44,720 2005 AND SHOWED FEMALES WITH CF 2496 02:06:44,720 --> 02:06:47,160 WHO BECAME PREGNANT HAD MORE 2497 02:06:47,160 --> 02:06:50,560 ILLNESS VISITS AND MORE 2498 02:06:50,560 --> 02:06:52,160 PULMONARY VISIT AND LOWER 2499 02:06:52,160 --> 02:06:54,240 QUALITY OF LIFE BUT DID NOT HAVE 2500 02:06:54,240 --> 02:06:55,680 ACCELERATED DISEASE PROGRESSION 2501 02:06:55,680 --> 02:06:57,240 AND THOSE FEMALES WHO BECAME 2502 02:06:57,240 --> 02:06:58,400 PREGNANT WERE HEALTHIER AT 2503 02:06:58,400 --> 02:07:02,920 BASELINE THAN THOSE WHO DIDN'T. 2504 02:07:02,920 --> 02:07:10,080 WE KNOW WITH LEXTEZIVA THAN 2505 02:07:10,080 --> 02:07:11,240 MAINTAIN THE CONDITION IN THE 2506 02:07:11,240 --> 02:07:11,520 LIVER. 2507 02:07:11,520 --> 02:07:15,600 WHAT DO WE KNOW ABOUT PREGNANCY 2508 02:07:15,600 --> 02:07:20,760 COMPLICATIONS IN FEMALES WITH 2509 02:07:20,760 --> 02:07:30,800 CF? 2510 02:07:31,440 --> 02:07:34,840 AND WE KNOW WITH DIABETES, 2511 02:07:34,840 --> 02:07:38,440 INFECTION, PRE-TERM LABOR AND 2512 02:07:38,440 --> 02:07:41,240 GESTATIONAL HYPERTENSION AND 2513 02:07:41,240 --> 02:07:44,080 PREECLAMPSIA AND THOSE BORN TO 2514 02:07:44,080 --> 02:07:45,800 THOSE MOTHERS HAD INCREASED 2515 02:07:45,800 --> 02:07:51,760 RATES OF CARDIAC ANOMALIES, 2516 02:07:51,760 --> 02:07:55,560 INCREASED JUANDICE AND PREMATURE 2517 02:07:55,560 --> 02:07:56,080 DELIVERY. 2518 02:07:56,080 --> 02:07:58,480 ONE OF THESE ARE DIRECTLY 2519 02:07:58,480 --> 02:08:00,120 RELATED TO CFTR OR THE HEALTH OF 2520 02:08:00,120 --> 02:08:02,920 THE WOMAN OR THE LEGACY DIET 2521 02:08:02,920 --> 02:08:09,000 WE'RE NOT SURE AT THIS POINT. 2522 02:08:09,000 --> 02:08:11,720 WE SAW DECREASED LUNG FUNCTION 2523 02:08:11,720 --> 02:08:14,480 WAS CORRELATED WITH DECREASED 2524 02:08:14,480 --> 02:08:16,720 GESTATIONAL AGE AND BIRTH 2525 02:08:16,720 --> 02:08:16,960 WEIGHT. 2526 02:08:16,960 --> 02:08:18,360 THE LOWER THE LUNG FUNCTION A 2527 02:08:18,360 --> 02:08:20,760 WOMAN HAD THE MORE LIKELY SHE 2528 02:08:20,760 --> 02:08:23,320 WOULD DELIVER AN INFANT WITH 2529 02:08:23,320 --> 02:08:25,080 LOWER BIRTH WEIGHT. 2530 02:08:25,080 --> 02:08:26,520 WHAT DO WE KNOW ABOUT MODULATORS 2531 02:08:26,520 --> 02:08:29,200 AND PREGNANCY FROM ANIMAL 2532 02:08:29,200 --> 02:08:31,360 REPRODUCTIVE MODELS? 2533 02:08:31,360 --> 02:08:34,440 LOOKING AT ANIMAL MODELS AND THE 2534 02:08:34,440 --> 02:08:36,440 INDIVIDUAL MODULATORS AT NORMAL 2535 02:08:36,440 --> 02:08:38,400 HUMAN DOSES WE DID NOT SEE 2536 02:08:38,400 --> 02:08:41,040 ISSUES BUT AT HIGH DOSES THERE 2537 02:08:41,040 --> 02:08:43,640 WAS DECREASED FETAL BODY WEIGHT 2538 02:08:43,640 --> 02:08:45,680 AND DECREASED BODY WEIGHT WITH 2539 02:08:45,680 --> 02:08:47,960 TEZ AND DETACHMENT FOR THE EARS 2540 02:08:47,960 --> 02:08:53,280 AND EYE OPENING AND DECREASED 2541 02:08:53,280 --> 02:09:03,680 FETAL BODY WEIGHT WITH 2542 02:09:05,240 --> 02:09:07,200 ELEXACAFTOR AND THAT'S RECENTLY 2543 02:09:07,200 --> 02:09:09,040 BEEN CHANGED SINCE 2015 THEY'VE 2544 02:09:09,040 --> 02:09:10,560 BEEN USING THE PREGNANCY AND 2545 02:09:10,560 --> 02:09:16,240 LACTATION LABELLING RULE. 2546 02:09:16,240 --> 02:09:18,400 AND LOOK AT CRITICAL DECISION 2547 02:09:18,400 --> 02:09:22,080 MAKING WHEN TREATING PREGNANT OR 2548 02:09:22,080 --> 02:09:22,680 LACTATING FEMALES. 2549 02:09:22,680 --> 02:09:24,120 THE SPONSOR WAS REQUIRED TO SHOW 2550 02:09:24,120 --> 02:09:26,240 WHETHER THERE WAS ADEQUATE AND 2551 02:09:26,240 --> 02:09:27,760 WELL CONTROLLED STUDIES IN 2552 02:09:27,760 --> 02:09:28,800 PREGNANT FEMALES TO SAY IF 2553 02:09:28,800 --> 02:09:30,560 THERE'S A DRUG ASSOCIATED RISK 2554 02:09:30,560 --> 02:09:32,080 OF MAJOR BIRTH DEFECT OR 2555 02:09:32,080 --> 02:09:34,120 MISCARRIAGE AND IN THE ANIMAL 2556 02:09:34,120 --> 02:09:35,360 STUDIES THE SPONSOR HAS TO SAY 2557 02:09:35,360 --> 02:09:38,160 HOW MUCH DRUG WAS GIVEN COMPARED 2558 02:09:38,160 --> 02:09:40,480 TO THE MAXIMUM RECOMMENDED HUMAN 2559 02:09:40,480 --> 02:09:40,800 DOSE. 2560 02:09:40,800 --> 02:09:43,800 SO WHAT WE'RE TRYING TO WEIGH IN 2561 02:09:43,800 --> 02:09:45,720 TERMS OF THE MODULATORS IN 2562 02:09:45,720 --> 02:09:48,280 PREGNANCY IS THE UNKNOWN RISK TO 2563 02:09:48,280 --> 02:09:49,840 THE FETUS BECAUSE THERE'S A 2564 02:09:49,840 --> 02:09:53,240 PAUCITY OF DATA IN HUMANS VERSUS 2565 02:09:53,240 --> 02:09:58,640 IF THE MOM DISCONTINUES THE 2566 02:09:58,640 --> 02:10:00,480 MODULATOR WILL VERY HAVE HEALTH 2567 02:10:00,480 --> 02:10:02,520 DECLINE OR INABILITY TO MAINTAIN 2568 02:10:02,520 --> 02:10:04,000 WEIGHT DURING PREGNANCY AND WHAT 2569 02:10:04,000 --> 02:10:05,120 IF SHE HAS A SEVERE 2570 02:10:05,120 --> 02:10:10,800 EXACERBATION? 2571 02:10:10,800 --> 02:10:12,920 THERE ARE REASONS TO BELIEVE AND 2572 02:10:12,920 --> 02:10:15,040 THERE'S A THOUGHT IT CAN CAUSE 2573 02:10:15,040 --> 02:10:16,120 SEVERE ISSUES. 2574 02:10:16,120 --> 02:10:21,280 THERE WAS A CASE SERIES OF 2575 02:10:21,280 --> 02:10:22,560 IVACAFTOR WITHDRAWAL SYNDROME 2576 02:10:22,560 --> 02:10:25,440 AND THERE WERE THREE CASES OF 2577 02:10:25,440 --> 02:10:26,160 DECLINE WITH WITHDRAWAL 2578 02:10:26,160 --> 02:10:28,200 INCLUDING UNFORTUNATELY IN ONE 2579 02:10:28,200 --> 02:10:30,280 PERSON WHO DIED AFTER WITHDRAWAL 2580 02:10:30,280 --> 02:10:31,760 OF IVACAFTOR. 2581 02:10:31,760 --> 02:10:34,400 THERE WAS ADDITIONALLY AN 2582 02:10:34,400 --> 02:10:35,760 ABSTRACT PRESENTED IN 2018 THAT 2583 02:10:35,760 --> 02:10:39,720 LOOKED AT ADULTS WHO WERE IN THE 2584 02:10:39,720 --> 02:10:44,600 PHASE 2 STUDIES OF ELEXACAFTOR 2585 02:10:44,600 --> 02:10:49,720 AND PEOPLE EXPERIENCED LUNG 2586 02:10:49,720 --> 02:11:00,240 FUNCTION DECLINE AND AND THEY 2587 02:11:02,080 --> 02:11:12,520 LOOK AT THE USE AND SUBSEQUENTLY 2588 02:11:14,360 --> 02:11:16,200 ELX/TEZ/VA AND WOMAN WHO CHOSE 2589 02:11:16,200 --> 02:11:18,880 TO STAY ON THEM. 2590 02:11:18,880 --> 02:11:24,960 IN 135 FEMALES WITH CF, USE OF 2591 02:11:24,960 --> 02:11:27,520 CFTR MODULATOR RESULTED IN POOR 2592 02:11:27,520 --> 02:11:29,560 MATERNAL COMPLICATIONS RELATED 2593 02:11:29,560 --> 02:11:31,800 TO MODULATOR THERAPY AND ONE WAS 2594 02:11:31,800 --> 02:11:35,600 A PULMONARY EXACERBATION AND ONE 2595 02:11:35,600 --> 02:11:38,120 WAS AN INCIDENT OF LEUKEMIA THAT 2596 02:11:38,120 --> 02:11:41,680 HASN'T BEEN REPORTED BEFORE OR 2597 02:11:41,680 --> 02:11:50,040 AFTER IN ASSOCIATION WITH 2598 02:11:50,040 --> 02:11:51,000 LUMAVA. 2599 02:11:51,000 --> 02:11:55,120 THE MISCARRIAGE RATE WAS LESS 2600 02:11:55,120 --> 02:12:00,640 THAN 10% AND CESSATION RESULTED 2601 02:12:00,640 --> 02:12:05,040 IN DECLINE AND INTEREST WERE NO 2602 02:12:05,040 --> 02:12:11,000 MODULATOR INCIDENTS. 2603 02:12:11,000 --> 02:12:12,680 ALL THE MODULATORS ARE PRESENT 2604 02:12:12,680 --> 02:12:17,520 IN BREAST MILK AND WE KNOW FROM 2605 02:12:17,520 --> 02:12:22,560 RATS ALL WHO WERE ADMINISTRATED, 2606 02:12:22,560 --> 02:12:23,800 IVACAFTOR DID DEVELOP CATARACTS 2607 02:12:23,800 --> 02:12:29,080 SO THERE'S A WARNING LABEL FOR 2608 02:12:29,080 --> 02:12:30,480 THAT. 2609 02:12:30,480 --> 02:12:41,000 ONE WOMAN CONTINUED LUMIE -- 2610 02:12:42,520 --> 02:12:43,720 LUMIVA AND THERE WERE CASES 2611 02:12:43,720 --> 02:12:47,680 WHERE THE INFANT HAD AN INCREASE 2612 02:12:47,680 --> 02:12:48,840 IN THE LFTs. 2613 02:12:48,840 --> 02:12:50,280 THE SECOND WAS ASSOCIATED WITH 2614 02:12:50,280 --> 02:12:54,400 THE MOM TAKING ANTIBIOTICS AS 2615 02:12:54,400 --> 02:12:57,240 WELL. 2616 02:12:57,240 --> 02:13:04,640 RECENTLY UNC SAW ELXTESIVA CAN 2617 02:13:04,640 --> 02:13:09,000 BE MEASURED IN THE INFANT AND 65 2618 02:13:09,000 --> 02:13:12,600 INFANTS BREAST FED WHILE 2619 02:13:12,600 --> 02:13:14,840 MODULATOR THERAPY DIDN'T HAVE 2620 02:13:14,840 --> 02:13:19,160 CATARACTS AND THERE WERE NO 2621 02:13:19,160 --> 02:13:22,120 ABNORMALITIES IN THE IFTs. 2622 02:13:22,120 --> 02:13:25,120 THERE'S DATA THAT SUGGESTS THERE 2623 02:13:25,120 --> 02:13:26,880 MAY BE ADVERSE HEALTH IMPACTS. 2624 02:13:26,880 --> 02:13:28,800 WE USED THE U.K. REGISTRY TO 2625 02:13:28,800 --> 02:13:30,280 LOOK AT THE QUESTION AND SHOWED 2626 02:13:30,280 --> 02:13:36,200 A DECREASE IN LUNG FUNCTION AND 2627 02:13:36,200 --> 02:13:41,240 DECREASE IN EXACERBATION AND 2628 02:13:41,240 --> 02:13:45,640 THROUGH DATA THROUGH CHART 2629 02:13:45,640 --> 02:13:49,880 COLLECTION HAVE ON THE 303 2630 02:13:49,880 --> 02:13:51,200 PREGNANCY AND THOSE ON 2631 02:13:51,200 --> 02:13:52,320 MODULATORS LOOKED LIKE THEY HAD 2632 02:13:52,320 --> 02:13:56,240 AN IMPROVEMENT IN THEIR 2633 02:13:56,240 --> 02:13:58,480 POST-PREGNANCY FEV1 AND THOSE 2634 02:13:58,480 --> 02:14:03,040 WHO WERE OFF MODULATORS HAD A 2635 02:14:03,040 --> 02:14:03,600 DECLINE. 2636 02:14:03,600 --> 02:14:12,920 WHAT WE'VE SEEN FEMALES WITH CF 2637 02:14:12,920 --> 02:14:21,160 HAVE REPRODUCTIVE ANATOMY ARE 2638 02:14:21,160 --> 02:14:24,280 SIMILAR AND AND WE NEED 2639 02:14:24,280 --> 02:14:25,880 PROSPECTIVE DATA AND 2640 02:14:25,880 --> 02:14:28,120 RETROSPECTIVE STUDIES OF 2641 02:14:28,120 --> 02:14:28,720 PARENTHOOD SHOW THERE'S SHORT 2642 02:14:28,720 --> 02:14:31,560 TERM HEALTH IMPACTS THAT MAY BE 2643 02:14:31,560 --> 02:14:32,520 MITIGATED BY MODULATOR USE. 2644 02:14:32,520 --> 02:14:36,160 I THINK WE STILL NEED TO KNOW 2645 02:14:36,160 --> 02:14:38,320 ARE THE UNKNOWN RISKS BALANCED 2646 02:14:38,320 --> 02:14:40,280 BY THE RISKS OF THE HEALTH OF 2647 02:14:40,280 --> 02:14:42,400 THE MOTHER, CLINICAL 2648 02:14:42,400 --> 02:14:44,200 DETERIORATION FOLLOWING 2649 02:14:44,200 --> 02:14:45,360 GESTATION AND FOLLOWING EXPOSURE 2650 02:14:45,360 --> 02:14:48,320 DO WE NEED TO EXAMINE BABY'S 2651 02:14:48,320 --> 02:14:50,240 EYES AND DOING LIVER FUNCTION 2652 02:14:50,240 --> 02:14:53,000 AND ARE THERE LONG-TERM EFFECTS 2653 02:14:53,000 --> 02:14:58,400 OF INFANTS AND DOES PARENTHOOD 2654 02:14:58,400 --> 02:15:01,000 IMPACT AND IS IT AFFECTED BY 2655 02:15:01,000 --> 02:15:01,560 MODULATOR USE. 2656 02:15:01,560 --> 02:15:02,760 THERE'S ONGOING STUDIES IN THE 2657 02:15:02,760 --> 02:15:05,480 SESSION AND WITH THAT I'LL SAY 2658 02:15:05,480 --> 02:15:06,560 THANKS TO ALL AND THE CF 2659 02:15:06,560 --> 02:15:07,600 FOUNDATION AND AGAIN YOU ALL FOR 2660 02:15:07,600 --> 02:15:12,960 HAVING US HERE TODAY. 2661 02:15:12,960 --> 02:15:13,560 >> THANK YOU. 2662 02:15:13,560 --> 02:15:16,320 THAT WAS AN INTERESTING TALK. 2663 02:15:16,320 --> 02:15:18,000 PLEASE POSE QUESTIONS OR THINGS 2664 02:15:18,000 --> 02:15:23,560 TO DISCUSS LATER ON IN THE CHAT. 2665 02:15:23,560 --> 02:15:26,760 DR. CATHY RAMOS IS AN ASSISTANT 2666 02:15:26,760 --> 02:15:29,040 PROFESSOR AT THE UNIVERSITY OF 2667 02:15:29,040 --> 02:15:33,480 WASHINGTON AND WILL TALK ABOUT 2668 02:15:33,480 --> 02:15:34,400 MODULATOR TREATMENT AND THE 2669 02:15:34,400 --> 02:15:44,720 TRANSPLANT COURSE. 2670 02:16:00,640 --> 02:16:06,960 >> I'M MERE TO TALK ABOUT HIGHLY 2671 02:16:06,960 --> 02:16:07,720 EFFECTIVE MODULATORS AND I HAVE 2672 02:16:07,720 --> 02:16:11,040 GRANT FUNDING FROM THE NIH AND 2673 02:16:11,040 --> 02:16:16,880 CFF AND CHEST FOUNDATION AND 2674 02:16:16,880 --> 02:16:17,120 VERTEX. 2675 02:16:17,120 --> 02:16:19,760 I REVIEW GRANTS FOR THE CFF AND 2676 02:16:19,760 --> 02:16:25,480 AN ADULT PULMONOLOGIST CARING 2677 02:16:25,480 --> 02:16:27,560 FOR PEOPLE WITH CF AND LUNG 2678 02:16:27,560 --> 02:16:28,840 TRANSPLANT RECIPIENTS. 2679 02:16:28,840 --> 02:16:32,200 I'LL TALK ABOUT TRANSPLANT FOR 2680 02:16:32,200 --> 02:16:33,960 LUNG DISEASE AND HIGHLY 2681 02:16:33,960 --> 02:16:35,560 EFFECTIVE MODULATOR ERA AND GIVE 2682 02:16:35,560 --> 02:16:37,520 BACKGROUND AND DATA FROM THE 2683 02:16:37,520 --> 02:16:40,520 CONSORTIUM AND THE USE OF 2684 02:16:40,520 --> 02:16:41,280 POSTTRANSPLANT MODULATORS AND 2685 02:16:41,280 --> 02:16:42,520 SHARE GAPS AND OPPORTUNITIES FOR 2686 02:16:42,520 --> 02:16:46,400 THE USE OF MODULATORS BEFORE AND 2687 02:16:46,400 --> 02:16:51,160 AFTER TRANSPLANT. 2688 02:16:51,160 --> 02:16:53,400 PEOPLE WITH CF AND FEV1 WERE 2689 02:16:53,400 --> 02:16:56,960 EXCLUDED FROM THE PHASE 3 TRIALS 2690 02:16:56,960 --> 02:17:02,040 OF THE CFTR MILD MODULATORS AND 2691 02:17:02,040 --> 02:17:04,840 THE CLINIC BENEFIT WAS SIMILAR 2692 02:17:04,840 --> 02:17:06,560 TO THOSE WITH A HIGHER FEV1. 2693 02:17:06,560 --> 02:17:09,840 THERE'S BEEN CASE SERIES WITH 2694 02:17:09,840 --> 02:17:12,200 PEOPLE WITH ADVANCED CF 2695 02:17:12,200 --> 02:17:13,280 CLINICALLY PRESCRIBED AND THE 2696 02:17:13,280 --> 02:17:15,400 IMPROVEMENT MAY BE MORE MODEST. 2697 02:17:15,400 --> 02:17:19,680 CLOSER TO 7% TO 9% COMPARED TO 2698 02:17:19,680 --> 02:17:21,360 14% AND IN RECENTLY PUBLISHED 2699 02:17:21,360 --> 02:17:23,440 FRENCH STUDIES THEY DEMONSTRATED 2700 02:17:23,440 --> 02:17:26,360 THAT 73% OF PATIENTS WHO WERE ON 2701 02:17:26,360 --> 02:17:28,640 LUNG TRANSPLANT WAITING LIST 2702 02:17:28,640 --> 02:17:32,440 WERE REMOVED AFTER STARTING ETI 2703 02:17:32,440 --> 02:17:34,440 AND THOSE UNDERGOING LUNG 2704 02:17:34,440 --> 02:17:36,720 TRANSPLANT EVALUATION NO LONGER 2705 02:17:36,720 --> 02:17:37,680 MET THE SEVERITY CRITERIA FOR 2706 02:17:37,680 --> 02:17:39,640 TRANSPLANT AND THE EFFECTS OF 2707 02:17:39,640 --> 02:17:44,560 ETI PERSIST FOR AT LEAST ONE 2708 02:17:44,560 --> 02:17:48,440 YEAR AFTER INITIATION. 2709 02:17:48,440 --> 02:17:53,600 IN AN OBSERVATIONAL STUDY THERE 2710 02:17:53,600 --> 02:17:55,320 WERE LOWER RISKS COMPARED TO A 2711 02:17:55,320 --> 02:17:58,000 COMPARATOR GROUP AND WHILE 2712 02:17:58,000 --> 02:18:00,280 DEATHS AMONG TRANSPLANTS STILL 2713 02:18:00,280 --> 02:18:03,640 OCCURRED FOR PEOPLE TREATED 2714 02:18:03,640 --> 02:18:07,840 WITWITH 2715 02:18:07,840 --> 02:18:10,800 IVACAFTOR WERE LOWER AND THIS IS 2716 02:18:10,800 --> 02:18:13,240 DATA FROM THE PUBLICLY AVAILABLE 2717 02:18:13,240 --> 02:18:16,840 WEBSITE LISTED AT THE BOTTOM. 2718 02:18:16,840 --> 02:18:18,800 YOU CAN SEE THE ANNUAL RATE OF 2719 02:18:18,800 --> 02:18:21,960 CF LUNG TRANSPLANT WAS BETWEEN 2720 02:18:21,960 --> 02:18:26,040 200 AND 300 PER YEAR AND UNTIL 2721 02:18:26,040 --> 02:18:27,760 2019 CF PATIENTS WERE 2722 02:18:27,760 --> 02:18:29,040 APPROXIMATELY 10% OF THE 2723 02:18:29,040 --> 02:18:31,960 U.S. TRANSPLANT RECIPIENTS AND 2724 02:18:31,960 --> 02:18:36,040 THE GRAPH ON THE OTHER SIDE HERE 2725 02:18:36,040 --> 02:18:43,680 SHOWS LUNG TRANSPLANT FOR ALL 2726 02:18:43,680 --> 02:18:45,720 DIAGNOSE AND THE NUMBER DROPPED 2727 02:18:45,720 --> 02:18:48,920 TO 78 AND IN 2021 IT DROPPED TO 2728 02:18:48,920 --> 02:18:50,920 JUST 43 PEOPLE WITH CF WHO WERE 2729 02:18:50,920 --> 02:18:51,480 TRANSPLANTED WITHIN THE 2730 02:18:51,480 --> 02:18:58,320 U.S. LESS THAN 2% OF ALL 2731 02:18:58,320 --> 02:19:06,680 TRANSPLANTS. 2732 02:19:06,680 --> 02:19:10,400 IN 2020 DATA FROM THE PATIENT 2733 02:19:10,400 --> 02:19:12,280 REGISTRY SHOWED 29 PEOPLE WHO 2734 02:19:12,280 --> 02:19:16,320 WERE TRANSPLANTED WERE ON ETI AT 2735 02:19:16,320 --> 02:19:20,240 THE TIME OF THE TRANSPLANT. 2736 02:19:20,240 --> 02:19:26,240 29 OF 78 BUT 152 TEAM DIED 2737 02:19:26,240 --> 02:19:29,000 WITHOUT TRANSPLANT AND ONLY 2738 02:19:29,000 --> 02:19:31,840 ABOUT 4 DEATHS WITHOUT LUNG 2739 02:19:31,840 --> 02:19:34,160 TRANSPLANT WERE DUE TO COVID-19 2740 02:19:34,160 --> 02:19:35,800 AND THE 2021 DATA FOR DEATH 2741 02:19:35,800 --> 02:19:36,960 WITHOUT TRANSPLANT ARE NOT YET 2742 02:19:36,960 --> 02:19:41,120 AVAILABLE. 2743 02:19:41,120 --> 02:19:46,400 IN SUMMARY OF MODULATOR AND 2744 02:19:46,400 --> 02:19:49,240 ADVANCED CF 1 DISEASE SOME 2745 02:19:49,240 --> 02:19:51,760 TREATED WITH MODULATOR MAY NEVER 2746 02:19:51,760 --> 02:19:56,680 NEED A LUNG TRANSPLANT AND 10% 2747 02:19:56,680 --> 02:19:59,480 ARE NOT ELIGIBLE AND 300,000 2748 02:19:59,480 --> 02:20:01,720 ALREADY HAVE ADVANCED LUNG 2749 02:20:01,720 --> 02:20:03,840 DISEASE WITH A FEV1 LESS THAN 2750 02:20:03,840 --> 02:20:09,920 40% OF PREDICTED AND MODULATORS 2751 02:20:09,920 --> 02:20:11,160 MAY DELAY LUNG TRANSPLANT BUT 2752 02:20:11,160 --> 02:20:14,440 THERE'S AN UNPREDICTABLE 2753 02:20:14,440 --> 02:20:17,280 LONG-TERM TRAJECTORY FOR PEOPLE 2754 02:20:17,280 --> 02:20:19,120 ON MODULATORS. 2755 02:20:19,120 --> 02:20:20,080 THE COMPLEXITY ARE LIKELY TO 2756 02:20:20,080 --> 02:20:22,000 INCREASE FOR THE INDIVIDUALS WHO 2757 02:20:22,000 --> 02:20:23,440 DO REQUIRE TRANSPLANT AND THE 2758 02:20:23,440 --> 02:20:26,080 TIMING OF TRANSPLANT SHOULD RELY 2759 02:20:26,080 --> 02:20:29,240 ON FEV1 PLUS OTHER FACTORS 2760 02:20:29,240 --> 02:20:31,880 THINGS LIKE OXYGEN AND 2761 02:20:31,880 --> 02:20:33,600 EXACERBATIONS AND INCREASINGLY 2762 02:20:33,600 --> 02:20:37,600 TRANSPLANT WILL BECOME A 2763 02:20:37,600 --> 02:20:39,600 VALUES-BASED DECISION AND MEANT 2764 02:20:39,600 --> 02:20:41,760 TO IMPROVE SURVIVAL AND MAY BE 2765 02:20:41,760 --> 02:20:43,640 MORE SO QUALITY OF LIFE. 2766 02:20:43,640 --> 02:20:46,480 AND PROJECTIONS SHOW EVEN IN 20 2767 02:20:46,480 --> 02:20:49,600 YEARS FROM NOW ABOUT 6% OF CFS 2768 02:20:49,600 --> 02:20:51,120 WILL HAVE ADVANCED CF LUNG 2769 02:20:51,120 --> 02:20:52,960 DISEASE AND BENEFIT FROM THE 2770 02:20:52,960 --> 02:20:53,240 TRANSPLANT. 2771 02:20:53,240 --> 02:20:57,040 NOW I WANT TO SHIFT TO THE 2772 02:20:57,040 --> 02:20:58,920 POST-TRANSPLANT TIME PERIOD AND 2773 02:20:58,920 --> 02:21:00,960 GIVE BACKGROUND AND DATA. 2774 02:21:00,960 --> 02:21:02,520 SO THIS FIGURE SHOWED THE 2775 02:21:02,520 --> 02:21:03,520 INTERNATIONAL SURVIVAL ESTIMATES 2776 02:21:03,520 --> 02:21:06,880 FOR ADULTS AFTER LUNG TRANSPLANT 2777 02:21:06,880 --> 02:21:08,720 BY DIAGNOSIS AND NOTE THE DATES 2778 02:21:08,720 --> 02:21:10,840 INCLUDE TRANSPLANTS DONE IN THE 2779 02:21:10,840 --> 02:21:13,560 1990s AND SURVIVAL AFTER LUNG 2780 02:21:13,560 --> 02:21:14,560 TRANSPLANT HAS IMPROVED OVER 2781 02:21:14,560 --> 02:21:14,920 TIME. 2782 02:21:14,920 --> 02:21:18,600 FOR ADULTS WITH CF, THE MEDIAN 2783 02:21:18,600 --> 02:21:20,160 SURVIVAL AFTER LUNG TRANSPLANT 2784 02:21:20,160 --> 02:21:23,400 IS 9.9 YEARS COMPARED TO 6 YEARS 2785 02:21:23,400 --> 02:21:28,760 FOR PEOPLE WITH COPD AND FOR 2786 02:21:28,760 --> 02:21:30,240 IDIOPATHIC PULMONARY FIBROSIS 2787 02:21:30,240 --> 02:21:37,320 AND THE ONE YEAR MEDIAN SURVIVL 2788 02:21:37,320 --> 02:21:47,760 IS LISTED AND PLAD IS THE 2789 02:21:48,800 --> 02:21:54,000 LEADING CAUSE OF DEATH POST 2790 02:21:54,000 --> 02:22:04,440 TRANSPLANT AND -- CLAD. 2791 02:22:05,200 --> 02:22:12,240 SINUS DISEASE AFTER LUNG 2792 02:22:12,240 --> 02:22:16,880 TRANSPLANT AND A RESERVOIR FOR 2793 02:22:16,880 --> 02:22:18,920 BACTERIAL PATHOGENS AND THERE'S 2794 02:22:18,920 --> 02:22:20,680 BEEN CONFLICTING RESULTS IN 2795 02:22:20,680 --> 02:22:24,760 SMALL STUDIES OF SINUS SURGERIES 2796 02:22:24,760 --> 02:22:30,000 FOR SINUSITIS AND THE OUTCOMES 2797 02:22:30,000 --> 02:22:35,000 BUT SURGICAL TECHNIQUES HAVE 2798 02:22:35,000 --> 02:22:36,720 EVOLVED AND THOUGHT FOR MORE 2799 02:22:36,720 --> 02:22:37,040 EFFECTIVE. 2800 02:22:37,040 --> 02:22:40,840 ONE STUDY SHOWED FOR SOME 2801 02:22:40,840 --> 02:22:42,120 PATIENTS THERE WAS AN 2802 02:22:42,120 --> 02:22:47,440 IMPROVEMENT IN FIVE-YEAR 2803 02:22:47,440 --> 02:22:52,200 SURVIVAL THE MODULATOR THERAPY 2804 02:22:52,200 --> 02:22:57,480 MAY ENHANCE ACTIVITY AGAINST 2805 02:22:57,480 --> 02:22:59,520 PSEUDOMONAS AND WE ALSO KNOW 2806 02:22:59,520 --> 02:23:01,800 SINUS DISEASE BEFORE TRANSPLANT 2807 02:23:01,800 --> 02:23:03,600 IMPROVED ON ETI. 2808 02:23:03,600 --> 02:23:06,760 SO WE DID AN ELECTRONIC HEALTH 2809 02:23:06,760 --> 02:23:08,160 RECORD BASED COHORT STUDY 2810 02:23:08,160 --> 02:23:10,760 BETWEEN OCTOBER 2019 AND 2811 02:23:10,760 --> 02:23:14,120 SEPTEMBER 2020 USING 15 SITES IN 2812 02:23:14,120 --> 02:23:15,560 THE LUNG TRANSPLANT CONSORTIUM 2813 02:23:15,560 --> 02:23:19,160 AND INCLUDED ALL RECIPIENTS WITH 2814 02:23:19,160 --> 02:23:20,280 ETI AFTER TRANSPLANT AND HAD 2815 02:23:20,280 --> 02:23:21,680 SEVERAL STUDY QUESTIONS 2816 02:23:21,680 --> 02:23:23,280 INCLUDING WHERE THE PATIENTS 2817 02:23:23,280 --> 02:23:27,120 WERE PRESCRIBING ETI AFTER LUNG 2818 02:23:27,120 --> 02:23:27,960 TRANSPLANT AND IMMUNE 2819 02:23:27,960 --> 02:23:29,200 SUPPRESSION DIFFICULT TO MANAGE 2820 02:23:29,200 --> 02:23:31,200 BECAUSE OF DRUG INTERACTIONS AND 2821 02:23:31,200 --> 02:23:33,880 OBSERVED EFFECTS ON A1C AND 2822 02:23:33,880 --> 02:23:36,160 HEMOGLOBIN TESTS AND IS THERE AN 2823 02:23:36,160 --> 02:23:36,880 ASSOCIATION WITH ANTIBIOTIC 2824 02:23:36,880 --> 02:23:38,880 PRESCRIPTION FREQUENCY AND WHAT 2825 02:23:38,880 --> 02:23:43,880 ARE THE REASONS FOR ETI? 2826 02:23:43,880 --> 02:23:45,240 SO BRIEFLY 95 PEOPLE WERE PRE 2827 02:23:45,240 --> 02:23:48,200 DESCRIBED ETI BUT ONLY 91 2828 02:23:48,200 --> 02:23:50,200 PATIENTS STARTED IT. 2829 02:23:50,200 --> 02:23:54,400 ONE OUT OF 95 HAD INSURANCE 2830 02:23:54,400 --> 02:23:59,440 DENIAL FOR THE MEDICATION BUT 44 2831 02:23:59,440 --> 02:24:02,360 OUT OF 95 HAD APPROVAL AND 2832 02:24:02,360 --> 02:24:07,000 PATIENTS WERE -- 95 OUT OF 95 2833 02:24:07,000 --> 02:24:11,480 HAD APPROVAL AND 39 PEOPLE 2834 02:24:11,480 --> 02:24:18,440 STOPPED ETI WHICH AIS A LARGE 2835 02:24:18,440 --> 02:24:19,640 PERCENTAGE UNDER TWO MONTHS. 2836 02:24:19,640 --> 02:24:23,280 THE INDICATIONS WAS A PRIMARY 2837 02:24:23,280 --> 02:24:24,200 OBJECTIVE GIVEN DIRECT LUNG 2838 02:24:24,200 --> 02:24:26,560 FUNCTION BENEFIT IS UNLIKELY AND 2839 02:24:26,560 --> 02:24:28,360 THE MOST COMMONLY REPORTED 2840 02:24:28,360 --> 02:24:31,240 CONDITION THAT FACTORED IN WAS 2841 02:24:31,240 --> 02:24:33,760 SINUS DISEASE FOLLOWED BY GI 2842 02:24:33,760 --> 02:24:36,840 SYMPTOMS AND DIABETES AND BMI 2843 02:24:36,840 --> 02:24:40,080 AND PATIENCE PREFERENCE WAS 2844 02:24:40,080 --> 02:24:42,960 OFTEN A FACTOR IN PRESCRIBING 2845 02:24:42,960 --> 02:24:43,200 ETI. 2846 02:24:43,200 --> 02:24:46,920 THE CLINIC OUTCOMES ARE PRE. 2847 02:24:46,920 --> 02:24:49,560 THE LUNG FUNCTION DOESN'T CHANGE 2848 02:24:49,560 --> 02:24:52,720 AND THE SIGNIFICANT CHANGES ARE 2849 02:24:52,720 --> 02:24:53,720 SHOWN. 2850 02:24:53,720 --> 02:24:57,680 THERE WAS A TREND TOWARDS BMI 2851 02:24:57,680 --> 02:25:02,120 AND HEMOGLOBIN IMPROVED FOR 2852 02:25:02,120 --> 02:25:12,640 THOSE WITH ELEVATED A1C AND HEME 2853 02:25:13,680 --> 02:25:19,120 -- HEMOGLOBIN IMPROVED FOR 2854 02:25:19,120 --> 02:25:29,600 PEOPLE AND THERE'S CAUTIOUS 2855 02:25:36,680 --> 02:25:38,680 INTERPRETATION BECAUSE OF 2856 02:25:38,680 --> 02:25:42,360 COVID-19 AND 39 STOPPED WHICH IS 2857 02:25:42,360 --> 02:25:42,520 43%. 2858 02:25:42,520 --> 02:25:46,160 SEVEN PEOPLE DID RESTART AND 45% 2859 02:25:46,160 --> 02:25:49,480 REMAINED OFF ETI. 2860 02:25:49,480 --> 02:25:53,200 THE REASONS PEOPLE STOPPED ARE 2861 02:25:53,200 --> 02:25:54,480 LISTED HERE AND SOME PEOPLE HAD 2862 02:25:54,480 --> 02:25:57,200 MORE THAN ONE REASON AND A 2863 02:25:57,200 --> 02:25:58,480 NUMBER STOPPED BECAUSE OF G.I. 2864 02:25:58,480 --> 02:25:59,440 SYMPTOMS AND SOME PEOPLE FELT 2865 02:25:59,440 --> 02:26:09,840 THERE WAS NO BENEFIT. 2866 02:26:17,840 --> 02:26:20,120 SOME HAD INCREASED BMI AND 2867 02:26:20,120 --> 02:26:23,360 INCREASE IN HEMOGLOBIN AND 2868 02:26:23,360 --> 02:26:27,000 DECREASE IN A1C AND DECREASED 2869 02:26:27,000 --> 02:26:28,480 ANTIBIOTICS AND THE LIMITATIONS 2870 02:26:28,480 --> 02:26:31,640 WE DIDN'T HAVE ANY SINUS SYMPTOM 2871 02:26:31,640 --> 02:26:33,520 DATA OR G.I. SYMPTOM DATA 2872 02:26:33,520 --> 02:26:35,280 BECAUSE THESE WERE IN ELECTRONIC 2873 02:26:35,280 --> 02:26:36,720 HEALTH RECORDS AND THE COVID-19 2874 02:26:36,720 --> 02:26:38,480 PANDEMIC IMPACTED OUR ABILITY TO 2875 02:26:38,480 --> 02:26:41,840 GET SOME OF THE DATA. 2876 02:26:41,840 --> 02:26:44,120 AND FURTHER STUDIES WANTED TO 2877 02:26:44,120 --> 02:26:45,160 DETERMINE WHETHER IT WOULD 2878 02:26:45,160 --> 02:26:48,760 REDUCE THE INCIDENTS OF CLAD 2879 02:26:48,760 --> 02:26:50,800 WITH CF AND LUNG TRANSPLANT. 2880 02:26:50,800 --> 02:26:53,640 THERE'S SEVERAL PITFALLS FOR 2881 02:26:53,640 --> 02:26:55,920 MODULATOR USE AFTER TRANSPLANT 2882 02:26:55,920 --> 02:26:57,840 INCLUDING NO EFFECT ON THE CFTR 2883 02:26:57,840 --> 02:26:59,960 AND THE DRUG INTERACTIONS AND 2884 02:26:59,960 --> 02:27:03,840 SIDE EFFECTS OF ETI AND THE 2885 02:27:03,840 --> 02:27:04,320 BENEFITS. 2886 02:27:04,320 --> 02:27:06,840 HERE I WANT TO SHARE THE 2887 02:27:06,840 --> 02:27:08,880 RESEARCH OPPORTUNITIES ON THE 2888 02:27:08,880 --> 02:27:09,800 PRE-TRANSPLANT SIDE THE TIMING 2889 02:27:09,800 --> 02:27:13,080 OF THE TRANSPLANT IS A BIG 2890 02:27:13,080 --> 02:27:13,320 QUESTION. 2891 02:27:13,320 --> 02:27:17,320 AND WE NEED TO LOOK AT FEV1 2892 02:27:17,320 --> 02:27:20,320 MARKERS OF DISEASE SEVERITY ON 2893 02:27:20,320 --> 02:27:23,400 MODULATORS AND MORE SENSITIVE 2894 02:27:23,400 --> 02:27:24,480 PHYSIOLOGIC MEASURES AND 2895 02:27:24,480 --> 02:27:26,480 FUNCTIONAL STATUS AND AS WAS 2896 02:27:26,480 --> 02:27:30,400 DISCUSSED YESTERDAY POSSIBLY 2897 02:27:30,400 --> 02:27:30,720 BIOMARKERS. 2898 02:27:30,720 --> 02:27:33,840 WE ALSO NEED TO PROVIDE DECISION 2899 02:27:33,840 --> 02:27:35,080 SUPPORT FOR PEOPLE CONSIDERING 2900 02:27:35,080 --> 02:27:37,800 LUNG TRANSPLANT AND INCREASED 2901 02:27:37,800 --> 02:27:40,240 ACCESS FOR PEOPLE WITH LOWER 2902 02:27:40,240 --> 02:27:41,840 SOCIO ECONOMIC STATUS OR 2903 02:27:41,840 --> 02:27:42,400 NON-WHITE RACE OR HISPANIC 2904 02:27:42,400 --> 02:27:46,720 ETHNICITY. 2905 02:27:46,720 --> 02:27:48,720 ON THE POST TRANSPLANT SIDE IT 2906 02:27:48,720 --> 02:27:50,480 WOULD BE GREAT TO DO SOMETHING 2907 02:27:50,480 --> 02:27:53,960 LIKE A PROMISE STUDY AND 2908 02:27:53,960 --> 02:27:56,360 EVALUATE IN AN OBSERVATIONAL 2909 02:27:56,360 --> 02:27:59,760 STUDY OF ETI AFTER LUNG 2910 02:27:59,760 --> 02:28:01,360 TRANSPLANT AND CLINICAL OUTCOMES 2911 02:28:01,360 --> 02:28:05,200 AND UNDERSTAND THE IMMUNOLOGIC 2912 02:28:05,200 --> 02:28:06,720 EFFECTS AND WHY DO LUNG 2913 02:28:06,720 --> 02:28:07,840 TRANSPLANT PATIENTS HAVE MORE 2914 02:28:07,840 --> 02:28:09,400 SIDE EFFECTS OR NOTICE BEING 2915 02:28:09,400 --> 02:28:10,680 THEIR SIDE EFFECTS BECAUSE 2916 02:28:10,680 --> 02:28:12,920 THEY'RE NOT HAVING THE PROFOUND 2917 02:28:12,920 --> 02:28:14,680 IMPACT ON THEIR PULMONARY 2918 02:28:14,680 --> 02:28:16,440 FUNCTION AND MAY BE ABLE TO 2919 02:28:16,440 --> 02:28:19,760 LEVERAGE THE HETEROGENEITY AND 2920 02:28:19,760 --> 02:28:22,720 PRESCRIBING PRACTICES FOR PEOPLE 2921 02:28:22,720 --> 02:28:24,760 IN TRANSPLANT AND BETTER WOULD 2922 02:28:24,760 --> 02:28:28,000 BE A RANDOMIZED CLINICAL TRIAL 2923 02:28:28,000 --> 02:28:29,200 AND IN IDENTIFYING THE 2924 02:28:29,200 --> 02:28:31,320 POPULATION TO BENEFIT FROM ETI 2925 02:28:31,320 --> 02:28:32,280 AFTER LUNG TRANSPLANT AND 2926 02:28:32,280 --> 02:28:34,160 FINALLY I THINK IT'S IMPORTANT 2927 02:28:34,160 --> 02:28:36,560 TO EVALUATE THE PHARMACO 2928 02:28:36,560 --> 02:28:38,360 KINETICS OF ETI IN THE SETTING 2929 02:28:38,360 --> 02:28:42,440 OF TRANSPLANT MEDICATIONS. 2930 02:28:42,440 --> 02:28:44,280 I WANT TO THANK THE CONSORTIUM 2931 02:28:44,280 --> 02:28:53,440 SITES AND THE INVESTIGATORS AND 2932 02:28:53,440 --> 02:28:54,400 THE NHLBI. 2933 02:28:54,400 --> 02:28:57,400 >> THANK YOU FOR THE TALK 2934 02:28:57,400 --> 02:29:00,360 DR. RAMOS. 2935 02:29:00,360 --> 02:29:03,560 THE NEXT SPEAKER IS FROM SEATTLE 2936 02:29:03,560 --> 02:29:05,680 CHILDREN'S WHERE HE'S A 2937 02:29:05,680 --> 02:29:09,400 PROFESSOR OF PEDIATRICS AND 2938 02:29:09,400 --> 02:29:14,000 CODIRECTS THE COORDINATING 2939 02:29:14,000 --> 02:29:14,240 CENTER. 2940 02:29:14,240 --> 02:29:16,400 >> THANK YOU FOR INVITING ME TO 2941 02:29:16,400 --> 02:29:16,600 TALK. 2942 02:29:16,600 --> 02:29:20,640 I WAS GIVEN THE TALK ON CF 2943 02:29:20,640 --> 02:29:22,680 ADULTS AND HEMT ON AGING AND THE 2944 02:29:22,680 --> 02:29:25,440 BENEFITS OF GIVING THE TALK 2945 02:29:25,440 --> 02:29:28,960 THERE'S NOT MUCH DATA ON I CAN 2946 02:29:28,960 --> 02:29:39,360 HYPOTHESIZE PRIMARILY. 2947 02:29:43,120 --> 02:29:53,480 THESE ARE MY DISCLOSURES. 2948 02:29:56,440 --> 02:29:57,800 I'LL HAVE A FUTURE OF WHAT ADULT 2949 02:29:57,800 --> 02:30:02,600 CARE MIGHT LOOK LIKE. 2950 02:30:02,600 --> 02:30:03,600 WE'VE SEEN THIS SLIDE BEFORE IN 2951 02:30:03,600 --> 02:30:08,560 THE WORKSHOP BUT THIS IS THE 2952 02:30:08,560 --> 02:30:10,480 RECENT PUBLISHED PRESENTED 2953 02:30:10,480 --> 02:30:13,520 SURVIVAL GRAPH THE USCF 2954 02:30:13,520 --> 02:30:15,280 FOUNDATION IN FIVE-YEAR 2955 02:30:15,280 --> 02:30:18,600 INCREMENTS THE PREDICTED MEDIAN 2956 02:30:18,600 --> 02:30:22,080 SURVIVAL FROM 2016 TO 2020. 2957 02:30:22,080 --> 02:30:24,880 IT HAS ACHIEVED 50 YEARS OF AGE 2958 02:30:24,880 --> 02:30:28,440 AND THE BOUNDARIES ARE 48 AND 51 2959 02:30:28,440 --> 02:30:31,000 YEARS BUT THAT'S AN ENORMOUS 2960 02:30:31,000 --> 02:30:31,800 MILESTONE MOST DID NOT THINK WE 2961 02:30:31,800 --> 02:30:40,800 WOULD ACHIEVE. 2962 02:30:40,800 --> 02:30:42,360 THIS IS THE NUMBER OF CHILDREN 2963 02:30:42,360 --> 02:30:43,960 AND ADULTS AND THE PROPORTION 2964 02:30:43,960 --> 02:30:48,600 AND IT'S BEEN NOTED IN MANY 2965 02:30:48,600 --> 02:30:51,200 REGISTRIES ACROSS THE GLOBE THE 2966 02:30:51,200 --> 02:30:54,800 ADULT POPULATION EXCEEDS THE 2967 02:30:54,800 --> 02:30:56,560 POPULATION RELATIVELY STABLE 2968 02:30:56,560 --> 02:30:59,280 BACK IN THE EARLY '90s WAS 2969 02:30:59,280 --> 02:31:01,560 ALMOST 70% CHILDREN AND NOW 2970 02:31:01,560 --> 02:31:03,880 ALMOST 60% ADULTS AND 40% 2971 02:31:03,880 --> 02:31:08,360 CHILDREN IN THE UNITED STATES. 2972 02:31:08,360 --> 02:31:09,120 OUR POPULATION IS CLEARLY 2973 02:31:09,120 --> 02:31:14,000 GROWING OLDER. 2974 02:31:14,000 --> 02:31:18,840 AND THAT'S A MANIFESTATION OF 2975 02:31:18,840 --> 02:31:22,240 THE EXCELLENT CARE PROVIDED BY 2976 02:31:22,240 --> 02:31:22,600 PEDIATRICIANS. 2977 02:31:22,600 --> 02:31:23,680 THERE'S BEEN ATTEMPTS TO WHAT 2978 02:31:23,680 --> 02:31:24,360 THE POPULATION WILL LOOK LIKE IN 2979 02:31:24,360 --> 02:31:31,320 THE FUTURE. 2980 02:31:31,320 --> 02:31:34,080 EYE NICE ANALYSIS WAS DONE BY A 2981 02:31:34,080 --> 02:31:35,280 TEAM IN EUROPE WHICH TRIED TO 2982 02:31:35,280 --> 02:31:39,120 ESTIMATE THE NUMBER OF ADULTS 2983 02:31:39,120 --> 02:31:41,280 LIVING WITH CF AND WHAT THEY 2984 02:31:41,280 --> 02:31:43,640 WOULD LOOK LIKE BETWEEN 2010 AND 2985 02:31:43,640 --> 02:31:44,040 2025. 2986 02:31:44,040 --> 02:31:46,120 THEY ESTIMATED THERE WOULD BE A 2987 02:31:46,120 --> 02:31:47,240 75% INCREASE IN THE ADULT 2988 02:31:47,240 --> 02:31:57,800 POPULATION IN THAT 15-YEAR GAP. 2989 02:32:21,560 --> 02:32:24,560 >> THIS WAS A HISTOGRAM BASED ON 2990 02:32:24,560 --> 02:32:27,000 THE POPULATION AS OF LAST FRIDAY 2991 02:32:27,000 --> 02:32:30,400 IN OUR ADULT CF CLINIC. 2992 02:32:30,400 --> 02:32:33,720 OUR POPULATION IS UNDER THE AGE 2993 02:32:33,720 --> 02:32:34,320 OF 30. 2994 02:32:34,320 --> 02:32:36,720 BETWEEN 30 AND 40 AND 15% 2995 02:32:36,720 --> 02:32:37,440 BETWEEN 30 AND 50. 2996 02:32:37,440 --> 02:32:41,040 ALMOST A THIRD OF OUR POPULATION 2997 02:32:41,040 --> 02:32:44,520 IS OVER 40. 2998 02:32:44,520 --> 02:32:53,200 WE HAVE OVER 60. 2999 02:32:53,200 --> 02:32:56,160 AND WHAT DO WE WORRY ABOUT AS 3000 02:32:56,160 --> 02:32:57,200 THE POPULATION AGES. 3001 02:32:57,200 --> 02:32:58,840 WE HAVE INCREASED POPULATION AT 3002 02:32:58,840 --> 02:33:02,000 THIS TIME LIVING WITH STRUCTURAL 3003 02:33:02,000 --> 02:33:03,400 LUNG DISEASE AND CHRONIC AIR 3004 02:33:03,400 --> 02:33:04,440 INFECTION. 3005 02:33:04,440 --> 02:33:09,880 THIS IS GOING TO BE A MAJOR 3006 02:33:09,880 --> 02:33:10,200 ISSUE. 3007 02:33:10,200 --> 02:33:14,360 I THINK THE CFTR MODULATION 3008 02:33:14,360 --> 02:33:17,000 IMPROVED THE OUTCOME AND LUNG 3009 02:33:17,000 --> 02:33:18,040 FUNCTION BUT NOT REVERSED IN 3010 02:33:18,040 --> 02:33:21,160 MOST OF THE PATIENTS THE KNOWN 3011 02:33:21,160 --> 02:33:22,080 STRUCTURAL LUNG DISEASE THEY 3012 02:33:22,080 --> 02:33:32,160 HAVE. 3013 02:33:40,000 --> 02:33:47,720 THERE'S THE EVOLUTION OF OBESITY 3014 02:33:47,720 --> 02:33:49,120 AND DIABETES IS ALREADY A HEALTH 3015 02:33:49,120 --> 02:33:50,280 PROBLEM. 3016 02:33:50,280 --> 02:33:51,200 THE NEXT PROBLEM COULD BE LIVER 3017 02:33:51,200 --> 02:33:59,680 DISEASE AND G.I. CANCERS. 3018 02:33:59,680 --> 02:34:01,400 WE DON'T KNOW A LOT YET. 3019 02:34:01,400 --> 02:34:03,960 WE CAN LOOK AT THE IVACAFTOR 3020 02:34:03,960 --> 02:34:04,440 EXPERIENCE AND THERE'S 3021 02:34:04,440 --> 02:34:10,680 PUBLICATIONS ON THE TOPIC. 3022 02:34:10,680 --> 02:34:15,360 WE LOOKED AT FEV1 DECLINE WITH 3023 02:34:15,360 --> 02:34:23,400 IVACAFTOR AND DECLINE WAS .91% 3024 02:34:23,400 --> 02:34:26,160 IVACAFTOR TREATMENT VERSUS A 3025 02:34:26,160 --> 02:34:29,640 GROUP OF HOMOZYGOUS COMPARISON 3026 02:34:29,640 --> 02:34:30,040 GROUP. 3027 02:34:30,040 --> 02:34:32,800 THE ACUTE IMPROVEMENT WITH 3028 02:34:32,800 --> 02:34:34,080 IVACAFTOR WAS STILL ASSOCIATED 3029 02:34:34,080 --> 02:34:35,640 WITH A DECLINE. 3030 02:34:35,640 --> 02:34:39,400 SO WHAT WILL WE SEE WITH 3031 02:34:39,400 --> 02:34:45,800 IVACAFTOR IS UNCLEAR. 3032 02:34:45,800 --> 02:34:48,640 WE LOOKED AT THE AGE EFFECT OF 3033 02:34:48,640 --> 02:34:50,840 TREATING PATIENTS WITH IVACAFTOR 3034 02:34:50,840 --> 02:34:57,080 AND WHAT THEY NOTED WAS 3035 02:34:57,080 --> 02:35:07,120 REMARKABLY STABLE OR LACK OF 3036 02:35:07,120 --> 02:35:10,680 DECLINE AND ONCE LUNG DISEASE 3037 02:35:10,680 --> 02:35:13,560 OCCURS YOU MAY HAVE DISEASE 3038 02:35:13,560 --> 02:35:14,080 PROGRESSION DESPITE THESE 3039 02:35:14,080 --> 02:35:24,240 THERAPIES. 3040 02:35:52,000 --> 02:35:57,360 YOU HAD A HAZARD RATIO OF 2.4 TO 3041 02:35:57,360 --> 02:36:07,880 INCREASE HAZARD OF GETTING CKD 3042 02:36:45,520 --> 02:36:46,120 WE DEMONSTRATE THREAD PATIENT 3043 02:36:46,120 --> 02:36:47,160 POPULATION IS AGE. 3044 02:36:47,160 --> 02:36:49,440 THIS IS THE RATE OF STAGE 5, 4 3045 02:36:49,440 --> 02:36:51,960 AND 3 OR GREATER THAN 3 CASES 3046 02:36:51,960 --> 02:36:54,120 BUT YOU CAN SEE THE POPULATION 3047 02:36:54,120 --> 02:36:56,600 BETWEEN 45 AND 55 ARE LIKELY THE 3048 02:36:56,600 --> 02:37:02,040 PATIENTS WHO HAD MORE OF OUR 3049 02:37:02,040 --> 02:37:04,360 CLASSIC CF NOTING MARKED 3050 02:37:04,360 --> 02:37:06,400 INCREASES IN STAGE 3CKD. 3051 02:37:06,400 --> 02:37:08,600 THERE WAS A STUDY WHICH NOTED 3052 02:37:08,600 --> 02:37:19,120 THE PREVALENCE OF 2.7% AND AND 3053 02:37:27,960 --> 02:37:31,200 CKD IS REMARKABLY COMMON AFTER 3054 02:37:31,200 --> 02:37:33,800 LUNG TRANSPLANT AND THE TWO-YEAR 3055 02:37:33,800 --> 02:37:36,760 RISK OF CKD WAS 35%. 3056 02:37:36,760 --> 02:37:40,640 THIS IS THE RISK OF RENAL 3057 02:37:40,640 --> 02:37:42,240 DYSFUNCTION IN THE POPULATION 3058 02:37:42,240 --> 02:37:44,360 PROPORTION ON THE Y AXIS IN 3059 02:37:44,360 --> 02:37:47,480 YEARS POST TRANSPLANT ON THE X 3060 02:37:47,480 --> 02:37:49,680 AND THERE'S NOT A LOT OF 3061 02:37:49,680 --> 02:37:51,280 FOLLOW-UP BEYOND TWO YEARS OF 3062 02:37:51,280 --> 02:37:55,400 TIME BUT STILL DEMONSTRATED 3063 02:37:55,400 --> 02:37:59,080 SUBSTANTIAL RISE IN CKD EVENTS. 3064 02:37:59,080 --> 02:38:01,360 THE INCREASED RISK IN KIDNEY 3065 02:38:01,360 --> 02:38:02,760 INJURY IS LIKELY SOMETHING WE'LL 3066 02:38:02,760 --> 02:38:05,400 BE ENCOUNTERING MORE SO THAN 3067 02:38:05,400 --> 02:38:06,080 LESS SO. 3068 02:38:06,080 --> 02:38:09,840 IF YOU HAZARD RATIO INCREASE BY 3069 02:38:09,840 --> 02:38:12,000 AGE, IF YOU ARE 25 TO 35 YEARS 3070 02:38:12,000 --> 02:38:13,120 OF AGE IT'S 1.6. 3071 02:38:13,120 --> 02:38:16,680 IF YOU'RE OVER 35 YEARS OF AGE 3072 02:38:16,680 --> 02:38:17,680 COMMONLY THE AGE OF PATIENTS 3073 02:38:17,680 --> 02:38:22,080 WOULD BE TRANSPLANTED AT IS 3074 02:38:22,080 --> 02:38:30,680 2.45. 3075 02:38:30,680 --> 02:38:32,760 HYPERTENSION IS ONE OF THE KNOWN 3076 02:38:32,760 --> 02:38:35,760 ADVERSE EVENTS DESCRIBED IN THE 3077 02:38:35,760 --> 02:38:37,560 PHASE 3 TRIAL. 3078 02:38:37,560 --> 02:38:39,360 IT'S KNOWN IN THE PACKAGE INSERT 3079 02:38:39,360 --> 02:38:41,840 AS ONE OF THE POTENTIAL ADVERSE 3080 02:38:41,840 --> 02:38:42,400 REACTIONS TO THE DRUG. 3081 02:38:42,400 --> 02:38:45,040 THEY NOTE 10% OF THE PATIENT 3082 02:38:45,040 --> 02:38:47,320 POPULATION IN THE TRIAL HAD A 3083 02:38:47,320 --> 02:38:48,720 DIASTOLIC PRESSURE OVER 90 AND 3084 02:38:48,720 --> 02:38:54,680 CHANGE OF GREATER THAN 5 3085 02:38:54,680 --> 02:38:57,080 MILLIMETERS OF MERCURY WHEN 3086 02:38:57,080 --> 02:38:57,680 TREATED IN THE SHORT-TERM 3087 02:38:57,680 --> 02:38:58,840 CLINICAL TRIAL. 3088 02:38:58,840 --> 02:39:00,320 THERE'S ALSO AN INTERESTING CASE 3089 02:39:00,320 --> 02:39:02,480 SERIES JUST PRESENTED WHICH IS 3090 02:39:02,480 --> 02:39:06,080 IN A CASE OF FOUR PATIENTS IN 3091 02:39:06,080 --> 02:39:10,200 JCF NOTING THE ONSET OF SYSTEMIC 3092 02:39:10,200 --> 02:39:11,000 HYPERTENSION WITHIN WEEKS OF 3093 02:39:11,000 --> 02:39:13,760 GETTING TREATED WITH ETI AND ALL 3094 02:39:13,760 --> 02:39:15,280 NEEDED TREATMENT FOR THEIR 3095 02:39:15,280 --> 02:39:15,640 HYPERTENSION. 3096 02:39:15,640 --> 02:39:17,680 IN THIS CASE SERIES THEY NOTED 3097 02:39:17,680 --> 02:39:19,680 COMPLICATED TO SOME EXTENT BY 3098 02:39:19,680 --> 02:39:22,520 SALT SUPPLEMENTATION BUT NOT 3099 02:39:22,520 --> 02:39:23,680 RESOLVED WITH SALT LIMITATION. 3100 02:39:23,680 --> 02:39:27,600 AND THERE'S ANIMAL MODELS AND 3101 02:39:27,600 --> 02:39:34,320 NOTE CFTR REDUCTION IN VASCULAR 3102 02:39:34,320 --> 02:39:35,920 TONE AND BRINGS OUT UNDERLYING 3103 02:39:35,920 --> 02:39:44,920 HYPERTENSION. 3104 02:39:44,920 --> 02:39:46,440 SO CARDIOVASCULAR DISEASE IN CF. 3105 02:39:46,440 --> 02:39:48,440 THIS IS A POTENTIAL. 3106 02:39:48,440 --> 02:39:51,320 I THINK THERE ARE RARE REPORTS 3107 02:39:51,320 --> 02:39:55,440 TO DATE OF ASYMPTOMATIC VASCULAR 3108 02:39:55,440 --> 02:39:56,440 DISEASE AND THERE WERE REPORTS 3109 02:39:56,440 --> 02:40:05,200 OF TWO PATIENTS PRESENTED IN JCF 3110 02:40:05,200 --> 02:40:13,160 AND YOUNG WOMEN WITH ST 3111 02:40:13,160 --> 02:40:23,400 ELEVATION MIs. 3112 02:40:50,880 --> 02:40:53,640 AND WE LOOK AT FIBROSIS AND 3113 02:40:53,640 --> 02:41:04,080 DESCRIBED AS AN SINUCITAL 3114 02:41:07,800 --> 02:41:08,840 DISEASE AND MAYBE LIVER DISEASE 3115 02:41:08,840 --> 02:41:11,520 WILL BE UNMANAGED AND NOTING 3116 02:41:11,520 --> 02:41:13,720 ETIs IS ASSOCIATED WITH THE 3117 02:41:13,720 --> 02:41:21,200 RATES OF INCREASE ABNORMAL EST 3118 02:41:21,200 --> 02:41:31,360 AND ALT. 3119 02:41:51,720 --> 02:41:55,160 AND THERE'S RISK OF LYMPHOID 3120 02:41:55,160 --> 02:41:56,840 LEUKEMIA AND TESTICULAR CANCER. 3121 02:41:56,840 --> 02:42:07,400 WHAT A WINDOW TO THE FUTURE AND 3122 02:42:10,720 --> 02:42:14,680 THIS PATIENT WAS HAD 3123 02:42:14,680 --> 02:42:16,640 BRONCHIECTASIS AND TREATED FOR 3124 02:42:16,640 --> 02:42:19,200 ABOUT 10 YEARS AFTER THE 3125 02:42:19,200 --> 02:42:21,240 PRESENTATION. 3126 02:42:21,240 --> 02:42:31,800 HE'S PANCREATIC SUFFICIENT AND 3127 02:42:36,000 --> 02:42:37,720 STARTED IVACAFTOR TO A POINT 3128 02:42:37,720 --> 02:42:41,560 WHERE HE COULD CARE FOR HIS WIFE 3129 02:42:41,560 --> 02:42:43,560 WITH PROGRESSIVE DEMENTIA. 3130 02:42:43,560 --> 02:42:48,280 HE LOOKS VERY DIFFERENT FROM ALL 3131 02:42:48,280 --> 02:42:50,240 THE CF EFFICIENT PATIENTS AND 3132 02:42:50,240 --> 02:42:53,080 DIABETES AND TYPE 2 AND AFTER 3133 02:42:53,080 --> 02:43:02,080 TREATMENT OF IVACAFTOR HE BECAME 3134 02:43:02,080 --> 02:43:12,080 OBESE. 3135 02:43:12,080 --> 02:43:17,480 AND I'VE NERVE SEEN A PATIENT 3136 02:43:17,480 --> 02:43:20,960 WITH A PATIENT WITH THIS DEVICE 3137 02:43:20,960 --> 02:43:21,960 IN THE SETTING OF CF. 3138 02:43:21,960 --> 02:43:25,920 WE MAY SEE THIS AS PATIENTS AGE 3139 02:43:25,920 --> 02:43:30,360 AND GET MORE COMMON CLASSIC 3140 02:43:30,360 --> 02:43:30,960 CARDIOVASCULARS THAN THE NORMAL 3141 02:43:30,960 --> 02:43:40,560 POPULATION. 3142 02:43:40,560 --> 02:43:43,080 THE MOST IMPORTANT QUESTION IS 3143 02:43:43,080 --> 02:43:45,920 WHIL CHRONIC LOWER AIR INFECTION 3144 02:43:45,920 --> 02:43:49,920 CONTINUE TO LEAD TO LOWER BUT 3145 02:43:49,920 --> 02:43:55,080 CONTINUED LUNG FUNCTION DECLINE. 3146 02:43:55,080 --> 02:43:59,440 THEY'RE LIKELY TO HAVE EVOLVING 3147 02:43:59,440 --> 02:44:06,080 CARE AND WHEN IT COMES TO 3148 02:44:06,080 --> 02:44:16,320 COMPLICATIONS. 3149 02:44:33,480 --> 02:44:42,160 AND WHAT ARE MORE -- 3150 02:44:42,160 --> 02:44:46,200 MORBIDITIES IN -- IMPROVE AND 3151 02:44:46,200 --> 02:44:47,680 THANK YOU FOR THE OPPORTUNITY. 3152 02:44:47,680 --> 02:44:49,280 >> THANK YOU. 3153 02:44:49,280 --> 02:44:51,160 THAT WAS AN INTERESTING TALK. 3154 02:44:51,160 --> 02:44:53,240 I THINK THERE'S SO MANY 3155 02:44:53,240 --> 02:44:54,760 QUESTIONS WE NEVER THOUGHT WE'D 3156 02:44:54,760 --> 02:44:55,600 NEED TO BE ASKING. 3157 02:44:55,600 --> 02:44:57,240 SO INTERESTING AND JUST A 3158 02:44:57,240 --> 02:45:02,320 REMINDER FOR EVERYBODY, PLEASE 3159 02:45:02,320 --> 02:45:13,160 POST ANY QUEST QUESTIONS OR TOPD 3160 02:45:13,160 --> 02:45:17,200 NOW TO JOHN BREWINGTON TALKING 3161 02:45:17,200 --> 02:45:22,760 ABOUT PERSONALIZED CARE AND 3162 02:45:22,760 --> 02:45:23,920 THERATYPING FOR VARIANTS. 3163 02:45:23,920 --> 02:45:28,880 >> I DON'T HAVE RELEVANT 3164 02:45:28,880 --> 02:45:29,200 DISCLOSURES. 3165 02:45:29,200 --> 02:45:31,280 WHEN I STARTED THINKING ABOUT 3166 02:45:31,280 --> 02:45:32,400 FOLKS AS PART OF THE CF 3167 02:45:32,400 --> 02:45:33,800 COMMUNITY WHO DON'T HAVE ACCESS 3168 02:45:33,800 --> 02:45:36,600 TO MODULATOR THERAPY WHICH BY 3169 02:45:36,600 --> 02:45:40,600 THE 2020 REPORT SUGGESTS IS 20% 3170 02:45:40,600 --> 02:45:42,080 OF THE CF POPULATION. 3171 02:45:42,080 --> 02:45:44,120 THE GROUP IS HARD TO 3172 02:45:44,120 --> 02:45:45,760 CHARACTERIZE. 3173 02:45:45,760 --> 02:45:47,640 IT'S VERY HETEROGENEOUS BUT 3174 02:45:47,640 --> 02:45:50,360 THERE'S THEMES TO RUN THROUGH. 3175 02:45:50,360 --> 02:45:51,640 GENETICALLY THE GROUP IS 3176 02:45:51,640 --> 02:45:57,600 ENRICHED FOR VARIANTS THIS 3177 02:45:57,600 --> 02:45:59,560 INCLUDES PRESUMED NONSENSE 3178 02:45:59,560 --> 02:46:07,880 VARIANTS AND UNCHARACTERIZED 3179 02:46:07,880 --> 02:46:14,680 MISSENSE VARIANTS AND INTRONIC 3180 02:46:14,680 --> 02:46:15,080 VAS 3181 02:46:15,080 --> 02:46:17,880 VARIANTS AND WHILE THERE'S 3182 02:46:17,880 --> 02:46:20,600 THEMES AND INDIVIDUALS HAVE 3183 02:46:20,600 --> 02:46:22,600 VARIANCE AND PEOPLE SMARTER THAN 3184 02:46:22,600 --> 02:46:25,720 ME ESTIMATED NOT ALL OF THE 3185 02:46:25,720 --> 02:46:27,760 VARIANTS CAUSE DISEASE ABOUT 3186 02:46:27,760 --> 02:46:33,480 HALF EXIST IN 5 IN 10 PEOPLE 3187 02:46:33,480 --> 02:46:34,360 ACROSS THE WORLD. 3188 02:46:34,360 --> 02:46:36,240 NOW, AS A GROUP THIS IS 3189 02:46:36,240 --> 02:46:37,440 TRADITIONALLY AN UNDER SERVED 3190 02:46:37,440 --> 02:46:37,720 POPULATION. 3191 02:46:37,720 --> 02:46:39,680 IT'S ENRICHED FOR PEOPLE WHO 3192 02:46:39,680 --> 02:46:41,320 DON'T IDENTIFY AS WHITE AND WHO 3193 02:46:41,320 --> 02:46:46,520 MAY IDENTIFY AS HISPANIC AND THE 3194 02:46:46,520 --> 02:46:49,360 NEXT TALK WILL TOUCH ON THIS SO 3195 02:46:49,360 --> 02:46:51,040 I'LL JUST STATE IT AND MOVE ON. 3196 02:46:51,040 --> 02:46:53,160 WHILE WE HAVEN'T BEEN TRACKING 3197 02:46:53,160 --> 02:46:54,720 THE GENOTYPE IN CLINICAL TRIAL 3198 02:46:54,720 --> 02:46:55,920 FOR MORE THAN 15 YEARS THOSE 3199 02:46:55,920 --> 02:46:58,320 TRACKED AND REPORTED OFTEN NOTE 3200 02:46:58,320 --> 02:47:01,000 WE HAVEN'T AN UNDER 3201 02:47:01,000 --> 02:47:04,280 REPRESENTATION OF PEOPLE IN 3202 02:47:04,280 --> 02:47:07,240 GROUP AND CLINICAL TRIALS BEFORE 3203 02:47:07,240 --> 02:47:08,960 MODULATORS AND INDIVIDUALS MAY 3204 02:47:08,960 --> 02:47:09,880 NOT BE UNDERSTOOD. 3205 02:47:09,880 --> 02:47:12,800 IT'S LOGICAL TO MOVE FORWARD AND 3206 02:47:12,800 --> 02:47:15,160 SAY THERE'S A FINITE PORTION, WE 3207 02:47:15,160 --> 02:47:17,600 DON'T KNOW WHAT SIZE BUT A 3208 02:47:17,600 --> 02:47:18,520 FINITE PORTION THAT MAY RESPOND 3209 02:47:18,520 --> 02:47:21,360 TO TREATMENTS WE ALREADY HAVE. 3210 02:47:21,360 --> 02:47:22,840 THEY SIMPLY DON'T HAVE ACCESS TO 3211 02:47:22,840 --> 02:47:23,200 THEM. 3212 02:47:23,200 --> 02:47:27,920 TO TREAT THE WHOLE GROUP WE'RE 3213 02:47:27,920 --> 02:47:29,720 GOING TO NEED AND A TOPIC BEYOND 3214 02:47:29,720 --> 02:47:31,320 THE DISCUSSION BIT THINK WHAT 3215 02:47:31,320 --> 02:47:32,880 ARE THE THINGS WE CAN DO NOW 3216 02:47:32,880 --> 02:47:34,680 WITH THE TOOLS WE HAVE FOR 3217 02:47:34,680 --> 02:47:35,840 INDIVIDUALS WHO MAY HAVE 3218 02:47:35,840 --> 02:47:45,280 BIOLOGIC BENEFIT FROM THE TOOLS. 3219 02:47:45,280 --> 02:47:46,960 PERSONALIZED CARE BECOMES VERY 3220 02:47:46,960 --> 02:47:47,240 IMPORTANT. 3221 02:47:47,240 --> 02:47:49,320 I'LL FOCUS ON MODULATORS AND I 3222 02:47:49,320 --> 02:47:51,520 ALWAYS LIKE TO HIGHLIGHT WE'VE 3223 02:47:51,520 --> 02:47:52,920 BEEN DOING PERSONALIZED CARE IN 3224 02:47:52,920 --> 02:47:55,000 CF FOR MANY YEARS TREATING 3225 02:47:55,000 --> 02:47:57,160 PATIENTS NOT JUST BECAUSE OF 3226 02:47:57,160 --> 02:48:00,200 THEIR DIAGNOSIS BUT BASED ON 3227 02:48:00,200 --> 02:48:01,680 SYMPTOMS AND SEVERITY OF DISEASE 3228 02:48:01,680 --> 02:48:01,960 AND MORE. 3229 02:48:01,960 --> 02:48:04,400 I WANT TO FOCUS ON CF MODULATION 3230 02:48:04,400 --> 02:48:07,120 FOR THIS TALK. 3231 02:48:07,120 --> 02:48:09,880 WE'LL USE THE WORD THERATYPING 3232 02:48:09,880 --> 02:48:11,640 WHICH MEANS FOCUS ON A RESULT 3233 02:48:11,640 --> 02:48:13,960 OPPOSED TO A MECHANISM. 3234 02:48:13,960 --> 02:48:15,480 NOT HOW DOES A DRUG WORK BUT 3235 02:48:15,480 --> 02:48:17,440 DOES IT WORK OR NOT. 3236 02:48:17,440 --> 02:48:19,080 THIS IS MORE RELEVANT FOR THE 3237 02:48:19,080 --> 02:48:20,880 MAJORITY OF PATIENTS AND 3238 02:48:20,880 --> 02:48:23,040 CLINICIANS WOULD SAY THE RESULT 3239 02:48:23,040 --> 02:48:25,480 IS MORE IMPORTANT THAN DETAILS 3240 02:48:25,480 --> 02:48:27,200 OF THE MECHANISM. 3241 02:48:27,200 --> 02:48:30,520 THIS CONCEPTUAL FRAMEWORK CAN BE 3242 02:48:30,520 --> 02:48:32,800 APPLIED TO MANY TREATMENTS NOT 3243 02:48:32,800 --> 02:48:34,960 JUST MODULATOR BUT I'LL FOCUS ON 3244 02:48:34,960 --> 02:48:43,080 MODULATORS TODAY. 3245 02:48:43,080 --> 02:48:46,960 THE FIRST IS IN VIVO STUDIES TO 3246 02:48:46,960 --> 02:48:48,560 IDENTIFY CHARACTERISTICS FOR 3247 02:48:48,560 --> 02:48:51,520 RESPONSE AND THOSE SUGGESTIVELY 3248 02:48:51,520 --> 02:48:55,520 OF RESIDUAL CFTR FUNCTION OR USE 3249 02:48:55,520 --> 02:49:00,320 A PERSON AS THEIR OWN CONTROL 3250 02:49:00,320 --> 02:49:01,920 AND THERE'S ALL RIGHT A SESSION 3251 02:49:01,920 --> 02:49:02,920 YESTERDAY TALKING ABOUT ANIMAL 3252 02:49:02,920 --> 02:49:04,640 MODELS AND MODULATOR STUDIES SO 3253 02:49:04,640 --> 02:49:05,920 I WON'T TOUCH ON THAT BUT 3254 02:49:05,920 --> 02:49:07,840 THERE'S A POTENTIAL ROLE THERE. 3255 02:49:07,840 --> 02:49:10,000 OVER THE NEXT FEW SLIDES WE'LL 3256 02:49:10,000 --> 02:49:13,360 FOCUS ON IN VITRO MODELS OF 3257 02:49:13,360 --> 02:49:15,320 THERATYPING AND HUMAN AND 3258 02:49:15,320 --> 02:49:18,320 NON-HUMAN CELL LINES FOR HIGH 3259 02:49:18,320 --> 02:49:19,800 SCALE, HIGH THROUGHPUT 3260 02:49:19,800 --> 02:49:21,560 REPRODUCIBILITY STUDY AND THOSE 3261 02:49:21,560 --> 02:49:22,560 SMALLER IN SCALE BUT PERHAPS 3262 02:49:22,560 --> 02:49:25,720 MORE PRECISE TO AN INDIVIDUAL. 3263 02:49:25,720 --> 02:49:27,880 I'LL START WITH THE FIRST WHICH 3264 02:49:27,880 --> 02:49:28,680 IS CELL LINES. 3265 02:49:28,680 --> 02:49:31,720 OUR PRIMARY EXPERIENCE IS AN 3266 02:49:31,720 --> 02:49:36,680 OVEREXPRESSION MODELS WHERE AN 3267 02:49:36,680 --> 02:49:38,520 EPITHELIAL ORIGIN CELL LINE 3268 02:49:38,520 --> 02:49:41,720 PRODUCES WHAT YOU PUT INTO IT 3269 02:49:41,720 --> 02:49:45,640 AND THERE'S A HISTOLOGY SLIDE I 3270 02:49:45,640 --> 02:49:47,360 ALWAYS INCLUDE TO REMIND US THE 3271 02:49:47,360 --> 02:49:49,120 THYROID IS EPITHELIAL IN ORIGIN 3272 02:49:49,120 --> 02:49:50,080 AND SO THERE'S A LOGICAL STEP TO 3273 02:49:50,080 --> 02:49:54,760 MAKE. 3274 02:49:54,760 --> 02:49:57,640 THE CELLS ARE EASY TO CULTURE 3275 02:49:57,640 --> 02:50:00,680 ONCE YOU KNOW WHAT YOU'RE DOING. 3276 02:50:00,680 --> 02:50:02,960 AND CREATE A HIGH SIGNAL TO 3277 02:50:02,960 --> 02:50:04,040 NOISE RATIO. 3278 02:50:04,040 --> 02:50:06,280 AS MOST KNOW THE CELLS HAVE A 3279 02:50:06,280 --> 02:50:07,640 GREAT TRACK RECORD FOR 3280 02:50:07,640 --> 02:50:10,040 DEVELOPMENT OF DRUG, REGULATORY 3281 02:50:10,040 --> 02:50:12,360 APPROVAL AND IN THE CASE OF 3282 02:50:12,360 --> 02:50:12,880 MODULATORS EXPANSION OF 3283 02:50:12,880 --> 02:50:15,360 REGULATORY ACCESS TO PEOPLE. 3284 02:50:15,360 --> 02:50:18,520 THE STUDY IN THE BOTTOM RIGHT 3285 02:50:18,520 --> 02:50:22,440 NOW OVER 10 YEARS OLD HAD 3286 02:50:22,440 --> 02:50:24,320 STUDIES TO DEMONSTRATE THE 3287 02:50:24,320 --> 02:50:27,600 BENEFITS OF IVACAFTOR AND USED 3288 02:50:27,600 --> 02:50:29,080 FOR LABEL EXPANSION. 3289 02:50:29,080 --> 02:50:33,280 LARGE LIBRARIES OF DATA EXIST 3290 02:50:33,280 --> 02:50:34,680 NOT ALL ACCESSIBLE BUT THEY 3291 02:50:34,680 --> 02:50:36,280 EXIST AND THEY'RE OUT THERE AND 3292 02:50:36,280 --> 02:50:39,160 THE WORK IS ONGOING. 3293 02:50:39,160 --> 02:50:40,080 THERE'S A FEW GAPS TO THINK 3294 02:50:40,080 --> 02:50:41,160 ABOUT FOR THE APPROACH. 3295 02:50:41,160 --> 02:50:46,640 THE FIRST IS WHAT'S THE RIGHT 3296 02:50:46,640 --> 02:50:49,760 MODEL AND FRTs HAVE BEEN WIDELY 3297 02:50:49,760 --> 02:50:52,040 ADOPTED AND METHODOLOGY FROM LAB 3298 02:50:52,040 --> 02:50:56,440 TO LAB MAY VARY AND THERE'S A 3299 02:50:56,440 --> 02:51:02,040 NEW STUDY ALMOST 15 YEARS OLD 3300 02:51:02,040 --> 02:51:03,880 NOW COMPARING THE CELLS ON THE X 3301 02:51:03,880 --> 02:51:07,680 AXIS AND THE HUMAN DERIVED LINE 3302 02:51:07,680 --> 02:51:09,160 ON THE Y AXIS. 3303 02:51:09,160 --> 02:51:10,960 THE BLACK DOTS ARE COMPOUNDS 3304 02:51:10,960 --> 02:51:14,520 THAT GENERALLY AGREE WITH EACH 3305 02:51:14,520 --> 02:51:16,720 OTHER AND THE WHITE DOTS THERE'S 3306 02:51:16,720 --> 02:51:18,040 DISAGREEMENT. 3307 02:51:18,040 --> 02:51:18,720 SO THE LINES DON'T ALL AGREE 3308 02:51:18,720 --> 02:51:23,040 WITH EACH OTHER. 3309 02:51:23,040 --> 02:51:25,280 IT'S ALSO DIFFICULT TO STUDY 3310 02:51:25,280 --> 02:51:27,280 SPLICE EFFICIENCY IN VARIANTS 3311 02:51:27,280 --> 02:51:29,720 BECAUSE THE GENIC CONSTRUCT 3312 02:51:29,720 --> 02:51:34,840 MEANS THERE'S NO INTRONS IT'S 3313 02:51:34,840 --> 02:51:36,800 BEEN SPLICED AND WHAT CHANGE THE 3314 02:51:36,800 --> 02:51:39,080 EFFICIENCY OF SPLICING CAN'T BE 3315 02:51:39,080 --> 02:51:40,480 WELL REPRESENTED IN THE MODELS. 3316 02:51:40,480 --> 02:51:41,760 THE APPLICATION OF THE 3317 02:51:41,760 --> 02:51:42,800 INDIVIDUAL IS ALSO SOMETHING OUT 3318 02:51:42,800 --> 02:51:43,280 IN QUESTION. 3319 02:51:43,280 --> 02:51:46,520 THERE'S LIMITED STUDIES THAT 3320 02:51:46,520 --> 02:51:48,880 LINK CFTR DATA TO CLINIC DATA 3321 02:51:48,880 --> 02:51:50,240 THOUGH THE LABEL EXPANSION HAS 3322 02:51:50,240 --> 02:51:54,080 BEEN SUCCESSFUL AND CLEARLY 3323 02:51:54,080 --> 02:51:57,880 WORKS IN BROAD STROKES. 3324 02:51:57,880 --> 02:52:00,160 ALSO WHILE FRT LIBRARY DATA HAS 3325 02:52:00,160 --> 02:52:01,400 BEEN USED THAT'S A CONVERSATION 3326 02:52:01,400 --> 02:52:02,040 BETWEEN THE PHARMACEUTICAL 3327 02:52:02,040 --> 02:52:03,400 COMPANY AND FDA. 3328 02:52:03,400 --> 02:52:06,200 IT'S UNCLEAR OF INDEPENDENT 3329 02:52:06,200 --> 02:52:07,360 GENERATED DATA WITH MODELS 3330 02:52:07,360 --> 02:52:11,320 MAKING ITS WAY UP TO REGULATORY 3331 02:52:11,320 --> 02:52:14,080 CHANGE OR EXPANSION PICKED UP BY 3332 02:52:14,080 --> 02:52:15,800 THE PHARMACEUTICAL COMPANIES. 3333 02:52:15,800 --> 02:52:19,320 I'LL MOVE ON TO PATIENT DERIVED 3334 02:52:19,320 --> 02:52:21,920 MODELS AND THERE'S A LOT OF 3335 02:52:21,920 --> 02:52:22,720 THEM. 3336 02:52:22,720 --> 02:52:28,480 SOME DEPEND GEOGRAPHICALLY. 3337 02:52:28,480 --> 02:52:30,880 GASTROINTESTINAL MODELS HAVE 3338 02:52:30,880 --> 02:52:38,040 BEEN USED IN EUROPE AND SHOW 3339 02:52:38,040 --> 02:52:41,480 RESCUES USING IVACAFTOR AND 3340 02:52:41,480 --> 02:52:45,080 LUMACAFTOR AND THE TRADITIONAL 3341 02:52:45,080 --> 02:52:47,440 USE OF THE CELLS ARE OBTAINED AT 3342 02:52:47,440 --> 02:52:50,840 THE TIME OF LUNG TRANSPLANT SO 3343 02:52:50,840 --> 02:52:54,320 QUITE INVASIVE AND NASAL CELLS 3344 02:52:54,320 --> 02:52:56,800 HAVE MANY CHARACTERISTICS OF THE 3345 02:52:56,800 --> 02:53:01,040 BRONCHIAL CELL MODELS AND SEEING 3346 02:53:01,040 --> 02:53:03,880 MORE STEM CELL DERIVED MODEL. 3347 02:53:03,880 --> 02:53:07,000 THEY GENERAL CAPITALIZE ON THE 3348 02:53:07,000 --> 02:53:12,040 TRANSPORT TO QUANTIFY CFTR 3349 02:53:12,040 --> 02:53:13,880 THROUGH ORGANOIDS OR ASSAYS. 3350 02:53:13,880 --> 02:53:16,080 THEY HAVE HIGHER APPLICATION TO 3351 02:53:16,080 --> 02:53:17,560 THE INDIVIDUAL REPRESENTING THE 3352 02:53:17,560 --> 02:53:18,480 GENOTYPE OF THE INDIVIDUAL FROM 3353 02:53:18,480 --> 02:53:19,440 WHERE THEY CAME BUT THE 3354 02:53:19,440 --> 02:53:22,280 THROUGHPUT IS NOT AS HIGH AS THE 3355 02:53:22,280 --> 02:53:25,400 FRT MODEL. 3356 02:53:25,400 --> 02:53:27,560 THERE'S A NUMBER OF GAPS. 3357 02:53:27,560 --> 02:53:29,600 FOR ONE, WHAT'S THE RIGHT MODEL. 3358 02:53:29,600 --> 02:53:31,760 THERE'S NO ONE PERFECT CHOICE. 3359 02:53:31,760 --> 02:53:35,960 WE SEE A STUDY FROM THE GROUP IN 3360 02:53:35,960 --> 02:53:37,640 LISBON AND THEY CORRELATED 3361 02:53:37,640 --> 02:53:38,920 RATHER NICELY WITHIN 3362 02:53:38,920 --> 02:53:39,200 INDIVIDUALS. 3363 02:53:39,200 --> 02:53:40,480 PERHAPS IT'S NOT WHICH IS BETTER 3364 02:53:40,480 --> 02:53:41,240 BUT WHICH ONE DO YOU HAVE ACCESS 3365 02:53:41,240 --> 02:53:44,240 TO. 3366 02:53:44,240 --> 02:53:46,360 AGAIN, GASTROINTESTINAL MODELS 3367 02:53:46,360 --> 02:53:47,360 HAVE BEEN WELL ADOPTED ACROSS 3368 02:53:47,360 --> 02:53:49,880 EUROPE BUT LESS SO IN THE 3369 02:53:49,880 --> 02:53:50,080 STATES. 3370 02:53:50,080 --> 02:53:51,800 THERE'S ALSO SITE TO SITE 3371 02:53:51,800 --> 02:53:54,240 VARIATION LIMITING THE ABILITY 3372 02:53:54,240 --> 02:53:57,600 TO SHARE AND COLLATE DATA AND 3373 02:53:57,600 --> 02:53:58,960 YOU HAVE INDIVIDUALS WITH TWO 3374 02:53:58,960 --> 02:54:01,560 RARE PHENOTYPES IT BECOMES A 3375 02:54:01,560 --> 02:54:03,040 GENETIC FINGERPRINT SO AT WHAT 3376 02:54:03,040 --> 02:54:05,360 POINT ARE YOU SHARING PHI IN THE 3377 02:54:05,360 --> 02:54:07,040 WORLD? 3378 02:54:07,040 --> 02:54:08,240 THERE'S ALSO THE QUESTION OF 3379 02:54:08,240 --> 02:54:09,960 FIDELITY OF THE RESULTS OF THE 3380 02:54:09,960 --> 02:54:11,720 MODELS AND CLINIC BENEFIT. 3381 02:54:11,720 --> 02:54:12,960 IN BROAD STROKES THEY PREDICT 3382 02:54:12,960 --> 02:54:14,760 THE BENEFIT HAPPENING IN 3383 02:54:14,760 --> 02:54:16,640 PATIENTS THE STUDY IN THE BOTTOM 3384 02:54:16,640 --> 02:54:19,240 RIGHT ALMOST FIVE YEARS OLD NOW 3385 02:54:19,240 --> 02:54:20,920 CONNECTING NASAL CELL DATA TO 3386 02:54:20,920 --> 02:54:21,600 LUNG FUNCTION FOLLOWING 3387 02:54:21,600 --> 02:54:24,640 TREATMENT WITH MODULATORS. 3388 02:54:24,640 --> 02:54:27,000 THROUGHPUT REMAINS LIMITED AND 3389 02:54:27,000 --> 02:54:27,560 REPRODUCIBILITY IS NOT AS 3390 02:54:27,560 --> 02:54:30,760 IMPRESSIVE AS WITH RTs. 3391 02:54:30,760 --> 02:54:33,440 THEY ARE GAP THAT NEED TO BE 3392 02:54:33,440 --> 02:54:33,720 ADDRESSED. 3393 02:54:33,720 --> 02:54:35,960 HOW CAN WE TAKE THEM FROM THE 3394 02:54:35,960 --> 02:54:38,160 LAB TO THE CLINIC AND CHANGE 3395 02:54:38,160 --> 02:54:39,560 PATIENT OUTCOMES? 3396 02:54:39,560 --> 02:54:43,960 THIS IS HAPPENING IN VARIOUS 3397 02:54:43,960 --> 02:54:44,160 FORM. 3398 02:54:44,160 --> 02:54:48,840 FOR FRT-BASED LIBRARIES HAS MADE 3399 02:54:48,840 --> 02:54:49,480 CHANGES IN THE LABEL EXPANSION 3400 02:54:49,480 --> 02:54:52,200 AND WHEN IT COMES TO PATIENT 3401 02:54:52,200 --> 02:54:54,280 DERIVED MODELS THE FOLKS IN 3402 02:54:54,280 --> 02:54:56,120 EUROPE ARE ONGOING WITH THE 3403 02:54:56,120 --> 02:55:02,920 STUDY LARGE SCALE ENROLLMENT FOR 3404 02:55:02,920 --> 02:55:13,440 ORGANOID TESTING AND OUR NEXT 3405 02:55:14,680 --> 02:55:21,200 SPEAKER IS LOOKING ATT IVACAFTO 3406 02:55:21,200 --> 02:55:23,640 RESPONSE AND THE DATA LIMITED 3407 02:55:23,640 --> 02:55:24,760 WITH SMALL CASE SERIES AND THE 3408 02:55:24,760 --> 02:55:26,040 NUMBERS ARE RELATIVELY SMALL. 3409 02:55:26,040 --> 02:55:29,480 THE FOUNDATION HAS FUNDED OUR 3410 02:55:29,480 --> 02:55:34,320 GROUP AS A NATIONAL RESOURCE 3411 02:55:34,320 --> 02:55:34,560 CENTER. 3412 02:55:34,560 --> 02:55:40,440 AND FROM OUR WORK OVER THE LAST 3413 02:55:40,440 --> 02:55:50,840 COUPLE YEARS AND WE'VE 3414 02:55:55,640 --> 02:55:57,400 SUCCESSFUL TO GET OFF-LABEL 3415 02:55:57,400 --> 02:55:59,080 COVERAGE OF DRUGS FOR 40 OF THE 3416 02:55:59,080 --> 02:55:59,600 59. 3417 02:55:59,600 --> 02:56:02,760 THE DRUGS THEY RESPONDED TO ARE 3418 02:56:02,760 --> 02:56:04,680 SHOWN IN THE BAR GRAPH IN THE 3419 02:56:04,680 --> 02:56:07,080 MIDDLE AND SHOWING THE X AXIS 3420 02:56:07,080 --> 02:56:09,840 AND MODULATED FUNCTION ON THE Y 3421 02:56:09,840 --> 02:56:11,120 AXIS AND THEY'RE TWO DIFFERENT 3422 02:56:11,120 --> 02:56:14,080 SCALES BUT ABOUT 50% BUMP IN 3423 02:56:14,080 --> 02:56:14,720 CFTR FUNCTION AS A RELATIVE 3424 02:56:14,720 --> 02:56:17,760 NUMBER. 3425 02:56:17,760 --> 02:56:24,680 IT'S A SIGNIFICANT IMPROVEMENT. 3426 02:56:24,680 --> 02:56:27,040 THE IMPACT OF THE DATA ON THE 3427 02:56:27,040 --> 02:56:28,520 REGULATORY EXPANSION IS UNCLEAR. 3428 02:56:28,520 --> 02:56:30,040 IF WE CAN'T CHANGE THE 3429 02:56:30,040 --> 02:56:33,640 REGULATORY IMPACT WE HAVE TO ASK 3430 02:56:33,640 --> 02:56:34,840 CAN WE GET OFF LABEL COVERAGE 3431 02:56:34,840 --> 02:56:36,240 AND THIS IS VARIABLE DEPENDING 3432 02:56:36,240 --> 02:56:39,920 ON THE INSURANCE COMPANY AND 3433 02:56:39,920 --> 02:56:40,240 INDIVIDUAL. 3434 02:56:40,240 --> 02:56:42,280 WITH TIME AND FAMILIARITY 3435 02:56:42,280 --> 02:56:43,640 ADVOCACY MAY CHANGE. 3436 02:56:43,640 --> 02:56:45,160 IT'S VARIANCE FROM LAB TO LAB 3437 02:56:45,160 --> 02:56:46,360 WITHIN THE INDIVIDUAL MODELS. 3438 02:56:46,360 --> 02:56:47,920 TOE RIGHT IS A STUDY FROM LAST 3439 02:56:47,920 --> 02:56:49,080 YEAR FOR THE PURPOSES OF THIS 3440 02:56:49,080 --> 02:56:54,040 TALK LOOKING AT A SINGLE CHANGE 3441 02:56:54,040 --> 02:56:56,880 IN IMMEDIATE COMPOSITION C AND 3442 02:56:56,880 --> 02:56:59,760 THERE'S DRASTIC DIFFERENCES IN 3443 02:56:59,760 --> 02:57:01,880 HOW IT'S MEASURED AND IT MAKES 3444 02:57:01,880 --> 02:57:03,480 IT HARD TO COLLATE DATA AND 3445 02:57:03,480 --> 02:57:05,920 COMPARE ACROSS LABS. 3446 02:57:05,920 --> 02:57:08,400 DESPITE THE GAPS I THINK THERE'S 3447 02:57:08,400 --> 02:57:09,560 A LOT OF PROMISE IN THE FUTURE 3448 02:57:09,560 --> 02:57:12,480 FOR NOT JUST MOVING FORWARD WITH 3449 02:57:12,480 --> 02:57:14,400 IMPACTING PATIENT CARE BUT ALSO 3450 02:57:14,400 --> 02:57:16,000 UNDERSTANDING MUTATION AGNOSTIC 3451 02:57:16,000 --> 02:57:18,160 THERAPIES IN THE GROUP. 3452 02:57:18,160 --> 02:57:21,120 STUDYING PERHAPS NON-CFTR 3453 02:57:21,120 --> 02:57:23,800 TARGETED DRUGS THAT TARGET THE 3454 02:57:23,800 --> 02:57:25,360 TISSUE OF ORIGIN AND 3455 02:57:25,360 --> 02:57:26,520 UNDERSTANDING THE RESPONSE 3456 02:57:26,520 --> 02:57:27,160 VARIANT. 3457 02:57:27,160 --> 02:57:29,160 WHY DO SOME RESPOND ROBUSTLY TO 3458 02:57:29,160 --> 02:57:34,600 MODULATORS AND SOME DON'T. 3459 02:57:34,600 --> 02:57:37,640 I'LL END HERE ROUGHLY ON TIMISH 3460 02:57:37,640 --> 02:57:40,760 AND SUMMARIZE PATIENTS WITH 3461 02:57:40,760 --> 02:57:44,040 ULTRA RARE VARIANTS ARE A 3462 02:57:44,040 --> 02:57:45,400 POPULATION THAT DESERVE MORE 3463 02:57:45,400 --> 02:57:47,080 STUDY AND WE'RE PATIENT ACCESS 3464 02:57:47,080 --> 02:57:48,400 AND PERSONALIZATION OF CARE WITH 3465 02:57:48,400 --> 02:57:49,800 MODULATORS AND I THINK THE 3466 02:57:49,800 --> 02:57:51,400 SYSTEMS CAN BE POWERFUL FOR OUR 3467 02:57:51,400 --> 02:57:55,000 FUTURE WORK AND SERVING THIS 3468 02:57:55,000 --> 02:57:56,480 POPULATION AND THE BROADER CF 3469 02:57:56,480 --> 02:57:58,400 POPULATION AS WELL. 3470 02:57:58,400 --> 02:58:02,280 A HUGE THANK YOU TO THE 3471 02:58:02,280 --> 02:58:05,000 ORGANIZERS FOR LETTING ME SPEAK 3472 02:58:05,000 --> 02:58:07,480 AND I'LL INTRODUCE THE NEXT 3473 02:58:07,480 --> 02:58:07,720 SPEAKER. 3474 02:58:07,720 --> 02:58:11,680 SHE'LL BE THE LAST SPEAKER FOR 3475 02:58:11,680 --> 02:58:13,640 THE SESSION AND FROM UC SAN 3476 02:58:13,640 --> 02:58:17,160 FRANCISCO AND LOOKING AT HEALTH 3477 02:58:17,160 --> 02:58:18,640 EQUITY AT THE POPULATION WITH 3478 02:58:18,640 --> 02:58:19,000 CYSTIC FIBROSIS. 3479 02:58:19,000 --> 02:58:29,240 >> THANK YOU. 3480 02:58:35,440 --> 02:58:37,040 >> CF OCCURS IN PEOPLE WITH ALL 3481 02:58:37,040 --> 02:58:38,280 RACES AND ETHNICITY AND THOUGH 3482 02:58:38,280 --> 02:58:48,720 IT'S A SOCIAL CONSTRUCT, 3483 02:59:37,520 --> 02:59:38,080 VARIANTS DIFFER BETWEEN GROUPS 3484 02:59:38,080 --> 02:59:41,000 AND I THINK EVEN MORE SURPRISING 3485 02:59:41,000 --> 02:59:42,880 IS THE PERCENTAGE OF POPULATION 3486 02:59:42,880 --> 02:59:45,000 HAS NOT FULLY GENOTYPED. 3487 02:59:45,000 --> 02:59:47,080 THESE ARE PATIENTS KNOWN TO HAVE 3488 02:59:47,080 --> 02:59:51,320 CF THAT HAVE EITHER ZERO OR ONE 3489 02:59:51,320 --> 02:59:54,200 VARIANT IDENTIFIED AND ONLY 3% 3490 02:59:54,200 --> 02:59:56,680 OF NON-HISPANIC WHITE PATIENTS 3491 02:59:56,680 --> 02:59:58,640 BETWEEN 8% TO 10% OF EVERYBODY 3492 02:59:58,640 --> 02:59:59,200 ELSE. 3493 02:59:59,200 --> 03:00:01,280 THIS IS REALLY IMPORTANT WHEN 3494 03:00:01,280 --> 03:00:01,920 WE'RE THINKING ABOUT MODULATOR 3495 03:00:01,920 --> 03:00:12,080 THERAPY. 3496 03:00:52,920 --> 03:00:56,600 AND YOU CAN SEE THERE'S 40% OF 3497 03:00:56,600 --> 03:01:02,040 VARIANTS IN EACH AGENT. 3498 03:01:02,040 --> 03:01:12,600 VARIANTS DIFFER BETWEEN GROUPS. 3499 03:01:16,320 --> 03:01:19,680 A 3500 03:01:19,680 --> 03:01:22,240 AND I RELY ON IDENTIFYING AT 3501 03:01:22,240 --> 03:01:24,360 LEAST ONE VARIANT IN ORDER TO 3502 03:01:24,360 --> 03:01:25,960 PREVENT HAVING A FALSE NEGATIVE 3503 03:01:25,960 --> 03:01:26,200 SCREEN. 3504 03:01:26,200 --> 03:01:31,080 FOR THIS STUDY WE LOOKED AT ONE 3505 03:01:31,080 --> 03:01:34,480 OF THE COMMONLY USED VARIANT 3506 03:01:34,480 --> 03:01:36,680 PANEL AND BASED ON REGISTRY DATA 3507 03:01:36,680 --> 03:01:38,360 FOR EACH RACE AND ETHNICITY. 3508 03:01:38,360 --> 03:01:44,480 THEN WE TOOK THE CENSUS DATA FOR 3509 03:01:44,480 --> 03:01:55,000 EACH STATE AND THE FREQUENCY IS 3510 03:03:15,400 --> 03:03:16,760 SO DIFFERENT. 3511 03:03:16,760 --> 03:03:17,960 IT REALLY EMPHASIZES THAT WE 3512 03:03:17,960 --> 03:03:18,880 NEED THE STUDIES IN DIFFERENT 3513 03:03:18,880 --> 03:03:29,080 POPULATIONS. 3514 03:03:37,040 --> 03:03:45,680 AND WE DID FULL GENE SEQUENCING 3515 03:03:45,680 --> 03:03:49,120 FOR THE PATIENTS AND WHAT WE 3516 03:03:49,120 --> 03:03:51,560 FOUND IS THOUGH THE TWO PLACES 3517 03:03:51,560 --> 03:03:59,520 WERE SO CLOSE GEOGRAPHICALLY, 3518 03:03:59,520 --> 03:04:05,160 AND SO THERE'S FREQUENT VARIANTS 3519 03:04:05,160 --> 03:04:06,360 THAT WERE FOUND IN MANY OTHER 3520 03:04:06,360 --> 03:04:09,440 HISPANIC AND LATINO POPULATIONS 3521 03:04:09,440 --> 03:04:16,000 NOT PRESENT AT ALL IN DOMINICAN 3522 03:04:16,000 --> 03:04:21,360 REPUBLIC AND 10% OF PUERTO RICAN 3523 03:04:21,360 --> 03:04:21,640 APPRECIATES. 3524 03:04:21,640 --> 03:04:27,080 THIS EMPHASIZES WE NEED TO STUDY 3525 03:04:27,080 --> 03:04:28,320 POPULATIONS AND ALL PATIENTS 3526 03:04:28,320 --> 03:04:38,800 NEED FULLING TO UNDERSTAND. 3527 03:04:42,200 --> 03:04:43,680 RACIAL AND ETHNIC MINORITIES AND 3528 03:04:43,680 --> 03:04:45,760 PEOPLE ARE LESS LIKELY TO BE 3529 03:04:45,760 --> 03:04:56,200 QUALIFIED FOR MODULATORS. 3530 03:05:18,520 --> 03:05:21,960 AND YOU CAN SEE THAT FOR THE 3531 03:05:21,960 --> 03:05:23,640 DIFFERENT MODULATORS THE 3532 03:05:23,640 --> 03:05:25,240 FREQUENCY OF QUALIFICATION BUT 3533 03:05:25,240 --> 03:05:27,920 WHEN YOU LOOK AT THE OTHER RACES 3534 03:05:27,920 --> 03:05:33,440 YOU CAN SEE THIS IS LESS. 3535 03:05:33,440 --> 03:05:35,800 80% AND YOU CAN SEE IT'S JUST 3536 03:05:35,800 --> 03:05:46,360 OVER 70% QUALIFIED FOR E-LAX CAF 3537 03:05:47,360 --> 03:05:49,840 FOR AND OVERALL THREE-QUARTERS 3538 03:05:49,840 --> 03:05:53,120 QUALIFY AND LOWER PERCENTAGE 3539 03:05:53,120 --> 03:05:56,920 QUALIFY FOR HIGHLY EFFECTIVE 3540 03:05:56,920 --> 03:06:01,600 MODULATORS AND UNFORTUNATELY 3541 03:06:01,600 --> 03:06:12,120 EVEN LOWER AND NOT ONLY DO THEY 3542 03:06:15,160 --> 03:06:20,120 NOT QUALIFY BUT HISTORICALLY 3543 03:06:20,120 --> 03:06:21,920 MINORITIZED PEOPLE ARE NOT 3544 03:06:21,920 --> 03:06:32,280 INCLUDE IN THE TRIALS. 3545 03:06:36,640 --> 03:06:39,680 AND WHEN WE LOOKED AT THIS 3546 03:06:39,680 --> 03:06:42,800 STUDIES THAT REPORTED IT ONLY 73 3547 03:06:42,800 --> 03:06:44,600 INCLUDED MINORITY SUBJECTS. 3548 03:06:44,600 --> 03:06:48,800 SO ABOUT OVER A QUARTER OF THE 3549 03:06:48,800 --> 03:06:58,600 STUDIES HAD 100% CAUCASIAN AND 3550 03:06:58,600 --> 03:07:02,840 100% WHITE AND WHEN WE LOOKED AT 3551 03:07:02,840 --> 03:07:05,560 THE ACTUAL PERCENTAGES INCLUDED 3552 03:07:05,560 --> 03:07:10,680 AT NO POINT DID THEY COME CLOSE 3553 03:07:10,680 --> 03:07:11,880 TO REFLECTING THE DIVERSITY OF 3554 03:07:11,880 --> 03:07:16,040 THE POPULATION AND UNDERSTANDING 3555 03:07:16,040 --> 03:07:16,960 DIFFERENCES IN DRUG RESPONSE OR 3556 03:07:16,960 --> 03:07:25,720 SIDE EFFECTS IN THE GROUPS. 3557 03:07:25,720 --> 03:07:27,760 SO MORE RECENTLY I LOOKED AT A 3558 03:07:27,760 --> 03:07:31,920 MORE UPDATED DATA ON MODULATOR 3559 03:07:31,920 --> 03:07:37,040 STUDIES AND IT STILL CONTINUES 3560 03:07:37,040 --> 03:07:47,280 TO BE QUITE LOW. 3561 03:07:52,680 --> 03:07:54,440 IN THE SMALL PERCENTAGE OF 3562 03:07:54,440 --> 03:07:55,920 STUDIES THEY'RE NOT INCLUDING 3563 03:07:55,920 --> 03:07:56,280 SUBJECTS. 3564 03:07:56,280 --> 03:07:58,360 THIS IS EVEN WHEN YOU'RE LOOKING 3565 03:07:58,360 --> 03:08:03,080 AT THE PERCENTAGE OF MINORITIES 3566 03:08:03,080 --> 03:08:04,600 THAT HAVE 508 IT'S STILL NOT 3567 03:08:04,600 --> 03:08:05,480 REFLECTIVE THE PATIENTS ARE 3568 03:08:05,480 --> 03:08:15,640 BEING INCLUDED. 3569 03:08:15,640 --> 03:08:17,800 AND I'LL GO THROUGH SOME OF THE 3570 03:08:17,800 --> 03:08:21,240 REASONS WHY BUT I'LL START BY 3571 03:08:21,240 --> 03:08:23,200 SAYING BESIDE THE FACT 3572 03:08:23,200 --> 03:08:26,960 ETHNICALLY WRONG THAT THE 3573 03:08:26,960 --> 03:08:29,640 PATIENT POPULATION IS BEING 3574 03:08:29,640 --> 03:08:30,120 EXCLUDED. 3575 03:08:30,120 --> 03:08:31,560 FIRST IT MATTERS OUR CF 3576 03:08:31,560 --> 03:08:34,200 POPULATION IS BECOMING MORE 3577 03:08:34,200 --> 03:08:34,520 DIVERSE. 3578 03:08:34,520 --> 03:08:35,760 THIS IS A LARGER PROBLEM OVER 3579 03:08:35,760 --> 03:08:35,960 TIME. 3580 03:08:35,960 --> 03:08:39,120 YOU CAN SEE THE DIVERSITY ON THE 3581 03:08:39,120 --> 03:08:42,400 LEFT AND EACH YEAR IF YOU LOOK 3582 03:08:42,400 --> 03:08:45,120 AT THE REGISTRY DATA THAT IS 3583 03:08:45,120 --> 03:08:46,120 BEING MORE DIVERSE. 3584 03:08:46,120 --> 03:08:49,240 THIS IS PROBABLY A REFLECTION OF 3585 03:08:49,240 --> 03:08:50,760 THE INCREASING DIVERSITY IN THE 3586 03:08:50,760 --> 03:08:51,880 U.S. POPULATION. 3587 03:08:51,880 --> 03:08:57,680 IT'S A REFLECTION OF NEWBORN 3588 03:08:57,680 --> 03:09:00,040 SCREENING. 3589 03:09:00,040 --> 03:09:06,800 THEY'RE NOT SEVERE ASTHMATICS 3590 03:09:06,800 --> 03:09:17,120 AND THE PATIENTS BEING DIG -- 3591 03:09:17,120 --> 03:09:19,600 DIAGNOSED AND THE POPULATION IS 3592 03:09:19,600 --> 03:09:20,440 MORE DIVERSE IN THE ADULT 3593 03:09:20,440 --> 03:09:21,440 POPULATION OVERALL. 3594 03:09:21,440 --> 03:09:24,000 THE SECOND REASON IT MATTERS IS 3595 03:09:24,000 --> 03:09:26,640 BECAUSE PRIOR TO MODULATORS, 3596 03:09:26,640 --> 03:09:29,040 THESE GROUPS HAVE WORSE 3597 03:09:29,040 --> 03:09:30,480 MORTALITY THAN NON-HISPANIC 3598 03:09:30,480 --> 03:09:30,720 WHITES. 3599 03:09:30,720 --> 03:09:33,480 YOU'LL SEE THEY HAVE 85% 3600 03:09:33,480 --> 03:09:35,840 INCREASE RISK OF DEATH AND BLACK 3601 03:09:35,840 --> 03:09:39,520 PATIENTS 48% INCREASE OF RISK 3602 03:09:39,520 --> 03:09:50,040 COMPARED TO NON-HISPANIC WHITES. 3603 03:09:50,920 --> 03:09:52,480 AND HISPANIC PATIENTS WERE DYING 3604 03:09:52,480 --> 03:09:54,000 SIX YEARS EARLIER THAN 3605 03:09:54,000 --> 03:09:56,000 NON-HISPANIC WHITE PATIENTS AND 3606 03:09:56,000 --> 03:09:58,040 IN CALIFORNIA THEY FOUND ONLY 3607 03:09:58,040 --> 03:10:01,920 73% OF HISPANIC PATIENTS SURVIVE 3608 03:10:01,920 --> 03:10:03,320 18 YEARS AFTER DIAGNOSIS 3609 03:10:03,320 --> 03:10:07,360 COMPARED TO 98% SURVIVAL OF 3610 03:10:07,360 --> 03:10:09,000 WHITE PATIENTS. 3611 03:10:09,000 --> 03:10:15,160 IT ALSO MATTERS BECAUSE HISPANIC 3612 03:10:15,160 --> 03:10:25,720 WHITE PATIENTS HAVE AND THERE'S 3613 03:11:07,080 --> 03:11:09,440 A DIFFERENCE AND IN OTHER DATA 3614 03:11:09,440 --> 03:11:12,120 WE CAN TALK ABOUT LATER IS THAT 3615 03:11:12,120 --> 03:11:14,160 NOT ONLY DO THEY HAVE INCREASED 3616 03:11:14,160 --> 03:11:16,400 MORTALITY AND DIFFERENCES IN 3617 03:11:16,400 --> 03:11:18,640 LUNG FUNCTION AND INFECTIONS ARE 3618 03:11:18,640 --> 03:11:19,560 DIFFERENT. 3619 03:11:19,560 --> 03:11:24,920 SO INCREASED PREVALENCE OF 3620 03:11:24,920 --> 03:11:27,200 PSEUDOMONAS AND STAPH IN 3621 03:11:27,200 --> 03:11:36,520 HISPANIC PATIENTS ALSO REQUIRE 3622 03:11:36,520 --> 03:11:39,000 PSEUDOMONAS TREATMENT AT A 3623 03:11:39,000 --> 03:11:39,840 YOUNGER AGE. 3624 03:11:39,840 --> 03:11:46,080 WE'RE EXPECTS THE DISPARITY TO 3625 03:11:46,080 --> 03:11:46,400 WI 3626 03:11:46,400 --> 03:11:48,280 WIDEN OVER TIME BECAUSE WE DON'T 3627 03:11:48,280 --> 03:11:49,760 HAVE DISEASE ALTERING MEDICATION 3628 03:11:49,760 --> 03:11:50,920 FOR MANY OF THEM. 3629 03:11:50,920 --> 03:11:55,920 WE HAVE ALL SEEN GRAPH LIKE THIS 3630 03:11:55,920 --> 03:11:57,400 AND HOW WILL WE INCREASE 3631 03:11:57,400 --> 03:11:58,360 RESEARCH DIVERSITY AND A WANT US 3632 03:11:58,360 --> 03:12:01,240 ALL TO TAKE A MOMENT AND REFLECT 3633 03:12:01,240 --> 03:12:04,880 ON THE PERSON WHO TOOK DECADES 3634 03:12:04,880 --> 03:12:05,640 TO BE DIAGNOSED BECAUSE HE 3635 03:12:05,640 --> 03:12:08,840 DIDN'T LOOK LIKE THE INCORRECTLY 3636 03:12:08,840 --> 03:12:10,280 PORTRAYED PICTURE AS TAUGHT IN 3637 03:12:10,280 --> 03:12:12,280 MEDICAL SCHOOL AND REFLECT ON 3638 03:12:12,280 --> 03:12:14,880 THE CHILD DIAGNOSED MONTHS OR 3639 03:12:14,880 --> 03:12:16,720 YEARS AFTER SYMPTOMS BECAUSE A 3640 03:12:16,720 --> 03:12:18,360 NEWBORN SCREENING WAS CREATED 3641 03:12:18,360 --> 03:12:20,520 FOR VARIANTS FOR ANOTHER RACE OR 3642 03:12:20,520 --> 03:12:24,000 ETHNICITY THAN THEY WERE. 3643 03:12:24,000 --> 03:12:25,280 REFLECT ON THE BABIES AND 3644 03:12:25,280 --> 03:12:27,720 CHILDREN AND TEENAGERS WHO DIED 3645 03:12:27,720 --> 03:12:34,200 YEARS YOUNGER THAN WHITE 3646 03:12:34,200 --> 03:12:35,200 COUNTERPARTS AND THOSE WHO ARE 3647 03:12:35,200 --> 03:12:36,200 WORSE FUNCTION AND QUALITY OF 3648 03:12:36,200 --> 03:12:36,400 LIFE. 3649 03:12:36,400 --> 03:12:41,840 THINK ABOUT ALL THE FAMILIES WHO 3650 03:12:41,840 --> 03:12:52,320 ARE HAVING -- THEY'RE MORE 3651 03:12:53,640 --> 03:12:55,840 LIKELY TO GET SECURITY CALLED ON 3652 03:12:55,840 --> 03:13:00,560 THEM TO THAN GET HAVE A TEAM 3653 03:13:00,560 --> 03:13:03,400 TREAT THEM THAT AND DON'T SOUND 3654 03:13:03,400 --> 03:13:05,880 LIKE THEM OR SPEAK LIKE THEM OR 3655 03:13:05,880 --> 03:13:07,720 LIKE THEM CULTURALLY AND THEY'VE 3656 03:13:07,720 --> 03:13:09,800 BEEN LEFT OUT OF TRIALS AND 3657 03:13:09,800 --> 03:13:12,200 DON'T HAVE THESE DRUGS AVAILABLE 3658 03:13:12,200 --> 03:13:14,040 TO THEM AND LEFT WITHOUT 3659 03:13:14,040 --> 03:13:14,680 LIFE-SAVING TREATMENT. 3660 03:13:14,680 --> 03:13:16,560 WHEN WE TAKE THE HEAVINESS OF 3661 03:13:16,560 --> 03:13:17,920 WHERE WE'RE AT FOR THE PATIENTS 3662 03:13:17,920 --> 03:13:22,080 AND THINK ABOUT WHAT CAN WE DO. 3663 03:13:22,080 --> 03:13:24,320 THINKING OF DIFFERENT LEVELS OF 3664 03:13:24,320 --> 03:13:24,560 BARRIERS. 3665 03:13:24,560 --> 03:13:28,320 ON THE FEDERAL LEVEL WE NEED ALL 3666 03:13:28,320 --> 03:13:30,120 STUDIES INCLUDING MINORITIZED 3667 03:13:30,120 --> 03:13:32,240 PATIENTS AND FOR MODULATORS IT 3668 03:13:32,240 --> 03:13:33,800 MEANS WE NEED TO BE INCLUDING 3669 03:13:33,800 --> 03:13:35,880 VARIANTS THAT ARE IN THESE 3670 03:13:35,880 --> 03:13:39,040 GROUPS ALSO WE NEED TO BE 3671 03:13:39,040 --> 03:13:41,520 RECRUITING PATIENTS OF OTHER 3672 03:13:41,520 --> 03:13:42,200 VARIANTS AS WELL. 3673 03:13:42,200 --> 03:13:45,640 ON A SYSTEM AND INSTITUTIONAL 3674 03:13:45,640 --> 03:13:46,960 LEVEL, WE HAVE DIVERSE 3675 03:13:46,960 --> 03:13:47,520 RESEARCHERS. 3676 03:13:47,520 --> 03:13:49,760 WE NEED TO BUILD BACK UP THE 3677 03:13:49,760 --> 03:13:55,880 TRUST IN THE MEDICAL SYSTEMS AND 3678 03:13:55,880 --> 03:13:56,960 NIH AND FDA. 3679 03:13:56,960 --> 03:14:02,440 ON A PERSONAL LEVEL WE NEED 3680 03:14:02,440 --> 03:14:04,640 RESEARCHERS TO BUILD 3681 03:14:04,640 --> 03:14:05,800 RELATIONSHIPS WITH THE 3682 03:14:05,800 --> 03:14:08,360 COMMUNITIES AND PATIENTS. 3683 03:14:08,360 --> 03:14:10,800 AND ON THE LANGUAGE REIMBURSE 3684 03:14:10,800 --> 03:14:14,160 MANY AND HEALTH LITERACY, HOW 3685 03:14:14,160 --> 03:14:15,400 CAN WE CARE IN INDIVIDUAL 3686 03:14:15,400 --> 03:14:25,920 RELATIONSHIP FOR THESE PATIENTS. 3687 03:14:39,800 --> 03:14:41,960 INDIVIDUAL RESEARCHERS CAN'T GO 3688 03:14:41,960 --> 03:14:43,800 TO THE FDA TO GET THESE 3689 03:14:43,800 --> 03:14:44,960 MODULATORS APPROVED BASED ON 3690 03:14:44,960 --> 03:14:48,480 STUDIES IT HAS TO GO TO THE DRUG 3691 03:14:48,480 --> 03:14:48,720 COMPANY. 3692 03:14:48,720 --> 03:14:51,680 AND THIS IS A PROBLEM OF ALL 3693 03:14:51,680 --> 03:14:53,960 PERSONALIZED MEDICINE THAT IS 3694 03:14:53,960 --> 03:14:55,240 GOING TO BE ONLY WHO IS INCLUDED 3695 03:14:55,240 --> 03:14:57,040 IN THE STUDIES AND WHO IS 3696 03:14:57,040 --> 03:14:58,680 INCLUDED IN THE VARIANTS OR WHO 3697 03:14:58,680 --> 03:15:03,480 WILL GET THE DRUGS AND SO THE CF 3698 03:15:03,480 --> 03:15:05,200 COMMUNITY CAN BE A LEADER IN 3699 03:15:05,200 --> 03:15:06,520 PRESCRIBED MEDICINE AND ETHICS 3700 03:15:06,520 --> 03:15:09,560 AND TO THINK ABOUT IF THIS DRUG 3701 03:15:09,560 --> 03:15:11,160 WAS AVAILABLE TO EVERYBODY IF 3702 03:15:11,160 --> 03:15:12,760 THIS DRUG WAS NOT EXPENSIVE WE 3703 03:15:12,760 --> 03:15:15,040 CAN USE IT OFF LABEL OR ONLABEL 3704 03:15:15,040 --> 03:15:21,000 FOR EVERYBODY TO SAY WHO 3705 03:15:21,000 --> 03:15:31,200 RESPONDS. 3706 03:15:41,320 --> 03:15:43,000 AND THE GOAL IS TO CURE CF AND 3707 03:15:43,000 --> 03:15:45,720 PROVIDE ALL PEOPLE WITH CF THE 3708 03:15:45,720 --> 03:15:46,760 OPPORTUNITY TO LIVE LONG 3709 03:15:46,760 --> 03:15:47,480 FULFILLING LIVES. 3710 03:15:47,480 --> 03:15:52,880 WITH THAT I'LL OPEN UP THE 3711 03:15:52,880 --> 03:15:59,480 DISCUSSION AND THANKS TO THE 3712 03:15:59,480 --> 03:16:02,200 SPEAKERS AND NHLBI FOR HOSTING 3713 03:16:02,200 --> 03:16:02,760 US TODAY. 3714 03:16:02,760 --> 03:16:05,000 >> THANK YOU TO OUR SPEAKERS FOR 3715 03:16:05,000 --> 03:16:05,480 GREAT TALKS. 3716 03:16:05,480 --> 03:16:08,280 AS WE GET UP TO THE PANEL VIEW 3717 03:16:08,280 --> 03:16:11,320 HERE I DID WANT TO LEAD OFF WITH 3718 03:16:11,320 --> 03:16:12,840 A QUESTION I ACTUALLY GOT 3719 03:16:12,840 --> 03:16:14,440 BRIEFLY MENTIONED IN THE LAST 3720 03:16:14,440 --> 03:16:18,400 SESSION AND I THINKING ABOUT 3721 03:16:18,400 --> 03:16:19,960 THIS ONE IT WILL BE FOR YOU. 3722 03:16:19,960 --> 03:16:25,080 IN THE CONVERSATIONS ABOUT THE 3723 03:16:25,080 --> 03:16:28,400 IN UTERO MODULATOR USE AND THE 3724 03:16:28,400 --> 03:16:29,520 THE QUESTIONS ABOUT FERTILITY 3725 03:16:29,520 --> 03:16:32,320 AND THE QUESTIONS TO BE THOUGHT 3726 03:16:32,320 --> 03:16:35,040 OF FOR THE PATIENT THROUGHOUT 3727 03:16:35,040 --> 03:16:38,840 THEIR LIFE IS THERE ABOUT ADULT 3728 03:16:38,840 --> 03:16:41,320 MALES STARTING OR REPRODUCTIVE 3729 03:16:41,320 --> 03:16:45,560 ASSISTED TECHNOLOGIES AND HOW 3730 03:16:45,560 --> 03:16:46,920 THAT MIGHT BE CHANGING? 3731 03:16:46,920 --> 03:16:57,360 >> FOR THE FIRST TIME IN 3732 03:17:04,200 --> 03:17:14,640 SPERM LASTS FOR ABOUT 80 DAYS 3733 03:17:52,240 --> 03:17:54,240 KNOW KNOW KNOW IF YOU COULD 3734 03:17:54,240 --> 03:17:56,960 TALK MORE ABOUT THE FREQUENT 3735 03:17:56,960 --> 03:17:58,680 STOPPING ON THE TRANSPLANTATIONS 3736 03:17:58,680 --> 03:18:00,400 AND SOME OF THE SIDE EFFECTS. 3737 03:18:00,400 --> 03:18:05,440 >> THANK YOU FOR THAT QUESTION, 3738 03:18:05,440 --> 03:18:14,400 SO WE NOTICED THAT THE 3739 03:18:14,400 --> 03:18:22,640 DISCONTINUATION RATE OF THE--A 3740 03:18:22,640 --> 03:18:25,080 LOT OF PEOPLE WHO STARTED FOR GI 3741 03:18:25,080 --> 03:18:27,160 REASONS FOR GI SYMPTOMS ENDED UP 3742 03:18:27,160 --> 03:18:30,360 STOPPING BECAUSE OF GI SYMPTOMS 3743 03:18:30,360 --> 03:18:33,360 AND I SUSPECT THAT ETI IS NOT 3744 03:18:33,360 --> 03:18:36,480 BENEFICIAL FOR TREATING GI 3745 03:18:36,480 --> 03:18:37,240 SYMPTOMS FOR LONG TRANSPLANT 3746 03:18:37,240 --> 03:18:39,960 BECAUSE THEY MAY BE RELATED TO 3747 03:18:39,960 --> 03:18:42,240 CERTAIN IMMUNE SUPPRESSION 3748 03:18:42,240 --> 03:18:43,280 MEDICATIONS. 3749 03:18:43,280 --> 03:18:45,000 AND THERE'S, YOU KNOW 3750 03:18:45,000 --> 03:18:47,280 CONTROVERSY ABOUT WHETHER IT'S 3751 03:18:47,280 --> 03:18:48,600 BENEFICIALOT NONTRANSPLANTED 3752 03:18:48,600 --> 03:18:50,640 PATIENTS GI SYMPTOMS AS WELL AND 3753 03:18:50,640 --> 03:18:53,760 I THINK PEOPLE GOT A LOT OF 3754 03:18:53,760 --> 03:19:04,240 ABDOMINAL PAIN AND ABDOMINAL 3755 03:19:07,600 --> 03:19:08,520 SYMPTOMS. 3756 03:19:08,520 --> 03:19:10,320 AND THERE ARE INSTANCES WHERE 3757 03:19:10,320 --> 03:19:12,320 PEOPLE STOPPED IT AND RESTARTED 3758 03:19:12,320 --> 03:19:13,840 IT AND IT'S HAPPENED SO IT SEEMS 3759 03:19:13,840 --> 03:19:15,480 LIKE IT'S A REAL PHENOMENON 3760 03:19:15,480 --> 03:19:16,680 THAT'S HAPPENING AND IT'S 3761 03:19:16,680 --> 03:19:18,440 POSSIBLE THAT MAYBE THEY HAVE 3762 03:19:18,440 --> 03:19:19,880 HYPER-ACTIVITY OF THEIR CFTR 3763 03:19:19,880 --> 03:19:23,760 CHANNELS AND IN THE NORMAL NONCF 3764 03:19:23,760 --> 03:19:25,560 LUNGS AND SO THAT WAS A THOUGHT. 3765 03:19:25,560 --> 03:19:27,520 THE STOPPING AND STARTING IS 3766 03:19:27,520 --> 03:19:28,720 REALLY DANGEROUS BECAUSE THE 3767 03:19:28,720 --> 03:19:30,480 DRUG ACTIONS AND SO, PATIENTS 3768 03:19:30,480 --> 03:19:31,880 JUST HAVE TO BE REALLY AWARE 3769 03:19:31,880 --> 03:19:34,320 THAT IF THEY'RE GOING TO STOP 3770 03:19:34,320 --> 03:19:36,720 THERE, THEY REALLY NEED TO TALK 3771 03:19:36,720 --> 03:19:44,400 TO THEIR TRANSPLANT TO ADJUST. 3772 03:19:44,400 --> 03:19:45,720 >> SO I HAVE A QUESTION FOR ALL 3773 03:19:45,720 --> 03:19:48,600 OF OUR PANEL BUT I WILL DIRECT 3774 03:19:48,600 --> 03:19:49,800 OUR ADULT PULL MONITORROLOGYIST 3775 03:19:49,800 --> 03:19:51,080 IN THE CREW, THERE'S BEEN GREAT 3776 03:19:51,080 --> 03:19:52,160 CONVERSATION IN THE CHANNEL 3777 03:19:52,160 --> 03:19:53,640 ABOUT TRANSITION AND WHAT DO WE 3778 03:19:53,640 --> 03:19:55,560 DO WITH PATIENTS AS THEY'RE 3779 03:19:55,560 --> 03:19:56,640 INCREASINGLY HEALTHY, DOES IT 3780 03:19:56,640 --> 03:19:57,680 CHANGE OUR PLANS WHICH AREN'T 3781 03:19:57,680 --> 03:20:00,960 ALWAYS THE BEST TO START WITH IN 3782 03:20:00,960 --> 03:20:03,680 CF CARE AND I WILL ADD ON TOP OF 3783 03:20:03,680 --> 03:20:05,160 THAT, MAYBE PARTICULARLY FOR YOU 3784 03:20:05,160 --> 03:20:06,920 CATHY, HOW DO WE START THE 3785 03:20:06,920 --> 03:20:09,520 TRANSITION AND THE PREPARATION 3786 03:20:09,520 --> 03:20:11,400 THAT WE TRY TO HAVE AT SOME 3787 03:20:11,400 --> 03:20:14,640 POINT THAT THINK ABOUT WHICH 3788 03:20:14,640 --> 03:20:16,280 PROGNOSIS, WHEN DO YOU START 3789 03:20:16,280 --> 03:20:17,760 TALKING ABOUT THINGS LIKE THOSE 3790 03:20:17,760 --> 03:20:18,840 CONVERSATIONS AND 1 THING THAT 3791 03:20:18,840 --> 03:20:23,040 WAS RAISED WAS WHO DO WE 3792 03:20:23,040 --> 03:20:25,240 TRANSITION TO IS THERE A 3793 03:20:25,240 --> 03:20:26,120 WORKFORCE PROBLEM FOR ADULTS 3794 03:20:26,120 --> 03:20:28,800 THAT ARE FOCUSING ON CARE, SO 3795 03:20:28,800 --> 03:20:29,760 THERE'S A GIANT BUNDLE OF 3796 03:20:29,760 --> 03:20:32,280 QUESTIONS THAT I WILL PASS TO 3797 03:20:32,280 --> 03:20:35,400 THE ADULT PULL MONITORROLOGYIST 3798 03:20:35,400 --> 03:20:37,640 AND SEE WHAT YOU HAVE TO SAY. 3799 03:20:37,640 --> 03:20:40,400 >> I WILL TALK ABOUT PROCINOSEIS 3800 03:20:40,400 --> 03:20:42,920 IN THE PEDIATRIC CLINIC, IT'S SO 3801 03:20:42,920 --> 03:20:44,960 IMPORTANT TO TELL PATIENTS AND 3802 03:20:44,960 --> 03:20:46,040 FAMILIES THAT WE KNOW IS BASED 3803 03:20:46,040 --> 03:20:47,480 ON THE PAST AND WHAT'S HAPPENED 3804 03:20:47,480 --> 03:20:49,160 IN THE PAST AND THINGS ARE 3805 03:20:49,160 --> 03:20:50,200 EVOLVING QUICKLY AND EVERY FEW 3806 03:20:50,200 --> 03:20:53,560 YEARS IT SEEMS THERE'S A NEW 3807 03:20:53,560 --> 03:20:56,040 VERY EFFECTIVE CF THERAPEUTIC 3808 03:20:56,040 --> 03:20:56,960 COMING ON LINE AND TELLING 3809 03:20:56,960 --> 03:21:00,280 PEOPLE THAT THE MEDIAN EXPECTED 3810 03:21:00,280 --> 03:21:03,160 AGE OF SURVIVAL IS 50 YEARS OLD, 3811 03:21:03,160 --> 03:21:05,480 THAT'S NOT OLD FOR LUNG 3812 03:21:05,480 --> 03:21:05,880 TRANSPLANTS. 3813 03:21:05,880 --> 03:21:07,560 SIXTY-FIVE YEAR-OLDS ARE 3814 03:21:07,560 --> 03:21:09,320 FREQUENTLY RANS PLANTED BUT CF 3815 03:21:09,320 --> 03:21:11,320 PATIENTS ARE DEFINED GETTING 3816 03:21:11,320 --> 03:21:13,280 EVOLUNTEERSUATED OR GOING TO A 3817 03:21:13,280 --> 03:21:14,520 TRANSPLANT BECAUSE THEY LIVE 3818 03:21:14,520 --> 03:21:15,760 LONG ENOUGH AND THEY FEEL LIKE 3819 03:21:15,760 --> 03:21:17,680 THEY BEAT THE ODDS BY LIVING TO 3820 03:21:17,680 --> 03:21:19,440 FOIRT SO I WORRY ABOUT THE 3821 03:21:19,440 --> 03:21:20,760 MENTAL HEALTH AND TELLS FOLKS 3822 03:21:20,760 --> 03:21:21,960 THEY SHOULD EXPECT TO LIVE TO 3823 03:21:21,960 --> 03:21:25,080 AGE 50 WHICH IS HOW THEY'RE 3824 03:21:25,080 --> 03:21:27,480 INTERPRETING THE STATISTIC. 3825 03:21:27,480 --> 03:21:29,200 BECAUSE, THEY MAY LIMIT THEIR 3826 03:21:29,200 --> 03:21:35,480 AMBITIONS AS WELL. 3827 03:21:35,480 --> 03:21:35,880 DRNCHL. 3828 03:21:35,880 --> 03:21:38,400 >> I WILL CHIME IN A BIT ABOUT 3829 03:21:38,400 --> 03:21:42,280 TRANSITION BECAUSE IT REMAINS A 3830 03:21:42,280 --> 03:21:44,000 KEY IN PROBLEMATIC AND PROBABLY 3831 03:21:44,000 --> 03:21:46,760 MORE SO NOW AND THAT'S IF YOU 3832 03:21:46,760 --> 03:21:47,520 GET THESE--THE TRANSITION WHEN 3833 03:21:47,520 --> 03:21:49,800 YOU'RE TRYING TO STAY ON YOUR 3834 03:21:49,800 --> 03:21:53,760 TRI CAFTA ON YOUR THERAPIES, THE 3835 03:21:53,760 --> 03:22:01,400 IMPACT THE IMPACT ON GOING OFF 3836 03:22:01,400 --> 03:22:03,640 ASK ON HAVING AND IT WILL BE 3837 03:22:03,640 --> 03:22:06,120 MORE PRONOUNCED OF SEC AND LOW 3838 03:22:06,120 --> 03:22:07,960 MEDICAL LITERACY AND MINORITY, 3839 03:22:07,960 --> 03:22:09,960 COMMUNITIES WHO ARE NOT--IT'S 3840 03:22:09,960 --> 03:22:10,800 JUST--IT SEEMS LIKE IT'S GOING 3841 03:22:10,800 --> 03:22:21,080 TO BE A PROBLEM. 3842 03:22:56,560 --> 03:22:58,360 --I THINK A LOT CAN BE LOST IN 3843 03:22:58,360 --> 03:23:00,080 THESE PERIODS AND IT'LL BE LOST 3844 03:23:00,080 --> 03:23:02,280 IN A PARTICULAR POPULATION 3845 03:23:02,280 --> 03:23:05,640 THAT'S VERY PROBLEMATIC. 3846 03:23:05,640 --> 03:23:07,400 >> I WAS GOING TO SAY, WE 3847 03:23:07,400 --> 03:23:09,400 PROBABLY NEED TO ADVICE THE 3848 03:23:09,400 --> 03:23:11,280 TRANSITION PROGRAM WE'RE USING 3849 03:23:11,280 --> 03:23:13,120 SO THAT WE EMPHASIZE LONGEVITY 3850 03:23:13,120 --> 03:23:17,400 AND THE THINGS THAT WILL ARISE 3851 03:23:17,400 --> 03:23:19,040 BECAUSE OF LONGEVITY AND AS WAS 3852 03:23:19,040 --> 03:23:20,640 MADE THE POINT IN THE CHAT WITH 3853 03:23:20,640 --> 03:23:23,760 GREG THAT WE NEED TO MAINTAIN 3854 03:23:23,760 --> 03:23:27,120 OUR DISCUSSIONS ABOUT TALKING TO 3855 03:23:27,120 --> 03:23:30,000 PEOPLE WHEN THEY'RE DIAGNOSED, 3856 03:23:30,000 --> 03:23:32,000 TO SOME EXTENT, AND THE 3857 03:23:32,000 --> 03:23:34,280 POSSIBILITIES OF REALLY HUGE 3858 03:23:34,280 --> 03:23:35,560 HEALTH WITH LOSS OF THEY SAID 3859 03:23:35,560 --> 03:23:37,360 ACCESS TO CARE OR ACCESS TO 3860 03:23:37,360 --> 03:23:39,400 THEIR SURANCE WHICH IS CRITICAL 3861 03:23:39,400 --> 03:23:42,840 OBVIOUSLY FOR PAYING FOR 3862 03:23:42,840 --> 03:23:45,760 $300,000 YEAR MED, NEXMED IS 3863 03:23:45,760 --> 03:23:47,360 JUST EXPENSIVE OR A COMBINATION 3864 03:23:47,360 --> 03:23:47,800 OF THEM. 3865 03:23:47,800 --> 03:23:49,000 >> YEAH AND THINKING ABOUT 3866 03:23:49,000 --> 03:23:50,440 ADHERENCE AND TAKING MEDICATIONS 3867 03:23:50,440 --> 03:23:52,360 BEFORE YOU HAVE SYMPTOMS OF THE 3868 03:23:52,360 --> 03:23:54,920 DISEASE, YOU THINK ABOUT PEOPLE 3869 03:23:54,920 --> 03:23:56,440 WHO ARE DESCRIBED ANTIHYPER 3870 03:23:56,440 --> 03:23:57,760 TENSIVES WHO ARE LESS ADHERENT 3871 03:23:57,760 --> 03:23:59,160 BEFORE THEY HAVE A HEART ATTACK 3872 03:23:59,160 --> 03:24:00,800 OR STROKE AND YOU KNOW REALLY 3873 03:24:00,800 --> 03:24:03,440 FOCUSING ON HOW WE CAN PREVENT 3874 03:24:03,440 --> 03:24:05,160 LUNG FUNCTION LOSS FOR PEOPLE 3875 03:24:05,160 --> 03:24:06,560 WHO ARE EITHER DON'T HAVE 3876 03:24:06,560 --> 03:24:09,160 ACCESS, BECAUSE THEY USE THEIR 3877 03:24:09,160 --> 03:24:10,720 INSURANCE OR OTHER REASONS THAT 3878 03:24:10,720 --> 03:24:14,920 IMPACT THEIR ABILITY TO ACTUALLY 3879 03:24:14,920 --> 03:24:15,880 OBTAIN MEDICATION AND PEOPLE WHO 3880 03:24:15,880 --> 03:24:17,760 YOU KNOW ARE YOUNG ADULTS AND 3881 03:24:17,760 --> 03:24:20,080 DON'T THINK IT'S IMPORTANT TO 3882 03:24:20,080 --> 03:24:20,600 TAKE IT YET. 3883 03:24:20,600 --> 03:24:21,840 >> I THINK THE OTHER ASPECT OF 3884 03:24:21,840 --> 03:24:23,640 THAT IS WE REALLY--THIS IS THE 3885 03:24:23,640 --> 03:24:25,480 POINT WHERE WE REALLY, REALLY 3886 03:24:25,480 --> 03:24:28,480 NEED TO GET THE ADULT CF 3887 03:24:28,480 --> 03:24:30,080 COMMUNITY INVOLVED AND HAVE THEM 3888 03:24:30,080 --> 03:24:31,920 HELP US CHANGE HOW WE'RE USING 3889 03:24:31,920 --> 03:24:33,520 CF RISE AND WAYS TO TRANSITION 3890 03:24:33,520 --> 03:24:34,920 PEOPLE BECAUSE WE REALLY NEED 3891 03:24:34,920 --> 03:24:36,120 THEIR INPUT, LIKE WHAT ARE THEY 3892 03:24:36,120 --> 03:24:37,880 WILLING TO DO NOW THAT PEOPLE 3893 03:24:37,880 --> 03:24:39,480 ARE HEALTHIER, BECAUSE WE CAN'T 3894 03:24:39,480 --> 03:24:40,440 JUST DICTATE AND SAY HEY, THIS 3895 03:24:40,440 --> 03:24:46,440 IS WHAT YOU SHOULD DO WITHOUT 3896 03:24:46,440 --> 03:24:46,880 GETTING THEIR INPUT. 3897 03:24:46,880 --> 03:24:48,560 >> AND I WILL HIGHLIGHT A 3898 03:24:48,560 --> 03:24:50,400 COMMENT THAT POPPED IN FROM 3899 03:24:50,400 --> 03:24:53,960 TRACEY WHERE IT SAID A SURVEY 3900 03:24:53,960 --> 03:24:58,120 THAT SAID IN ADULT WOMEN OVER 40 3901 03:24:58,120 --> 03:25:02,800 WITH CF, THAT THERE'S NO PC P. 3902 03:25:02,800 --> 03:25:04,200 SO REALISTICALLY THERE'S FEWER 3903 03:25:04,200 --> 03:25:06,600 COMPLICATIONS OUTSIDE OF WHAT WE 3904 03:25:06,600 --> 03:25:07,880 AS PULL MONITORROLOGYIST THRAIN 3905 03:25:07,880 --> 03:25:09,880 WITH AND DEAL WITH IN MEDIATE 3906 03:25:09,880 --> 03:25:12,560 RICKS, THERE'S MUCH, MUCH, MORE 3907 03:25:12,560 --> 03:25:14,040 IN ADULTS SO THAT ACCORD NATION 3908 03:25:14,040 --> 03:25:19,880 OF CARE IS A BIG BEAR TO TACKLE. 3909 03:25:19,880 --> 03:25:20,920 >> WITH OUR CONVERSATION, 3910 03:25:20,920 --> 03:25:22,440 THERE'S BEEN A BUNCH OF 3911 03:25:22,440 --> 03:25:27,600 QUESTIONS ABOUT USING NF1 3912 03:25:27,600 --> 03:25:29,320 TRIALS, GAINING ACCESS WITH 3913 03:25:29,320 --> 03:25:31,520 INSURANCE, THERE'S BEEN THIS 3914 03:25:31,520 --> 03:25:33,480 ONGOING DEBATE ABOUT CAN YOU 3915 03:25:33,480 --> 03:25:36,240 TAKE SOME OF THESE RESPONSE IN 3916 03:25:36,240 --> 03:25:38,120 STEREOTYPING AND REALLY HOW DOES 3917 03:25:38,120 --> 03:25:40,720 IT CORRELATE TO FEV1, SO I WAS 3918 03:25:40,720 --> 03:25:42,160 INTERESTED YOU TALK ABOUT THOSE 3919 03:25:42,160 --> 03:25:45,160 40 PATIENTS THAT YOU DID GET 3920 03:25:45,160 --> 03:25:45,560 OFFLABEL USE FOR. 3921 03:25:45,560 --> 03:25:46,960 YOU KNOW IF YOU COULD SPEAK A 3922 03:25:46,960 --> 03:25:48,880 LITTLE BIT TO WHAT YOU KNOW AND 3923 03:25:48,880 --> 03:25:59,160 WHAT YOU FOUND. 3924 03:26:05,680 --> 03:26:06,680 DRNCHL--YOU KNOW WE ALL DO THIS 3925 03:26:06,680 --> 03:26:09,120 IN PRACTICES AND LOTS OF OTHER 3926 03:26:09,120 --> 03:26:11,400 DISEASES SOMEONE IN ASTHMA, I 3927 03:26:11,400 --> 03:26:15,720 START THEM ON INHALER CORTICO 3928 03:26:15,720 --> 03:26:18,800 STEROIDS, BUT IT'S NOT FINANCIAL 3929 03:26:18,800 --> 03:26:19,840 PRACTICAL AND THIRD PARTIES 3930 03:26:19,840 --> 03:26:21,560 AGREE SO I HAVE TO HAVE ANOTHER 3931 03:26:21,560 --> 03:26:22,560 MECHANISM FOR IT. 3932 03:26:22,560 --> 03:26:23,680 THERE ARE STUDIES THAT HAVE BEEN 3933 03:26:23,680 --> 03:26:25,600 FUNDED TO DID THIS IN SMALL 3934 03:26:25,600 --> 03:26:27,600 NUMBERS SO THEY'RE GETTING THE 3935 03:26:27,600 --> 03:26:28,880 DATA PRECISION ON THAT, ERIC AND 3936 03:26:28,880 --> 03:26:32,440 HIS GROUP ARE DOING THIS FOR 3937 03:26:32,440 --> 03:26:33,960 PEOPLE WHO HAVE EVIDENCE SO THAT 3938 03:26:33,960 --> 03:26:36,400 PRECISION IS STILL OUT THERE, AS 3939 03:26:36,400 --> 03:26:38,160 FAR AS CONNECTION OF YOU KNOW 3940 03:26:38,160 --> 03:26:38,800 STEREOTYPING AND WHATEVER FORM 3941 03:26:38,800 --> 03:26:41,560 IT MAY BE TO THE CLINICAL DATA, 3942 03:26:41,560 --> 03:26:43,880 THERE'S LOTS AND LOTS OF 3943 03:26:43,880 --> 03:26:46,760 DIFFERENT WAYS TO LOOK AT IT. 3944 03:26:46,760 --> 03:26:57,320 IT ALL DEPENDS ON THE COHORT AND 3945 03:26:59,400 --> 03:27:00,600 OBVIOUSLY NO PERSONAL 3946 03:27:00,600 --> 03:27:01,880 CONNECTIONS WITH THE NONCELL 3947 03:27:01,880 --> 03:27:02,600 MODELS BECAUSE THAT'S DIDN'T 3948 03:27:02,600 --> 03:27:04,120 COME FROM AN INDIVIDUAL OR AN 3949 03:27:04,120 --> 03:27:06,440 INDIVIDUAL THAT'S BEING COMPARED 3950 03:27:06,440 --> 03:27:06,640 TO. 3951 03:27:06,640 --> 03:27:07,640 ALL OF THOSE STUDIES WHEN YOU 3952 03:27:07,640 --> 03:27:09,640 LOOK AT THEM, THERE'S A 3953 03:27:09,640 --> 03:27:10,920 CORRELATION, BENEFIT IN THE 3954 03:27:10,920 --> 03:27:11,880 MODEL DOES CORRELATE WITH 3955 03:27:11,880 --> 03:27:13,160 BENEFIT OF THE PATIENT BUT THE 3956 03:27:13,160 --> 03:27:14,080 PRECISION OF THAT ISN'T CLEAR 3957 03:27:14,080 --> 03:27:15,520 AND THE PORTION IN THE VARIANTS 3958 03:27:15,520 --> 03:27:17,120 AND THE DIFFERENT MODELS AND THE 3959 03:27:17,120 --> 03:27:19,160 WAY PEOPLE DO IT, IT'S DIFFICULT 3960 03:27:19,160 --> 03:27:20,920 TO GATHER THAT TICKET AND GET A 3961 03:27:20,920 --> 03:27:22,880 HIGH LEVEL LOOK AT IT AND IN OUR 3962 03:27:22,880 --> 03:27:27,560 DATA, MEGAN WE'RE DOING REAL 3963 03:27:27,560 --> 03:27:28,760 WORLD TYPING WHERE THE DATA 3964 03:27:28,760 --> 03:27:29,600 COLLECTION AFTER PATIENTS ARE 3965 03:27:29,600 --> 03:27:31,040 STARTED ON DRUGS IS REALLY 3966 03:27:31,040 --> 03:27:32,560 WHATEVER IS GATHERED IN CLINICAL 3967 03:27:32,560 --> 03:27:33,800 CARE, ESPECIALLY OVER THE LAST 2 3968 03:27:33,800 --> 03:27:35,480 YEARS HAS BEEN HIGHLY LIMITED 3969 03:27:35,480 --> 03:27:38,160 AND SCATTERED, AND MAKE ITS VERY 3970 03:27:38,160 --> 03:27:39,120 DIFFICULT TO LOOK, IT MIRRORS 3971 03:27:39,120 --> 03:27:40,600 WHAT WE SEE IN THE PUBLISHED 3972 03:27:40,600 --> 03:27:42,240 LITERATURE WHICH IS THE BROAD 3973 03:27:42,240 --> 03:27:42,920 STROKES, DEFINITELY A 3974 03:27:42,920 --> 03:27:44,440 CORRELATION BUT IT'S HARD TO 3975 03:27:44,440 --> 03:27:47,320 REALLY DRILL IN ON HOW PRECISE 3976 03:27:47,320 --> 03:27:48,280 THAT PREDICTION IS. 3977 03:27:48,280 --> 03:27:49,600 I WOULD ACTUALLY TAKE IT A STEP 3978 03:27:49,600 --> 03:27:50,880 FURTHER AND SAY, THAT YOU KNOW 3979 03:27:50,880 --> 03:27:55,440 IF WE ACCEPT AND BELIEVE THE 3980 03:27:55,440 --> 03:27:56,720 PREDICTION, WHAT'S THE CUT OFF? 3981 03:27:56,720 --> 03:27:58,480 WHAT IS OR ISN'T A RESPONSE? 3982 03:27:58,480 --> 03:28:00,720 WHAT'S THE NUMBER THAT MATTERS? 3983 03:28:00,720 --> 03:28:02,440 AND AGAIN WITH VARIANTS IT'S 3984 03:28:02,440 --> 03:28:05,320 DIFFICULT TO PUT YOUR FINGER ON 3985 03:28:05,320 --> 03:28:11,040 THAT. 3986 03:28:11,040 --> 03:28:11,840 >> IT'S VERY TRICKY. 3987 03:28:11,840 --> 03:28:13,120 WE'VE BEEN DOING OFF LABEL FOR 3988 03:28:13,120 --> 03:28:15,040 ALMOST A DECADE NOW AND WE'VE 3989 03:28:15,040 --> 03:28:17,440 HAD VARYING SUCCESS WITH 3990 03:28:17,440 --> 03:28:18,720 INSURANCE COMPANIES, BUT 3991 03:28:18,720 --> 03:28:22,240 ALMOST--WE REALLY MAKE A CASE 3992 03:28:22,240 --> 03:28:24,640 FOR BEFORE, LIKE, EXACERBATIONS, 3993 03:28:24,640 --> 03:28:25,840 LUNG FUNCTION, DECLINE, 3994 03:28:25,840 --> 03:28:27,560 INFECTIONS, LIKE ALL THE 3995 03:28:27,560 --> 03:28:28,600 MORBIDITY. 3996 03:28:28,600 --> 03:28:30,920 WE WILL SOMETIMES BEG FOR A 3997 03:28:30,920 --> 03:28:33,320 MONTH, 2, MONTH, 3 MONTHS FOR AN 3998 03:28:33,320 --> 03:28:35,000 INSURANCE COMPANY FOR A DRUG AND 3999 03:28:35,000 --> 03:28:38,560 THEN GIVE THEM BACK DATA SO 4000 03:28:38,560 --> 03:28:40,200 SWEAT CHANGES, WEIGHT CHANGES, 4001 03:28:40,200 --> 03:28:41,000 LUNG FUNCTION AND WE'VE BEEN 4002 03:28:41,000 --> 03:28:44,440 ABLE TO HAVE PATIENTS WITH RARE 4003 03:28:44,440 --> 03:28:47,520 DE NOVO MUTATIONS GET ACCESS BUT 4004 03:28:47,520 --> 03:28:49,280 WE REALLY NEED LIKE A PATH FOR 4005 03:28:49,280 --> 03:28:51,160 EVERYBODY FOR THIS, RIGHT? 4006 03:28:51,160 --> 03:28:53,440 YOU CAN'T JUST BE IF YOU'RE AT A 4007 03:28:53,440 --> 03:28:55,440 CERTAIN CENTER WHERE THE CF 4008 03:28:55,440 --> 03:28:56,960 PROVIDER IS MORE LIKELY TO DO 4009 03:28:56,960 --> 03:28:58,280 THIS, FOR INSTANCE OTHER 4010 03:28:58,280 --> 03:28:59,200 CENTERS, WHETHER YOU GET THE 4011 03:28:59,200 --> 03:29:01,120 DRUG OR NOT AND THEN ALSO LIKE 4012 03:29:01,120 --> 03:29:03,600 YOU WERE DISCUSSING IT MAKE ITS 4013 03:29:03,600 --> 03:29:04,480 DIFFICULT TO PUBLISH 4014 03:29:04,480 --> 03:29:05,840 WITHOUT--YOU KNOW WITH KEEPING 4015 03:29:05,840 --> 03:29:09,680 THEIR INFORMATION PRIVATE, 4016 03:29:09,680 --> 03:29:09,880 RIGHT? 4017 03:29:09,880 --> 03:29:11,440 THERE'S JUST A LOT OF 4018 03:29:11,440 --> 03:29:11,840 CHALLENGES. 4019 03:29:11,840 --> 03:29:13,600 IT WOULD BE REALLY NICE IF WE 4020 03:29:13,600 --> 03:29:14,960 COULD COME TOGETHER AS A GROUP 4021 03:29:14,960 --> 03:29:16,880 TO COME UP WITH LIKE WHAT ARE 4022 03:29:16,880 --> 03:29:20,440 THE THINGS TO MONITOR AFTER 4023 03:29:20,440 --> 03:29:20,640 THERAPY. 4024 03:29:20,640 --> 03:29:22,760 IF THERE COULD BE SOME UNIVERSAL 4025 03:29:22,760 --> 03:29:24,400 LANGUAGE THAT PEOPLE COULD USE 4026 03:29:24,400 --> 03:29:26,200 FOR LETTERS FOR INSURANCE 4027 03:29:26,200 --> 03:29:27,160 COMPANIES, ADVOCACY FOR 4028 03:29:27,160 --> 03:29:28,040 INSURANCE, BUT WE REALLY NEED TO 4029 03:29:28,040 --> 03:29:30,360 COME UP WITH A BETTER WAY TO GO 4030 03:29:30,360 --> 03:29:40,840 FORWARD WITH THESE PATIENTS. 4031 03:29:43,880 --> 03:29:45,200 >> --IT IS INCREDIBLE LOAMACYY 4032 03:29:45,200 --> 03:29:47,320 DISAPPOINTING WHEN IT DOESN'T 4033 03:29:47,320 --> 03:29:51,440 WORK AS WELL AND I'VE HAD A FEW 4034 03:29:51,440 --> 03:29:53,000 PATIENTS WHO WE'VE SENT OVER TO 4035 03:29:53,000 --> 03:29:55,440 DR. GREEN'S LAB AND IT'S REALLY 4036 03:29:55,440 --> 03:29:57,160 SAD, IT'S SORT OF LIKE COMPOUNDS 4037 03:29:57,160 --> 03:30:04,480 THE FACT THAT THEY'RE NOT 4038 03:30:04,480 --> 03:30:04,840 ELIGIBLE. 4039 03:30:04,840 --> 03:30:06,320 I COMPLETELY AGREE, I DON'T WANT 4040 03:30:06,320 --> 03:30:09,760 TO CUT YOU OFF, BUT THAT'S THE 4041 03:30:09,760 --> 03:30:11,640 DOWN SIDE OF WORKING FOR 4042 03:30:11,640 --> 03:30:12,240 PERSONAL RESOLUTION, THE GOAL 4043 03:30:12,240 --> 03:30:14,160 STOCK EXCHANGE UNDERSTAND IS IT 4044 03:30:14,160 --> 03:30:16,240 IF THERE'S BENEFIT, AND THERE'S 4045 03:30:16,240 --> 03:30:17,360 EXPECTATION MANAGEMENT AROUND 4046 03:30:17,360 --> 03:30:18,600 THAT'S VERY DIFFICULT AND I 4047 03:30:18,600 --> 03:30:20,800 TOTALLY AGREE THAT HAVING THE 4048 03:30:20,800 --> 03:30:21,840 OPPORTUNITY TO HARMONIZE 4049 03:30:21,840 --> 03:30:22,920 PRACTICES ACROSS GROUPS FOR 4050 03:30:22,920 --> 03:30:24,000 THIS, COULD CERTAINLY HELP WITH 4051 03:30:24,000 --> 03:30:25,440 THAT AND WE CAN SHARE THINGS 4052 03:30:25,440 --> 03:30:27,960 THAT WORK WELL AND DON'T WORK 4053 03:30:27,960 --> 03:30:28,160 WELL. 4054 03:30:28,160 --> 03:30:30,520 >> I WAS GOING TO SECOND WITH 4055 03:30:30,520 --> 03:30:34,880 WHAT CATHY SAID THAT YOU HAVE AN 4056 03:30:34,880 --> 03:30:37,320 EXPECTATION THAT WE AS PROVIDERS 4057 03:30:37,320 --> 03:30:38,880 COLLECTION THAT FOR THE TRIAL. 4058 03:30:38,880 --> 03:30:40,480 AND I WANT TO COMMENT ABOUT 4059 03:30:40,480 --> 03:30:41,440 SENDING CELLS TO YOUR LAB AND 4060 03:30:41,440 --> 03:30:46,200 THAT IS I THINK A PATIENT THAT 4061 03:30:46,200 --> 03:30:47,560 BECAUSE OF THEIR RESPONSE THE 4062 03:30:47,560 --> 03:30:48,920 WHOLE GROUP OF PATIENTS GOT 4063 03:30:48,920 --> 03:30:50,080 ACCESS TO THE DRUG AND ANOTHER 4064 03:30:50,080 --> 03:30:51,680 GROUP OF PATIENT WHO IS CAME TO 4065 03:30:51,680 --> 03:30:53,440 OUR CLINIC WHOSE SIBLING HAD 4066 03:30:53,440 --> 03:30:55,840 STUDIES IN YOUR LAB, THEREFORE, 4067 03:30:55,840 --> 03:31:05,160 I WAS ABLE TO ORDER TRICAFTA, 4068 03:31:05,160 --> 03:31:07,160 PRETTY EASILY IT WAS 4069 03:31:07,160 --> 03:31:07,560 REMARKABLYICISMEM. 4070 03:31:07,560 --> 03:31:08,920 HOW DO WE MAKE MORE OF THAT 4071 03:31:08,920 --> 03:31:11,120 UNIVERSALLY KNOWN AND YOU KNOW 4072 03:31:11,120 --> 03:31:13,480 HOW DO WE--I JUST COMMENT ON 4073 03:31:13,480 --> 03:31:14,720 THAT, BECAUSE I THOUGHT THOSE 4074 03:31:14,720 --> 03:31:16,360 WERE GREAT EXAMPLES OF THERAPY 4075 03:31:16,360 --> 03:31:17,920 ANDA TYPING HOW 1 PERSON WAS A 4076 03:31:17,920 --> 03:31:19,920 GREAT ADVANTAGE TO MULTIPLE 4077 03:31:19,920 --> 03:31:20,320 PEOPLE. 4078 03:31:20,320 --> 03:31:21,680 >> YEAH, FOR SURE, CHRIS. 4079 03:31:21,680 --> 03:31:23,800 AND I WILL SAY UNFORTUNATELY 4080 03:31:23,800 --> 03:31:25,760 THAT'S THE MINORITY OF 4081 03:31:25,760 --> 03:31:27,120 OPPORTUNITIES IN THIS SPACE, AND 4082 03:31:27,120 --> 03:31:28,840 AT THE END OF THE DAY, A LOT OF 4083 03:31:28,840 --> 03:31:30,800 IT COMES DOWN TO WHAT THE THIRD 4084 03:31:30,800 --> 03:31:32,120 PARTY PAYORS ARE WILLING TO 4085 03:31:32,120 --> 03:31:35,320 ACCEPT AS RATIONAL TO TRY THE 4086 03:31:35,320 --> 03:31:35,680 DRUG. 4087 03:31:35,680 --> 03:31:37,640 WE HAVE IT IN GREAT SUCCESS IN 4088 03:31:37,640 --> 03:31:40,040 SOME GROUPS WITH EXPANDING, 4089 03:31:40,040 --> 03:31:41,400 ESPECIALLY IN SIBLINGS AND 4090 03:31:41,400 --> 03:31:41,800 THINGS LIKE THAT. 4091 03:31:41,800 --> 03:31:46,440 SOME OF THAT COMES BACK AROUND 4092 03:31:46,440 --> 03:31:47,840 AND THERE ARE SOME IMPORTANT 4093 03:31:47,840 --> 03:31:49,040 QUESTIONS WHICH IS HOW DO YOU 4094 03:31:49,040 --> 03:31:51,320 SHARE THESE DATA AND DO IT IN A 4095 03:31:51,320 --> 03:31:51,960 RESPONSIBLE FASHION. 4096 03:31:51,960 --> 03:31:53,560 YOU KNOW IT'S DIFFERENT FROM 4097 03:31:53,560 --> 03:31:54,400 FRTs WHERE YOU'RE SHARING 4098 03:31:54,400 --> 03:31:55,600 INFORMATION ABOUT A SIMPLE 4099 03:31:55,600 --> 03:31:57,680 VARIANT IF YOU'RE SHARING A 4100 03:31:57,680 --> 03:31:58,760 PATIENT GENO TYPE ESPECIALLY 4101 03:31:58,760 --> 03:31:59,960 ULTRA RARE AT SOME POINT, YOU 4102 03:31:59,960 --> 03:32:01,480 HAVE TO ASK, IS THIS ACCEPTABLE 4103 03:32:01,480 --> 03:32:03,320 TO SHARE AND CERTAINLY YOU CAN 4104 03:32:03,320 --> 03:32:04,640 GET PATIENT CONSENT AND THINGS 4105 03:32:04,640 --> 03:32:07,640 LIKE THAT TO DO THAT BUT WIDE 4106 03:32:07,640 --> 03:32:10,800 SPREAD SORT OF COALITION SHARING 4107 03:32:10,800 --> 03:32:12,920 DOES BECOME DIFFICULT. 4108 03:32:12,920 --> 03:32:13,880 IF WE HAVE INFRASTRUCTURE IN 4109 03:32:13,880 --> 03:32:15,400 PLACE WHERE WE CAN TALK THROUGH 4110 03:32:15,400 --> 03:32:16,520 AND WORK THROUGH DIFFERENCES 4111 03:32:16,520 --> 03:32:19,120 FROM LAB TO LAB AND COAALATE 4112 03:32:19,120 --> 03:32:20,440 DATA AND PULL OUT INDIVIDUAL 4113 03:32:20,440 --> 03:32:21,920 VARIANTS THAT ARE RESPONSIVE 4114 03:32:21,920 --> 03:32:23,520 THEN WE HAVE THE ABILITY TO 4115 03:32:23,520 --> 03:32:25,520 BUILD THAT AND SHARE IT IN A 4116 03:32:25,520 --> 03:32:27,600 MORE RESPONSIBLEY WAY. 4117 03:32:27,600 --> 03:32:28,760 BUT THE--IT'S SOMETHING THAT I 4118 03:32:28,760 --> 03:32:30,320 THINK HAS GREAT PROMISE THAT 4119 03:32:30,320 --> 03:32:32,080 HASN'T REALLY BEEN TAPPED INTO 4120 03:32:32,080 --> 03:32:32,320 AS WELL. 4121 03:32:32,320 --> 03:32:33,040 I THINK 1 OF THE BING THINGS 4122 03:32:33,040 --> 03:32:34,560 THAT ALL OF US AND I'M 4123 03:32:34,560 --> 03:32:35,520 PARTICULARLY GUILTY OF THIS NEED 4124 03:32:35,520 --> 03:32:37,160 TO DO MORE AND MAKE SURE THAT 4125 03:32:37,160 --> 03:32:40,680 WHEN WE FIND THESE VARIANTS THAT 4126 03:32:40,680 --> 03:32:42,120 ARE CONSISTENTLY RESPONSIVE, 4127 03:32:42,120 --> 03:32:43,600 MAKING SURE THEY'RE OUT THERE IN 4128 03:32:43,600 --> 03:32:44,640 THE LITERATURE AND PEOPLE PICK 4129 03:32:44,640 --> 03:32:46,440 UP ON IT AND KNOW THIS IS 4130 03:32:46,440 --> 03:32:48,960 SOMETHING TO CHASE AND GO AFTER 4131 03:32:48,960 --> 03:32:50,240 DR. MRK GARY DO YOU HAVE 4132 03:32:50,240 --> 03:32:53,680 THOUGHTS ON THAT WITH YOUR WORK 4133 03:32:53,680 --> 03:32:58,080 IN THIS SPACE? 4134 03:32:58,080 --> 03:32:59,160 >> I MEAN, THERE'S JUST SO MUCH 4135 03:32:59,160 --> 03:33:00,760 THAT GOES INTO ALL OF THIS, 4136 03:33:00,760 --> 03:33:01,120 RIGHT? 4137 03:33:01,120 --> 03:33:03,880 THERE'S JUST SO MUCH MORE WE CAN 4138 03:33:03,880 --> 03:33:04,360 DO WITH THIS. 4139 03:33:04,360 --> 03:33:06,600 ONE OF THE INTERESTING THINGS TO 4140 03:33:06,600 --> 03:33:08,400 ME IS THAT YOU'RE THINKING ABOUT 4141 03:33:08,400 --> 03:33:12,320 THE NATURAL HISTORY OF CF, AND 4142 03:33:12,320 --> 03:33:15,040 HOW WE DON'T--WE STILL DON'T 4143 03:33:15,040 --> 03:33:16,040 REALLY UNDERSTAND FULLY THE 4144 03:33:16,040 --> 03:33:18,240 NATURAL HISTORY IN CERTAIN 4145 03:33:18,240 --> 03:33:19,080 GROUPS BEFORE MODULATORS, AND 4146 03:33:19,080 --> 03:33:22,440 HOW IMPORTANT IT'S GOING TO BE 4147 03:33:22,440 --> 03:33:24,680 WHEN WE UNDERSTAND THE HISTORY 4148 03:33:24,680 --> 03:33:25,840 OF AFTER MODULATORS AS WELL, AND 4149 03:33:25,840 --> 03:33:28,120 HOW IT WILL BE GETTING DIFFERENT 4150 03:33:28,120 --> 03:33:29,920 GROUPS AS WELL. 4151 03:33:29,920 --> 03:33:31,680 SO YOU KNOW THE CHAT, LOTS OF 4152 03:33:31,680 --> 03:33:34,320 QUESTIONS ON THE SITE OVER HERE 4153 03:33:34,320 --> 03:33:37,400 BUT JUST THINK BEING, YOU KNOW 4154 03:33:37,400 --> 03:33:40,920 SOCIOECONOMIC STATUS, HOW THAT 4155 03:33:40,920 --> 03:33:42,560 WILL BE AFFECTING DISEASE 4156 03:33:42,560 --> 03:33:45,400 TRAJECTORY GOING FORWARD, RACE 4157 03:33:45,400 --> 03:33:47,440 AND ETHNICITY, HOW DECEASED AND 4158 03:33:47,440 --> 03:33:48,720 DIFFERENT AND THINKING ABOUT 4159 03:33:48,720 --> 03:33:50,360 WHEN YOU'RE DESIGNING, SO FROM 4160 03:33:50,360 --> 03:33:51,800 THE NIH POINT, WHEN YOU'RE 4161 03:33:51,800 --> 03:33:52,560 DESIGNING CLINICAL TRIALS AND 4162 03:33:52,560 --> 03:33:54,080 THINKING ABOUT PATIENTS ARE 4163 03:33:54,080 --> 03:33:56,880 COMING IN DIFFERENT DEC 4164 03:33:56,880 --> 03:33:58,280 TRAJECTORIES AND IN MEASURING A 4165 03:33:58,280 --> 03:33:59,400 RESPONSE AND REALLY THE 4166 03:33:59,400 --> 03:34:03,400 IMPORTANCE OF LOOKING AT THESE 4167 03:34:03,400 --> 03:34:04,200 SUBGROUPS, COLLECTING THE 4168 03:34:04,200 --> 03:34:07,320 INFORMATION IN THE SUBGROUPS AS 4169 03:34:07,320 --> 03:34:07,760 WELL. 4170 03:34:07,760 --> 03:34:09,440 SO AND THEN ENROLLING ENOUGH 4171 03:34:09,440 --> 03:34:12,960 PATIENTS TO LOOK AT DIFFERENCES, 4172 03:34:12,960 --> 03:34:13,200 RIGHT? 4173 03:34:13,200 --> 03:34:14,440 SO I JUST THINK THAT THERE'S A 4174 03:34:14,440 --> 03:34:16,680 LOT OF WORK TO BE DONE AND IT 4175 03:34:16,680 --> 03:34:20,840 REALLY STARTS WITH AWARENESS AS 4176 03:34:20,840 --> 03:34:21,040 WELL. 4177 03:34:21,040 --> 03:34:22,680 >> I THINK IT HAS TO BE CRITICAL 4178 03:34:22,680 --> 03:34:23,800 THESE STUDIES ARE DESIGNED 4179 03:34:23,800 --> 03:34:25,040 REALLY CAREFUL AND WE HAD TO 4180 03:34:25,040 --> 03:34:26,840 THINK ABOUT HOW WE'RE FRAMING 4181 03:34:26,840 --> 03:34:28,400 THE QUESTION, BECAUSE JUST 4182 03:34:28,400 --> 03:34:29,680 ASSUMING THERE'S A BIOLOGICAL 4183 03:34:29,680 --> 03:34:33,520 DIFFERENCE BASED ON RACE IS--MY 4184 03:34:33,520 --> 03:34:35,840 POOR ASSUMPTION IS WE'VE SEEN IT 4185 03:34:35,840 --> 03:34:38,520 WITH PFTs AND OTHER DATA MAYBE 4186 03:34:38,520 --> 03:34:39,560 THERE ARE EPIGENETIC PHENOMENA 4187 03:34:39,560 --> 03:34:40,920 THAT ARE OCCURRING BECAUSE OF 4188 03:34:40,920 --> 03:34:44,040 SYSTEMIC RACISM THAT ARE 4189 03:34:44,040 --> 03:34:45,560 IMPACTING OUTCOMES WE CAN'T JUST 4190 03:34:45,560 --> 03:34:47,040 SAY BLACK PEOPLE DON'T RESPOND 4191 03:34:47,040 --> 03:34:48,840 TO MODULATORS BECAUSE OF XYZ, 4192 03:34:48,840 --> 03:34:50,000 BECAUSE RACE IS A SOCIAL 4193 03:34:50,000 --> 03:34:52,720 CONSTRUCT AND IF YOU LOOK AT 1 4194 03:34:52,720 --> 03:34:54,680 GENE IN AFFRIC ATHERE'S NOT 1 4195 03:34:54,680 --> 03:34:56,680 SPECIFIC MUTATION THAT OCCURS IN 4196 03:34:56,680 --> 03:34:57,840 EVERY AFRICAN THAT'S NOT FOUND 4197 03:34:57,840 --> 03:34:58,840 IN EUROPEANS FOR EXAMPLE, SO WE 4198 03:34:58,840 --> 03:35:00,160 HAVE TO BE CAREFUL HOW WE FRAME 4199 03:35:00,160 --> 03:35:07,000 THE QUESTION AND HOW WE ASK AND 4200 03:35:07,000 --> 03:35:08,840 ANSWER THE QUESTIONS. 4201 03:35:08,840 --> 03:35:11,000 YEAH, I THINK THEY WANT A SIMPLE 4202 03:35:11,000 --> 03:35:12,560 EXPLANATION AND THAT'S NOT THE 4203 03:35:12,560 --> 03:35:15,160 CASE. 4204 03:35:15,160 --> 03:35:16,080 IT'S VERY COMPLICATED AND THAT'S 4205 03:35:16,080 --> 03:35:17,640 WHY WE NEED TO BE COLLECTING 4206 03:35:17,640 --> 03:35:28,160 LOTS OF DIFFERENT INFORMATION 4207 03:35:29,360 --> 03:35:29,960 ABOUT THESE GROUPS. 4208 03:35:29,960 --> 03:35:31,360 THERE ARE SO MANY TREATMENTS 4209 03:35:31,360 --> 03:35:32,760 ACROSS THE LIFETIME MAY BE 4210 03:35:32,760 --> 03:35:34,520 DIFFERENT, THAT THERE'S SO MANY 4211 03:35:34,520 --> 03:35:37,600 DIFFERENT BIOLOGICAL SOCIAL 4212 03:35:37,600 --> 03:35:39,080 FACTORS FROM THE AIR THEY 4213 03:35:39,080 --> 03:35:49,560 BREATHE TO THE TREATMENTS 4214 03:35:50,640 --> 03:35:52,320 THEY'RE GIVEN THAT'S WHY THESE 4215 03:35:52,320 --> 03:35:53,360 ARE SO IMPORTANT IN THESE 4216 03:35:53,360 --> 03:35:54,720 STUDIES TO THINK ABOUT THEM AND 4217 03:35:54,720 --> 03:35:55,360 ADDRESS THEM. 4218 03:35:55,360 --> 03:35:56,360 AND INCLUDING THEM ON THE 4219 03:35:56,360 --> 03:35:57,640 PLANNING AND THINKING ABOUT LIKE 4220 03:35:57,640 --> 03:36:00,400 WHAT ARE THERE RESEARCH 4221 03:36:00,400 --> 03:36:01,480 PRIORITIES LIKE WHAT ARE--YOU 4222 03:36:01,480 --> 03:36:04,480 KNOW WE JUST NEED TO BE--IT 4223 03:36:04,480 --> 03:36:07,040 NEEDS TO BE A REAL SHIFT IN OUR 4224 03:36:07,040 --> 03:36:08,800 PARADIGM WHEN WE'RE THINK BEING 4225 03:36:08,800 --> 03:36:09,040 THIS. 4226 03:36:09,040 --> 03:36:13,240 SO, YOU KNOW THERE'S BEEN 4227 03:36:13,240 --> 03:36:14,760 SOME--IN SOME OF THE LOW HANGING 4228 03:36:14,760 --> 03:36:16,720 FRUIT, SO HERE WE ARE AT NHLBI, 4229 03:36:16,720 --> 03:36:18,240 SO WHEN WE'RE THINK BEING WHAT 4230 03:36:18,240 --> 03:36:19,440 TRIALS ARE BEING FUNDED AND 4231 03:36:19,440 --> 03:36:20,840 WE'RE LOOKING AT THE GRANTS AND 4232 03:36:20,840 --> 03:36:23,080 LOOKING AT DAT BEING REPORTED 4233 03:36:23,080 --> 03:36:24,360 BACK, WE NEED TO THINK ABOUT 4234 03:36:24,360 --> 03:36:26,200 WHERE THESE TRIALS BEING 4235 03:36:26,200 --> 03:36:28,720 CONDUCTED, ARE THEY IN A PLACE 4236 03:36:28,720 --> 03:36:30,000 WHERE THEY HAVE A DIFFERENCE 4237 03:36:30,000 --> 03:36:32,320 POPULATION TO RECRUIT FROM WHAT 4238 03:36:32,320 --> 03:36:34,640 ARE THEY DOING TO RECRUIT A 4239 03:36:34,640 --> 03:36:35,440 DIVERSE POPULATION? 4240 03:36:35,440 --> 03:36:38,040 DO WE HAVE MATERIALS TRANSLATED 4241 03:36:38,040 --> 03:36:39,280 IN SPANISH FOR EXAMPLE? 4242 03:36:39,280 --> 03:36:43,040 DO WE HAVE DIVERSE RESEARCH 4243 03:36:43,040 --> 03:36:43,360 COORDINATORS. 4244 03:36:43,360 --> 03:36:44,920 IS IT EVEN ON THE RADAR? 4245 03:36:44,920 --> 03:36:46,200 IF YOU'RE NOT THINK BEING IT 4246 03:36:46,200 --> 03:36:47,520 WHICH I THINK HAS BEEN SORT OF 4247 03:36:47,520 --> 03:36:49,160 THE CASE, LIKE ARE WE LOOKING AS 4248 03:36:49,160 --> 03:36:51,040 WE'RE GOING ON AND BEING LIKE, 4249 03:36:51,040 --> 03:36:54,120 GOSH, WE ARE ONLY ENROLLING 4250 03:36:54,120 --> 03:36:54,680 NONHISPANIC WHITE PATIENTS. 4251 03:36:54,680 --> 03:36:56,760 IT NEEDS TO BE A PAUSE IN SAYING 4252 03:36:56,760 --> 03:36:59,600 WHY, WHAT CAN WE DO TO CHANGE 4253 03:36:59,600 --> 03:36:59,800 THAT? 4254 03:36:59,800 --> 03:37:01,720 WHAT DO WE NEED TO ADJUST GOING 4255 03:37:01,720 --> 03:37:02,000 ON? 4256 03:37:02,000 --> 03:37:02,720 WHEN WE'RE THINKING ABOUT THOSE 4257 03:37:02,720 --> 03:37:04,600 OF US WHO ARE EDITORS, THOSE OF 4258 03:37:04,600 --> 03:37:06,280 US WHO ARE VIEWERS, WHEN YOU GET 4259 03:37:06,280 --> 03:37:07,720 THAT PAPER, ARE YOU LOOKING TO 4260 03:37:07,720 --> 03:37:09,640 SEE, IS RACE AND ETHNICITY 4261 03:37:09,640 --> 03:37:12,360 THERE, I MEAN I WAS SHOCKED WHEN 4262 03:37:12,360 --> 03:37:14,040 IT WAS LIKE NEW ENGLAND JOURNAL 4263 03:37:14,040 --> 03:37:15,120 OF MEDICINE, NO RACE AND 4264 03:37:15,120 --> 03:37:18,640 ETHNICITY AND I WILL SAY THAT I 4265 03:37:18,640 --> 03:37:21,640 WROTE IMMEDIATE RESPONSE BACK 4266 03:37:21,640 --> 03:37:22,520 AND THE--THE--I WAS TOLD IT 4267 03:37:22,520 --> 03:37:24,120 COULD NOT BE PUT IN BECAUSE 4268 03:37:24,120 --> 03:37:25,280 THERE WASN'T SPACE FOR THAT 4269 03:37:25,280 --> 03:37:27,600 INFORMATION AND THAT MEANS IT'S 4270 03:37:27,600 --> 03:37:28,760 NOT A PRIORITY, RIGHT? 4271 03:37:28,760 --> 03:37:30,440 LIKE, THAT MEANS THAT THAT'S 4272 03:37:30,440 --> 03:37:32,680 CONSIDERED TO BE NONRELEVANT 4273 03:37:32,680 --> 03:37:34,320 INFORMATION WHICH IS SO FAR FROM 4274 03:37:34,320 --> 03:37:35,840 THE TRUTH. 4275 03:37:35,840 --> 03:37:38,600 SO, I THINK ON ALL LEVELS, WE 4276 03:37:38,600 --> 03:37:42,280 NEED TO BE KEEPING THIS 4277 03:37:42,280 --> 03:37:44,520 AWARENESS, SO, MAYBE IT JUST 4278 03:37:44,520 --> 03:37:46,280 NEEDS TO BE--NIH NEEDS TO GO 4279 03:37:46,280 --> 03:37:48,720 FROM WELL, YOU NEED TO REPORT 4280 03:37:48,720 --> 03:37:50,000 RACE AND ETHNICITY TO WHAT IS 4281 03:37:50,000 --> 03:37:54,640 THE BASE LINE OF RACE AND 4282 03:37:54,640 --> 03:37:57,080 ETHNICITY OF YOUR OVERALL 4283 03:37:57,080 --> 03:37:57,360 POPULATION? 4284 03:37:57,360 --> 03:37:58,920 WHERE ARE YOU GOING TO RECRUIT 4285 03:37:58,920 --> 03:37:59,160 FROM? 4286 03:37:59,160 --> 03:38:00,240 WHAT ARE YOUR GOALS? 4287 03:38:00,240 --> 03:38:01,560 WHAT PERCENTAGE DO YOU NEED TO 4288 03:38:01,560 --> 03:38:04,160 RECRUIT TO LOOK AT DIFFERENCE IN 4289 03:38:04,160 --> 03:38:04,840 BIOMARKERS, RIGHT? 4290 03:38:04,840 --> 03:38:07,520 LIKE, BECAUSE I THINK IF 4291 03:38:07,520 --> 03:38:08,880 YOU--WHATEVER POPULATION, THAT 4292 03:38:08,880 --> 03:38:10,240 YOU'RE CREATING BIOMARKERS FOR, 4293 03:38:10,240 --> 03:38:11,800 THAT YOU'RE CREATING DRUGS FOR, 4294 03:38:11,800 --> 03:38:14,240 THAT'S THE ONLY POPULATION THAT 4295 03:38:14,240 --> 03:38:16,960 YOUR RESULTS WILL BE RELEVANT 4296 03:38:16,960 --> 03:38:17,240 FOR. 4297 03:38:17,240 --> 03:38:19,240 SO THERE'S SO MANY WAYS WE CAN 4298 03:38:19,240 --> 03:38:20,840 ALL MAKE A CHANGE ON THIS. 4299 03:38:20,840 --> 03:38:23,480 BUT IT'S GOING TO BE AT TIMES 4300 03:38:23,480 --> 03:38:24,800 HARD WORK. 4301 03:38:24,800 --> 03:38:27,120 SO--BUT, YOU KNOW, I THINK, YOU 4302 03:38:27,120 --> 03:38:32,080 KNOW FUNDING IS A REAL GOOD 4303 03:38:32,080 --> 03:38:33,360 INCENTIVE SO, I THINK WE JUST 4304 03:38:33,360 --> 03:38:34,840 NEED TO AT ALL LEVELS BE WORKING 4305 03:38:34,840 --> 03:38:36,680 ON THIS AND THINKING BIG. 4306 03:38:36,680 --> 03:38:39,880 AND YOU KNOW THE CF FOUNDATION, 4307 03:38:39,880 --> 03:38:43,880 IS BIG CHANGES GOING ON AND I 4308 03:38:43,880 --> 03:38:45,680 THINK THE NEXT NICAC, WE WILL 4309 03:38:45,680 --> 03:38:48,080 SEE MORE OF THAT PRESENTED BUT 4310 03:38:48,080 --> 03:38:58,640 THERE'S JUST A LOT OF WORK RIGHT 4311 03:39:08,600 --> 03:39:08,720 NOW. 4312 03:39:08,720 --> 03:39:11,320 >> --1 THAT CAME UP WITH MENTAL 4313 03:39:11,320 --> 03:39:13,520 HEALTH DECLINE OR HEALTH ISSUES 4314 03:39:13,520 --> 03:39:14,800 ON MODULATOR THERAPY THAT'S OUT 4315 03:39:14,800 --> 03:39:15,080 THERE. 4316 03:39:15,080 --> 03:39:17,520 CERTAINLY IN THE ADULT 4317 03:39:17,520 --> 03:39:19,920 POPULATIONS, AND THEN ALSO TO 4318 03:39:19,920 --> 03:39:22,200 TIE INTO THAT WHAT ARE THE 4319 03:39:22,200 --> 03:39:23,560 HEALTH CONDITIONS THAT REALLY 4320 03:39:23,560 --> 03:39:26,520 NEED GREATER ATTENTION AND THEY 4321 03:39:26,520 --> 03:39:28,280 REALLY NEED TO FOCUS CHRIS, I 4322 03:39:28,280 --> 03:39:30,160 KNOW YOU MENTIONED RENAL 4323 03:39:30,160 --> 03:39:31,680 DISEASE, AND DIABETES, BUT ANY 4324 03:39:31,680 --> 03:39:32,760 OF THE THINGS ARE CRITICAL 4325 03:39:32,760 --> 03:39:34,520 THINGS WE SHOULD BE FOCUSING ON 4326 03:39:34,520 --> 03:39:35,920 ACROSS THE LIFE SPAN TO PREPARE 4327 03:39:35,920 --> 03:39:37,880 FOR AN AGING POPULATION. 4328 03:39:37,880 --> 03:39:40,960 >> I WOULD HAVE TO--1 OF MY 4329 03:39:40,960 --> 03:39:42,080 SLIDES ACTUALLY SKIPPED OVER 4330 03:39:42,080 --> 03:39:43,520 WHICH IS MOST IMPORTANT, WHERE 4331 03:39:43,520 --> 03:39:45,920 IT WAS, WHERE IT WAS? 4332 03:39:45,920 --> 03:39:50,480 IT WAS ABOUT OBESITY AND IT IS 4333 03:39:50,480 --> 03:39:52,920 JUST--I HAVE A PATIENT WHO 4334 03:39:52,920 --> 03:39:55,880 GAINED 60-POUNDS IN 3 MONTHS ON 4335 03:39:55,880 --> 03:39:57,400 TRICAFTA, IT IS THERE, THE 4336 03:39:57,400 --> 03:39:58,680 PROPORTION OF CENTERS NOW HAVING 4337 03:39:58,680 --> 03:40:00,360 OBESITY AS AN ISSUE IN THEIR 4338 03:40:00,360 --> 03:40:01,200 HEALTHCARE SYSTEM, THE INFRANCIS 4339 03:40:01,200 --> 03:40:02,400 COLLINS SPHRUCTURE TO ADDRESS OR 4340 03:40:02,400 --> 03:40:05,880 THINK ABOUT OBESE IS REALLY, 4341 03:40:05,880 --> 03:40:07,120 REALLY, HAS NOT BEEN FROM THE 4342 03:40:07,120 --> 03:40:09,040 CENTER, I KNOW FROM TALKS 4343 03:40:09,040 --> 03:40:10,200 YESTERDAY, THEY'RE OBVIOUSLY 4344 03:40:10,200 --> 03:40:11,160 REDOING THE NUTRITION GUIDELINES 4345 03:40:11,160 --> 03:40:12,560 BUT IT'S GOING TO BE A REAL 4346 03:40:12,560 --> 03:40:15,680 ISSUE IF YOU THINK OF DIABETES 4347 03:40:15,680 --> 03:40:17,960 AND OBESITY TOGETHER AND A 4348 03:40:17,960 --> 03:40:18,520 CHRONIC LUNG INFECTION. 4349 03:40:18,520 --> 03:40:23,000 IF YOU THINK ABOUT AN 4350 03:40:23,000 --> 03:40:24,360 INFLAMMATORY MELUE, THAT WILL BE 4351 03:40:24,360 --> 03:40:26,040 CHALLENGING AND THAT COULD BE A 4352 03:40:26,040 --> 03:40:27,840 REAL ISSUE LATER IN LIFE AS 4353 03:40:27,840 --> 03:40:31,040 PATIENTS AGE WITH CF, SO I THINK 4354 03:40:31,040 --> 03:40:31,840 IT'S--I WOULD COMMENT ON THAT 4355 03:40:31,840 --> 03:40:35,720 BECAUSE I THINK IT WAS 4356 03:40:35,720 --> 03:40:36,840 UNDERREPRESENTED THERE. 4357 03:40:36,840 --> 03:40:38,120 AND MANAGING THESE CHRONIC DRUGS 4358 03:40:38,120 --> 03:40:40,360 FOR A LIFETIME AND UNDERSTANDING 4359 03:40:40,360 --> 03:40:41,200 THEIR LONG-TERM COMPLICATIONS IS 4360 03:40:41,200 --> 03:40:44,040 GOING TO BE REALLY IMPORTANT. 4361 03:40:44,040 --> 03:40:45,360 >> CHRIS, ARE THEY GOING TO BE 4362 03:40:45,360 --> 03:40:47,360 ON IT FOR A LIFETIME OR IS THERE 4363 03:40:47,360 --> 03:40:48,680 SOMETHING DIFFERENT AND BETTER? 4364 03:40:48,680 --> 03:40:51,800 THAT'S WHAT I TALK TO ALL MY 4365 03:40:51,800 --> 03:40:52,240 ADULTS ABOUT. 4366 03:40:52,240 --> 03:40:56,640 I DON'T THINK THEY WILL BE ON 4367 03:40:56,640 --> 03:40:57,680 TRICAF TA. 4368 03:40:57,680 --> 03:40:59,960 >> I DON'T THINK WE WILL BE ON 4369 03:40:59,960 --> 03:41:01,960 IT FOR LIFETIME BUT HOPE LOOFULY 4370 03:41:01,960 --> 03:41:03,120 GET A LIFETIME CURE, THAT WOULD 4371 03:41:03,120 --> 03:41:10,480 BE DIFFERENT WE WILL SEE BUT, I 4372 03:41:10,480 --> 03:41:11,440 THINK OUR GENE THERAPY IS THERE 4373 03:41:11,440 --> 03:41:12,840 BUT THEY WILL BE ON THESE DRUGS 4374 03:41:12,840 --> 03:41:15,520 FOR A LONG TIME OR SIMILAR DRUGS 4375 03:41:15,520 --> 03:41:17,840 I ASSUME JUST GIVEN THE 4376 03:41:17,840 --> 03:41:19,200 CHALLENGES OF MOVING GENE 4377 03:41:19,200 --> 03:41:19,560 THERAPY FORWARD. 4378 03:41:19,560 --> 03:41:21,760 >> AND I WANTED TO ADD ABOUT 4379 03:41:21,760 --> 03:41:23,200 MALIGNANCY IS ANOTHER THING TO 4380 03:41:23,200 --> 03:41:25,000 KEEP AN EYE ON OVER TIME AND 4381 03:41:25,000 --> 03:41:26,480 DOES HIGHLY EFFECTIVE MODULATOR 4382 03:41:26,480 --> 03:41:29,800 THERAPY REDUCE THE RATE OF 4383 03:41:29,800 --> 03:41:31,920 MALIGNANCY OF CFTR IS A TUMOR 4384 03:41:31,920 --> 03:41:33,240 SUPPRESSOR AND YOU'RE FIXING THE 4385 03:41:33,240 --> 03:41:35,200 FUNCTION THERE, I THINK THAT 4386 03:41:35,200 --> 03:41:37,240 POST TRANSPLANT, THIS GETS 4387 03:41:37,240 --> 03:41:38,680 POO-POOED A LOT WHEN I TALK 4388 03:41:38,680 --> 03:41:40,240 ABOUT IT, SO I DIDN'T INCLUDE IT 4389 03:41:40,240 --> 03:41:42,520 TODAY BUT COULD WE START 4390 03:41:42,520 --> 03:41:44,360 MODULATORS AND POST TRANSPLANT 4391 03:41:44,360 --> 03:41:46,720 POPULATION AND REDUCE THEIR RISK 4392 03:41:46,720 --> 03:41:49,040 OF PTLD OR TRANSPLANT 4393 03:41:49,040 --> 03:41:49,600 LYMPHOPROLIFERATIVE DISORDER 4394 03:41:49,600 --> 03:41:52,200 BECAUSE THEY HAVE SUCH A HIGH 4395 03:41:52,200 --> 03:41:54,840 RATE, EVEN ACCOUNTING FOR EBV 4396 03:41:54,840 --> 03:41:56,920 MISMATCHING, THEY'RE AT A HIGHER 4397 03:41:56,920 --> 03:41:59,040 RATE OF GEYE CANCERS SO WE FIX 4398 03:41:59,040 --> 03:42:01,120 IF WE FIX IT POST TRANSPLANT 4399 03:42:01,120 --> 03:42:02,600 COULD WE AFFECT THEIR RISK FOR 4400 03:42:02,600 --> 03:42:03,640 MALIGNANCY AND I DON'T THINK WE 4401 03:42:03,640 --> 03:42:05,200 WILL KNOW THAT UNTIL WE HAVE A 4402 03:42:05,200 --> 03:42:06,920 REGISTRY FULL OF PEOPLE ON 4403 03:42:06,920 --> 03:42:08,240 VERSUS NOT ON MODULATEDDORS, IT 4404 03:42:08,240 --> 03:42:12,280 WILL NOT BE A MULTICENTERRED 4405 03:42:12,280 --> 03:42:14,160 TRIAL, I CAN SEE AN IMPACT ON 4406 03:42:14,160 --> 03:42:14,440 THAT. 4407 03:42:14,440 --> 03:42:16,080 CATHY IT'S A GREAT QUESTION, IT 4408 03:42:16,080 --> 03:42:17,880 GOES BACK TO DISCUSSION 4409 03:42:17,880 --> 03:42:19,720 YESTERDAY, MATTERS WHEN IN LIFE 4410 03:42:19,720 --> 03:42:21,240 THEY WERE INITIATED THEIR 4411 03:42:21,240 --> 03:42:22,400 MODULATOR AND HOW IT WOULD 4412 03:42:22,400 --> 03:42:23,360 CHANGE THE CANCER RISK. 4413 03:42:23,360 --> 03:42:25,840 IT'S DIFFERENT IF YOU START 4414 03:42:25,840 --> 03:42:27,280 SOMEBODY WHOSE 40 VERSUS 4415 03:42:27,280 --> 03:42:29,360 SOMEBODY WHO'S 4 MONTHS OLD. 4416 03:42:29,360 --> 03:42:29,960 , ALL RIGHT. 4417 03:42:29,960 --> 03:42:33,320 WELL, I JUST GOT THE MESSAGE 4418 03:42:33,320 --> 03:42:35,600 THAT IT'S TIME TO WRAP BECAUSE 4419 03:42:35,600 --> 03:42:36,000 LUNCH IS UPCOMING. 4420 03:42:36,000 --> 03:42:38,120 BEFORE WE DO, I WANT TO 4421 03:42:38,120 --> 03:42:38,600 HIGHLIGHT THERE'S BEEN 4422 03:42:38,600 --> 03:42:40,320 INCREDIBLE CONVERSATION IN THE 4423 03:42:40,320 --> 03:42:41,280 CHAT THINKING ABOUT ENROLLMENT 4424 03:42:41,280 --> 03:42:42,280 OF PATIENTS IN SUBJECTS AND 4425 03:42:42,280 --> 03:42:43,840 STUDIES AND HOW DO WE MAKE SURE 4426 03:42:43,840 --> 03:42:45,240 THAT WE'RE INCLUSIVE IN THE 4427 03:42:45,240 --> 03:42:46,440 STUDY DESIGNS, SO, PLEASE MAKE 4428 03:42:46,440 --> 03:42:48,240 SURE YOU LOOK THROUGH THAT, 4429 03:42:48,240 --> 03:42:50,840 REALLY GOOD CONCEPTS OF 4430 03:42:50,840 --> 03:42:51,280 CONVERSATIONS THERE. 4431 03:42:51,280 --> 03:42:52,720 I WILL SAY A HUGE THANK TO YOU 4432 03:42:52,720 --> 03:42:53,520 EVERYBODY FOR THEIR ATTENTION 4433 03:42:53,520 --> 03:42:56,640 AND TO OUR SPEAKERS, DR. ANY 4434 03:42:56,640 --> 03:42:57,120 LAST MINUTE THOUGHTS. 4435 03:42:57,120 --> 03:43:02,360 >> I WAS GOING TO SAY, THERE'S 4436 03:43:02,360 --> 03:43:02,960 INCREDIBLE RESOURCES, AGREANCE, 4437 03:43:02,960 --> 03:43:04,120 DISCUSSIONS IN THE CHAT, THE 4438 03:43:04,120 --> 03:43:05,960 CHAT IS BEING SAVED AND WILL BE 4439 03:43:05,960 --> 03:43:08,040 AVAILABLE AND TELL BE GOOD. 4440 03:43:08,040 --> 03:43:09,480 BUT WE WANT TO THANK OW 4441 03:43:09,480 --> 03:43:10,800 SPEAKERS, THIS WAS AMAZE, 4442 03:43:10,800 --> 03:43:12,880 AMAZING WORK YOU ARE DOING, AND 4443 03:43:12,880 --> 03:43:15,560 JUST FOR EVERYBODY HERE, WE JUST 4444 03:43:15,560 --> 03:43:17,280 THANK YOU, IT'S REALLY EXCITING 4445 03:43:17,280 --> 03:43:19,240 ABOUT THE FUTURE OF CF, THIS IS 4446 03:43:19,240 --> 03:43:22,240 JUST INCREDIBLE THE WORK THAT'S 4447 03:43:22,240 --> 03:43:23,200 BEING DONE IT'S AMAZING TO THINK 4448 03:43:23,200 --> 03:43:26,040 ABOUT THE THINGS WE DISCUSS NOW, 4449 03:43:26,040 --> 03:43:26,240 RIGHT? 4450 03:43:26,240 --> 03:43:27,560 PREGNANCY, AGING, LIKE IT'S 4451 03:43:27,560 --> 03:43:28,520 JUST--IT'S JUST A WHOLE NEW 4452 03:43:28,520 --> 03:43:29,840 WORLD AND IT'S JUST EXCITING 4453 03:43:29,840 --> 03:43:31,360 PLACE TO BE, SO WE THANK 4454 03:43:31,360 --> 03:43:34,160 EVERYBODY SO MUCH AND WE THANK 4455 03:43:34,160 --> 03:43:36,080 THE NHLBI FOR MAKING THIS A 4456 03:43:36,080 --> 03:43:36,920 PRIORITY, THANK YOU, THANK YOU 4457 03:43:36,920 --> 03:43:38,520 AND I HOPE EVERYBODY HAS A GOOD 4458 03:43:38,520 --> 03:43:40,280 LUNCH AND WE SEE YOU IN JUST A 4459 03:43:40,280 --> 03:43:44,280 LITTLE BIT. 4460 03:43:44,280 --> 03:43:45,600 >>HELLO, I WOULD LIKE TO 4461 03:43:45,600 --> 03:43:46,640 WELCOME EVERYONE BACK TO THE 4462 03:43:46,640 --> 03:43:47,400 SESSION TODAY. 4463 03:43:47,400 --> 03:43:50,720 WE ARE SOPHISTICATED SESSION 5 4464 03:43:50,720 --> 03:43:51,720 TITLED ADVANCING CLINICAL CARE 4465 03:43:51,720 --> 03:43:53,640 AND OUTCOMES FOR PATIENTS WITH 4466 03:43:53,640 --> 03:43:56,160 CF IF THE MOST MODULATOR ERA. 4467 03:43:56,160 --> 03:43:58,520 WE WILL HAVE ANOTHER SERIES OF 4468 03:43:58,520 --> 03:44:00,240 TALKS FOLLOWED BY A COMMUNITY 4469 03:44:00,240 --> 03:44:01,760 MEMBER PERSPECTIVE AS THE LAST 4470 03:44:01,760 --> 03:44:02,800 TALK IN THIS SESSION. 4471 03:44:02,800 --> 03:44:08,840 I DO WANT TO MAKE A FEW NOTES OF 4472 03:44:08,840 --> 03:44:09,880 CHANGE HERE, OUR 2 MODERATORS 4473 03:44:09,880 --> 03:44:12,440 FOR THIS SESSION WILL ACTUALLY 4474 03:44:12,440 --> 03:44:17,480 BE DR. HAMLET AND 4475 03:44:17,480 --> 03:44:18,880 DR. ROSE NFELD AND OUR COMMUNITY 4476 03:44:18,880 --> 03:44:20,120 PERSPECTIVE WE HEARD FROM MISS 4477 03:44:20,120 --> 03:44:22,600 LAWRENCE TODAY SO WE WILL HAVE 4478 03:44:22,600 --> 03:44:24,360 MISS JENNIFER KYLE GIVING OUR 4479 03:44:24,360 --> 03:44:25,160 COMMUNITY MEMBER PERSPECTIVE 4480 03:44:25,160 --> 03:44:27,240 HERE SO SORRY FOR THAT THE 4481 03:44:27,240 --> 03:44:28,320 CONFUSION, THAT INFORMATION 4482 03:44:28,320 --> 03:44:29,400 SHOULD BE UPDATED IN THE PROGRAM 4483 03:44:29,400 --> 03:44:30,480 BOOK FOR YOU AND WE WILL POST 4484 03:44:30,480 --> 03:44:32,440 THAT IN THE CHAT. 4485 03:44:32,440 --> 03:44:33,800 AND WITH THAT I WILL TURN THIS 4486 03:44:33,800 --> 03:44:37,400 OVER TO THE MODERATORS OF 4487 03:44:37,400 --> 03:44:38,040 SESSION 5. 4488 03:44:38,040 --> 03:44:39,400 >> THANK YOU. 4489 03:44:39,400 --> 03:44:40,880 WELCOME BACK EVERYONE. 4490 03:44:40,880 --> 03:44:42,480 IT IS STILL MORNING ON THE WEST 4491 03:44:42,480 --> 03:44:44,920 COAST SO WE'RE JUST GETTING 4492 03:44:44,920 --> 03:44:45,280 GOING HERE. 4493 03:44:45,280 --> 03:44:47,040 OUR NEXT SESSION ADVANCING 4494 03:44:47,040 --> 03:44:48,880 CLINICAL CARE AND OUTCOMES FOR 4495 03:44:48,880 --> 03:44:51,240 PATIENTS IN THE POST MODULATOR 4496 03:44:51,240 --> 03:44:53,240 ERA WE WILL EXPLORE THE NEED FOR 4497 03:44:53,240 --> 03:44:55,920 NOVEL OUTCOME MEASURES TO INSURE 4498 03:44:55,920 --> 03:44:56,920 OPTIMAL MONITORING AND DISEASE 4499 03:44:56,920 --> 03:44:57,880 PROGRESSION AND SERVE AS 4500 03:44:57,880 --> 03:44:59,200 CLINICAL TRIALS AND NEW 4501 03:44:59,200 --> 03:44:59,560 THERAPEUTICS. 4502 03:44:59,560 --> 03:45:05,360 WE HAVE A GREAT LINE UP 4503 03:45:05,360 --> 03:45:14,280 DR. ZACHARY CLEVELAND WILL BE 4504 03:45:14,280 --> 03:45:15,640 PRESENTING, AND DR. HEATHER BEAN 4505 03:45:15,640 --> 03:45:18,440 WILL TALK ABOUT ASPECTS OF CF 4506 03:45:18,440 --> 03:45:19,400 HEALTH, DR. NATALIE WEST COULD 4507 03:45:19,400 --> 03:45:21,280 NOT BE HERE TODAY BUT SHE 4508 03:45:21,280 --> 03:45:25,160 RECORDED HER TALK AND WILL BE 4509 03:45:25,160 --> 03:45:28,960 REVIEWING THE CHANGING LANDSCAPE 4510 03:45:28,960 --> 03:45:31,160 OF PULMONARY VASCALATIONS IN THE 4511 03:45:31,160 --> 03:45:36,360 POST MODULATOR ERA, AND 4512 03:45:36,360 --> 03:45:37,400 DR. [INDISCERNIBLE] WILL PRESENT 4513 03:45:37,400 --> 03:45:39,280 ON DISEASE MONITORING AND AS YOU 4514 03:45:39,280 --> 03:45:40,800 HEARD, WE WILL CONCLUDE OUR 4515 03:45:40,800 --> 03:45:42,760 SESSION WITH MISS JENNIFER KYLE 4516 03:45:42,760 --> 03:45:45,480 WE ARE THRILLED TO HAVE HER 4517 03:45:45,480 --> 03:45:46,640 SHARE HER PERSONAL EXPERIENCE AS 4518 03:45:46,640 --> 03:45:49,520 1 OF OUR COMMUNITY CF RESEARCH 4519 03:45:49,520 --> 03:45:50,640 PARTNERS AND WITH THAT I WOULD 4520 03:45:50,640 --> 03:45:52,000 LIKE TO WELCOME DR. CLEVELAND 4521 03:45:52,000 --> 03:45:54,360 WHO IS THE ASSOCIATE DIRECTOR 4522 03:45:54,360 --> 03:45:55,480 FOR PULMONARY ENERGY RESEARCH 4523 03:45:55,480 --> 03:45:56,960 AND ASSOCIATE PROFESSOR AT 4524 03:45:56,960 --> 03:45:57,640 CINCINNATI CHILDREN'S HOSPITAL 4525 03:45:57,640 --> 03:46:05,880 AND UNIVERSITY OF SIN SEN 4526 03:46:05,880 --> 03:46:06,240 ILLEGALSEN ATY. 4527 03:46:06,240 --> 03:46:07,080 >> ALL RIGHT, LET'S SEE IF WE 4528 03:46:07,080 --> 03:46:13,040 CAN MAKE THIS GO. 4529 03:46:13,040 --> 03:46:14,920 ALL RIGHT, THANK YOU FOR THE 4530 03:46:14,920 --> 03:46:15,640 INTRODUCTION, I'M HERE TODAY TO 4531 03:46:15,640 --> 03:46:17,680 TALK ABOUT THE ROLE THAT IMAGING 4532 03:46:17,680 --> 03:46:21,320 IS LIKELY TO PLAY IN CF LUNG 4533 03:46:21,320 --> 03:46:23,720 DISEASE IN THE HIGHLY EFFECTIVE 4534 03:46:23,720 --> 03:46:24,200 MODULATOR THERAPY. 4535 03:46:24,200 --> 03:46:26,120 I WILL BEGIN BY THINKING ABOUT 4536 03:46:26,120 --> 03:46:26,720 MAJOR OPPORTUNITIES GOING 4537 03:46:26,720 --> 03:46:28,760 FORWARD, THAT IS WE HAVE THE 4538 03:46:28,760 --> 03:46:29,560 ABILITY TO QUANTIFY 4539 03:46:29,560 --> 03:46:39,720 PATHOPHYSIOLOGY AND PEOPLE WITH 4540 03:46:39,720 --> 03:46:43,560 NORMAL SPIROMETRY, AND TRULY 4541 03:46:43,560 --> 03:46:44,800 ABNORMALITIES OF THE LUNGS. 4542 03:46:44,800 --> 03:46:46,480 I WOULD ALSO SAY THAT 1 OF THE 4543 03:46:46,480 --> 03:46:51,800 THINGS WE MIGHT BE ABLE TO DO IS 4544 03:46:51,800 --> 03:46:53,680 IDENTIFY SUBCLINICAL AS WE 4545 03:46:53,680 --> 03:46:56,680 PREPARE FOR GERIATRIC CF IN 20 4546 03:46:56,680 --> 03:46:57,040 YEARS FROM NOW. 4547 03:46:57,040 --> 03:46:58,600 NOW BEFORE I CAN MOVE ON TO 4548 03:46:58,600 --> 03:46:59,680 THOSE LOFTY NOTIONS I NEED TO 4549 03:46:59,680 --> 03:47:02,120 TALK ABOUT WHAT EXISTS RIGHT 4550 03:47:02,120 --> 03:47:02,600 NOW. 4551 03:47:02,600 --> 03:47:05,800 AND FOR YEARS PRIMARILY WHAT WE 4552 03:47:05,800 --> 03:47:08,520 HAVE THOUGHT ABOUT IS SPI 4553 03:47:08,520 --> 03:47:10,920 ROMETRY IN THE CONTEXT OF LUNG 4554 03:47:10,920 --> 03:47:13,800 DISEASE, THIS HAS CHANGED AS WE 4555 03:47:13,800 --> 03:47:15,520 TALKED ABOUT IN THIS MEETING SO 4556 03:47:15,520 --> 03:47:15,760 FAR. 4557 03:47:15,760 --> 03:47:17,800 IT'S IMPACTING HOW WE WRITE OUR 4558 03:47:17,800 --> 03:47:18,040 GRANTS. 4559 03:47:18,040 --> 03:47:20,000 I MADE THIS GRANT 5 OR 6 YEARS 4560 03:47:20,000 --> 03:47:21,600 AGO, WHERE WE TALKED ABOUT 4561 03:47:21,600 --> 03:47:24,120 DEVELOPING NEW TECHNOLOGY WITH 4562 03:47:24,120 --> 03:47:24,960 HYPER CHLORRA SWREEN WHICH I 4563 03:47:24,960 --> 03:47:27,160 WILL TALK ABOUT IN A MOMENT AND 4564 03:47:27,160 --> 03:47:29,160 AS SAD AS TD CF SITUATION IS, 4565 03:47:29,160 --> 03:47:31,240 IT'S ANI DEAL SITUATION TO 4566 03:47:31,240 --> 03:47:34,000 VALIDATE NEW TECH AS AN 4567 03:47:34,000 --> 03:47:36,960 OBJECTIVE LUNG DISEASE, AND IT'S 4568 03:47:36,960 --> 03:47:40,120 UNPREDICTABLE AND TIME COURSE 4569 03:47:40,120 --> 03:47:40,600 LIKE SYNTHESIS, COPD. 4570 03:47:40,600 --> 03:47:44,760 IF I TOLD THAT STORY, THE 4571 03:47:44,760 --> 03:47:50,560 REALITY IS FOR MANY OF OUR CF, 4572 03:47:50,560 --> 03:47:53,200 THEY'RE GOING TO BE SPI ROUGH 4573 03:47:53,200 --> 03:47:55,120 ATOM METICALLY NORMAL THROUGHOUT 4574 03:47:55,120 --> 03:47:56,640 PEDIATRIC CAN AND INTO ADULT 4575 03:47:56,640 --> 03:47:59,000 CARE, SO WE NEED A NEW HANDLE ON 4576 03:47:59,000 --> 03:48:00,560 CF LUNG DISEASE, SINCE THE 4577 03:48:00,560 --> 03:48:02,840 1980S, 1 OF THE IDEAS HAS BEEN 4578 03:48:02,840 --> 03:48:05,080 FORWARDED IS WE USE CT IMAGING 4579 03:48:05,080 --> 03:48:12,000 WHICH IS SUPERIOR MEASURE OF 4580 03:48:12,000 --> 03:48:13,400 LUNG PATHOLOGIES TO SPIROMETRY 4581 03:48:13,400 --> 03:48:15,600 AND IT'S EASY TO SEA WHY. 4582 03:48:15,600 --> 03:48:18,600 IS MY AUDYE A PROBLEM? 4583 03:48:18,600 --> 03:48:20,160 >> SO, WE CAN HEAR YOU. 4584 03:48:20,160 --> 03:48:22,520 >> OKAY, SORRY THERE WAS A 4585 03:48:22,520 --> 03:48:24,360 COMMENT I SAW, IN ANY CASE 4586 03:48:24,360 --> 03:48:26,640 THERE'S A LOT OF CLASSIC 4587 03:48:26,640 --> 03:48:28,520 PATHOLOGY THAT'S SEEN IN THE CF 4588 03:48:28,520 --> 03:48:30,480 LUNG AIR TRAPPING CAUSED BY 4589 03:48:30,480 --> 03:48:31,560 OBJECTIVE DISEASE, IN THE DENSE 4590 03:48:31,560 --> 03:48:34,040 STRUCTURE WHICH IS WE CALL 4591 03:48:34,040 --> 03:48:34,840 CONSOLIDATIONS OR GRAWND 4592 03:48:34,840 --> 03:48:38,960 CAPACITY, AND VARIETY OF AIR WAY 4593 03:48:38,960 --> 03:48:44,760 ABNORMALITIES, MUCUS PLUGGING 4594 03:48:44,760 --> 03:48:46,600 AND ULTIMATELY BRONCHIECTASIS, 4595 03:48:46,600 --> 03:48:50,800 AND HAVE A DILATED AIR WAY THAT 4596 03:48:50,800 --> 03:48:51,320 EXCEEDS THE CHEST. 4597 03:48:51,320 --> 03:48:56,160 ANOTHER GRAY WAY OF CT, 4598 03:48:56,160 --> 03:48:56,560 OOPS--WRONG WAY. 4599 03:48:56,560 --> 03:48:57,920 SORRY, TECHNICAL DIFFICULTIES 4600 03:48:57,920 --> 03:48:58,120 HERE. 4601 03:48:58,120 --> 03:48:59,120 IS IT'S TRULY QUANTITATIVE IN 4602 03:48:59,120 --> 03:49:01,200 THE SENSE WE CAN MEASURE RADIO 4603 03:49:01,200 --> 03:49:03,320 SENSITY AND THAT TELLS US HOW 4604 03:49:03,320 --> 03:49:04,600 DENSE THE LUNG TISSUE REALLY IS, 4605 03:49:04,600 --> 03:49:08,200 WE KNOW FROM THE COPD WORLD THAT 4606 03:49:08,200 --> 03:49:10,920 IF YOU MEASURE NEGATIVE 950 HU 4607 03:49:10,920 --> 03:49:13,040 OR LESS, WE HAVE CLINICAL 4608 03:49:13,040 --> 03:49:15,480 EMPHYSEMA AND THAT HAS BEEN 4609 03:49:15,480 --> 03:49:18,240 VALIDATED HISTOLOGICALLY FOR 4610 03:49:18,240 --> 03:49:18,680 DECADES. 4611 03:49:18,680 --> 03:49:22,880 NOW THIS RAISES AN INTERESTING 4612 03:49:22,880 --> 03:49:26,560 PROBLEM IN CF BECAUSE IF WE LOOK 4613 03:49:26,560 --> 03:49:27,600 AT THIS--THESE--MANY OF THESE 4614 03:49:27,600 --> 03:49:29,240 PEOPLE, WE SEE ACTUALLY LOW 4615 03:49:29,240 --> 03:49:33,560 DENSITY TISSUE MUCH LIKE WE SEE 4616 03:49:33,560 --> 03:49:36,160 IN EMPHYSEMA PATIENTS BUT IT'S 4617 03:49:36,160 --> 03:49:36,760 RELATIVE UNRECOGNIZED WITHIN 4618 03:49:36,760 --> 03:49:37,960 CLINICAL CARE RIGHT NOW AND 4619 03:49:37,960 --> 03:49:39,320 UNDERSTANDING THIS IS 4620 03:49:39,320 --> 03:49:41,040 CHALLENGING BECAUSE LUNG DENSITY 4621 03:49:41,040 --> 03:49:42,680 CHANGES WITH TIME, AND IF WE 4622 03:49:42,680 --> 03:49:45,360 WANT TO UNDERSTAND WHAT IS TRULY 4623 03:49:45,360 --> 03:49:47,240 ABNORMAL WE HAVE TO DEFINE 4624 03:49:47,240 --> 03:49:49,120 NORMAL WHICH MEANS WE NEED 4625 03:49:49,120 --> 03:49:52,120 NORMATIVE EQUATIONS WHICH WE 4626 03:49:52,120 --> 03:49:53,640 HAVE FOR SPIROMETRY, ALL THE WAY 4627 03:49:53,640 --> 03:49:55,360 DOWN TO THE PEDIATRIC WELL AND 4628 03:49:55,360 --> 03:49:58,040 NOT MANY ARE GOING TO VOLUNTEER 4629 03:49:58,040 --> 03:50:00,000 THEIR 5 YEAR-OLD TO BE RADIATED 4630 03:50:00,000 --> 03:50:02,360 EVEN WITH A LOW DOSE CT PROTOCOL 4631 03:50:02,360 --> 03:50:04,440 TO GET NORMATIVE DATA. 4632 03:50:04,440 --> 03:50:06,520 EVEN IN PEOPLE WITH CF WHO HAVE 4633 03:50:06,520 --> 03:50:07,920 ESTABLISHED LUNG DISEASE BUT ARE 4634 03:50:07,920 --> 03:50:09,200 FEELING BETTER BECAUSE THERE ARE 4635 03:50:09,200 --> 03:50:10,800 ALL THESE HIGHLY EFFECTIVE 4636 03:50:10,800 --> 03:50:13,000 THERAPIES, HOW MUCH CAN WE 4637 03:50:13,000 --> 03:50:16,760 REALLY JUSTIFY ROUTINE 4638 03:50:16,760 --> 03:50:18,120 DIAGNOSTIC RADIOLOGY TO 4639 03:50:18,120 --> 03:50:19,160 UNDERSTAND BRONCH YECT SIS. 4640 03:50:19,160 --> 03:50:21,120 AND I SAY THAT BECAUSE I DON'T 4641 03:50:21,120 --> 03:50:31,520 FIND THESE PARTICULARLY 4642 03:50:48,800 --> 03:50:49,040 MEANINGFUL. 4643 03:50:49,040 --> 03:50:49,640 --STANDARD CARDIAC SCAN BUT IF 4644 03:50:49,640 --> 03:50:51,600 YOU LOOK AT THE ARROW IN THE 4645 03:50:51,600 --> 03:50:54,440 LUNG WHERE THE RUBBER MEETS THE 4646 03:50:54,440 --> 03:50:55,240 ROAD PHYSIOLOGICALLY, IT'S 4647 03:50:55,240 --> 03:50:57,280 LITERALLY A BLACK BOX AND TO 4648 03:50:57,280 --> 03:50:57,880 OVERCOME THIS CHALLENGE WHICH 4649 03:50:57,880 --> 03:51:00,080 HAS TO DO WITH THE MAGNETIC 4650 03:51:00,080 --> 03:51:01,560 PROPERTIES ALONE ARE CENTERED, 4651 03:51:01,560 --> 03:51:03,320 OTHERS AROUND THE WORLD HAVE 4652 03:51:03,320 --> 03:51:05,320 DEVELOPED ECHO TIME MRI, THAT IS 4653 03:51:05,320 --> 03:51:08,200 RATHER THAN ENCODE THE DATA WITH 4654 03:51:08,200 --> 03:51:09,880 THE TIME CONSTANT OF MINIMILLI 4655 03:51:09,880 --> 03:51:12,000 SECONDS AND THE SIGNALING IN A 4656 03:51:12,000 --> 03:51:13,760 MILLI SECOND IN THE LUNG TISSUE, 4657 03:51:13,760 --> 03:51:15,520 WE GO TO 10S OF MICROSECONDS AND 4658 03:51:15,520 --> 03:51:17,560 WE'RE ABLE TO GET QUANTITATIVE 4659 03:51:17,560 --> 03:51:18,760 RECOVERY OF SIGNAL INTENSITY AND 4660 03:51:18,760 --> 03:51:21,080 THIS ALLOWS US TO SEE PATHOLOGY 4661 03:51:21,080 --> 03:51:25,240 LIKE MUCUS PLUGGING, AIR WAY 4662 03:51:25,240 --> 03:51:26,120 DILATION, ET CETERA. 4663 03:51:26,120 --> 03:51:27,760 AND HERE'S WORK BY MY COLLEAGUES 4664 03:51:27,760 --> 03:51:30,440 JASON WOODS AND HIS POST DOC 4665 03:51:30,440 --> 03:51:33,200 DAVID ROACH WHERE THEY LOOK IN 4666 03:51:33,200 --> 03:51:34,320 TODDLERS WITH LUNG ABNORMALITIES 4667 03:51:34,320 --> 03:51:36,280 IN CF AND WE'RE ABLE TO SEE THE 4668 03:51:36,280 --> 03:51:39,160 SAME SORT OF PATHOLOGIES 1 SEES 4669 03:51:39,160 --> 03:51:41,960 IN CT WITH UT MRI AND WHEN THEY 4670 03:51:41,960 --> 03:51:43,720 SCORED THESE IMAGES USING THE 4671 03:51:43,720 --> 03:51:44,760 STANDARD BRODY SCORE DEVELOPED 4672 03:51:44,760 --> 03:51:47,360 BY OUR SIN SUDDEN ATY CHILDREN'S 4673 03:51:47,360 --> 03:51:49,000 HOSPITALLAL AN BRODY THEY SAW A 4674 03:51:49,000 --> 03:51:50,080 REASONABLY GOOD CORLEAGZ 4675 03:51:50,080 --> 03:51:52,000 SUGGESTING WE CAN ACTUALLY GET 4676 03:51:52,000 --> 03:51:52,800 DIAGNOSTIC AND PROGNOSTICLY 4677 03:51:52,800 --> 03:51:55,440 USEFUL INFORMATION WITH THE 4678 03:51:55,440 --> 03:51:55,920 UTSMAZE MRI. 4679 03:51:55,920 --> 03:51:57,600 NOTICE IN WAS A NUMBER OF YEARS 4680 03:51:57,600 --> 03:51:59,240 AGO, WE PUSHED THE TECHNOLOGY 4681 03:51:59,240 --> 03:52:01,440 MUCH FARTHER THIS, IS OUR 4682 03:52:01,440 --> 03:52:03,080 STATE-OF-THE-ART RIGHT NOW HIGH 4683 03:52:03,080 --> 03:52:05,480 RESOLUTION UT MRI AND I WANT TO 4684 03:52:05,480 --> 03:52:06,600 SHOW 1 FEATURE HERE THAT'S 4685 03:52:06,600 --> 03:52:08,160 EXCITING TO US THAT IF YOU LOOK 4686 03:52:08,160 --> 03:52:12,120 INTO THE PERIPHERY OF THE LUNG 4687 03:52:12,120 --> 03:52:13,280 YOU SLEEP APNEA AND OBESITYY 4688 03:52:13,280 --> 03:52:15,120 THESE REGIONS WHERE WE'RE SEEING 4689 03:52:15,120 --> 03:52:16,200 AIR TRAPPING ON THE IMAGES WHICH 4690 03:52:16,200 --> 03:52:17,360 IS SOMETHING THAT WAS VERY 4691 03:52:17,360 --> 03:52:21,000 DIFFICULT TO DO PRIOR TO THIS 4692 03:52:21,000 --> 03:52:21,920 EVEN WITH UTE. 4693 03:52:21,920 --> 03:52:23,680 NOW WHAT'S EXCITING IN TERMS OF 4694 03:52:23,680 --> 03:52:25,200 CLINICAL DISSEMINATION IS THAT 4695 03:52:25,200 --> 03:52:26,640 ALL OF THE MAJOR MRI 4696 03:52:26,640 --> 03:52:28,840 MANUFACTURES RIGHT NOW HAVE 4697 03:52:28,840 --> 03:52:30,240 RESEARCH SEQUENCES FOR SOME 4698 03:52:30,240 --> 03:52:31,360 FLAVOR OF UT MRI AND I WOULD 4699 03:52:31,360 --> 03:52:32,680 SUSPECT IN THE NEXT 5 YEARS OR 4700 03:52:32,680 --> 03:52:35,640 SO, WE WILL SEE THIS AS A 4701 03:52:35,640 --> 03:52:38,160 CLINICAL SEQUENCE FDA APPROVED 4702 03:52:38,160 --> 03:52:39,440 WHICH MEANS A CLINICIAN CAN 4703 03:52:39,440 --> 03:52:40,960 ORDER MUCH THE SAME WAY YOU 4704 03:52:40,960 --> 03:52:42,640 WOULD A CT PROTOCOL NOW. 4705 03:52:42,640 --> 03:52:45,160 SO WHAT CAN WE DO FOR FUNCTION. 4706 03:52:45,160 --> 03:52:47,960 THAT IS WHAT DO WE DO TO MOVE 4707 03:52:47,960 --> 03:52:49,960 AWAY FROM OUR OLD FRIEND 4708 03:52:49,960 --> 03:52:52,160 SPIROMETRY, WE WOULD LOVE TO 4709 03:52:52,160 --> 03:52:54,640 IMAGE THE GASES OXYGEN AND CO2, 4710 03:52:54,640 --> 03:52:56,080 BUT FOR TECHNICAL REASONS WE 4711 03:52:56,080 --> 03:52:59,880 CAN'T SO WE IMCANCER CENTER A 4712 03:52:59,880 --> 03:53:02,320 SURROGATE GAS, XENON 129, IT'S 4713 03:53:02,320 --> 03:53:04,040 CHEMISTRY INERT, NONRADIO 4714 03:53:04,040 --> 03:53:05,640 ARCTIVE AND OBSERVABLE IN MR AND 4715 03:53:05,640 --> 03:53:07,480 WE HAVE THE POTENTIAL TO IMAGE 4716 03:53:07,480 --> 03:53:07,800 LUNG FUNCTION. 4717 03:53:07,800 --> 03:53:10,080 IF YOU DO THIS NAIVELY YOU DON'T 4718 03:53:10,080 --> 03:53:11,360 GET MUCH OF ANYTHING USEFUL 4719 03:53:11,360 --> 03:53:12,880 BECAUSE THE GASES ARE LOW 4720 03:53:12,880 --> 03:53:15,040 DENSITY, ABOUT A FACTOR OF 4721 03:53:15,040 --> 03:53:17,360 10,000 LESS THAN WATER. 4722 03:53:17,360 --> 03:53:21,360 SO WE USE A TECHNIQUE CALLED 4723 03:53:21,360 --> 03:53:23,880 HYDRO CHLORRIZATION, FROM A 4724 03:53:23,880 --> 03:53:24,640 PHYSICIST, PREPARED GAS, GET A 4725 03:53:24,640 --> 03:53:26,680 SIGNATURES NOX FAMILY ACTIVATOR 4726 03:53:26,680 --> 03:53:27,880 INTENSITY INCREASE OF A FACTOR 4727 03:53:27,880 --> 03:53:30,640 OF 10,000, PUT THE GAS IN A BAG, 4728 03:53:30,640 --> 03:53:32,400 HAVE THE SUBJECT INHALE THE GAS 4729 03:53:32,400 --> 03:53:34,320 WHERE IT REACHES THE ALVEOLAR 4730 03:53:34,320 --> 03:53:36,040 SPACES AS A CIRCUIT FOR 4731 03:53:36,040 --> 03:53:37,800 VENTILATION AND WHEN WE DO THIS, 4732 03:53:37,800 --> 03:53:39,400 THIS SIGNAL BECOMES SOMETHING 4733 03:53:39,400 --> 03:53:39,800 LIKE THIS. 4734 03:53:39,800 --> 03:53:43,120 THIS IS A INHALED BREATH OF 4735 03:53:43,120 --> 03:53:44,480 XENON 129 AFTER HIGH 4736 03:53:44,480 --> 03:53:47,120 POLARIZATION, AND THE SIGNAL 4737 03:53:47,120 --> 03:53:47,640 INTENSITY FOR REGIONAL 4738 03:53:47,640 --> 03:53:49,160 VENTILATION AND IF YOU LOOK AT 4739 03:53:49,160 --> 03:53:50,680 THE APEX OF THE LUNG, YOU WILL 4740 03:53:50,680 --> 03:53:52,320 SEE RAT BITES OUT OF IT AND 4741 03:53:52,320 --> 03:53:54,960 THAT'S WHERE THIS SUBJECT OF CF 4742 03:53:54,960 --> 03:53:56,600 WE SEE OBSTRUCTIVE LUNG DISEASE 4743 03:53:56,600 --> 03:53:58,960 AND THEREFORE NO VENTILATION IN 4744 03:53:58,960 --> 03:53:59,680 THAT REGION. 4745 03:53:59,680 --> 03:54:01,320 AND BECAUSE THESE IMAGERS ARE 4746 03:54:01,320 --> 03:54:03,640 JUST 3D DATA SETS WE CAN 4747 03:54:03,640 --> 03:54:05,000 ACTUALLY QUANTIFY THE IMPAIRMENT 4748 03:54:05,000 --> 03:54:07,840 FAIRLY EASILY, THAT IS WE PUT A 4749 03:54:07,840 --> 03:54:09,560 SIGNAL INTENSITY ACROSS THE DATA 4750 03:54:09,560 --> 03:54:12,280 SET AND DEFINE A THRESHOLD WHICH 4751 03:54:12,280 --> 03:54:14,240 WE SAY ANYTHING BELOW THAT IS 4752 03:54:14,240 --> 03:54:15,640 ABNORMAL INTENSITY AND CALCULATE 4753 03:54:15,640 --> 03:54:16,440 THE PERCENTAGE. 4754 03:54:16,440 --> 03:54:20,400 NOW IN YOUNG PEOPLE WITH CF, IF 4755 03:54:20,400 --> 03:54:22,480 YOU LOOKED AT SPIROMETRY IN 25 4756 03:54:22,480 --> 03:54:25,040 PEOPLE YOU WOULD SAY REAL TEF 4757 03:54:25,040 --> 03:54:27,360 LIE NORMAL NUMBERS, YOU NEED 4758 03:54:27,360 --> 03:54:29,120 MUCH LARGER TO SIGNIFICANCE WITH 4759 03:54:29,120 --> 03:54:29,760 HEALTHY CONTROLS. 4760 03:54:29,760 --> 03:54:31,120 HOWEVER THE VENTILATION DEFECT 4761 03:54:31,120 --> 03:54:33,000 SHOWS STRONG DIFFERENCES IN IN 4762 03:54:33,000 --> 03:54:33,480 POPULATION. 4763 03:54:33,480 --> 03:54:36,800 THIS WAS PREMODDULATOR BUT THE 4764 03:54:36,800 --> 03:54:37,640 STORY IS SIMILAR. 4765 03:54:37,640 --> 03:54:38,440 WHAT'S MOST INTERESTING, 4766 03:54:38,440 --> 03:54:43,400 HOWEVER, LOOK AT THE PEOPLE WHO 4767 03:54:43,400 --> 03:54:44,440 ARE SPIROMETTICRY NORMAL, IF YOU 4768 03:54:44,440 --> 03:54:46,480 LOOK AT THE IMAGES YOU SEE 4769 03:54:46,480 --> 03:54:47,040 SOMETHING STRIKING, YOU DON'T 4770 03:54:47,040 --> 03:54:50,640 NEED TO BE A RADIOLOGIST OR PULL 4771 03:54:50,640 --> 03:54:51,480 MONITORROLOGYIST AND SAYING THAT 4772 03:54:51,480 --> 03:54:53,120 KID IS ON A DIFFERENT TRAJECTORY 4773 03:54:53,120 --> 03:54:55,120 THAN THE KID SHOWN IN C AND D. 4774 03:54:55,120 --> 03:54:57,880 SO THIS SORT OF SENSITIVITY THAT 4775 03:54:57,880 --> 03:54:58,520 VENTILATION IMAGING CAN PROVIDE 4776 03:54:58,520 --> 03:55:03,160 IN THE AGE OF HIGHLY EFFECTIVE 4777 03:55:03,160 --> 03:55:03,560 MODULAR THERAPY. 4778 03:55:03,560 --> 03:55:06,120 IT'S ALSO NOT THE ONLY CONTRAST 4779 03:55:06,120 --> 03:55:08,120 FROM MRI, WHICH IS A STRENGTH OF 4780 03:55:08,120 --> 03:55:10,560 MRI, WE CAN MEASURE HOW FAR A 4781 03:55:10,560 --> 03:55:12,720 MOLECULE OR ATOM FUSES IN A 4782 03:55:12,720 --> 03:55:13,240 GIVEN TIME PERIOD. 4783 03:55:13,240 --> 03:55:14,920 THIS HAS BEEN USE INDEED THE 4784 03:55:14,920 --> 03:55:16,240 CONTEXT OF EMPHYSEMA, WHEN WE 4785 03:55:16,240 --> 03:55:18,720 MEASURE AN APPARENT CO EFFICIENT 4786 03:55:18,720 --> 03:55:21,720 WITH MRI IN THE LUNG FOR 4787 03:55:21,720 --> 03:55:23,480 EXTENON, WE MEASURE IN THE LUNG 4788 03:55:23,480 --> 03:55:25,680 BECAUSE DIFFUSION OF THE GASES 4789 03:55:25,680 --> 03:55:28,480 CAN STRAIN BY COLLISIONS WITH 4790 03:55:28,480 --> 03:55:30,120 THE ALVEOLAR WALL, BUT IF WE 4791 03:55:30,120 --> 03:55:31,520 HAVE THOSE DESTRUCTIONS IN THOSE 4792 03:55:31,520 --> 03:55:39,280 WALLS WE SEE A MUCH LARGER CO 4793 03:55:39,280 --> 03:55:41,000 EFFUSION, THAT APPROACHES THE 4794 03:55:41,000 --> 03:55:44,200 DIFFUSION METHOD, IN THE MODEL. 4795 03:55:44,200 --> 03:55:46,200 WE SEE THIS IN COPD AND WHAT I 4796 03:55:46,200 --> 03:55:48,240 FOUND WHEN I CAME TO CINCINNATI, 4797 03:55:48,240 --> 03:55:50,640 IF YOU DO THE SAME EXPERIMENT IN 4798 03:55:50,640 --> 03:55:54,680 A SUBJECT WITH CF, YOU SEE 4799 03:55:54,680 --> 03:55:55,400 PATHOLOGICALLY ENLARGED ALVEOLAR 4800 03:55:55,400 --> 03:55:57,720 SPACES IN A SUBSET OF CF, PEOPLE 4801 03:55:57,720 --> 03:55:59,480 WITH CF AND YOU DON'T SEE IT AT 4802 03:55:59,480 --> 03:56:01,120 ALL IN THE CONTROLS AND WHAT'S 4803 03:56:01,120 --> 03:56:02,680 FASCINATING IS YOU TEND TO SEE 4804 03:56:02,680 --> 03:56:03,640 THIS ON THE PERIPHERY OF THE 4805 03:56:03,640 --> 03:56:06,400 LUNG THAT IS YOU HAVE 4806 03:56:06,400 --> 03:56:07,200 PATHOLOGICALLY LOW TISSUE 4807 03:56:07,200 --> 03:56:08,840 DENSITY OR LOW STRUCTURAL 4808 03:56:08,840 --> 03:56:12,160 INTEGRITY NEAR THE SURFACE WHICH 4809 03:56:12,160 --> 03:56:15,040 MAY EXPLAIN WHY PEOPLE WITH CF 4810 03:56:15,040 --> 03:56:16,600 HAVE THE THORAX THAN THE GENERAL 4811 03:56:16,600 --> 03:56:17,440 POPULATION, SO THIS IS AGAIN 4812 03:56:17,440 --> 03:56:20,240 SOMETHING WE NEED TO BE AWARE OF 4813 03:56:20,240 --> 03:56:21,520 AND LOOK FORWARD TO, LOOK OUT 4814 03:56:21,520 --> 03:56:26,280 FOR AS WE MOVE INTO OLDER AND 4815 03:56:26,280 --> 03:56:27,680 OLDER PATIENT CARE AND WE CAN 4816 03:56:27,680 --> 03:56:30,360 NOW GET AT THIS WITHOUT THE NEED 4817 03:56:30,360 --> 03:56:31,280 FOR IONIZING RADIATION. 4818 03:56:31,280 --> 03:56:33,880 A FINAL CONTRAST WE CAN GET FROM 4819 03:56:33,880 --> 03:56:36,640 XENON MRI AND WE CAN REASONABLY 4820 03:56:36,640 --> 03:56:38,520 DETECT GAS EXCHANGE IN THE LUNG 4821 03:56:38,520 --> 03:56:40,000 BECAUSE XENON HAS A LARGE 4822 03:56:40,000 --> 03:56:40,960 SENSITIVITY TO THE CHEMICAL 4823 03:56:40,960 --> 03:56:44,400 ENVIRONMENT SO WHEN IT DESOLVES 4824 03:56:44,400 --> 03:56:46,440 IN THE PULMONARY TISSUES WE SEE 4825 03:56:46,440 --> 03:56:48,320 UNIQUE FREQUENCIES IN THE RED 4826 03:56:48,320 --> 03:56:50,600 BLOOD CELLS, THE TISSUES AND THE 4827 03:56:50,600 --> 03:56:52,680 GAS PHASE WHICH WE EXPLORED FOR 4828 03:56:52,680 --> 03:56:53,200 VENTILATION IMAGE. 4829 03:56:53,200 --> 03:56:58,760 NOW THIS IS WORK DONE BY MY 4830 03:56:58,760 --> 03:56:59,840 COLLEAGUE LAURA [INDISCERNIBLE] 4831 03:56:59,840 --> 03:57:01,880 WHO PRESENTED THIS AT ACS, WE 4832 03:57:01,880 --> 03:57:02,960 CAN GET NORMATIVE DAT WHICH 4833 03:57:02,960 --> 03:57:04,880 WE'RE JUST BEGINNING TO DO AND 4834 03:57:04,880 --> 03:57:07,840 WHAT SHE HAS FOUND WHEN COMPARED 4835 03:57:07,840 --> 03:57:10,960 TO HEALTHY AGE MATCHED SUBJECT 4836 03:57:10,960 --> 03:57:13,280 SYSTEM WE HAVE A PATHOLOGICAL 4837 03:57:13,280 --> 03:57:15,840 INCREASE IN THE MEMBRANE SIGNAL 4838 03:57:15,840 --> 03:57:19,560 IN CF LIKELY DUE TO SUBCLINICAL 4839 03:57:19,560 --> 03:57:21,320 INFLAMMATION IN THE ALVEOLAR 4840 03:57:21,320 --> 03:57:21,720 SPACES THEMSELVES. 4841 03:57:21,720 --> 03:57:26,120 SO WHERE DOES THIS LEAVE US IN 4842 03:57:26,120 --> 03:57:29,360 TERMS OF CLINICAL DISSEMINATION? 4843 03:57:29,360 --> 03:57:31,280 THIS IS A SLIDE PROVIDED TO ME 4844 03:57:31,280 --> 03:57:34,120 BY MY COLLEAGUE [INDISCERNIBLE] 4845 03:57:34,120 --> 03:57:39,400 AT POLAREAN WHO MAKES THE 4846 03:57:39,400 --> 03:57:39,880 XENONSPADES POLARIZERS. 4847 03:57:39,880 --> 03:57:43,520 THE LIGHT BIEW IS THE ABILITY TO 4848 03:57:43,520 --> 03:57:49,080 DO THE XE MRI, AND THE PURPLE 4849 03:57:49,080 --> 03:57:53,600 SITES ARE POTENTIAL SITES IN THE 4850 03:57:53,600 --> 03:57:55,800 COMING YEARS, RIGHT NOW XENON IS 4851 03:57:55,800 --> 03:57:57,000 APPROVED FOR CLINICAL USE IN THE 4852 03:57:57,000 --> 03:57:57,400 UK. 4853 03:57:57,400 --> 03:57:59,400 WE HAVE RECENTLY COMPLETED 4854 03:57:59,400 --> 03:58:00,200 SUCCESSFULLY THE PHASE 3 4855 03:58:00,200 --> 03:58:04,240 CLINICAL TRIAL FOR XENON MRI IN 4856 03:58:04,240 --> 03:58:05,800 ADULTS IN THE U.S. 4857 03:58:05,800 --> 03:58:09,480 WE EXPECT FDA APPROVAL FOR 4858 03:58:09,480 --> 03:58:11,560 XENON MRI LATE THERAPY AND YEAR, 4859 03:58:11,560 --> 03:58:13,440 CANADA FALLS THROUGH SHORTLY 4860 03:58:13,440 --> 03:58:13,720 THEREAFTER. 4861 03:58:13,720 --> 03:58:17,440 SO THIS NOW LEAVES US IN A 4862 03:58:17,440 --> 03:58:21,600 SITUATION WHERE WE HAVE THIS 4863 03:58:21,600 --> 03:58:23,720 REALLY INTERESTING TECHNOLOGY IN 4864 03:58:23,720 --> 03:58:27,200 A HANDFUL OF SPECIALIZED SITES, 4865 03:58:27,200 --> 03:58:28,400 HOW DO WE DISSEMINATE IT MORE 4866 03:58:28,400 --> 03:58:29,400 BROADLY AND I THINK 1 TECHNOLOGY 4867 03:58:29,400 --> 03:58:31,040 TRANSFER WE CAN DO WITH THESE 4868 03:58:31,040 --> 03:58:32,600 VERY SENSITIVE TOOL SYSTEM WE 4869 03:58:32,600 --> 03:58:35,600 CAN VALIDATE MORE EASILY 4870 03:58:35,600 --> 03:58:37,280 DISSEMINATED TOOLS THIS, IS AN 4871 03:58:37,280 --> 03:58:39,440 EXAMPLE OF WORK WITH MY 4872 03:58:39,440 --> 03:58:40,680 COLLEAGUE CANNED WHAT WHO MANY 4873 03:58:40,680 --> 03:58:44,360 OF YOU KNOW AND HIS TEAM WHERE 4874 03:58:44,360 --> 03:58:45,680 HE'S DEVELOPED PROTEOMIC MARKERS 4875 03:58:45,680 --> 03:58:50,640 OVER THE YEARS USING SPIROMETRY 4876 03:58:50,640 --> 03:58:51,920 TO SEGGREGATE POPULATIONS IF WE 4877 03:58:51,920 --> 03:58:57,560 DO THIS WITH XENON IN 4878 03:58:57,560 --> 03:58:59,520 SPIROMETRIC POPULATIONS WE CAN 4879 03:58:59,520 --> 03:59:02,480 SEE DIFFERENCES IN PEOPLE WITH 4880 03:59:02,480 --> 03:59:10,160 SERUM PROTEOMICS THAT HAVE 4881 03:59:10,160 --> 03:59:10,640 SPASESSIVE STATISTICAL 4882 03:59:10,640 --> 03:59:10,960 SIGNIFICANCE. 4883 03:59:10,960 --> 03:59:11,840 SO I THINK WE CAN MOVE THIS 4884 03:59:11,840 --> 03:59:14,280 FORWARD AND DO THINGS THAT I 4885 03:59:14,280 --> 03:59:16,360 THINK ARE VERY, VERY SIMILAR 4886 03:59:16,360 --> 03:59:17,800 WITH YOUR FAVORITE OMICs, 4887 03:59:17,800 --> 03:59:19,920 METRICS TAB O LOAMICS 4888 03:59:19,920 --> 03:59:21,520 EPIGENOMICS, THOSE SORTS OF 4889 03:59:21,520 --> 03:59:22,280 THINGS. 4890 03:59:22,280 --> 03:59:23,680 AND A SIMILAR APPROACH COULD BE 4891 03:59:23,680 --> 03:59:25,440 USED IN LIVER AND GUT 4892 03:59:25,440 --> 03:59:28,280 COMPLICATIONS WHERE WE USE 4893 03:59:28,280 --> 03:59:30,160 SIMILAR TOOLS TO DISSEMINATE 4894 03:59:30,160 --> 03:59:31,520 BIOMARKERS EARLY IN THE DISEASE. 4895 03:59:31,520 --> 03:59:33,400 SO THAT I GUESS I WILL END WITH 4896 03:59:33,400 --> 03:59:34,240 MY ACKNOWLEDGMENTS WHICH ARE 4897 03:59:34,240 --> 03:59:35,680 KIND OF MY DISCLOSURES, PEOPLE 4898 03:59:35,680 --> 03:59:37,080 PAY FOR THE MONEY, ALL OTHER 4899 03:59:37,080 --> 03:59:39,440 PEOPLE DO REAL WORK AND I'M A 4900 03:59:39,440 --> 03:59:40,440 PHYSICAL CHEMIST BY TRAINING SO 4901 03:59:40,440 --> 03:59:41,800 TAKE EVERYTHING I SAY WITH A 4902 03:59:41,800 --> 03:59:42,440 GRAIN OF SALT. 4903 03:59:42,440 --> 03:59:43,320 THANKS AGAIN FOR THE OPPORTUNITY 4904 03:59:43,320 --> 03:59:45,040 TO SPEAK AND I'M HOPING TO 4905 03:59:45,040 --> 03:59:47,760 ANSWER ANY QUESTIONS YOU FOLKS 4906 03:59:47,760 --> 03:59:58,320 HAVE IF THERE'S TIME REMAINING. 4907 03:59:58,800 --> 04:00:02,600 AND I WILL TRY TO STOP 4908 04:00:02,600 --> 04:00:02,960 SHARINGING. 4909 04:00:02,960 --> 04:00:03,800 IT WENT OFF SCREEN. 4910 04:00:03,800 --> 04:00:04,920 >> SO WE'RE ACTUALLY GOING TO 4911 04:00:04,920 --> 04:00:09,800 TAKE QUESTIONS AT THE END IN THE 4912 04:00:09,800 --> 04:00:10,440 MODERATED DISCUSSION; IN GREAT 4913 04:00:10,440 --> 04:00:13,880 AND I WOULD LIKE TO INTRODUCE 4914 04:00:13,880 --> 04:00:15,000 DR. HEATHER BEAN. 4915 04:00:15,000 --> 04:00:16,080 >> HI, EVERYONE, THANK YOU SO 4916 04:00:16,080 --> 04:00:19,240 MUCH TO WILL THE ORGANIZERS FOR 4917 04:00:19,240 --> 04:00:24,720 INVITING ME TO PRESENT ON BREATH 4918 04:00:24,720 --> 04:00:25,600 ANALYSIS TODAY. 4919 04:00:25,600 --> 04:00:28,920 AND MY SLIDES SHOULD BE 4920 04:00:28,920 --> 04:00:30,200 MOMENTARILY MY CHRIS CLOSURES 4921 04:00:30,200 --> 04:00:31,480 REEL KEEPSAKES STROONT THIS 4922 04:00:31,480 --> 04:00:32,920 PRESENTATION IS THAT I'M A 4923 04:00:32,920 --> 04:00:35,480 RECIPIENT OF CF FOUNDATION AND 4924 04:00:35,480 --> 04:00:38,920 NIH GRAND FUNDING FOR BREATH IR 4925 04:00:38,920 --> 04:00:39,280 MARKER RESEARCH. 4926 04:00:39,280 --> 04:00:41,760 JUST TO GET US ON THE SAME PAGE 4927 04:00:41,760 --> 04:00:42,920 ABOUT EXHALED BREATH, I AM GOING 4928 04:00:42,920 --> 04:00:44,640 TO GIVE SOME VERY HIGH LEVEL 4929 04:00:44,640 --> 04:00:46,320 OVERVIEW FOR A FEW MINUES BEFORE 4930 04:00:46,320 --> 04:00:51,120 I GET INTO DATA. 4931 04:00:51,120 --> 04:00:53,760 EXHALED BREATH IS 1 OF THE 3 4932 04:00:53,760 --> 04:00:55,480 MAIN WASTE TREMES OF OUR BODY, 4933 04:00:55,480 --> 04:01:06,000 WE WILL THINK FEAS FECES, AND 4934 04:01:06,680 --> 04:01:08,840 URINE AS WASTE, ALL THE GASEOUS 4935 04:01:08,840 --> 04:01:12,560 WASTE THAT IS COLLECTED DIOF 4936 04:01:12,560 --> 04:01:14,000 THEALLY IS TRAN PORTED TO THE 4937 04:01:14,000 --> 04:01:15,920 LUNG FOR EXKRIEWGZ AND THEREFORE 4938 04:01:15,920 --> 04:01:17,680 THE BREATH CONTAINS INFORMATION 4939 04:01:17,680 --> 04:01:18,480 NOT ONLY ON THE HELT OF THE 4940 04:01:18,480 --> 04:01:20,400 LUNGS BUT IT ALSO CONTAINS 4941 04:01:20,400 --> 04:01:23,720 INFORMATION ON THE HEALTH OF ANY 4942 04:01:23,720 --> 04:01:25,400 OTHER BODILY SYSTEM. 4943 04:01:25,400 --> 04:01:27,480 AND IF YOU ARE COLLECTING BREATH 4944 04:01:27,480 --> 04:01:28,800 AND LOOKING FOR BREATH 4945 04:01:28,800 --> 04:01:30,240 BIOMARKERS SPECIFIC TO THE LUNG, 4946 04:01:30,240 --> 04:01:32,280 VERSUS SPECIFIC TO THE BREATH, 4947 04:01:32,280 --> 04:01:33,920 THERE ARE BREATHING MANEUVERS 4948 04:01:33,920 --> 04:01:36,520 THAT CAN BE INFORMED ON FOR 4949 04:01:36,520 --> 04:01:44,560 THOSE VERSUS BLOOD BIOMARKERS. 4950 04:01:44,560 --> 04:01:44,840 NEXT SLIDE. 4951 04:01:44,840 --> 04:01:46,000 JUST FOR TERMINOLOGY, I THINK A 4952 04:01:46,000 --> 04:01:49,240 LOT OF PEOPLE HAVE HEARD OF 4953 04:01:49,240 --> 04:01:50,560 EXHALED BREATH CONDENSATE, BUT 4954 04:01:50,560 --> 04:01:52,440 THAT'S ACTUALLY ONLY 1 PART OF 4955 04:01:52,440 --> 04:01:53,880 EXHALED BREATH. 4956 04:01:53,880 --> 04:01:56,360 EXHALED GREGHT IS GENERALLY 4957 04:01:56,360 --> 04:01:57,280 CATEGORIZED INTO 2 MAIN 4958 04:01:57,280 --> 04:02:01,600 FRACTIONS, THERE'S THE EXHALE 4959 04:02:01,600 --> 04:02:06,640 BREATH CONDENSATE OR EBC AND THE 4960 04:02:06,640 --> 04:02:08,480 VOCs ACCIDENT THE EXHALE 4961 04:02:08,480 --> 04:02:10,960 BREATH CONDENSATE IS TRACKED 4962 04:02:10,960 --> 04:02:12,280 THROUGH A CHILLED TUBE AND THOSE 4963 04:02:12,280 --> 04:02:16,760 ARE GOING TO CONTAIN MOLECULES 4964 04:02:16,760 --> 04:02:18,480 OF LOWER VOLATILITY BUT HIGHER 4965 04:02:18,480 --> 04:02:21,960 MOLECULAR WEIGHT, ALSO GREATER 4966 04:02:21,960 --> 04:02:22,760 POLARIZEDARRIZABILITY, AND IN 4967 04:02:22,760 --> 04:02:24,360 THAT FRACTION, YOU WILL FIND 4968 04:02:24,360 --> 04:02:29,320 THINGS LIKE HUMAN METABOLITES, 4969 04:02:29,320 --> 04:02:31,520 MICROBIAL METABOLITES, 4970 04:02:31,520 --> 04:02:32,960 XENOBIOTICS INCLUDING DRUGS, 4971 04:02:32,960 --> 04:02:34,480 PEPTIDES, VIRUS PARTICLES WHICH 4972 04:02:34,480 --> 04:02:36,880 IS HOW WE'RE ALL GIVING EACH 4973 04:02:36,880 --> 04:02:38,840 OTHER COVID AND EVEN EPITHELIAL 4974 04:02:38,840 --> 04:02:41,520 CELLS CAN BE FOUND IN EBC. 4975 04:02:41,520 --> 04:02:44,600 WHATEVER REMAINS AFTER YOU 4976 04:02:44,600 --> 04:02:46,960 CONDENSE OUT THE CONDENSATE IS 4977 04:02:46,960 --> 04:02:49,360 THE NONCONDENSABLE FRACTION AND 4978 04:02:49,360 --> 04:02:50,760 THOSE ARE THE COMPOUNDS, THEY 4979 04:02:50,760 --> 04:02:52,840 WILL BE SMALL MOLECULES 4980 04:02:52,840 --> 04:02:54,040 TYPICALLY LESS THAN 300 ATOMIC 4981 04:02:54,040 --> 04:02:56,160 MASS UNITS AND THEY WILL BE OF 4982 04:02:56,160 --> 04:02:58,280 HIGH MOTILITY AND OF COURSE WE 4983 04:02:58,280 --> 04:02:59,560 WILL SEE ATMOSHPHERIC AND ROOM 4984 04:02:59,560 --> 04:03:06,520 AIR IN THAT FRKS BUT ALSO HUMAN 4985 04:03:06,520 --> 04:03:07,920 METABOLITES, MICROBIAL AND EXTEN 4986 04:03:07,920 --> 04:03:09,680 O BITE METRICS TAB O LOAMICS AS 4987 04:03:09,680 --> 04:03:09,880 WELL. 4988 04:03:09,880 --> 04:03:10,200 NEXT SLIDE. 4989 04:03:10,200 --> 04:03:12,840 SO GIVE YOU JUST A VERY FEW 4990 04:03:12,840 --> 04:03:14,360 EXAMPLES OF BREATH STUDIES THAT 4991 04:03:14,360 --> 04:03:16,120 ARE RELEVANT TO MONITORING CF 4992 04:03:16,120 --> 04:03:22,200 HEALTH TO SHOW YOU SOME 4993 04:03:22,200 --> 04:03:22,960 FEASIBILITY AND CLINICAL UTILITY 4994 04:03:22,960 --> 04:03:25,160 EVIDENCE, I WILL GIVE YOU INFECT 4995 04:03:25,160 --> 04:03:26,680 YOWZ DISEASE MANAGEMENT, AND I 4996 04:03:26,680 --> 04:03:28,600 WILL ALSO GIVE EXAMPLES OF 4997 04:03:28,600 --> 04:03:29,400 NONINFECTIOUS DISEASE MANAGEMENT 4998 04:03:29,400 --> 04:03:31,840 THAT WOULD BE RELEVANT TO CF, IN 4999 04:03:31,840 --> 04:03:33,280 THE UPPER RIGHT HAND CORNER OF 5000 04:03:33,280 --> 04:03:34,120 THE FOLLOWING SLIDES YOU WILL 5001 04:03:34,120 --> 04:03:38,840 SEE 1 OF THESE 2 SYMBOLS EVEN 5002 04:03:38,840 --> 04:03:39,880 VOCs OR EBC, AND THAT WILL 5003 04:03:39,880 --> 04:03:41,280 TELL YOU WHICH BREATH WAS 5004 04:03:41,280 --> 04:03:42,680 COLLECTED AND STUDIES FOR THAT 5005 04:03:42,680 --> 04:03:51,040 PARTICULAR ANALYSIS. 5006 04:03:51,040 --> 04:03:52,320 NEXT SLIDE EMPLOY THIS WAS A 5007 04:03:52,320 --> 04:03:55,560 STUDY THAT WAS PERFORMED IN A 5008 04:03:55,560 --> 04:03:56,840 POPULATION FOR DETECTION AND 5009 04:03:56,840 --> 04:03:59,840 DIGITEXTIS OF PNEUMONIA USING PC 5010 04:03:59,840 --> 04:04:01,800 R TECHNOLOGY, IN THIS STUDY, 5011 04:04:01,800 --> 04:04:04,000 SOME COLLEAGUES COLLECTED 5012 04:04:04,000 --> 04:04:05,080 EXHALED BREATH CONDENSATE AND 5013 04:04:05,080 --> 04:04:08,720 THEN THEY PERFORM REALTIME PC R 5014 04:04:08,720 --> 04:04:11,320 ON THAT CONDEN SITE AMPLIFYING 5015 04:04:11,320 --> 04:04:14,400 THE GENE OF SARS COV 2 IN ORDER 5016 04:04:14,400 --> 04:04:14,880 TO DIAGNOSE COVID-19. 5017 04:04:14,880 --> 04:04:17,480 ON THE LEFT YOU'RE SEEING A PLOT 5018 04:04:17,480 --> 04:04:22,080 OF THE VIRAL RNA LOAD AND EXHALE 5019 04:04:22,080 --> 04:04:24,120 CONDENSATE AS A LOG TRANSFORM 5020 04:04:24,120 --> 04:04:26,680 ATA AND AS A FUNCTION FROM THE 5021 04:04:26,680 --> 04:04:28,240 DAYS DISEASE ONSET OR SYMPTOM 5022 04:04:28,240 --> 04:04:28,560 ONSET. 5023 04:04:28,560 --> 04:04:30,560 AND ON THE LEFT YOU'RE SEEING 5024 04:04:30,560 --> 04:04:32,320 THE DATA FOR THE WUHAN STRAIN, 5025 04:04:32,320 --> 04:04:34,280 ON THE RIGHT YOU'RE SEEING THE 5026 04:04:34,280 --> 04:04:36,040 DATA FOR THE DELTA STRAIN WHICH 5027 04:04:36,040 --> 04:04:38,480 IS 2 SEPARATE STUDIES THAT ARE 5028 04:04:38,480 --> 04:04:40,200 RECENTLY PUBLISHED IN GENERAL 5029 04:04:40,200 --> 04:04:41,480 BREATH RESEARCH. 5030 04:04:41,480 --> 04:04:43,240 AND WHAT THEY ARE OBSERVING IS 5031 04:04:43,240 --> 04:04:45,240 THAT ON THE LEFT, WE'RE SEEING 5032 04:04:45,240 --> 04:04:48,040 JUST THE DATA FOR PEOPLE WHO ARE 5033 04:04:48,040 --> 04:04:49,080 SPONTANEOUSLY BREATHING, THIS IS 5034 04:04:49,080 --> 04:04:50,680 NOT SHOWING THE VENTILATED 5035 04:04:50,680 --> 04:04:50,880 REGIONS. 5036 04:04:50,880 --> 04:04:53,000 CAN YOU SEE THERE'S A DECREASE 5037 04:04:53,000 --> 04:04:56,440 IN VIRAL LOAD SINCE THE TIME OF 5038 04:04:56,440 --> 04:04:57,920 SYMPTOM ONSET, GENERALLY THE 5039 04:04:57,920 --> 04:05:00,360 SENSITIVITY AT 2 DAYS WAS 86%, 5040 04:05:00,360 --> 04:05:02,240 BUT IT DROPS THEREAFTER, AS THE 5041 04:05:02,240 --> 04:05:04,560 VIRAL LOAD IN THE EXHALE BREATH 5042 04:05:04,560 --> 04:05:06,160 CONDENSATE DROPS BUT THE LOAD 5043 04:05:06,160 --> 04:05:07,040 WAS STRONGLY ASSOCIATE WIDE 5044 04:05:07,040 --> 04:05:08,800 SYMPTOMS AND THE NEED FOR 5045 04:05:08,800 --> 04:05:11,400 VENTILATION IN ALL OF THEIR 5046 04:05:11,400 --> 04:05:11,960 PATIENTS. 5047 04:05:11,960 --> 04:05:14,240 FOR THEIR VENTILATED PATIENTS 5048 04:05:14,240 --> 04:05:16,720 THE RNA DETECTABLE LOAD WILL BE 5049 04:05:16,720 --> 04:05:17,480 HIGH FOR VENTILATION. 5050 04:05:17,480 --> 04:05:20,720 THIS WAS A SMALL PILOT STUDY BUT 5051 04:05:20,720 --> 04:05:22,800 IT WAS REPLICATED IN THE DELTA 5052 04:05:22,800 --> 04:05:25,240 STRAIN, SO IT LOOKS VERY 5053 04:05:25,240 --> 04:05:27,000 PROMISING FOR BEING ABLE TO 5054 04:05:27,000 --> 04:05:27,720 DETECT VIRAL PATHOGENS AND 5055 04:05:27,720 --> 04:05:30,240 ANOTHER SET OF RESEARCHERS, ON, 5056 04:05:30,240 --> 04:05:32,080 A COUPLE YEARS AGO DID A STUDY 5057 04:05:32,080 --> 04:05:34,840 ON PC R IN AN EXHALE BREATH 5058 04:05:34,840 --> 04:05:40,440 CONDENSE 8 TO DETECT BACTERIAL 5059 04:05:40,440 --> 04:05:41,960 PATHOGENS THAT ARE THEY 5060 04:05:41,960 --> 04:05:47,360 DEMONSTRATED THAT IT'S FEASIBLE 5061 04:05:47,360 --> 04:05:49,320 WITH FOLLOW UP WITH LARGER 5062 04:05:49,320 --> 04:05:51,040 SAMPLE SIZES TO DETERMINE THE 5063 04:05:51,040 --> 04:06:00,480 CLINICAL UTILITY. 5064 04:06:00,480 --> 04:06:01,320 NEXT SLIDE. 5065 04:06:01,320 --> 04:06:05,960 MY COLLEAGUES AND I, WE HAVE 5066 04:06:05,960 --> 04:06:13,280 BEEN CONDUCTING A STUDY CALLED 5067 04:06:13,280 --> 04:06:23,840 IMPACT BREATH THAT IS--HOPEFULLY 5068 04:06:26,320 --> 04:06:28,360 YOU'RE ALL SEEING THAT AS WELL, 5069 04:06:28,360 --> 04:06:29,560 THAT'S OBSCURING YOUR VIEW, SO 5070 04:06:29,560 --> 04:06:38,680 IN THIS STUDY, WE ARE 5071 04:06:38,680 --> 04:06:39,520 IDENTIFYING AND VALIDATING. 5072 04:06:39,520 --> 04:06:41,560 >> WE ARE SEEING THAT. 5073 04:06:41,560 --> 04:06:43,000 >> TECHNICAL SERVICES IS RUNNING 5074 04:06:43,000 --> 04:06:53,560 THE SLIDE SO THEY'LL NEED TO FIX 5075 04:06:57,880 --> 04:06:58,040 THAT. 5076 04:06:58,040 --> 04:06:58,440 >> OKAY, GREAT. 5077 04:06:58,440 --> 04:07:00,480 SO IN THE STUDY WE ARE LOOKING 5078 04:07:00,480 --> 04:07:03,560 TO VALIDATE BREATH BIOMARKERS 5079 04:07:03,560 --> 04:07:05,800 FOR DIAGNOSING PSEUDOMOANUS 5080 04:07:05,800 --> 04:07:06,800 POSITIVE VERSUS PSEUDOMOANUS 5081 04:07:06,800 --> 04:07:07,760 NEGATIVE PATIENTS. 5082 04:07:07,760 --> 04:07:10,880 THE OVERALL STUDY DESIGN WAS TO 5083 04:07:10,880 --> 04:07:13,720 ENROLL 288 PERSONS WITH CF FROM 5084 04:07:13,720 --> 04:07:15,080 4 CLINICAL SITES THAT ARE 5085 04:07:15,080 --> 04:07:16,920 PARTNERING WITH US AND WITH HALF 5086 04:07:16,920 --> 04:07:20,880 OF THOSE PEOPLE ENROLLED BEING 5087 04:07:20,880 --> 04:07:22,600 PSEUDOMOANUS POSITIVE IS THE 5088 04:07:22,600 --> 04:07:26,200 GOAL, I WANT TO UNDERSCORE THAT 5089 04:07:26,200 --> 04:07:30,560 OUR DIAGNOSTIC CRITERIA IS THE 5090 04:07:30,560 --> 04:07:32,280 LEAD CHRONIC PROTECTION, 5091 04:07:32,280 --> 04:07:34,640 PSEUDOMOANUS NEGATIVE IS THE 5092 04:07:34,640 --> 04:07:36,960 UNINFECTED OR INFECTED COHORT, 5093 04:07:36,960 --> 04:07:37,840 SO INTERMITTENTLY INFECTED 5094 04:07:37,840 --> 04:07:39,000 INDIVIDUALS ARE EXCLUDED FROM 5095 04:07:39,000 --> 04:07:41,120 THIS STUDY. 5096 04:07:41,120 --> 04:07:42,160 NEXT SLIDE. 5097 04:07:42,160 --> 04:07:44,360 SO IN PRELIMINARY FINDINGS OF 5098 04:07:44,360 --> 04:07:46,560 THIS STUDY, AT THIS POINT WHERE 5099 04:07:46,560 --> 04:07:50,040 WE HAVE A HUNDRED 56 PERSONs 5100 04:07:50,040 --> 04:07:51,880 ENROLLED WE HAVE LOOKED AT THE 5101 04:07:51,880 --> 04:08:02,400 DATA FROM 80 SUBJECTS WE THEN 5102 04:08:13,880 --> 04:08:14,880 TOOK THOSE BIOMARKERS AND 5103 04:08:14,880 --> 04:08:20,400 APPLIED THEM TO DATA FROM AN 5104 04:08:20,400 --> 04:08:22,120 INDEPENDENT DATA SET FROM 76 5105 04:08:22,120 --> 04:08:24,200 SUBJECTS WHERE THE DATA WERE 5106 04:08:24,200 --> 04:08:25,680 ANALYZED OUT OF BRITISH COLUMBIA 5107 04:08:25,680 --> 04:08:27,720 AND WE FIND THAT THE ABOUT I O 5108 04:08:27,720 --> 04:08:32,800 MARKERS IDENTIFIED AT ASU WERE 5109 04:08:32,800 --> 04:08:35,840 GIVING ABOUT 90% SENSITIVITY AND 5110 04:08:35,840 --> 04:08:36,560 SPECIFICITY FOR DIAGNOSING 5111 04:08:36,560 --> 04:08:38,440 PSEUDOMOAN ISOTOPE IN THE 5112 04:08:38,440 --> 04:08:41,520 SUBJECTS WE ANALYZED AT ASU AND 5113 04:08:41,520 --> 04:08:43,560 WHEN WE APPLIED THAT BIOMARKERS 5114 04:08:43,560 --> 04:08:45,000 WE WERE SEEING SIMILAR RESULTS. 5115 04:08:45,000 --> 04:08:48,640 WE HAVE A FOLLOW UP STUDY 5116 04:08:48,640 --> 04:08:51,440 PLANNED FOR THE EARLY DEFEKS 5117 04:08:51,440 --> 04:08:53,480 THEN USING BIOMARKERS SO LOOKING 5118 04:08:53,480 --> 04:08:54,560 AT THOSE INTERMITTENTLY AFFECTED 5119 04:08:54,560 --> 04:08:56,400 SUBJECTS AND ALSO SEEING IF 5120 04:08:56,400 --> 04:09:00,080 THESE BIOMARKERS ARE USEFUL FOR 5121 04:09:00,080 --> 04:09:09,440 MONITORING ANTIBIOTIC TREATMENT. 5122 04:09:09,440 --> 04:09:10,080 NEXT SLIDE. 5123 04:09:10,080 --> 04:09:12,640 >> ANALYZING BREATH CAN BE 5124 04:09:12,640 --> 04:09:16,280 USEFUL FOR MONITORING 5125 04:09:16,280 --> 04:09:18,480 CO-MORBIDITIES AND THERAPIES FOR 5126 04:09:18,480 --> 04:09:21,040 CF, THIS WAS A STUDY WHERE THEY 5127 04:09:21,040 --> 04:09:27,520 LOOKED AT PATIENTS WHO WERE 5128 04:09:27,520 --> 04:09:30,760 RECEIVING LUM ACAFTOR/IVACAFTOR 5129 04:09:30,760 --> 04:09:33,400 TREATMENT OVER 12 MONTHS. 5130 04:09:33,400 --> 04:09:34,920 IN THESE TIME POINTS WHICH 5131 04:09:34,920 --> 04:09:36,080 YOU'RE GOING TO SEE BOTH THE 5132 04:09:36,080 --> 04:09:38,920 LEFT AND THE RIGHT IS THAT 5133 04:09:38,920 --> 04:09:41,200 MEASUREMENT 1 IS BEFORE THE 5134 04:09:41,200 --> 04:09:43,080 THERAPY WAS INITIATED, 5135 04:09:43,080 --> 04:09:46,040 MEASUREMENTS 2-5 WERE COLLECTED 5136 04:09:46,040 --> 04:09:50,440 QUARTERLY AFTER THE START OF 5137 04:09:50,440 --> 04:09:50,960 THERAPY. 5138 04:09:50,960 --> 04:09:52,640 WHAT THEY OBSERVED IS THAT THEY 5139 04:09:52,640 --> 04:09:54,880 SAW SUSTAINED CHANGE IN BREATH 5140 04:09:54,880 --> 04:09:56,280 OF EOCs EVEN THOUGH THERE WAS 5141 04:09:56,280 --> 04:09:57,720 A TEMPORARY CHANGE IN THE MIKE 5142 04:09:57,720 --> 04:10:00,120 ROY BIOME, SO ON THE RIGHT WE'RE 5143 04:10:00,120 --> 04:10:03,160 LOOKING AT THE PSEUDOMOAN 5144 04:10:03,160 --> 04:10:04,240 ISOTOPE DETERMINED FROM 5145 04:10:04,240 --> 04:10:04,960 METAGENOMICS ANALYSIS AND YOU 5146 04:10:04,960 --> 04:10:07,120 CAN SEE THERE'S A DECLINE UP TO 5147 04:10:07,120 --> 04:10:10,160 ABOUT 6 MONTHS AFTER THE START 5148 04:10:10,160 --> 04:10:11,800 OF THERAPY IN GENERAL OVER THE 5149 04:10:11,800 --> 04:10:13,200 POPULATION AND THAT LOW 5150 04:10:13,200 --> 04:10:15,000 REBOUNDS, BUT ON THE LEFT, WE'RE 5151 04:10:15,000 --> 04:10:18,080 LOOKING AT THE PATTERN OF BREATH 5152 04:10:18,080 --> 04:10:22,600 VOCs AND YOU CAN SEE THAT ONCE 5153 04:10:22,600 --> 04:10:24,120 THEY INITTIAITED THERAPY, THEIR 5154 04:10:24,120 --> 04:10:26,560 VOCs HAD A SUSTAINED CHANGE, 5155 04:10:26,560 --> 04:10:28,440 EVEN THOUGH THE MICROBIOME WAS 5156 04:10:28,440 --> 04:10:32,040 SORT OF REBOUNDING TO PRETHERAPY 5157 04:10:32,040 --> 04:10:34,400 LEVELS, AND AN ANALYSIS OF THE 5158 04:10:34,400 --> 04:10:36,080 VOCs THAT WERE DETECTED 5159 04:10:36,080 --> 04:10:39,040 SUGGESTED THESE ARE ACTUALLY 5160 04:10:39,040 --> 04:10:41,240 VOCs RELATED TO HOST 5161 04:10:41,240 --> 04:10:44,200 INFLAMMATION ANDOXIDATIVE STRESS 5162 04:10:44,200 --> 04:10:45,200 PATHWAYS, THEREFORE NOT DIRECTLY 5163 04:10:45,200 --> 04:10:47,840 RELATED TO THE LUNG INFECTIONS. 5164 04:10:47,840 --> 04:10:50,760 SO BREATH, MIGHT ALSO BE USEFUL 5165 04:10:50,760 --> 04:10:53,000 TO MONITOR THE PHYSIOLOGICAL 5166 04:10:53,000 --> 04:10:56,880 RESPONSE TO MODULATOR THERAPY. 5167 04:10:56,880 --> 04:10:57,200 NEXT SLIDE. 5168 04:10:57,200 --> 04:11:00,280 AND THEN THIS IS A STUDY OUT OF 5169 04:11:00,280 --> 04:11:03,720 THE EMORY GROUP TO LOOK AT 5170 04:11:03,720 --> 04:11:05,560 METABOLITE BIOMARKERS OF 5171 04:11:05,560 --> 04:11:06,920 PULMONARY EXACERBATION, IN THIS 5172 04:11:06,920 --> 04:11:10,800 STUDY, THEY HAD COHORTS OF 5173 04:11:10,800 --> 04:11:11,720 EXACERBATED PATIENTS, PATIENTS 5174 04:11:11,720 --> 04:11:13,560 WHO HAVE STABLE LUNG DISEASE, 5175 04:11:13,560 --> 04:11:17,000 AND ALSO PATIENTS WHO ARE IN A 5176 04:11:17,000 --> 04:11:17,560 PREEXACERBATION STATE. 5177 04:11:17,560 --> 04:11:25,880 ON THE LEFT WE SEE THEIR CROSS 5178 04:11:25,880 --> 04:11:27,680 VALIDATED CLASSIFICATION MODEL 5179 04:11:27,680 --> 04:11:29,920 PREDICTION OF ACUTE DISEASE AND 5180 04:11:29,920 --> 04:11:31,680 THE SENSITIVITY AND SPECIFICITY 5181 04:11:31,680 --> 04:11:34,560 FOR THE PEDIATRIC AND ADULT 5182 04:11:34,560 --> 04:11:36,320 COHORTS ON THE BOTTOM LEFT. 5183 04:11:36,320 --> 04:11:39,200 INTERESTINGLY THEY COULD ALSO 5184 04:11:39,200 --> 04:11:43,160 SEE A SIGNATURE FOR 5185 04:11:43,160 --> 04:11:43,960 PREEXACERBATION DISEASE WHICH 5186 04:11:43,960 --> 04:11:46,760 YOU WILL SEE ON THE RIGHT AGAIN 5187 04:11:46,760 --> 04:11:48,280 WAS GOOD WITH SENSITIVITY AND 5188 04:11:48,280 --> 04:11:48,600 SPECIFICITY. 5189 04:11:48,600 --> 04:11:57,240 SO THIS IS SHOWING SOME PROMISE 5190 04:11:57,240 --> 04:11:58,240 AGAIN FOR IDENTIFYING PATIENTS 5191 04:11:58,240 --> 04:12:08,760 WHO ARE AT RISK OF ENTERING INTO 5192 04:12:09,920 --> 04:12:11,000 EXACERBATION STATE. 5193 04:12:11,000 --> 04:12:13,960 AND IN THIS STUDY THIS IS AN 5194 04:12:13,960 --> 04:12:24,520 EXAMPLE OF USING BREATH ANALYSIS 5195 04:12:25,480 --> 04:12:27,000 IN THIS STUDY THEY WERE LOOKING 5196 04:12:27,000 --> 04:12:29,200 AT IEWGING THE ABSORPTION OF 5197 04:12:29,200 --> 04:12:33,200 MIXED TRIGLYCERIDES THAT WERE 5198 04:12:33,200 --> 04:12:34,720 STABLY ISOTOPICALLY LABELED WITH 5199 04:12:34,720 --> 04:12:36,320 CARBON 13 AND WHAT THEY'RE 5200 04:12:36,320 --> 04:12:37,920 MEASURING FOR IS THE ABILITY OF 5201 04:12:37,920 --> 04:12:42,680 THE PATIENT TO ABSORB THOSE 5202 04:12:42,680 --> 04:12:43,520 TRIGLYCERIDES AND TO METABOLIZE 5203 04:12:43,520 --> 04:12:46,520 THEM AND MEASURING THE 5204 04:12:46,520 --> 04:12:54,480 ABSORPTION OF MONITORING THE 5205 04:12:54,480 --> 04:12:55,760 EXHALATION OF THE BREATH TEST TO 5206 04:12:55,760 --> 04:12:58,480 THE GOLD STABBED ARD OF CO 5207 04:12:58,480 --> 04:12:59,440 EFFICIENT OF FAT ABSORPTION AND 5208 04:12:59,440 --> 04:13:02,360 THEY ALSO DID THE SAME THING 5209 04:13:02,360 --> 04:13:05,240 WITH THE FECAL ELAST ACE IN 5210 04:13:05,240 --> 04:13:05,640 THESE SAME SUBJECTS. 5211 04:13:05,640 --> 04:13:07,680 AND THEY SAW THE EQUIVALENT 5212 04:13:07,680 --> 04:13:11,080 AREAS UNDER THE RECEIVER 5213 04:13:11,080 --> 04:13:13,960 OPERATOR CURVE FOR THE FECAL 5214 04:13:13,960 --> 04:13:15,240 ELASTASE, AND SHOWING THAT THE 5215 04:13:15,240 --> 04:13:20,800 BREATH TEST WOULD HAVE THE SAME 5216 04:13:20,800 --> 04:13:21,360 DIAGNOSTIC SENSITIVITY OR 5217 04:13:21,360 --> 04:13:25,000 EFCASEY IN THE CLINIC. 5218 04:13:25,000 --> 04:13:26,800 NEXT SLIDE. 5219 04:13:26,800 --> 04:13:29,160 THANK YOU. 5220 04:13:29,160 --> 04:13:31,800 SO BREATH HAS AMAZING BREADTH, 5221 04:13:31,800 --> 04:13:35,200 IT CAN BE APPLIED TO MANY 5222 04:13:35,200 --> 04:13:37,240 CONDITIONS, CERTAINLY PULMONARY 5223 04:13:37,240 --> 04:13:40,040 CONDITIONS, THAT HAVE BEEN WELL 5224 04:13:40,040 --> 04:13:41,360 DEMONSTRATED, FOR MONITORING 5225 04:13:41,360 --> 04:13:42,680 INFECTIONS, BUT ALSO MONITORING 5226 04:13:42,680 --> 04:13:44,720 TREATMENT AND THERE'S REALLY 5227 04:13:44,720 --> 04:13:48,840 BEAUTIFUL PILOT DATA ON 5228 04:13:48,840 --> 04:13:51,680 MONITORING EABT BI ATTIC THERAPY 5229 04:13:51,680 --> 04:13:52,280 AND LUNG INFECTIONS. 5230 04:13:52,280 --> 04:13:54,320 BREATH IS ALSO USEFUL FOR 5231 04:13:54,320 --> 04:13:57,280 MONITORING EXTRA MULL MONITORARY 5232 04:13:57,280 --> 04:13:58,480 DISEASEs IN HEALTH AND IF 5233 04:13:58,480 --> 04:14:00,760 THERE'S A CONDITION THAT YOU 5234 04:14:00,760 --> 04:14:04,960 THINK MIGHT BENEFIT FROM BREATH 5235 04:14:04,960 --> 04:14:06,880 ANALYSIS AND NOT NECESSARILY IN 5236 04:14:06,880 --> 04:14:09,640 CF, BUT POTENTIALLY IN OTHER 5237 04:14:09,640 --> 04:14:14,360 SIMILAR SORTS OF DISEASES THAT 5238 04:14:14,360 --> 04:14:17,560 WOULD SHOW IT'S POTENTIAL OF 5239 04:14:17,560 --> 04:14:18,080 CLINICAL FEASIBILITY. 5240 04:14:18,080 --> 04:14:18,400 NEXT SLIDE. 5241 04:14:18,400 --> 04:14:20,320 AND I JUST WANT TO HIGHLIGHT 5242 04:14:20,320 --> 04:14:26,280 THAT BREATH ANALYSIS IS MOVING 5243 04:14:26,280 --> 04:14:27,320 CLOSER TOWARDS APPLICATION IN 5244 04:14:27,320 --> 04:14:29,760 THE CLINIC IN APRIL, THE FDA 5245 04:14:29,760 --> 04:14:31,160 ISSUED AN EMERGENCY USE 5246 04:14:31,160 --> 04:14:32,800 AUTHORIZATION FOR THE FIRST 5247 04:14:32,800 --> 04:14:33,840 COVID-19 DIAGNOSTIC BREATH TEST 5248 04:14:33,840 --> 04:14:36,280 AND THESE WERE VOC BREATH TESTS 5249 04:14:36,280 --> 04:14:39,240 AND YOU SEE THIS SUBJECT HERE 5250 04:14:39,240 --> 04:14:43,920 BREATHING INTO A MINIATURIZED 5251 04:14:43,920 --> 04:14:49,600 GC, AND THIS INSPECT IR COVID-19 5252 04:14:49,600 --> 04:14:52,080 BREATHAALIZER HAD A 91 5253 04:14:52,080 --> 04:14:54,240 SENSITIVITY AND 99% SPECIFICITY 5254 04:14:54,240 --> 04:14:54,560 FOR COVID-19. 5255 04:14:54,560 --> 04:14:55,120 NEXT SLIDE. 5256 04:14:55,120 --> 04:15:05,360 LASTLY I WANT TO HIGHLIGHT THAT 5257 04:15:05,360 --> 04:15:06,880 HOME COLLECTION FOR THE FUTURE, 5258 04:15:06,880 --> 04:15:09,560 THERE'S BEEN NICE PILOT STUDIES 5259 04:15:09,560 --> 04:15:12,360 GOING ON FOR THE EXHALE BREATH 5260 04:15:12,360 --> 04:15:14,360 CONDENSATE, THIS IS THE SAMPLE, 5261 04:15:14,360 --> 04:15:15,440 COLLECTING AND THEN RETURNED TO 5262 04:15:15,440 --> 04:15:17,160 THE LAB FOR ANALYSIS BUT DIRECT 5263 04:15:17,160 --> 04:15:18,920 HOME TESTING WHERE YOU BREATHE 5264 04:15:18,920 --> 04:15:20,440 INTO SOMETHING HOOKED UP TO A 5265 04:15:20,440 --> 04:15:22,120 COMPUTER OR A PHONE AT HOME, 5266 04:15:22,120 --> 04:15:23,720 THAT'S A LITTLE FARTHER OUT BUT 5267 04:15:23,720 --> 04:15:26,800 HOME COLLECTION IS DEFINITELY 5268 04:15:26,800 --> 04:15:29,560 FEASIBLE THE NEAR FUTURE. 5269 04:15:29,560 --> 04:15:30,080 NEXT SLIDE. 5270 04:15:30,080 --> 04:15:32,240 AND THIS IS MY LAST SLIDE, I 5271 04:15:32,240 --> 04:15:33,760 WANT TO EYE LIGHT GAPS AND 5272 04:15:33,760 --> 04:15:36,080 OPPORTUNITIES IN IN FIELD. 5273 04:15:36,080 --> 04:15:39,480 SO, WE'VE SEEN FROM COVID-19 5274 04:15:39,480 --> 04:15:41,160 THAT DIRECT DETECTION OF 5275 04:15:41,160 --> 04:15:47,200 MICROBIAL DNA AND RNA FROM EBC 5276 04:15:47,200 --> 04:15:48,040 HAS BEEN DEMONSTRATED AND I 5277 04:15:48,040 --> 04:15:52,800 THINK THE NEXT STEPS WILL BE 5278 04:15:52,800 --> 04:15:55,000 WHAT CLEANLY-MEANINGFUL 5279 04:15:55,000 --> 04:15:56,680 THRESHOLDS WILL BE ESTABLISHED 5280 04:15:56,680 --> 04:15:58,680 FOR CF LUNG DISEASE. 5281 04:15:58,680 --> 04:16:01,160 IDENTIFICATION AND VALIDATION OF 5282 04:16:01,160 --> 04:16:03,240 INFECTION BIOMARKERS IS RELIANT 5283 04:16:03,240 --> 04:16:06,000 UPON ACCESS TO SPUTUM OR LAVAGE. 5284 04:16:06,000 --> 04:16:09,680 WE NEED TO BENCHMARK BIOMARKERS 5285 04:16:09,680 --> 04:16:10,600 AGAINST CURRENTLY ACCEPTED GOLD 5286 04:16:10,600 --> 04:16:12,480 STANDARDS AND WE KNOW WE ARE 5287 04:16:12,480 --> 04:16:14,480 LOSING ACCESS TO THESE 5288 04:16:14,480 --> 04:16:15,600 SPECIMENS, SO LEVERAGING 5289 04:16:15,600 --> 04:16:18,520 EXISTING CF CLINICAL STUDIES 5290 04:16:18,520 --> 04:16:21,520 WOULD BE IDEAL, BREATH SAMPLING 5291 04:16:21,520 --> 04:16:22,520 IS NONINVASIVE AND THEREFORE 5292 04:16:22,520 --> 04:16:23,680 IT'S GENERALLY PRETTY EASY TO 5293 04:16:23,680 --> 04:16:26,720 ADD IT TO AN IRB AND THERE'S 5294 04:16:26,720 --> 04:16:29,640 NOT--THERE'S A LOW BARRIER OR A 5295 04:16:29,640 --> 04:16:34,280 LOW BURDEN FOR PATIENTS TO GIVE 5296 04:16:34,280 --> 04:16:34,960 THAT ADDITIONAL SAMPLE. 5297 04:16:34,960 --> 04:16:36,520 AND WE COULD ALSO CERTAINLY 5298 04:16:36,520 --> 04:16:38,040 STUDY OTHER PATIENTS AND LUNG 5299 04:16:38,040 --> 04:16:43,000 DISEASES SUCH AS PERSONS WITH 5300 04:16:43,000 --> 04:16:45,120 NONCF BRONCH YECTA SIS, THERE'S 5301 04:16:45,120 --> 04:16:47,440 ALSO INTEREST IN NG O AND 5302 04:16:47,440 --> 04:16:48,760 BREATH, BUT CURRENTLY 5303 04:16:48,760 --> 04:16:50,080 GOVERNMENTALLY THE EFFORTS THAT 5304 04:16:50,080 --> 04:16:52,880 ARE FRAGMENTED AND SILOED SO 5305 04:16:52,880 --> 04:16:53,560 INTERAGENCY GOVERNMENTAL 5306 04:16:53,560 --> 04:16:54,160 COLLABORATION WOULD CERTAINLY 5307 04:16:54,160 --> 04:16:56,360 SPEED PROGRESS IN THAT AREA. 5308 04:16:56,360 --> 04:16:59,560 AND THAT'S IT FOR ME. 5309 04:16:59,560 --> 04:17:02,960 I WANT TO NOW TEE UP A 5310 04:17:02,960 --> 04:17:04,280 PRESENTATION FROM DR. NATALIE 5311 04:17:04,280 --> 04:17:06,040 ELLIOTT WEST WHO IS AN ASSISTANT 5312 04:17:06,040 --> 04:17:09,080 PROFESSOR OF MEDICINE AT JOHNS 5313 04:17:09,080 --> 04:17:09,920 HOPKINS UNIVERSITY IS AND SHE'S 5314 04:17:09,920 --> 04:17:12,800 GOING TO BE TELLING US ABOUT 5315 04:17:12,800 --> 04:17:23,320 PULMONARY EXACERBATIONS IN THE 5316 04:17:40,880 --> 04:17:41,400 AREA OF HEMT. 5317 04:17:41,400 --> 04:17:42,760 >> GOOD AFTERNOON MY NAME IS 5318 04:17:42,760 --> 04:17:46,800 NATALIE WEST AND I WILL DISCUSS 5319 04:17:46,800 --> 04:17:48,680 PULMONARY EXACERBATIONS IN THE 5320 04:17:48,680 --> 04:17:50,720 HEMT ERA, I WOULD LIKE TO THANK 5321 04:17:50,720 --> 04:17:55,480 THE NIH FOR RECORDING THIS 5322 04:17:55,480 --> 04:17:56,800 PRESENTATION IN ADVANCE AS I 5323 04:17:56,800 --> 04:17:59,320 WILL BE AWAY AT A FAMILY FUNERAL 5324 04:17:59,320 --> 04:18:00,400 DURING THIS TALK. 5325 04:18:00,400 --> 04:18:01,960 I CURRENTLY HAVE SEVERAL GRANTS 5326 04:18:01,960 --> 04:18:07,760 AREYALATED TO RESEARCH AND 5327 04:18:07,760 --> 04:18:11,200 PULMONARY EXACERBATIONS THROUGH 5328 04:18:11,200 --> 04:18:12,760 THE CYSTIC FIBROSIS FOUNDATION, 5329 04:18:12,760 --> 04:18:13,520 WE WILL DISCIPLINARY CUSS WHAT 5330 04:18:13,520 --> 04:18:18,360 WE KNOW ABOUT HIGHLY EFFECTIVE 5331 04:18:18,360 --> 04:18:21,080 MODULATOR THERAPY, AFFECTS OF 5332 04:18:21,080 --> 04:18:22,200 PULMONARY EXACERBATIONS, GAPS 5333 04:18:22,200 --> 04:18:23,280 AND KNOWLEDGE, OPPORTUNITIES TO 5334 04:18:23,280 --> 04:18:24,240 LEARN MORE AND 2 CLINICAL TRIALS 5335 04:18:24,240 --> 04:18:25,400 THAT ARE ONGOING TO HELP US 5336 04:18:25,400 --> 04:18:28,680 ANSWER SOME OF THESE QUESTIONS. 5337 04:18:28,680 --> 04:18:30,720 SO WHAT DO WE KNOW ABOUT 5338 04:18:30,720 --> 04:18:31,040 EXACERBATION. 5339 04:18:31,040 --> 04:18:33,200 WE'VE KNOWN FOR A LONG TIME THEY 5340 04:18:33,200 --> 04:18:34,160 HAVE OCCURRED FREQUENTLY IN THE 5341 04:18:34,160 --> 04:18:37,800 LIVES OF PEOPLE WITH CF. 5342 04:18:37,800 --> 04:18:39,640 THEY'RE ASSOCIATE WIDE WORSE 5343 04:18:39,640 --> 04:18:42,240 OUTCOMES, LOSS OF LUNG FUNCTION, 5344 04:18:42,240 --> 04:18:43,880 INCREASE IN RESPIRATORY 5345 04:18:43,880 --> 04:18:45,920 SYMPTOMS, WORSE QUALITY OF LIFE 5346 04:18:45,920 --> 04:18:48,360 AND EVEN SHORTENED LIFE 5347 04:18:48,360 --> 04:18:48,640 SURVILAL. 5348 04:18:48,640 --> 04:18:50,400 THERE'S CURRENTLY NOT A WIDELY 5349 04:18:50,400 --> 04:18:51,320 ACCEPTED DEFINITION OF 5350 04:18:51,320 --> 04:18:51,920 EXACERBATION BUT GENERALLY WE 5351 04:18:51,920 --> 04:18:54,240 THINK OF THEM IN PARTICULAR 5352 04:18:54,240 --> 04:18:56,000 SEVERE EXACERBATION AS INCREASED 5353 04:18:56,000 --> 04:18:58,960 SYMPTOMS AND/OR DECREASE LUNG 5354 04:18:58,960 --> 04:19:00,600 FUNCTIONS COUPLED WITH THE 5355 04:19:00,600 --> 04:19:03,000 DECISION TO TREAT WITH THE 5356 04:19:03,000 --> 04:19:04,040 ANTIBODY. 5357 04:19:04,040 --> 04:19:06,200 SO WE DO HAVE GUIDELINES FOR 5358 04:19:06,200 --> 04:19:08,400 TREATMENT OF EXACERBATIONS WHICH 5359 04:19:08,400 --> 04:19:10,960 WERE ESTABLISHED IN 2009BIAN 5360 04:19:10,960 --> 04:19:11,280 EXPERT PANEL. 5361 04:19:11,280 --> 04:19:13,240 AND WHAT THE EXPERTS REALLY HAD 5362 04:19:13,240 --> 04:19:16,720 GENERAL AGREEMENT ON IS THAT 5363 04:19:16,720 --> 04:19:18,800 DURING EXACERBATION WE SHOULD BE 5364 04:19:18,800 --> 04:19:19,640 CONTINUING CHRONIC MEDICATIONS 5365 04:19:19,640 --> 04:19:21,120 AND AIR WAY CLEARANCE. 5366 04:19:21,120 --> 04:19:22,320 HOWEVER, AT THE TIME THERE WAS 5367 04:19:22,320 --> 04:19:23,720 NOT A LET OF THE EVIDENCE TO 5368 04:19:23,720 --> 04:19:28,360 GUIDE US ON DURATION OF IV 5369 04:19:28,360 --> 04:19:29,040 ANTIBIOTICS, TREATMENT WHETHER 5370 04:19:29,040 --> 04:19:31,520 AT HOME OR IN THE HOSPITAL, THE 5371 04:19:31,520 --> 04:19:33,840 ROLE OF INHALED ANTIBIOTICS, THE 5372 04:19:33,840 --> 04:19:35,000 NUMBER OF ANTIBIOTICS WE SHOULD 5373 04:19:35,000 --> 04:19:37,120 USE AND THE DOSING OF EACH OF 5374 04:19:37,120 --> 04:19:42,720 THOSE EABT BIOTICS AND HOW 5375 04:19:42,720 --> 04:19:49,920 COTTERY CO STEROIDS EXACERBATES 5376 04:19:49,920 --> 04:19:52,240 AND GENERALLY FOR MILD 5377 04:19:52,240 --> 04:19:53,680 EXACERBATION WE USE MILD 5378 04:19:53,680 --> 04:19:56,080 ANTIBIOTICS AND/OR SEVERE, THAT 5379 04:19:56,080 --> 04:19:57,760 MAY REQUIRE HOSPITALIZATION. 5380 04:19:57,760 --> 04:19:59,400 SO'RESHORTLY AFTER THESE 5381 04:19:59,400 --> 04:20:01,240 GUIDELINES WERE PUBLISHED THE CF 5382 04:20:01,240 --> 04:20:02,400 FOUNDATION SUNNEDDED AND 5383 04:20:02,400 --> 04:20:05,160 SUPPORTED A STOP PROGRAM, 5384 04:20:05,160 --> 04:20:06,720 STANDARDIZE TREATMENT OF 5385 04:20:06,720 --> 04:20:07,360 PULMONARY EXACERBATION WHICH I'M 5386 04:20:07,360 --> 04:20:09,400 A PART OF AND WE ARE TASKED TO 5387 04:20:09,400 --> 04:20:11,520 DESIGN AND CONDUCT CLINICAL 5388 04:20:11,520 --> 04:20:12,600 TRIALS, TO PROVIDE ECHEDZ TO 5389 04:20:12,600 --> 04:20:13,920 START ANSWERING SOME OF THESE 5390 04:20:13,920 --> 04:20:17,360 QUESTIONS WE JUST DISCUSSED. 5391 04:20:17,360 --> 04:20:22,080 SO THE FIRST THING WE DID WAS 5392 04:20:22,080 --> 04:20:24,480 STOP AND THAT WAS ABOUT 220 5393 04:20:24,480 --> 04:20:26,040 PATIENTS WHO HAD BEEN ADMITTED 5394 04:20:26,040 --> 04:20:29,000 TO THE HOSPITAL NEEDING IV 5395 04:20:29,000 --> 04:20:30,320 ANTIBIOTIC THERAPY FOR THEIR 5396 04:20:30,320 --> 04:20:31,600 EXACERBATION, AND WE COLLECTED A 5397 04:20:31,600 --> 04:20:34,680 LOT OF DAT AND WE USE THAD DATA 5398 04:20:34,680 --> 04:20:36,160 TO DESIGN THE FIRST RANDOMIZED 5399 04:20:36,160 --> 04:20:37,960 CONTROL TRIAL WHICH WE CALL STOP 5400 04:20:37,960 --> 04:20:40,160 2 AND WE EVALUATED THE EFFICACY 5401 04:20:40,160 --> 04:20:44,040 AND SAFETY OF DIFFERENT 5402 04:20:44,040 --> 04:20:46,480 DURATIONS OF IV ANTIBIOTIC 5403 04:20:46,480 --> 04:20:48,360 THERAPY FOR EXACERBATIONS IN 5404 04:20:48,360 --> 04:20:50,440 ADULTS WITH CF, IT WAS 5405 04:20:50,440 --> 04:20:55,640 RANDOMIZED AND CONTROL AND IT 5406 04:20:55,640 --> 04:20:56,120 WAS OPEN LABELED. 5407 04:20:56,120 --> 04:20:57,640 AND I WILL WALK YOU THROUGH OUR 5408 04:20:57,640 --> 04:21:00,480 PROTOCOL HERE AND SO, ON THE LOW 5409 04:21:00,480 --> 04:21:02,880 OF THE SCREEN, YOU WILL SEE THE 5410 04:21:02,880 --> 04:21:06,200 DAYS LISTED, SO ON DAYS 0, A TON 5411 04:21:06,200 --> 04:21:07,520 OF EXACERBATION OUR PARTICIPANTS 5412 04:21:07,520 --> 04:21:10,320 WERE ENROLLED AND AT THAT POINT 5413 04:21:10,320 --> 04:21:12,080 WE MEASURED LUNG FUNCTION FEV1 5414 04:21:12,080 --> 04:21:17,440 AND WE MEASURED A SYMPTOM SCORE 5415 04:21:17,440 --> 04:21:19,440 CALLED THE CRISSAND WE REPEATED 5416 04:21:19,440 --> 04:21:22,240 THESE BETWEEN DAY 7-10. 5417 04:21:22,240 --> 04:21:25,440 AND IF PARTICIPANTS HAD AN 5418 04:21:25,440 --> 04:21:27,440 IMPROVEMENT IN 8%, AND 5419 04:21:27,440 --> 04:21:30,560 IMPROVEMENT IN THE CRISSOR 5420 04:21:30,560 --> 04:21:31,960 SYMPTOM SCORE BY 11-POINTS SO 5421 04:21:31,960 --> 04:21:34,040 THEY WERE FEELING BETTER, THEN 5422 04:21:34,040 --> 04:21:36,840 WE DEEMED THEM EARLY ROBUST 5423 04:21:36,840 --> 04:21:37,360 RESPONDER. 5424 04:21:37,360 --> 04:21:38,520 E. R. R. 5425 04:21:38,520 --> 04:21:40,320 AND THAT POINT ANYWHERE BETWEEN 5426 04:21:40,320 --> 04:21:43,480 DAY 7 AND 10 THEY RANDOMIZED 10 5427 04:21:43,480 --> 04:21:45,560 VERSUS 14 DAYS. 5428 04:21:45,560 --> 04:21:47,800 AND OUR HYPOTHESIS FOR THIS ARM 5429 04:21:47,800 --> 04:21:49,520 WAS THAT 10 DAYS WAS NOT 5430 04:21:49,520 --> 04:21:51,080 INFERIOR TO 14 DAYS. 5431 04:21:51,080 --> 04:21:52,600 IF PARTICIPANTS DID NOT MEET 5432 04:21:52,600 --> 04:21:54,160 BOTH OF THOSE CRITERIA, THEY 5433 04:21:54,160 --> 04:21:57,720 WERE DEEMED A NONEARLY ROBUST 5434 04:21:57,720 --> 04:21:59,560 RESPONDER AND NERR, AT THAT 5435 04:21:59,560 --> 04:22:02,480 POINT DAY 7-10 RANDOMIZE TO 5436 04:22:02,480 --> 04:22:04,080 EITHER 14 VERSUS 21 DAYS. 5437 04:22:04,080 --> 04:22:06,480 AND OUR HYPOTHESIS HERE WAS THAT 5438 04:22:06,480 --> 04:22:12,000 21 DAYS IS SUPERIOR TO 14 DAYS. 5439 04:22:12,000 --> 04:22:15,160 AND THEN VISIT 3 OCCURRED 14 5440 04:22:15,160 --> 04:22:17,200 DAYS AFTER ANTIBIOTIC THERAPY. 5441 04:22:17,200 --> 04:22:20,080 AND SO HERE'S OUR TOP LINE 5442 04:22:20,080 --> 04:22:23,000 RESULTS ON THE X-AXIS YOU SEE AS 5443 04:22:23,000 --> 04:22:25,000 FROM THE IV ANTIBIOTIC START AND 5444 04:22:25,000 --> 04:22:27,440 ON THE Y-AXIS YOU SEE THE 5445 04:22:27,440 --> 04:22:28,840 PERCENT PREDICTED AND YOU CAN 5446 04:22:28,840 --> 04:22:30,280 SEE STARTING ON DAY 0 EXPW LET'S 5447 04:22:30,280 --> 04:22:32,440 LOOK AT THE E. R. R.OT FIRST. 5448 04:22:32,440 --> 04:22:35,720 THERE WAS AN IMPROVEMENT THAT AT 5449 04:22:35,720 --> 04:22:37,160 LEAST WITH 8% BY CRITERIA IN 5450 04:22:37,160 --> 04:22:39,720 ORDER TO BE IN THE E. R. R. PLUS 5451 04:22:39,720 --> 04:22:41,480 THE PROVEN SYMPTOMS AND THEN YOU 5452 04:22:41,480 --> 04:22:42,840 SEE THERE'S REALLY NO DIFFERENCE 5453 04:22:42,840 --> 04:22:44,520 BETWEEN THE 10 DAY ARM, WHICH IS 5454 04:22:44,520 --> 04:22:48,560 HERE IN GRAY, AND THE BLACK 14 5455 04:22:48,560 --> 04:22:54,520 DAY ARM AND INDEED THERE WAS NO 5456 04:22:54,520 --> 04:22:55,000 STATISTICAL SIGNIFICANT 5457 04:22:55,000 --> 04:22:58,080 DIFFERENCE SO WE CONCLUDED THAT 5458 04:22:58,080 --> 04:23:01,280 10 DAYS WAS NOT NEAR 14 AND DOWN 5459 04:23:01,280 --> 04:23:02,760 BELOW IS THE NONEARLY ROBUST 5460 04:23:02,760 --> 04:23:04,800 RESPONDER ARM AND YOU CAN SEE 5461 04:23:04,800 --> 04:23:06,240 THEY'RE ALMOST IDENTICAL AND 5462 04:23:06,240 --> 04:23:08,560 HERE WE CONCLUDED 21 DAYS WAS 5463 04:23:08,560 --> 04:23:09,280 NOT SUPERIOR TO 14. 5464 04:23:09,280 --> 04:23:13,360 AND SO HERE WHAT WE INCLUDED 5465 04:23:13,360 --> 04:23:14,200 FROM RESEARCH PURPOSES IS THAT 5466 04:23:14,200 --> 04:23:17,440 WE CAN USE A 14 DAY STANDARDIZED 5467 04:23:17,440 --> 04:23:19,320 DURATION IN ORDER TO START 5468 04:23:19,320 --> 04:23:20,720 ANSWERING ADDITIONAL QUESTIONS 5469 04:23:20,720 --> 04:23:24,040 IN PULL MANORY EXACERBATION. 5470 04:23:24,040 --> 04:23:26,520 SO WHAT DO WE KNOW ABOUT HIGHLY 5471 04:23:26,520 --> 04:23:29,480 EFFECTIVE MODULATOR THERAPY AND 5472 04:23:29,480 --> 04:23:29,880 INVESTOR RELATION? 5473 04:23:29,880 --> 04:23:31,280 SO THIS WAS GREAT, THIS WAS A 5474 04:23:31,280 --> 04:23:33,960 PICTURE FROM BACK IN 2018 WHEN 5475 04:23:33,960 --> 04:23:37,480 FDA APPROVED THE NEW BREAK 5476 04:23:37,480 --> 04:23:43,840 THROUGH THERAPY PARTICULARLY 5477 04:23:43,840 --> 04:23:45,320 TRIFACTA, AND IVACAFTA, APPROVED 5478 04:23:45,320 --> 04:23:47,760 FOR 90% OF OUR PATIENTS WITH CF, 5479 04:23:47,760 --> 04:23:49,120 SO LET'S REWIND A BIT AND GO 5480 04:23:49,120 --> 04:23:52,720 BACK TO THE CLINICAL TRIAL FIRST 5481 04:23:52,720 --> 04:23:57,120 OF IVACAFTOR, AND THAT'S ALSOA 5482 04:23:57,120 --> 04:23:57,760 HIGHLY EFFECTIVE MODULATOR 5483 04:23:57,760 --> 04:23:58,640 THERAPY AND THIS DESCRIBED FROM 5484 04:23:58,640 --> 04:24:00,160 THE CLIENICAL TRIAL AND 5485 04:24:00,160 --> 04:24:02,280 LOOKINGAL DECREASE IN RATE OF 5486 04:24:02,280 --> 04:24:03,000 EXACERBATION OVER THE 6 MONTH 5487 04:24:03,000 --> 04:24:05,200 TIME TOWARD AND SO ON THE Y-AXIS 5488 04:24:05,200 --> 04:24:06,600 YOU SEE THE PROPORTION OF EVENTS 5489 04:24:06,600 --> 04:24:09,320 SO THOSE THAT DID NOT HAVE AN 5490 04:24:09,320 --> 04:24:11,960 EXACERBATION AND YOU CAN SEE 5491 04:24:11,960 --> 04:24:12,760 THIS CLEAR STATISTICAL 5492 04:24:12,760 --> 04:24:13,120 DIFFERENCE. 5493 04:24:13,120 --> 04:24:17,480 IT WAS ALMOST A 50/60% DROP IN 5494 04:24:17,480 --> 04:24:19,080 EXACERBATION, AND SHOWN 5495 04:24:19,080 --> 04:24:21,600 DIFFERENTLY IN THE CAFTOR 5496 04:24:21,600 --> 04:24:24,120 TRIALS, BUT LOOKING HERE WE SEE 5497 04:24:24,120 --> 04:24:26,800 THE REDUCTION OF ALL 5498 04:24:26,800 --> 04:24:29,200 EXACERBATION WAS 63% AND THEN 5499 04:24:29,200 --> 04:24:31,320 VERY DRAMATIC REDUCTIONS IN 5500 04:24:31,320 --> 04:24:33,560 THOSE EXACERBATIONS THAT LED TO 5501 04:24:33,560 --> 04:24:34,240 HOSPITALIZATIONS OR THOSE 5502 04:24:34,240 --> 04:24:38,280 NEEDING TO BE TREATING WITH IV 5503 04:24:38,280 --> 04:24:38,640 ANTIBIOTICS. 5504 04:24:38,640 --> 04:24:40,000 AND HERE WE REALLY SEE, THIS IS 5505 04:24:40,000 --> 04:24:41,280 GOING TO BE KIND OF IMPORTANT TO 5506 04:24:41,280 --> 04:24:44,560 THE GAPS WE HAVE IN OUR 5507 04:24:44,560 --> 04:24:47,280 QUESTIONS IS IN 202,020, THE 5508 04:24:47,280 --> 04:24:49,280 DRAMATIC INCREASE THAT WERE 5509 04:24:49,280 --> 04:24:50,200 ELIGIBLE FOR MODULATORS THAT 5510 04:24:50,200 --> 04:24:54,200 WERE ON THEM SO ABOUT 86% OF 5511 04:24:54,200 --> 04:24:57,040 2020 WERE ON MODULATORS THAT 5512 04:24:57,040 --> 04:24:57,360 WERE ELIGIBLE. 5513 04:24:57,360 --> 04:25:01,560 SO WHAT ARE THE GAPS IN 5514 04:25:01,560 --> 04:25:01,880 KNOWLEDGE? 5515 04:25:01,880 --> 04:25:06,800 SO WHAT IS THE TRUE PULMONARY 5516 04:25:06,800 --> 04:25:09,840 EXACERBATION RATE IN PEOPLE WITH 5517 04:25:09,840 --> 04:25:10,400 CF ON HEMT? 5518 04:25:10,400 --> 04:25:12,000 I JUST SHOWED YOU IN A CLINICAL 5519 04:25:12,000 --> 04:25:14,360 TRIAL BUT NOW IN A MUCH BROADER 5520 04:25:14,360 --> 04:25:16,760 GENERAL POPULATION, WHAT IS THE 5521 04:25:16,760 --> 04:25:17,480 TRUE EXACERBATION RATE? 5522 04:25:17,480 --> 04:25:21,040 AND THEN WE'RE USED TO SEEING 5523 04:25:21,040 --> 04:25:23,600 BIG LUNG FUNCTION DROP DURING 5524 04:25:23,600 --> 04:25:25,880 EXACERBATION IN THE PREHEMT ERA, 5525 04:25:25,880 --> 04:25:27,680 IT'S NOW THAT EVERYONE'S ON, 5526 04:25:27,680 --> 04:25:29,920 MOST PEOPLE ARE ON HIGHLY 5527 04:25:29,920 --> 04:25:31,600 EFFECTIVE MODULATOR THERAPY IS 5528 04:25:31,600 --> 04:25:34,040 THAT LUNG FUNCTION THE SAME WHEN 5529 04:25:34,040 --> 04:25:34,840 WE'RE DIAGNOSING EXACERBATIONS 5530 04:25:34,840 --> 04:25:36,360 OR ARE THEY DIFFERENT? 5531 04:25:36,360 --> 04:25:38,960 AND THEN HOW ARE OUR PATIENTS 5532 04:25:38,960 --> 04:25:39,280 PRESENTING? 5533 04:25:39,280 --> 04:25:43,720 HAS THE CLINICAL PRESENTATION 5534 04:25:43,720 --> 04:25:44,200 CHANGED? 5535 04:25:44,200 --> 04:25:46,480 WE'RE USED TO SEE SPUTUM 5536 04:25:46,480 --> 04:25:47,560 PRACTICES DUKS, COUGH, WEIGHT 5537 04:25:47,560 --> 04:25:51,800 LOSS, HAS THAT CHANGED OR THE 5538 04:25:51,800 --> 04:25:52,880 PRESENTATION DIFFERENT? 5539 04:25:52,880 --> 04:25:54,240 AND WHAT DOES LUNG FUNCTION 5540 04:25:54,240 --> 04:25:56,480 RECOVERY LOOK LIKE, WE KNOW THAT 5541 04:25:56,480 --> 04:25:59,360 EXACERBATIONS LEAD TO PERMANENT 5542 04:25:59,360 --> 04:26:00,880 LUNG FUNCTION LOSS BEFORE MOST 5543 04:26:00,880 --> 04:26:04,160 OUR PATIENTS WERE ON HIGHLY 5544 04:26:04,160 --> 04:26:05,560 EFFECTIVE MODULATOR THERAPY. 5545 04:26:05,560 --> 04:26:06,240 HAS THAT CHANGED? 5546 04:26:06,240 --> 04:26:08,160 AND HOW SHOULD WE BE TREATING 5547 04:26:08,160 --> 04:26:09,200 EXACERBATIONS AND PEOPLE ON CF 5548 04:26:09,200 --> 04:26:11,360 WHO ARE ON HIGHLY EFFECTIVE 5549 04:26:11,360 --> 04:26:12,560 MODULATOR THERAPY SHOULD WE 5550 04:26:12,560 --> 04:26:14,080 REALLY BE TREATING AS 5551 04:26:14,080 --> 04:26:16,440 AGGRESSIVELY WITH IV ANTIBIOTIC 5552 04:26:16,440 --> 04:26:18,920 THERAPY, OR ORAL ANTIBIOTICS BE 5553 04:26:18,920 --> 04:26:19,200 SUFFICIENT? 5554 04:26:19,200 --> 04:26:24,040 SO HERE'S THE GAPS WE DON'T KNOW 5555 04:26:24,040 --> 04:26:24,600 THE ANSWERS TO. 5556 04:26:24,600 --> 04:26:27,400 BUT WE DO HAVE SOME HINTS TO THE 5557 04:26:27,400 --> 04:26:28,360 ANSWERS. 5558 04:26:28,360 --> 04:26:31,480 SO THIS IS FROM THE CF 5559 04:26:31,480 --> 04:26:32,800 FOUNDATION PATIENT REGISTRY, 5560 04:26:32,800 --> 04:26:35,040 PUBLISH INDEED 2021, BUT ONLY 5561 04:26:35,040 --> 04:26:36,560 THAT INCLUDES DAILY BASIS THEA 5562 04:26:36,560 --> 04:26:36,960 UP TO 2020. 5563 04:26:36,960 --> 04:26:39,880 AND THIS IS LOOKING ON THE 5564 04:26:39,880 --> 04:26:43,600 X-AXIS FROM THIS YEAR FROM 5565 04:26:43,600 --> 04:26:44,760 2006-2020 AND THE PERCENT OF 5566 04:26:44,760 --> 04:26:47,440 INDIVIDUALS WHO WERE TREATED 5567 04:26:47,440 --> 04:26:49,360 WITH IV ANTIBIOTICS FOR 5568 04:26:49,360 --> 04:26:52,120 PULMONARY EXACERBATION, AND THEN 5569 04:26:52,120 --> 04:26:53,800 IN ORANGE IS OUR CHILDREN AND 5570 04:26:53,800 --> 04:26:55,360 GREEN IS ADLEASENTS AND BLUES 5571 04:26:55,360 --> 04:26:57,280 ARE ADULTS, CAN YOU SEE THERE 5572 04:26:57,280 --> 04:27:00,320 WAS DRAMATIC DROP AT THE END OF 5573 04:27:00,320 --> 04:27:02,200 2019 AND 2020 AND THAT CO 5574 04:27:02,200 --> 04:27:04,680 INSIDES WHEN OUR PATIENTS GOT ON 5575 04:27:04,680 --> 04:27:07,400 HIGHEE EFFECTIVE MODULATOR 5576 04:27:07,400 --> 04:27:09,720 THERAPY. 5577 04:27:09,720 --> 04:27:12,320 ANDEE WE LOOKED AT STOP 2, SO 5578 04:27:12,320 --> 04:27:13,400 STOP 2 WAS ALMOST A THOUSAND 5579 04:27:13,400 --> 04:27:15,640 PATIENT WHO IS HAD AN 5580 04:27:15,640 --> 04:27:16,720 EXACERBATION SO LARGE CLINICAL 5581 04:27:16,720 --> 04:27:18,440 TRIAL FOR OUR CF COMMUNITY, AND 5582 04:27:18,440 --> 04:27:20,200 WE LOOKED AT WHAT LUNG FUNCTION 5583 04:27:20,200 --> 04:27:22,440 WAS DOING IN THOSE THAT WERE ON 5584 04:27:22,440 --> 04:27:23,720 MODULATORS AND THOSE THAT WERE 5585 04:27:23,720 --> 04:27:24,560 NOT. 5586 04:27:24,560 --> 04:27:26,440 I WANT TO CLARIFY THOUGH, STOP 5587 04:27:26,440 --> 04:27:29,040 2, THE CLINICAL TRIAL ENDED IN 5588 04:27:29,040 --> 04:27:35,680 EARLY 2019 SO THIS WAS BEFORE 5589 04:27:35,680 --> 04:27:37,080 THE CAFTOR THERAPIES WERE 5590 04:27:37,080 --> 04:27:37,360 APPROVED. 5591 04:27:37,360 --> 04:27:39,280 SO WE LOOKING AT THE 6 MONTH 5592 04:27:39,280 --> 04:27:41,800 AVERAGE BEFORE THE EXACERBATION 5593 04:27:41,800 --> 04:27:44,560 COMPARED TO WHAT THE FEV1 WAS AT 5594 04:27:44,560 --> 04:27:46,720 THE TIME OF THE EXACERBATION AND 5595 04:27:46,720 --> 04:27:49,040 WE COMPARED THE GROUPS, THOSE 5596 04:27:49,040 --> 04:27:51,760 THAT WERE MODULATORS AND THOSE 5597 04:27:51,760 --> 04:27:52,360 THAT WERE NOT. 5598 04:27:52,360 --> 04:27:53,760 THERE WAS NO STATISTICAL 5599 04:27:53,760 --> 04:27:54,920 DIFFERENCE BETWEEN THE 2. 5600 04:27:54,920 --> 04:27:59,400 IN FACT IT WAS 8.1% PREDICTED 5601 04:27:59,400 --> 04:27:59,720 DIFFERENCE. 5602 04:27:59,720 --> 04:28:02,120 HOWEVER WE DID SEE A DIFFERENCE 5603 04:28:02,120 --> 04:28:03,320 IN HOW PATIENTS FELT. 5604 04:28:03,320 --> 04:28:05,920 SO IN THE CRISS SCORE, THE SIGNS 5605 04:28:05,920 --> 04:28:07,840 AND SIVENL TOMS AT PRESENTATION, 5606 04:28:07,840 --> 04:28:09,800 SO LOOKINGA THE CRISS SCORE 5607 04:28:09,800 --> 04:28:12,680 THERE WAS A DIFFERENCE THAT WAS 5608 04:28:12,680 --> 04:28:13,800 STATISTICALLY SIGNIFICANT AND 5609 04:28:13,800 --> 04:28:15,760 THOSE NOT ON MODULATORS ACTUALLY 5610 04:28:15,760 --> 04:28:18,440 FELT WORSE AT THE BEGINNING OF 5611 04:28:18,440 --> 04:28:19,280 THE EXACERBATION COMPARED TO 5612 04:28:19,280 --> 04:28:22,360 THOSE THAT WERE ON MODULATORS. 5613 04:28:22,360 --> 04:28:24,480 AND THEN LOOKING AT LUNG 5614 04:28:24,480 --> 04:28:27,120 FUNCTION RECOVERY, SO THIS 5615 04:28:27,120 --> 04:28:29,600 GROUP, ANALYZED THE IVACAFTOR 5616 04:28:29,600 --> 04:28:31,640 TRIALS IN THOSE PATIENTS IN G551 5617 04:28:31,640 --> 04:28:33,640 D SO THIS WAS 1 ABOUT 160 5618 04:28:33,640 --> 04:28:35,640 PATIENTS OR SO AND LOOKEDDA THE 5619 04:28:35,640 --> 04:28:37,160 THOSE THAT HAD EXACERBATION SO 5620 04:28:37,160 --> 04:28:42,360 WHILE WE KNOW THAT THE IVACAFTOR 5621 04:28:42,360 --> 04:28:43,480 TREATMENT GREATLY REDUCED 5622 04:28:43,480 --> 04:28:44,520 EXACERBATION, THEY LOOKEDDA THE 5623 04:28:44,520 --> 04:28:46,480 LONG-TERM RECOVERY WHICH WAS 5624 04:28:46,480 --> 04:28:50,320 DEFINED AS WHAT THE LUNG 5625 04:28:50,320 --> 04:28:52,520 FUNCTION WAS LOOKING AT THE END 5626 04:28:52,520 --> 04:28:53,600 OF THE 6 MONTH CLINICAL TRIAL 5627 04:28:53,600 --> 04:28:55,160 AND LOOKING AT SHORT-TERM 5628 04:28:55,160 --> 04:28:55,920 RECOVERY SOPHISTICATEDY ANYWHERE 5629 04:28:55,920 --> 04:28:59,320 BETWEEN 2 AND 8 WEEKS FOR 5630 04:28:59,320 --> 04:28:59,960 TREATMENT DURING EXACERBATION 5631 04:28:59,960 --> 04:29:02,080 AND THERE WAS NO DIFFERENT IN 5632 04:29:02,080 --> 04:29:10,240 LUNG FUNCTION RECOVER EXPE FROM 5633 04:29:10,240 --> 04:29:11,440 THOSE EXACERBATION, WHEN WE 5634 04:29:11,440 --> 04:29:14,200 LOOKED AT STOP 2 IT SHOWED MORE 5635 04:29:14,200 --> 04:29:14,440 RESULTS. 5636 04:29:14,440 --> 04:29:17,080 SO WHAT ARE OUR OPPORTUNITIES? 5637 04:29:17,080 --> 04:29:18,240 SO OUR EXACERBATION IN PEOPLE 5638 04:29:18,240 --> 04:29:20,400 WITH CF WHO ARE ON HIGHLY 5639 04:29:20,400 --> 04:29:21,240 EFFECTIVE MODULATOR THERAPY ARE 5640 04:29:21,240 --> 04:29:26,400 THEY MORE SIMILAR TO THOSE WITH 5641 04:29:26,400 --> 04:29:28,280 NONCF BRONCH ECTOMYOSIN SIS AND 5642 04:29:28,280 --> 04:29:29,640 I THINK THERE'S AN OPPORTUNITY 5643 04:29:29,640 --> 04:29:30,960 ACROSS THESE 2 DISEASE STATES IN 5644 04:29:30,960 --> 04:29:32,760 ORDER TO BOOST NUMBERS AND TRY 5645 04:29:32,760 --> 04:29:35,760 TO COME UP WITH AN ANSWER TO 5646 04:29:35,760 --> 04:29:36,000 THAT. 5647 04:29:36,000 --> 04:29:37,720 THERE'S ALSO AN OPPORTUNITY TO 5648 04:29:37,720 --> 04:29:39,440 NOW DEFINE THE COMMON SYMPTOMS 5649 04:29:39,440 --> 04:29:41,000 AND LUNG FUNCTION DECLINE THAT 5650 04:29:41,000 --> 04:29:43,760 PEOPLE WITH CF PRESENT WITH AT 5651 04:29:43,760 --> 04:29:47,680 THE TIME OF THE EXACERBATION AS 5652 04:29:47,680 --> 04:29:49,560 WELL AS EVALUATING FOR THE 5653 04:29:49,560 --> 04:29:50,520 EXACERBATION AND THERE'S 2 5654 04:29:50,520 --> 04:29:52,000 CURRENT CLINICAL TRIALS THAT I 5655 04:29:52,000 --> 04:29:53,560 THINK COULD HELP US WITH SOME OF 5656 04:29:53,560 --> 04:29:55,360 THESE QUESTIONS. 5657 04:29:55,360 --> 04:29:57,560 SO OUR STOP PROGRAM WE HAVE NOW 5658 04:29:57,560 --> 04:29:58,680 DEVELOPED A PLATFORM OF PROTOCOL 5659 04:29:58,680 --> 04:30:01,640 THAT CAN BE USED TO CONDUCT 5660 04:30:01,640 --> 04:30:03,840 MULTIPLE CLINICAL TRIALS IN 5661 04:30:03,840 --> 04:30:07,640 EXACERBATION, WE CALL THIS STOP 5662 04:30:07,640 --> 04:30:09,280 360 IN THE FIRST 1 WE WILL BE 5663 04:30:09,280 --> 04:30:10,360 RUNNING THAT SHOULD BE UPAND 5664 04:30:10,360 --> 04:30:13,360 RUNNING BY THE END OF 2022 IS 5665 04:30:13,360 --> 04:30:17,400 WHAT WE'RE CALLING THE AG STUDY 5666 04:30:17,400 --> 04:30:19,680 OR AMINO GLYCOICIDE, AND WE'RE 5667 04:30:19,680 --> 04:30:22,400 COMPARING TREATMENT OF AN IV 5668 04:30:22,400 --> 04:30:30,640 BETA LACTAM, AND HERO 2 WILL OB 5669 04:30:30,640 --> 04:30:36,280 STUDY IS A 1 YEAR OBSERVATIONAL 5670 04:30:36,280 --> 04:30:41,920 STUDY SYMPTOMS ON THOSE FOR 5671 04:30:41,920 --> 04:30:42,240 THE--CAFTORs. 5672 04:30:42,240 --> 04:30:44,400 AND BOTH OF THESE CAN BE USED TO 5673 04:30:44,400 --> 04:30:45,480 TRACK EXACERBATIONS AND GATHER A 5674 04:30:45,480 --> 04:30:51,040 LOT OF THE DATA WE'VE JUST BEEN 5675 04:30:51,040 --> 04:30:51,400 DISCUSSING. 5676 04:30:51,400 --> 04:30:53,680 I WOULD LIKE TO JUST GIVE CREDIT 5677 04:30:53,680 --> 04:30:56,480 TO MY STOP STUDY CO 5678 04:30:56,480 --> 04:30:59,000 INVESTIGATORS WHO HELPED RUN THE 5679 04:30:59,000 --> 04:31:01,480 STOP 360 PLATFORM TRIALS. 5680 04:31:01,480 --> 04:31:03,400 >> THANK YOU VERY MUCH. 5681 04:31:03,400 --> 04:31:04,920 VERY SORRY TO MISS YOU ALL LIVE, 5682 04:31:04,920 --> 04:31:07,720 I WOULD LIKE TO THANK CHRIS 5683 04:31:07,720 --> 04:31:09,960 GOSES WHO WAS OFFERED TO STEP IN 5684 04:31:09,960 --> 04:31:12,800 FOR MY BEHALF FOR THE IMRKS & A 5685 04:31:12,800 --> 04:31:13,040 SESSION. 5686 04:31:13,040 --> 04:31:21,440 THANK YOU. 5687 04:31:21,440 --> 04:31:21,760 DID EMPLOY. 5688 04:31:21,760 --> 04:31:22,800 >> THANK YOU DR. WEST AND I 5689 04:31:22,800 --> 04:31:25,200 WOULD LIKE TO INTRODUCE 5690 04:31:25,200 --> 04:31:26,320 DR. MARRING WET ROSEN FELD FROM 5691 04:31:26,320 --> 04:31:27,360 THE UNIVERSITY OF WASHINGTON TO 5692 04:31:27,360 --> 04:31:32,760 TALK TO US ABOUT REMOTE 5693 04:31:32,760 --> 04:31:33,280 MONITORING TOOLS. 5694 04:31:33,280 --> 04:31:35,160 >> GREAT, WELL I WOULD LIKE TO 5695 04:31:35,160 --> 04:31:37,360 BEGIN BY THANKING THE ORGANIZERS 5696 04:31:37,360 --> 04:31:39,800 FOR INVITING ME TO SPEAK WITH 5697 04:31:39,800 --> 04:31:40,120 YOU TODAY. 5698 04:31:40,120 --> 04:31:41,520 I'M SO RETURN OF RESULTSRY 5699 04:31:41,520 --> 04:31:43,080 NATALIE WASN'T ABLE TO JOIN US 5700 04:31:43,080 --> 04:31:43,280 TODAY. 5701 04:31:43,280 --> 04:31:44,080 NEXT SLIDE. 5702 04:31:44,080 --> 04:31:48,280 HERE ARE MY DISCLOSURES. 5703 04:31:48,280 --> 04:31:51,400 NEXT SLIDE, SO I WILL BEGIN BY 5704 04:31:51,400 --> 04:31:52,680 DISCUSSING OPPORTUNITIES AND 5705 04:31:52,680 --> 04:31:54,040 CHALLENGES RELATE TOAD REMOTE 5706 04:31:54,040 --> 04:31:55,240 END POINTS. 5707 04:31:55,240 --> 04:31:57,440 I AM FOCUSING MOSTLY ON CLINICAL 5708 04:31:57,440 --> 04:31:59,680 TRIALS TODAY BUT THERE IS 5709 04:31:59,680 --> 04:32:01,160 OBVIOUSLY GREAT APPLICABILITY TO 5710 04:32:01,160 --> 04:32:02,480 CLINICAL CARE AS WELL. 5711 04:32:02,480 --> 04:32:05,720 SO I THINK WE'RE ALL LEARNING, 5712 04:32:05,720 --> 04:32:08,960 THANKS TO COVID ABOUT THE UNIQUE 5713 04:32:08,960 --> 04:32:10,160 OPPORTUNITIES AND CHALLENGES OF 5714 04:32:10,160 --> 04:32:12,360 ASCERTAINING WHAT USED TO BE 5715 04:32:12,360 --> 04:32:14,720 IN-PERSON END POINTSA THE HOME. 5716 04:32:14,720 --> 04:32:17,720 FIRST OF ALL THIS DECREASES 5717 04:32:17,720 --> 04:32:21,720 BARRIERS TO CLINICAL TRIAL 5718 04:32:21,720 --> 04:32:23,000 ENROLLMENT AND CAN PROMOTE 5719 04:32:23,000 --> 04:32:26,320 ACCESS TO CLINICAL TRIALS FOR 5720 04:32:26,320 --> 04:32:31,520 THOSE HERETOFORE HAD 2 HIGH 5721 04:32:31,520 --> 04:32:33,920 BARRIERS TO PARTICIPATE, AND 5722 04:32:33,920 --> 04:32:35,920 ETHNIC RACIAL, GEOGRAPHIC, AGE, 5723 04:32:35,920 --> 04:32:38,280 ET CETERA. 5724 04:32:38,280 --> 04:32:42,520 IN ADDITION, REMOTE END POINTS 5725 04:32:42,520 --> 04:32:48,040 FOR NO TOUCH CLINICAL TRIALS, 5726 04:32:48,040 --> 04:32:55,120 GREAT WORK IN CONCERT WITH 5727 04:32:55,120 --> 04:32:57,000 INCIDENCE HAVING MORE REMOTE 5728 04:32:57,000 --> 04:32:58,040 ACCESS, THE IDEA BEHIND THIS IS 5729 04:32:58,040 --> 04:33:00,280 TO BRING THE TRIAL DOWN TO THE 5730 04:33:00,280 --> 04:33:01,800 PATIENT AND DECREASE 5731 04:33:01,800 --> 04:33:03,280 PARTICIPATION, BUT IN ADDITION 5732 04:33:03,280 --> 04:33:04,680 IT HAS SOME REALLY IMPORTANT 5733 04:33:04,680 --> 04:33:06,320 CONSEQUENCES IN TERMS OF THE 5734 04:33:06,320 --> 04:33:08,520 DATA COLLECTED AS WELL BECAUSE 5735 04:33:08,520 --> 04:33:11,200 THE MORE FREQUENT GRANULAR DATA 5736 04:33:11,200 --> 04:33:12,480 COLLECTION ENABLED BY HOME 5737 04:33:12,480 --> 04:33:13,760 COLLECTION FIRST OF ALL ALLOWS 5738 04:33:13,760 --> 04:33:15,640 THE DATA TO BE ASCERTAIN INDEED 5739 04:33:15,640 --> 04:33:18,920 A REAL WORLD SETTING, ALSO COULD 5740 04:33:18,920 --> 04:33:20,720 POTENTIALLY DETECT CHANGES SUCH 5741 04:33:20,720 --> 04:33:22,120 AS EXACERBATIONS EARLIER, AND 5742 04:33:22,120 --> 04:33:24,520 WE'VE SEEN PLENTY OF EVIDENCE 5743 04:33:24,520 --> 04:33:29,960 ABOUT THAL AFTERNOON, AND 5744 04:33:29,960 --> 04:33:31,560 POTENTIALLY, MORE INFORMATION 5745 04:33:31,560 --> 04:33:32,480 COULD MITIGATE VARIABILITY 5746 04:33:32,480 --> 04:33:33,960 THAT'S ASSOCIATE WIDE HOME 5747 04:33:33,960 --> 04:33:36,560 COLLECTION AND POTENTIALLY, 5748 04:33:36,560 --> 04:33:38,120 POTENTIALLY, I'M NOT A BETTING 5749 04:33:38,120 --> 04:33:40,560 PERSON, REDUCE SAMPLE SIZES ARE 5750 04:33:40,560 --> 04:33:47,160 CLINICAL TRIALS. 5751 04:33:47,160 --> 04:33:47,480 NEXT SLIDE. 5752 04:33:47,480 --> 04:33:50,440 HOWEVER, WE HAVE TO BE REALLY 5753 04:33:50,440 --> 04:33:51,360 CLEAR ABOUT THE CHALLENGEs AS 5754 04:33:51,360 --> 04:33:54,800 WELL AND MAKE SURE WE'RE 5755 04:33:54,800 --> 04:33:56,320 DEVELOPING THE REMOTE END POINT 5756 04:33:56,320 --> 04:33:59,400 COLLECTION PROCEDURES IN A WAY 5757 04:33:59,400 --> 04:34:02,200 THAT IS MEETING THE NEEDS OF OUR 5758 04:34:02,200 --> 04:34:05,200 PARTICIPANTS AND OF OUR RESEARCH 5759 04:34:05,200 --> 04:34:05,840 COORDINATORS, ABSOLUTELY 5760 04:34:05,840 --> 04:34:07,640 CRITICAL SO OF COURSE THERE ARE 5761 04:34:07,640 --> 04:34:09,880 ACCESS ISSUES THAT HAVE HUGE 5762 04:34:09,880 --> 04:34:12,400 EQUITY AND DIVERSITY 5763 04:34:12,400 --> 04:34:14,960 IMPLICATIONS AROUND ACCESS TO 5764 04:34:14,960 --> 04:34:15,800 RELIABLE BROAD BAND. 5765 04:34:15,800 --> 04:34:17,640 PEOPLE SHOULDN'T BE DRIVING TO 5766 04:34:17,640 --> 04:34:19,600 THE NEAREST WAL-MART TO GET 5767 04:34:19,600 --> 04:34:20,440 WIMBERLYIFY TO DO ROUGH ATOM 5768 04:34:20,440 --> 04:34:23,920 MOTE PROCEED IRBS AND ISSUES 5769 04:34:23,920 --> 04:34:25,520 AROUND DIGITAL LITERACY. 5770 04:34:25,520 --> 04:34:27,400 ALSO THOUGH, I TALKED ABOUT THE 5771 04:34:27,400 --> 04:34:29,080 OPPORTUNITY TO DECREASE 5772 04:34:29,080 --> 04:34:30,320 PARTICIPANT BURDEN IRONICALLY IF 5773 04:34:30,320 --> 04:34:32,120 WE'RE NOT CAREFUL WE CAN 5774 04:34:32,120 --> 04:34:33,160 INCREASE PARTICIPANT BURDEN AS 5775 04:34:33,160 --> 04:34:34,720 WELL AS BURDEN ON RESEARCH STAFF 5776 04:34:34,720 --> 04:34:35,880 BECAUSE OF HAVING PROCEDURES 5777 04:34:35,880 --> 04:34:37,840 THAT ARE DONE PREQUENTLY AND OF 5778 04:34:37,840 --> 04:34:39,440 RESEARCH STAFF NEEDING TO TRAIN 5779 04:34:39,440 --> 04:34:41,040 PARTICIPANTS IN HOW TO DO THESE 5780 04:34:41,040 --> 04:34:43,920 PROCEDURES AND THEN MONITOR 5781 04:34:43,920 --> 04:34:44,240 ADHERENCE. 5782 04:34:44,240 --> 04:34:47,240 DATA QUALITY IS A HUGE ISSUE. 5783 04:34:47,240 --> 04:34:50,360 WE NEED TO BE DOING REMOTE END 5784 04:34:50,360 --> 04:34:51,280 POINT COLLECTION AROUND END 5785 04:34:51,280 --> 04:34:53,160 POINTS THAT WE ACTUALLY TRUST, 5786 04:34:53,160 --> 04:34:54,840 ARE THEY ACCURATE, RELIABLE? 5787 04:34:54,840 --> 04:34:57,320 WHAT'S THE VARIABILITY COMPARED 5788 04:34:57,320 --> 04:34:58,680 TO IN-PERSON COLLECTION? 5789 04:34:58,680 --> 04:35:01,000 ADHERENCE IS A HUGE ISSUE, TOO, 5790 04:35:01,000 --> 04:35:02,960 PARTICIPANTS IN CF CLINICAL 5791 04:35:02,960 --> 04:35:06,480 TRIALS HAVE BUSY LIVES AND MAY 5792 04:35:06,480 --> 04:35:09,360 NOT FEEL THAT IT'S GOING 5793 04:35:09,360 --> 04:35:13,320 BENEFITING TO DO BURDENSOME 5794 04:35:13,320 --> 04:35:16,440 PROCEDURES TO TOO FREQUENTLY. 5795 04:35:16,440 --> 04:35:17,360 ACTIVE VERSUS PASSIVE DATA 5796 04:35:17,360 --> 04:35:19,000 COLLECTION, BUT FOR THE ACTIVE 5797 04:35:19,000 --> 04:35:19,960 DATA COLLECTION, PEOPLE NEED TO 5798 04:35:19,960 --> 04:35:22,240 BE TRAIN INDEED HOW TO DO THE 5799 04:35:22,240 --> 04:35:23,720 PROCEDURES APPROPRIATELY AT HOME 5800 04:35:23,720 --> 04:35:24,800 AND THEN, WE'RE ALL FEELING THAT 5801 04:35:24,800 --> 04:35:26,720 THIS IS SUCH A RAPIDLY EVOLVING 5802 04:35:26,720 --> 04:35:28,240 FIELD WITH NEW TECHNOLOGIES 5803 04:35:28,240 --> 04:35:29,000 CONDITIONALLING OUT ALL THE 5804 04:35:29,000 --> 04:35:30,920 TIME, HOW DO WE VALIDATE THEM, 5805 04:35:30,920 --> 04:35:32,840 WHEN WE GET DONE VALIDATING THEM 5806 04:35:32,840 --> 04:35:34,160 ARE THEY OUT OF DATE? 5807 04:35:34,160 --> 04:35:35,440 AND THE WHOLE ISSUE WHICH I WILL 5808 04:35:35,440 --> 04:35:36,880 NOT ADDRESS TODAY BUT COULD BE 5809 04:35:36,880 --> 04:35:38,880 ADDRESSED IN THE Q&A OR IN THE 5810 04:35:38,880 --> 04:35:40,560 BREAK OUT AROUND FDA CLEARANCE 5811 04:35:40,560 --> 04:35:47,880 OF REMOTE CLINICAL TRIALS. 5812 04:35:47,880 --> 04:35:48,360 NEXT SLIDE, PLEASE? 5813 04:35:48,360 --> 04:35:50,720 SO WE HAVE BEEN FOCUSING SO MUCH 5814 04:35:50,720 --> 04:35:54,040 ON THE MULTIORGAN VIEW OF CF AND 5815 04:35:54,040 --> 04:35:58,080 I WILL BE AS A PULL 5816 04:35:58,080 --> 04:35:59,280 MONITORROLOGYIST FOCUSING ON THE 5817 04:35:59,280 --> 04:36:00,240 MULL MONITORARY END POINTS BUT 5818 04:36:00,240 --> 04:36:03,400 THEREYA A POSSIBILITY OF REMOTE 5819 04:36:03,400 --> 04:36:08,120 SWEAT COLLECTION, OF GI SAMPLES, 5820 04:36:08,120 --> 04:36:10,840 AND OF INFECTION PARTICULARLY 5821 04:36:10,840 --> 04:36:21,280 RELEVANT TO OUR TO PEOPLE. 5822 04:36:26,760 --> 04:36:30,720 SO AS I MENTIONED I WILL FOCUS 5823 04:36:30,720 --> 04:36:32,280 ON HOME SPIROMETRY, BUT PATIENT 5824 04:36:32,280 --> 04:36:37,320 REPORTED OUTCOMES IN THE CRISSOR 5825 04:36:37,320 --> 04:36:38,960 THE DOMAIN FOR EXACERBATION 5826 04:36:38,960 --> 04:36:39,920 SYMPTOMS ARE REALLY IMPORTANT 5827 04:36:39,920 --> 04:36:41,920 BUT OTHER THINGS CAN BE 5828 04:36:41,920 --> 04:36:43,560 EVALUATED ELECTRONICALLY AT HOME 5829 04:36:43,560 --> 04:36:44,160 PARTICULARLY RELATED TO MORE 5830 04:36:44,160 --> 04:36:47,680 GENERAL QUALITY OF LIFE. 5831 04:36:47,680 --> 04:36:49,800 OXYGEN SATURATION COULD BE 5832 04:36:49,800 --> 04:36:52,000 HELPFUL. 5833 04:36:52,000 --> 04:36:54,040 SAMPLE COLLECTION EITHER VIA 5834 04:36:54,040 --> 04:36:55,840 SPUTUM OR EXHALED BREATH, THAT 5835 04:36:55,840 --> 04:36:57,040 PART SOUNDS VERY EXCITING, I 5836 04:36:57,040 --> 04:36:58,080 LOOK FORWARD TO 5837 04:36:58,080 --> 04:36:58,560 FUTURE--POTENTIAL IRB 5838 04:36:58,560 --> 04:36:59,360 DEVELOPMENTS THERE AND THEN 5839 04:36:59,360 --> 04:37:02,920 THERE ARE MANY OPPORTUNITIES FOR 5840 04:37:02,920 --> 04:37:03,720 PASSIVE PULMONARY END POINT 5841 04:37:03,720 --> 04:37:04,920 COLLECTION AS WELL. 5842 04:37:04,920 --> 04:37:06,320 A DIGITAL COUGH MONITOR EITHER 5843 04:37:06,320 --> 04:37:09,800 PLACED BY THE BEDSIDE OR 5844 04:37:09,800 --> 04:37:10,920 POTENTIALLY IN AN AMBULATORY 5845 04:37:10,920 --> 04:37:13,120 SETTING AND THAT'S A BIT MORE 5846 04:37:13,120 --> 04:37:17,920 CHALLENGING BECAUSE OF PRIVACY 5847 04:37:17,920 --> 04:37:19,160 ISSUES, ACTIGRAPHY, HEART RATE, 5848 04:37:19,160 --> 04:37:21,600 SLEEP SO THESE WILL BE VERY, 5849 04:37:21,600 --> 04:37:28,600 VERY RAPIDLY DEVELOPING FIELDS. 5850 04:37:28,600 --> 04:37:28,960 NEXT SLIDE. 5851 04:37:28,960 --> 04:37:31,200 SO I JUST WANT TO REVIEW A FEW 5852 04:37:31,200 --> 04:37:32,640 OF THE STUDIES THAT ARE ONGOING 5853 04:37:32,640 --> 04:37:34,320 PARTICULARLY IN A COUPLE 5854 04:37:34,320 --> 04:37:34,920 COUNTRIES IN EUROPE. 5855 04:37:34,920 --> 04:37:36,800 LOOK FORWARD TO HEARING MORE 5856 04:37:36,800 --> 04:37:38,280 ABOUT THESE WHEN WE'RE GOING TO 5857 04:37:38,280 --> 04:37:39,120 THE EUROPEAN SOCIETY MEET 5858 04:37:39,120 --> 04:37:41,560 NEGLIGENCE A FEW DAYS. 5859 04:37:41,560 --> 04:37:43,680 THE FIRST IS DR. [INDISCERNIBLE] 5860 04:37:43,680 --> 04:37:46,040 AND COLLEAGUES OUT OF THE 5861 04:37:46,040 --> 04:37:48,600 NETHERLANDS ARE PERFORMING THIS 5862 04:37:48,600 --> 04:37:49,520 WONDERFUL DIGITAL BIOMARKER 5863 04:37:49,520 --> 04:37:51,400 STUDY WHICH IS A COHORT STUDY OF 5864 04:37:51,400 --> 04:37:55,120 60 DAYS WITH ASTHMA, 30 WITH CF 5865 04:37:55,120 --> 04:37:56,600 AND 128 WITH HEALTHY CONTROLS 5866 04:37:56,600 --> 04:37:59,280 AND THE OVERARCHING AIM IS TO 5867 04:37:59,280 --> 04:38:00,520 BEGIN CLINICAL VALIDATION OF THE 5868 04:38:00,520 --> 04:38:04,040 MARKERS I LISTED HERE. 5869 04:38:04,040 --> 04:38:04,320 NEXT SLIDE. 5870 04:38:04,320 --> 04:38:06,240 AND THIS IS JUST A--JUST A 5871 04:38:06,240 --> 04:38:08,200 TEASER OF SOME OF THEIR RESULTS, 5872 04:38:08,200 --> 04:38:09,920 OBVIOUSLY THEY WILL HAVE MORE 5873 04:38:09,920 --> 04:38:14,360 RESULTS COMING OUT, BUT HERE YOU 5874 04:38:14,360 --> 04:38:20,480 CAN SEE HOME SPIROMETRY ON THE 5875 04:38:20,480 --> 04:38:21,640 Z-AXIS AND RESPIRATORY SYMPTOM 5876 04:38:21,640 --> 04:38:23,600 SCORE IN PANEL A, AND DAYS OR 5877 04:38:23,600 --> 04:38:25,160 AFTER TREATMENT OF AN 5878 04:38:25,160 --> 04:38:26,120 EXACERBATION IN PANEL B AND YOU 5879 04:38:26,120 --> 04:38:29,680 CAN SEE THE EXPECTED ASSOCIATION 5880 04:38:29,680 --> 04:38:31,880 SO IT'S FEV AS RESPIRATORY 5881 04:38:31,880 --> 04:38:34,160 SYMPTOMS AS IT GETS WORSE, FEV 5882 04:38:34,160 --> 04:38:36,160 SCORE GETS LOWER AND SIMILARLY 5883 04:38:36,160 --> 04:38:39,080 FEV 1 SCORE DECLINES PRIOR TO AN 5884 04:38:39,080 --> 04:38:40,120 EXACERBATION AND IMPROVES AGAIN 5885 04:38:40,120 --> 04:38:41,520 WITH TREATMENT. 5886 04:38:41,520 --> 04:38:43,080 SO JUSTA A TEASER OF THE KINDS 5887 04:38:43,080 --> 04:38:45,080 OF THINGS WE'RE HOPING TO SEE AS 5888 04:38:45,080 --> 04:38:47,200 WE BEGIN TO QUOTE VALIDATE THESE 5889 04:38:47,200 --> 04:38:57,680 HOME COLLECTION END POINTS. 5890 04:38:58,240 --> 04:38:58,960 NEXT SLIDE. 5891 04:38:58,960 --> 04:39:02,560 >> I ALSO WANTED TO POINT OUT 5892 04:39:02,560 --> 04:39:04,600 THE CLIMB-CF STUDY AND THE 5893 04:39:04,600 --> 04:39:06,240 CONNECT CF STUDY, WE DON'T HAVE 5894 04:39:06,240 --> 04:39:07,800 RESULTS YET BUT BOTH WILL ARE 5895 04:39:07,800 --> 04:39:09,280 VIED VALUABLE DATA ABOUT HOME 5896 04:39:09,280 --> 04:39:10,200 COLLECTION OF VARIOUS DIFFERENT 5897 04:39:10,200 --> 04:39:11,920 END POINTS IN CHILDREN AND 5898 04:39:11,920 --> 04:39:16,520 ADULTS WITH CYSTIC FIBROSIS. 5899 04:39:16,520 --> 04:39:16,880 NEXT SLIDE. 5900 04:39:16,880 --> 04:39:18,520 I DID WANT TO CALL OUT THE 5901 04:39:18,520 --> 04:39:19,840 WONDERFUL WORK DONE BY ALEX 5902 04:39:19,840 --> 04:39:23,520 PAINTER AS WELL AS NICOLE HAMLET 5903 04:39:23,520 --> 04:39:26,320 AND OTHERS AT THE TDN, IT'S A 5904 04:39:26,320 --> 04:39:29,120 REANALYSIS OF OF THE EICE DATA, 5905 04:39:29,120 --> 04:39:30,440 YOU REMEMBER ABOUT A DECADE AGO, 5906 04:39:30,440 --> 04:39:35,480 THIS STUDY THAT WAS EVALUATING 5907 04:39:35,480 --> 04:39:36,920 HOME SPIROMETRY AND HOME SYMPTOM 5908 04:39:36,920 --> 04:39:39,400 COLLECTION AS A POTENTIAL WAY TO 5909 04:39:39,400 --> 04:39:40,720 DETECT EXACERBATIONS EARLIER IN 5910 04:39:40,720 --> 04:39:42,200 A RANDOMIZED CONTROL DESIGN, I 5911 04:39:42,200 --> 04:39:45,320 WON'T REVIEW THE STUDY ITSELF, 5912 04:39:45,320 --> 04:39:48,840 BUT THIS PARTICULAR REANALYSIS, 5913 04:39:48,840 --> 04:39:51,080 EVALUATED THE 12th MONTH 5914 04:39:51,080 --> 04:39:52,320 CHANGE IN FEV 1 AMONG 5915 04:39:52,320 --> 04:39:56,320 PARTICIPANTS IN THE TRIAL AND 5916 04:39:56,320 --> 04:39:57,520 COMPARING CLINIC SPIROMETRY, 5917 04:39:57,520 --> 04:39:59,240 CLINIC IN BLUE, HOME IN ORANGE 5918 04:39:59,240 --> 04:40:00,640 AND WHAT YOU CAN SEE IS THAT THE 5919 04:40:00,640 --> 04:40:02,800 POINT ESTIMATE FOR THE 12 MONTH 5920 04:40:02,800 --> 04:40:05,480 CHANGE WAS ALWAYS A BIT SMALLER 5921 04:40:05,480 --> 04:40:07,440 WITH THE HOME COMPARED TO THE 5922 04:40:07,440 --> 04:40:09,320 CLINICS BUT NOT ALL THAT 5923 04:40:09,320 --> 04:40:09,600 DIFFERENT. 5924 04:40:09,600 --> 04:40:10,640 CLOSER THAN WHAT WE HAD FEARED 5925 04:40:10,640 --> 04:40:14,360 AND THIS IS WITH OLD FASHIONED 5926 04:40:14,360 --> 04:40:16,080 SPIROMETRY, THE TECHNOLOGY HAS 5927 04:40:16,080 --> 04:40:17,520 IMPROVED MARKEDLY SINCE THEN BUT 5928 04:40:17,520 --> 04:40:19,040 THERE'S MORE VARIABILITY IN THAT 5929 04:40:19,040 --> 04:40:21,240 12 MONTH CHANGE WITH THE HOME 5930 04:40:21,240 --> 04:40:23,520 THAN THE OFFICE SPIRORDER OF 5931 04:40:23,520 --> 04:40:24,240 MICRONSETRY. 5932 04:40:24,240 --> 04:40:24,960 NEXT SLIDE, PLEASE. 5933 04:40:24,960 --> 04:40:27,960 ANOTHER BIG ISSUE IS WHETHER 5934 04:40:27,960 --> 04:40:29,520 HOME SPIROMETRY NEEDS TO BE 5935 04:40:29,520 --> 04:40:30,680 COACHED REMOTELY BY A RESEARCH 5936 04:40:30,680 --> 04:40:32,000 STAFF NUMBER OR UNCOACHED AND I 5937 04:40:32,000 --> 04:40:33,320 THINK WE NEED TO LEARN MORE IN 5938 04:40:33,320 --> 04:40:35,320 THIS AREA, BUT THIS IS 5939 04:40:35,320 --> 04:40:36,800 PRELIMINARY DATA FROM THE 5940 04:40:36,800 --> 04:40:41,760 PROMISE STUDY WHICH SHOWS THAT 5941 04:40:41,760 --> 04:40:44,800 BOTH OF THEM GAVE RESULTS THAT 5942 04:40:44,800 --> 04:40:50,040 WERE NOT THAT DIFFERENT FROM THE 5943 04:40:50,040 --> 04:40:51,520 OFFICE SPIROMETRY AND WITH MORE 5944 04:40:51,520 --> 04:40:53,240 VALID AND RELIABLE ABILITY HAS 5945 04:40:53,240 --> 04:40:55,920 BEEN SO MAC IT IS MEASUREMENTS 5946 04:40:55,920 --> 04:40:58,240 WE ARE COACHED AND OF COURSE AS 5947 04:40:58,240 --> 04:41:00,280 WELL. 5948 04:41:00,280 --> 04:41:00,640 NEXT SLIDE. 5949 04:41:00,640 --> 04:41:04,520 >> SO I WANT TO MOVE NOW TO AN 5950 04:41:04,520 --> 04:41:06,120 UPCOMING STUDY IN--THAT I'M 5951 04:41:06,120 --> 04:41:08,000 LEADING ALONG WITH OTHER 5952 04:41:08,000 --> 04:41:12,080 WONDERFUL COLLEAGUES, THIS IS 5953 04:41:12,080 --> 04:41:13,200 CFF SPONSORED STUDY CALLED 5954 04:41:13,200 --> 04:41:23,480 OUTREACH AND IT'S A MULTICENTER, 5955 04:41:23,480 --> 04:41:26,440 PROSPECTIVE STUDY OF HOME 5956 04:41:26,440 --> 04:41:27,520 SPIROMETRY, AS CLINICAL TRIAL 5957 04:41:27,520 --> 04:41:30,760 END POINT AND OVERARCHING 5958 04:41:30,760 --> 04:41:32,480 OBJECTIVE TO EVALUATE 5959 04:41:32,480 --> 04:41:36,120 FEASIBILITY OF REPLACING OR 5960 04:41:36,120 --> 04:41:37,720 AUGMENTS OFFICE SPIROMETRY, WITH 5961 04:41:37,720 --> 04:41:39,040 HOME AND COMPARING HOME TO 5962 04:41:39,040 --> 04:41:41,400 OFFICE, AND THIS STUDY IS SLATED 5963 04:41:41,400 --> 04:41:43,160 TO START IN THE FALL OF THIS 5964 04:41:43,160 --> 04:41:44,200 COMING YEAR SO STAY TUNED AND 5965 04:41:44,200 --> 04:41:47,520 THANKS TO ALL OF YOU WHO WILL BE 5966 04:41:47,520 --> 04:41:48,680 SITES IN THE STUDY. 5967 04:41:48,680 --> 04:41:49,040 NEXT SLIDE. 5968 04:41:49,040 --> 04:41:50,560 AS WE WENT THROUGH THE PLANNING 5969 04:41:50,560 --> 04:41:52,280 PROCESS, FOR THIS STUDY, AND AS 5970 04:41:52,280 --> 04:41:53,440 MORE AND MORE PUBLICATIONS ARE 5971 04:41:53,440 --> 04:41:56,120 COMING OUT ON A REMOTE END POINT 5972 04:41:56,120 --> 04:41:57,560 ASKER TAINMENT I WANTED TO SHIFT 5973 04:41:57,560 --> 04:42:00,440 TO TALKING ABOUT EMERGING SORT 5974 04:42:00,440 --> 04:42:00,920 OF OVERARCHING THEMES. 5975 04:42:00,920 --> 04:42:02,520 THE FIRST IS THE IMPORTANCE OF 5976 04:42:02,520 --> 04:42:03,840 UNDERSTANDING THE PARTICIPANT 5977 04:42:03,840 --> 04:42:05,640 AND RESEARCH STAFF EXPERIENCE. 5978 04:42:05,640 --> 04:42:07,120 THIS IS REALLY NEW TERRITORY 5979 04:42:07,120 --> 04:42:09,000 WHERE IN A WAY WE'RE ASKING 5980 04:42:09,000 --> 04:42:10,720 PARTICIPANTS AND RESEARCH STAFF 5981 04:42:10,720 --> 04:42:12,240 TO DO SOMETHING SO DIFFERENT 5982 04:42:12,240 --> 04:42:14,840 FROM WHAT WE'VE DONE FOR YEARS 5983 04:42:14,840 --> 04:42:16,480 AND WE NEED TO REALLY KEEP IN 5984 04:42:16,480 --> 04:42:19,240 MIND THAT WE NEED TO CO PRODUCE 5985 04:42:19,240 --> 04:42:20,360 THESE STUDIES AND UNDERSTAND 5986 04:42:20,360 --> 04:42:23,080 WHAT THE PARTICIPANT AND 5987 04:42:23,080 --> 04:42:24,520 RESEARCH STAFF EXPERIENCE IS, 5988 04:42:24,520 --> 04:42:27,440 ARE THESE MEASURES FEASIBLE, 5989 04:42:27,440 --> 04:42:28,360 ACCEPTABLE, AND THAT'S GOING TO 5990 04:42:28,360 --> 04:42:29,840 BE CRITICAL IN MAKING THESE 5991 04:42:29,840 --> 04:42:35,600 TRIALS A SUCCESS RATHER THAN A 5992 04:42:35,600 --> 04:42:36,120 FAILURE. 5993 04:42:36,120 --> 04:42:40,760 ALSO PARTICULARLY FOR HOME 5994 04:42:40,760 --> 04:42:44,080 SPIROMETRY, AND PUTTING TOGETHER 5995 04:42:44,080 --> 04:42:45,280 CLEAR APPROPRIATE TRAINING 5996 04:42:45,280 --> 04:42:46,200 MATERIALS AND TRAINING 5997 04:42:46,200 --> 04:42:47,120 PROCEDURES FOR OUR PARTICIPANTS 5998 04:42:47,120 --> 04:42:50,800 AND ALSO FOR THE RESEARCH STAFF. 5999 04:42:50,800 --> 04:42:53,200 WE HAD FOR HOME SPIROMETRY SUCH 6000 04:42:53,200 --> 04:42:56,760 DISSEMINATION NEXT TO THE 6001 04:42:56,760 --> 04:42:58,200 FOUNDATION OF HOME SPIROMETRY, 6002 04:42:58,200 --> 04:43:00,560 WE MAY HAVE TO HAVE PATIENTS 6003 04:43:00,560 --> 04:43:02,920 UNLEARN PRACTICES THAT DIFFER IN 6004 04:43:02,920 --> 04:43:05,560 A RESEARCH SETTING FROM THOSE IN 6005 04:43:05,560 --> 04:43:05,960 THE CLINICAL CARE. 6006 04:43:05,960 --> 04:43:06,480 >> 2-MINUTE WARNING. 6007 04:43:06,480 --> 04:43:08,000 >> AND I CAN'T EMPHASIZE O 6008 04:43:08,000 --> 04:43:09,040 IMPORTANT CO PRODUCTION IS, 6009 04:43:09,040 --> 04:43:10,480 WE'VE BEEN DOING THIS IN THE 6010 04:43:10,480 --> 04:43:11,800 OUTREACH STUDY AND I AM SO 6011 04:43:11,800 --> 04:43:14,200 HUMBLE THAT I'VE LEARNED SO MUCH 6012 04:43:14,200 --> 04:43:16,240 FROM THE PEOPLE WITH CF AND THE 6013 04:43:16,240 --> 04:43:17,280 RESEARCH COORDINATORS WHO VAIOF 6014 04:43:17,280 --> 04:43:20,840 THED IN THE OR REALLY LED THE CO 6015 04:43:20,840 --> 04:43:21,120 PRODUCTION. 6016 04:43:21,120 --> 04:43:26,120 AND FINALLY, I WANTED TO TOUCH 6017 04:43:26,120 --> 04:43:28,360 ON THE CHALLENGES PARTICULARLY 6018 04:43:28,360 --> 04:43:28,960 IN PEDIATRIC STUDIES. 6019 04:43:28,960 --> 04:43:36,800 NEXT SLIDE, SO AS A PEDIATRIC 6020 04:43:36,800 --> 04:43:39,200 PULL MONITOR OLOGIST, THERE WILL 6021 04:43:39,200 --> 04:43:40,560 BE DIFFERENT ABILITIES FOR THESE 6022 04:43:40,560 --> 04:43:41,920 KIDS IN THE AGE RANGES I'VE SEWN 6023 04:43:41,920 --> 04:43:44,080 HERE TO BE ABLE TO DO FOR 6024 04:43:44,080 --> 04:43:45,760 EXAMPLE, HOME SPIROMETRY OR 6025 04:43:45,760 --> 04:43:47,560 OTHER HOME PROCEDURES, SO THEN 6026 04:43:47,560 --> 04:43:50,360 THERE'S THE QUESTION OF HOW DO 6027 04:43:50,360 --> 04:43:51,400 PARENTS GET INVOLVED, WHOSE 6028 04:43:51,400 --> 04:43:53,000 SMART PHONE IS USED? 6029 04:43:53,000 --> 04:43:54,720 HOW DO THE PARENTS FACILITATE 6030 04:43:54,720 --> 04:43:58,360 THE PATIENT DOING THE PROCEDURE 6031 04:43:58,360 --> 04:43:59,200 WITHOUT ELIMINATING THEIR 6032 04:43:59,200 --> 04:44:00,920 AUTONOMY OR WITHOUT BEING OVER 6033 04:44:00,920 --> 04:44:02,360 BEARING, OR WITHOUT GIVING 6034 04:44:02,360 --> 04:44:03,280 RESULTS THAT AREN'T REFLECTIVE 6035 04:44:03,280 --> 04:44:04,840 OF WHAT THE KID IS DOING SO 6036 04:44:04,840 --> 04:44:06,520 THESE ARE ALL JUST RAPIDLY 6037 04:44:06,520 --> 04:44:09,000 EVOLVING AREAS THAT WE'RE STILL 6038 04:44:09,000 --> 04:44:09,640 TRYING TO UNDERSTAND. 6039 04:44:09,640 --> 04:44:13,200 AND YOU KNOW KIDS MAY DEVELOP IN 6040 04:44:13,200 --> 04:44:14,240 DIFFERENT WAYS, DIFFERENT AGES 6041 04:44:14,240 --> 04:44:16,640 IN DIFFERENT KIDS BUT WE STILL 6042 04:44:16,640 --> 04:44:18,280 HAVE TO PROCEED STANDARDIZED 6043 04:44:18,280 --> 04:44:22,120 GUIDANCE OR MAY HAVE TO STRATIFY 6044 04:44:22,120 --> 04:44:23,680 AGES SO IT'S COMPLEX BUT REALLY 6045 04:44:23,680 --> 04:44:25,920 IMPORTANT TO TACKLE. 6046 04:44:25,920 --> 04:44:26,720 NEXT SLIDE. 6047 04:44:26,720 --> 04:44:28,200 SO JUST, I'LL BRIEFLY FINISH 6048 04:44:28,200 --> 04:44:30,640 WITH A LITTLE BIT ABOUT OTHER 6049 04:44:30,640 --> 04:44:34,600 ORGANS, SORRY DON'T MEAN TO THEM 6050 04:44:34,600 --> 04:44:39,040 A SHORT EFTHIMIOS, THEY'RE 6051 04:44:39,040 --> 04:44:40,600 EQUALLY IMPORTANT, BUT THESE ARE 6052 04:44:40,600 --> 04:44:43,040 NOT MY AREA OF EXPERTISE. 6053 04:44:43,040 --> 04:44:43,360 >> SLIDE. 6054 04:44:43,360 --> 04:44:46,880 SO THERE ARE TANTALIZING NEW 6055 04:44:46,880 --> 04:44:48,920 WEARABLES, SWEAT CHLORIDE 6056 04:44:48,920 --> 04:44:50,800 DEVICES THAT AREN'T YET READY 6057 04:44:50,800 --> 04:44:52,240 FOR PRIME TIME BUT THEY'RE QUITE 6058 04:44:52,240 --> 04:44:53,880 EXCITING AND IT MAY BE IN THE 6059 04:44:53,880 --> 04:44:56,520 FUTURE WE CAN COLLECT AN AND 6060 04:44:56,520 --> 04:45:01,480 EVEN ANALYZE SWEAT CHLORIDE 6061 04:45:01,480 --> 04:45:01,960 CONCENTRATION REMOTELY. 6062 04:45:01,960 --> 04:45:03,560 SILL A LONG WAY TO GO BUT 6063 04:45:03,560 --> 04:45:05,280 SOMETHING TO KEEPOT RADAR FOR 6064 04:45:05,280 --> 04:45:06,760 THE FUTURE EMPLOY. 6065 04:45:06,760 --> 04:45:07,160 >> NEXT SLIDE. 6066 04:45:07,160 --> 04:45:10,360 >> THESE COULD BE USED TO LOOK 6067 04:45:10,360 --> 04:45:12,640 AT PHARMA CODYNAMMICS IF 6068 04:45:12,640 --> 04:45:13,960 INDIVIDUALS RESPONDING AND IN 6069 04:45:13,960 --> 04:45:16,720 TERMS OF CHLORIDE, COULD BE USED 6070 04:45:16,720 --> 04:45:18,960 FOR N-1 TRIALS AS WE TALKED 6071 04:45:18,960 --> 04:45:19,520 ABOUT EARLIER TODAY, 6072 04:45:19,520 --> 04:45:21,400 PARTICULARLY FOR DOSE ADJUSTMENT 6073 04:45:21,400 --> 04:45:23,920 AND IMPORTANTLY FOR NEW BORN 6074 04:45:23,920 --> 04:45:24,960 SCREENING, PARTICULARLY IN 6075 04:45:24,960 --> 04:45:26,240 STATES LIKE WASHINGTON WHERE 6076 04:45:26,240 --> 04:45:29,200 NEWBORNS CAN LIVE FAR AWAY FROM 6077 04:45:29,200 --> 04:45:31,120 A CFF ACCREDITED LAB, THERE'S A 6078 04:45:31,120 --> 04:45:32,480 REAL CHALLENGE GETTING TIMINGLY 6079 04:45:32,480 --> 04:45:34,440 SWEAT CHLORIDES AND THIS COULD 6080 04:45:34,440 --> 04:45:38,240 BE USED AS A SCREENING STEP TO 6081 04:45:38,240 --> 04:45:40,000 MORE RAPIDLY IDENTIFY BABIES WHO 6082 04:45:40,000 --> 04:45:41,840 HAVE A POSITIVE NEW BORN 6083 04:45:41,840 --> 04:45:44,040 SCREENING WHO ACTUALLY HAVE CF. 6084 04:45:44,040 --> 04:45:44,360 NEXT SLIDE. 6085 04:45:44,360 --> 04:45:46,400 AND THEN JUST TO END ON ANOTHER 6086 04:45:46,400 --> 04:45:48,480 EXCITING NOTE, I THINK WE'RE ALL 6087 04:45:48,480 --> 04:45:50,680 FAMILIAR WITH CONTINUOUS GLUCOSE 6088 04:45:50,680 --> 04:45:53,440 MONITORING, AND THIS HAS HUGE 6089 04:45:53,440 --> 04:45:54,840 PROMISE CURRENTLY BUT ALSO IN 6090 04:45:54,840 --> 04:45:56,360 THE HIGHEE EFFECTIVE MODULATOR 6091 04:45:56,360 --> 04:45:57,080 ERA. 6092 04:45:57,080 --> 04:46:00,200 IT COULD HELP TO ELUCIDATE THE 6093 04:46:00,200 --> 04:46:04,040 EFFECTS OF HEMT ON GLYCEMIC 6094 04:46:04,040 --> 04:46:04,400 CONTROL. 6095 04:46:04,400 --> 04:46:10,960 IT'S ALREADY USED TO EVALUATE 6096 04:46:10,960 --> 04:46:12,360 GLYCEMIC CONTROL ON PREGNANT 6097 04:46:12,360 --> 04:46:14,680 PEOPLE AND MODULATORS IN THE MAY 6098 04:46:14,680 --> 04:46:20,120 FLOW ARES AND COULD BE USED TO 6099 04:46:20,120 --> 04:46:21,760 REPLACE FTDDs AND WHEN LINKED 6100 04:46:21,760 --> 04:46:22,960 TO AN INSULIN PUMP WHERE THEY 6101 04:46:22,960 --> 04:46:27,200 TALK TO EACH OTHER COULD BE A 6102 04:46:27,200 --> 04:46:29,080 BIONIC PANCREAS CLOSE SYSTEM FOR 6103 04:46:29,080 --> 04:46:29,600 MANAGING CFRD. 6104 04:46:29,600 --> 04:46:30,120 NEXT SLIDE. 6105 04:46:30,120 --> 04:46:37,280 THIS IS JUST A STUDY BY SKULLY 6106 04:46:37,280 --> 04:46:40,080 AND THE GROUP, LOOKED AT CGM 6107 04:46:40,080 --> 04:46:42,080 MEASUREMENTS 14 DAYS PRIOR TO 6108 04:46:42,080 --> 04:46:43,360 AND FOLLOWING INITIATION OF ETI 6109 04:46:43,360 --> 04:46:46,480 AND YOU CAN SEE IMPROVEMENT IN 6110 04:46:46,480 --> 04:46:49,000 ALL INDICES AFTER INITIATION OF 6111 04:46:49,000 --> 04:46:51,000 ETI, A LOT MORE WORK TO BE DONE 6112 04:46:51,000 --> 04:46:52,800 BUT JUST A SUGGESTION OF HOW IT 6113 04:46:52,800 --> 04:46:53,560 CAN BE HELPFUL. 6114 04:46:53,560 --> 04:46:53,840 NEXT SLIDE. 6115 04:46:53,840 --> 04:46:56,000 SO I WOULD LIKE TO END WITH 6116 04:46:56,000 --> 04:46:57,440 ACKNOWLEDGES TO MY CO 6117 04:46:57,440 --> 04:46:59,440 INVESTIGATORS ON THE OUTREACH 6118 04:46:59,440 --> 04:47:01,440 STUDY, THE CFF THERAPEUTICS 6119 04:47:01,440 --> 04:47:02,880 DEVELOPMENT NETWORK AND 6120 04:47:02,880 --> 04:47:03,680 RECORDING CENTER WITHOUT WHICH 6121 04:47:03,680 --> 04:47:04,800 ANY OF THIS WOULD BE POSSIBLE 6122 04:47:04,800 --> 04:47:15,320 AND THEN MY SPONSORS, THANK YOU 6123 04:47:23,000 --> 04:47:24,600 SO MUCH. 6124 04:47:24,600 --> 04:47:28,880 >> NTHANK YOU DR. ROSENFELD, AND 6125 04:47:28,880 --> 04:47:30,120 NOW I WOULD LOAMACYIC TO 6126 04:47:30,120 --> 04:47:32,840 INTRODUCE OUR FINAL SPEAKER FOR 6127 04:47:32,840 --> 04:47:34,440 THIS SESSION, JENNIFER KYLE 6128 04:47:34,440 --> 04:47:35,680 COMMUNITY MEMBER PERSPECTIVE? 6129 04:47:35,680 --> 04:47:37,880 I AM 57 LIVING WITH CF AND I'M 6130 04:47:37,880 --> 04:47:40,240 HERE TO SHARE MY PERSONAL JOWRN 6131 04:47:40,240 --> 04:47:42,480 O MODULATOR THERAPY WITH YOU. 6132 04:47:42,480 --> 04:47:46,080 SO I WAS A LATE DIAGNOSIS AT 37. 6133 04:47:46,080 --> 04:47:51,800 MY GENES ARE THE A455 E, AND THE 6134 04:47:51,800 --> 04:47:52,360 R347 H. 6135 04:47:52,360 --> 04:47:53,920 EVEN THOUGH I WAS DIAGNOSED 6136 04:47:53,920 --> 04:47:55,520 LATE, THE SIGNS WERE THERE FROM 6137 04:47:55,520 --> 04:47:59,200 AN EARLY AGE THAT I HAD CF. 6138 04:47:59,200 --> 04:48:04,280 THERE WERE MULTIPLE 6139 04:48:04,280 --> 04:48:05,360 HOSPITALIZATIONS FOR INFECTIONS. 6140 04:48:05,360 --> 04:48:07,800 AT AGE 11 I HAD A FULL SPINAL 6141 04:48:07,800 --> 04:48:09,520 FUSION WITH A HERRINGTON ROD AND 6142 04:48:09,520 --> 04:48:11,080 AFTER THAT I STARTED 6143 04:48:11,080 --> 04:48:12,480 EXPERIENCING MY FIRST GI ISSUES 6144 04:48:12,480 --> 04:48:14,320 AND BECAME VERY NUTRITION 6145 04:48:14,320 --> 04:48:15,680 CONSCIOUS LEARNING WHO TO EAT IN 6146 04:48:15,680 --> 04:48:18,880 ORDER TO FEEL BETTER. 6147 04:48:18,880 --> 04:48:20,440 FROM MY LATE TEENS INTO MY EARLY 6148 04:48:20,440 --> 04:48:24,360 50S I HAD A TOTAL OF 6 SINUS 6149 04:48:24,360 --> 04:48:24,600 SURGERIES. 6150 04:48:24,600 --> 04:48:28,680 IN 20 FLEAN I WAS FIRST 6151 04:48:28,680 --> 04:48:30,200 PRESCRIBED COLIDECO, I WAS ON IT 6152 04:48:30,200 --> 04:48:32,320 NEAR 9 DAYS AND EXPERIENCED 6153 04:48:32,320 --> 04:48:34,160 SEVERE DEPRESSION WITH SUICIDAL 6154 04:48:34,160 --> 04:48:36,000 THOUGHTS SO MY CF DOCTOR FELT IT 6155 04:48:36,000 --> 04:48:39,320 WAS IMPORTANT TO STOP TAKING THE 6156 04:48:39,320 --> 04:48:39,920 MEDICATION. 6157 04:48:39,920 --> 04:48:43,440 IN FEBRUARY OF 2021, I STARTED 6158 04:48:43,440 --> 04:48:46,280 ON TRICAFTA, BUT DUE TO MY 6159 04:48:46,280 --> 04:48:47,560 ISSUES WITH COLIDECO, WE DECIDED 6160 04:48:47,560 --> 04:48:51,040 TO START ON THE 2 ORANGE PILLS 6161 04:48:51,040 --> 04:48:52,120 FOR THE FIRST 2 WEEKS. 6162 04:48:52,120 --> 04:48:55,000 DURING THAT TIME I DID 6163 04:48:55,000 --> 04:48:56,480 EXPERIENCE A SLIGHT PUDGIER AND 6164 04:48:56,480 --> 04:48:57,720 AN INCREASE IN MY LUNG FUNCTION 6165 04:48:57,720 --> 04:48:59,200 WHICH I THINK THEY'RE CALLING 6166 04:48:59,200 --> 04:49:01,200 THE BUMP, AND I WAS NORMALLY 6167 04:49:01,200 --> 04:49:03,040 AROUND A 70 AND I WEPT UP TO AN 6168 04:49:03,040 --> 04:49:07,000 82 AND THEN I PLATEAUED AT A 79. 6169 04:49:07,000 --> 04:49:08,840 FOR THE FIRST TIME IN MY LIFE, 6170 04:49:08,840 --> 04:49:12,040 MY SINUSES WERE CLEAR WITH NO 6171 04:49:12,040 --> 04:49:13,720 INFECTION, AND MY SPUTUM 6172 04:49:13,720 --> 04:49:14,920 CULTURES WERE COMING BACK CLEAR. 6173 04:49:14,920 --> 04:49:16,720 DURING THAT FIRST 2 WEEKS I ALSO 6174 04:49:16,720 --> 04:49:20,000 NOTICED AN INCREASE IN MY 6175 04:49:20,000 --> 04:49:22,960 EXERCISE RECOVERY AND TOLERANCE 6176 04:49:22,960 --> 04:49:26,520 WHICH WAS REALLY FUN. 6177 04:49:26,520 --> 04:49:28,000 SO AFTER THE 2 WEEKS WE DECIDED 6178 04:49:28,000 --> 04:49:30,880 TO START THE EVENING DOSE, BUT 6179 04:49:30,880 --> 04:49:33,440 ABOUT A MONTH INTO THAT, I DID 6180 04:49:33,440 --> 04:49:34,440 START EXPERIENCING DEPRESSION 6181 04:49:34,440 --> 04:49:36,440 AGAIN, SO WE THOUGHT IT BEST TO 6182 04:49:36,440 --> 04:49:37,800 STOP THE EVENING DOSE SINCE IT 6183 04:49:37,800 --> 04:49:39,640 SEEMED THAT I WAS GETTING THE 6184 04:49:39,640 --> 04:49:41,480 FULL BENEFIT FROM THE 2 ORANGE 6185 04:49:41,480 --> 04:49:44,040 PILLS IN THE MORNING. 6186 04:49:44,040 --> 04:49:47,240 I DID NOTICE THAT I HAD MANY 6187 04:49:47,240 --> 04:49:50,480 FRIENDS WHO HAD EXPERIENCED 6188 04:49:50,480 --> 04:49:52,720 EXCESSIVE WEIGHT GAIN ON 6189 04:49:52,720 --> 04:49:54,120 TRICAFTA, AND I DID NOT WANT TO 6190 04:49:54,120 --> 04:49:56,080 HAVE THAT EXPERIENCE SO I WAS 6191 04:49:56,080 --> 04:49:57,960 QUITE STRICT WITH MY DIET AND 6192 04:49:57,960 --> 04:50:00,440 EXERCISE WHILE ON TRICAFTA, I 6193 04:50:00,440 --> 04:50:02,360 DID NOTICE THAT I WAS 6194 04:50:02,360 --> 04:50:05,720 EXPERIENCING A FORM OF BRAIN 6195 04:50:05,720 --> 04:50:07,160 FOG, SLEEP DISRUPTION AND 6196 04:50:07,160 --> 04:50:09,000 INCREASED JOINT PAIN WHICH ALSO 6197 04:50:09,000 --> 04:50:10,000 SEEMS COMMON WITH THE FRIENDS 6198 04:50:10,000 --> 04:50:12,760 THAT I SPEAK TO. 6199 04:50:12,760 --> 04:50:15,560 IN THE FIRST 6 MONTHS ON 6200 04:50:15,560 --> 04:50:18,160 TRICAFTA, I FELT THE GOOD 6201 04:50:18,160 --> 04:50:19,120 OUTWEIGHED THE BAD. 6202 04:50:19,120 --> 04:50:21,640 OT EIGHTH MONTH I WENT FOR MY 6203 04:50:21,640 --> 04:50:23,880 BLOOD WORK AND THIS IS WHERE THE 6204 04:50:23,880 --> 04:50:24,560 SITUATION CHANGED. 6205 04:50:24,560 --> 04:50:26,560 WHILE MY PROVIDER WAS NOT OVERLY 6206 04:50:26,560 --> 04:50:28,240 CONCERNED WITH MY LAB RESULTS I 6207 04:50:28,240 --> 04:50:29,640 WAS SINCE THIS WAS OUT OF MY 6208 04:50:29,640 --> 04:50:31,920 NORM FOR MY BODY AND IN OCTOBER 6209 04:50:31,920 --> 04:50:35,520 OF 2021 MY CHOLESTEROL SHOT UP 6210 04:50:35,520 --> 04:50:38,760 TO A 224 WITH MY LDL COMING IN 6211 04:50:38,760 --> 04:50:40,240 AT 124. 6212 04:50:40,240 --> 04:50:43,200 MY GLUCOSE WHICH FORMALLY HOVERS 6213 04:50:43,200 --> 04:50:45,840 IN THE LOW 40S, WENT UP TO A 75 6214 04:50:45,840 --> 04:50:49,360 AND MY HEMODPLOABIN WENT UP TO 6215 04:50:49,360 --> 04:50:49,600 5.3. 6216 04:50:49,600 --> 04:50:51,600 I DECIDED TO GO COMPLETELY VEGAN 6217 04:50:51,600 --> 04:50:54,320 TO TRY TO COMBAT THE CHOLESTEROL 6218 04:50:54,320 --> 04:50:55,440 ISSUES AND AFTER SPEAKING WITH 6219 04:50:55,440 --> 04:50:56,960 MY DOCTOR, WE BOTH AGREEN CELLED 6220 04:50:56,960 --> 04:50:59,040 TO LOWER ME TO 1 ORANGE PILL 6221 04:50:59,040 --> 04:51:01,640 WHICH I THEN STARTED TAKING IN 6222 04:51:01,640 --> 04:51:03,000 THE EVENING. 6223 04:51:03,000 --> 04:51:05,000 IN NOVEMBER OF 2021, I WENT TO 6224 04:51:05,000 --> 04:51:07,880 SEE MY RHEUMATOLOGIST FOR 6225 04:51:07,880 --> 04:51:08,600 INCREASED OFTIO ARTHRITIS PAIN 6226 04:51:08,600 --> 04:51:12,920 AND ISSUES AND SHE ALSO RAN A 6227 04:51:12,920 --> 04:51:14,920 WHOLE BUNCH OF BLOOD WORK ON ME. 6228 04:51:14,920 --> 04:51:17,160 AT THAT TIME MY GLUCOSE HAD 6229 04:51:17,160 --> 04:51:21,600 CLIMBED TO 110 AND I HAD A 6230 04:51:21,600 --> 04:51:22,760 C-ANKIO SCORE OF 1.40. 6231 04:51:22,760 --> 04:51:25,440 A WHITE BLOOD CELL SCORE OF 6232 04:51:25,440 --> 04:51:26,000 6-10. 6233 04:51:26,000 --> 04:51:30,680 AN AST SCORE OF 51, ALT SCORE OF 6234 04:51:30,680 --> 04:51:32,760 36. 6235 04:51:32,760 --> 04:51:35,360 AND AN ANTIU1 RNPSPOIZ SCORE OF 6236 04:51:35,360 --> 04:51:37,120 20, ALL SIGNS THAT SOMETHING WAS 6237 04:51:37,120 --> 04:51:38,680 CHANGING IN MY BODY. 6238 04:51:38,680 --> 04:51:39,920 I DID REPORT THESE FIND I GUESS 6239 04:51:39,920 --> 04:51:42,520 TO MY CLINIC BUT AGAIN THEY WERE 6240 04:51:42,520 --> 04:51:43,320 NOT OVERLY CONCERNED. 6241 04:51:43,320 --> 04:51:45,320 BUT I WAS. 6242 04:51:45,320 --> 04:51:47,440 IN JANUARY OF 2022, MY CLINIC 6243 04:51:47,440 --> 04:51:48,800 REPEATED MY BLOOD WORK. 6244 04:51:48,800 --> 04:51:51,400 MY CHOLESTEROL DID DROP TO A 6245 04:51:51,400 --> 04:51:54,640 176, NOT SURE IF WAS DUE TO THE 6246 04:51:54,640 --> 04:51:56,200 DECREASE IN TRICAFTA OR THE 6247 04:51:56,200 --> 04:51:58,200 VEGAN DIET BUT I WAS HAPPY IT 6248 04:51:58,200 --> 04:52:00,720 CAME DOWN, BUT MY GLUCOSE 6249 04:52:00,720 --> 04:52:02,360 CONTINUED TO CLIMB AND IT WAS 6250 04:52:02,360 --> 04:52:04,480 NOW AT A 122 AND HIGH HEMOGLOBIN 6251 04:52:04,480 --> 04:52:07,280 WAS STILL HOLDING UP AT A 5.3. 6252 04:52:07,280 --> 04:52:08,560 SO IN FEBRUARY I MADE THE 6253 04:52:08,560 --> 04:52:13,120 DECISION ALONG WITH MY DOCTOR TO 6254 04:52:13,120 --> 04:52:14,520 STOP TAKING TRICAFA. 6255 04:52:14,520 --> 04:52:16,120 I WILL FOLLOW UP WITH MY NEW 6256 04:52:16,120 --> 04:52:19,280 CLINIC IN JULY AS I AM MOVING 6257 04:52:19,280 --> 04:52:21,440 TOMORROW TO KENTUCKY AND SO I 6258 04:52:21,440 --> 04:52:25,240 WILL BE ATTENDING THE VANDERBILT 6259 04:52:25,240 --> 04:52:26,920 CLINIC IN NASHVILLE, TENSE 6260 04:52:26,920 --> 04:52:27,600 CONTINUOUS, SO HERE'S WHEY WOULD 6261 04:52:27,600 --> 04:52:29,400 LIKE TO TELL YOU THAT THE GOOD 6262 04:52:29,400 --> 04:52:32,320 NEWS, IS AFTER COMING OFF 6263 04:52:32,320 --> 04:52:34,240 TRICAFTA IN FEBRUARY, MY SINUSES 6264 04:52:34,240 --> 04:52:36,640 HAVE REMAINED ABSOLUTELY CLEAR. 6265 04:52:36,640 --> 04:52:38,960 I SAW MY ENT LAST WEEK, THEY 6266 04:52:38,960 --> 04:52:40,680 SCOPED ME AND EVERYTHING WAS 6267 04:52:40,680 --> 04:52:41,120 BEAUTIFUL. 6268 04:52:41,120 --> 04:52:43,520 MY LUNG FUNCTION HAS HELD AT A 6269 04:52:43,520 --> 04:52:45,880 79 WHICH I AM ABSOLUTELY 6270 04:52:45,880 --> 04:52:46,520 THRILLED ABOUT. 6271 04:52:46,520 --> 04:52:48,160 AND I FEEL LIKE MYSELF AGAIN. 6272 04:52:48,160 --> 04:52:52,560 I HAVE TO SAY I AM HAPPY THAT I 6273 04:52:52,560 --> 04:52:55,240 AM OFF TRICAFTA, ALSO MY 6274 04:52:55,240 --> 04:52:56,320 OSTEOARTHRITIS PAIN AS GONE AWAY 6275 04:52:56,320 --> 04:52:58,920 SO NOW I LOOK FORWARD TO THE 6276 04:52:58,920 --> 04:53:00,600 MRNA THERAPIES AND GENETIC 6277 04:53:00,600 --> 04:53:01,680 THERAPIES THAT ARE COMING DOWN 6278 04:53:01,680 --> 04:53:03,200 THE ROAD, I HOPE 1 DAY THAT I 6279 04:53:03,200 --> 04:53:06,520 CAN BE IN A CLINICAL TRIAL FOR 1 6280 04:53:06,520 --> 04:53:08,520 OF THESE AND ARE LOOK TO WHAT 6281 04:53:08,520 --> 04:53:10,080 THE FUTURE WILL HOLD FOR US AS 6282 04:53:10,080 --> 04:53:12,680 WE FIGURE OUT THE ROAD TO THESE 6283 04:53:12,680 --> 04:53:14,640 MODULATOR THERAPIES A LITTLE BIT 6284 04:53:14,640 --> 04:53:14,880 BETTER. 6285 04:53:14,880 --> 04:53:16,880 SO I WOULD LIKE TO THANK YOU FOR 6286 04:53:16,880 --> 04:53:17,960 LISTENING TO MY STORY TODAY AND 6287 04:53:17,960 --> 04:53:19,360 AT THIS TIME, I WOULD LIKE TO 6288 04:53:19,360 --> 04:53:29,920 OPEN IT UP TO THE QANDA SESSION. 6289 04:53:31,400 --> 04:53:31,960 >> THANK YOU SO. 6290 04:53:31,960 --> 04:53:33,680 >> THANK YOU THAT WAS INCREDIBLY 6291 04:53:33,680 --> 04:53:35,880 HUMBLING AND IT SHOWS US HOW 6292 04:53:35,880 --> 04:53:37,240 EVERY STORY IS UNIQUE AND 6293 04:53:37,240 --> 04:53:39,440 IMPORTANT AND WHY WE ARE ALL, 6294 04:53:39,440 --> 04:53:45,240 ALL HERE AND GOOD LUCK ON YOUR 6295 04:53:45,240 --> 04:53:45,440 MOVE. 6296 04:53:45,440 --> 04:53:47,000 >> WE'RE HAPPY TO HAVE EVERYBODY 6297 04:53:47,000 --> 04:53:47,200 HERE. 6298 04:53:47,200 --> 04:53:53,720 I THINK WE ARE READY TO START 6299 04:53:53,720 --> 04:53:54,320 WITH THE QUESTIONS. 6300 04:53:54,320 --> 04:53:59,080 I WILL PULL THEM UP. 6301 04:53:59,080 --> 04:54:02,560 I FOR 1 THINK WE HAVE TO BE 6302 04:54:02,560 --> 04:54:03,040 PATIENT. 6303 04:54:03,040 --> 04:54:04,800 I AM SO ANXIOUS FOR ALL OF THESE 6304 04:54:04,800 --> 04:54:09,240 OUTCOMES TO BE READY FROM MY 6305 04:54:09,240 --> 04:54:11,240 PERSPECTIVE, BOTH FROM, YOU KNOW 6306 04:54:11,240 --> 04:54:12,720 NEEDS OUTCOMES FOR OUR STUDIES 6307 04:54:12,720 --> 04:54:16,640 BUT ALSO OF COURSE FOR, YOU 6308 04:54:16,640 --> 04:54:17,680 KNOW, JUST ADVANCING OUR 6309 04:54:17,680 --> 04:54:20,160 KNOWLEDGE ABOUT HOW THIS DISEASE 6310 04:54:20,160 --> 04:54:21,040 IS ACTUALLY PROGRESSING FOR 6311 04:54:21,040 --> 04:54:22,880 EVERYBODY WHETHER OR NOT YOU'RE 6312 04:54:22,880 --> 04:54:27,520 ON MODULATORS OR NOT. 6313 04:54:27,520 --> 04:54:28,280 OUR FIRST QUESTION, ACTUALLY 6314 04:54:28,280 --> 04:54:31,680 FIRST I WANT TO INTRODUCE 6315 04:54:31,680 --> 04:54:32,880 DR. GOSS WHO IS JOINING US. 6316 04:54:32,880 --> 04:54:36,000 HE SUFFICIENCY 1 OF THE MULTIPLE 6317 04:54:36,000 --> 04:54:37,200 PIs ON THE STOP STUDY AND WE 6318 04:54:37,200 --> 04:54:38,960 HAVE A LOT OF QUESTIONS FROM 6319 04:54:38,960 --> 04:54:42,320 DR. WEST TO TALK ABOUT THE STOP 6320 04:54:42,320 --> 04:54:44,600 STUDY AND EXACERBATIONS AND HE'S 6321 04:54:44,600 --> 04:54:46,880 GRACIOUSLY JOINING US TO BE ABLE 6322 04:54:46,880 --> 04:54:48,920 TO ASK THOSE QUESTIONS AND ON 6323 04:54:48,920 --> 04:54:51,720 THAT NOTE LET ME THROW THE FIRST 6324 04:54:51,720 --> 04:54:53,720 QUESTION YOUR WAY, CHRIS, CHRIS 6325 04:54:53,720 --> 04:54:55,680 WE A HARD TIME AGREEING ON THE 6326 04:54:55,680 --> 04:54:58,200 DEFINITION OF EXACERBATION IN 6327 04:54:58,200 --> 04:55:00,280 THE PREMODDULATOR ERA, HOW WILL 6328 04:55:00,280 --> 04:55:01,840 WE AGREE NOW. 6329 04:55:01,840 --> 04:55:04,040 >> YEAH, WE--WE WENT, I THINK--I 6330 04:55:04,040 --> 04:55:05,560 THINK BRUCE MARSHAL CALLED FOR A 6331 04:55:05,560 --> 04:55:08,800 DEFINITION, I THINK HIS PAPER 6332 04:55:08,800 --> 04:55:09,560 WAS 1999. 6333 04:55:09,560 --> 04:55:11,280 WE ALL COME TOGETHER AND AGREE 6334 04:55:11,280 --> 04:55:12,120 ON A DEVELOPMENTAL ENDOCRINOLOGY 6335 04:55:12,120 --> 04:55:13,560 MISSION AND AS YOU CAN SEE WE 6336 04:55:13,560 --> 04:55:15,960 ARE 2022 WITH NO CLEAR 6337 04:55:15,960 --> 04:55:16,320 DEFINITION. 6338 04:55:16,320 --> 04:55:19,280 I THINK IT'S VERY CHALLENGING, 6339 04:55:19,280 --> 04:55:23,160 AND I THINK THERE'S A BROAD 6340 04:55:23,160 --> 04:55:24,200 PHENOTYPE OF EXACERBATION. 6341 04:55:24,200 --> 04:55:25,760 I THINK WE SETTLED FOR THE 6342 04:55:25,760 --> 04:55:28,400 PURPOSE OF CLINICAL TRIALS TO 6343 04:55:28,400 --> 04:55:31,400 DEFINE IT BASICALLY ON THE 6344 04:55:31,400 --> 04:55:32,440 PHYSICIAN DEFINED DEFINITION OF 6345 04:55:32,440 --> 04:55:34,520 INITIATION OF TREATMENT WHICH IS 6346 04:55:34,520 --> 04:55:35,080 SORT OF CIRCULAR. 6347 04:55:35,080 --> 04:55:37,480 DEFINED BY THE UT COME, I MEAN 6348 04:55:37,480 --> 04:55:39,320 BY THE TREATMENT YOU GIVE. 6349 04:55:39,320 --> 04:55:40,840 HOWEVER, I THINK IT HAS BEEN 6350 04:55:40,840 --> 04:55:42,400 USEFUL AND I DON'T--I DON'T 6351 04:55:42,400 --> 04:55:45,600 KNOW, I THINK WITH THE CHANGING 6352 04:55:45,600 --> 04:55:46,960 DYNAMIC OF EXACERBATION, IT MAY 6353 04:55:46,960 --> 04:55:52,440 BE MORE CHALLENGING TO COME TO A 6354 04:55:52,440 --> 04:55:52,720 DEFINITION. 6355 04:55:52,720 --> 04:55:54,400 WE DO COLLECT STANDARD 6356 04:55:54,400 --> 04:55:55,320 INFORMATION ABOUT EACH 6357 04:55:55,320 --> 04:55:56,920 EXACERBATION WHICH HELPED US AT 6358 04:55:56,920 --> 04:55:59,080 LEAST DESCRIBE THESE DIFFERENT 6359 04:55:59,080 --> 04:56:00,880 VARIETIES AND THERE'S AN ONGOING 6360 04:56:00,880 --> 04:56:02,880 PROJECT RIGHT NOW TO FIGURE OUT 6361 04:56:02,880 --> 04:56:04,320 IF DIFFERENT PHENOTYPES OF 6362 04:56:04,320 --> 04:56:05,920 EXACERBATION, BUT I THINK, IT'S 6363 04:56:05,920 --> 04:56:07,000 BEEN CHALLENGING AND I THINK 6364 04:56:07,000 --> 04:56:08,520 THAT THERE ARE MANY REASONS WHY 6365 04:56:08,520 --> 04:56:17,800 WE HAVEN'T COME DO A STANDARD 6366 04:56:17,800 --> 04:56:19,400 DEFINITION. 6367 04:56:19,400 --> 04:56:20,520 ALTHOUGH, NONCF BRONCHIECTASIS 6368 04:56:20,520 --> 04:56:20,800 HAS. 6369 04:56:20,800 --> 04:56:26,000 WE CAN ALSO TRY I THINK I STILL 6370 04:56:26,000 --> 04:56:27,840 REMEMBER MARGARET ROH 6371 04:56:27,840 --> 04:56:28,880 SENFELLED'S GREAT SLIDE WHERE 6372 04:56:28,880 --> 04:56:30,880 SHE SHOWS A SLIDE AND SHE KNOWS 6373 04:56:30,880 --> 04:56:31,960 WE KNOW 1 WHEN WE SEE 1. 6374 04:56:31,960 --> 04:56:36,840 I THINK WE ARE ATA CHALLENGE 6375 04:56:36,840 --> 04:56:40,280 THERE SO USING THESE DATA WE 6376 04:56:40,280 --> 04:56:42,040 HAVE, MIGHT HELP IN THAT 6377 04:56:42,040 --> 04:56:43,320 DEFINITION PROCESS. 6378 04:56:43,320 --> 04:56:45,640 >> I WOULD LIKE TO FOLLOW UP AND 6379 04:56:45,640 --> 04:56:47,280 SAY,Y HAVE A UNIQUE EXPERIENCE 6380 04:56:47,280 --> 04:56:50,040 OF YOU JOINING US BOTH BEING AND 6381 04:56:50,040 --> 04:56:54,040 OFF A MODULATOR DO YOU RECALL 6382 04:56:54,040 --> 04:56:55,080 HAVING AN EXACERBATION BEFORE 6383 04:56:55,080 --> 04:56:57,240 HAND AND AFTER HAND AND HOW THAT 6384 04:56:57,240 --> 04:56:58,360 MAY HAVE DIFFERED? 6385 04:56:58,360 --> 04:57:00,240 I WOULD LOVE TO HEAR YOU KNOW 6386 04:57:00,240 --> 04:57:00,760 THAT EXPERIENCE? 6387 04:57:00,760 --> 04:57:02,280 >> THIS WILL BE AWESOME BECAUSE 6388 04:57:02,280 --> 04:57:05,960 I JUST HAD AN EXACERBATION. 6389 04:57:05,960 --> 04:57:08,280 SO THAT'S WHY I WENT TO MY ENT. 6390 04:57:08,280 --> 04:57:10,520 SO BEFORE WHEN I WOULD HAVE AN 6391 04:57:10,520 --> 04:57:12,120 EXACERBATION, I WOULD ABSOLUTELY 6392 04:57:12,120 --> 04:57:14,040 BE IN THE HOSPITAL GETTING MY 6393 04:57:14,040 --> 04:57:15,680 CENTRAL LINE PUT IN AND WOULD BE 6394 04:57:15,680 --> 04:57:20,080 ON OF COURSE A 14 DAYS OF IV 6395 04:57:20,080 --> 04:57:20,360 ANTIBIOTICS. 6396 04:57:20,360 --> 04:57:23,680 SO AT THIS TIME WHEN I STARTED 6397 04:57:23,680 --> 04:57:25,000 THE EXACERBATION, I CALLED MY 6398 04:57:25,000 --> 04:57:26,960 CLINIC AND I SPOKE TO MY DOCTOR 6399 04:57:26,960 --> 04:57:29,160 AND I SAID, I FEEL LIKE I SHOULD 6400 04:57:29,160 --> 04:57:30,880 BE IN THE HOSPITAL BUT I'M GOING 6401 04:57:30,880 --> 04:57:34,400 TO GO SEE MY ENT FIRST. 6402 04:57:34,400 --> 04:57:35,600 LET'S SEE WHAT THEY SAY, IF THEY 6403 04:57:35,600 --> 04:57:37,320 TELL ME THIS IS BAD, I WILL CALL 6404 04:57:37,320 --> 04:57:41,280 YOU AND WE'LL GET ME IN, SO SHE 6405 04:57:41,280 --> 04:57:43,320 AGREED AND THEY TOLD ME MY 6406 04:57:43,320 --> 04:57:45,880 SINUSES WERE BEAUTIFUL AND THAT 6407 04:57:45,880 --> 04:57:46,880 THE ORAL ANTIBIOTICS HIALREADY 6408 04:57:46,880 --> 04:57:49,720 BEEN TAKING WERE WORKING, I 6409 04:57:49,720 --> 04:57:51,040 THOUGHT, THIS IS--I ACTUALLY 6410 04:57:51,040 --> 04:57:52,080 STARTED CRYING BECAUSE YOU DON'T 6411 04:57:52,080 --> 04:57:54,280 EVER HEAR THAT SO I BURST INTO 6412 04:57:54,280 --> 04:57:56,200 TEARS WHICH THE NORMAL WAY TO 6413 04:57:56,200 --> 04:57:58,680 HANDLE THAT NEWS. 6414 04:57:58,680 --> 04:58:00,080 AND I WAS SO HAPPY THAT I DIDN'T 6415 04:58:00,080 --> 04:58:01,760 HAVE TO GO IN THE HOSPITAL, I 6416 04:58:01,760 --> 04:58:03,880 DIDN'T HAVE TO GO ON IVs AND I 6417 04:58:03,880 --> 04:58:06,160 KNEW I WAS GOING TO BE OKAY AND 6418 04:58:06,160 --> 04:58:08,840 FOR THE FIRST TIME EVER I COULD 6419 04:58:08,840 --> 04:58:11,640 FIGHT AN INFECTION WITH JUST 6420 04:58:11,640 --> 04:58:13,800 ORAL ANTIBIOTICS, THAT WAS 6421 04:58:13,800 --> 04:58:14,640 CRAZY. 6422 04:58:14,640 --> 04:58:16,120 IT WAS ABSOLUTELY CRAZY. 6423 04:58:16,120 --> 04:58:20,320 SO I AM OVER THE MOON. 6424 04:58:20,320 --> 04:58:21,920 WORDS CANNOT EXPRESS WHAT THAT 6425 04:58:21,920 --> 04:58:22,320 DOES FOR ME. 6426 04:58:22,320 --> 04:58:26,520 >> THANK YOU FOR SHARING THAT 6427 04:58:26,520 --> 04:58:26,800 EXPERIENCE. 6428 04:58:26,800 --> 04:58:28,640 >> NICOLE CAN I ASK A QUESTION, 6429 04:58:28,640 --> 04:58:30,400 TO CHRIS AS WELL, CHRIS THIS IS 6430 04:58:30,400 --> 04:58:33,280 MEANT TO BE A BIT PROVOCATIVE, 6431 04:58:33,280 --> 04:58:36,840 BUT WITH THE DRAMATIC DECLINE IN 6432 04:58:36,840 --> 04:58:37,400 EXACERBATION, RATES RELATED 6433 04:58:37,400 --> 04:58:39,280 SOMEWHAT TO COVID AND SOMEWHAT 6434 04:58:39,280 --> 04:58:41,360 TO HEMT, DOES THAT PUT THE STOP 6435 04:58:41,360 --> 04:58:43,560 360 PLATFORM OUT OF BUSINESS? 6436 04:58:43,560 --> 04:58:47,480 OR LESS JOKINGLY, HOW ARE YOU 6437 04:58:47,480 --> 04:58:49,080 REVISING YOUR ANTICIPATED TRIALS 6438 04:58:49,080 --> 04:58:53,440 BASED ON A MUCH LOWER RATE OF IV 6439 04:58:53,440 --> 04:58:53,720 ANTIBIOTICS? 6440 04:58:53,720 --> 04:59:04,200 >> YEAH, THAT'S A GREAT 6441 04:59:04,680 --> 04:59:04,880 QUESTION. 6442 04:59:04,880 --> 04:59:07,600 I THINK WHAT WE'VE LEARNED IN 6443 04:59:07,600 --> 04:59:10,960 THE CLINICS IS AN ADULT UPTAKE 6444 04:59:10,960 --> 04:59:12,400 IN INFECTIONS IN, SINCE 6445 04:59:12,400 --> 04:59:13,880 EVERYONE'S WONDERING OUT IN 6446 04:59:13,880 --> 04:59:17,120 PUBLIC AGAIN AND GET RESPIRATORY 6447 04:59:17,120 --> 04:59:19,120 VIRUSES AND THOSE ARE PRETTY 6448 04:59:19,120 --> 04:59:20,640 IMPORTANT IN WHATEVER--SOMEONE 6449 04:59:20,640 --> 04:59:22,920 WHO HAS A CHRONIC LOWER 6450 04:59:22,920 --> 04:59:32,840 AEOINFECTION, SO WE DID USE DATA 6451 04:59:32,840 --> 04:59:38,280 FROM 2020 FOR WHAT WE CAN DO IN 6452 04:59:38,280 --> 04:59:39,720 THIS THERE, SO THAT'S BEEN 6453 04:59:39,720 --> 04:59:41,200 HELPFUL TO ANTICIPATE WHAT'S 6454 04:59:41,200 --> 04:59:41,600 GOING TO HAPPEN. 6455 04:59:41,600 --> 04:59:44,240 BASED ON SOME OF OUR DATA ANYWAY 6456 04:59:44,240 --> 04:59:47,240 FROM WHAT WE KNOW OF PEOPLE ON 6457 04:59:47,240 --> 04:59:51,320 MODULATORS AND THAT MEANS 6458 04:59:51,320 --> 04:59:52,960 PRIMARILY IVACAFTOR, WE DO THINK 6459 04:59:52,960 --> 04:59:54,320 THE DROP FOR EXACERBATION IS 6460 04:59:54,320 --> 04:59:57,520 SIMILAR AND WE WILL SEE IF THAT 6461 04:59:57,520 --> 04:59:58,600 CONTINUES WITH TRICAFTA, BECAUSE 6462 04:59:58,600 --> 05:00:00,760 IT'S CERTAINLY BETTER THAN 6463 05:00:00,760 --> 05:00:05,320 IVACAFT, ON R, ALONE AND THEN 6464 05:00:05,320 --> 05:00:06,840 MAYBE THEY COME LESS OFTEN BUT 6465 05:00:06,840 --> 05:00:08,480 THEY STILL REQUIRE INTENSIVE 6466 05:00:08,480 --> 05:00:10,160 THERAPY BUT ONLY TIME WILL TELL 6467 05:00:10,160 --> 05:00:11,600 BUT WE INCREASE, WE HAVE LOTS OF 6468 05:00:11,600 --> 05:00:14,600 SITES AND WE HAVE A BIT MORE 6469 05:00:14,600 --> 05:00:16,000 PROLONGED ENROLLMENT PERIOD FOR 6470 05:00:16,000 --> 05:00:16,280 THE TRIAL. 6471 05:00:16,280 --> 05:00:20,040 SO I THINK WE WILL BE OKAY BUT 6472 05:00:20,040 --> 05:00:23,840 TIME WILL TELL. 6473 05:00:23,840 --> 05:00:26,040 >> THANK YOU. 6474 05:00:26,040 --> 05:00:26,680 GO, AHEAD. 6475 05:00:26,680 --> 05:00:28,200 >> GO,A HEAD, YOU CAN TELL IT'S 6476 05:00:28,200 --> 05:00:29,480 HARD TO REHEARSE IT, OUR NEXT 6477 05:00:29,480 --> 05:00:30,920 QUESTION IS FOR HEATHER THOUGH 6478 05:00:30,920 --> 05:00:32,520 EVERYONE CAN CHIME IN, DO OTHERS 6479 05:00:32,520 --> 05:00:34,400 IN THE FIELD FEEL IT'S IMPORTANT 6480 05:00:34,400 --> 05:00:36,600 TO CONSIDER WHETHER CANDIDATE 6481 05:00:36,600 --> 05:00:38,920 BIOMARKERS OF INFECTION ARE HOST 6482 05:00:38,920 --> 05:00:40,960 DERIVED OR OF MICROBIAL ORIGIN, 6483 05:00:40,960 --> 05:00:44,440 OR IS THIS AN AREA OF 6484 05:00:44,440 --> 05:00:44,800 CONTROVERSY? 6485 05:00:44,800 --> 05:00:47,080 >> I SAW THAT QUESTION CAME IN 6486 05:00:47,080 --> 05:00:48,720 FROM LUKE, FEEL LIKE WE'VE HAD 6487 05:00:48,720 --> 05:00:53,000 THIS DISCUSSION IN THE PAST. 6488 05:00:53,000 --> 05:00:55,920 I THINK THAT IT DEPENDS ON WHAT 6489 05:00:55,920 --> 05:00:57,560 YOU'RE USING THE BIOMARKERS FOR. 6490 05:00:57,560 --> 05:00:59,000 SO IF YOU'RE USING IT FOR 6491 05:00:59,000 --> 05:01:03,400 DIAGNOSIS ISSUING I THINK THAT 6492 05:01:03,400 --> 05:01:04,840 IT DOESN'T REALLY MATTER, IF YOU 6493 05:01:04,840 --> 05:01:06,360 ARE DIAGNOSING AN INFECTION 6494 05:01:06,360 --> 05:01:08,280 BASED ON A BIOMARKER THAT'S 6495 05:01:08,280 --> 05:01:09,120 DERIVE FRIDAY THE PATHOGEN OR 6496 05:01:09,120 --> 05:01:14,800 THE HOST OR THE HOST PATHOGEN 6497 05:01:14,800 --> 05:01:16,640 INTERACTION, THE--SO LONG AS IT 6498 05:01:16,640 --> 05:01:24,000 HOLDS UP WHEN YOU ARE LOOKING AT 6499 05:01:24,000 --> 05:01:25,600 CONTROLLING FOR SENSITIVITY AND 6500 05:01:25,600 --> 05:01:27,400 SPECIFICITY, AND IT MEETS--IT'S 6501 05:01:27,400 --> 05:01:30,160 MEETING A NEED FOR TAKING A 6502 05:01:30,160 --> 05:01:31,360 CLINICAL ACTION, I DON'T BEING 6503 05:01:31,360 --> 05:01:32,200 THAT IT REALLY MATTERS. 6504 05:01:32,200 --> 05:01:35,480 IF YOU ARE USING THAT 6505 05:01:35,480 --> 05:01:37,600 INFORMATION TO HELP YOU CHOOSE A 6506 05:01:37,600 --> 05:01:41,760 THERAPY, THEN IT MIGHT BE MORE 6507 05:01:41,760 --> 05:01:43,360 IMPORTANT TO KNOW IF THAT 6508 05:01:43,360 --> 05:01:44,960 PARTICULAR MICROBE WILL BE 6509 05:01:44,960 --> 05:01:46,160 SENSITIVE TO THAT PARTICULAR 6510 05:01:46,160 --> 05:01:48,120 ANTIBIOTIC AND THEN IT MIGHT BE 6511 05:01:48,120 --> 05:01:52,720 MUCH MORE IMPORTANT TO 6512 05:01:52,720 --> 05:01:53,880 UNDERSTAND THE BIOLOGICAL 6513 05:01:53,880 --> 05:01:55,400 ORIGEIGE OF THAT BIOMARKER SO I 6514 05:01:55,400 --> 05:01:57,880 THINK IT MATTERS ON HOW YOU'RE 6515 05:01:57,880 --> 05:02:01,360 USING THAT INFORMATION. 6516 05:02:01,360 --> 05:02:02,160 >> THANK YOU. 6517 05:02:02,160 --> 05:02:04,520 >> GREAT. 6518 05:02:04,520 --> 05:02:05,240 QUESTION FOR ZACH. 6519 05:02:05,240 --> 05:02:07,000 LOT OF ACRONYMS IN. 6520 05:02:07,000 --> 05:02:08,720 >> CURRENT TIME REQUIRED TO 6521 05:02:08,720 --> 05:02:10,920 REQUIRE UTE MRI AIM KNOWLEDGES 6522 05:02:10,920 --> 05:02:12,480 AND RESPIRATORY MOTION AFFECT 6523 05:02:12,480 --> 05:02:13,480 IMAGE QUALITY ESPECIALLY IN 6524 05:02:13,480 --> 05:02:14,520 YOUNG CHILDREN WHO CAN'T HOLD 6525 05:02:14,520 --> 05:02:20,160 THEIR BREATH AND HAVE HIGH RR? 6526 05:02:20,160 --> 05:02:20,960 >> REZONING PIRATTORY RATES. 6527 05:02:20,960 --> 05:02:21,200 >> YES. 6528 05:02:21,200 --> 05:02:22,760 >> SO I THINK THE BEST IMAGES WE 6529 05:02:22,760 --> 05:02:25,440 SHOW YOU WE CAN GET DOWN AND 6530 05:02:25,440 --> 05:02:27,800 AROUND 5 MINUTES PLUS OR MINUS. 6531 05:02:27,800 --> 05:02:29,120 THERE ARE--THERE ARE MECHANISMS 6532 05:02:29,120 --> 05:02:31,440 WITH WHICH YOU CAN ACCELERATE 6533 05:02:31,440 --> 05:02:32,920 THAT, IT'S CALLED COMPRETIONZED 6534 05:02:32,920 --> 05:02:35,040 SENSING AND IT'S THE INVERSE OF 6535 05:02:35,040 --> 05:02:37,720 A JPEG WHERE YOU--AND THAT 6536 05:02:37,720 --> 05:02:39,560 YOU--IN A JPEG YOU HAVE A HIGH 6537 05:02:39,560 --> 05:02:42,000 RESOLUTION IMAGE AND YOU THROW 6538 05:02:42,000 --> 05:02:42,680 AWAY REDUNDANT INFORMATION AND 6539 05:02:42,680 --> 05:02:44,520 SHRINK IT DOWN, AND YOU SAY, YOU 6540 05:02:44,520 --> 05:02:45,520 KNOW WHERE THOSE REDUNDANT 6541 05:02:45,520 --> 05:02:47,000 SPACES WILL BE SO YOU ONLY 6542 05:02:47,000 --> 05:02:48,600 REQUIRE THE DATA YOU NEED TO 6543 05:02:48,600 --> 05:02:49,720 MAKE SOMETHING FAITHFUL TO THE 6544 05:02:49,720 --> 05:02:51,240 EDGES IN YOUR IMAGE, SO THAT CAN 6545 05:02:51,240 --> 05:02:53,640 SPEED IT UP FURTHER. 6546 05:02:53,640 --> 05:02:55,640 ONE OF THE STRENGTHS OF THESE 6547 05:02:55,640 --> 05:02:57,800 UTE TYPE SEQUENCES I DIDN'T GO 6548 05:02:57,800 --> 05:03:00,560 INTO IS THEY'RE INTRINSICALLY 6549 05:03:00,560 --> 05:03:00,960 ROBUST MOTION. 6550 05:03:00,960 --> 05:03:03,240 JUST YOU CAN ACTUALLY MAKE A 6551 05:03:03,240 --> 05:03:05,200 DESEBT LOOKING LUNG IMAGE 6552 05:03:05,200 --> 05:03:06,600 COMPLETELY UNGATED, SO IF THE 6553 05:03:06,600 --> 05:03:08,800 KID IS TURNING CIRCLES THAT WILL 6554 05:03:08,800 --> 05:03:12,120 BE A PROBLEM, BUT IF IT'S JUST 6555 05:03:12,120 --> 05:03:13,640 NORMAL WIGGLING IT'S PRETTY 6556 05:03:13,640 --> 05:03:13,880 ROBUST. 6557 05:03:13,880 --> 05:03:16,160 ANOTHER INTERESTING THING IS WE 6558 05:03:16,160 --> 05:03:18,360 ACTUALLY DID THE SIGNAL DISEASE 6559 05:03:18,360 --> 05:03:19,520 MODULATED BY THE RESPIRATORY 6560 05:03:19,520 --> 05:03:20,920 WAVE FORM IN AN UNDERSTANDABLE 6561 05:03:20,920 --> 05:03:23,320 WAY SO WE CAN DO OUR IMAGE 6562 05:03:23,320 --> 05:03:24,640 RECONSTRUCTIONS THAT MINIMIZES 6563 05:03:24,640 --> 05:03:27,480 THE IMPACT OF MOTION. 6564 05:03:27,480 --> 05:03:29,280 SO WE--WE ROUTINELY MAKE UT 6565 05:03:29,280 --> 05:03:31,560 IMAGES OF 5 YEAR-OLDS AND MY 6566 05:03:31,560 --> 05:03:36,280 COLLEAGUES JASON AND NORA, 6567 05:03:36,280 --> 05:03:37,640 REGULARLY DONYONATAL IMAGING AND 6568 05:03:37,640 --> 05:03:41,040 THEY ARE VERY SQUIRMY, SO, IT'S 6569 05:03:41,040 --> 05:03:43,240 NONTRIVIAL BUT IF YOU HAVE TECHS 6570 05:03:43,240 --> 05:03:45,320 WHO ARE USED TO DOING IT THEY 6571 05:03:45,320 --> 05:03:50,800 CAN MAYBE IT HAPPEN. 6572 05:03:50,800 --> 05:03:52,720 >> GREAT, OKAY, THIS IS FUNDY, 6573 05:03:52,720 --> 05:03:54,160 THE NEXT QUESTION FOR HEATHER IS 6574 05:03:54,160 --> 05:03:56,160 FROM ME, SO IN YOUR EVALUATION 6575 05:03:56,160 --> 05:03:58,560 OF EXHALED BREATH TO CORRECTLY 6576 05:03:58,560 --> 05:04:00,680 CLASSIFY PA POSITIVE VERSUS PA 6577 05:04:00,680 --> 05:04:01,960 NEGATIVE PATIENTS WHICH WAS 6578 05:04:01,960 --> 05:04:04,440 SUPER EXCITING DID YOU CLASSIFY 6579 05:04:04,440 --> 05:04:06,840 THEM AS PA POSITIVE VERSUS PA 6580 05:04:06,840 --> 05:04:09,160 NEGATIVE EXCLUSIVELY ON THE 6581 05:04:09,160 --> 05:04:14,320 PACEIS OF SPUTUM SAMPLES OR OP 6582 05:04:14,320 --> 05:04:15,040 ORAL PHARYNGIAL SAMPLES. 6583 05:04:15,040 --> 05:04:18,360 >> NO, FOR THAT STUDY WE WERE 6584 05:04:18,360 --> 05:04:19,760 RELYING ON SPUTUM CULTURE BUT 6585 05:04:19,760 --> 05:04:23,400 NOT JUST ON THE DAY OF 6586 05:04:23,400 --> 05:04:24,480 COLLECTION, BUT ALSO HISTORICAL, 6587 05:04:24,480 --> 05:04:28,040 SO IN ORDER TO ENROLL, THEY WELL 6588 05:04:28,040 --> 05:04:30,480 TO MEET THE LEADS CRITERIA SO 6589 05:04:30,480 --> 05:04:31,960 THAT MEANT THEY WERE GOING TO 6590 05:04:31,960 --> 05:04:34,120 HAVE A HISTORICAL POSITIVE 6591 05:04:34,120 --> 05:04:34,360 RECORD. 6592 05:04:34,360 --> 05:04:36,760 WE ALSO ARE CONSIDERING WHAT 6593 05:04:36,760 --> 05:04:38,520 HAPPENS IN THEIR CLINICAL RECORD 6594 05:04:38,520 --> 05:04:40,720 UP TO 6 MONTHS AFTER WE 6595 05:04:40,720 --> 05:04:42,200 COLLECTED THAT BREATH SAMPLE 6596 05:04:42,200 --> 05:04:44,200 JUST IN CASE, IN PARTICULAR, 6597 05:04:44,200 --> 05:04:48,320 SOMEONE WHO WAS CLASSIFIED AS 6598 05:04:48,320 --> 05:04:48,920 PSEUDOMOANIS NEGATIVE GAME 6599 05:04:48,920 --> 05:04:50,320 POSITIVE AT THE TIME OF 6600 05:04:50,320 --> 05:04:54,080 COLLECTION, WE SEE REALLY GOOD 6601 05:04:54,080 --> 05:04:56,560 CONCORDANCE BETWEEN OUR 6602 05:04:56,560 --> 05:04:57,920 CLASSIFICATION OF PSEUDOMOANUS 6603 05:04:57,920 --> 05:04:59,280 POSITIVE VERSUS NEGATIVE AND 6604 05:04:59,280 --> 05:05:02,440 THEN THERE ARE OVERALL CLINICAL 6605 05:05:02,440 --> 05:05:04,520 RECORD BECAUSE OF THOSE 6606 05:05:04,520 --> 05:05:06,160 ENROLLMENT CRITERIA, WE DON'T 6607 05:05:06,160 --> 05:05:07,320 SEE AS GOOD CONCORDANCE IF WE 6608 05:05:07,320 --> 05:05:09,160 TRY TO LOOK AT STAFF, I THINK 6609 05:05:09,160 --> 05:05:11,400 SOME OF THAT IS CHALLENGING 6610 05:05:11,400 --> 05:05:13,160 BECAUSE OF INFECTION VERSUS 6611 05:05:13,160 --> 05:05:14,600 COLKNOWIZATION AND THAT'S WHY WE 6612 05:05:14,600 --> 05:05:18,040 DIDN'T TACKLE STAFF, RIGHT OUT 6613 05:05:18,040 --> 05:05:18,360 OF THE GATE. 6614 05:05:18,360 --> 05:05:20,360 BUT ALSO, I THINK IF WE TAKE A 6615 05:05:20,360 --> 05:05:21,920 BROADER PICTURE AND LOOK MORE IN 6616 05:05:21,920 --> 05:05:22,960 THEIR CLINICAL RECORD AND NOT 6617 05:05:22,960 --> 05:05:24,880 JUST THEIR DAY OF CULTURE, 6618 05:05:24,880 --> 05:05:28,040 HISTORY AT THE DAY OF BREATH 6619 05:05:28,040 --> 05:05:29,480 COLLECTION, IT WILL CRYSTALLIZE 6620 05:05:29,480 --> 05:05:32,280 THAT INFORMATION A LITTLE BIT 6621 05:05:32,280 --> 05:05:32,520 BETTER. 6622 05:05:32,520 --> 05:05:35,520 WE DID NOT USE OP SWABS, WE KNOW 6623 05:05:35,520 --> 05:05:38,360 THE PROBLEM OF OP PER DETUCTING 6624 05:05:38,360 --> 05:05:41,640 PSEUDOMOANUS AND THIS STUDY IS 6625 05:05:41,640 --> 05:05:43,400 DESIGNED TO LOOK AT THE 6626 05:05:43,400 --> 05:05:44,600 SUPERIORITY OF BREATH OVER OP TO 6627 05:05:44,600 --> 05:05:46,360 SEE IF WE CAN AT LEAST DO BETTER 6628 05:05:46,360 --> 05:05:49,600 THAN OP IN THE ABSENCE OF 6629 05:05:49,600 --> 05:05:49,840 SPUTUM. 6630 05:05:49,840 --> 05:05:55,440 >> THANK YOU VERY MUCH. 6631 05:05:55,440 --> 05:05:57,320 I CAN DO THIS TOO BECAUSE IT'S 6632 05:05:57,320 --> 05:05:58,280 ANOTHER QUESTION FOR YOU. 6633 05:05:58,280 --> 05:06:01,160 DO WE KNOW ANYTHING ABOUT VOCs 6634 05:06:01,160 --> 05:06:04,400 FROM NONCF NORMAL VOLUNTEERS? 6635 05:06:04,400 --> 05:06:05,720 CAN VOCs DETECT PA BELOW THE 6636 05:06:05,720 --> 05:06:08,360 LEVEL OF DETECTION FROM A NORMAL 6637 05:06:08,360 --> 05:06:12,960 CLINICAL APPROACH WITH SPUTUM OR 6638 05:06:12,960 --> 05:06:13,520 THROAT SWAB? 6639 05:06:13,520 --> 05:06:14,120 >> SO I TOUCH OFFICE OF 6640 05:06:14,120 --> 05:06:15,360 DIVERSITY THE SECOND PART OF THE 6641 05:06:15,360 --> 05:06:16,920 QUESTION A MOMENT AGO THAT WHAT 6642 05:06:16,920 --> 05:06:19,000 WE'RE LOOKING FOR IS A BREATH 6643 05:06:19,000 --> 05:06:21,080 TEST THAT CAN OUTPERFORM OP SWAB 6644 05:06:21,080 --> 05:06:22,200 AS FAR AS SENSITIVITY GOES. 6645 05:06:22,200 --> 05:06:26,200 BUT WE ARE HAVING TO USE SPUTUM 6646 05:06:26,200 --> 05:06:28,120 PRIMARILY AS OUR CLINICAL GOLD 6647 05:06:28,120 --> 05:06:31,480 STANDARD SO THERE'S SOME TRICKY 6648 05:06:31,480 --> 05:06:33,680 CONSIDERATIONS AS WE'RE DOING 6649 05:06:33,680 --> 05:06:36,680 OUR STUDY DESIGN THERE. 6650 05:06:36,680 --> 05:06:38,200 WE DON'T KNOW, IT'S A GREAT 6651 05:06:38,200 --> 05:06:40,280 QUESTION OF LIKE HOW LOW CAN YOU 6652 05:06:40,280 --> 05:06:42,880 GO AS FAR AS PSEUDOMOANUS 6653 05:06:42,880 --> 05:06:44,520 INFECTION IS CONCERNED BEFORE WE 6654 05:06:44,520 --> 05:06:44,760 DETECT. 6655 05:06:44,760 --> 05:06:45,920 REALLY THE NEXT PHASE OF OUR 6656 05:06:45,920 --> 05:06:46,880 STUDY WILL ADDRESS THAT, WHERE 6657 05:06:46,880 --> 05:06:49,960 WE'RE GOING TO SEE IF WE CAN 6658 05:06:49,960 --> 05:06:52,840 PICK UP INFECTIONS USING BREATH 6659 05:06:52,840 --> 05:06:54,440 EARLIER, FOR SOMEBODY WHO'S 6660 05:06:54,440 --> 05:06:55,800 GETTING A NEW ONSET INFECTION 6661 05:06:55,800 --> 05:06:57,800 AND NEW DIAGNOSIS, IF WE CAN DO 6662 05:06:57,800 --> 05:07:00,240 BETTER THAN OP SWABS FOR PICKING 6663 05:07:00,240 --> 05:07:03,520 UP THOSE INFECTIONS EARLIER ON. 6664 05:07:03,520 --> 05:07:08,480 SO THAT'S AN OPEN QUESTION, WHEN 6665 05:07:08,480 --> 05:07:12,680 IT COMES TO PSEUDOMONUS 6666 05:07:12,680 --> 05:07:13,840 VOLATILES AND POPULATIONS, THE 6667 05:07:13,840 --> 05:07:16,040 STUDY WE'RE CONDUCTING IS NOT 6668 05:07:16,040 --> 05:07:17,640 ENROLLING ANYBODY WHO IS DOES 6669 05:07:17,640 --> 05:07:19,040 NOT HAVE CF, THERE ARE OTHER 6670 05:07:19,040 --> 05:07:20,360 STUDIES THAT HAVE BEEN PERFORMED 6671 05:07:20,360 --> 05:07:24,920 OUTSIDE OF THE CF POPULATION 6672 05:07:24,920 --> 05:07:27,880 THAT SHOWS THAT YOU CAN USE IT 6673 05:07:27,880 --> 05:07:30,120 TO DIAGNOSE VENTILATOR ASSISTED 6674 05:07:30,120 --> 05:07:30,960 PNEUMONIA FOR INSTANCE BUT 6675 05:07:30,960 --> 05:07:33,480 THERE'S NOT BEEN A STUDY THAT 6676 05:07:33,480 --> 05:07:36,280 TRIED TO BROADLY IDENTIFY BREATH 6677 05:07:36,280 --> 05:07:37,600 VOCs FOR PSEUDOMOANUS 6678 05:07:37,600 --> 05:07:40,280 DIAGNOSIS REGARDLESS OF WHAT THE 6679 05:07:40,280 --> 05:07:42,840 CAUSE OF INFECTION WAS, THE ROOT 6680 05:07:42,840 --> 05:07:45,280 CAUSE AND THEN LOOKING AT VOCs 6681 05:07:45,280 --> 05:07:47,000 IN THE HUMAN POPULATION MORE 6682 05:07:47,000 --> 05:07:47,240 BROADLY. 6683 05:07:47,240 --> 05:07:51,360 MOST OF THE STUDIES ARE ON THE 6684 05:07:51,360 --> 05:07:53,440 SCALE OF MAYBE UP TO 50 6685 05:07:53,440 --> 05:07:53,720 SUBJECTS. 6686 05:07:53,720 --> 05:07:54,840 THIS STUDY THAT WE--WE--YOU 6687 05:07:54,840 --> 05:07:58,480 DOING WITH IMPACT BREATH IS A 6688 05:07:58,480 --> 05:07:59,440 COUPLE HUNDRED AND THAT'S VERY 6689 05:07:59,440 --> 05:08:02,760 MUCH ON THE LARGE SIDE AS FAR AS 6690 05:08:02,760 --> 05:08:03,200 OUR FIELD GOES. 6691 05:08:03,200 --> 05:08:04,640 REALLY WHAT WE NEED TO DO IS GET 6692 05:08:04,640 --> 05:08:07,840 TO THE THOUSANDS OF SUBJECTS AND 6693 05:08:07,840 --> 05:08:09,040 THERE'S AN INITIATIVE BREWING 6694 05:08:09,040 --> 05:08:11,680 THAT WILL BE LAUNCHING SOON TO 6695 05:08:11,680 --> 05:08:12,360 ADDRESS THAT. 6696 05:08:12,360 --> 05:08:14,000 AND I CAN'T TALK ABOUT DETAILS 6697 05:08:14,000 --> 05:08:17,800 BUT IT WILL BECOME PUBLIC IN A 6698 05:08:17,800 --> 05:08:27,960 FEW WEEKS. 6699 05:08:35,120 --> 05:08:35,400 >> FANTASTIC. 6700 05:08:35,400 --> 05:08:38,320 I HAVE A QUESTION FOR YOU 6701 05:08:38,320 --> 05:08:41,640 MARGARET AND AWLTS IN THINKING 6702 05:08:41,640 --> 05:08:42,440 ABOUT MELANIE'S COMMENTS 6703 05:08:42,440 --> 05:08:43,760 YESTERDAY IN TALKING ABOUT 6704 05:08:43,760 --> 05:08:45,200 REMOTE VERSUS IN PERSON, AND I 6705 05:08:45,200 --> 05:08:47,720 WOULD LIKE TO HEAR JENNIFER'S 6706 05:08:47,720 --> 05:08:55,520 PERSPECTIVE ON THIS AS WELL AS 6707 05:08:55,520 --> 05:08:56,600 YOU COMPLETE OUTREACH, HOW DO 6708 05:08:56,600 --> 05:08:58,160 YOU EVALUATE AND WHAT THE RIGHT 6709 05:08:58,160 --> 05:09:01,760 BALANCE EVEN THOUGH WE COULD 6710 05:09:01,760 --> 05:09:02,440 ACHIEVE PERHAPS REPLACE, YOU 6711 05:09:02,440 --> 05:09:05,360 KNOW SOME OF OUR CLINIC VISITS 6712 05:09:05,360 --> 05:09:07,360 WITH REMOTE VISITS FOR RESEARCH? 6713 05:09:07,360 --> 05:09:08,680 >> THANK YOU FOR THAT QUESTION, 6714 05:09:08,680 --> 05:09:10,160 JENNIFER DO YOU WANT TO ANSWER 6715 05:09:10,160 --> 05:09:11,960 BEFORE I DIVE IN, I WOULD LOVE 6716 05:09:11,960 --> 05:09:14,520 TO HEAR YOUR PERIS SPECTIVE? 6717 05:09:14,520 --> 05:09:14,800 >> SURE. 6718 05:09:14,800 --> 05:09:18,320 YEAH, BECAUSE MY CLINICS ARE SO 6719 05:09:18,320 --> 05:09:22,480 FAR AWAY FROM ME I CAN SEE IT 6720 05:09:22,480 --> 05:09:23,000 FROM BOTH SIDES. 6721 05:09:23,000 --> 05:09:24,120 THERE ARE TIMES WHEN I KNOW IT'S 6722 05:09:24,120 --> 05:09:26,000 IMPORTANT TO GO INTO YOUR CLINIC 6723 05:09:26,000 --> 05:09:27,320 WHEN YOU START TO HAVE SOMETHING 6724 05:09:27,320 --> 05:09:30,320 CHANGE AND YOU WANT TO HAVE THE 6725 05:09:30,320 --> 05:09:31,520 DOCTOR RIELT THERE SO YOU CAN 6726 05:09:31,520 --> 05:09:35,920 FIND OUT WHAT'S GOING ON BUT 6727 05:09:35,920 --> 05:09:37,920 THERE ARE MANY TIMES WHEN I'VE 6728 05:09:37,920 --> 05:09:39,800 DRIVEN MY HOUR TO MY CLINIC 6729 05:09:39,800 --> 05:09:41,440 GOING WHY WOULD I DO THIS AND I 6730 05:09:41,440 --> 05:09:44,360 WOULD LOVE TO HAVE THE REMOTE 6731 05:09:44,360 --> 05:09:46,880 APPOINTMENT FROM HOME AND KNOW 6732 05:09:46,880 --> 05:09:49,200 DONE WITH THE VISIT IN ABOUT 20 6733 05:09:49,200 --> 05:09:49,760 MINUTES OR SO. 6734 05:09:49,760 --> 05:09:54,040 SO I SEE THE BENEFITS TO BOTH. 6735 05:09:54,040 --> 05:09:54,760 I REALLY DO. 6736 05:09:54,760 --> 05:09:56,560 AND I SEE ALSO THE DOWN SIDE TO 6737 05:09:56,560 --> 05:09:57,040 BOTH. 6738 05:09:57,040 --> 05:10:02,360 I THINK THERE'S NO HARM IN 6739 05:10:02,360 --> 05:10:03,800 REPLACING YOU ROUTINE CLINIC 6740 05:10:03,800 --> 05:10:04,760 VISIT IF SOMETHING'S CHANGED 6741 05:10:04,760 --> 05:10:06,040 WITH THE PATIENT, WHY GO? 6742 05:10:06,040 --> 05:10:08,360 WHY NOT JUST HAVE IT DONE 6743 05:10:08,360 --> 05:10:09,760 REMOTELY, IT MAKES MORE SENSE 6744 05:10:09,760 --> 05:10:11,440 FOR EVERYBODY, YOU'RE SAYING THE 6745 05:10:11,440 --> 05:10:13,080 DOCTORS TIME, STAFF'S TIME, AS 6746 05:10:13,080 --> 05:10:16,840 WELL AS YOUR OWN TIME. 6747 05:10:16,840 --> 05:10:18,520 SO I THINK THERE'S NOTHING BUT A 6748 05:10:18,520 --> 05:10:20,160 GOOD BENEFIT AND THE MORE WE 6749 05:10:20,160 --> 05:10:23,040 DIVE INTO HOW TO DO THESE THINGS 6750 05:10:23,040 --> 05:10:25,000 FROM HOME LIKE THE SPIROMETRY 6751 05:10:25,000 --> 05:10:25,680 COLLECTION, SPUTUM COLLECTIONS 6752 05:10:25,680 --> 05:10:29,280 AND WE GET VERY SAVVY AT IT. 6753 05:10:29,280 --> 05:10:31,960 I JUST SEE IT BEING MORE OF A 6754 05:10:31,960 --> 05:10:32,640 PLUS THAN ANYTHING. 6755 05:10:32,640 --> 05:10:33,840 WE COULD GET TO THE BOTTOM OF 6756 05:10:33,840 --> 05:10:38,160 ISSUES A LOT FASTER AND QUICKER 6757 05:10:38,160 --> 05:10:38,720 THAT WAY. 6758 05:10:38,720 --> 05:10:40,600 I'M ALL FOR IT, I THINK IT'S A 6759 05:10:40,600 --> 05:10:41,760 WONDERFUL THING AND I'M GLAD 6760 05:10:41,760 --> 05:10:45,440 YEAR GOING IN THAT DIRECTION 6761 05:10:45,440 --> 05:10:45,680 EMPLOY. 6762 05:10:45,680 --> 05:10:47,600 >> THANK YOU SO MUCH, SO NICOLE 6763 05:10:47,600 --> 05:10:50,040 ENGEAJ NOTHING THE CO PRODUCTION 6764 05:10:50,040 --> 05:10:52,160 PROCESS HAS LEGALLY BEEN SUCH 6765 05:10:52,160 --> 05:10:54,560 A-HIV DON'T MEAN TO SOUND 6766 05:10:54,560 --> 05:10:56,920 SACCHARANT BUT IT'S BEEN 6767 05:10:56,920 --> 05:10:58,880 HUMBLING AND SUCH A POSITIVE 6768 05:10:58,880 --> 05:11:00,880 EXPERIENCE SO I WOULD HIGHLY 6769 05:11:00,880 --> 05:11:02,280 RECOMMEND IT, IF NOT THINK WE 6770 05:11:02,280 --> 05:11:03,480 SHOULD REQUIRE IF FOR ALL 6771 05:11:03,480 --> 05:11:05,280 STUDIES BUT AT ANY RATE WE BEGAN 6772 05:11:05,280 --> 05:11:06,560 WITH FOCUS GROUPS WITH PEOPLE 6773 05:11:06,560 --> 05:11:11,040 WITH CF AND THEN SEPARATE FOCUS 6774 05:11:11,040 --> 05:11:12,440 GROUPS WITH RESEARCH 6775 05:11:12,440 --> 05:11:14,320 COORDINATORS AROUND BARRIERS AND 6776 05:11:14,320 --> 05:11:15,240 OPPORTUNITIES FOR HOME 6777 05:11:15,240 --> 05:11:16,400 SPIROMETRY, AND THAT HELPED US 6778 05:11:16,400 --> 05:11:18,200 TO DEVELOP INITIAL MATERIALS AND 6779 05:11:18,200 --> 05:11:20,280 THEN WE'VE BEEN DOING THIS VERY 6780 05:11:20,280 --> 05:11:21,840 INTENSIVE 6 MONTH PROCESS OF CO 6781 05:11:21,840 --> 05:11:23,400 PRODUCING ALL OF THE EDUCATION 6782 05:11:23,400 --> 05:11:26,640 AND TRAINING MATERIALS AND 6783 05:11:26,640 --> 05:11:27,880 PROCEDURES FOR TRAINING AND HOME 6784 05:11:27,880 --> 05:11:29,760 SPIROMETRY WITH A GROUP OF 6 6785 05:11:29,760 --> 05:11:32,480 INDIVIDUALS, 3 WITH CF AND 3 WHO 6786 05:11:32,480 --> 05:11:34,280 ARE RESEARCH COORDINATORS 1 OF 6787 05:11:34,280 --> 05:11:36,720 WHO AM IS A RESPIRATORY 6788 05:11:36,720 --> 05:11:38,000 THERAPIST BECAUSE IT HAS BEEN 6789 05:11:38,000 --> 05:11:38,800 AMAZING BECAUSE PEOPLE COME UP 6790 05:11:38,800 --> 05:11:40,640 WITH IDEAS THAT NO 1 INDIVIDUAL 6791 05:11:40,640 --> 05:11:41,320 MIGHT NECESSARILY HAVE THOUGHT 6792 05:11:41,320 --> 05:11:44,720 OF AND THEN IT KIND OF BECOMES A 6793 05:11:44,720 --> 05:11:45,200 SYNERGISTIC DISCUSSION. 6794 05:11:45,200 --> 05:11:46,600 IT'S A LOT OF WORK WE HAVE A LOT 6795 05:11:46,600 --> 05:11:48,920 OF WORK STILL TO DO ON THESE 6796 05:11:48,920 --> 05:11:50,200 MATERIALS BUT I TRULY BELIEVE 6797 05:11:50,200 --> 05:11:51,400 THEY'RE GOING TO BE SO MUCH 6798 05:11:51,400 --> 05:11:53,000 BETTER BECAUSE OF THIS 6799 05:11:53,000 --> 05:11:54,640 EXPERIENCE, AND AGAIN I CAN'T 6800 05:11:54,640 --> 05:11:55,840 REITERATE HOW MUCH I LEARNED. 6801 05:11:55,840 --> 05:11:58,720 THE THING I WOULD SAY IS WE 6802 05:11:58,720 --> 05:12:00,440 FOCUSED VERY NARROWLY ON HOME 6803 05:12:00,440 --> 05:12:03,560 SPIROMETRY AND ON HOW TO DO IT 6804 05:12:03,560 --> 05:12:03,880 APPROPRIATELY. 6805 05:12:03,880 --> 05:12:05,680 BUT I DON'T KNOW THAT THERE'S 6806 05:12:05,680 --> 05:12:06,880 BEEN ANYONE WHRO'S ENGAGE INDEED 6807 05:12:06,880 --> 05:12:08,960 A PROCESS OF CO PRODUCTION MORE 6808 05:12:08,960 --> 05:12:09,920 GENERALLY AROUND CLINICAL TRIALS 6809 05:12:09,920 --> 05:12:11,480 OF THE FUTURE AND WHAT ARE THE 6810 05:12:11,480 --> 05:12:16,040 KIND OF HOW DO YOU TAKE THE BEST 6811 05:12:16,040 --> 05:12:17,960 OF HOME VISITS OR HOME ASKER 6812 05:12:17,960 --> 05:12:19,120 TAINMENT VERSUS CLINIC AND WHAT 6813 05:12:19,120 --> 05:12:20,040 FEELS LIKE THE RIGHT BALANCE AND 6814 05:12:20,040 --> 05:12:21,120 WHAT ARE THE QUESTIONS AND I 6815 05:12:21,120 --> 05:12:23,120 THINK THAT WOULD BE JUST SUCH AN 6816 05:12:23,120 --> 05:12:24,680 IMPORTANT OPPORTUNITY ON MY TO 6817 05:12:24,680 --> 05:12:27,680 DO LIST IS TO REACH OUT TO 6818 05:12:27,680 --> 05:12:28,800 MELANIE FROM YESTERDAY AND GET 6819 05:12:28,800 --> 05:12:30,200 HER PERSPECTIVE AND I THINK THAT 6820 05:12:30,200 --> 05:12:34,960 THAT MORE BROAD QUESTION, 6821 05:12:34,960 --> 05:12:36,240 THERE'S VALUABLE CO PRODUCTION 6822 05:12:36,240 --> 05:12:36,600 WORK. 6823 05:12:36,600 --> 05:12:39,400 I ALSO HAVE TO CALL OUT THE CF 6824 05:12:39,400 --> 05:12:43,480 COMMUNITY VOICE HAS JUST BEEN 6825 05:12:43,480 --> 05:12:49,560 AMAZING IN FACILITATING ALL OF 6826 05:12:49,560 --> 05:12:49,920 THIS. 6827 05:12:49,920 --> 05:12:50,240 >> GREAT. 6828 05:12:50,240 --> 05:12:52,160 ZACH, QUESTION FOR YOU IN YOUR 6829 05:12:52,160 --> 05:12:54,320 TALK YOU MENTIONED USING 6830 05:12:54,320 --> 05:12:55,120 IMCANCER CENTERING TO STUDY ALL 6831 05:12:55,120 --> 05:12:56,200 THR ACTIVITIES AND PROJECTSYS 6832 05:12:56,200 --> 05:12:57,400 WHICH HAS BEEN A TOPIC 6833 05:12:57,400 --> 05:13:00,280 THROUGHOUT THE CONFERENCE, WHAT 6834 05:13:00,280 --> 05:13:01,800 ARE YOUR THOUGHTS ON THE TIME 6835 05:13:01,800 --> 05:13:04,080 SPAN NEEDED TO EVALUATE THAT FOR 6836 05:13:04,080 --> 05:13:06,240 THIS END POINT ESPECIALLY IN 6837 05:13:06,240 --> 05:13:08,560 RELATION TO YOU KNOW TEASING OUT 6838 05:13:08,560 --> 05:13:10,040 WHAT'S RELATED TO THE 6839 05:13:10,040 --> 05:13:10,640 [INDISCERNIBLE] VERSUS PERHAPS 6840 05:13:10,640 --> 05:13:13,840 PICKING UP ON WHAT COULD BE 6841 05:13:13,840 --> 05:13:16,000 RELATED TO NATURAL DISEASE 6842 05:13:16,000 --> 05:13:16,280 PROGRESSION? 6843 05:13:16,280 --> 05:13:16,640 >> OH BOY. 6844 05:13:16,640 --> 05:13:20,000 HIT ME WITH AN EASY 1. 6845 05:13:20,000 --> 05:13:21,680 I WILL TAKE A SLIGHT STEP BACK 6846 05:13:21,680 --> 05:13:22,000 FROM THAT. 6847 05:13:22,000 --> 05:13:23,760 I THINK THERE'S A COUPLE OF 6848 05:13:23,760 --> 05:13:25,960 THINGS WE CAN KIND OF LEARN WITH 6849 05:13:25,960 --> 05:13:28,800 IMAGES THAT WILL ASK US TO 6850 05:13:28,800 --> 05:13:30,240 BETTER ASK THE QUESTIONS IN 6851 05:13:30,240 --> 05:13:32,600 GENERAL BUT WE SEE THESE LARGE 6852 05:13:32,600 --> 05:13:34,200 FEV1 IMPROVEMENTS IN THE 6853 05:13:34,200 --> 05:13:36,680 CLINICAL TRIAL, AND HOW MUCH OF 6854 05:13:36,680 --> 05:13:41,680 THAT IS A RESOLUTION OF A MORE 6855 05:13:41,680 --> 05:13:42,840 ESTABLISHED PATHOLOGY, BUT WE 6856 05:13:42,840 --> 05:13:45,520 JUST CLEARED OUT A BUNCH OF 6857 05:13:45,520 --> 05:13:47,520 MUCUS PLUGS, THAT'S SOMETHING WE 6858 05:13:47,520 --> 05:13:49,720 CAN GET AT, THAT SORT OF, 6859 05:13:49,720 --> 05:13:51,480 UNDERSTANDING IS THAT JUST A 6860 05:13:51,480 --> 05:13:52,520 FIRST PASS CLEARANCE ISSUE OR 6861 05:13:52,520 --> 05:13:54,960 ARE WE ACTUALLY REMOVING AIR WAY 6862 05:13:54,960 --> 05:13:56,120 INFLAMMATION AND THINGS LIKE 6863 05:13:56,120 --> 05:13:56,320 THAT? 6864 05:13:56,320 --> 05:13:58,000 I THINK WE HAVE TO ASK THOSE 6865 05:13:58,000 --> 05:14:00,240 QUESTIONS IN A MEANINGFUL WAY 6866 05:14:00,240 --> 05:14:04,160 BEFORE WE CAN REALLY START 6867 05:14:04,160 --> 05:14:04,600 THINKING MEANINGFULLY 6868 05:14:04,600 --> 05:14:05,560 THROUGHOUT, LIKE WHAT ARE WE 6869 05:14:05,560 --> 05:14:06,640 FIXING WITH THE THERAPIES WE 6870 05:14:06,640 --> 05:14:08,840 HAVE RIGHT NOW AND IF WE ASK 6871 05:14:08,840 --> 05:14:10,080 THOSE QUESTIONS BETTER AND I 6872 05:14:10,080 --> 05:14:12,480 THINK IMAGING CAN HELP, THEN WE 6873 05:14:12,480 --> 05:14:14,800 CAN ASK MORE PRECISE QUESTIONS 6874 05:14:14,800 --> 05:14:15,280 GOING FORWARD. 6875 05:14:15,280 --> 05:14:18,680 MEANING IF THERE'S NO MUSIC WITH 6876 05:14:18,680 --> 05:14:21,040 PLUGS LEFT, WE CAN BE MORE KAF 6877 05:14:21,040 --> 05:14:23,480 CLEAR ABOUT REMOVING SOME OF THE 6878 05:14:23,480 --> 05:14:24,960 PHYSIO THERAPY. 6879 05:14:24,960 --> 05:14:26,720 SO, I THINK I SIDE STEPPED YOUR 6880 05:14:26,720 --> 05:14:31,160 QUESTION A BIT BUT I THINK THE 6881 05:14:31,160 --> 05:14:31,800 THERAPY WITHDRAWAL QUESTIONS, 6882 05:14:31,800 --> 05:14:32,960 WE'RE GOING TO DO IT ANYWAY AND 6883 05:14:32,960 --> 05:14:35,280 THE PATIENTS ARE DOING IT 6884 05:14:35,280 --> 05:14:36,960 THEMSELVES BUT I THINK IT 6885 05:14:36,960 --> 05:14:38,080 MIGHT--THE SCIENCE OF IT NEEDS 6886 05:14:38,080 --> 05:14:42,080 TO HIT 1 STEP BACK. 6887 05:14:42,080 --> 05:14:43,240 >> CHRIS WHAT DID YOU LEARN MORE 6888 05:14:43,240 --> 05:14:44,320 ABOUT THE DIFFERENCE BETWEEN 6889 05:14:44,320 --> 05:14:46,240 HIGH AND LOW RESPONDERS IN THE 6890 05:14:46,240 --> 05:14:48,040 STOP 2 STUDY PARTICULARLY IN 6891 05:14:48,040 --> 05:14:50,240 REGARD TO WHAT WE NEED TO TREAT 6892 05:14:50,240 --> 05:14:52,440 BEYOND INFECTION AND 6893 05:14:52,440 --> 05:14:52,760 INFLAMMATION? 6894 05:14:52,760 --> 05:14:57,480 >> YEAH, THAT'S A GREAT 6895 05:14:57,480 --> 05:14:57,960 QUESTION. 6896 05:14:57,960 --> 05:15:00,920 IT'S VERY INTERESTING, THE LUNG 6897 05:15:00,920 --> 05:15:02,400 FUNCTION WEB CONNECTED POSITED 6898 05:15:02,400 --> 05:15:04,120 THAT THE LUNG FUNCTION WOULD BE 6899 05:15:04,120 --> 05:15:06,840 VERY DIFFERENT AT A RIVAL BEFORE 6900 05:15:06,840 --> 05:15:07,920 THE EXACERBATION THAT THOSE THAT 6901 05:15:07,920 --> 05:15:09,440 HAD A POOR RESPONSE WOULD HAVE 6902 05:15:09,440 --> 05:15:10,960 MORE ADVANCED DISEASE BUT THE 6903 05:15:10,960 --> 05:15:12,080 FEV1 ON AVERAGE IS ABOUT THE 6904 05:15:12,080 --> 05:15:12,800 SAME. 6905 05:15:12,800 --> 05:15:15,080 THEY WERE OLDER, WHICH SORT OF 6906 05:15:15,080 --> 05:15:19,840 SUGGESTS SORT OF MORE ADVANCE TD 6907 05:15:19,840 --> 05:15:21,720 DISEASE ALTHOUGH LUNG FUNCTION 6908 05:15:21,720 --> 05:15:23,640 CLASSICALLIER THAT HAD A DELAYED 6909 05:15:23,640 --> 05:15:25,280 RESPONSE OR A NONEARLY ROBUST 6910 05:15:25,280 --> 05:15:27,120 RESPONSE, THEY HAD MORE 6911 05:15:27,120 --> 05:15:29,840 DIABETES, SO, THAT HAD THE 6912 05:15:29,840 --> 05:15:32,920 DELAYED RESPONSE SO MAYBE, MAYBE 6913 05:15:32,920 --> 05:15:33,520 GLUCOSE CONTROL, CRITICAL 6914 05:15:33,520 --> 05:15:36,960 GLUCOSE CONTROL IS REAL REALLY 6915 05:15:36,960 --> 05:15:39,680 IMPORTANT IN MODULATING CF 6916 05:15:39,680 --> 05:15:40,520 EXACERBATIONS STEROID USE WAS 6917 05:15:40,520 --> 05:15:41,960 VERY SIMILAR IN BOTH, SO YOU 6918 05:15:41,960 --> 05:15:44,040 THINK ABOUT IT, BUT WE DIDN'T 6919 05:15:44,040 --> 05:15:46,560 REALLY--THE QUESTION STILL IS 6920 05:15:46,560 --> 05:15:49,320 OUT THERE, WHETHER STEROIDS WITH 6921 05:15:49,320 --> 05:15:51,240 MODULATION WITH STEROIDS LIKE 6922 05:15:51,240 --> 05:15:52,280 COPD HAS A BENEFIT. 6923 05:15:52,280 --> 05:15:55,360 WE DO KNOW THAT SIGHT OF CARE 6924 05:15:55,360 --> 05:15:56,800 MATTERS AND THAT'S AND THAT'S A 6925 05:15:56,800 --> 05:15:58,840 TOPIC OF ANOTHER STUDY THAT 6926 05:15:58,840 --> 05:16:00,040 WE'RE SORT OF TRYING TO DEVELOP 6927 05:16:00,040 --> 05:16:01,320 IN THIS CO MANAGEMENT THING OF 6928 05:16:01,320 --> 05:16:02,640 WHAT WE CAN DO BETTER FOR 6929 05:16:02,640 --> 05:16:05,120 PATIENTS WHO CHOOSE TO GET IV 6930 05:16:05,120 --> 05:16:06,200 ANTIBIOTICSA HOME BECAUSE WE 6931 05:16:06,200 --> 05:16:08,040 CLEARLY, THE EVIDENCE IS SORT OF 6932 05:16:08,040 --> 05:16:09,920 PILING UP THAT AS ADULTS AND 6933 05:16:09,920 --> 05:16:11,720 CHILDREN IF THEY GET TREATED AT 6934 05:16:11,720 --> 05:16:13,120 HOME, MAYBE THEY DON'T DO AS 6935 05:16:13,120 --> 05:16:14,440 WELL, IT'S MUCH MORE COMMON IN,A 6936 05:16:14,440 --> 05:16:16,280 DULT CENTERS TO USE HOME 6937 05:16:16,280 --> 05:16:17,960 CELTINGS SO THEY'RE BOTH SORT OF 6938 05:16:17,960 --> 05:16:19,360 SOME BIOLOGIC THINGS MAYBE BE 6939 05:16:19,360 --> 05:16:21,600 PLAYING A ROLE THAT WE 6940 05:16:21,600 --> 05:16:23,000 DON'T--THERE'S NOT A--THERE'S A 6941 05:16:23,000 --> 05:16:26,000 STUDY FOR ANALYSIS JUST ABOUT TO 6942 05:16:26,000 --> 05:16:28,440 START OR REALLY RAMP UP WHICH IS 6943 05:16:28,440 --> 05:16:29,520 UNDERSTANDING WHETHER STEROIDS 6944 05:16:29,520 --> 05:16:30,880 PROVIDED ANY BENEFIT, THERE IS A 6945 05:16:30,880 --> 05:16:34,720 CLINICAL TRIAL IN EUROPE, SORRY 6946 05:16:34,720 --> 05:16:36,280 IN CANADA STUDYING IMPACT 6947 05:16:36,280 --> 05:16:39,200 STEROIDS TO LATE POOR RESPONDERS 6948 05:16:39,200 --> 05:16:40,160 IN THESE EXACERBATIONS SO THEY 6949 05:16:40,160 --> 05:16:41,200 WILL HAVE THAT ANSWER IN THE 6950 05:16:41,200 --> 05:16:42,480 NEXT YEAR OR SO. 6951 05:16:42,480 --> 05:16:45,880 SO THOSE ARE JUST IDEAS BUT I 6952 05:16:45,880 --> 05:16:46,720 THINK THERE'S--THERE ARE 6953 05:16:46,720 --> 05:16:48,120 BIOSPECIMENS IN THIS STUDY, SO 6954 05:16:48,120 --> 05:16:50,360 THERE ARE WAYS TO LOOK AT 6955 05:16:50,360 --> 05:16:53,040 BIOMARKERS, THAT HAVE NOT BEEN 6956 05:16:53,040 --> 05:16:58,720 DONE YET TO THINK ABOUT IT. 6957 05:16:58,720 --> 05:16:59,240 THERE'S--THOSE RESOURCES 6958 05:16:59,240 --> 05:17:00,600 HOPEFULLY CAN LEAD TO BETTER 6959 05:17:00,600 --> 05:17:02,440 UNDERSTANDING OF THE BIOLOGY OF 6960 05:17:02,440 --> 05:17:03,840 EXACERBATION SO CAN YOU SEE WHAT 6961 05:17:03,840 --> 05:17:07,240 WE'RE MISSING BUT I DO THINK, I 6962 05:17:07,240 --> 05:17:08,880 THINK THE PHENOTYPE EXACERBATION 6963 05:17:08,880 --> 05:17:10,480 IS HELPFUL BECAUSE TREATMENT MAY 6964 05:17:10,480 --> 05:17:20,720 BE DIFFERENT BASED ON YOUR 6965 05:17:20,720 --> 05:17:21,120 PHENOTYPE. 6966 05:17:21,120 --> 05:17:23,360 >> NEXT QUESTION, IS NOT FOR A 6967 05:17:23,360 --> 05:17:25,800 SPECIFIC PERSON, IS THIS IS 6968 05:17:25,800 --> 05:17:29,120 RELATED TO JENNIFER'S EXPERIENCE 6969 05:17:29,120 --> 05:17:31,960 IN TERMS OF HER IVACAFTOR 6970 05:17:31,960 --> 05:17:35,880 EXPERIENCE AND HOW YOU STARTED 6971 05:17:35,880 --> 05:17:41,640 TRICAF TA ANTICIPATING WHAT 6972 05:17:41,640 --> 05:17:43,840 COULD HAPPEN DID WE ANTICIPATE 6973 05:17:43,840 --> 05:17:46,320 MENTAL HEALTH COMPLICATIONS WITH 6974 05:17:46,320 --> 05:17:49,120 HIGHLY EFFECTIVE MODULATORS AND 6975 05:17:49,120 --> 05:17:51,160 TRICAFAND ARE THE CURRENT 6976 05:17:51,160 --> 05:17:52,360 APPROACHES FOR MANAGING THESE 6977 05:17:52,360 --> 05:17:52,960 SIDE EFFECTS? 6978 05:17:52,960 --> 05:17:54,800 I DON'T KNOW MAYBE CHRIS AND 6979 05:17:54,800 --> 05:17:57,160 MARGARET CAN TACKLE THIS FROM A 6980 05:17:57,160 --> 05:18:02,800 PEDIATRIC AND ADULT PERSPECTIVE. 6981 05:18:02,800 --> 05:18:04,280 >> I THINK MOST OF THE WORK IS 6982 05:18:04,280 --> 05:18:05,360 ON THE ADULT SIDE. 6983 05:18:05,360 --> 05:18:09,880 WE DID NOT ANTICIPATE THIS. 6984 05:18:09,880 --> 05:18:10,040 NO. 6985 05:18:10,040 --> 05:18:11,320 AND THERE'S CLEAR EVIDENCE THAT 6986 05:18:11,320 --> 05:18:15,280 MENTAL HEALTH ISSUES ARE 6987 05:18:15,280 --> 05:18:16,760 EEMERGENCYING POST TRICAFA. 6988 05:18:16,760 --> 05:18:18,040 THE MECHANISTIC LINK IS SOMEWHAT 6989 05:18:18,040 --> 05:18:19,440 UNCLEAR BUT ALL OF US HAD THAT 6990 05:18:19,440 --> 05:18:20,600 EXPERIENCE WITH OUR PATIENTS AND 6991 05:18:20,600 --> 05:18:22,720 WE DON'T HAVE A STANDARDIZED 6992 05:18:22,720 --> 05:18:26,360 APPROACH EXCEPT FOR CO DECISION 6993 05:18:26,360 --> 05:18:27,840 MAKING AND OFTEN TIMES STOPPING 6994 05:18:27,840 --> 05:18:30,600 IT UNTIL THE DEPRESSION HAS 6995 05:18:30,600 --> 05:18:31,720 HOPEFULLY IMPROVED AND THEN 6996 05:18:31,720 --> 05:18:33,000 THINKING ABOUT STARTING UP AGAIN 6997 05:18:33,000 --> 05:18:35,800 IN A SLOWER WAY, BUT THERE'S NOT 6998 05:18:35,800 --> 05:18:37,200 A STANDARDIZED APPROACH IN AN 6999 05:18:37,200 --> 05:18:41,960 AREA THAT'S BEGGING FOR 7000 05:18:41,960 --> 05:18:42,240 RESEARCH. 7001 05:18:42,240 --> 05:18:43,520 >> I WOULD SECOND TO SAY BEGGING 7002 05:18:43,520 --> 05:18:45,240 FOR RESEARCH IS REALLY WHAT IT 7003 05:18:45,240 --> 05:18:48,680 NEEDS AND WE DO ENCOUNTER THIS 7004 05:18:48,680 --> 05:18:50,840 NOT TOO INFREQUENTLY AND WE WORK 7005 05:18:50,840 --> 05:18:52,920 WITH PATIENTS LIKE JENNIFER, WE 7006 05:18:52,920 --> 05:18:54,800 DO A LOT OF DOSE ADJUSTMENT 7007 05:18:54,800 --> 05:19:00,080 WHICH HAS NO PHARMA COBASIS AND 7008 05:19:00,080 --> 05:19:01,080 IN TRIALS AND PHARMACOKINETICS 7009 05:19:01,080 --> 05:19:02,720 BUT IT SEEPS TO WORK. 7010 05:19:02,720 --> 05:19:04,280 WE FLIP MORNING DOSES TO EVENING 7011 05:19:04,280 --> 05:19:05,800 DOSES, TO HOPE THAT YOU SLEEP 7012 05:19:05,800 --> 05:19:07,400 THROUGH THIS PERIOD WHERE YOU 7013 05:19:07,400 --> 05:19:11,160 MAY NOTE THIS EFFECT IN YOUR 7014 05:19:11,160 --> 05:19:14,560 COGNITION, SO THAT WE DO A LOT 7015 05:19:14,560 --> 05:19:15,840 OF AD LIB WITHOUT KNOWING AND 7016 05:19:15,840 --> 05:19:17,320 THERE COULD BE DIFFERENCES IN 7017 05:19:17,320 --> 05:19:18,840 BLOOD LEVELS, WHAT IF SOMEONE'S 7018 05:19:18,840 --> 05:19:19,800 JUST DIFFERENCES IN METABOLISM 7019 05:19:19,800 --> 05:19:21,280 AND IF THE DRUG LEADS TO THE 7020 05:19:21,280 --> 05:19:21,720 SIDE EFFECT. 7021 05:19:21,720 --> 05:19:26,080 SO I THINK THAT THERE'S WORK 7022 05:19:26,080 --> 05:19:27,600 ONGOING, WE KNOW CFTRs IN THE 7023 05:19:27,600 --> 05:19:29,120 BRAIN, WE DEEPT KNOW WHAT IT 7024 05:19:29,120 --> 05:19:30,640 DOES AND I THINK THERE'S A LOT 7025 05:19:30,640 --> 05:19:32,440 OF THINGS THAT TURNING ON A 7026 05:19:32,440 --> 05:19:33,480 PROTEIN THAT'S BEEN OFF MIGHT DO 7027 05:19:33,480 --> 05:19:36,360 THAT WE HAVE TO BE JUST 7028 05:19:36,360 --> 05:19:38,480 COGNIZANT AND AWARE, THIS IS A 7029 05:19:38,480 --> 05:19:39,560 DISCOVERY PERIOD, WE HAVE TO 7030 05:19:39,560 --> 05:19:42,240 LISTEN TO OUR PATIENTS AND SAY, 7031 05:19:42,240 --> 05:19:43,760 HMM, THAT'S VERY ODD. 7032 05:19:43,760 --> 05:19:44,840 AND AGAIN THE ACTUAL TREATMENT 7033 05:19:44,840 --> 05:19:45,880 RESPONSES AND WHAT WE'RE DOING 7034 05:19:45,880 --> 05:19:48,240 ON THE GROUND IS JUST, I THINK 7035 05:19:48,240 --> 05:19:51,240 WE'RE ALL INVENTING A PATH WITH 7036 05:19:51,240 --> 05:19:52,280 PATIENTS AND IT'S--I HAVE 7037 05:19:52,280 --> 05:19:54,880 PATIENT WHO IS TAKE TRICAFTA 3 7038 05:19:54,880 --> 05:19:57,080 TIMES A WEEK, IS THERE A ARM 7039 05:19:57,080 --> 05:19:58,720 ANYWHERE IN THE CLINICAL TRIAL 7040 05:19:58,720 --> 05:20:00,680 THAT SAYS DOSE, MONDAY, 7041 05:20:00,680 --> 05:20:02,400 WEDNESDAY, FRIDAY, 1 PILL, 7042 05:20:02,400 --> 05:20:03,760 MONDAY, WEDNESDAY, FRIDAY, MUCH 7043 05:20:03,760 --> 05:20:05,200 LIKE JENNIFER IF THE PATIENT 7044 05:20:05,200 --> 05:20:07,640 SAYS, MY LUNGS ARE CLEAR, I FEEL 7045 05:20:07,640 --> 05:20:09,480 GREAT, MY SPIROMETRY HASN'T GONE 7046 05:20:09,480 --> 05:20:12,000 DOWN, THERE MAY BE SOME--IT 7047 05:20:12,000 --> 05:20:13,880 WOULD BE NICE TO HARNESS FIRST 7048 05:20:13,880 --> 05:20:15,880 OUR UNDERSTANDING OF SOME OF 7049 05:20:15,880 --> 05:20:18,240 THESE UNINTENDED EFFECTS OF THE 7050 05:20:18,240 --> 05:20:19,880 DRUG, BOTH GOOD AND BAD, AND 7051 05:20:19,880 --> 05:20:22,360 REALLY HAVE A GOOD CATALOG TO 7052 05:20:22,360 --> 05:20:23,440 EDUCATE PATIENTS BEFORE 7053 05:20:23,440 --> 05:20:29,200 THEY--YOU KNOW HELP THEM MAKE 7054 05:20:29,200 --> 05:20:30,680 DECISIONWHAT TO DO. 7055 05:20:30,680 --> 05:20:31,560 >> WELL, PROVOCATIVE QUESTION, I 7056 05:20:31,560 --> 05:20:33,600 WILL ALSO I THINK INSPIRED BY 7057 05:20:33,600 --> 05:20:35,880 JENNIFER'S EXPERIENCE, WHAT DO 7058 05:20:35,880 --> 05:20:38,480 WE THINK ABOUT CYCLING ON ANDAVE 7059 05:20:38,480 --> 05:20:38,880 OF MODULATORS? 7060 05:20:38,880 --> 05:20:42,560 IS THERE A BENEFIT TO REDUCING 7061 05:20:42,560 --> 05:20:43,720 EXACERBATIONS AND REDUCED SIDE 7062 05:20:43,720 --> 05:20:43,960 EFFECTS? 7063 05:20:43,960 --> 05:20:45,400 FIRST OF ALL LET ME ASK 7064 05:20:45,400 --> 05:20:46,640 JENNIFER, WOULD YOU EVER 7065 05:20:46,640 --> 05:20:49,600 CONSIDER GOING BACK ON TRICAFTA 7066 05:20:49,600 --> 05:20:52,040 AND UNDER WHAT CIRCUMSTANCE? 7067 05:20:52,040 --> 05:20:53,360 >> DURING MY RECENT 7068 05:20:53,360 --> 05:20:55,760 EXACERBATION, I WENT ON DURING 7069 05:20:55,760 --> 05:20:58,360 THAT WEEK TO HELP ABSORB THE 7070 05:20:58,360 --> 05:20:59,880 ANTIBIOTIC BETTER SO THAT WAS 7071 05:20:59,880 --> 05:21:01,840 THE WHOLE PURPOSE OF TAKING IT, 7072 05:21:01,840 --> 05:21:03,960 BUT I ONLY TOOK 1 PILL, 1 ORANGE 7073 05:21:03,960 --> 05:21:09,400 PILL IN THE MORNING WITH THE 7074 05:21:09,400 --> 05:21:11,360 ANTIBIOTIC AND YOU KNOW I DON'T 7075 05:21:11,360 --> 05:21:12,920 KNOW, DID IT HELP? 7076 05:21:12,920 --> 05:21:14,560 I CAN ONLY ASSUME MAYBE IT DID? 7077 05:21:14,560 --> 05:21:17,000 AS SOON AS I FINISHED THE COURSE 7078 05:21:17,000 --> 05:21:19,480 OF ANTIBIOTICS I STOPPED THE 7079 05:21:19,480 --> 05:21:20,600 TRICAFTA BECAUSE WHAT HAPPENED 7080 05:21:20,600 --> 05:21:23,800 AS SOON AS I WENT BACK ON IS MY 7081 05:21:23,800 --> 05:21:25,760 OFTIO ARTHRITIS FLAIRED RIGHT 7082 05:21:25,760 --> 05:21:26,080 BACK UP AGAIN. 7083 05:21:26,080 --> 05:21:27,800 SO I'M A BIG RUNNER, I WENT OUT 7084 05:21:27,800 --> 05:21:30,240 FOR A RUN NEAR THE TAIL END OF 7085 05:21:30,240 --> 05:21:31,320 THE EXACERBATION BECAUSE I WAS 7086 05:21:31,320 --> 05:21:33,080 FEELING BETTER AND HAD TO LIMP 7087 05:21:33,080 --> 05:21:35,280 MY WAY HOME DUE TO HIP PAIN. 7088 05:21:35,280 --> 05:21:36,800 SO NOW THAT I'VE BEEN OFF OF IT 7089 05:21:36,800 --> 05:21:38,480 FOR ABOUT A WEEK, I WENT OUT FOR 7090 05:21:38,480 --> 05:21:42,080 A RUN THIS MORNING, PAIN FREE. 7091 05:21:42,080 --> 05:21:43,120 ABSOLUTELY PAIN FREE, ABSOLUTELY 7092 05:21:43,120 --> 05:21:43,720 FINE. 7093 05:21:43,720 --> 05:21:45,680 SO THERE IS SOME LINK THEIR ALSO 7094 05:21:45,680 --> 05:21:49,160 TO THAT BUT YES, I HAVE BEEN 7095 05:21:49,160 --> 05:21:50,640 TALKING ABOUT CYCLING ON AND OFF 7096 05:21:50,640 --> 05:21:52,800 FOR MONTHS NOW, THAT I THINK 7097 05:21:52,800 --> 05:21:55,640 THERE'S A BENEFIT TO DOING THIS 7098 05:21:55,640 --> 05:21:56,920 AND THAT'S SOMETHING ELSE THAT'S 7099 05:21:56,920 --> 05:21:58,240 PROBABLY GOING TO NEED TO BE 7100 05:21:58,240 --> 05:22:01,040 STUDIED DOWN THE ROAD. 7101 05:22:01,040 --> 05:22:02,720 >> AS A PEDIATRICIAN I ALSO NEED 7102 05:22:02,720 --> 05:22:05,800 TO THROW OUT A WORD OF CAUTION 7103 05:22:05,800 --> 05:22:07,040 BECAUSE IF OUR GOAL EVENTUALLY 7104 05:22:07,040 --> 05:22:10,480 WILL BE ABLE TO INITTIAIT 7105 05:22:10,480 --> 05:22:11,920 TRICAFTA BEFORE THAT HAS BEEN 7106 05:22:11,920 --> 05:22:14,320 STRUCTURAL AIR WAY DAMAGE AND 7107 05:22:14,320 --> 05:22:16,200 WHILE THE PANCREATIC DAMAGE IS 7108 05:22:16,200 --> 05:22:17,840 STILL EVOLVING AND REALLY 7109 05:22:17,840 --> 05:22:19,800 INTERVENING EARLY, EVEN MAYBE IN 7110 05:22:19,800 --> 05:22:21,360 UTERO AS THE DOCTOR WAS 7111 05:22:21,360 --> 05:22:23,240 DISCUSSING THIS MORNING, I THINK 7112 05:22:23,240 --> 05:22:24,600 THERE ARE POTENTIAL LYE 7113 05:22:24,600 --> 05:22:27,520 SIGNIFICANT RISKS IN CYCLING OR 7114 05:22:27,520 --> 05:22:29,880 STOPPING AND STARTING IN WHICH 7115 05:22:29,880 --> 05:22:31,640 THERE COULD BE DAMAGE THEN 7116 05:22:31,640 --> 05:22:33,440 COULDN'T BE REVERSED THINKING 7117 05:22:33,440 --> 05:22:36,120 FOR EXAMPLE OF A FERRET MODEL. 7118 05:22:36,120 --> 05:22:38,680 SO IT'S JUST SUCH A TRICK EXPE 7119 05:22:38,680 --> 05:22:39,480 HUMBLING SITUATION WHEN 7120 05:22:39,480 --> 05:22:42,880 OBVIOUSLY PEOPLE ARE HAVING CLER 7121 05:22:42,880 --> 05:22:44,160 CUT INTOLERABLE OR TOLERABLE 7122 05:22:44,160 --> 05:22:46,680 SIDE EFFECTS THAT RAISES ISSUES 7123 05:22:46,680 --> 05:22:47,720 AROUND DOSING AND SO FORTH, BUT 7124 05:22:47,720 --> 05:22:49,520 IF WE ARE TRYING TO PREVENT 7125 05:22:49,520 --> 05:22:52,720 DAMAGE IN THE FIRST PLACE, IT 7126 05:22:52,720 --> 05:23:03,200 COULD BE A SCARY THING TO DO. 7127 05:23:05,880 --> 05:23:11,240 >> COULD I THOUGHT OUT A THOUGHT 7128 05:23:11,240 --> 05:23:13,000 EXPERIMENT, DEPRESSION IS A 7129 05:23:13,000 --> 05:23:13,920 COMMOFLICATED THING, I WONDER IF 7130 05:23:13,920 --> 05:23:15,680 WE COULD LOOK AS A FIELD IS 7131 05:23:15,680 --> 05:23:16,680 DEPRESSION THAP HAPPENS WHEN 7132 05:23:16,680 --> 05:23:17,760 PEOPLE GO INTO RETIREMENT, HAVE 7133 05:23:17,760 --> 05:23:19,800 YOU A GROUP OF PEOPLE WHO HAD 7134 05:23:19,800 --> 05:23:22,120 THEIR DAILY LIFE NOW COMPLETELY 7135 05:23:22,120 --> 05:23:23,520 DISRUPTED, A LOT OF PEOPLE WITH 7136 05:23:23,520 --> 05:23:27,120 CF, THEIR JOB IS STAYING ALIVE 7137 05:23:27,120 --> 05:23:27,760 AND NONAPOPTOTIC THAT'S NOT 7138 05:23:27,760 --> 05:23:30,920 THERE IN THE SAME WAY I WONDER 7139 05:23:30,920 --> 05:23:33,200 HOW MUCH THAT MASSIVE CHANGE IN 7140 05:23:33,200 --> 05:23:39,240 LIFE COURSE IS CONTRIBUTING TO 7141 05:23:39,240 --> 05:23:39,560 DEPRESSION? 7142 05:23:39,560 --> 05:23:41,520 >> YEAH, STEVE MADE A NICE 7143 05:23:41,520 --> 05:23:42,840 COMMENT IN THE--YOU KNOW OUR 7144 05:23:42,840 --> 05:23:44,040 UNDERSTANDING OF WHETHER 7145 05:23:44,040 --> 05:23:46,560 DEPRESSION AND ANXIETY ARE 7146 05:23:46,560 --> 05:23:48,400 CORRECTLY CAUSEALLY LINKED IN 7147 05:23:48,400 --> 05:23:49,920 THE DRUG IS CHALLENGING, PATIENT 7148 05:23:49,920 --> 05:23:51,520 GOES ON DRUG, EXPERIENCES 7149 05:23:51,520 --> 05:23:53,040 SYMPTOMS, TAKES OFF DRUG, 7150 05:23:53,040 --> 05:23:54,920 SYMPTOMS GOES AWAY, STARTS DRUG 7151 05:23:54,920 --> 05:23:56,800 AGAIN, SYMPTOM COMES BACK. 7152 05:23:56,800 --> 05:23:58,360 BUT WE DON'T HAVE MUCH OF A 7153 05:23:58,360 --> 05:24:00,920 COLLECTIVE UNDERSTANDING OF 7154 05:24:00,920 --> 05:24:02,400 THAT. 7155 05:24:02,400 --> 05:24:04,840 AND IT'S VERY MUCH AN INDIVIDUAL 7156 05:24:04,840 --> 05:24:05,560 PATIENT DECISION THAT'S BEEN 7157 05:24:05,560 --> 05:24:07,880 ANYTHING ON ACROSS THE COUNTRY 7158 05:24:07,880 --> 05:24:10,160 WITH UNUSUAL AND ELABRATIVE 7159 05:24:10,160 --> 05:24:12,840 SOLUTIONS FETAL COMPARTMENT THE 7160 05:24:12,840 --> 05:24:15,440 PROBLEM. 7161 05:24:15,440 --> 05:24:17,320 SO IT DOES AFFECT, YOU KNOW 7162 05:24:17,320 --> 05:24:18,880 COMING OUT OF 2 AND HALF YEARS 7163 05:24:18,880 --> 05:24:20,320 OF PANDEMIC, MOST OF US ARE NOT 7164 05:24:20,320 --> 05:24:21,880 HAPPY BUT THERE'S A GOOD POINT 7165 05:24:21,880 --> 05:24:24,160 TO WHETHER WE HAVE THE CAUSAL 7166 05:24:24,160 --> 05:24:25,280 LINK SQUARED AWAY AND WHETHER 7167 05:24:25,280 --> 05:24:27,440 THESE RMENTS THAT MANY OF US AS 7168 05:24:27,440 --> 05:24:29,320 CLINICIANS HAVE BEEN DOING ARE 7169 05:24:29,320 --> 05:24:30,280 REALLY--BUT I WOULD SORT OF 7170 05:24:30,280 --> 05:24:32,200 CAUTION THE IDEA OF GOING ON AND 7171 05:24:32,200 --> 05:24:33,640 COMING OFF ENTIRELY, WE'VE HAD A 7172 05:24:33,640 --> 05:24:34,560 BUNCH OF ADMISSIONS THAT HAVE 7173 05:24:34,560 --> 05:24:38,880 BEEN DUE TO RUNNING, BEING 7174 05:24:38,880 --> 05:24:40,400 DISCONTINUED FROM TRICAFTA DUE 7175 05:24:40,400 --> 05:24:41,920 TO INSURANCE PROBLEMS, SO, THERE 7176 05:24:41,920 --> 05:24:45,320 IS A DOWN SIDE PARTICULARLY 7177 05:24:45,320 --> 05:24:46,280 PATIENT MODERATE TO SEVERE 7178 05:24:46,280 --> 05:24:48,840 DISEASE COMING OFF CAN BE QUITE 7179 05:24:48,840 --> 05:24:50,520 PROFOUND EFFECTS ON LUNG 7180 05:24:50,520 --> 05:24:53,320 FUNCTION. 7181 05:24:53,320 --> 05:24:54,880 >> AND IMEAN AN AREA IN OUR 7182 05:24:54,880 --> 05:24:55,840 ANIMAL MODELS MIGHT BE ABLE TO 7183 05:24:55,840 --> 05:24:57,680 LOOK AT AS WELL, AND I DO WANT 7184 05:24:57,680 --> 05:24:59,920 TO ACKNOWLEDGE THE WORK OF THE 7185 05:24:59,920 --> 05:25:03,120 CF FOUNDATION'S MENTAL HEALTH 7186 05:25:03,120 --> 05:25:05,080 CONSORTIUM THAT IS TAKE A DEEP 7187 05:25:05,080 --> 05:25:09,800 DIVE INTO MANY OF THESE 7188 05:25:09,800 --> 05:25:11,080 QUESTIONS INCLUDING TAILORING 7189 05:25:11,080 --> 05:25:13,040 NEW MENTAL HEALTH QUESTIONNAIRE 7190 05:25:13,040 --> 05:25:16,200 SPECIFIC FOR CF, SO MORE, YOU 7191 05:25:16,200 --> 05:25:17,840 KNOW RESEARCH TO COME WITH THE 7192 05:25:17,840 --> 05:25:20,160 HELP OF THIS GROUP. 7193 05:25:20,160 --> 05:25:21,320 THERE'S A QUESTION FOR ALL, 7194 05:25:21,320 --> 05:25:23,080 COULD ANY OF THE SPEAKERS 7195 05:25:23,080 --> 05:25:26,960 COMMENT ON THE POTENTIAL ROLE OF 7196 05:25:26,960 --> 05:25:27,920 ELECTRICAL INDEPENDENCE 7197 05:25:27,920 --> 05:25:31,240 SOMOGRAFY ON THE ASSESS OF OF 7198 05:25:31,240 --> 05:25:38,880 EARLY TO MILD CF LUNG DISEASE. 7199 05:25:38,880 --> 05:25:39,160 >> NO. 7200 05:25:39,160 --> 05:25:42,120 THERE ARE A NUMBER OF 7201 05:25:42,120 --> 05:25:42,840 NONINVASIVE EASY MEASURES THAT 7202 05:25:42,840 --> 05:25:49,920 NEED TO BE MORE FULLY STUDIED, 7203 05:25:49,920 --> 05:25:51,840 ISOOMETRY IS BUT IMPEDE ENSEL IS 7204 05:25:51,840 --> 05:25:53,160 DEFINITELY ANOTHER 1 AND I THINK 7205 05:25:53,160 --> 05:25:55,640 WE DON'T NEED TO PUT ALL OF OUR 7206 05:25:55,640 --> 05:25:59,080 EGGS IN THE LCI AND MBW BASKET 7207 05:25:59,080 --> 05:26:03,240 THERE, SOME OF THESE ARE EASY 7208 05:26:03,240 --> 05:26:05,160 BREATHING, SIMPLE MANEUVERS THAT 7209 05:26:05,160 --> 05:26:09,120 COULD BE READILY INCORPORATED 7210 05:26:09,120 --> 05:26:11,560 INTO THE CLINICAL SETTINGS AND 7211 05:26:11,560 --> 05:26:12,120 NEED MORE EVALUATION. 7212 05:26:12,120 --> 05:26:12,680 >> AND I WOULD SECOND THE 7213 05:26:12,680 --> 05:26:16,240 COMMENT THAT IF YOU LOOK AT THE 7214 05:26:16,240 --> 05:26:17,160 CATEGORIZATION OF LUNG FUNCTION 7215 05:26:17,160 --> 05:26:19,240 IN THE CF FOUNDATION REGISTRY 7216 05:26:19,240 --> 05:26:20,960 REPORTS EVERYONE TOOK A JUMP OUT 7217 05:26:20,960 --> 05:26:21,880 OF CATEGORIES. 7218 05:26:21,880 --> 05:26:25,960 SO, WE CLEARLY NEED TO BE ABLE 7219 05:26:25,960 --> 05:26:27,680 TO FOLLOW CLINICALLY A MILD 7220 05:26:27,680 --> 05:26:28,640 DISEASE AND MILDER DISEASE AS 7221 05:26:28,640 --> 05:26:29,960 MORE AND MORE PEOPLE GET ON 7222 05:26:29,960 --> 05:26:31,400 THESE DRUGS EARLIER AND EARLIER 7223 05:26:31,400 --> 05:26:33,200 IN LIFE. 7224 05:26:33,200 --> 05:26:35,400 AND HOW DO WE--AND OUR ABILITY 7225 05:26:35,400 --> 05:26:36,920 TO DETECT CHANGE AND HAVE CHANGE 7226 05:26:36,920 --> 05:26:40,360 LINKED TO A TREATMENT THAT HAS 7227 05:26:40,360 --> 05:26:41,040 BENEFIT WILL BE REALLY 7228 05:26:41,040 --> 05:26:41,320 IMPORTANT. 7229 05:26:41,320 --> 05:26:45,080 SO I DO THINK WE HAVE TO AS 7230 05:26:45,080 --> 05:26:45,960 BROADLY THINK ABOUT DIFFERENT 7231 05:26:45,960 --> 05:26:47,640 WAYS OF MEASURING AND THINKING 7232 05:26:47,640 --> 05:26:51,440 ABOUT LUNG FUNCTION JUST LIKE 7233 05:26:51,440 --> 05:26:52,960 NRI, IN WAYS TO DETECT CHANGE 7234 05:26:52,960 --> 05:26:55,240 AND UNDERSTAND WHAT A MEANINGFUL 7235 05:26:55,240 --> 05:26:56,920 DIFFERENCE IS IN ALL OF THESE 7236 05:26:56,920 --> 05:26:57,200 INSTRUMENTS. 7237 05:26:57,200 --> 05:26:58,720 IT TAKE ACE LOT OF WORK TO 7238 05:26:58,720 --> 05:26:59,840 CREATE THE MEANINGFUL DIFFERENCE 7239 05:26:59,840 --> 05:27:01,080 IN ANY OUTCOMPREHEND MEASURE, 7240 05:27:01,080 --> 05:27:03,240 MEANING CAN YOU TAKE--WE'VE 7241 05:27:03,240 --> 05:27:06,280 BEEN, YOU KNOW LCI HAS HAD A 7242 05:27:06,280 --> 05:27:07,880 TREMENDOUS AMOUNT OF ENERGY PUT 7243 05:27:07,880 --> 05:27:09,080 IN AND IT'S CHALLENGING TO DO 7244 05:27:09,080 --> 05:27:10,280 AND WE'RE GETTING THERE BUT 7245 05:27:10,280 --> 05:27:12,800 AGAIN, I THINK WE CAN'T JUST 7246 05:27:12,800 --> 05:27:15,040 STEER TOWARD 1 OR 2 OUTCOME 7247 05:27:15,040 --> 05:27:17,720 MEASURES AND WE HAVE TO EVOLVE. 7248 05:27:17,720 --> 05:27:18,000 >> GREAT. 7249 05:27:18,000 --> 05:27:19,880 WE HAVE TIME FOR 1 MORE QUESTION 7250 05:27:19,880 --> 05:27:22,520 IN THE FULL CIRCLE MOMENT WE 7251 05:27:22,520 --> 05:27:23,920 STARTED WITH EXACERBATIONS, WE 7252 05:27:23,920 --> 05:27:25,160 WILL END WITH EXACERBATIONS, 7253 05:27:25,160 --> 05:27:26,880 CHRIS OR ALL IF YOU CAN COMMENT 7254 05:27:26,880 --> 05:27:30,240 ON THE ROBUSTNESS OF THE FIES 7255 05:27:30,240 --> 05:27:31,440 DEFINITION OF EXACERBATION BUT I 7256 05:27:31,440 --> 05:27:33,400 WOULD BROADEN THAT JUST TO BE 7257 05:27:33,400 --> 05:27:38,440 WITH, YOU KNOW CURRENTLY USING 7258 05:27:38,440 --> 05:27:40,000 THE FUKs, THERE'S 5 7259 05:27:40,000 --> 05:27:40,640 EXACERBATIONS DEFINITIONS OUT 7260 05:27:40,640 --> 05:27:41,800 THERE, WHICH WE DO IN THE MEAN 7261 05:27:41,800 --> 05:27:45,600 TIME SHOULD WE CONTINUE TO USE 7262 05:27:45,600 --> 05:27:45,880 THEM? 7263 05:27:45,880 --> 05:27:47,320 >> I'LL JUST COMMENT A LITTLE 7264 05:27:47,320 --> 05:27:47,520 BIT. 7265 05:27:47,520 --> 05:27:49,240 I THINK THIS IDEA OF A SYSTEM 7266 05:27:49,240 --> 05:27:54,360 THAT LOOKS AT VALUES AND LUNG 7267 05:27:54,360 --> 05:27:57,960 FUNCTION VALUES AND PATIENT DATA 7268 05:27:57,960 --> 05:27:59,480 TO SUGGEST TO PATIENT/PROVIDER 7269 05:27:59,480 --> 05:28:01,840 THAT THEY MAY BE HAVE AN 7270 05:28:01,840 --> 05:28:03,160 EXACERBATION MAYBE OF REAL 7271 05:28:03,160 --> 05:28:04,680 VALUE, I THINK WANE MORGAN HAS 7272 05:28:04,680 --> 05:28:06,160 BEEN VERY CONCERNED FOR A LONG 7273 05:28:06,160 --> 05:28:08,040 TIME THAT THERE ARE EPISODES 7274 05:28:08,040 --> 05:28:10,440 WHERE LUNG FUNCTION GOES DOWN 7275 05:28:10,440 --> 05:28:11,520 WHICH ARE EXACERBATIONS THAT ARE 7276 05:28:11,520 --> 05:28:14,160 MISSED THAT MAY HAVE IMPACTS ON 7277 05:28:14,160 --> 05:28:16,640 PATIENTS LONG-TERM OUTCOME. 7278 05:28:16,640 --> 05:28:18,560 SO I THINK--I THINK THEY'RE ALL 7279 05:28:18,560 --> 05:28:20,400 DIFFERENT TOOLS, THEY ALL HAVE 7280 05:28:20,400 --> 05:28:21,520 THEIR STRENGTHS AND WEAKNESSES, 7281 05:28:21,520 --> 05:28:23,640 IF WE HAD A BIOMARKER THAT SAID 7282 05:28:23,640 --> 05:28:26,560 YOU HAVE AN EXACERBATION AND IT 7283 05:28:26,560 --> 05:28:27,960 WAS INCREDIBLY ACCURATE AND 7284 05:28:27,960 --> 05:28:29,000 PREDICTIVE, THAT WOULD BE 7285 05:28:29,000 --> 05:28:30,760 WONDERFUL BUT WE DON'T, WE HAVE 7286 05:28:30,760 --> 05:28:32,600 A COLLECTION OF PATIENT REPORTED 7287 05:28:32,600 --> 05:28:34,280 SYMPTOMS AND FEELINGS WHICH ARE 7288 05:28:34,280 --> 05:28:35,720 REALLY IMPORTANT BECAUSE OFTEN 7289 05:28:35,720 --> 05:28:36,760 THAT'S WHAT DRIVES THE PATIENT 7290 05:28:36,760 --> 05:28:39,640 CALL TO OFFICE AND THEN 7291 05:28:39,640 --> 05:28:41,360 OBJECTIVE MEASURES THAT MAYBE 7292 05:28:41,360 --> 05:28:41,840 INFLUX. 7293 05:28:41,840 --> 05:28:44,040 SO I THINK 1 THING WE HAVE TO BE 7294 05:28:44,040 --> 05:28:46,080 CAREFUL OF IS IF EXACERBATIONS 7295 05:28:46,080 --> 05:28:47,240 ARE CHANGING AS JENNIFER NOTED 7296 05:28:47,240 --> 05:28:51,680 WE HAVE TO BE VERY RESPONSIVE IN 7297 05:28:51,680 --> 05:28:53,120 LOOKING AT THE DATA AND SEE IF 7298 05:28:53,120 --> 05:28:57,040 WE SHOULD ADAPT TO CHANGING 7299 05:28:57,040 --> 05:28:57,280 TIMES. 7300 05:28:57,280 --> 05:28:58,440 >> WELL, THANK YOU EVERYONE. 7301 05:28:58,440 --> 05:29:00,120 THIS IS THE CONCLUSION OF OUR 7302 05:29:00,120 --> 05:29:02,760 Q&A SESSION BUT WE ARE READY NOW 7303 05:29:02,760 --> 05:29:11,280 TO TRANSITION SO I WILL HAND IT 7304 05:29:11,280 --> 05:29:12,960 BACK OVER TO [INDISCERNIBLE]. 7305 05:29:12,960 --> 05:29:14,800 >> SO THOSE WHO WEREN'T HERE, 7306 05:29:14,800 --> 05:29:17,800 WE'RE GOING TO OPEN UP THE BREAK 7307 05:29:17,800 --> 05:29:19,200 OUT ROOMS MOMENTARILY AND THERE 7308 05:29:19,200 --> 05:29:21,120 WILL BE A SMALL BOX ON THE 7309 05:29:21,120 --> 05:29:23,680 BOTTOM OF THE ZOOM WINDOW WITH 4 7310 05:29:23,680 --> 05:29:25,960 GRAY BOXES, THAT YOU CLICK AND 7311 05:29:25,960 --> 05:29:27,160 YOU CAN SELECT THE BREAK OUT 7312 05:29:27,160 --> 05:29:28,240 THAT YOU'RE INTERESTED IN. 7313 05:29:28,240 --> 05:29:29,720 SO WE HAVE THE INFORMATION HERE 7314 05:29:29,720 --> 05:29:31,360 BUT YOU ALSO MAY WANT TO CHECK 7315 05:29:31,360 --> 05:29:34,440 THE PROGRAM BOOK FOR MORE 7316 05:29:34,440 --> 05:29:34,960 INFORMATION. 7317 05:29:34,960 --> 05:29:36,240 AND THE MODERATORS WILL BE MOVED 7318 05:29:36,240 --> 05:29:38,760 INTO THAT BREAK OUT ROOM 7319 05:29:38,760 --> 05:29:39,120 AUTOMATICALLY. 7320 05:29:39,120 --> 05:29:41,000 AND SO WE HAVE MODERATORS IN THE 7321 05:29:41,000 --> 05:29:42,760 ROOM TO GUIDE THE DISCUSSION. 7322 05:29:42,760 --> 05:29:45,200 THERE WILL BE A PERIOD OF OPEN 7323 05:29:45,200 --> 05:29:47,160 TIME FOR DISCUSSION AMONGST THE 7324 05:29:47,160 --> 05:29:49,760 ROOM, AND THEN, WE'RE GOING TO 7325 05:29:49,760 --> 05:29:51,840 BE USING A CROWD SOURCING WHITE 7326 05:29:51,840 --> 05:29:53,680 BOARDING TOOL WHICH WILL ALLOW 7327 05:29:53,680 --> 05:29:55,680 YOU TO VOTE AND VOTE YOUR 7328 05:29:55,680 --> 05:29:56,920 PRIORITIES FROM THE DISCUSSION 7329 05:29:56,920 --> 05:29:59,200 TOWARDS THE END OF THE 7330 05:29:59,200 --> 05:29:59,880 BRAINSTORMING SESSION, SO WE'RE 7331 05:29:59,880 --> 05:30:00,960 GOING TO BE IN THE BREAK OUT 7332 05:30:00,960 --> 05:30:02,520 ROOMS FOR ABOUT AN HOUR. 7333 05:30:02,520 --> 05:30:06,920 AT THE END OF THE BREAK OUT HOUR 7334 05:30:06,920 --> 05:30:08,360 WE ASK THAT THE ATTENDEES LEAVE 7335 05:30:08,360 --> 05:30:12,240 THE BREAK OUT ROOMS FOR A 15 7336 05:30:12,240 --> 05:30:14,200 MINUTE BREAK AND THIS WILL ALLOW 7337 05:30:14,200 --> 05:30:16,200 THE MODERATORS TO COLLECT THE 7338 05:30:16,200 --> 05:30:17,800 THOUGHTS AND CLOSE OUT THOSE 7339 05:30:17,800 --> 05:30:22,480 BRAINSTORMING 7340 05:30:22,480 --> 05:30:23,240 BRAINSTORMING BOARDS WE WILL 7341 05:30:23,240 --> 05:30:24,520 WORK OFF OF SO AT THIS TEEM WE 7342 05:30:24,520 --> 05:30:25,480 WILL CLOSE OUT THE ROOM AND YOU 7343 05:30:25,480 --> 05:30:26,440 CAN MAKE YOUR SELECTIONS. 7344 05:30:26,440 --> 05:30:33,440 WELCOME BACK. 7345 05:30:33,440 --> 05:30:34,080 WE ARE GOING TO HAVE A REPORT 7346 05:30:34,080 --> 05:30:43,200 FROM EACH OF THE BREAKOUTS, 7347 05:30:43,200 --> 05:30:43,920 ABOUT 10 MINUTES EACH AND 7348 05:30:43,920 --> 05:30:44,160 THEN 7349 05:30:44,160 --> 05:30:48,640 WE ARE GOING TO SHOW THE 7350 05:30:48,640 --> 05:30:50,960 BOARDS FROM EACH OF THE 7351 05:30:50,960 --> 05:30:51,600 BREAKOUT ROOMS 7352 05:30:51,600 --> 05:30:55,360 INDIVIDUALLY ALLOWING THE 7353 05:30:55,360 --> 05:30:56,040 MODERATORS OF THAT SESSION 7354 05:30:56,040 --> 05:31:00,760 TO REPORT OUT. 7355 05:31:00,760 --> 05:31:01,360 AND THEN WHAT WE HAVE DONE 7356 05:31:01,360 --> 05:31:03,480 WITH THE TOP THREE-FIVE AREAS 7357 05:31:03,480 --> 05:31:06,920 THAT WERE MOST UPVOTED FROM 7358 05:31:06,920 --> 05:31:09,120 EACH OF THE THREE ROOMS, WE 7359 05:31:09,120 --> 05:31:11,400 CONSOLIDATED INTO A FOURTH 7360 05:31:11,400 --> 05:31:11,800 BOARD 7361 05:31:11,800 --> 05:31:13,360 THAT WE WILL USED TO HAVE A 7362 05:31:13,360 --> 05:31:13,800 GENERAL DISCUSSION 7363 05:31:13,800 --> 05:31:14,520 FOR THE LAST 30 MINUTES OF 7364 05:31:14,520 --> 05:31:14,720 THE 7365 05:31:14,720 --> 05:31:15,320 MEETING 7366 05:31:15,320 --> 05:31:15,920 SO THE GENERAL DISCUSSION 7367 05:31:15,920 --> 05:31:18,120 WILL 7368 05:31:18,120 --> 05:31:18,440 BE MODERATED 7369 05:31:18,440 --> 05:31:20,680 BY OUR WORKSHOP COCHAIRS, 7370 05:31:20,680 --> 05:31:23,120 BUT WE ARE ALSO WELCOMING 7371 05:31:23,120 --> 05:31:24,200 THE SPEAKERS 7372 05:31:24,200 --> 05:31:26,440 AND BREAKOUT SESSION 7373 05:31:26,440 --> 05:31:26,760 MODERATORS 7374 05:31:26,760 --> 05:31:27,280 TO PARTICIPATE IN THAT 7375 05:31:27,280 --> 05:31:28,560 DISCUSSION AS WELL. 7376 05:31:28,560 --> 05:31:29,200 SO WITH THAT I AM GOING TO 7377 05:31:29,200 --> 05:31:29,400 ASK 7378 05:31:29,400 --> 05:31:36,640 THAT WE PULL UP THE 7379 05:31:36,640 --> 05:31:39,440 FIRST PAGE FROM THE BREAKOUT, 7380 05:31:39,440 --> 05:31:48,400 ON BREAKOUT SESSION 1. 7381 05:31:48,400 --> 05:31:50,520 APOLOGIZE. SOMEONE MESSAGED 7382 05:31:50,520 --> 05:31:54,880 THAT YOU CANNOT SEE ME. 7383 05:31:54,880 --> 05:32:05,000 -- -- 7384 05:32:08,000 --> 05:32:09,800 AND THEN I WILL TURN IT OVER 7385 05:32:09,800 --> 05:32:10,440 TO THE MODERATORS FROM 7386 05:32:10,440 --> 05:32:10,720 SESSION 7387 05:32:10,720 --> 05:32:14,880 1. 7388 05:32:14,880 --> 05:32:20,600 >> HI EVERYONE. 7389 05:32:20,600 --> 05:32:24,800 I'M JESS PITTMAN. 7390 05:32:24,800 --> 05:32:27,360 I WILL TRY TO SUMMARIZE WHAT 7391 05:32:27,360 --> 05:32:30,360 WE TALKED ABOUT IN OUR GROUP. 7392 05:32:30,360 --> 05:32:31,360 WE TALKED ABOUT STARTING OR 7393 05:32:31,360 --> 05:32:32,760 NOT STARTINGAGMT WITH 7394 05:32:32,760 --> 05:32:34,920 PATIENTS WITH MILD DISEASE 7395 05:32:34,920 --> 05:32:36,360 WITH A RELATIVELY HEAVY FOCUS 7396 05:32:36,360 --> 05:32:38,880 ON PEDIATRIC PATIENTS, 7397 05:32:38,880 --> 05:32:39,520 PARTICULARLY YOUNG PEDIATRIC 7398 05:32:39,520 --> 05:32:41,200 PATIENTS. 7399 05:32:41,200 --> 05:32:43,280 WE INITIALLY STARTED OFF 7400 05:32:43,280 --> 05:32:44,640 TALKING ABOUT OFF LABEL 7401 05:32:44,640 --> 05:32:45,200 DISCUSSION ABOUT HOW YOU 7402 05:32:45,200 --> 05:32:46,480 MIGHT 7403 05:32:46,480 --> 05:32:52,080 INITIATE THERAPY IN INFANTS 7404 05:32:52,080 --> 05:32:55,080 WITH TRICAFTA (PHONETIC) 7405 05:32:55,080 --> 05:32:55,600 FOR INSTANCE AND WHEN 7406 05:32:55,600 --> 05:32:55,920 PATIENTS 7407 05:32:55,920 --> 05:32:58,440 ARE AGE ELIGIBLE, 7408 05:32:58,440 --> 05:32:59,000 PARTICULARLY IF THAT AGE 7409 05:32:59,000 --> 05:33:00,920 CONTINUES TO GO LOWER 7410 05:33:00,920 --> 05:33:02,960 WHAT WILL BE THE FACTORS THAT 7411 05:33:02,960 --> 05:33:03,800 DROVE US TO 7412 05:33:03,800 --> 05:33:05,480 EITHER ENCOURAGE INITIATION 7413 05:33:05,480 --> 05:33:07,720 OR CONSIDER DELAY. 7414 05:33:07,720 --> 05:33:12,280 THE BIGGEST PART OF OUR 7415 05:33:12,280 --> 05:33:14,400 DISCUSSION, WITH SORT OF 7416 05:33:14,400 --> 05:33:14,680 TOGGLED 7417 05:33:14,680 --> 05:33:15,640 BETWEEN IF YOU DELAY THERAPY 7418 05:33:15,640 --> 05:33:23,720 HOW WOULD YOU MONITOR IT 7419 05:33:23,720 --> 05:33:26,280 TO MORE OF A PRO THERAPY 7420 05:33:26,280 --> 05:33:26,840 DISCUSSION ABOUT WHY YOU 7421 05:33:26,840 --> 05:33:27,080 WOULD 7422 05:33:27,080 --> 05:33:27,680 DELAY THERAPY AND THERE WAS A 7423 05:33:27,680 --> 05:33:32,720 LOT OF DISCUSSION ABOUT THE 7424 05:33:32,720 --> 05:33:33,320 PRIMARY PREVENTION ASPECT, 7425 05:33:33,320 --> 05:33:33,520 CAN 7426 05:33:33,520 --> 05:33:35,000 WE PREVENT THE EARLIEST LUNG 7427 05:33:35,000 --> 05:33:37,760 DISEASE? 7428 05:33:37,760 --> 05:33:38,360 CAN WE HAVE A CHANCE ABOUT 7429 05:33:38,360 --> 05:33:38,920 RECOVERING OR MAINTAINING 7430 05:33:38,920 --> 05:33:39,400 PANCREATIC FUNCTION. 7431 05:33:39,400 --> 05:33:45,960 CAN WE MAINTAIN VASTDEFIN 7432 05:33:45,960 --> 05:33:47,800 (PHONETIC) CAN WE AVOID 7433 05:33:47,800 --> 05:33:50,840 (INDISCERNIBLE), 7434 05:33:50,840 --> 05:33:51,440 CRITICALLY LINKED TO LUNG 7435 05:33:51,440 --> 05:33:54,360 FUNCTION. 7436 05:33:54,360 --> 05:33:55,120 SHOULD WE BE DOING EVERYTHING 7437 05:33:55,120 --> 05:33:56,080 WE CAN TO ENCOURAGE ADEQUATE 7438 05:33:56,080 --> 05:33:58,480 GROWTH, 7439 05:33:58,480 --> 05:34:00,000 OPTIMAL HEIGHT IN THIS 7440 05:34:00,000 --> 05:34:02,760 PATIENT'S WHICH WE WOULD 7441 05:34:02,760 --> 05:34:07,800 PRESUME THAT MODULATOR 7442 05:34:07,800 --> 05:34:08,080 THERAPY 7443 05:34:08,080 --> 05:34:08,760 WOULD DO AND WE HAD A LOT OF 7444 05:34:08,760 --> 05:34:09,400 DISCUSSION THAT JUST BECAUSE 7445 05:34:09,400 --> 05:34:10,040 WE CANNOT FIND THE DISEASE, 7446 05:34:10,040 --> 05:34:10,240 WE 7447 05:34:10,240 --> 05:34:12,200 DO NOT HAVE THE TOOLS, DOES 7448 05:34:12,200 --> 05:34:14,520 NOT MEAN THAT THEY ARE NOT 7449 05:34:14,520 --> 05:34:18,160 THERE YET. 7450 05:34:18,160 --> 05:34:19,080 ONE PERSON COMMENTED 7451 05:34:19,080 --> 05:34:20,520 SUCCINCTLY THAT THE RISKS OF 7452 05:34:20,520 --> 05:34:21,160 EARLY THERAPY ARE DWARFED BY 7453 05:34:21,160 --> 05:34:24,960 THE KNOWN RISK OF EARLY CF. 7454 05:34:24,960 --> 05:34:25,880 WE ALSO HAVE A LOT OF UNKNOWN 7455 05:34:25,880 --> 05:34:30,080 RISK OF CF AS OUR PATIENT 7456 05:34:30,080 --> 05:34:30,680 CONTINUES TO BE HEALTHIER AND 7457 05:34:30,680 --> 05:34:31,680 LIVE LONGER AND ARE LIVING 7458 05:34:31,680 --> 05:34:33,160 INTO SORT OF SENIOR YEARS AND 7459 05:34:33,160 --> 05:34:33,760 WHAT THAT LOOKS LIKE. 7460 05:34:33,760 --> 05:34:36,280 --- 7461 05:34:36,280 --> 05:34:36,760 WE DID HAVE A LOT OF 7462 05:34:36,760 --> 05:34:37,360 CONVERSATION ALSO ABOUT 7463 05:34:37,360 --> 05:34:42,000 LONG-TERM RISKS OFHEMT, 7464 05:34:42,000 --> 05:34:44,520 SPECIFICALLY THINKING ABOUT 7465 05:34:44,520 --> 05:34:45,760 THE LONG-TERM IMPACT IN YOUNG 7466 05:34:45,760 --> 05:34:47,200 CHILDREN, CHILDREN WHO ARE 7467 05:34:47,200 --> 05:34:49,960 RAPIDLY GROWING AND HAVE A 7468 05:34:49,960 --> 05:34:50,440 LOT OF NEUROCOGNITIVE 7469 05:34:50,440 --> 05:34:52,520 DEVELOPMENT IN PARTICULAR. 7470 05:34:52,520 --> 05:34:54,800 SO THERE WAS A DISCUSSION 7471 05:34:54,800 --> 05:34:55,440 ABOUT HOW WE MIGHT GET BETTER 7472 05:34:55,440 --> 05:34:59,160 SAFETY AND EFFICACY LONG-TERM 7473 05:34:59,160 --> 05:35:02,520 AND THINK ABOUT MONITORING 7474 05:35:02,520 --> 05:35:03,160 SOME OF THOSE NEUROCOGNITIVE 7475 05:35:03,160 --> 05:35:03,680 IMPACTS OR POTENTIAL 7476 05:35:03,680 --> 05:35:07,720 NEUROCOGNITIVE IMPACTS, 7477 05:35:07,720 --> 05:35:08,360 PARTICULAR THINKING ABOUT HOW 7478 05:35:08,360 --> 05:35:09,000 INITIATION AT DIFFERENT AGES 7479 05:35:09,000 --> 05:35:10,560 AND DEVELOPMENTAL STATES 7480 05:35:10,560 --> 05:35:10,800 MIGHT 7481 05:35:10,800 --> 05:35:19,360 IMPACT SIDE EFFECT PROFILE. 7482 05:35:19,360 --> 05:35:21,080 --- 7483 05:35:21,080 --> 05:35:23,000 ANOTHER TOPIC THAT WAS 7484 05:35:23,000 --> 05:35:30,000 EMPHASIZED WAS THE USE OF 7485 05:35:30,000 --> 05:35:35,600 SWWEAT CHLORIDE AS A USEFUL 7486 05:35:35,600 --> 05:35:37,920 BIOMARKER, 7487 05:35:37,920 --> 05:35:40,760 WE HAD CONFLICTING DATA ABOUT 7488 05:35:40,760 --> 05:35:41,320 OLDER PATIENTS PARTICULAR 7489 05:35:41,320 --> 05:35:43,200 WITH 7490 05:35:43,200 --> 05:35:44,520 RESPONSE, PART OF THIS 7491 05:35:44,520 --> 05:35:45,120 CONVERSATION THAT WE HAD WAS 7492 05:35:45,120 --> 05:35:46,440 HMMM THIS MIGHT LOOK 7493 05:35:46,440 --> 05:35:46,720 DIFFERENT 7494 05:35:46,720 --> 05:35:47,960 IF YOU DID NOT HAVE EXISTING 7495 05:35:47,960 --> 05:35:51,760 LUNG DISEASE. 7496 05:35:51,760 --> 05:35:54,080 MIGHT YOU SEE A TIGHTER 7497 05:35:54,080 --> 05:35:54,640 CORRELATION BETWEEN SWEAT 7498 05:35:54,640 --> 05:35:55,160 CHLORIDE RESPONSE AND 7499 05:35:55,160 --> 05:36:00,520 PRESERVATION OF LUNG FUNCTION 7500 05:36:00,520 --> 05:36:01,160 AND NUTRITIONAL IMPROVEMENTS 7501 05:36:01,160 --> 05:36:02,520 IN PATIENTS WHO HAD NOT 7502 05:36:02,520 --> 05:36:03,120 DEVELOPED SIGNIFICANT LUNG 7503 05:36:03,120 --> 05:36:05,440 DISEASE OR WHAT WE PERCEIVE 7504 05:36:05,440 --> 05:36:05,640 AS 7505 05:36:05,640 --> 05:36:06,640 PERMANENT LUNG DISEASE. 7506 05:36:06,640 --> 05:36:07,800 --- 7507 05:36:07,800 --> 05:36:09,640 THERE WAS SOME CONCERN AND 7508 05:36:09,640 --> 05:36:12,600 PERHAPS MAY ALREADY BE 7509 05:36:12,600 --> 05:36:14,920 HAPPENING THAT SWEAT CHLORIDE 7510 05:36:14,920 --> 05:36:15,520 HAS TO BE USED AS EITHER A 7511 05:36:15,520 --> 05:36:17,240 MEASURE OF WHETHER THE 7512 05:36:17,240 --> 05:36:17,520 PATIENT 7513 05:36:17,520 --> 05:36:21,320 HAS AN ADEQUATE RESPONSE TO 7514 05:36:21,320 --> 05:36:21,520 BE 7515 05:36:21,520 --> 05:36:23,280 WILLING TO PAY FOR MODULATOR 7516 05:36:23,280 --> 05:36:23,760 THERAPY OR TO MONITOR 7517 05:36:23,760 --> 05:36:26,520 ADHERENCE AND THIS WAS 7518 05:36:26,520 --> 05:36:27,120 BROUGHT 7519 05:36:27,120 --> 05:36:29,600 UP AS A PROBE POTENTIALLY OR 7520 05:36:29,600 --> 05:36:30,160 AT LEAST THESE POTENTIAL 7521 05:36:30,160 --> 05:36:31,000 USEFUL MODALITY IN TERMS OF 7522 05:36:31,000 --> 05:36:31,600 PATIENTS WHO DON'T SEEM TO BE 7523 05:36:31,600 --> 05:36:32,160 DOING WELL ON MODULATOR 7524 05:36:32,160 --> 05:36:34,080 THERAPY. 7525 05:36:34,080 --> 05:36:34,640 IS IT WORTH GETTING SWEAT 7526 05:36:34,640 --> 05:36:38,640 CHLORIDE TO SEE EITHER 7527 05:36:38,640 --> 05:36:40,320 RESPONSE OR APPEARANCE AS 7528 05:36:40,320 --> 05:36:41,280 OPPOSED TO LAYERING ON OTHER 7529 05:36:41,280 --> 05:36:41,600 THERAPIES. 7530 05:36:41,600 --> 05:36:43,080 --- 7531 05:36:43,080 --> 05:36:44,720 SPECIFICALLY TALKING ABOUT 7532 05:36:44,720 --> 05:36:47,200 SOME OF THE MODIFIED DOSING 7533 05:36:47,200 --> 05:36:50,800 REGIMEN MENTIONED IN THE 7534 05:36:50,800 --> 05:36:52,520 PREVIOUS SESSION, IN THE 7535 05:36:52,520 --> 05:36:59,040 QUESTION BLOCK, 7536 05:36:59,040 --> 05:37:01,960 IS SWEAT CHLORIDE USEFUL TO 7537 05:37:01,960 --> 05:37:02,480 MONITOR FOR A MINIMAL 7538 05:37:02,480 --> 05:37:03,000 THRESHOLD RESPONSE TO 7539 05:37:03,000 --> 05:37:03,280 LOWERING 7540 05:37:03,280 --> 05:37:03,880 YOUR DOSE TO GET WHAT YOU 7541 05:37:03,880 --> 05:37:04,120 WERE 7542 05:37:04,120 --> 05:37:04,720 GETTING BEFORE IN TERMS OF 7543 05:37:04,720 --> 05:37:05,000 EFFICACY? 7544 05:37:05,000 --> 05:37:07,240 --- 7545 05:37:07,240 --> 05:37:08,520 AND THE FINAL THING WE TALKED 7546 05:37:08,520 --> 05:37:10,680 ABOUT AS I MENTIONED EARLIER 7547 05:37:10,680 --> 05:37:12,600 WAS THE NEED FOR EFFICACY 7548 05:37:12,600 --> 05:37:19,680 AMONG LONG-TERM DATA IN 7549 05:37:19,680 --> 05:37:19,880 YOUNG 7550 05:37:19,880 --> 05:37:20,560 CHILDREN AND INFANTS AND 7551 05:37:20,560 --> 05:37:20,800 THERE 7552 05:37:20,800 --> 05:37:21,440 WAS SOME DISCUSSION THAT SOME 7553 05:37:21,440 --> 05:37:22,040 OF THE ONGOING LONGITUDINAL 7554 05:37:22,040 --> 05:37:25,720 STUDIES AT LEAST BEGIN TO 7555 05:37:25,720 --> 05:37:26,560 ANSWER THESE QUESTIONS BUT IF 7556 05:37:26,560 --> 05:37:27,080 WE ARE TALKING ABOUT 7557 05:37:27,080 --> 05:37:27,880 INITIATION AT INFANCY, THAT 7558 05:37:27,880 --> 05:37:28,720 DATA DOES NOT EXIST YET. 7559 05:37:28,720 --> 05:37:32,440 --- 7560 05:37:32,440 --> 05:37:32,960 LOOKING SPECIFICALLY AT 7561 05:37:32,960 --> 05:37:33,560 REDUCING RISK OF INFECTION 7562 05:37:33,560 --> 05:37:33,760 AND 7563 05:37:33,760 --> 05:37:34,920 LUNG INFECTION DECLINE, 7564 05:37:34,920 --> 05:37:35,560 THINKING MORE ABOUT REAL-TIME 7565 05:37:35,560 --> 05:37:39,440 EFFICACY DATA, 7566 05:37:39,440 --> 05:37:42,080 LONGER, LARGER LONGITUDINAL 7567 05:37:42,080 --> 05:37:42,360 STUDIES 7568 05:37:42,360 --> 05:37:43,080 AND THEN AS I MENTIONED 7569 05:37:43,080 --> 05:37:46,640 EARLIER 7570 05:37:46,640 --> 05:37:47,240 WITH ALL OF THE CONCERNS 7571 05:37:47,240 --> 05:37:47,440 ABOUT 7572 05:37:47,440 --> 05:37:53,480 MENTAL HEALTH IN OLDER ADULTS 7573 05:37:53,480 --> 05:37:54,080 WE ECHOED THESE CONCERNS IN 7574 05:37:54,080 --> 05:37:55,160 CHILDREN AND THE POTENTIAL 7575 05:37:55,160 --> 05:37:56,920 COGNITIVE IMPACT 7576 05:37:56,920 --> 05:37:57,520 IN THINKING ABOUT HOW WE 7577 05:37:57,520 --> 05:37:57,720 COULD 7578 05:37:57,720 --> 05:37:59,040 OR SHOULD 7579 05:37:59,040 --> 05:38:02,360 BE PROACTIVELY MONITORING 7580 05:38:02,360 --> 05:38:04,880 FOR CHANGES IN DEVELOPMENT. 7581 05:38:04,880 --> 05:38:07,360 AND DO WE NEED TO THINK ABOUT 7582 05:38:07,360 --> 05:38:08,600 ALTERING OUR CLINICAL MODEL 7583 05:38:08,600 --> 05:38:14,000 THINKING ABOUT OUR NICU 7584 05:38:14,000 --> 05:38:14,400 FOLLOW-UP CLINICS. 7585 05:38:14,400 --> 05:38:15,000 IS THAT A MODALITY THAT WE 7586 05:38:15,000 --> 05:38:15,440 NEED TO CONSIDER? 7587 05:38:15,440 --> 05:38:17,480 --- 7588 05:38:17,480 --> 05:38:19,040 WE HAD A LOT OF CONVERSATION 7589 05:38:19,040 --> 05:38:22,080 ABOUT WHAT THE -- MAY BE 7590 05:38:22,080 --> 05:38:22,920 DOING 7591 05:38:22,920 --> 05:38:23,440 IN THE BRAIN AS WELL. 7592 05:38:23,440 --> 05:38:24,880 AND THERE WAS SOME DISCUSSION 7593 05:38:24,880 --> 05:38:26,800 ABOUT DRUG LEVELS AND WHETHER 7594 05:38:26,800 --> 05:38:29,480 OR NOT WE REALLY KNOW WHAT IT 7595 05:38:29,480 --> 05:38:39,520 THERAPEUTIC DRUG LEVEL IS 7596 05:38:39,520 --> 05:38:40,160 WHETHER MOST DRUG LEVELS ARE 7597 05:38:40,160 --> 05:38:41,280 BASED PRIMARILY ON SAFETY AS 7598 05:38:41,280 --> 05:38:41,760 OPPOSED TO EFFICACY. 7599 05:38:41,760 --> 05:38:43,040 WHILE MAINTAINING SAFETY, 7600 05:38:43,040 --> 05:38:45,200 DO WE EVEN HAVE THAT DATA FOR 7601 05:38:45,200 --> 05:38:45,560 OUR PATIENTS? 7602 05:38:45,560 --> 05:38:49,560 --- 7603 05:38:49,560 --> 05:38:50,160 IN THE LAST QUESTION WHICH 7604 05:38:50,160 --> 05:38:51,760 SORT OF LINKS TO THINKING 7605 05:38:51,760 --> 05:38:54,000 ABOUT DISCONTINUING OTHER 7606 05:38:54,000 --> 05:38:55,600 THERAPIES, DO WE HAVE OTHER 7607 05:38:55,600 --> 05:38:56,680 DATA ON HOW MUCH THERAPIES 7608 05:38:56,680 --> 05:38:56,880 MAY 7609 05:38:56,880 --> 05:38:57,880 INTERACT OR IMPACT THE 7610 05:38:57,880 --> 05:39:02,480 RESPONSE TO OTHER CF 7611 05:39:02,480 --> 05:39:04,040 THERAPIES? 7612 05:39:04,040 --> 05:39:06,600 DID I MISS ANYTHING? 7613 05:39:06,600 --> 05:39:08,120 >> THAT WAS AWESOME. 7614 05:39:08,120 --> 05:39:10,160 >> YOU DID REALLY WELL JESS, 7615 05:39:10,160 --> 05:39:18,600 THANK YOU. 7616 05:39:18,600 --> 05:39:20,160 >> ALL RIGHT GREAT. 7617 05:39:20,160 --> 05:39:22,160 THANK YOU. 7618 05:39:22,160 --> 05:39:23,160 WE CAN MOVE ON TO THE REPORT 7619 05:39:23,160 --> 05:39:26,320 OUT FROM BREAKOUT 2. 7620 05:39:26,320 --> 05:39:26,920 PULL UP THE BOARD FOR THAT 7621 05:39:26,920 --> 05:39:33,040 ROOM NOW. 7622 05:39:33,040 --> 05:39:43,160 -- -- 7623 05:40:11,440 --> 05:40:14,280 >> SO OUR TOPIC WAS 7624 05:40:14,280 --> 05:40:14,560 ADVANCING 7625 05:40:14,560 --> 05:40:15,200 CLINICAL CARE AND OUTCOMES IN 7626 05:40:15,200 --> 05:40:17,040 THE POST MODULATOR AREA. 7627 05:40:17,040 --> 05:40:18,200 WE TALKED A LITTLE BIT AT THE 7628 05:40:18,200 --> 05:40:20,520 START ABOUT WHETHER THERE 7629 05:40:20,520 --> 05:40:20,760 WERE 7630 05:40:20,760 --> 05:40:26,600 THINGS WE COULD LEARN ABOUT 7631 05:40:26,600 --> 05:40:30,440 NON-CF BRONCHIECTATIC 7632 05:40:30,440 --> 05:40:34,200 PHENOTYPE, 7633 05:40:34,200 --> 05:40:34,800 DEFINITIONS OF EXACERBATION 7634 05:40:34,800 --> 05:40:35,840 AND WE THOUGHT THERE MIGHT BE 7635 05:40:35,840 --> 05:40:38,280 WORKING TO JUST TO GET THOSE 7636 05:40:38,280 --> 05:40:38,880 THINGS DONE BEFORE WE COULD 7637 05:40:38,880 --> 05:40:39,560 GATHER A WHOLE LOT OF LESSONS 7638 05:40:39,560 --> 05:40:50,080 THAT COULD BE APPLIED TO CF 7639 05:40:50,720 --> 05:40:56,720 BRONCHIECTASIS, 7640 05:40:56,720 --> 05:40:57,360 AND TO GET THE NUMBERS NEEDED 7641 05:40:57,360 --> 05:40:57,960 FOR GOOD EFFECTIVE TRIALS. 7642 05:40:57,960 --> 05:41:00,600 --- 7643 05:41:00,600 --> 05:41:02,160 WE MOVED TO WHAT WAS NEEDED 7644 05:41:02,160 --> 05:41:02,360 TO 7645 05:41:02,360 --> 05:41:02,880 UNDERSTAND DISEASE AND 7646 05:41:02,880 --> 05:41:03,160 FORWARD 7647 05:41:03,160 --> 05:41:03,640 IN THIS ERA. 7648 05:41:03,640 --> 05:41:05,560 WE TALKED ABOUT THE NEED FOR 7649 05:41:05,560 --> 05:41:08,240 WAYS TO MEASURE MICROBIOLOGY, 7650 05:41:08,240 --> 05:41:09,760 MAY BE WAYS TO ASSESS 7651 05:41:09,760 --> 05:41:11,200 MICROBIOLOGY BETTER. 7652 05:41:11,200 --> 05:41:14,560 YOU HEARD SOME THINGS ABOUT 7653 05:41:14,560 --> 05:41:15,200 EXHALED BREATH THAT MIGHT BE 7654 05:41:15,200 --> 05:41:17,080 USEFUL FOR THAT. 7655 05:41:17,080 --> 05:41:18,720 WE TALKED ABOUT THE NEED TO 7656 05:41:18,720 --> 05:41:18,920 REALLY 7657 05:41:18,920 --> 05:41:20,920 EXPAND OUR MEASURES ACROSSTHE 7658 05:41:20,920 --> 05:41:22,680 LIFESPAN. 7659 05:41:22,680 --> 05:41:27,080 SO LOOKING AT EVERYONE FROM 7660 05:41:27,080 --> 05:41:30,920 MIDTEENS ALL THE WAY TO OLDER 7661 05:41:30,920 --> 05:41:31,240 FOLKS 7662 05:41:31,240 --> 05:41:32,600 NOW THAT THE LIFESPAN IS 7663 05:41:32,600 --> 05:41:33,200 EXPANDED AND HOW TO DO THAT 7664 05:41:33,200 --> 05:41:38,960 AND HOW, WE CAN MEASURE, AND 7665 05:41:38,960 --> 05:41:39,560 WE HEARD ABOUT IMAGING AND 7666 05:41:39,560 --> 05:41:40,120 EXHALED BREATH THAT MIGHT 7667 05:41:40,120 --> 05:41:40,360 WORK. 7668 05:41:40,360 --> 05:41:42,680 --- 7669 05:41:42,680 --> 05:41:43,200 ONE PROBLEM THAT GET 7670 05:41:43,200 --> 05:41:43,480 DISCUSSED 7671 05:41:43,480 --> 05:41:44,680 A LITTLE BIT WITH SOME OF 7672 05:41:44,680 --> 05:41:51,200 THESE PATIENTS CAN'T 7673 05:41:51,200 --> 05:41:56,840 EXPECTORATE SPUTUM ANYMORE. 7674 05:41:56,840 --> 05:41:59,160 WE TALKED ABOUT THE 7675 05:41:59,160 --> 05:42:00,160 POSSIBILITY AND NEED FOR 7676 05:42:00,160 --> 05:42:02,000 INITIATIVES FROM EACH OF THE 7677 05:42:02,000 --> 05:42:07,200 IRS, AND SEE IF THERE WERE 7678 05:42:07,200 --> 05:42:07,760 SOME OF THESE MONITORING 7679 05:42:07,760 --> 05:42:08,040 METHODS. 7680 05:42:08,040 --> 05:42:09,760 --- 7681 05:42:09,760 --> 05:42:13,240 WE GOT INTO BIOMARKERS A LOT 7682 05:42:13,240 --> 05:42:14,760 AND THE BIG THING THAT CAME 7683 05:42:14,760 --> 05:42:15,400 OUT OF OUR DISCUSSION WAS THE 7684 05:42:15,400 --> 05:42:16,800 NEED TO KIND OF DEVELOP THESE 7685 05:42:16,800 --> 05:42:18,320 NEW BIOMARKERS WHILE AT THE 7686 05:42:18,320 --> 05:42:18,920 SAME TIME NOT THROWING OUT 7687 05:42:18,920 --> 05:42:23,000 SOME OF THE OLD BIOMARKERS IN 7688 05:42:23,000 --> 05:42:23,600 THE THINGS WE HAVE COME TO 7689 05:42:23,600 --> 05:42:23,920 DEPEND ON. 7690 05:42:23,920 --> 05:42:27,080 SO PARALLEL DEVELOPMENT, 7691 05:42:27,080 --> 05:42:28,760 USING 7692 05:42:28,760 --> 05:42:29,960 MEASUREMENTS WHILE AT THE 7693 05:42:29,960 --> 05:42:30,160 SAME 7694 05:42:30,160 --> 05:42:30,760 TIME TRYING TO DEVELOP NEW 7695 05:42:30,760 --> 05:42:32,240 ONES. 7696 05:42:32,240 --> 05:42:32,680 AND SOME OF THESE 7697 05:42:32,680 --> 05:42:33,040 MEASUREMENTS 7698 05:42:33,040 --> 05:42:34,920 THAT WE ARE USED TO ARE GOING 7699 05:42:34,920 --> 05:42:36,800 TO HAVE CEILING EFFECTS WHERE 7700 05:42:36,800 --> 05:42:39,360 THEY MAY NOT BE SENSITIVE 7701 05:42:39,360 --> 05:42:40,000 ANYMORE AND WE NEED TO DECIDE 7702 05:42:40,000 --> 05:42:43,040 AND PRIORITIZE TRYING TO FIND 7703 05:42:43,040 --> 05:42:43,640 WAYS TO WORK AROUND THAT OR 7704 05:42:43,640 --> 05:42:44,160 YOU INSTRUMENTS TO WORK 7705 05:42:44,160 --> 05:42:44,440 AROUND 7706 05:42:44,440 --> 05:42:44,640 THAT. 7707 05:42:44,640 --> 05:42:46,040 --- 7708 05:42:46,040 --> 05:42:46,600 WE TALKED A LOT ABOUT THE 7709 05:42:46,600 --> 05:42:46,840 FACT 7710 05:42:46,840 --> 05:42:53,000 THAT THERE ARE BANK SPECIMENS 7711 05:42:53,000 --> 05:42:53,600 FROM SOME OF THESE STUDIES 7712 05:42:53,600 --> 05:42:55,000 THAT HAVE BEEN PUT AWAY AND 7713 05:42:55,000 --> 05:42:55,680 MAYBE PEOPLE ARE NOT AS AWARE 7714 05:42:55,680 --> 05:42:56,840 OF THEIR AVAILABILITY AND 7715 05:42:56,840 --> 05:42:57,080 THAT 7716 05:42:57,080 --> 05:42:58,960 THEY MIGHT BE A BIG RESOURCE 7717 05:42:58,960 --> 05:43:00,120 FOR PEOPLE THEY KNEW ABOUT 7718 05:43:00,120 --> 05:43:02,520 THEM AND COULD ACCESS THEM, 7719 05:43:02,520 --> 05:43:07,120 AND THE FOUNDATION IS WORKING 7720 05:43:07,120 --> 05:43:07,640 TOWARDS DOING THAT, AND 7721 05:43:07,640 --> 05:43:07,920 TRYING 7722 05:43:07,920 --> 05:43:08,440 TO MAKE THOSE RESOURCES 7723 05:43:08,440 --> 05:43:08,760 AVAILABLE. 7724 05:43:08,760 --> 05:43:10,680 --- 7725 05:43:10,680 --> 05:43:11,240 AND THAT THERE MIGHT BE A 7726 05:43:11,240 --> 05:43:11,480 NEED 7727 05:43:11,480 --> 05:43:12,920 FOR SOME FUNDING MECHANISMS 7728 05:43:12,920 --> 05:43:15,080 THAT WOULD LET PEOPLE GET IN 7729 05:43:15,080 --> 05:43:16,840 THERE AND USE THOSE SAMPLES 7730 05:43:16,840 --> 05:43:17,520 INTO SECONDARY ANALYSIS ON 7731 05:43:17,520 --> 05:43:18,880 SOME SAMPLES WE GATHERED. 7732 05:43:18,880 --> 05:43:20,000 --- 7733 05:43:20,000 --> 05:43:20,600 WE HAD SOME OF THE SPECIFIC 7734 05:43:20,600 --> 05:43:24,680 STUDIES LISTED THERE. 7735 05:43:24,680 --> 05:43:28,240 WE WERE WONDERING ABOUT HOW 7736 05:43:28,240 --> 05:43:28,840 ACCESSIBLE THE SAMPLES WERE. 7737 05:43:28,840 --> 05:43:30,480 --- 7738 05:43:30,480 --> 05:43:31,080 WE TALKED A LOT ABOUT THE 7739 05:43:31,080 --> 05:43:31,320 NEED 7740 05:43:31,320 --> 05:43:33,840 TO DEVELOP NEW BIOMARKERS AND 7741 05:43:33,840 --> 05:43:36,640 CORRELATE THEM. 7742 05:43:36,640 --> 05:43:38,560 A LOT OF THE BIOMARKER 7743 05:43:38,560 --> 05:43:39,160 DISCUSSIONS CAME BACK TO THE 7744 05:43:39,160 --> 05:43:40,640 IDEA THAT 7745 05:43:40,640 --> 05:43:42,920 IT WAS A GOOD IDEA TO PURSUE 7746 05:43:42,920 --> 05:43:43,520 THESE THINGS. WE PROBABLY 7747 05:43:43,520 --> 05:43:43,760 NEED 7748 05:43:43,760 --> 05:43:48,880 TO SPREAD OUT OUR EFFORTS AND 7749 05:43:48,880 --> 05:43:50,120 NOT JUST FOCUS IN ONE 7750 05:43:50,120 --> 05:43:50,760 DIRECTION, NEED SOME TIME TO 7751 05:43:50,760 --> 05:43:53,640 DEVELOP THOSE BIOMARKERS 7752 05:43:53,640 --> 05:43:54,680 WITH THE DATA THAT IS OUT 7753 05:43:54,680 --> 05:43:55,280 THERE SO WE KNOW WHAT THEY 7754 05:43:55,280 --> 05:43:55,640 ACTUALLY MEAN. 7755 05:43:55,640 --> 05:43:57,280 --- 7756 05:43:57,280 --> 05:43:59,000 WE DID HAVE SOME DISCUSSION 7757 05:43:59,000 --> 05:44:00,960 ABOUT A TRIAL DESIGN, MORE 7758 05:44:00,960 --> 05:44:01,480 FLEXIBLE TRIAL DESIGNS, 7759 05:44:01,480 --> 05:44:03,880 PRAGMATIC TRIALS AND THERE 7760 05:44:03,880 --> 05:44:06,360 WERE PROS AND CONS AND HOW 7761 05:44:06,360 --> 05:44:06,960 USEFUL THAT WOULD BE FOR 7762 05:44:06,960 --> 05:44:09,320 DEVELOPING NEW THERAPIES. 7763 05:44:09,320 --> 05:44:11,560 I THINK ONE THING WE TALKED 7764 05:44:11,560 --> 05:44:13,960 ABOUT IN DEVELOPING SOME OF 7765 05:44:13,960 --> 05:44:14,520 THE SURROGATES WE NEED TO 7766 05:44:14,520 --> 05:44:15,760 INVOLVE REGULATORY AGENCIES 7767 05:44:15,760 --> 05:44:18,560 BECAUSE AT THE END OF THE 7768 05:44:18,560 --> 05:44:18,800 DAY, 7769 05:44:18,800 --> 05:44:19,400 THEY WILL MAKE THE DECISIONS 7770 05:44:19,400 --> 05:44:21,800 ABOUT WHAT THEY CONSIDER TO 7771 05:44:21,800 --> 05:44:22,000 BE 7772 05:44:22,000 --> 05:44:22,600 GOOD SURROGATES IN TERMS OF 7773 05:44:22,600 --> 05:44:25,200 GETTING APPROVAL FOR DRUGS. 7774 05:44:25,200 --> 05:44:25,840 SO THEY REALLY NEED TO BE 7775 05:44:25,840 --> 05:44:26,440 INVOLVED FROM THE BEGINNING 7776 05:44:26,440 --> 05:44:26,640 OF 7777 05:44:26,640 --> 05:44:26,880 THAT. 7778 05:44:26,880 --> 05:44:28,040 --- 7779 05:44:28,040 --> 05:44:30,080 WHEN I DID IT CAME OUT THAT 7780 05:44:30,080 --> 05:44:30,680 STUCK WITH ME IS THAT WE 7781 05:44:30,680 --> 05:44:30,920 WOULD 7782 05:44:30,920 --> 05:44:31,360 EVENTUALLY NEED A 7783 05:44:31,360 --> 05:44:34,880 (INDISCERNIBLE) OF DIFFERENT 7784 05:44:34,880 --> 05:44:36,840 INDICATORS, 7785 05:44:36,840 --> 05:44:38,320 TO PURSUE ANY NEW THERAPIES 7786 05:44:38,320 --> 05:44:38,920 AND I THINK THAT IS BEEN A 7787 05:44:38,920 --> 05:44:42,920 GOOD THEME THROUGHOUT CF 7788 05:44:42,920 --> 05:44:44,520 RESEARCH AS WE HAVE DEVELOPED 7789 05:44:44,520 --> 05:44:46,680 SOME OF THESE BIOMARKERS THAT 7790 05:44:46,680 --> 05:44:49,800 OVER THE YEARS HAVE LET US 7791 05:44:49,800 --> 05:44:50,400 ESTABLISH MECHANISMS ACROSS 7792 05:44:50,400 --> 05:44:50,960 WHEN TESTING A THERAPY. 7793 05:44:50,960 --> 05:44:53,560 --- 7794 05:44:53,560 --> 05:44:55,120 BONNIE AND RHONDA, WHAT DID I 7795 05:44:55,120 --> 05:45:04,760 MISS? 7796 05:45:04,760 --> 05:45:09,080 LACKING IN RESPONSE, THING 7797 05:45:09,080 --> 05:45:10,680 THAT IS A PRETTY GOOD SUMMARY 7798 05:45:10,680 --> 05:45:11,280 OF WHAT THE GROUP DISCUSSED. 7799 05:45:11,280 --> 05:45:14,320 >> I WANT TO THROW OUT TIM, 7800 05:45:14,320 --> 05:45:14,960 THAT IF PEOPLE WANT TO LOOK 7801 05:45:14,960 --> 05:45:15,520 AT 7802 05:45:15,520 --> 05:45:21,560 THE 1ST, 2ND, 3RD, 4TH 7803 05:45:21,560 --> 05:45:26,040 QUESTIONS, WE DID IT. 7804 05:45:26,040 --> 05:45:28,840 >> THANKS FOR LETTING ME KNOW. 7805 05:45:28,840 --> 05:45:29,560 I DIDN'T REALIZE THE HEADERS 7806 05:45:29,560 --> 05:45:31,320 WERE MISSING. 7807 05:45:31,320 --> 05:45:35,160 >> SORRY I WAS MUTED. 7808 05:45:35,160 --> 05:45:37,640 TIM, I THINK YOU DID A GREAT 7809 05:45:37,640 --> 05:45:40,320 JOB OF SUMMARIZING, WHICH WAS 7810 05:45:40,320 --> 05:45:42,920 A VERY ROBUST DISCUSSION. I 7811 05:45:42,920 --> 05:45:43,200 DO 7812 05:45:43,200 --> 05:45:44,520 THINK THAT WHEN WE WERE 7813 05:45:44,520 --> 05:45:47,040 TALKING ABOUT DIFFERENT 7814 05:45:47,040 --> 05:45:50,240 OUTCOMES IN BIOMARKERS, NOT 7815 05:45:50,240 --> 05:45:54,920 ONLY DO WE WANT TO SEE YOUNG, 7816 05:45:54,920 --> 05:45:57,000 MILD PATIENTS BUT WE ALSO 7817 05:45:57,000 --> 05:45:57,200 HAVE 7818 05:45:57,200 --> 05:45:58,440 TO THINK ABOUT THE AGING 7819 05:45:58,440 --> 05:45:59,400 PATIENTS, SO BOTH EXTREMITIES 7820 05:45:59,400 --> 05:46:00,720 OF THE LIFESPAN. 7821 05:46:00,720 --> 05:46:04,840 AND ALSO, THAT WE REALLY WANT 7822 05:46:04,840 --> 05:46:07,720 TO THINK ABOUT ALL ORGANS. 7823 05:46:07,720 --> 05:46:10,920 SO I THINK SOMEBODY SAID 7824 05:46:10,920 --> 05:46:11,160 ABOVE 7825 05:46:11,160 --> 05:46:11,840 AND BELOW THE DIAPHRAGM, EVEN 7826 05:46:11,840 --> 05:46:20,320 LIKE HOW DO WE DO BETTER 7827 05:46:20,320 --> 05:46:21,000 IMAGING, EARLY PANCREATIC AND 7828 05:46:21,000 --> 05:46:22,800 LIVER DISEASE? 7829 05:46:22,800 --> 05:46:23,480 --- 7830 05:46:23,480 --> 05:46:34,000 AND FOR EXAMPLE THE CFQ IR 7831 05:46:34,440 --> 05:46:34,920 (PHONETIC), IF WE LOOK AT 7832 05:46:34,920 --> 05:46:35,520 MANY 7833 05:46:35,520 --> 05:46:37,200 TRIALS EVALUATED. 7834 05:46:37,200 --> 05:46:39,440 WHY ARE WE NOT USING OTHER 7835 05:46:39,440 --> 05:46:41,960 SCORES ARE MUCH MORE GLOBAL? 7836 05:46:41,960 --> 05:46:43,480 SO THOSE ARE A COUPLE OF KEY 7837 05:46:43,480 --> 05:46:48,480 THINGS. 7838 05:46:48,480 --> 05:46:50,520 -- -- 7839 05:46:50,520 --> 05:46:54,000 >> THANK YOU BREAKOUT ROOM 2. 7840 05:46:54,000 --> 05:46:55,760 SO WE CAN PULL OUT THE ROOM 7841 05:46:55,760 --> 05:46:59,440 SLIDE FOR ROOM 3. 7842 05:46:59,440 --> 05:47:02,640 AND I INVITE THE MODERATORS 7843 05:47:02,640 --> 05:47:02,840 TO 7844 05:47:02,840 --> 05:47:04,360 GIVE THEIR REPORT OUT. 7845 05:47:04,360 --> 05:47:09,600 >> THANKS MAURA. 7846 05:47:09,600 --> 05:47:12,280 I CAN SEE OUR BOARD IS UP. 7847 05:47:12,280 --> 05:47:12,880 THANK YOU TO EVERYBODY WHO 7848 05:47:12,880 --> 05:47:13,080 WAS 7849 05:47:13,080 --> 05:47:20,280 A BREAKOUT ROOM 3, I'M TRACY 7850 05:47:20,280 --> 05:47:20,800 -- WE HAD A VERY BROAD 7851 05:47:20,800 --> 05:47:21,440 DISCUSSION ACROSS A RANGE OF 7852 05:47:21,440 --> 05:47:22,880 TOPS AND YOU WILL SEE THAT AS 7853 05:47:22,880 --> 05:47:23,880 I START THIS REPORT OUT. 7854 05:47:23,880 --> 05:47:25,080 JUST BUILDING ON WHAT 7855 05:47:25,080 --> 05:47:25,600 BREAKOUT 7856 05:47:25,600 --> 05:47:30,920 SESSION 2 JUST TALKED ABOUT, 7857 05:47:30,920 --> 05:47:32,760 WE HAD A ROBUST DISCUSSION 7858 05:47:32,760 --> 05:47:33,680 ABOUT AGE-RELATED DISEASE AND 7859 05:47:33,680 --> 05:47:35,160 COMORBID CONDITIONS IN CF AND 7860 05:47:35,160 --> 05:47:37,080 WHAT WAS GOING TO BE UNIQUE 7861 05:47:37,080 --> 05:47:39,320 TO 7862 05:47:39,320 --> 05:47:40,840 CF AND DIFFERENT FROM THE 7863 05:47:40,840 --> 05:47:41,480 GENERAL POPULATION, AND THAT 7864 05:47:41,480 --> 05:47:42,040 MORE RESEARCH WAS NEEDED 7865 05:47:42,040 --> 05:47:42,280 HERE. 7866 05:47:42,280 --> 05:47:45,040 --- 7867 05:47:45,040 --> 05:47:45,600 WE REALLY TALKED ABOUT 7868 05:47:45,600 --> 05:47:47,080 INCORPORATING SCREENING FOR 7869 05:47:47,080 --> 05:47:49,200 DISEASES OF AGING, OR 7870 05:47:49,200 --> 05:47:51,760 COMPLICATIONS OF AGING. 7871 05:47:51,760 --> 05:47:52,320 AND REALLY THAT EXPERTISE 7872 05:47:52,320 --> 05:47:56,760 NEEDED TO TREAT SUCH ISSUES. 7873 05:47:56,760 --> 05:47:57,320 AND I THINK THAT WHAT WAS 7874 05:47:57,320 --> 05:47:58,800 BROUGHT OUT IN THE DISCUSSION 7875 05:47:58,800 --> 05:47:59,360 WAS THAT IT IS REALLY NOT 7876 05:47:59,360 --> 05:48:04,240 CLEAR TO AS WHAT IS A 7877 05:48:04,240 --> 05:48:06,560 COMPLICATION OF AGING OR A 7878 05:48:06,560 --> 05:48:07,080 COMPLICATION OF HIGHLY 7879 05:48:07,080 --> 05:48:09,960 EFFECTIVE MODULATOR THERAPY, 7880 05:48:09,960 --> 05:48:10,600 OR JUST SOMETHING THAT IS 7881 05:48:10,600 --> 05:48:13,200 ASSOCIATED WITH RENEWING CFTR 7882 05:48:13,200 --> 05:48:20,240 FUNCTION. 7883 05:48:20,240 --> 05:48:20,840 WE TALK SPECIFICALLY ABOUT 7884 05:48:20,840 --> 05:48:26,280 CARDIOVASCULAR DISEASE 7885 05:48:26,280 --> 05:48:29,400 HYPERTENSION, OBESITY AND 7886 05:48:29,400 --> 05:48:30,000 DIABETES, AND SCREENING FOR 7887 05:48:30,000 --> 05:48:33,360 CANCER WHICH INCLUDED G.I. 7888 05:48:33,360 --> 05:48:38,600 CANCER, TESTICULAR CANCER, 7889 05:48:38,600 --> 05:48:41,760 CERVICAL CANCER. 7890 05:48:41,760 --> 05:48:42,400 AND I WILL GO IN THE ORDER OF 7891 05:48:42,400 --> 05:48:43,000 THOSE DOWN THE COLUMN SO WE 7892 05:48:43,000 --> 05:48:43,600 WILL JUMP AROUND A LITTLE 7893 05:48:43,600 --> 05:48:45,120 BIT. 7894 05:48:45,120 --> 05:48:46,840 WE DID TALK ABOUT THE USE OF 7895 05:48:46,840 --> 05:48:47,440 HIGHLY EFFECTIVE MODULATOR 7896 05:48:47,440 --> 05:48:48,960 THERAPY IN UTERO AMONG 7897 05:48:48,960 --> 05:48:52,040 PREGNANT PEOPLE WITH CF. 7898 05:48:52,040 --> 05:48:55,960 OR PREGNANT PEOPLE WHO ARE CF 7899 05:48:55,960 --> 05:48:56,600 CARRIERS, PREGNANT WITH THE 7900 05:48:56,600 --> 05:48:58,800 CHILD WITH CF. 7901 05:48:58,800 --> 05:49:00,480 --- 7902 05:49:00,480 --> 05:49:02,680 THERE WAS A ROBUST DISCUSSION 7903 05:49:02,680 --> 05:49:03,360 IN THE Q&A BEFORE AND EARLIER 7904 05:49:03,360 --> 05:49:05,920 IN THE CHAT, AND THAT 7905 05:49:05,920 --> 05:49:06,680 CONTINUED A BIT DURING OUR 7906 05:49:06,680 --> 05:49:07,280 BREAKUP. 7907 05:49:07,280 --> 05:49:07,960 --- 7908 05:49:07,960 --> 05:49:10,440 THE NEXT THING THAT GARNERED 7909 05:49:10,440 --> 05:49:13,120 A 7910 05:49:13,120 --> 05:49:14,760 GOOD PORTION OF THE VOTE IN 7911 05:49:14,760 --> 05:49:18,320 THE DISCUSSION, AND WE TALKED 7912 05:49:18,320 --> 05:49:19,120 ABOUT, IS HOW DO WE PARTNER 7913 05:49:19,120 --> 05:49:20,520 WITH PRIMARY CARE PROVIDERS 7914 05:49:20,520 --> 05:49:22,720 AND PROVIDE THEM WITH 7915 05:49:22,720 --> 05:49:23,320 SUPPLEMENTAL OR ADDITIONAL 7916 05:49:23,320 --> 05:49:23,960 EDUCATION AND TRAINING ABOUT 7917 05:49:23,960 --> 05:49:28,440 WHAT MODERN CF LOOKS LIKE? 7918 05:49:28,440 --> 05:49:29,520 AND HOW DO WE SUCCESSFULLY 7919 05:49:29,520 --> 05:49:29,720 ADD 7920 05:49:29,720 --> 05:49:33,080 THEM INTO THE CF CARE MODEL 7921 05:49:33,080 --> 05:49:34,640 AND PARTNER WITH THEM? 7922 05:49:34,640 --> 05:49:36,440 --- 7923 05:49:36,440 --> 05:49:38,840 WE TALKED ABOUT WITH EMERGING 7924 05:49:38,840 --> 05:49:39,560 DISEASE MANIFESTATIONS, WHAT 7925 05:49:39,560 --> 05:49:42,760 OTHER PARTNERSHIPS WITH 7926 05:49:42,760 --> 05:49:43,400 SUBSPECIALTY PROVIDERS DO WE 7927 05:49:43,400 --> 05:49:43,960 NEED AND WHO NEEDS TO BE 7928 05:49:43,960 --> 05:49:45,520 BROUGHT TO THE TABLE IN THE 7929 05:49:45,520 --> 05:49:50,520 CHANGING DEMOGRAPHICS IN CF? 7930 05:49:50,520 --> 05:49:52,480 THIS WAS BROUGHT UP 7931 05:49:52,480 --> 05:49:53,840 SPECIFICALLY WITH THE GROWING 7932 05:49:53,840 --> 05:49:54,480 FREQUENCY OF PREGNANCIES AND 7933 05:49:54,480 --> 05:49:55,600 THE NEED TO PARTNER WITH 7934 05:49:55,600 --> 05:50:01,000 OBSTETRICIANS. 7935 05:50:01,000 --> 05:50:01,640 BUT REALLY IT RANGES ACROSS A 7936 05:50:01,640 --> 05:50:02,640 LOT OF DISEASE MANIFESTATIONS 7937 05:50:02,640 --> 05:50:03,160 AS SUMMARIZED ABOVE. 7938 05:50:03,160 --> 05:50:06,760 --- 7939 05:50:06,760 --> 05:50:07,360 WE TALKED ABOUT TRANSPLANT 7940 05:50:07,360 --> 05:50:07,560 AND 7941 05:50:07,560 --> 05:50:08,120 WE TALKED ABOUT HOW MORE 7942 05:50:08,120 --> 05:50:13,600 RESEARCH TO ECHO DR. RAIMOS 7943 05:50:13,600 --> 05:50:14,680 FROM BEFORE IS NEEDED IN THE 7944 05:50:14,680 --> 05:50:17,600 TIMING OF TRANSPLANTS AND 7945 05:50:17,600 --> 05:50:18,200 INCREASED ACCESS AS WELL AS 7946 05:50:18,200 --> 05:50:23,320 THE NEED FOR OBSERVATIONAL 7947 05:50:23,320 --> 05:50:25,560 STUDIES OF USE OF HIGHLY 7948 05:50:25,560 --> 05:50:27,960 EFFECTIVE MODULATORS, POST 7949 05:50:27,960 --> 05:50:28,600 TRANSPLANT OR IN CONJUNCTION 7950 05:50:28,600 --> 05:50:29,200 WITH TRANSPLANT MEDICATIONS. 7951 05:50:29,200 --> 05:50:34,040 --- 7952 05:50:34,040 --> 05:50:34,640 IN THE LAST TWO THINGS IN 7953 05:50:34,640 --> 05:50:34,840 THIS 7954 05:50:34,840 --> 05:50:35,440 COLUMN THAT WE TOUCHED UPON 7955 05:50:35,440 --> 05:50:36,040 WERE THE NEED FOR ROBUST 7956 05:50:36,040 --> 05:50:38,640 TRANSITION PROGRAM AND AN 7957 05:50:38,640 --> 05:50:39,480 EVIDENCE-BASED TRANSITION 7958 05:50:39,480 --> 05:50:41,040 PROGRAM RELATED TO THE MOVE 7959 05:50:41,040 --> 05:50:41,920 FROM PEDIATRIC TO ADULT 7960 05:50:41,920 --> 05:50:42,520 FACING 7961 05:50:42,520 --> 05:50:44,720 CF CARE. 7962 05:50:44,720 --> 05:50:49,520 AND THE FOCUS ON LIFESTYLE 7963 05:50:49,520 --> 05:50:50,080 BEHAVIORS TO PREVENT SOME 7964 05:50:50,080 --> 05:50:50,640 DISEASES ASSOCIATED WITH 7965 05:50:50,640 --> 05:50:50,880 AGING 7966 05:50:50,880 --> 05:50:51,640 THAT WAS SUMMARIZED ABOVE. 7967 05:50:51,640 --> 05:50:54,920 --- 7968 05:50:54,920 --> 05:50:55,760 IN THE SECOND BUCKET, 7969 05:50:55,760 --> 05:50:58,800 WE REALLY HAD A GREAT 7970 05:50:58,800 --> 05:50:59,400 DISCUSSION ON PERSONALIZED 7971 05:50:59,400 --> 05:51:03,440 MEDICINE AND THERATYPING. 7972 05:51:03,440 --> 05:51:06,840 AND REALLY THE NEED TO 7973 05:51:06,840 --> 05:51:09,000 MAXIMIZE OPPORTUNITIES FOR 7974 05:51:09,000 --> 05:51:19,520 BANKING PATIENTS BIOSPECIMENS 7975 05:51:21,080 --> 05:51:21,560 A BIG EXAMPLE WAS EXPLANTED 7976 05:51:21,560 --> 05:51:24,160 LUNGS, 7977 05:51:24,160 --> 05:51:26,760 AND ASSESSETI RESPONSE IN 7978 05:51:26,760 --> 05:51:27,440 SELF-CONTAINED MUTATIONS 7979 05:51:27,440 --> 05:51:31,720 MORE COMMONLY FOUND IN PEOPLE 7980 05:51:31,720 --> 05:51:33,440 OF COLOR AND WE DISCUSSED 7981 05:51:33,440 --> 05:51:34,080 RESEARCH ALIGNED WITH THE NEW 7982 05:51:34,080 --> 05:51:38,360 DEMANDS IN AN AREA OF HEMT: 7983 05:51:38,360 --> 05:51:39,000 ADHERENCE, MENTAL HEALTH AND 7984 05:51:39,000 --> 05:51:39,400 SUBSTANCE ABUSE. 7985 05:51:39,400 --> 05:51:43,680 --- 7986 05:51:43,680 --> 05:51:44,280 AND JUMPING BACK THIS IDEA OF 7987 05:51:44,280 --> 05:51:45,360 REALLY MORE ROBUST 7988 05:51:45,360 --> 05:51:46,760 PHARMACOGENETICS STUDIES TO 7989 05:51:46,760 --> 05:51:47,360 BETTER UNDERSTAND VARIABLE 7990 05:51:47,360 --> 05:51:48,640 RESPONSES TO HEMTS. 7991 05:51:48,640 --> 05:51:55,800 --- 7992 05:51:55,800 --> 05:51:57,480 AND IN THE LAST COLUMN WE 7993 05:51:57,480 --> 05:51:59,640 SPENT A GOOD PORTION OF OUR 7994 05:51:59,640 --> 05:52:06,440 TIME TALKING ABOUT ADDRESSING 7995 05:52:06,440 --> 05:52:07,000 RACIAL AND ETHNIC HEALTH 7996 05:52:07,000 --> 05:52:07,960 DISPARITIES INCLUDING 7997 05:52:07,960 --> 05:52:08,520 PARTICIPATION IN CLINICAL 7998 05:52:08,520 --> 05:52:09,520 TRIALS. 7999 05:52:09,520 --> 05:52:10,480 WE TALKED ABOUT ADDRESSING 8000 05:52:10,480 --> 05:52:14,520 TRUST AND PROVIDER BIAS, AS 8001 05:52:14,520 --> 05:52:18,840 BARRIERS TO PARTICIPATION IN 8002 05:52:18,840 --> 05:52:19,440 CLINICAL CARE AND CLINICAL 8003 05:52:19,440 --> 05:52:21,960 RESEARCH. 8004 05:52:21,960 --> 05:52:23,200 REALLY THE NEED TO RAISE 8005 05:52:23,200 --> 05:52:23,680 AWARENESS IN THESE 8006 05:52:23,680 --> 05:52:24,360 POPULATIONS 8007 05:52:24,360 --> 05:52:27,240 FOR SWEAT TESTING, GENE 8008 05:52:27,240 --> 05:52:29,320 TESTING AND MONITORING TO 8009 05:52:29,320 --> 05:52:30,160 IMPROVE RECRUITMENT 8010 05:52:30,160 --> 05:52:30,920 STRATEGIES 8011 05:52:30,920 --> 05:52:35,440 REALLY TRAIN OUR CF CLINICAL 8012 05:52:35,440 --> 05:52:36,000 AND RESEARCH TEAMS AND BE 8013 05:52:36,000 --> 05:52:37,840 PROACTIVE ABOUT DIVERSITY, 8014 05:52:37,840 --> 05:52:38,360 EQUITY AND INCLUSION. 8015 05:52:38,360 --> 05:52:44,040 --- 8016 05:52:44,040 --> 05:52:44,560 TO BE INTENTIONAL ABOUT 8017 05:52:44,560 --> 05:52:47,280 INCLUDING BIPOC, PREGNANT 8018 05:52:47,280 --> 05:52:50,600 PEOPLE AND THE INTERNATIONAL 8019 05:52:50,600 --> 05:52:51,240 COMMUNITY IN OUR STUDIES AND 8020 05:52:51,240 --> 05:52:52,840 TO ADDRESS THE RELUCTANCE TO 8021 05:52:52,840 --> 05:52:54,960 PARTICIPATE IN STUDIES THAT 8022 05:52:54,960 --> 05:52:55,560 MAY NOT HAVE DIRECT BENEFIT 8023 05:52:55,560 --> 05:52:57,080 FROM THE RESEARCH 8024 05:52:57,080 --> 05:52:57,440 DEVELOPMENT, 8025 05:52:57,440 --> 05:52:58,960 AND THE USE OF RECRUITMENT 8026 05:52:58,960 --> 05:52:59,960 TARGETS 8027 05:52:59,960 --> 05:53:00,960 THAT ARE REPRESENTATIVE OF 8028 05:53:00,960 --> 05:53:01,440 DISEASE PREVALENCE. 8029 05:53:01,440 --> 05:53:03,360 --- 8030 05:53:03,360 --> 05:53:06,240 WE SPECIFICALLY DOVE INTO HOW 8031 05:53:06,240 --> 05:53:06,840 THESE POPULATIONS WERE LESS 8032 05:53:06,840 --> 05:53:07,960 LIKE IT TO BE REFERRED FOR 8033 05:53:07,960 --> 05:53:10,880 TRANSPLANT. 8034 05:53:10,880 --> 05:53:12,840 SO REALLY SOME ATTENTION PAID 8035 05:53:12,840 --> 05:53:14,960 TO THE REFERRAL PROCESS, AND 8036 05:53:14,960 --> 05:53:15,600 WE TALKED ABOUT SOME ONGOING 8037 05:53:15,600 --> 05:53:20,640 INITIATIVES FROM THE CFF LUNG 8038 05:53:20,640 --> 05:53:22,760 TRANSPLANT CONSORTIUM AND 8039 05:53:22,760 --> 05:53:23,400 PROGRAMS TO IDENTIFY PATIENTS 8040 05:53:23,400 --> 05:53:24,080 WITH RARE MUTATIONS AND TO 8041 05:53:24,080 --> 05:53:26,680 MAKE SURE THAT THEY WERE 8042 05:53:26,680 --> 05:53:26,880 BEING 8043 05:53:26,880 --> 05:53:27,480 REFERRED IN A TIMELY AND 8044 05:53:27,480 --> 05:53:27,880 APPROPRIATE WAY. 8045 05:53:27,880 --> 05:53:30,520 --- 8046 05:53:30,520 --> 05:53:31,120 AND LASTLY WE TALKED ABOUT 8047 05:53:31,120 --> 05:53:31,320 THE 8048 05:53:31,320 --> 05:53:32,560 REALLY DID NOT FIT IN A 8049 05:53:32,560 --> 05:53:32,840 BUCKET 8050 05:53:32,840 --> 05:53:34,920 BUT I THINK IT IS SOMETHING 8051 05:53:34,920 --> 05:53:35,120 WE 8052 05:53:35,120 --> 05:53:35,720 ALL RECOGNIZE, IS THAT WE 8053 05:53:35,720 --> 05:53:38,640 HAVE A VERY POWERFUL TOOL IN 8054 05:53:38,640 --> 05:53:42,920 CF, WHICH IS THE CF 8055 05:53:42,920 --> 05:53:43,560 REGISTRATION WHILE BALANCING 8056 05:53:43,560 --> 05:53:46,440 THE FACT THAT DATA ENTRY CAN 8057 05:53:46,440 --> 05:53:49,400 BE BURDENSOME WE MAY BE ABLE 8058 05:53:49,400 --> 05:53:50,560 TO LEVERAGE THIS RESOURCE TO 8059 05:53:50,560 --> 05:53:52,320 TRACK ALL THE PHENOTYPES 8060 05:53:52,320 --> 05:53:52,560 USING 8061 05:53:52,560 --> 05:53:53,080 THIS TOOL AS WELL AS 8062 05:53:53,080 --> 05:53:54,240 PARTNERING WITH THE TDN. 8063 05:53:54,240 --> 05:53:55,160 --- 8064 05:53:55,160 --> 05:54:02,600 SO THAT IS BREAKOUT 3 IN 8065 05:54:02,600 --> 05:54:10,240 SUMMARY AND I WANT TO HAVE 8066 05:54:10,240 --> 05:54:10,760 COLLYN, GABRIELLE AND 8067 05:54:10,760 --> 05:54:11,320 KATHERINE TO FILL IN THE 8068 05:54:11,320 --> 05:54:11,840 BLANKS IN THINGS THAT I 8069 05:54:11,840 --> 05:54:12,960 MISSED. 8070 05:54:12,960 --> 05:54:16,480 >> THAT WAS A GREAT SUMMARY. 8071 05:54:16,480 --> 05:54:17,080 I DON'T HAVE ANYTHING OTHER 8072 05:54:17,080 --> 05:54:17,680 THAN TO REMIND THE COMMENT 8073 05:54:17,680 --> 05:54:18,760 THAT PAUL MADE. 8074 05:54:18,760 --> 05:54:19,360 THERE IS AN OPPORTUNITY TO 8075 05:54:19,360 --> 05:54:25,920 INTEGRATE THE REGISTRY WITH 8076 05:54:25,920 --> 05:54:26,520 DMRS, AND THAT SEEMS TO BE 8077 05:54:26,520 --> 05:54:27,160 UNDERUTILIZED AND THAT MAY BE 8078 05:54:27,160 --> 05:54:27,800 SOMETHING WE WANT TO LOOK AT 8079 05:54:27,800 --> 05:54:29,880 TOO. 8080 05:54:29,880 --> 05:54:31,880 >> I AGREE. 8081 05:54:31,880 --> 05:54:32,680 I THINK IT WAS A GREAT 8082 05:54:32,680 --> 05:54:34,000 SUMMARY. 8083 05:54:34,000 --> 05:54:35,920 -- -- 8084 05:54:35,920 --> 05:54:38,920 >> GREAT, THANK YOU SESSION 3 8085 05:54:38,920 --> 05:54:41,600 FOR YOUR REPORT OUT. 8086 05:54:41,600 --> 05:54:42,520 NOW WE ARE GOING TO BRING UP 8087 05:54:42,520 --> 05:54:45,600 THE BOARD FOR 8088 05:54:45,600 --> 05:54:49,200 THE SUMMARY OF THE DAY. 8089 05:54:49,200 --> 05:54:53,600 WHAT YOU WILL SEE HERE IN 8090 05:54:53,600 --> 05:54:53,800 THIS 8091 05:54:53,800 --> 05:54:54,400 SLIDE IS THAT IT WILL HAVE 8092 05:54:54,400 --> 05:54:54,600 THE 8093 05:54:54,600 --> 05:54:56,600 CATEGORIES THAT RECEIVED THE 8094 05:54:56,600 --> 05:54:57,400 MOST VOTES FROM EACH OF THE 8095 05:54:57,400 --> 05:54:58,400 THREE BREAKOUT ROOMS. 8096 05:54:58,400 --> 05:55:02,600 AND SO I WILL INVITE THE 8097 05:55:02,600 --> 05:55:07,000 WORKSHOP CO-CHAIRS TO TURN ON 8098 05:55:07,000 --> 05:55:07,680 THE CAMERAS AND HELP MODERATE 8099 05:55:07,680 --> 05:55:08,320 DISCUSSION ON SOME OF THE 8100 05:55:08,320 --> 05:55:10,080 THEMES. 8101 05:55:10,080 --> 05:55:12,720 ALSO WE ARE NOT SHOWING 8102 05:55:12,720 --> 05:55:14,600 YESTERDAY'S TOPICS BUT FOR 8103 05:55:14,600 --> 05:55:15,160 THOSE THAT WERE HERE, WE 8104 05:55:15,160 --> 05:55:18,920 SHOULD THINK ABOUT WAYS SOME 8105 05:55:18,920 --> 05:55:19,720 OF THE TOPICS HERE MAY 8106 05:55:19,720 --> 05:55:19,960 OVERLAP 8107 05:55:19,960 --> 05:55:20,960 OR HARMONIZE WITH SOME OF 8108 05:55:20,960 --> 05:55:21,560 THOSE DISCUSSED YESTERDAY AS 8109 05:55:21,560 --> 05:55:22,000 WELL. 8110 05:55:22,000 --> 05:55:23,240 --- 8111 05:55:23,240 --> 05:55:26,600 AND WE WILL INVITE ANYONE TO 8112 05:55:26,600 --> 05:55:27,280 PARTICIPATE WITH COMMENTS OR 8113 05:55:27,280 --> 05:55:28,680 QUESTIONS IN THE CHAT AND 8114 05:55:28,680 --> 05:55:28,920 THEN 8115 05:55:28,920 --> 05:55:31,920 ALSO IF ANY OF THE BREAKOUT 8116 05:55:31,920 --> 05:55:34,880 MODERATORS OR TODAY'S 8117 05:55:34,880 --> 05:55:35,200 SPEAKERS 8118 05:55:35,200 --> 05:55:37,280 WANT TO WEIGH IN, YOU ARE 8119 05:55:37,280 --> 05:55:39,720 WELCOME TO COME OFF OF MUTE 8120 05:55:39,720 --> 05:55:41,880 AND PARTICIPATE AS WELL. 8121 05:55:41,880 --> 05:55:45,200 >> MAURA, I WOULD LIKE TO 8122 05:55:45,200 --> 05:55:45,520 BOTH 8123 05:55:45,520 --> 05:55:49,120 COLLIN AND I ARE UNABLE TO 8124 05:55:49,120 --> 05:55:50,960 TURN ON OUR CAMERAS. 8125 05:55:50,960 --> 05:55:52,360 >> YEAH I DID MESSAGE OUR A/V 8126 05:55:52,360 --> 05:55:54,080 TEAM. 8127 05:55:54,080 --> 05:55:55,440 THERE WE GO, I CAN SEE YOU 8128 05:55:55,440 --> 05:55:58,880 NOW! 8129 05:55:58,880 --> 05:55:59,480 >> I WANT TO THANK EVERYONE 8130 05:55:59,480 --> 05:56:05,280 FOR PARTICIPATING, IN SINCE 8131 05:56:05,280 --> 05:56:05,480 WE 8132 05:56:05,480 --> 05:56:06,920 ARE GETTING TOWARDS THE END 8133 05:56:06,920 --> 05:56:07,120 OF 8134 05:56:07,120 --> 05:56:07,760 THE MEETING, THERE'S SO MANY 8135 05:56:07,760 --> 05:56:08,400 GREAT TOPICS BROUGHT UP IN 8136 05:56:08,400 --> 05:56:08,600 THE 8137 05:56:08,600 --> 05:56:13,080 LAST TWO DAYS IN THE SPEAKERS 8138 05:56:13,080 --> 05:56:13,720 AND THE BREAKOUT SESSIONS AND 8139 05:56:13,720 --> 05:56:14,280 SINCE WE ARE WINDING THIS 8140 05:56:14,280 --> 05:56:15,000 DOWN, 8141 05:56:15,000 --> 05:56:17,480 ONE THING WE SHOULD MAKE SURE 8142 05:56:17,480 --> 05:56:18,960 IS THAT IF THERE ARE ANY 8143 05:56:18,960 --> 05:56:20,120 TOPICS PEOPLE FEEL WE HAVE 8144 05:56:20,120 --> 05:56:20,320 NOT 8145 05:56:20,320 --> 05:56:21,720 TALKED ABOUT THAT ARE WORTH 8146 05:56:21,720 --> 05:56:23,600 HAVING A FEW MINUTES TO 8147 05:56:23,600 --> 05:56:24,240 DISCUSS, I REALLY APPRECIATE 8148 05:56:24,240 --> 05:56:26,560 IT. 8149 05:56:26,560 --> 05:56:28,120 THINK IT WAS THE LAST 8150 05:56:28,120 --> 05:56:28,400 SESSION, 8151 05:56:28,400 --> 05:56:30,400 THE LAST BREAKOUT THAT 8152 05:56:30,400 --> 05:56:32,600 MENTIONED UNDERSTANDING WHY 8153 05:56:32,600 --> 05:56:34,480 THERE ARE VARIABLE RESPONSES 8154 05:56:34,480 --> 05:56:38,240 TO HEMPT. 8155 05:56:38,240 --> 05:56:38,840 WE DID NOT TALK ABOUT THAT 8156 05:56:38,840 --> 05:56:39,040 TOO 8157 05:56:39,040 --> 05:56:40,760 MUCH TODAY. WE TALKED ABOUT 8158 05:56:40,760 --> 05:56:42,920 PEOPLE NOT BEING ELIGIBLE. 8159 05:56:42,920 --> 05:56:43,520 IT IS A REALLY INTERESTING 8160 05:56:43,520 --> 05:56:45,000 QUESTION. 8161 05:56:45,000 --> 05:56:45,640 SO MANY OF OUR PATIENTS HAVE 8162 05:56:45,640 --> 05:56:48,040 RESPONDED TO TRIPLE THERAPY, 8163 05:56:48,040 --> 05:56:51,720 BUT IF WE BACK IT UP A SEC, 8164 05:56:51,720 --> 05:56:59,560 WHEN WE HAD (INDISCERNIBLE) 8165 05:56:59,560 --> 05:57:00,160 WHICH MOST OF US AGREE DID 8166 05:57:00,160 --> 05:57:00,360 NOT 8167 05:57:00,360 --> 05:57:02,240 HAVE A PROFOUND EFFECT ON THE 8168 05:57:02,240 --> 05:57:02,760 PATIENT'S WE DID HAVE A 8169 05:57:02,760 --> 05:57:04,240 HANDFUL OF PEOPLE WHO HAD 8170 05:57:04,240 --> 05:57:09,520 THOSE THERAPIES THAT WERE 8171 05:57:09,520 --> 05:57:11,000 HIGHLY EFFECTIVE SO THERE ARE 8172 05:57:11,000 --> 05:57:16,960 DIFFERENCES IN THE WAY 8173 05:57:16,960 --> 05:57:17,600 PATIENTS' RESPONSES THAT WAS 8174 05:57:17,600 --> 05:57:18,240 ONE TOPIC WE HAVE NOT TALKED 8175 05:57:18,240 --> 05:57:18,960 ABOUT, IS THERE AN 8176 05:57:18,960 --> 05:57:19,280 OPPORTUNITY 8177 05:57:19,280 --> 05:57:20,520 TO BETTER UNDERSTAND AND 8178 05:57:20,520 --> 05:57:22,440 OPTIMIZE THESE THERAPIES? 8179 05:57:22,440 --> 05:57:23,080 I DON'T KNOW IF THERE ARE 8180 05:57:23,080 --> 05:57:24,440 OTHER TOPICS THAT PEOPLE 8181 05:57:24,440 --> 05:57:25,480 WANTED TO BRING UP THAT WERE 8182 05:57:25,480 --> 05:57:29,600 LESS DISCUSSED. 8183 05:57:29,600 --> 05:57:34,160 -- -- 8184 05:57:34,160 --> 05:57:35,080 RON MENTIONED THAT THEY 8185 05:57:35,080 --> 05:57:35,360 TALKED 8186 05:57:35,360 --> 05:57:40,400 ABOUT IT IN BREAKOUT 1 AS 8187 05:57:40,400 --> 05:57:42,920 WELL 8188 05:57:42,920 --> 05:57:49,800 AND THE DOSE SUGGESTIONS AND 8189 05:57:49,800 --> 05:57:50,720 PHARMACOGENETICS SUGGESTIONS 8190 05:57:50,720 --> 05:57:52,520 AS WELL. 8191 05:57:52,520 --> 05:57:53,120 WHAT IS THE RIGHT DOES OF 8192 05:57:53,120 --> 05:57:54,880 THIS 8193 05:57:54,880 --> 05:57:55,640 MEDICATION? 8194 05:57:55,640 --> 05:57:56,600 FOR ADULTS AT LEAST THERE IS 8195 05:57:56,600 --> 05:58:00,840 ONE GUIDELINE, AND IN OUR 8196 05:58:00,840 --> 05:58:06,960 CLINIC WE ARE THINKING TO 8197 05:58:06,960 --> 05:58:07,600 TINKER WITH THAT MAY BE, TO 8198 05:58:07,600 --> 05:58:08,200 ORANGE PILLS ONE BLUE PILL 8199 05:58:08,200 --> 05:58:08,400 MAY 8200 05:58:08,400 --> 05:58:10,840 NOT BE THE BEST FOR ALL, 8201 05:58:10,840 --> 05:58:11,880 UNDERSTANDING THAT ONE SIZE 8202 05:58:11,880 --> 05:58:12,520 DOES NOT FIT ALL, THAT COULD 8203 05:58:12,520 --> 05:58:13,000 BE SOMETHING WE CAN 8204 05:58:13,000 --> 05:58:13,720 INVESTIGATE MORE. 8205 05:58:13,720 --> 05:58:15,800 JOHN? 8206 05:58:15,800 --> 05:58:18,240 >> I WANT TO RESPOND TO YOUR 8207 05:58:18,240 --> 05:58:19,120 FIRST COMMENT ABOUT THE NEW 8208 05:58:19,120 --> 05:58:21,400 PHENOTYPES. 8209 05:58:21,400 --> 05:58:24,320 I THINK THAT AS A FIELD 8210 05:58:24,320 --> 05:58:26,640 WE NEED TO GET COORDINATED TO 8211 05:58:26,640 --> 05:58:26,880 THINK 8212 05:58:26,880 --> 05:58:27,480 10 YEARS FROM NOW WHAT IS IT 8213 05:58:27,480 --> 05:58:30,960 WE WISH WE HAD DONE NOW. 8214 05:58:30,960 --> 05:58:31,520 ONE OF THE THINGS I THINK 8215 05:58:31,520 --> 05:58:36,960 ABOUT, 8216 05:58:36,960 --> 05:58:37,640 AS PULLING GENOME INFORMATION 8217 05:58:37,640 --> 05:58:39,240 IS GOING TO BE EASIER AND 8218 05:58:39,240 --> 05:58:40,480 EASIER, 8219 05:58:40,480 --> 05:58:43,800 THE PROCESS AND UNDERSTAND 8220 05:58:43,800 --> 05:58:46,200 POLYMORPHISMS OR CHANGES IN 8221 05:58:46,200 --> 05:58:49,400 GENE FUNCTION ACROSS 8222 05:58:49,400 --> 05:58:50,560 INDIVIDUALS. SOME OF THE 8223 05:58:50,560 --> 05:58:53,640 THINGS THAT I THINK WE 8224 05:58:53,640 --> 05:58:54,200 TALKED 8225 05:58:54,200 --> 05:58:54,840 ABOUT IN THE SESSION I WAS IN 8226 05:58:54,840 --> 05:58:55,440 IS HOW TO COORDINATE THE NEW 8227 05:58:55,440 --> 05:58:57,200 PHENOTYPES TO THE TDM WHILE 8228 05:58:57,200 --> 05:58:58,800 NOT MAKING IT OVERLY 8229 05:58:58,800 --> 05:58:59,120 CUMBERSOME. 8230 05:58:59,120 --> 05:59:04,920 ARE WE BANKING DNA FROM 8231 05:59:04,920 --> 05:59:07,080 PATIENTS THAT ARE YOU GOING 8232 05:59:07,080 --> 05:59:09,080 TO 8233 05:59:09,080 --> 05:59:11,600 THE TDN OR GOING TO THE 8234 05:59:11,600 --> 05:59:11,880 CLINIC 8235 05:59:11,880 --> 05:59:14,520 TO GET CARE. 8236 05:59:14,520 --> 05:59:15,160 >> I DON'T IF YOU GUYS 8237 05:59:15,160 --> 05:59:18,960 DISCUSSED THIS, BUT IF 8238 05:59:18,960 --> 05:59:19,200 ANYBODY 8239 05:59:19,200 --> 05:59:20,920 WANTS TO DISCUSS THE LEVEL OF 8240 05:59:20,920 --> 05:59:26,040 BANKING DNA BECOMES HIGHER 8241 05:59:26,040 --> 05:59:26,640 LEVEL OF ISSUE OF CONSENT 8242 05:59:26,640 --> 05:59:26,880 WITH 8243 05:59:26,880 --> 05:59:28,160 REGULAR SPECIMENS, AND I 8244 05:59:28,160 --> 05:59:28,400 DON'T 8245 05:59:28,400 --> 05:59:29,040 KNOW IF THAT WOULD COMPLICATE 8246 05:59:29,040 --> 05:59:32,080 THINGS. 8247 05:59:32,080 --> 05:59:32,720 IF ANYBODY WANTS TO WEIGH IN 8248 05:59:32,720 --> 05:59:34,080 ON THAT. 8249 05:59:34,080 --> 05:59:37,520 -- -- 8250 05:59:37,520 --> 05:59:42,880 >> I THINK -- 8251 05:59:42,880 --> 05:59:46,120 POST-COVID COUGH THERE -- 8252 05:59:46,120 --> 05:59:49,280 I THINK THAT GROWING UP WITH 8253 05:59:49,280 --> 05:59:51,600 THAT SAME GENERAL IDEA, 8254 05:59:51,600 --> 05:59:54,040 WHETHER OR NOT WE NEED TO HAVE 8255 05:59:54,040 --> 05:59:55,440 MORE PROTOCOLS IN PLACE 8256 05:59:55,440 --> 05:59:58,240 TO DO 8257 05:59:58,240 --> 05:59:59,000 SORT OF TARGETED COLLECTION 8258 05:59:59,000 --> 06:00:02,520 FOR CERTAININFORMATIVE 8259 06:00:02,520 --> 06:00:03,200 COHORTS. 8260 06:00:03,200 --> 06:00:06,240 FOR INSTANCE, WE HAD A LOT OF 8261 06:00:06,240 --> 06:00:09,560 CASE REPORTS OF PEOPLE GOING 8262 06:00:09,560 --> 06:00:12,920 OFF OF MODULATORS. 8263 06:00:12,920 --> 06:00:14,720 CASE REPORTS, DO WE REALLY 8264 06:00:14,720 --> 06:00:19,080 NEED TO DOUBLE DOWN AND START 8265 06:00:19,080 --> 06:00:20,560 BUILDING A COHORT? 8266 06:00:20,560 --> 06:00:22,920 SHOULD WE BE DOING SOME 8267 06:00:22,920 --> 06:00:29,600 COLLECTION OF SAMPLES? 8268 06:00:29,600 --> 06:00:32,480 WE COULD BE DOING CASE 8269 06:00:32,480 --> 06:00:32,760 STUDIES 8270 06:00:32,760 --> 06:00:33,360 IN LOOKING BACK AT SOME OF 8271 06:00:33,360 --> 06:00:34,480 THE 8272 06:00:34,480 --> 06:00:35,480 MARKERS TO INFORM WHO IS 8273 06:00:35,480 --> 06:00:38,800 TOLERATING AND WHO IS NOT. 8274 06:00:38,800 --> 06:00:39,320 THAT IS A MORE GENERAL 8275 06:00:39,320 --> 06:00:44,000 QUESTION. 8276 06:00:44,000 --> 06:00:54,560 >> GARY MIGHT SPEAK GENETICS. 8277 06:00:55,480 --> 06:00:56,920 >> IT IS SOMETHING WE HAVE 8278 06:00:56,920 --> 06:00:57,560 BEEN TALKING ABOUT FOR SOME 8279 06:00:57,560 --> 06:00:58,480 TIME, WHETHER WE SHOULD BANK 8280 06:00:58,480 --> 06:00:59,880 DNA. 8281 06:00:59,880 --> 06:01:02,560 WE HAVE ADDRESSED THIS ISSUE 8282 06:01:02,560 --> 06:01:04,440 ALREADY SEVERAL TIMES WITHIN 8283 06:01:04,440 --> 06:01:05,840 THE FOUNDATION. 8284 06:01:05,840 --> 06:01:07,960 THERE ARE AGREEMENT TO BE SET 8285 06:01:07,960 --> 06:01:09,560 UP WITH DIFFERENT 8286 06:01:09,560 --> 06:01:09,920 INSTITUTIONS 8287 06:01:09,920 --> 06:01:12,000 BETWEEN UNIVERSITY OF 8288 06:01:12,000 --> 06:01:14,960 WASHINGTON, HOPKINS AND 8289 06:01:14,960 --> 06:01:17,880 UNIVERSITY OF NORTH CAROLINA, 8290 06:01:17,880 --> 06:01:20,520 5000 INDIVIDUALS HAVE GONE 8291 06:01:20,520 --> 06:01:23,520 GENOME SEQUENCING AND THERE 8292 06:01:23,520 --> 06:01:24,960 HAVE BEEN QUITE A BIT OF NEW 8293 06:01:24,960 --> 06:01:27,240 REVELATIONS WITH MODIFIED 8294 06:01:27,240 --> 06:01:29,040 GENES, INDIVIDUAL RARE 8295 06:01:29,040 --> 06:01:31,000 VARIANTS APPEARED TO BE 8296 06:01:31,000 --> 06:01:36,600 INTERESTING IN THESE DATA 8297 06:01:36,600 --> 06:01:36,800 SETS 8298 06:01:36,800 --> 06:01:38,360 HAVE MADE AVAILABLE TO 8299 06:01:38,360 --> 06:01:38,800 EVERYONE WHETHER 8300 06:01:38,800 --> 06:01:39,960 IT IS USEFUL TO COLLECT 8301 06:01:39,960 --> 06:01:42,880 ADDITIONAL DNA, FOR EXAMPLE 8302 06:01:42,880 --> 06:01:50,480 THE CHECK ON THE C STUDY 8303 06:01:50,480 --> 06:01:50,720 WILL 8304 06:01:50,720 --> 06:01:51,320 BE INTERESTING BECAUSE YOU 8305 06:01:51,320 --> 06:01:51,520 CAN 8306 06:01:51,520 --> 06:01:52,000 LOOK AT THE ISSUE OF 8307 06:01:52,000 --> 06:01:53,560 PHARMACODYNAMICS, 8308 06:01:53,560 --> 06:01:55,000 INDIVIDUALS WHO HAD A GOOD 8309 06:01:55,000 --> 06:01:56,600 RESPONSE IN SWEAT CHLORIDES 8310 06:01:56,600 --> 06:01:58,720 VERSUS POOR RESPONSE IN 8311 06:01:58,720 --> 06:01:59,240 RESPONSE TO THE TRIPLE 8312 06:01:59,240 --> 06:01:59,640 COMBINATION. 8313 06:01:59,640 --> 06:02:03,440 --- 8314 06:02:03,440 --> 06:02:04,000 GENETIC MARKERS OF DRUG 8315 06:02:04,000 --> 06:02:04,840 METABOLISM CLEARLY WELL 8316 06:02:04,840 --> 06:02:05,120 WORKED 8317 06:02:05,120 --> 06:02:05,600 OUT FOR A VARIETY OF 8318 06:02:05,600 --> 06:02:05,920 DIFFERENT 8319 06:02:05,920 --> 06:02:07,720 COMPOUNDS. 8320 06:02:07,720 --> 06:02:11,280 I WOULD THINK THAT FOR 8321 06:02:11,280 --> 06:02:13,360 (INDISCERNIBLE) AND THE OTHER 8322 06:02:13,360 --> 06:02:13,960 MODULATORS THERE ARE LIKELY 8323 06:02:13,960 --> 06:02:14,520 TO 8324 06:02:14,520 --> 06:02:16,240 BE A VARIANCE THAT HUMANS 8325 06:02:16,240 --> 06:02:16,840 CARRY THAT WOULD CHANGE THE 8326 06:02:16,840 --> 06:02:17,880 RATE OF METABOLISM AND WE 8327 06:02:17,880 --> 06:02:24,440 COULD DO THE STUDY IF WE 8328 06:02:24,440 --> 06:02:26,520 WANT, 8329 06:02:26,520 --> 06:02:27,120 WE JUST NEED HIGH-QUALITY 8330 06:02:27,120 --> 06:02:27,440 PHENOTYPING. 8331 06:02:27,440 --> 06:02:29,720 OBTAINING THE DNA SIMPLER, 8332 06:02:29,720 --> 06:02:31,360 JUST KNOWING WHEN THE PATIENT 8333 06:02:31,360 --> 06:02:34,720 WAS ON THE DRUG, OFF THE DRUG 8334 06:02:34,720 --> 06:02:35,320 OR HAD A PROBLEM WITH THE 8335 06:02:35,320 --> 06:02:35,920 DRUG. AND IT WOULD COLLECT 8336 06:02:35,920 --> 06:02:37,240 THE 8337 06:02:37,240 --> 06:02:39,200 DATA WE COULD ADDRESS A 8338 06:02:39,200 --> 06:02:44,480 VARIETY OF OTHER THINGS 8339 06:02:44,480 --> 06:02:48,600 REGARDING NOT ONLY CF ITSELF 8340 06:02:48,600 --> 06:02:49,160 BUT THE OTHER GENES THAT 8341 06:02:49,160 --> 06:02:50,520 CONTRIBUTE TO THE VARIATION 8342 06:02:50,520 --> 06:02:54,880 BUT INCOMING FROM THE POINT 8343 06:02:54,880 --> 06:02:55,400 OF VIEW AS A MEDICAL 8344 06:02:55,400 --> 06:02:57,280 GENETICIST SO ADMIT MY BIAS, 8345 06:02:57,280 --> 06:02:57,440 I 8346 06:02:57,440 --> 06:02:58,040 DO LOOK THROUGH THE LENS OF 8347 06:02:58,040 --> 06:02:59,920 THE GENOME BUT IT IS 8348 06:02:59,920 --> 06:03:01,720 SOMETHING 8349 06:03:01,720 --> 06:03:02,320 THAT WE COLLECT IS NOW WE 8350 06:03:02,320 --> 06:03:02,520 WILL 8351 06:03:02,520 --> 06:03:04,360 DO THIS FROM THE PERSPECTIVE 8352 06:03:04,360 --> 06:03:04,960 OF BEING AVAILABLE TO THE 8353 06:03:04,960 --> 06:03:05,640 STUDIES. 8354 06:03:05,640 --> 06:03:11,000 CHINA? 8355 06:03:11,000 --> 06:03:15,600 >> THANK YOU GARY. 8356 06:03:15,600 --> 06:03:16,160 ARE YOU SPEAKING ON THE 8357 06:03:16,160 --> 06:03:16,920 SPECIFIC ISSUE? 8358 06:03:16,920 --> 06:03:19,880 >> YES I AM. 8359 06:03:19,880 --> 06:03:21,040 I THINK THAT WE PROBABLY NEED 8360 06:03:21,040 --> 06:03:24,640 TO THINK BIGGER THAN DNA 8361 06:03:24,640 --> 06:03:27,440 BECAUSE YOU KNOW THERE'S BEEN 8362 06:03:27,440 --> 06:03:27,600 8363 06:03:27,600 --> 06:03:28,120 A FANTASTIC AMOUNT OF 8364 06:03:28,120 --> 06:03:28,760 INFORMATION THAT HAS COME OUT 8365 06:03:28,760 --> 06:03:31,920 OF THE DNA SEQUENCE. 8366 06:03:31,920 --> 06:03:32,600 WHAT WE REALLY NEED TO BE 8367 06:03:32,600 --> 06:03:38,560 LOOKING AT, TRANSCRIPTOMIC, 8368 06:03:38,560 --> 06:03:40,680 MAY BE EPIGENETIC CHANGES. WE 8369 06:03:40,680 --> 06:03:41,600 WON'T GET THAT INFORMATION 8370 06:03:41,600 --> 06:03:43,760 JUST BY BANKING DNA. 8371 06:03:43,760 --> 06:03:46,000 TESTING MORE BROADLY 8372 06:03:46,000 --> 06:03:46,640 ABOUT WHAT ARE THE QUESTIONS 8373 06:03:46,640 --> 06:03:49,120 WE ARE ASKING, 8374 06:03:49,120 --> 06:03:49,640 AND REALLY WHAT ARE THE 8375 06:03:49,640 --> 06:03:50,240 MOLECULAR AGENTS WE NEED TO 8376 06:03:50,240 --> 06:03:51,960 ASK. 8377 06:03:51,960 --> 06:03:53,480 >> THAT WAS SOMETHING THAT 8378 06:03:53,480 --> 06:03:55,880 CAME UP IN OUR GROUP AS WELL. 8379 06:03:55,880 --> 06:03:56,440 IT IS ONE THING TO FREE 8380 06:03:56,440 --> 06:03:57,400 SAMPLES, 8381 06:03:57,400 --> 06:04:00,320 BUT DO WE WANT TO PUT THEM IN 8382 06:04:00,320 --> 06:04:01,160 RNA LATER SO WE CAN DO 8383 06:04:01,160 --> 06:04:06,920 (INDISCERNIBLE) -- DO WE NEED 8384 06:04:06,920 --> 06:04:09,360 TO LOOK AT CELLS? 8385 06:04:09,360 --> 06:04:12,800 >> YOU CANNOT BUY BIOPS THE 8386 06:04:12,800 --> 06:04:14,800 LIVER, ONE OF THE MOST 8387 06:04:14,800 --> 06:04:15,560 IMPORTANT ONES. THAT ARE 8388 06:04:15,560 --> 06:04:18,200 PRACTICALITIES 8389 06:04:18,200 --> 06:04:19,080 TO WHAT WE ARE ABLE TO DO ON 8390 06:04:19,080 --> 06:04:19,720 THE COST BUT WE NEED TO START 8391 06:04:19,720 --> 06:04:20,560 SOMEWHERE AND I THINK HEARING 8392 06:04:20,560 --> 06:04:24,320 THE CF PATIENTS, PEOPLE WITH 8393 06:04:24,320 --> 06:04:27,480 CF TALK ABOUT WHAT THEY'RE 8394 06:04:27,480 --> 06:04:29,840 GOING THROUGH, I THINK 8395 06:04:29,840 --> 06:04:31,000 ESPECIALLY THE ONES THAT ARE 8396 06:04:31,000 --> 06:04:32,000 HAVING PROBLEMS IN THE UNIQUE 8397 06:04:32,000 --> 06:04:35,520 PHENOTYPES AND MODULATORS 8398 06:04:35,520 --> 06:04:36,680 WOULD BE MORE THAN HAPPY TO 8399 06:04:36,680 --> 06:04:40,880 FILL OUT DETAILED PHENOTYPIC 8400 06:04:40,880 --> 06:04:41,520 DATA, OR ASSIST IN GETTING IT 8401 06:04:41,520 --> 06:04:46,760 ENTERED AND ACCURATE. 8402 06:04:46,760 --> 06:04:47,400 BECAUSE I KNOW IT IS A BURDEN 8403 06:04:47,400 --> 06:04:49,760 FOR THE DOCS. 8404 06:04:49,760 --> 06:04:50,800 >> I THINK WE MIGHT MISS THE 8405 06:04:50,800 --> 06:04:54,080 KEY FEATURES. OBVIOUSLY DNA 8406 06:04:54,080 --> 06:04:54,280 IS 8407 06:04:54,280 --> 06:04:55,000 EASIEST ACCESS AND IT WILL 8408 06:04:55,000 --> 06:04:55,840 TELL US ABOUT CERTAIN THINGS 8409 06:04:55,840 --> 06:04:59,280 IN OLD TISSUES, 8410 06:04:59,280 --> 06:05:04,480 GOES BACK MANY YEARS. 8411 06:05:04,480 --> 06:05:10,520 THE CFTR GENE WOULD NOT BE 8412 06:05:10,520 --> 06:05:11,200 FOUND IF WE WERE NOT WORKING 8413 06:05:11,200 --> 06:05:11,800 ON THE GENES THAT EXPRESSED 8414 06:05:11,800 --> 06:05:12,920 IT. 8415 06:05:12,920 --> 06:05:13,560 SO IF WE ARE WANTING TO LOOK 8416 06:05:13,560 --> 06:05:15,480 FORWARD 10 YEARS, 8417 06:05:15,480 --> 06:05:18,520 WHAT WOULD WE WISH WE HAD 8418 06:05:18,520 --> 06:05:20,240 DONE? 8419 06:05:20,240 --> 06:05:20,840 I THINK THAT WILL BE A VERY 8420 06:05:20,840 --> 06:05:21,360 IMPORTANT THING. 8421 06:05:21,360 --> 06:05:26,560 >> I'D LIKE TO GIVE GOSHAN 8422 06:05:26,560 --> 06:05:26,840 (PHONETIC) 8423 06:05:26,840 --> 06:05:28,520 A CHANCE TO TALK. 8424 06:05:28,520 --> 06:05:29,080 HE HAS BEEN PATIENTLY 8425 06:05:29,080 --> 06:05:35,040 WAITING. 8426 06:05:35,040 --> 06:05:38,640 >> THANK YOU FOR THIS 8427 06:05:38,640 --> 06:05:48,360 WONDERFUL SYMPOSIUM. 8428 06:05:48,360 --> 06:05:50,000 PROBABLY WHAT IS MISSING IS 8429 06:05:50,000 --> 06:05:53,520 THE IMMUNE EFFECT. 8430 06:05:53,520 --> 06:05:54,920 APPARENTLY PATIENTS CAN BE 8431 06:05:54,920 --> 06:05:55,200 INFECTED. 8432 06:05:55,200 --> 06:05:56,760 AFTER THE INFECTION THE 8433 06:05:56,760 --> 06:05:58,360 INFORMATION TYPICALLY IS THE 8434 06:05:58,360 --> 06:06:03,480 IMMUNE DEFECT. 8435 06:06:03,480 --> 06:06:05,640 SO SINCE WE ARE TALKING ABOUT 8436 06:06:05,640 --> 06:06:07,440 A FUTURE RESEARCH. 8437 06:06:07,440 --> 06:06:08,520 THIS PROBABLY IS ONE OF THE 8438 06:06:08,520 --> 06:06:11,600 MOST IMPORTANT AREAS AND AN 8439 06:06:11,600 --> 06:06:14,040 UNDERSTUDIED AREA. 8440 06:06:14,040 --> 06:06:16,960 WITHOUT A GOOD, STRONG, 8441 06:06:16,960 --> 06:06:22,040 COMPETENT IMMUNE SYSTEM, THE 8442 06:06:22,040 --> 06:06:24,680 PATIENTS WILL HAVE HIGHLY 8443 06:06:24,680 --> 06:06:25,640 INFLAMMATORY RESPONSE AND 8444 06:06:25,640 --> 06:06:27,520 MANIFESTATION. 8445 06:06:27,520 --> 06:06:30,880 AND APPARENTLY NEUTROPHILS 8446 06:06:30,880 --> 06:06:31,080 AND 8447 06:06:31,080 --> 06:06:32,520 MONOCYTES, MACROPHAGES OF THE 8448 06:06:32,520 --> 06:06:33,800 MOST IMPORTANT DEFENSE IN THE 8449 06:06:33,800 --> 06:06:35,160 LUNG. 8450 06:06:35,160 --> 06:06:36,400 THEY ARE THE PREDOMINANT 8451 06:06:36,400 --> 06:06:37,840 NUMBERS IN THE DISEASE TO 8452 06:06:37,840 --> 06:06:39,120 LUNG. 8453 06:06:39,120 --> 06:06:43,600 I WOULD ADD THIS POINT. 8454 06:06:43,600 --> 06:06:45,480 HOPEFULLY WE WILL DRAW SOME 8455 06:06:45,480 --> 06:06:47,680 ATTENTION TO THIS AREA. 8456 06:06:47,680 --> 06:06:48,520 >> THANK YOU FOR BRINGING 8457 06:06:48,520 --> 06:06:48,760 THAT 8458 06:06:48,760 --> 06:06:51,760 UP. 8459 06:06:51,760 --> 06:06:52,360 DO YOU WANT TO SPEAK TO IF 8460 06:06:52,360 --> 06:06:52,560 YOU 8461 06:06:52,560 --> 06:06:53,920 THINK SOME OF THESE IMMUNE 8462 06:06:53,920 --> 06:06:55,160 DEFECTS WILL BE CORRECTED BY 8463 06:06:55,160 --> 06:06:55,800 MODULATORS? 8464 06:06:55,800 --> 06:06:58,960 >> THAT IS A COMPLICATED 8465 06:06:58,960 --> 06:06:59,440 ISSUE. 8466 06:06:59,440 --> 06:07:00,760 WHEN THE IMMUNE CELLS RECRUIT 8467 06:07:00,760 --> 06:07:03,960 TO THE LUNG AND THE DRUG 8468 06:07:03,960 --> 06:07:09,400 LEVELS OR ACTION MODE MAY BE 8469 06:07:09,400 --> 06:07:10,400 DIFFERENT AND THEY ARE NOT AS 8470 06:07:10,400 --> 06:07:12,560 EFFECTIVE AS IN THE BLOOD. 8471 06:07:12,560 --> 06:07:18,960 SO THEREFORE, THAT IS WHY THE 8472 06:07:18,960 --> 06:07:21,880 MODULATOR SEROTY ARE NOT 8473 06:07:21,880 --> 06:07:22,800 COMPLETELY EFFECTIVE LEAVING 8474 06:07:22,800 --> 06:07:24,920 THE IMMUNE CELLS OUT, THAT IS 8475 06:07:24,920 --> 06:07:27,680 A PROBLEM FOR THE FIELD. 8476 06:07:27,680 --> 06:07:29,160 >> SINCE WE ARE SPEAKING OF 8477 06:07:29,160 --> 06:07:30,200 IMMUNE CELLS, I DON'T KNOW IF 8478 06:07:30,200 --> 06:07:37,360 JAY COLES ONCE ARGUE THAT 8479 06:07:37,360 --> 06:07:37,600 T-17 8480 06:07:37,600 --> 06:07:38,800 CELLS OF THE MOST IMPORTANT 8481 06:07:38,800 --> 06:07:41,440 CELLS FOR THE RESPONSE. I 8482 06:07:41,440 --> 06:07:43,760 AGREE. I AM A NATIVE INDIAN 8483 06:07:43,760 --> 06:07:44,760 PERSON AND I THINK THAT 8484 06:07:44,760 --> 06:07:46,320 UNDERSTANDING HOW IMMUNE 8485 06:07:46,320 --> 06:07:46,880 CELLS 8486 06:07:46,880 --> 06:07:48,440 CONTRIBUTE TO INFLAMMATION IS 8487 06:07:48,440 --> 06:07:50,120 IMPORTANT BUT THERE ARE MANY 8488 06:07:50,120 --> 06:07:50,680 IMMUNE CELLS. THAT WAS A 8489 06:07:50,680 --> 06:07:52,400 TOPIC. 8490 06:07:52,400 --> 06:07:54,640 INFORMATION CAME UP MANY 8491 06:07:54,640 --> 06:07:55,240 TIMES, I THINK IN THE LAST 8492 06:07:55,240 --> 06:07:56,360 TWO 8493 06:07:56,360 --> 06:08:01,520 DAYS, SPECIFICALLY DISCUSSING 8494 06:08:01,520 --> 06:08:01,720 8495 06:08:01,720 --> 06:08:02,320 MEDIATORS OF INFLAMMATION AT 8496 06:08:02,320 --> 06:08:02,520 A 8497 06:08:02,520 --> 06:08:03,160 CELLULAR/MOLECULAR LEVEL WITH 8498 06:08:03,160 --> 06:08:04,360 NOT TALK ABOUT IT AS MUCH BUT 8499 06:08:04,360 --> 06:08:05,560 AN IMPORTANT AREA. 8500 06:08:05,560 --> 06:08:13,000 >> THANK YOU. 8501 06:08:13,000 --> 06:08:15,200 >> ONE OF THE HOT TOPICS HERE 8502 06:08:15,200 --> 06:08:16,520 IN TERMS OF THE LONG-TERM 8503 06:08:16,520 --> 06:08:22,440 RISKS OF AGMT, TRYING TO POST 8504 06:08:22,440 --> 06:08:25,720 OR UNDERSTAND THE QUESTION 8505 06:08:25,720 --> 06:08:25,920 OF, 8506 06:08:25,920 --> 06:08:26,520 DO WE REALLY HAVE THE RIGHT 8507 06:08:26,520 --> 06:08:27,640 TOOLS IN PLACE TO MONITOR 8508 06:08:27,640 --> 06:08:30,760 THESE RISKS? 8509 06:08:30,760 --> 06:08:33,200 THAT TO ME POINTS TO A MORE 8510 06:08:33,200 --> 06:08:35,920 OF 8511 06:08:35,920 --> 06:08:38,520 AN AP-SURVEILLANCE TYPE OF 8512 06:08:38,520 --> 06:08:40,880 DATABASE, SOMETHING WE HAVE 8513 06:08:40,880 --> 06:08:42,840 NEVER DONE BEFORE AND THERE 8514 06:08:42,840 --> 06:08:43,400 ARE CHALLENGES OF COURSE 8515 06:08:43,400 --> 06:08:46,520 SORTING OUT WHAT IS RELATED 8516 06:08:46,520 --> 06:08:52,040 TO 8517 06:08:52,040 --> 06:08:52,640 TRIKAFTA VERSUS THE DISEASE 8518 06:08:52,640 --> 06:08:59,280 ITSELF BUT IF YOU STEP BACK 8519 06:08:59,280 --> 06:08:59,920 COLLECTING THE DATA COULD BE 8520 06:08:59,920 --> 06:09:00,080 A 8521 06:09:00,080 --> 06:09:02,960 VERY IMPORTANT RESOURCE, 8522 06:09:02,960 --> 06:09:06,040 AS WE ARE DEVELOPING THE 8523 06:09:06,040 --> 06:09:06,680 GENETIC THERAPIES AND WE ARE 8524 06:09:06,680 --> 06:09:07,240 GOING TO NEED SOME REALLY 8525 06:09:07,240 --> 06:09:07,480 GOOD 8526 06:09:07,480 --> 06:09:08,600 COMPARATIVE DATA TO COMPARE 8527 06:09:08,600 --> 06:09:10,400 SOME OF THE LONG-TERM RISKS 8528 06:09:10,400 --> 06:09:10,600 OF 8529 06:09:10,600 --> 06:09:13,400 THE GENETIC THERAPIES. 8530 06:09:13,400 --> 06:09:14,720 AND WHAT TYPES OF OUTCOMES 8531 06:09:14,720 --> 06:09:16,280 SHOULD WE BE CLOSELY 8532 06:09:16,280 --> 06:09:17,120 CAPTURING, 8533 06:09:17,120 --> 06:09:21,520 AND HAVE DATA ON IN OUR 8534 06:09:21,520 --> 06:09:23,000 PATIENTS TO SET US UP FOR 8535 06:09:23,000 --> 06:09:23,240 THAT 8536 06:09:23,240 --> 06:09:26,160 AS WELL. 8537 06:09:26,160 --> 06:09:28,240 --- 8538 06:09:28,240 --> 06:09:31,680 IF I COULD PIGGYBACK ON THAT, 8539 06:09:31,680 --> 06:09:38,600 THINKING ABOUT IF WE ARE 8540 06:09:38,600 --> 06:09:41,080 MOVING TO TRIKAFTA IN THREE 8541 06:09:41,080 --> 06:09:43,520 MONTH OLD AND WHETHER OR NOT 8542 06:09:43,520 --> 06:09:44,800 WE SHOULD HAVE MORE EMPHASIS 8543 06:09:44,800 --> 06:09:45,440 ON NEUROCOGNITIVE EVALUATION 8544 06:09:45,440 --> 06:09:46,960 OR THINGS OF THAT NATURE, 8545 06:09:46,960 --> 06:09:49,760 DEVELOPMENTAL ASSESSMENTS; I 8546 06:09:49,760 --> 06:09:55,080 KNOW THAT WE HAD CFTR QUALITY 8547 06:09:55,080 --> 06:09:55,720 OF LIFE ASSESSMENTS BUT THAT 8548 06:09:55,720 --> 06:09:56,840 IS DIFFERENT THAN THINKING 8549 06:09:56,840 --> 06:09:57,480 ABOUT EITHER MENTAL HEALTH OR 8550 06:09:57,480 --> 06:10:00,280 COGNITIVE/BEHAVIORAL IMPACTS 8551 06:10:00,280 --> 06:10:02,120 THAT I THINK A LOT OF US 8552 06:10:02,120 --> 06:10:02,720 EXPRESSED CONCERN FOR IN OUR 8553 06:10:02,720 --> 06:10:06,160 BREAKOUT SESSION. 8554 06:10:06,160 --> 06:10:07,280 >> THIS IS BONNIE. 8555 06:10:07,280 --> 06:10:10,120 CAN YOU HEAR ME? 8556 06:10:10,120 --> 06:10:16,000 >> YES. 8557 06:10:16,000 --> 06:10:21,360 >> WE HAVE THE WHOLE ISSUE OF 8558 06:10:21,360 --> 06:10:23,320 SAFETY WHICH IS INTERESTING 8559 06:10:23,320 --> 06:10:23,960 BECAUSE WE WERE PLANNING 8560 06:10:23,960 --> 06:10:26,520 BEGINNING WITH YOUNGER KIDS, 8561 06:10:26,520 --> 06:10:32,600 WE ARE NOT LOOKING AT THE 8562 06:10:32,600 --> 06:10:42,960 SAFETY OF THE DRUG, 8563 06:10:45,120 --> 06:10:46,920 SPECIFICALLY NOT COLLECTING 8564 06:10:46,920 --> 06:10:49,800 ADVERSE EVENTS FROM THE DRUG 8565 06:10:49,800 --> 06:10:50,680 BECAUSE IT WOULD BE A VERY 8566 06:10:50,680 --> 06:10:51,320 DIFFERENT APPROACH WE STARTED 8567 06:10:51,320 --> 06:10:54,680 TO DO THAT AND SO WE ARE 8568 06:10:54,680 --> 06:10:55,080 GETTING HISTORY. 8569 06:10:55,080 --> 06:10:56,880 BUT IN THE PAST WE HAVEN'T 8570 06:10:56,880 --> 06:10:57,480 REALLY THOUGHT ABOUT DOING 8571 06:10:57,480 --> 06:10:59,960 THAT 8572 06:10:59,960 --> 06:11:02,680 BUT I THINK IT IS VERY 8573 06:11:02,680 --> 06:11:03,320 INTERESTING THAT YOU BRING IT 8574 06:11:03,320 --> 06:11:05,040 UP. 8575 06:11:05,040 --> 06:11:07,040 WE DID DISCUSS THE 8576 06:11:07,040 --> 06:11:07,640 NEUROCOGNITIVE A LOT, WE 8577 06:11:07,640 --> 06:11:12,040 LOOKED INTO IT AND INTO THE 8578 06:11:12,040 --> 06:11:16,280 FEASIBILITY OF IT. 8579 06:11:16,280 --> 06:11:18,320 THE PROBLEM IS YOU HAVE TO 8580 06:11:18,320 --> 06:11:18,920 HAVE TRAINED PSYCHOLOGISTS 8581 06:11:18,920 --> 06:11:21,440 DOING A LOT OF THESE TESTS. 8582 06:11:21,440 --> 06:11:22,040 IT IS INCREDIBLY IMPORTANT 8583 06:11:22,040 --> 06:11:22,240 BUT 8584 06:11:22,240 --> 06:11:25,560 IT WOULD HAVE TO BE A 8585 06:11:25,560 --> 06:11:26,000 SUBGROUP, REALLY 8586 06:11:26,000 --> 06:11:26,360 UNDERSTANDING 8587 06:11:26,360 --> 06:11:27,960 WHAT TESTS, AT WHAT TIME AND 8588 06:11:27,960 --> 06:11:30,080 WHO IS GOING TO DO IT. 8589 06:11:30,080 --> 06:11:31,320 SO I THINK IT IS PROBABLY 8590 06:11:31,320 --> 06:11:32,800 WORTH THE INVESTMENT BUT IT 8591 06:11:32,800 --> 06:11:33,000 IS 8592 06:11:33,000 --> 06:11:33,800 NOT LIKE GETTING 8593 06:11:33,800 --> 06:11:44,000 (INDISCERNIBLE). 8594 06:11:44,000 --> 06:11:48,120 >> SUE? 8595 06:11:48,120 --> 06:11:51,080 >> THANK YOU VERY MUCH. 8596 06:11:51,080 --> 06:11:53,280 I WANT TO POINT OUT SOMETHING 8597 06:11:53,280 --> 06:11:53,720 THAT I NOTED IN THE 8598 06:11:53,720 --> 06:11:54,520 CONVERSATIONS YESTERDAY AND 8599 06:11:54,520 --> 06:11:59,520 TODAY, THE IDEA THAT NEW CF. 8600 06:11:59,520 --> 06:12:03,080 THERE WAS AN ANALOGY MADE TO 8601 06:12:03,080 --> 06:12:05,240 PULMONARY DYSPLASIA, 8602 06:12:05,240 --> 06:12:07,040 TRANSITIONING FROM THE OLD TO 8603 06:12:07,040 --> 06:12:08,600 THE NEW. I THINK IT WAS A 8604 06:12:08,600 --> 06:12:09,080 GOOD 8605 06:12:09,080 --> 06:12:11,000 ANALOGY. I WANT TO SAY THAT 8606 06:12:11,000 --> 06:12:11,920 WHAT WE KNOW ABOUT CF IN THE 8607 06:12:11,920 --> 06:12:14,560 PAST HAS BEEN BASED ON 8608 06:12:14,560 --> 06:12:18,720 ANALYSIS OF LUNG EXPLANTS. 8609 06:12:18,720 --> 06:12:19,280 AND WE ARE NOT RECEIVING 8610 06:12:19,280 --> 06:12:19,520 THOSE 8611 06:12:19,520 --> 06:12:20,600 THESE DAYS, THAT IS A GOOD 8612 06:12:20,600 --> 06:12:22,080 THING. 8613 06:12:22,080 --> 06:12:23,560 BUT IF WE'RE GOING TO 8614 06:12:23,560 --> 06:12:28,880 CHARACTERIZE WHAT I ALLOW 8615 06:12:28,880 --> 06:12:32,200 MYSELF TO CALL THE NEW CF, WE 8616 06:12:32,200 --> 06:12:34,960 NEED A SOURCE OF CELLS AND 8617 06:12:34,960 --> 06:12:35,840 TISSUE. 8618 06:12:35,840 --> 06:12:39,600 AND HOW WE CAN COLLECT THE 8619 06:12:39,600 --> 06:12:42,000 SAMPLES 8620 06:12:42,000 --> 06:12:43,400 I THINK SHOULD BE SOMETHING 8621 06:12:43,400 --> 06:12:43,960 THAT SHOULD BE PUT ON THE 8622 06:12:43,960 --> 06:12:46,840 LIST 8623 06:12:46,840 --> 06:12:50,760 OF TO-DO'S. 8624 06:12:50,760 --> 06:12:51,360 AND AGAIN THERE WAS A LONG 8625 06:12:51,360 --> 06:12:55,400 DISCUSSION ABOUT THINKING 8626 06:12:55,400 --> 06:12:58,960 (CORRECTION) BANKING DNA, 8627 06:12:58,960 --> 06:13:00,800 BANKING CHROMATIN, 8628 06:13:00,800 --> 06:13:02,480 COLLECT CELLS FROM DIFFERENT 8629 06:13:02,480 --> 06:13:06,320 REGIONS OF THE AIRWAY, AND 8630 06:13:06,320 --> 06:13:10,840 ALSO OTHER TISSUES SO WE CAN 8631 06:13:10,840 --> 06:13:11,400 REALLY UNDERSTAND WHAT IS 8632 06:13:11,400 --> 06:13:16,480 GOING ON WITH CF IN THE AGE 8633 06:13:16,480 --> 06:13:17,600 OF 8634 06:13:17,600 --> 06:13:17,840 HTMT. 8635 06:13:17,840 --> 06:13:28,080 THANK YOU. 8636 06:13:28,560 --> 06:13:31,680 >> THANK YOU SUE. 8637 06:13:31,680 --> 06:13:32,280 ARE THERE OTHER TOPICS THAT 8638 06:13:32,280 --> 06:13:32,880 PEOPLE FEEL MAY HAVE BEEN 8639 06:13:32,880 --> 06:13:43,360 MISSED TODAY OR YESTERDAY? 8640 06:13:43,880 --> 06:13:49,360 THIS IDEA OF BANKING HAS BEEN 8641 06:13:49,360 --> 06:13:57,360 -- LIKE WHAT JOHN SAID, IN 10 8642 06:13:57,360 --> 06:14:02,440 YEARS WHAT WOULD WE THINK OF 8643 06:14:02,440 --> 06:14:06,360 WE SHOULD HAVE DONE? 8644 06:14:06,360 --> 06:14:07,200 REPOSITORIES OBVIOUSLY THERE 8645 06:14:07,200 --> 06:14:10,160 IS A FUNDING ISSUE. 8646 06:14:10,160 --> 06:14:10,920 THE ONE THING THIS COMMUNITY 8647 06:14:10,920 --> 06:14:11,560 IS SO GOOD AT IS WORKING AS A 8648 06:14:11,560 --> 06:14:14,480 TEAM. 8649 06:14:14,480 --> 06:14:15,120 OBVIOUSLY, THERE ARE PATIENTS 8650 06:14:15,120 --> 06:14:17,920 ALL OVER THE COUNTRY, AND IN 8651 06:14:17,920 --> 06:14:18,960 ORDER TO DO A LOT OF THE 8652 06:14:18,960 --> 06:14:20,400 CLINICAL TRIALS WE HAVE HAD 8653 06:14:20,400 --> 06:14:20,600 TO 8654 06:14:20,600 --> 06:14:21,200 WORK AS A TEAM AND IT SEEMS 8655 06:14:21,200 --> 06:14:23,200 THAT THESE NEW STUDIES 8656 06:14:23,200 --> 06:14:23,440 WHETHER 8657 06:14:23,440 --> 06:14:24,520 CLINICAL TRIALS ARE USING 8658 06:14:24,520 --> 06:14:25,440 SAMPLES TO DISCOVER NEW 8659 06:14:25,440 --> 06:14:29,000 BIOMARKERS AND NEW END POINTS 8660 06:14:29,000 --> 06:14:31,400 SOMETHING WE CAN DO WELL AS 8661 06:14:31,400 --> 06:14:31,920 TEAMS, AND THIS CAME UP 8662 06:14:31,920 --> 06:14:32,880 YESTERDAY DURING THE FINAL 8663 06:14:32,880 --> 06:14:33,480 DISCUSSION AS WELL BECAUSE 8664 06:14:33,480 --> 06:14:36,560 PART OF THE TEAM IS THE BASIC 8665 06:14:36,560 --> 06:14:38,440 SCIENTISTS, AND THIS IS WHAT 8666 06:14:38,440 --> 06:14:39,040 HAS BEEN GREAT ABOUT THIS 8667 06:14:39,040 --> 06:14:39,720 MEETING PEOPLE WHO CAN SAY OH 8668 06:14:39,720 --> 06:14:44,840 I CAN DO THIS IN MY -- MODEL 8669 06:14:44,840 --> 06:14:48,840 OR IN MY IN VITRO MODEL, 8670 06:14:48,840 --> 06:14:50,680 PEOPLE WHO CAN MODEL UNDER 8671 06:14:50,680 --> 06:14:50,880 THE 8672 06:14:50,880 --> 06:14:56,480 STATISTICS AND WITH 8673 06:14:56,480 --> 06:14:58,880 CLINICIANS. 8674 06:14:58,880 --> 06:14:59,440 AND THE IDEA THAT WE ARE 8675 06:14:59,440 --> 06:15:01,920 TALKING ABOUT, NEW GUIDELINES 8676 06:15:01,920 --> 06:15:03,320 AND PARADIGM SHIFTING ABOUT 8677 06:15:03,320 --> 06:15:03,960 HOW WE THINK ABOUT A LOT OF 8678 06:15:03,960 --> 06:15:06,560 THINGS. 8679 06:15:06,560 --> 06:15:07,160 THAT WAS A LOT OF TOPICS I 8680 06:15:07,160 --> 06:15:08,360 THROUGHOUT AT ONCE. 8681 06:15:08,360 --> 06:15:09,000 I DON'T KNOW IF ANYBODY ELSE 8682 06:15:09,000 --> 06:15:13,720 WANTS TO EXTRAPOLATE FURTHER. 8683 06:15:13,720 --> 06:15:15,440 JOHN, YOUR MICROPHONE IS 8684 06:15:15,440 --> 06:15:17,720 LIVE. 8685 06:15:17,720 --> 06:15:18,240 I THOUGHT MAYBE YOU HAD 8686 06:15:18,240 --> 06:15:19,680 SOMETHING TO SAY. 8687 06:15:19,680 --> 06:15:20,640 >> I WAS READING THE CHAT AS 8688 06:15:20,640 --> 06:15:23,240 YOU WERE TALKING TOO ABOUT 8689 06:15:23,240 --> 06:15:23,560 THE 8690 06:15:23,560 --> 06:15:30,000 BANKING OF SAMPLES AND HAVING 8691 06:15:30,000 --> 06:15:34,080 NASAL EPITHELIUM EASY TO GET. 8692 06:15:34,080 --> 06:15:37,640 AND IN MY HEAD, HAVING HEARD 8693 06:15:37,640 --> 06:15:40,400 SOME OF THE STORIES, HOW 8694 06:15:40,400 --> 06:15:42,680 CELLS 8695 06:15:42,680 --> 06:15:43,200 IN VITRO THAT MIGHT BE 8696 06:15:43,200 --> 06:15:47,000 POLARIZED FROM THE NOSE, HOW 8697 06:15:47,000 --> 06:15:50,920 THOSE AIRWAY EPITHELS WORK, 8698 06:15:50,920 --> 06:15:53,440 MODERATORS. 8699 06:15:53,440 --> 06:15:55,280 IS THAT GOING TO INFORM WHITE 8700 06:15:55,280 --> 06:15:55,920 PERSON HAS MIGRAINES OR THEIR 8701 06:15:55,920 --> 06:15:58,400 LIVER FUNCTION TESTS WERE UP? 8702 06:15:58,400 --> 06:16:00,320 WHAT I STRUGGLE WITH IS THAT 8703 06:16:00,320 --> 06:16:04,880 THE HIGHLY EFFECTIVE 8704 06:16:04,880 --> 06:16:05,520 MODULATORS ARE AFFECTING THE 8705 06:16:05,520 --> 06:16:07,440 ENTIRE BODY, 8706 06:16:07,440 --> 06:16:10,720 AND A LOT OF ORGANS AFFECT 8707 06:16:10,720 --> 06:16:10,920 CF, 8708 06:16:10,920 --> 06:16:11,520 SOME DOING BETTER AND SOME 8709 06:16:11,520 --> 06:16:14,040 WORSE. 8710 06:16:14,040 --> 06:16:14,880 HOW DO YOU COORDINATE 8711 06:16:14,880 --> 06:16:15,160 THINKING 8712 06:16:15,160 --> 06:16:15,680 ABOUT THAT MULTIORGAN 8713 06:16:15,680 --> 06:16:18,280 COMMUNICATION AND SO FORTH TO 8714 06:16:18,280 --> 06:16:19,920 UNDERSTAND WHAT IS AT THE 8715 06:16:19,920 --> 06:16:20,160 ROOT 8716 06:16:20,160 --> 06:16:20,720 OF THAT AND HOW CAN YOU 8717 06:16:20,720 --> 06:16:23,200 PREDICT IT IN A PARTICULAR 8718 06:16:23,200 --> 06:16:24,880 PATIENT? 8719 06:16:24,880 --> 06:16:27,840 NOT TOTALLY EXACTLY IN 8720 06:16:27,840 --> 06:16:30,960 RESPONSE TO WHAT YOU WERE 8721 06:16:30,960 --> 06:16:37,080 SAYING KATIE. 8722 06:16:37,080 --> 06:16:39,040 I DON'T KNOW THE ANSWER BUT 8723 06:16:39,040 --> 06:16:39,960 STARTING WITH ORGANIZING WHAT 8724 06:16:39,960 --> 06:16:42,280 THE PHENOTYPES ARE, AND AS 8725 06:16:42,280 --> 06:16:44,880 MUCH CLINICAL DATA FOR THE 8726 06:16:44,880 --> 06:16:48,280 BASIC RESEARCHERS TOO SO THEY 8727 06:16:48,280 --> 06:16:51,240 CAN THINK ABOUT THE QUESTIONS 8728 06:16:51,240 --> 06:16:52,840 AND FORMULATE HYPOTHESES THAT 8729 06:16:52,840 --> 06:16:56,560 HOPEFULLY WILL BE CLINICALLY 8730 06:16:56,560 --> 06:16:57,120 RELEVANT WHEN TESTED IN 8731 06:16:57,120 --> 06:16:57,360 ANIMAL 8732 06:16:57,360 --> 06:16:57,640 MODELS. 8733 06:16:57,640 --> 06:17:01,520 I AM STRUGGLING WITH THAT. 8734 06:17:01,520 --> 06:17:02,680 I DON'T FEEL IT CAME OUT WITH 8735 06:17:02,680 --> 06:17:03,280 THAT LIST AFTER THIS ENTIRE 8736 06:17:03,280 --> 06:17:05,080 MEETING. 8737 06:17:05,080 --> 06:17:08,600 I THINK IT IS MAINLY BECAUSE 8738 06:17:08,600 --> 06:17:09,720 PEOPLE LIKE CHRIS 8739 06:17:09,720 --> 06:17:12,520 THAT WERE TALKING ABOUT 8740 06:17:12,520 --> 06:17:15,320 YOU KNOW THE VARIOUS CASE 8741 06:17:15,320 --> 06:17:17,840 STUDIES, IT IS NOT BEING 8742 06:17:17,840 --> 06:17:18,160 ORGANIZED 8743 06:17:18,160 --> 06:17:19,000 IN SOME SORT OF WAY 8744 06:17:19,000 --> 06:17:19,320 INDEFINITELY 8745 06:17:19,320 --> 06:17:22,080 THIS IS WHERE THE CF 8746 06:17:22,080 --> 06:17:22,720 FOUNDATION SHOULD BE ABLE TO 8747 06:17:22,720 --> 06:17:24,240 HELP. 8748 06:17:24,240 --> 06:17:25,560 >> SO YOU ARE SAYING IN TERMS 8749 06:17:25,560 --> 06:17:29,080 OF ADVERSE EFFECTS OR OFF 8750 06:17:29,080 --> 06:17:30,880 TARGET POTENTIALLY WE HAVE 8751 06:17:30,880 --> 06:17:33,040 BEEN SEEING CASE REPORTS AND 8752 06:17:33,040 --> 06:17:34,160 IF WE COULD AGGREGATE THAT 8753 06:17:34,160 --> 06:17:34,400 DATA? 8754 06:17:34,400 --> 06:17:37,000 >> YEAH. 8755 06:17:37,000 --> 06:17:38,800 THAT INCLUDING PATIENTS THAT 8756 06:17:38,800 --> 06:17:40,920 ARE DOING BETTER WHEN THEY 8757 06:17:40,920 --> 06:17:42,240 COME OFF. 8758 06:17:42,240 --> 06:17:43,880 IT IS AMAZING TO KEEP LUNG 8759 06:17:43,880 --> 06:17:46,520 FUNCTION. 8760 06:17:46,520 --> 06:17:48,840 THERE ARE A LOT OF QUESTIONS 8761 06:17:48,840 --> 06:17:49,480 ABOUT HOW THIS CAN BE TACKLED 8762 06:17:49,480 --> 06:17:53,400 I THINK IN A NUMBER OF ANIMAL 8763 06:17:53,400 --> 06:17:54,080 MODELS THAT HAVE ALREADY BEEN 8764 06:17:54,080 --> 06:17:55,480 MADE. 8765 06:17:55,480 --> 06:17:56,960 I AM HAVING TROUBLE 8766 06:17:56,960 --> 06:17:59,720 FORMULATING WHAT IS MOST 8767 06:17:59,720 --> 06:18:01,120 CLINICALLY PRESSING 8768 06:18:01,120 --> 06:18:05,000 FOR THE COMMUNITY. 8769 06:18:05,000 --> 06:18:09,400 >> I WOULD SECOND THAT. 8770 06:18:09,400 --> 06:18:09,960 IF THE ANIMAL MODELS ARE 8771 06:18:09,960 --> 06:18:10,200 GOING 8772 06:18:10,200 --> 06:18:11,160 TO KEEP PACE WITH CLINICAL 8773 06:18:11,160 --> 06:18:13,440 EXPERIENCE WE HAVE TO HAVE 8774 06:18:13,440 --> 06:18:15,320 SORT OF 8775 06:18:15,320 --> 06:18:15,920 REGULAR CONVERSATIONS ABOUT 8776 06:18:15,920 --> 06:18:18,640 WHAT CLINICAL EXPERIENCE IS. 8777 06:18:18,640 --> 06:18:28,080 OTHERWISE I AM AFRAID THAT 8778 06:18:28,080 --> 06:18:28,280 THE 8779 06:18:28,280 --> 06:18:29,600 ANIMAL SPACE WILL BE ASKING 8780 06:18:29,600 --> 06:18:30,680 OLD QUESTIONS, OR NOT THE 8781 06:18:30,680 --> 06:18:30,920 MOST 8782 06:18:30,920 --> 06:18:31,920 RELEVANT QUESTIONS. 8783 06:18:31,920 --> 06:18:33,880 >> GOOD POINT. 8784 06:18:33,880 --> 06:18:39,480 COMMUNICATION AND DIALOGUE. 8785 06:18:39,480 --> 06:18:39,960 OBVIOUSLY WE HAVE OUR 8786 06:18:39,960 --> 06:18:41,360 SCIENTIFIC MEETINGS BUT 8787 06:18:41,360 --> 06:18:42,560 MAYBE, 8788 06:18:42,560 --> 06:18:43,160 A MORE CENTRAL REPOSITORY OF 8789 06:18:43,160 --> 06:18:45,080 THESE CONCERNS. 8790 06:18:45,080 --> 06:18:46,320 >> AND IS A WHITE PAPER COMES 8791 06:18:46,320 --> 06:18:48,720 OUT OF THIS RFA, LISTING 8792 06:18:48,720 --> 06:18:50,200 THOSE 8793 06:18:50,200 --> 06:18:54,080 QUESTIONS AND THE PRESSING 8794 06:18:54,080 --> 06:18:56,720 AREAS WILL BE VERY IMPORTANT. 8795 06:18:56,720 --> 06:18:59,040 JP YOU HAVE YOUR HAND UP. 8796 06:18:59,040 --> 06:19:02,760 >> THIS IS A NEW PARADIGM 8797 06:19:02,760 --> 06:19:03,320 WHERE ALL OF A SUDDEN THE 8798 06:19:03,320 --> 06:19:07,280 CLINICAL CARE HAS SHIFTED 8799 06:19:07,280 --> 06:19:08,040 INDEPENDENTLY OF THE ANIMAL 8800 06:19:08,040 --> 06:19:10,400 MODELS. 8801 06:19:10,400 --> 06:19:11,000 ALL OF A SUDDEN THE 8802 06:19:11,000 --> 06:19:14,040 INFORMATION FLOW HAS TO GO IN 8803 06:19:14,040 --> 06:19:15,080 THE OTHER DIRECTION. 8804 06:19:15,080 --> 06:19:16,160 IT SHOULD GO IN BOTH 8805 06:19:16,160 --> 06:19:19,040 DIRECTIONS. OH, WE ARE SEEING 8806 06:19:19,040 --> 06:19:21,520 THIS IN THE CLINIC. 8807 06:19:21,520 --> 06:19:23,080 HOW CAN OUR ANIMALS HELP US 8808 06:19:23,080 --> 06:19:23,600 UNDERSTAND THIS BETTER? 8809 06:19:23,600 --> 06:19:27,040 IT CREATES A NEW PARADIGM. 8810 06:19:27,040 --> 06:19:29,440 IT IS EXCITING BUT IT 8811 06:19:29,440 --> 06:19:29,720 REQUIRES 8812 06:19:29,720 --> 06:19:30,360 THINKING ABOUT ENSURING THAT 8813 06:19:30,360 --> 06:19:31,160 THOSE DIALOGUES HAPPEN IN THE 8814 06:19:31,160 --> 06:19:33,040 WAY THAT THEY NEED TO. 8815 06:19:33,040 --> 06:19:34,560 >> I DO THINK THAT ONE THING 8816 06:19:34,560 --> 06:19:38,560 -- LOOKING AT THE CHAT -- ONE 8817 06:19:38,560 --> 06:19:40,840 THING THAT WE ARE LOOKING 8818 06:19:40,840 --> 06:19:42,880 ABOUT IS WE HAVE THE 8819 06:19:42,880 --> 06:19:43,160 REGISTRY. 8820 06:19:43,160 --> 06:19:43,920 IT DOES TAKE HUMAN 8821 06:19:43,920 --> 06:19:47,960 EFFORT TO ADD IN NEW 8822 06:19:47,960 --> 06:19:49,520 CATEGORIES AND NEW DATA, 8823 06:19:49,520 --> 06:19:52,760 IT IS HEAVY LIFTING TO GET 8824 06:19:52,760 --> 06:19:53,400 EMRS TO TALK TO THE REGISTRY 8825 06:19:53,400 --> 06:19:58,160 BUT I THINK 8826 06:19:58,160 --> 06:19:58,640 MOST CENTERS HAVE AN 8827 06:19:58,640 --> 06:19:59,320 INDIVIDUAL DEDICATED TO THAT. 8828 06:19:59,320 --> 06:20:01,360 MANY OF THE 8829 06:20:01,360 --> 06:20:02,120 CENTERS HAVE AN INDIVIDUAL 8830 06:20:02,120 --> 06:20:04,600 DEDICATED TO DATA ENTRY, 8831 06:20:04,600 --> 06:20:05,240 NOT TRIVIAL TASK THAT WE HAVE 8832 06:20:05,240 --> 06:20:07,520 INFRASTRUCTURE BUILT IN. 8833 06:20:07,520 --> 06:20:09,120 DO WE WANT TO ADD MORE 8834 06:20:09,120 --> 06:20:10,840 CATEGORIES TO WHAT IS IN THE 8835 06:20:10,840 --> 06:20:11,440 REGISTRY SO WE CAN HAVE AN 8836 06:20:11,440 --> 06:20:13,080 IDEA OF ARE THERE ADVERSE 8837 06:20:13,080 --> 06:20:17,200 EFFECTS? 8838 06:20:17,200 --> 06:20:19,000 ARE THERE PEOPLE WHO HAVE HAD 8839 06:20:19,000 --> 06:20:19,960 BETTER OR WORSE RESPONSES? 8840 06:20:19,960 --> 06:20:20,600 AND THAT IS IN THE REGISTRY 8841 06:20:20,600 --> 06:20:22,160 FOR STUDY. 8842 06:20:22,160 --> 06:20:24,040 >> I WAS GOING TO SAY, THAT 8843 06:20:24,040 --> 06:20:24,240 IS 8844 06:20:24,240 --> 06:20:24,880 THE OTHER VISA WAS GOING TO 8845 06:20:24,880 --> 06:20:29,040 WEIGH IN, BUT I SHUT UP. 8846 06:20:29,040 --> 06:20:31,000 THE DECISIONS ABOUT WHAT GETS 8847 06:20:31,000 --> 06:20:31,640 ADDED TO THE REGISTRY, 8848 06:20:31,640 --> 06:20:32,280 CAREFULLY THOUGHT OUT BECAUSE 8849 06:20:32,280 --> 06:20:35,000 THERE'S ALWAYS A RISK OF 8850 06:20:35,000 --> 06:20:35,600 DIMINISHING RETURN WHEN YOU 8851 06:20:35,600 --> 06:20:39,200 HAVE TOO MUCH INFORMATION. 8852 06:20:39,200 --> 06:20:39,760 THAT BEING SAID THERE HAS 8853 06:20:39,760 --> 06:20:41,480 BEEN 8854 06:20:41,480 --> 06:20:42,000 SOME SUCCESS USING SOME 8855 06:20:42,000 --> 06:20:43,200 ENHANCED REGISTRY COLLECTION 8856 06:20:43,200 --> 06:20:43,760 AROUND SPECIAL EVENTS IN 8857 06:20:43,760 --> 06:20:45,440 POPULATION. 8858 06:20:45,440 --> 06:20:46,840 I THINK THAT IS GREAT 8859 06:20:46,840 --> 06:20:47,120 FEEDBACK 8860 06:20:47,120 --> 06:20:47,760 THAT CAN BE TAKEN BACK TO THE 8861 06:20:47,760 --> 06:20:48,160 REGISTER TEAM. 8862 06:20:48,160 --> 06:20:50,040 >> JOHN? 8863 06:20:50,040 --> 06:20:52,120 >> ONE OTHER THING WITH HIS 8864 06:20:52,120 --> 06:20:52,920 AUDIENCE. 8865 06:20:52,920 --> 06:20:55,640 IT WOULD BE GOOD TO MENTION 8866 06:20:55,640 --> 06:20:55,960 -- 8867 06:20:55,960 --> 06:20:56,560 SHIFTING GEARS A LITTLE BIT 8868 06:20:56,560 --> 06:20:56,840 -- 8869 06:20:56,840 --> 06:21:01,320 AT THE NIH CFRD WORKSHOP 8870 06:21:01,320 --> 06:21:06,680 SIMILAR TO THIS, AFTER 8871 06:21:06,680 --> 06:21:06,960 HEARING 8872 06:21:06,960 --> 06:21:08,320 THE PATIENT TALK ABOUT HER 8873 06:21:08,320 --> 06:21:11,440 EXPERIENCE, I CAME AWAY -- 8874 06:21:11,440 --> 06:21:11,960 MOST CAME AWAY WITH THE 8875 06:21:11,960 --> 06:21:20,240 MEETING -- THAT THE CLINICIAN 8876 06:21:20,240 --> 06:21:20,840 THAT WE NEED TO TRYING TO 8877 06:21:20,840 --> 06:21:21,080 TAKE 8878 06:21:21,080 --> 06:21:25,480 CARE OF CF PATIENTS, IN THAT 8879 06:21:25,480 --> 06:21:27,080 PARTICULAR AREA THERE WAS 8880 06:21:27,080 --> 06:21:27,320 POOR 8881 06:21:27,320 --> 06:21:29,320 COMMUNICATION BETWEEN 8882 06:21:29,320 --> 06:21:29,960 PULMONARY, INTERNAL MEDICINE 8883 06:21:29,960 --> 06:21:32,040 AND ENDOCRINE FOR EXAMPLE. 8884 06:21:32,040 --> 06:21:33,760 AND AS I HEAR ABOUT ALL THE 8885 06:21:33,760 --> 06:21:35,200 OTHER PHENOTYPES THAT ARE 8886 06:21:35,200 --> 06:21:39,960 EMERGING, OBESITY, MENTAL 8887 06:21:39,960 --> 06:21:42,920 ILLNESS, THAT IS SOMETHING 8888 06:21:42,920 --> 06:21:43,800 THAT WE MAY WANT TO TRY 8889 06:21:43,800 --> 06:21:44,520 TO EMPHASIZE COMING OUT OF 8890 06:21:44,520 --> 06:21:46,440 THIS MEETING. 8891 06:21:46,440 --> 06:21:49,800 THAT THE TYPE OF CLINICIAN 8892 06:21:49,800 --> 06:21:51,600 THAT NEEDS TO BE TRAINED TO 8893 06:21:51,600 --> 06:21:56,560 PROVIDE SPECIALIST CARE OF CF 8894 06:21:56,560 --> 06:21:57,080 PATIENTS NEEDS TO BE 8895 06:21:57,080 --> 06:21:57,960 RETHOUGHT. 8896 06:21:57,960 --> 06:21:59,040 I DON'T KNOW WHAT THAT MEANS 8897 06:21:59,040 --> 06:21:59,680 BECAUSE I AM NOT A CLINICIAN 8898 06:21:59,680 --> 06:22:01,240 BUT THE CF FOUNDATION HAS 8899 06:22:01,240 --> 06:22:02,240 SOME 8900 06:22:02,240 --> 06:22:03,400 REALLY GOOD PROGRAMS AND 8901 06:22:03,400 --> 06:22:04,000 FELLOWSHIPS THAT MIGHT BE 8902 06:22:04,000 --> 06:22:07,400 HELPFUL. 8903 06:22:07,400 --> 06:22:13,160 >> WE HAVE -- IS EVERYONE 8904 06:22:13,160 --> 06:22:13,400 ABLE 8905 06:22:13,400 --> 06:22:14,800 TO TURN UNDER MIC? 8906 06:22:14,800 --> 06:22:16,040 OR JUST THE SPEAKERS? 8907 06:22:16,040 --> 06:22:19,320 >> EVERYONE. 8908 06:22:19,320 --> 06:22:28,680 >> BECAUSE WE HAD SOMEONE IN 8909 06:22:28,680 --> 06:22:29,320 CHAT TO JOIN US TO TALK ABOUT 8910 06:22:29,320 --> 06:22:34,600 THE SUBJECT. 8911 06:22:34,600 --> 06:22:44,960 ELIAH? (PHONETIC) 8912 06:22:47,320 --> 06:22:48,480 >> I CAN TALK BUT I CANNOT 8913 06:22:48,480 --> 06:22:50,040 SHOW MY VIDEO. SORRY. 8914 06:22:50,040 --> 06:22:50,600 THANK YOU FOR LETTING ME 8915 06:22:50,600 --> 06:22:53,720 TALK. 8916 06:22:53,720 --> 06:22:54,680 I CAN SHOW MY VIDEO. 8917 06:22:54,680 --> 06:22:56,880 HI. 8918 06:22:56,880 --> 06:23:05,360 SO, I'M A PEDIATRIC 8919 06:23:05,360 --> 06:23:05,960 GASTROENTEROLOGIST FROM THE 8920 06:23:05,960 --> 06:23:07,000 UNIVERSITY OF IOWA AND 8921 06:23:07,000 --> 06:23:07,520 COLLABORATE WITH JOHN 8922 06:23:07,520 --> 06:23:08,560 ENGELHARDT ACTUALLY FOR SOME 8923 06:23:08,560 --> 06:23:09,680 OF THE BASIC SCIENCE STUDIES 8924 06:23:09,680 --> 06:23:11,360 IN FERRETS AND PIGS. 8925 06:23:11,360 --> 06:23:14,800 I'M THE MAIN PI OF THE 8926 06:23:14,800 --> 06:23:18,480 (INDISCERNIBLE) STUDY, GOING 8927 06:23:18,480 --> 06:23:20,840 ON FOR OVER 10 YEARS, SO WE 8928 06:23:20,840 --> 06:23:22,240 HAVE A COHORT OF CHILDREN 8929 06:23:22,240 --> 06:23:24,200 WITH 8930 06:23:24,200 --> 06:23:24,800 ACUTE AND CHRONIC 8931 06:23:24,800 --> 06:23:26,560 PANCREATITIS. 8932 06:23:26,560 --> 06:23:27,960 WE HAVE OVER 800 CHILDREN 8933 06:23:27,960 --> 06:23:28,200 THAT 8934 06:23:28,200 --> 06:23:29,000 WE HAVE BEEN FOLLOWING FOR A 8935 06:23:29,000 --> 06:23:29,880 WHILE. 8936 06:23:29,880 --> 06:23:35,240 AND ABOUT 1/3 HAVE CFTR 8937 06:23:35,240 --> 06:23:39,760 MUTATIONS; SOME HAVE CF, SO 8938 06:23:39,760 --> 06:23:42,680 THEY HAVE TO BE PANCREATIC 8939 06:23:42,680 --> 06:23:43,200 SUFFICIENT OF COURSE TO 8940 06:23:43,200 --> 06:23:44,360 CONTINUE TO HAVE PANCREATITIS. 8941 06:23:44,360 --> 06:23:44,920 IT IS A VERY IMPACTFUL 8942 06:23:44,920 --> 06:23:46,920 DISEASE. 8943 06:23:46,920 --> 06:23:57,440 SO THEY HAVE -- PANCREATITIS 8944 06:24:09,200 --> 06:24:09,680 AND OVERTIME IT WILL TURN 8945 06:24:09,680 --> 06:24:09,920 INTO 8946 06:24:09,920 --> 06:24:14,760 CHRONIC PANCREATITIS. 8947 06:24:14,760 --> 06:24:15,400 WE HAVE PEDIATRICS AND ADULTS 8948 06:24:15,400 --> 06:24:16,120 AND OF COURSE IT IS PANCREAS 8949 06:24:16,120 --> 06:24:18,440 FOCUSED LOOKING POSSIBLY FOR 8950 06:24:18,440 --> 06:24:20,600 BIOMARKERS AND PANCREAS IS AT 8951 06:24:20,600 --> 06:24:21,240 A DISADVANTAGE IN THAT WE DO 8952 06:24:21,240 --> 06:24:23,960 NOT HAVE VERY GOOD END POINTS 8953 06:24:23,960 --> 06:24:25,200 TO DECIDE WHAT IS EXACTLY THE 8954 06:24:25,200 --> 06:24:28,400 RIGHT THING TO REALLY DECIDE 8955 06:24:28,400 --> 06:24:31,920 WHAT IS THE BEST WAY TO SEE 8956 06:24:31,920 --> 06:24:35,600 HOW THE PANCREAS DAMAGE 8957 06:24:35,600 --> 06:24:35,880 OCCURS 8958 06:24:35,880 --> 06:24:40,320 AND THAT IS ONE OF THE RECENT 8959 06:24:40,320 --> 06:24:40,880 BEEN INVOLVED WITH A PIG 8960 06:24:40,880 --> 06:24:41,120 MODEL 8961 06:24:41,120 --> 06:24:48,320 AND THE FERRET MODEL. 8962 06:24:48,320 --> 06:24:49,200 IF SOMETHING COMES UP I WILL 8963 06:24:49,200 --> 06:24:50,800 BE HAPPY TO SHARE WITH THE CF 8964 06:24:50,800 --> 06:24:52,160 COMMUNITY. 8965 06:24:52,160 --> 06:24:54,920 WE ARE IMPRESSED WITH THE CF 8966 06:24:54,920 --> 06:24:57,360 FOUNDATION AND HOW THE CFTR 8967 06:24:57,360 --> 06:24:59,800 MODULATORS HAVE EVOLVED. 8968 06:24:59,800 --> 06:25:01,880 THERE ARE OF COURSE GREAT 8969 06:25:01,880 --> 06:25:02,120 CASE 8970 06:25:02,120 --> 06:25:04,440 REPORTS IN PEDIATRICS AND 8971 06:25:04,440 --> 06:25:08,760 ADULT HOW CFTR MODULATORS 8972 06:25:08,760 --> 06:25:09,000 HAVE 8973 06:25:09,000 --> 06:25:11,160 BEEN SUCCESSFUL IN DECREASING 8974 06:25:11,160 --> 06:25:15,160 THE NUMBER OF PANCREATITIS 8975 06:25:15,160 --> 06:25:17,560 ATTACKS IN PATIENTS, AND 8976 06:25:17,560 --> 06:25:17,800 BEING 8977 06:25:17,800 --> 06:25:19,320 PANCREATIC SUFFICIENT. 8978 06:25:19,320 --> 06:25:20,160 UNFORTUNATELY THAT HAS NOT 8979 06:25:20,160 --> 06:25:23,800 HELPED US INSPIRING THE 8980 06:25:23,800 --> 06:25:24,640 PHARMA 8981 06:25:24,640 --> 06:25:29,600 IN GETTING THIS FOR THE 8982 06:25:29,600 --> 06:25:32,520 PEDIATRIC PATIENTS. 8983 06:25:32,520 --> 06:25:33,160 BUT PEDIATRIC PANCREATITIS IS 8984 06:25:33,160 --> 06:25:34,840 MOSTLY A GENETIC DISEASE, 1/3 8985 06:25:34,840 --> 06:25:38,240 OF THE PATIENTS OUT OF THE 8986 06:25:38,240 --> 06:25:38,440 800 8987 06:25:38,440 --> 06:25:39,080 PATIENTS THAT WE HAVE IN THIS 8988 06:25:39,080 --> 06:25:48,000 COHORT HAVE A CFTR MUTATION. 8989 06:25:48,000 --> 06:25:50,920 SO THOSE PATIENTS ARE 8990 06:25:50,920 --> 06:25:51,440 DESPERATE FOR TREATMENT. 8991 06:25:51,440 --> 06:25:52,080 AND WE ARE HOPING THAT WE CAN 8992 06:25:52,080 --> 06:25:53,200 AT SOME POINT MAKE THAT 8993 06:25:53,200 --> 06:25:54,560 AVAILABLE TO OUR PATIENTS. 8994 06:25:54,560 --> 06:25:55,120 THANK YOU FOR LETTING ME 8995 06:25:55,120 --> 06:25:57,160 TALK. 8996 06:25:57,160 --> 06:25:57,760 >> THANK YOU FOR THAT 8997 06:25:57,760 --> 06:26:08,040 PERSPECTIVE. 8998 06:26:11,680 --> 06:26:12,120 >> WE HAVE ABOUT THREE 8999 06:26:12,120 --> 06:26:12,400 MINUTES 9000 06:26:12,400 --> 06:26:14,840 BEFORE THE MEETING IS 9001 06:26:14,840 --> 06:26:15,120 SUPPOSED 9002 06:26:15,120 --> 06:26:17,480 TO CLOSE. I INVITE TO 9003 06:26:17,480 --> 06:26:18,720 PARTICIPATE IN THE AUDIENCE 9004 06:26:18,720 --> 06:26:18,920 IF 9005 06:26:18,920 --> 06:26:19,480 YOU HAVE ANY COMMENTS YOU 9006 06:26:19,480 --> 06:26:19,720 WANT 9007 06:26:19,720 --> 06:26:20,320 TO RAISE PUT THEM IN THE 9008 06:26:20,320 --> 06:26:21,400 CHAT. 9009 06:26:21,400 --> 06:26:22,040 OBVIOUSLY WE WILL NOT GET TO 9010 06:26:22,040 --> 06:26:22,920 THEM THE LAST THREE MINUTES 9011 06:26:22,920 --> 06:26:27,920 BUT WE ARE COLLECTING THE 9012 06:26:27,920 --> 06:26:28,160 CHAT 9013 06:26:28,160 --> 06:26:28,760 TOGETHER WITH THE INFORMATION 9014 06:26:28,760 --> 06:26:30,280 WE HAVE BEEN TAKING 9015 06:26:30,280 --> 06:26:30,600 THROUGHOUT 9016 06:26:30,600 --> 06:26:31,160 THE MEETING AND WE WILL 9017 06:26:31,160 --> 06:26:32,600 RECONVENE THIS WORKSHOP 9018 06:26:32,600 --> 06:26:43,080 PLANNING TEAM TO DISCUSS IT. 9019 06:26:43,080 --> 06:26:44,640 AND ALSO WE MAY END UP 9020 06:26:44,640 --> 06:26:44,880 CALLING 9021 06:26:44,880 --> 06:26:45,480 ON SOME OF YOU ALL OLD AS 9022 06:26:45,480 --> 06:26:46,080 SUBJECT MATTER EXPERTS, WE 9023 06:26:46,080 --> 06:26:46,920 MAY 9024 06:26:46,920 --> 06:26:50,560 NEED ADDITIONAL INFORMATION 9025 06:26:50,560 --> 06:26:51,320 FROM A COMMUNITY PERSPECTIVE 9026 06:26:51,320 --> 06:26:54,080 ABOUT WHAT WE NEED TO DO AND 9027 06:26:54,080 --> 06:26:54,600 THE OPPORTUNITY TO MOVE 9028 06:26:54,600 --> 06:26:55,160 RESEARCH FORWARD IN THE 9029 06:26:55,160 --> 06:26:57,040 FIELD. 9030 06:26:57,040 --> 06:26:59,760 I WILL LEAVE THE CHAT OPEN 9031 06:26:59,760 --> 06:27:01,960 HERE FOR THE NEXT COUPLE OF 9032 06:27:01,960 --> 06:27:02,560 MINUTES AND THEN DEFER BACK 9033 06:27:02,560 --> 06:27:02,760 TO 9034 06:27:02,760 --> 06:27:03,400 OUR WORKSHOP COCHAIRS TO SEE 9035 06:27:03,400 --> 06:27:04,960 IF THEY HAVE ANY CLOSING 9036 06:27:04,960 --> 06:27:05,600 REMARKS, THEY WOULD LIKE TO 9037 06:27:05,600 --> 06:27:06,320 ADD. 9038 06:27:06,320 --> 06:27:08,800 >> I WILL JUMP IN. 9039 06:27:08,800 --> 06:27:15,640 FIRST OF ALL WE NEED TO 9040 06:27:15,640 --> 06:27:15,840 THINK 9041 06:27:15,840 --> 06:27:16,440 EVERYBODY FOR THIS 2-DAY 9042 06:27:16,440 --> 06:27:17,600 INCREDIBLE MARATHON. 9043 06:27:17,600 --> 06:27:19,520 WE HAVE A LOT OF WORK TO DO. 9044 06:27:19,520 --> 06:27:20,920 WE NEED EVERYBODY. 9045 06:27:20,920 --> 06:27:24,360 WE NEED A NEW PIPELINE. 9046 06:27:24,360 --> 06:27:24,960 WE NEED YOU RESEARCHERS TO 9047 06:27:24,960 --> 06:27:26,000 COME INTO THE PIPELINE SO AS 9048 06:27:26,000 --> 06:27:26,600 MUCH AS YOU CAN INSPIRE AND 9049 06:27:26,600 --> 06:27:31,000 EXPAND THAT WILL BE ONE OF 9050 06:27:31,000 --> 06:27:31,720 OUR 9051 06:27:31,720 --> 06:27:32,360 CHALLENGES MOVING INTO THE 9052 06:27:32,360 --> 06:27:33,560 FUTURE. 9053 06:27:33,560 --> 06:27:38,960 I REALLY WANT TO THANK THE 9054 06:27:38,960 --> 06:27:45,480 NIH, AND YOU IN PARTICULAR 9055 06:27:45,480 --> 06:27:46,920 MARRAH FOR ENVISIONING THIS 9056 06:27:46,920 --> 06:27:47,560 CONFERENCE AND THANK YOU FOR 9057 06:27:47,560 --> 06:27:48,160 BRINGING US TOGETHER AND WE 9058 06:27:48,160 --> 06:27:48,720 LOOK FORWARD TO THE NEXT 9059 06:27:48,720 --> 06:27:49,200 STEPS. 9060 06:27:49,200 --> 06:27:50,720 THIS IS A CONTINUATION OF 9061 06:27:50,720 --> 06:27:51,240 JUST 9062 06:27:51,240 --> 06:27:56,200 A WHOLE NEW WORLD AS WE MOVE 9063 06:27:56,200 --> 06:27:58,080 FORWARD WITH OUR RESEARCH. 9064 06:27:58,080 --> 06:27:59,040 I AM INSPIRED AND I HOPE 9065 06:27:59,040 --> 06:28:02,920 EVERYBODY ELSE IS TO CONTINUE 9066 06:28:02,920 --> 06:28:06,560 THIS IMPORTANT WORK. 9067 06:28:06,560 --> 06:28:07,200 >> YEAH AND I WILL PIGGYBACK 9068 06:28:07,200 --> 06:28:09,080 ON THAT. 9069 06:28:09,080 --> 06:28:10,760 AS I MENTIONED TO YOU ALL IN 9070 06:28:10,760 --> 06:28:12,320 OUR EARLY CONVERSATIONS, THIS 9071 06:28:12,320 --> 06:28:14,880 WAS A BIG TASK. 9072 06:28:14,880 --> 06:28:15,440 THERE ARE A LOT OF TOPICS 9073 06:28:15,440 --> 06:28:15,680 THAT 9074 06:28:15,680 --> 06:28:20,440 WERE COVERED. 9075 06:28:20,440 --> 06:28:21,040 THERE ARE SOME THINGS THAT 9076 06:28:21,040 --> 06:28:21,640 MAYBE WE DID NOT SUFFICIENTLY 9077 06:28:21,640 --> 06:28:22,240 COVER, BUT THAT IS WHAT WE 9078 06:28:22,240 --> 06:28:23,280 HAVE ALL OF THESE RESOURCE 9079 06:28:23,280 --> 06:28:25,880 MATERIALS THAT WE WILL LOOK 9080 06:28:25,880 --> 06:28:26,080 AT 9081 06:28:26,080 --> 06:28:26,600 AND I THINK THERE IS 9082 06:28:26,600 --> 06:28:26,880 POTENTIAL 9083 06:28:26,880 --> 06:28:27,480 FOR ADDITIONAL PROGRAMMING 9084 06:28:27,480 --> 06:28:27,680 THE 9085 06:28:27,680 --> 06:28:28,080 FUTURE. 9086 06:28:28,080 --> 06:28:28,600 THAT CAN BE A LOT OF 9087 06:28:28,600 --> 06:28:28,880 DIFFERENT 9088 06:28:28,880 --> 06:28:31,680 THINGS. 9089 06:28:31,680 --> 06:28:32,280 IT CAN BE STATEMENT PAPERS 9090 06:28:32,280 --> 06:28:34,640 FROM YOU IN THE COMMUNITY, 9091 06:28:34,640 --> 06:28:35,280 FUNDING OPPORTUNITIES THAT 9092 06:28:35,280 --> 06:28:35,480 OUR 9093 06:28:35,480 --> 06:28:36,040 ORGANIZATIONS THINK ABOUT 9094 06:28:36,040 --> 06:28:36,280 HERE 9095 06:28:36,280 --> 06:28:39,720 AT THE NIH OR THE CYSTIC 9096 06:28:39,720 --> 06:28:44,160 FIBROSIS FOUNDATION, 9097 06:28:44,160 --> 06:28:44,760 IT COULD ALSO BE ADDITIONAL 9098 06:28:44,760 --> 06:28:45,400 WORKSHOPS OR EVEN FORMING NEW 9099 06:28:45,400 --> 06:28:45,920 PARTNERSHIPS AND 9100 06:28:45,920 --> 06:28:46,280 RELATIONSHIPS 9101 06:28:46,280 --> 06:28:47,160 THAT WE NEED TO HAVE IN ORDER 9102 06:28:47,160 --> 06:28:47,880 TO ADDRESS SOME OF THESE 9103 06:28:47,880 --> 06:28:50,080 GAPS. 9104 06:28:50,080 --> 06:28:51,000 WE ARE GOING TO BE THINKING 9105 06:28:51,000 --> 06:28:54,000 ABOUT THESE CREATIVELY AND AS 9106 06:28:54,000 --> 06:28:56,640 I MENTIONED BOTH DAYS, MY 9107 06:28:56,640 --> 06:29:03,320 EMAIL BOXES OPEN TO ANYBODY. 9108 06:29:03,320 --> 06:29:06,520 IF YOU WANT TO EMAIL ME AND 9109 06:29:06,520 --> 06:29:06,920 YOU HAVE IDEAS 9110 06:29:06,920 --> 06:29:07,320 OUT-OF-THE-BOX, 9111 06:29:07,320 --> 06:29:07,960 IN THE BOX I AM HAPPY TO HEAR 9112 06:29:07,960 --> 06:29:08,160 IT. 9113 06:29:08,160 --> 06:29:08,840 >> I WANT TO THANK ALL OF THE 9114 06:29:08,840 --> 06:29:09,440 SPEAKERS AND ATTENDEES FOR 9115 06:29:09,440 --> 06:29:10,000 THIS REALLY INTERACTIONAL 9116 06:29:10,000 --> 06:29:11,280 MEETING. 9117 06:29:11,280 --> 06:29:13,160 ALL OF THE CONTRIBUTIONS OF 9118 06:29:13,160 --> 06:29:14,800 THE CHAT AND THE QUESTIONS 9119 06:29:14,800 --> 06:29:15,000 AND 9120 06:29:15,000 --> 06:29:15,920 THE BREAKOUTS REALLY MADE 9121 06:29:15,920 --> 06:29:16,160 THIS 9122 06:29:16,160 --> 06:29:17,600 A REALLY INFORMATIVE MEETING. 9123 06:29:17,600 --> 06:29:19,600 THANK YOU TO EVERYBODY. 9124 06:29:19,600 --> 06:29:22,000 >> I ECHO ALL THE COMMENTS. 9125 06:29:22,000 --> 06:29:23,360 IT HAS BEEN GREAT. 9126 06:29:23,360 --> 06:29:27,640 THANKS TO EVERYBODY. 9127 06:29:27,640 --> 06:29:33,280 >> ALL RIGHT. THANK YOU. 9128 06:29:33,280 --> 06:29:34,920 ONE LAST THING BEFORE 9129 06:29:34,920 --> 06:29:35,240 EVERYONE 9130 06:29:35,240 --> 06:29:35,880 LEAVES. OUR WORKSHOP SUPPORT 9131 06:29:35,880 --> 06:29:37,640 TEAM 9132 06:29:37,640 --> 06:29:40,200 IS DROPPING IN A SURVEY FOR 9133 06:29:40,200 --> 06:29:40,800 THIS WORKSHOP AND WE WOULD 9134 06:29:40,800 --> 06:29:43,000 LIKE YOUR FEEDBACK AND YOU 9135 06:29:43,000 --> 06:29:44,520 WILL ALSO RECEIVE THIS VIA 9136 06:29:44,520 --> 06:29:45,800 EMAIL AND IF YOU WOULD ANSWER 9137 06:29:45,800 --> 06:29:47,640 THE SURVEY IT WOULD HELP US A 9138 06:29:47,640 --> 06:29:50,560 LOT AND HELP US STRUCTURE 9139 06:29:50,560 --> 06:29:51,200 FUTURE WORKSHOPS HERE AT THE 9140 06:29:51,200 --> 06:29:54,280 NHLBI. 9141 06:29:54,280 --> 06:29:55,640 AND ONE MORE THING I WANT TO 9142 06:29:55,640 --> 06:29:58,560 GIVE TO THE CYSTIC FIBROSIS 9143 06:29:58,560 --> 06:30:06,120 FOUNDATION, THE NIAID AND 9144 06:30:06,120 --> 06:30:06,680 NIDDK ARE IN THE PLANNING 9145 06:30:06,680 --> 06:30:06,920 TEAM 9146 06:30:06,920 --> 06:30:07,520 AND WOULD NOT BE ABLE TO DO 9147 06:30:07,520 --> 06:30:07,960 THIS WITHOUT YOUR 9148 06:30:07,960 --> 06:30:08,600 PARTICIPATION SUPPORT. THANK 9149 06:30:08,600 --> 06:30:10,440 YOU, 9150 06:30:10,440 --> 06:30:11,040 AND I REALLY APPRECIATE THE 9151 06:30:11,040 --> 06:30:12,920 PARTNERSHIP THAT WE HAVE AND 9152 06:30:12,920 --> 06:30:14,120 WITH THAT I WILL LET EVERYONE 9153 06:30:14,120 --> 06:30:14,760 GO AND WISH EVERYONE A HAPPY 9154 06:30:14,760 --> 06:30:15,080 WEEKEND. 9155 06:30:15,080 --> 00:00:00,000 THANK YOU.