1 00:00:05,960 --> 00:00:08,800 >> I'M DR. QUING LU WITH THE 2 00:00:08,800 --> 00:00:11,400 NATIONAL HEART, LUNG AND BLOOD 3 00:00:11,400 --> 00:00:13,400 INSTITUTE. 4 00:00:13,400 --> 00:00:15,920 I'M HAPPY TO REPORT WE HAVE 274 5 00:00:15,920 --> 00:00:18,400 PEOPLE HAVE SIGNED UP FOR THIS 6 00:00:18,400 --> 00:00:21,240 WORKSHOP. 7 00:00:21,240 --> 00:00:24,840 AND I KNOW EVERYBODY HAS BUSY 8 00:00:24,840 --> 00:00:26,760 SCHEDULE AND TOTAL WE HAVE 274 9 00:00:26,760 --> 00:00:27,200 SIGNED UP. 10 00:00:27,200 --> 00:00:29,240 I'M SO HAPPY TO SEE YOU ALL HERE 11 00:00:29,240 --> 00:00:31,480 VIRTUALLY. 12 00:00:31,480 --> 00:00:35,720 AS YOU MAY KNOW, OUR DIVISION 13 00:00:35,720 --> 00:00:36,960 DIRECTOR DR. JAMES KEIGHLEY 14 00:00:36,960 --> 00:00:39,120 WOULD LIKE TO BE HERE TO WELCOME 15 00:00:39,120 --> 00:00:42,040 YOU HOWEVER, HE IS HAVING 16 00:00:42,040 --> 00:00:43,320 ANOTHER MEETING RIGHT NOW AND HE 17 00:00:43,320 --> 00:00:45,320 CANNOT ESCAPE. 18 00:00:45,320 --> 00:00:50,800 HE WILL JOIN AT A LATER TIME. 19 00:00:50,800 --> 00:00:52,960 I ALSO HEARD THE NHLBI DIRECTOR, 20 00:00:52,960 --> 00:00:55,040 DR. GIBBONS MAY DROP IN DURING 21 00:00:55,040 --> 00:00:56,600 THE WORKSHOP WHICH IS VERY 22 00:00:56,600 --> 00:00:56,880 EXCITING. 23 00:00:56,880 --> 00:01:02,720 I WOULD LIKE TO INTRODUCE OUR 24 00:01:02,720 --> 00:01:12,760 DEPUTY DIRECTOR, DR 25 00:01:12,760 --> 00:01:15,640 DRDR 26 00:01:15,640 --> 00:01:17,240 DR. MATUTE-BELLO HE WAS 27 00:01:17,240 --> 00:01:20,680 PROFESSOR OF MEDICINE AT THE 28 00:01:20,680 --> 00:01:23,640 UNIVERSITY OF WASHINGTON AND 29 00:01:23,640 --> 00:01:24,400 PHYSICIAN AT THE V.A. HEALTH 30 00:01:24,400 --> 00:01:26,840 CARE SYSTEMS. 31 00:01:26,840 --> 00:01:28,680 HE RECEIVED HIS M.D. DEGREE FROM 32 00:01:28,680 --> 00:01:30,480 THE CENTRAL UNIVERSITY OF 33 00:01:30,480 --> 00:01:32,880 VENEZUELA AND COMPLETED HIS 34 00:01:32,880 --> 00:01:35,680 INTERNAL MEDICINE INTERNSHIP AND 35 00:01:35,680 --> 00:01:39,400 RESIDENCY AT THE ALBERT EINSTEIN 36 00:01:39,400 --> 00:01:41,600 MEDICAL CENTER IN PHILADELPHIA 37 00:01:41,600 --> 00:01:47,560 AND PULMONARY FELLOWSHIP IN 38 00:01:47,560 --> 00:01:48,560 SEATTLE. 39 00:01:48,560 --> 00:01:56,080 HE HAS BOOKS AND IS THE PRIMARY 40 00:01:56,080 --> 00:02:06,640 INTEREST IN LUNG TRANSPLANT AND 41 00:02:10,000 --> 00:02:11,160 YOU MAY OPEN THE WORKSHOP. 42 00:02:11,160 --> 00:02:14,520 >> I'M PLEASED TO SEE MORE THAN 43 00:02:14,520 --> 00:02:16,160 270 PARTICIPANTS HAVE SIGNED ON 44 00:02:16,160 --> 00:02:17,160 TO THE WORKSHOP. 45 00:02:17,160 --> 00:02:18,520 THEY COME FROM ACROSS THE UNITED 46 00:02:18,520 --> 00:02:21,400 STATES, EUROPE, CANADA, 47 00:02:21,400 --> 00:02:21,680 AUSTRALIA. 48 00:02:21,680 --> 00:02:27,560 AND I THINK THIS LEVEL OF 49 00:02:27,560 --> 00:02:30,320 INTEREST IN ENTHUSIASM HIGHLIGHT 50 00:02:30,320 --> 00:02:32,200 THE INTEREST IN THE TOPIC. 51 00:02:32,200 --> 00:02:33,360 WELCOME TO NHLBI. 52 00:02:33,360 --> 00:02:35,760 THE NHLBI MISSION IS TO PROVIDE 53 00:02:35,760 --> 00:02:38,400 GLOBAL LEADERSHIP FOR RESEARCH, 54 00:02:38,400 --> 00:02:39,080 TRAINING AND EDUCATION PROGRAMS 55 00:02:39,080 --> 00:02:41,920 THAT PROMOTE THE PREVENTION AND 56 00:02:41,920 --> 00:02:43,320 TREATMENT OF HEART, LUNG AND 57 00:02:43,320 --> 00:02:44,760 BLOOD DISEASES AND ENHANCE THE 58 00:02:44,760 --> 00:02:46,720 HEALTH OF ALL INDIVIDUALS. 59 00:02:46,720 --> 00:02:51,560 SO THEY CAN LIVE LONGER AND MORE 60 00:02:51,560 --> 00:02:52,320 FULFILLING LIVES. 61 00:02:52,320 --> 00:02:54,520 OUR GOALS ARE TO UNDERSTAND 62 00:02:54,520 --> 00:02:57,480 HUMAN BIOLOGY, REDUCE HUMAN 63 00:02:57,480 --> 00:02:59,200 DISEASE, DEVELOP WORKFORCE 64 00:02:59,200 --> 00:02:59,720 RESOURCES AND ADVANCE 65 00:02:59,720 --> 00:03:03,400 TRANSLATIONAL RESEARCH. 66 00:03:03,400 --> 00:03:06,120 AT THE DIVISION OF LUNG DISEASES 67 00:03:06,120 --> 00:03:07,520 WE ARE RESPONSIBLE FOR 68 00:03:07,520 --> 00:03:10,200 MONITORING THE LATEST RESEARCH 69 00:03:10,200 --> 00:03:11,000 DEVELOPMENTS IN THE SCIENTIFIC 70 00:03:11,000 --> 00:03:12,920 COMMUNITY AS WELL AS IDENTIFYING 71 00:03:12,920 --> 00:03:15,320 RESEARCH GAPS AND NEEDS 72 00:03:15,320 --> 00:03:16,760 OBTAINING ADVICE FROM EXPERTS IN 73 00:03:16,760 --> 00:03:19,520 THE FIELD AND IMPLEMENTING 74 00:03:19,520 --> 00:03:20,000 PROGRAMS TO ADDRESS NEW 75 00:03:20,000 --> 00:03:22,480 OPPORTUNITIES. 76 00:03:22,480 --> 00:03:24,600 THIS WORKSHOP BRIDGING THE GAP 77 00:03:24,600 --> 00:03:26,560 BETWEEN CLINICAL AND BASIC 78 00:03:26,560 --> 00:03:28,680 RESEARCH TO UNDERSTAND COPD 79 00:03:28,680 --> 00:03:31,320 MECHANISMS IS HIGHLY RELEVANT TO 80 00:03:31,320 --> 00:03:32,000 THESE GOALS. 81 00:03:32,000 --> 00:03:34,720 I DON'T HAVE TO TELL THIS 82 00:03:34,720 --> 00:03:39,040 AUDIENCE THAT COPD IS THE THIRD 83 00:03:39,040 --> 00:03:40,320 LEADING CAUSE OF DEATH IN THE 84 00:03:40,320 --> 00:03:42,360 UNITED STATES ALONE AND COSTS UP 85 00:03:42,360 --> 00:03:45,280 TO $55 BILLION PER YEAR. 86 00:03:45,280 --> 00:03:50,400 SMOKING CESSATION AND OTHER 87 00:03:50,400 --> 00:03:52,120 CURRENT THERAPIES CAN REDUCE 88 00:03:52,120 --> 00:03:54,320 SYMPTOMS BUT DO NO REVERSE 89 00:03:54,320 --> 00:03:55,160 DISEASE PROGRESSION. 90 00:03:55,160 --> 00:03:59,440 THE MAJOR REASON IS WE LACK 91 00:03:59,440 --> 00:04:00,120 FUNDAMENTAL UNDERSTANDING OF 92 00:04:00,120 --> 00:04:02,040 COPD MECHANISMS. 93 00:04:02,040 --> 00:04:05,400 NOW, AS YOU KNOW, MAJOR 94 00:04:05,400 --> 00:04:06,880 LONGITUDINAL OBSERVATIONAL 95 00:04:06,880 --> 00:04:09,360 COHORT STUDIES OF COPD PATIENTS 96 00:04:09,360 --> 00:04:11,560 HAVE COLLECTED ENORMOUS CLINICAL 97 00:04:11,560 --> 00:04:17,080 IMAGING GENETIC AND OTHER 98 00:04:17,080 --> 00:04:18,640 MULTIOMICS THAT INCREASED THE 99 00:04:18,640 --> 00:04:21,040 UNDERSTANDING OF PATHOPHYSIOLOGY 100 00:04:21,040 --> 00:04:24,080 AND PATHOGENESIS OF COPD IN 101 00:04:24,080 --> 00:04:25,520 PARALLEL SIGNIFICANT PROGRESS 102 00:04:25,520 --> 00:04:28,720 HAS ALSO BEEN MADE IN THE BASIC 103 00:04:28,720 --> 00:04:30,080 SCIENCE PHASE. 104 00:04:30,080 --> 00:04:32,560 NOVEL AND PROMISING HYPOTHESISES 105 00:04:32,560 --> 00:04:36,760 HAVE BEEN RAISED AND TESTS FOR 106 00:04:36,760 --> 00:04:39,040 COPD ONSET AND PROGRESSION AND 107 00:04:39,040 --> 00:04:42,440 THIS IS EXCITING AND 108 00:04:42,440 --> 00:04:43,040 ENCOURAGING. 109 00:04:43,040 --> 00:04:46,040 HOWEVER, THE FINDINGS OF COPD 110 00:04:46,040 --> 00:04:48,760 CLINICAL RESEARCH HAVE NOT 111 00:04:48,760 --> 00:04:55,600 READILY MAPPED TO RESEARCH AND 112 00:04:55,600 --> 00:04:57,440 THERE'S A GAP IN RESEARCH IN 113 00:04:57,440 --> 00:04:58,160 COPD. 114 00:04:58,160 --> 00:04:59,480 THE PURPOSE OF THE WORKSHOP IS 115 00:04:59,480 --> 00:05:01,160 TO BRING TOGETHER CLINICAL AND 116 00:05:01,160 --> 00:05:04,200 BASIC SCIENTISTS IN COPD TO 117 00:05:04,200 --> 00:05:06,600 IDENTIFY THE CURRENT STATE OF 118 00:05:06,600 --> 00:05:08,320 SCIENCE, CRITICAL KNOWLEDGE 119 00:05:08,320 --> 00:05:10,640 GAPS, KEY CHALLENGES AND 120 00:05:10,640 --> 00:05:14,440 BARRIERS AND OPPORTUNITIES IN 121 00:05:14,440 --> 00:05:15,600 UNDERSTANDING COPD PATHOBIOLOGY 122 00:05:15,600 --> 00:05:18,400 AND PATHOGENESIS. 123 00:05:18,400 --> 00:05:19,840 IT IS ANTICIPATED SPEAKERS AND 124 00:05:19,840 --> 00:05:22,920 PARTICIPANTS WILL DISCUSS HOW TO 125 00:05:22,920 --> 00:05:24,240 TRANSLATE THE KNOWLEDGE GAINED 126 00:05:24,240 --> 00:05:25,800 FROM MAJOR CLINICAL 127 00:05:25,800 --> 00:05:28,400 OBSERVATIONAL STUDIES TO KEY 128 00:05:28,400 --> 00:05:29,720 QUESTIONS THAT CAN BE ADDRESSED 129 00:05:29,720 --> 00:05:31,840 BY BASIC MECHANISTIC RESEARCH. 130 00:05:31,840 --> 00:05:35,320 WE PROBABLY CAN DO THAT BY 131 00:05:35,320 --> 00:05:37,080 TAKING ADVANTAGE OF NEW 132 00:05:37,080 --> 00:05:38,920 TECHNOLOGY AND MODEL SYSTEMS. 133 00:05:38,920 --> 00:05:41,200 IT IS OUR HOPE THAT THIS 134 00:05:41,200 --> 00:05:43,560 WORKSHOP WILL HELP SHAPE A 135 00:05:43,560 --> 00:05:45,800 RESEARCH VISION AND AGENDA ON 136 00:05:45,800 --> 00:05:47,760 HOW TO MOVE COPD RESEARCH 137 00:05:47,760 --> 00:05:50,160 FORWARD FOR MECHANISTIC STUDIES. 138 00:05:50,160 --> 00:05:54,840 WE FURTHER HOPE THAT A DEEPER 139 00:05:54,840 --> 00:05:57,960 UNDERSTANDING OF COPD PATHOGENIC 140 00:05:57,960 --> 00:05:59,360 MECHANISMS WILL LEAD TO 141 00:05:59,360 --> 00:06:01,080 DISCOVERY OF THERAPEUTIC 142 00:06:01,080 --> 00:06:01,880 STRATEGIES BEYOND TREATMENT 143 00:06:01,880 --> 00:06:05,520 SYSTEM AND DISEASE MODIFYING 144 00:06:05,520 --> 00:06:05,800 APPROACHES. 145 00:06:05,800 --> 00:06:07,880 I BELIEVE THIS WORKSHOP IS 146 00:06:07,880 --> 00:06:09,400 NECESSARY AND TIMELY. 147 00:06:09,400 --> 00:06:11,560 I AM HAPPY TO SEE A VERY DIVERSE 148 00:06:11,560 --> 00:06:14,720 AND INCLUSIVE PANEL OF EXPERTS 149 00:06:14,720 --> 00:06:15,720 AND PARTICIPANTS. 150 00:06:15,720 --> 00:06:18,400 THANK YOU AGAIN FOR YOUR 151 00:06:18,400 --> 00:06:18,720 PARTICIPATION. 152 00:06:18,720 --> 00:06:20,600 I AM LOOKING FORWARD TO A 153 00:06:20,600 --> 00:06:22,200 SUCCESSFUL AND PRODUCTIVE 154 00:06:22,200 --> 00:06:24,680 WORKSHOP AND WORK WITH YOU IN 155 00:06:24,680 --> 00:06:27,560 THE FUTURE TO PROMOTE LUNG AND 156 00:06:27,560 --> 00:06:32,000 SLEEP HEALTH. 157 00:06:32,000 --> 00:06:38,600 THANK YOU, DR. MATUTE-BELLO. 158 00:06:38,600 --> 00:06:43,840 I'D LIKE TO THANK OUR CO-CHAIRS 159 00:06:43,840 --> 00:06:51,280 DR. HUANG AND BLALOCK FOR THEIR 160 00:06:51,280 --> 00:06:52,160 CONCEPTION AND PLANNING AND 161 00:06:52,160 --> 00:06:53,960 EXPRESS OUR GRATITUDE TO ALL 162 00:06:53,960 --> 00:06:57,520 SECTION CO-CHAIRS, SPEAKERS, 163 00:06:57,520 --> 00:07:00,520 PANELISTS, DISCUSSANTS AND ALL 164 00:07:00,520 --> 00:07:04,800 OF YOU FOR WORKING HARD DAY AND 165 00:07:04,800 --> 00:07:06,880 NIGHT TO ADVANCE COPD RESEARCH 166 00:07:06,880 --> 00:07:08,760 AND IMPROVE THE QUALITY OF LIFE 167 00:07:08,760 --> 00:07:11,080 WITH INDIVIDUALS WITH COPD OR 168 00:07:11,080 --> 00:07:11,760 OTHER LUNG DISEASE. 169 00:07:11,760 --> 00:07:14,960 WE THANK YOU FOR YOUR INSIGHT 170 00:07:14,960 --> 00:07:18,880 AND YOU CONTRIBUTION TO THIS 171 00:07:18,880 --> 00:07:19,160 WORKSHOP. 172 00:07:19,160 --> 00:07:23,360 I WOULD ALSO PARTICULARLY LIKE 173 00:07:23,360 --> 00:07:24,800 TO THANK MANY COLLEAGUES FROM 174 00:07:24,800 --> 00:07:25,960 THE DIFFERENT PARTS OF THE GLOBE 175 00:07:25,960 --> 00:07:29,320 WHO HAVE TO OVERCOME SIGNIFICANT 176 00:07:29,320 --> 00:07:32,040 TIME ZONE DIFFERENCES AND 177 00:07:32,040 --> 00:07:32,960 SACRIFICE THEIR SLEEP TO 178 00:07:32,960 --> 00:07:35,040 PARTICIPATE IN THIS WORKSHOP. 179 00:07:35,040 --> 00:07:36,680 I KNOW THIS IS PROBABLY MIDNIGHT 180 00:07:36,680 --> 00:07:39,720 IN YOUR TIME. 181 00:07:39,720 --> 00:07:40,480 THANK YOU. 182 00:07:40,480 --> 00:07:42,800 THE NHLBI DIVISION OF LUNG 183 00:07:42,800 --> 00:07:45,000 DISEASE WOULD ALSO LIKE TO THANK 184 00:07:45,000 --> 00:07:46,240 ALL PEOPLE WITH OR WITHOUT COPD 185 00:07:46,240 --> 00:07:48,880 WHO HAVE PARTICIPATED IN THE 186 00:07:48,880 --> 00:07:49,480 RESEARCH DISCUSSED TODAY AND 187 00:07:49,480 --> 00:07:59,200 TOMORROW. 188 00:07:59,200 --> 00:08:00,240 WITHOUT THEIR PARTICIPATION WE 189 00:08:00,240 --> 00:08:02,000 COULD NOT MOVE THE FIELD 190 00:08:02,000 --> 00:08:03,120 FORWARD. 191 00:08:03,120 --> 00:08:05,200 WE ARE GRATEFUL TO DR. WRIGHT 192 00:08:05,200 --> 00:08:09,840 FROM THE COPD FOUNDATION WHO 193 00:08:09,840 --> 00:08:11,240 JOINED WITH US AND PROVIDE 194 00:08:11,240 --> 00:08:16,920 INSIGHT FROM THE PATIENT 195 00:08:16,920 --> 00:08:27,160 PERSPECTIVES. 196 00:08:29,360 --> 00:08:31,560 AND IT WOULD NOT BE ABLE TO 197 00:08:31,560 --> 00:08:33,800 ORGANIZE WITHOUT THE TEAM'S HELP 198 00:08:33,800 --> 00:08:35,480 AND LAST BUT NOT LEAST I WOULD 199 00:08:35,480 --> 00:08:44,320 LIKE TO THANK THE DOD LEADERSHIP 200 00:08:44,320 --> 00:08:54,840 AND DR. PUNTURIERI FOR THEIR 201 00:09:03,200 --> 00:09:03,400 SUGGESTIONS. 202 00:09:03,400 --> 00:09:09,480 AND THE PURPOSE OF THIS WORKSHOP 203 00:09:09,480 --> 00:09:13,000 IS TO BRING TOGETHER CLINIC AND 204 00:09:13,000 --> 00:09:14,280 BASIC SCIENCE AND IDENTIFY THE 205 00:09:14,280 --> 00:09:16,640 CURRENT STATE OF SCIENCE, 206 00:09:16,640 --> 00:09:18,200 CRITICAL KNOWLEDGE GABZ, KEY 207 00:09:18,200 --> 00:09:22,320 CHALLENGES AND THE BARRIERS AND 208 00:09:22,320 --> 00:09:23,520 OPPORTUNITY IN UNDERSTANDING OF 209 00:09:23,520 --> 00:09:27,000 COPD PATHOPHYSIOLOGY AND 210 00:09:27,000 --> 00:09:27,320 PATHOGENESIS. 211 00:09:27,320 --> 00:09:29,560 WE LOOK FORWARD TO YOUR 212 00:09:29,560 --> 00:09:31,040 ACTIONABLE AND IMPLEMENTABLE 213 00:09:31,040 --> 00:09:33,160 IDEAS AND RECOMMENDATION. 214 00:09:33,160 --> 00:09:33,960 THANK YOU AGAIN FOR YOUR 215 00:09:33,960 --> 00:09:34,320 PARTICIPATION. 216 00:09:34,320 --> 00:09:36,400 I LOOK FORWARD TO A SUCCESSFUL 217 00:09:36,400 --> 00:09:39,200 AND PRODUCTIVE WORKSHOP AND 218 00:09:39,200 --> 00:09:40,680 WORKING WITH YOU IN THE FUTURE 219 00:09:40,680 --> 00:09:44,240 TO PROMOTE LUNG AND SLEEP 220 00:09:44,240 --> 00:09:44,480 HEALTH. 221 00:09:44,480 --> 00:09:50,280 NEXT I WOULD LIKE TO SAY A FEW 222 00:09:50,280 --> 00:09:52,680 THINGS ABOUT THE MEETING 223 00:09:52,680 --> 00:09:52,960 LOGISTIC. 224 00:09:52,960 --> 00:09:54,600 THE WORKSHOP IS VIDEOCAST AND 225 00:09:54,600 --> 00:09:58,840 LIVE STREAMED. 226 00:09:58,840 --> 00:10:00,360 THE RECORDING WILL BE AVAILABLE 227 00:10:00,360 --> 00:10:04,360 IN THE NIH VIDEOCAST PAST EVENT 228 00:10:04,360 --> 00:10:10,840 APPROXIMATELY ONE WEEK FROM THE 229 00:10:10,840 --> 00:10:11,560 EVENT. 230 00:10:11,560 --> 00:10:16,240 SECOND, TIME IS GIVEN TO EACH 231 00:10:16,240 --> 00:10:18,680 PRESENTATIONS. 232 00:10:18,680 --> 00:10:21,240 AND AT THE END OF THE 90 MINUTE 233 00:10:21,240 --> 00:10:22,400 PRESENTATION SECTION THERE WILL 234 00:10:22,400 --> 00:10:24,040 BE A 60-MINUTE DISCUSSION. 235 00:10:24,040 --> 00:10:26,240 SO AUDIENCE, PLEASE HOLD YOUR 236 00:10:26,240 --> 00:10:30,000 QUESTIONS TO THE OPEN 237 00:10:30,000 --> 00:10:30,600 DISCUSSIONS. 238 00:10:30,600 --> 00:10:32,120 AUDIENCE YOU CAN ALSO USE THE 239 00:10:32,120 --> 00:10:36,320 CHAT BOX TO ASK QUESTIONS DURING 240 00:10:36,320 --> 00:10:38,800 THE PRESENTATIONS. 241 00:10:38,800 --> 00:10:42,480 THE CO-CHAIR AND PROGRAM STAFF 242 00:10:42,480 --> 00:10:48,880 WILL MONITOR CHAT TO MAKE SURE 243 00:10:48,880 --> 00:10:51,040 ALL QUESTIONS GET ADDRESSED AND 244 00:10:51,040 --> 00:10:52,960 PRESENTERS ARE ENCOURAGED TO 245 00:10:52,960 --> 00:10:59,520 ANSWER IN THE CHAT THE TECHNICAL 246 00:10:59,520 --> 00:11:01,360 QUESTIONS AND QUESTIONS 247 00:11:01,360 --> 00:11:03,520 ADDRESSED IN THE OPEN DISCUSSION 248 00:11:03,520 --> 00:11:08,600 SECTION. 249 00:11:08,600 --> 00:11:10,400 DISCUSSANTS AND PANELISTS ARE 250 00:11:10,400 --> 00:11:12,320 ENCOURAGED TO USE RAISING HAND 251 00:11:12,320 --> 00:11:12,960 FUNCTION AND OPEN CAMERA WITH 252 00:11:12,960 --> 00:11:20,160 THE TALK. 253 00:11:20,160 --> 00:11:26,960 IF A SPEAKER DOES NOT HAVE A 254 00:11:26,960 --> 00:11:28,840 DISCLOSURE SLIDE YOU CAN 255 00:11:28,840 --> 00:11:31,840 PRESENTATION IT BEFORE YOUR 256 00:11:31,840 --> 00:11:32,280 PRESENTATIONS. 257 00:11:32,280 --> 00:11:34,680 WE DIDN'T EMPHASIZE IT IN DRY 258 00:11:34,680 --> 00:11:37,920 RUN BUT IT'S OKAY IF YOU DO NOT 259 00:11:37,920 --> 00:11:40,120 HAVE SLIGHT BUT STATE IF YOU 260 00:11:40,120 --> 00:11:42,480 HAVE FINANCIAL AD OR NOT. 261 00:11:42,480 --> 00:11:44,280 AND OUR SUPPORT TEAM ALREADY 262 00:11:44,280 --> 00:11:47,800 SAID TO SAVE THE BANDWIDTH, 263 00:11:47,800 --> 00:11:49,680 PLEASE KEEP CAMERA OFF OR AUDIO 264 00:11:49,680 --> 00:11:54,240 MUTES WHEN NOT TALKING. 265 00:11:54,240 --> 00:11:57,040 THE SUPPORT STAFF TEAM WILL BE 266 00:11:57,040 --> 00:11:58,200 HERE TO RESPOND TO TECHNICAL 267 00:11:58,200 --> 00:11:59,040 QUESTIONS OR QUESTIONS DURING 268 00:11:59,040 --> 00:12:05,360 THE WORKSHOP. 269 00:12:05,360 --> 00:12:09,280 NOW, I WOULD LIKE TO INTRODUCE 270 00:12:09,280 --> 00:12:15,120 OUR CO-CHAIRS, DR. HAN FROM THE 271 00:12:15,120 --> 00:12:20,760 UNIVERSITY OF MICHIGAN AND 272 00:12:20,760 --> 00:12:21,360 DRDR 273 00:12:21,360 --> 00:12:24,600 DRDR 274 00:12:24,600 --> 00:12:26,960 DR. BLALOCK FROM THE UNIVERSITY 275 00:12:26,960 --> 00:12:32,080 OF BIRMINGHAM. 276 00:12:32,080 --> 00:12:36,360 DR. HAN AND DR. BLALOCK THE 277 00:12:36,360 --> 00:12:37,680 FLOOR IS YOURS. 278 00:12:37,680 --> 00:12:41,080 >> I'D LIKE TO WELCOME ALL 279 00:12:41,080 --> 00:12:42,560 PARTICIPATING IN THE MEETING AND 280 00:12:42,560 --> 00:12:44,600 GIVE A PARTICULAR THANKS TO THE 281 00:12:44,600 --> 00:12:44,880 INVITEES. 282 00:12:44,880 --> 00:12:50,560 WHEN WE STARTED WORKING ON THIS 283 00:12:50,560 --> 00:12:53,600 PROJECT I THOUGHT SCHEDULING WAS 284 00:12:53,600 --> 00:12:55,560 GOING TO BE BE AN ABSOLUTE 285 00:12:55,560 --> 00:12:55,800 NIGHTMARE. 286 00:12:55,800 --> 00:12:57,400 BECAUSE OF THE ENTHUSIASM AND 287 00:12:57,400 --> 00:12:58,960 ACCOMMODATING NATURE OF ALL THE 288 00:12:58,960 --> 00:13:02,680 PEOPLE WE INVITED IT TURNED OUT 289 00:13:02,680 --> 00:13:03,840 TO BE VERY EASY. 290 00:13:03,840 --> 00:13:08,560 FOR THAT I THANK YOU. 291 00:13:08,560 --> 00:13:17,680 I BELIEVE MEILAN WANTS TO GIVE 292 00:13:17,680 --> 00:13:18,280 THE CHARGE. 293 00:13:18,280 --> 00:13:20,360 >> MOST HAVE PARTICIPATED IN 294 00:13:20,360 --> 00:13:21,480 WORKSHOP AND THOSE TRADITIONALLY 295 00:13:21,480 --> 00:13:23,200 HAVE ALWAYS BEEN AMAZING 296 00:13:23,200 --> 00:13:24,960 EXPERIENCES AND WE WISH WE COULD 297 00:13:24,960 --> 00:13:30,080 HAVE OFFERED THIS IN PERSON BUT 298 00:13:30,080 --> 00:13:32,560 AS IT IS THIS IS THE MOST IDEAL 299 00:13:32,560 --> 00:13:32,800 FORMAT. 300 00:13:32,800 --> 00:13:34,880 ON THE UPSIDE, I DO NOT REMEMBER 301 00:13:34,880 --> 00:13:37,440 AN IN-PERSON WORKSHOP WHERE WE 302 00:13:37,440 --> 00:13:39,520 HAD OVER 250 PEOPLE THAT WERE 303 00:13:39,520 --> 00:13:40,720 ABLE TO PARTICIPATE AND I SEE 304 00:13:40,720 --> 00:13:46,280 RIGHT NOW OUR PARTICIPANTS ARE 305 00:13:46,280 --> 00:13:47,920 HOVERING AROUND 130. 306 00:13:47,920 --> 00:13:49,800 THAT'S EXCITING TO ME AND I'LL 307 00:13:49,800 --> 00:13:53,920 ECHO WHAT ED SAID IN THAT WE'RE 308 00:13:53,920 --> 00:13:55,120 JUST HONORED THAT SO MANY PEOPLE 309 00:13:55,120 --> 00:13:58,800 WERE ENTHUSIASTIC ABOUT 310 00:13:58,800 --> 00:14:03,960 PARTICIPATING AND JUST FROM A 311 00:14:03,960 --> 00:14:05,360 PERSONAL PERSPECTIVE WE'VE BEEN 312 00:14:05,360 --> 00:14:08,360 HOPING FOR BREAKTHROUGHS IN COPD 313 00:14:08,360 --> 00:14:10,480 FOR A LONG TIME AND I THINK 314 00:14:10,480 --> 00:14:13,240 WE'RE STARTING TO GET A LOT OF 315 00:14:13,240 --> 00:14:14,560 INFORMATION COMING OUT IN THE 316 00:14:14,560 --> 00:14:19,520 LAST FEW YEARS THAT I THINK 317 00:14:19,520 --> 00:14:23,520 POISES FOR BREAKTHROUGHS AND TO 318 00:14:23,520 --> 00:14:25,280 PROVIDE OVERVIEW FOR THE 319 00:14:25,280 --> 00:14:26,160 WORKSHOP, AS YOU PROBABLY 320 00:14:26,160 --> 00:14:28,080 ALREADY SAW FROM THE AGENDA 321 00:14:28,080 --> 00:14:30,360 WE'RE ACTUALLY BROKEN INTO FOUR 322 00:14:30,360 --> 00:14:31,480 DISTINCT SECTIONS. 323 00:14:31,480 --> 00:14:33,800 TWO THAT WILL OCCUR TODAY AND 324 00:14:33,800 --> 00:14:35,840 TWO THAT WILL OCCUR TOMORROW 325 00:14:35,840 --> 00:14:37,800 WITH THE LAST SESSION REALLY 326 00:14:37,800 --> 00:14:39,840 BEING FOCUSSING PRIMARILY ON 327 00:14:39,840 --> 00:14:42,680 DISCUSSION AND WRAP UP. 328 00:14:42,680 --> 00:14:47,840 ONE OF THE GOALS OF THIS 329 00:14:47,840 --> 00:14:51,080 WORKSHOP IS TO BRING CLINICAL 330 00:14:51,080 --> 00:14:52,880 RESEARCHERS AND BASIC SCIENTISTS 331 00:14:52,880 --> 00:14:53,120 TOGETHER. 332 00:14:53,120 --> 00:14:57,120 YOU'LL SEE FROM EVEN THE CHAIRS 333 00:14:57,120 --> 00:14:58,360 MORE OF A CLINICAL RESEARCHER 334 00:14:58,360 --> 00:15:01,280 AND ED IS MORE OF A BASIC 335 00:15:01,280 --> 00:15:02,760 SCIENCE RESEARCHER IN COPD AND 336 00:15:02,760 --> 00:15:05,920 THAT'S REALLY THE THEME FOR 337 00:15:05,920 --> 00:15:06,960 TODAY IS TO BRING BOTH GROUPS 338 00:15:06,960 --> 00:15:10,920 TOGETHER TO SEE HOW WE CAN 339 00:15:10,920 --> 00:15:11,800 TRANSLATE THE SCIENCE AND 340 00:15:11,800 --> 00:15:13,000 RESEARCH CHALLENGES TO 341 00:15:13,000 --> 00:15:14,360 UNDERSTAND WHAT THE 342 00:15:14,360 --> 00:15:16,400 OPPORTUNITIES ARE FOR COPD 343 00:15:16,400 --> 00:15:18,640 PARTICULARLY WITH RESPECT TO 344 00:15:18,640 --> 00:15:21,120 PATHOBIOLOGY AND PATHOGENESIS. 345 00:15:21,120 --> 00:15:26,080 WE REALIZE WE ARE NOT ABLE TO 346 00:15:26,080 --> 00:15:28,120 COVER EVERY TOPIC BUT STILL WE 347 00:15:28,120 --> 00:15:32,960 BROUGHT A LOT PEOPLE TOGETHER 348 00:15:32,960 --> 00:15:40,240 AND CAN BRING THIS FORWARD WITH 349 00:15:40,240 --> 00:15:41,560 RESPECT TO PATHOGENESIS. 350 00:15:41,560 --> 00:15:44,000 IN THIS MORNING'S SESSION YOU'LL 351 00:15:44,000 --> 00:15:45,680 SEE INFORMATION FROM SOME OF THE 352 00:15:45,680 --> 00:15:49,000 MAJOR COPD COHORTS OR WE'RE 353 00:15:49,000 --> 00:15:50,720 HONORED TO HAVE OUR COLLEAGUES 354 00:15:50,720 --> 00:15:58,160 FROM AUSTRALIA TO ABOUT THE 355 00:15:58,160 --> 00:16:01,680 TASMANIAN COHORT AS WELL AND HOW 356 00:16:01,680 --> 00:16:02,440 EPIDEMIOLOGIC STUDIES 357 00:16:02,440 --> 00:16:03,200 CONTRIBUTED TO THE DISEASE AND 358 00:16:03,200 --> 00:16:06,400 WE'LL HAVE A SECTION ON MODELS 359 00:16:06,400 --> 00:16:11,120 FOR STUDYING COPD AND THIS IS 360 00:16:11,120 --> 00:16:12,760 MOVED BEYOND THE TRADITIONAL 361 00:16:12,760 --> 00:16:15,560 ANIMAL MODELS AND NOW INCLUDES 362 00:16:15,560 --> 00:16:19,240 MORE SOPHISTICATED SYSTEMS LIKE 363 00:16:19,240 --> 00:16:21,200 ORGANOID SYSTEMS AND I'M EXCITED 364 00:16:21,200 --> 00:16:24,040 FOR THAT SESSION AS WELL AND 365 00:16:24,040 --> 00:16:27,520 THEN WE HAVE A SESSION TOMORROW 366 00:16:27,520 --> 00:16:29,160 DEDICATED TO UNDERSTANDING SOME 367 00:16:29,160 --> 00:16:30,280 OF THE DIFFERENT MECHANISMS 368 00:16:30,280 --> 00:16:33,680 BEHIND INJURY IN COPD. 369 00:16:33,680 --> 00:16:35,160 NOW, OBVIOUSLY WE CAN'T COVER 370 00:16:35,160 --> 00:16:36,760 EVERY SINGLE POTENTIAL PATHWAY 371 00:16:36,760 --> 00:16:39,320 THAT MIGHT BE IMPLICATED BUT WE 372 00:16:39,320 --> 00:16:42,320 WILL DO OUR BEST TO GET A BROAD 373 00:16:42,320 --> 00:16:44,360 OVERVIEW AND THEN AT THE END 374 00:16:44,360 --> 00:16:45,480 WE'RE JUST GOING TO WRAP 375 00:16:45,480 --> 00:16:48,240 EVERYTHING UP BY TRYING TO 376 00:16:48,240 --> 00:16:50,400 UNDERSTAND WHERE WE NEED TO MOVE 377 00:16:50,400 --> 00:16:50,800 FORWARD. 378 00:16:50,800 --> 00:16:53,880 WHAT ARE THE IMPORTANT TESTABLE 379 00:16:53,880 --> 00:16:54,960 HYPOTHESES WE AS A RESEARCH 380 00:16:54,960 --> 00:16:56,840 COMMUNITY SHOULD BE DOING NEXT. 381 00:16:56,840 --> 00:16:58,160 HOW COULD WE BETTER COLLABORATE 382 00:16:58,160 --> 00:16:58,440 TOGETHER. 383 00:16:58,440 --> 00:17:03,040 I WOULD HOPE THAT'S A MAJOR 384 00:17:03,040 --> 00:17:05,000 OUTPUT OF THIS WORKSHOP. 385 00:17:05,000 --> 00:17:08,200 I THINK WE'RE ALSO ENVISIONING 386 00:17:08,200 --> 00:17:09,680 THERE BE AN EXECUTIVE SUMMARY 387 00:17:09,680 --> 00:17:11,520 PEOPLE WILL HELP PARTICIPATE ON 388 00:17:11,520 --> 00:17:14,200 WITH RESPECT TO AUTHORSHIP. 389 00:17:14,200 --> 00:17:15,920 I BELIEVE WE'VE BEEN SLOTTED 390 00:17:15,920 --> 00:17:17,920 UNTIL 10:30 FOR THIS BUT I DON'T 391 00:17:17,920 --> 00:17:20,040 KNOW THAT WE NEED TO KEEP GOING. 392 00:17:20,040 --> 00:17:22,760 IT MAY BE BEST JUST TO GO AHEAD 393 00:17:22,760 --> 00:17:25,720 AND JUMP INTO OUR FIRST SESSION 394 00:17:25,720 --> 00:17:28,680 UNLESS ED OR ANYONE FROM THE NIH 395 00:17:28,680 --> 00:17:30,040 HAD ANY OTHER COMMENTS BEFORE WE 396 00:17:30,040 --> 00:17:32,400 JUMP INTO OUR FIRST SESSION. 397 00:17:32,400 --> 00:17:34,160 >> YEAH, YOU ARE CHAIR. 398 00:17:34,160 --> 00:17:34,840 >> OKAY. 399 00:17:34,840 --> 00:17:37,080 I HAVE A FUNNY FEELING WE'LL 400 00:17:37,080 --> 00:17:39,720 WISH FOR EXTRA TIME ON THE BACK 401 00:17:39,720 --> 00:17:41,920 END SO I'LL TAKE THE CHAIR'S 402 00:17:41,920 --> 00:17:45,560 PREROGATIVE AND MOVE US FORWARD. 403 00:17:45,560 --> 00:17:48,360 THIS FIRST SECTION IS GOING TO 404 00:17:48,360 --> 00:17:51,440 BE CO-CHAIRED BY DR. JEFFERY 405 00:17:51,440 --> 00:17:53,960 CURTIS A PROFESSOR OF INTERNAL 406 00:17:53,960 --> 00:17:57,200 MEDICINE IN CRITICAL CARE HERE 407 00:17:57,200 --> 00:18:04,040 IN ANN ARBOR AT THE V.A. MEDICAL 408 00:18:04,040 --> 00:18:07,840 CENTER AND STEPHANIE CHRISTENSON 409 00:18:07,840 --> 00:18:10,120 PROFESSOR OF MEDICINE 410 00:18:10,120 --> 00:18:11,560 UNIVERSITY, SAN FRANCISCO AND 411 00:18:11,560 --> 00:18:16,280 LOOK AT THE COHORTS INCLUDING 412 00:18:16,280 --> 00:18:17,440 COPD, SPIROMICS, MESA HEALTH 413 00:18:17,440 --> 00:18:21,320 STUDY AND THE TASMANIAN HEALTH 414 00:18:21,320 --> 00:18:21,520 STUDIES. 415 00:18:21,520 --> 00:18:23,720 WE HAVE A LOT OF PRESENTERS FROM 416 00:18:23,720 --> 00:18:29,000 ALL OVER THE WORLD AND THEY'LL 417 00:18:29,000 --> 00:18:38,280 BE HELPING UNDERSTAND WHAT WE 418 00:18:38,280 --> 00:18:40,880 CAN TAKEAWAY FROM THIS. 419 00:18:40,880 --> 00:18:43,280 I'LL TURN THIS OVER TO OUR 420 00:18:43,280 --> 00:18:45,760 CO-CHAIRS DR. CURTIS AND 421 00:18:45,760 --> 00:18:50,600 DR. CHRISTENSON. 422 00:18:50,600 --> 00:18:52,080 >> THANK YOU SO MUCH. 423 00:18:52,080 --> 00:18:53,600 >> THANK YOU FOR BEING HERE. 424 00:18:53,600 --> 00:18:59,360 JUST TO GIVE A LAYOUT TO THIS 425 00:18:59,360 --> 00:19:01,760 SESSION, WE HAVE SEVERAL COHORTS 426 00:19:01,760 --> 00:19:03,480 TO GET THROUGH IN THE FIRST HOUR 427 00:19:03,480 --> 00:19:08,640 AND A HALF AND THEN THERE'S AN 428 00:19:08,640 --> 00:19:10,760 HOUR FOR DISCUSSION AFTERWORDS. 429 00:19:10,760 --> 00:19:12,120 UNLESS YOU HAVE FURTHER COMMENTS 430 00:19:12,120 --> 00:19:15,480 I THINK WE WANTED TO HEAR FROM 431 00:19:15,480 --> 00:19:20,720 THE P.I.'S OF THE COHORTS ON 432 00:19:20,720 --> 00:19:26,280 WHAT THEY THINK OF THE STATE OF 433 00:19:26,280 --> 00:19:27,360 CLINICAL RESEARCH. 434 00:19:27,360 --> 00:19:28,840 DID YOU WANT TO INTRODUCE COPD 435 00:19:28,840 --> 00:19:29,600 GENE, JEF? 436 00:19:29,600 --> 00:19:32,240 >> THAT'S WHAT I WAS TYPING. 437 00:19:32,240 --> 00:19:40,440 PLEASED TO INTRODUCE DR. ED 438 00:19:40,440 --> 00:19:49,800 SILVERMAN AND DR. CRAPO. 439 00:19:49,800 --> 00:19:51,880 >> IT'S A PLEASURE TO BE HERE TO 440 00:19:51,880 --> 00:19:55,200 TALK ABOUT THIS LONGITUDINAL 441 00:19:55,200 --> 00:19:56,840 STUDY TO UNDERSTAND 442 00:19:56,840 --> 00:19:58,200 SUSCEPTIBILITY AND PROGRESSION 443 00:19:58,200 --> 00:19:59,560 OF COPD. 444 00:19:59,560 --> 00:20:02,240 THIS SLIDE SUMMARIZES OUR 445 00:20:02,240 --> 00:20:04,240 PERSONAL FINANCIAL RELATIONSHIP. 446 00:20:04,240 --> 00:20:06,280 SO COPD GENE HAS A NUMBER OF 447 00:20:06,280 --> 00:20:06,600 GOALS. 448 00:20:06,600 --> 00:20:10,760 WE WANT TO TRY TO IDENTIFY NEW 449 00:20:10,760 --> 00:20:14,000 GENETIC LOCI THAT INFLUENCE 450 00:20:14,000 --> 00:20:15,400 SUSCEPTIBILITY FOR AND COPD AND 451 00:20:15,400 --> 00:20:16,600 RELATED PHENOTYPES. 452 00:20:16,600 --> 00:20:18,840 WE WOULD LIKE TO RECLASSIFY THE 453 00:20:18,840 --> 00:20:20,880 SYNDROME INTO SUBTYPES THAT 454 00:20:20,880 --> 00:20:24,160 SHARE A COMMON PATHOGENESIS, 455 00:20:24,160 --> 00:20:24,800 GENETICS, BIOMARKERS PROGRESS 456 00:20:24,800 --> 00:20:27,120 AND RESPONSE TO THERAPY AND 457 00:20:27,120 --> 00:20:28,600 WOULD LIKE TO CHARACTERIZE THE 458 00:20:28,600 --> 00:20:29,880 PATTERNS OF DISEASE PROGRESSION 459 00:20:29,880 --> 00:20:33,320 AND ULTIMATE WE WANT THIS WORK 460 00:20:33,320 --> 00:20:37,440 TO LEAD TO IMPROVED CLINIC 461 00:20:37,440 --> 00:20:39,480 PRACTICE WITH EARLIER 462 00:20:39,480 --> 00:20:40,800 IDENTIFICATION OF COPD PATIENTS 463 00:20:40,800 --> 00:20:45,000 AND IDENTIFY THERAPIES AND 464 00:20:45,000 --> 00:20:46,360 APPROACH TO DISEASE PREVENTION. 465 00:20:46,360 --> 00:20:48,640 JAMES WILL TALK ABOUT THE 466 00:20:48,640 --> 00:20:48,960 COHORT. 467 00:20:48,960 --> 00:20:54,800 >> THE COHORT IS OVER 10,000 468 00:20:54,800 --> 00:20:55,800 PEOPLE WHOSE PRIMARY CRITERIA 469 00:20:55,800 --> 00:21:01,720 FOR COMING IN IS THEY SMOKED AND 470 00:21:01,720 --> 00:21:04,880 45 TO 80 AND 455 NON-SMOKING 471 00:21:04,880 --> 00:21:05,320 CONTROLS. 472 00:21:05,320 --> 00:21:07,640 WE LOOKED AT THEM DETAILED AT 473 00:21:07,640 --> 00:21:10,840 BASELINE AT FIVE YEAR AND 474 00:21:10,840 --> 00:21:11,920 10-YEAR FOLLOW-UP. 475 00:21:11,920 --> 00:21:17,040 IN MONTHS WE'LL START A 15-YEAR 476 00:21:17,040 --> 00:21:17,320 FOLLOW-UP. 477 00:21:17,320 --> 00:21:20,280 THIS IS THE DISTRIBUTION OF MORE 478 00:21:20,280 --> 00:21:22,680 THAN 10,000 PEOPLE IN OUR 479 00:21:22,680 --> 00:21:22,920 COHORT. 480 00:21:22,920 --> 00:21:24,520 AND IT'S IMPORTANT THAT MORE 481 00:21:24,520 --> 00:21:27,120 THAN HALF OF THEM DID NOT HAVE 482 00:21:27,120 --> 00:21:33,440 COPD AS DEFINED BY LOW F EV1 483 00:21:33,440 --> 00:21:34,560 RATIO AND THERE'S ABOUT 40% OF 484 00:21:34,560 --> 00:21:36,800 THE COHORT IN THE UPPER LEFT 485 00:21:36,800 --> 00:21:40,760 QUADRANT IS THE QUADRANT WE CALL 486 00:21:40,760 --> 00:21:44,080 PRISM PRESERVED RACIAL IMPAIRED 487 00:21:44,080 --> 00:21:44,360 SPIROMETRY. 488 00:21:44,360 --> 00:21:45,840 WE FOUND A GREAT DEAL OF DISEASE 489 00:21:45,840 --> 00:21:47,200 IN THESE QUADRANTS. 490 00:21:47,200 --> 00:21:47,880 SEVERE DISEASE. 491 00:21:47,880 --> 00:21:50,200 WE FOUND UNIQUE PATTERNS OF 492 00:21:50,200 --> 00:21:50,480 PROGRESSION. 493 00:21:50,480 --> 00:21:52,400 SO THE BEGINNING OF THE DISEASE 494 00:21:52,400 --> 00:21:54,120 WE THINK IS IN THE RIGHT UPPER 495 00:21:54,120 --> 00:21:55,080 QUADRANT WE NEED TO UNDERSTAND 496 00:21:55,080 --> 00:21:59,440 AND SHOULD BE A MAJOR TOPIC OF 497 00:21:59,440 --> 00:22:00,000 DISCUSSIONS IN THIS COHORT. 498 00:22:00,000 --> 00:22:03,560 THIS COHORT IS ABOUT TWO-THIRDS 499 00:22:03,560 --> 00:22:06,320 NON-HISPANIC WHITE, ONE-THIRD 500 00:22:06,320 --> 00:22:06,960 AFRICAN AMERICAN AND DISTRIBUTED 501 00:22:06,960 --> 00:22:09,280 BETWEEN MALE AND FEMALE. 502 00:22:09,280 --> 00:22:14,880 ONE OF OUR QUESTIONS IS HOW DO 503 00:22:14,880 --> 00:22:16,640 PEOPLE PROGRESS FROM SO-CALLED 504 00:22:16,640 --> 00:22:19,840 NORMAL TO REACH THE LOWER LEFT 505 00:22:19,840 --> 00:22:21,200 QUADRANT WITH HIGH MORBIDITY AND 506 00:22:21,200 --> 00:22:22,240 MORTALITY AND SOMETHING WE'LL 507 00:22:22,240 --> 00:22:26,080 TALK ABOUT. 508 00:22:26,080 --> 00:22:30,440 WE IDENTIFY THIS IS NOT ONE 509 00:22:30,440 --> 00:22:30,680 DISEASE. 510 00:22:30,680 --> 00:22:34,640 IT'S A PATTERN OF MANY DISEASE. 511 00:22:34,640 --> 00:22:38,480 WE'RE EMPHASIZES ONE DOESN'T 512 00:22:38,480 --> 00:22:43,720 HAVE MUCH EMPHYSEMA IN THE LATE 513 00:22:43,720 --> 00:22:45,480 IN THE PROCESS AND THERE'S A LOT 514 00:22:45,480 --> 00:22:47,200 OF AIRWAY WALL THICKENING YOU 515 00:22:47,200 --> 00:22:48,960 CAN PICK UP ON CT. 516 00:22:48,960 --> 00:22:54,200 AND THIS IS IN CONTRAST WITH OUR 517 00:22:54,200 --> 00:23:03,560 EMPHYSEMA DISEASE CLASSIC WITH 518 00:23:03,560 --> 00:23:07,840 PATTERNS IN EMPHYSEMA HAS LITTLE 519 00:23:07,840 --> 00:23:09,920 AIRWAY DISEASE SO TWO SEPARATE 520 00:23:09,920 --> 00:23:10,680 GROUPS. 521 00:23:10,680 --> 00:23:13,080 THE POINT IS WE DON'T CONSIDER 522 00:23:13,080 --> 00:23:14,800 COPD 1 DISEASE AND CT IS A MAJOR 523 00:23:14,800 --> 00:23:18,360 FACTOR IN HELPING UNDERSTAND THE 524 00:23:18,360 --> 00:23:20,120 DIFFERENCES. 525 00:23:20,120 --> 00:23:22,720 THIS IS -- WE USED A.I. IN 526 00:23:22,720 --> 00:23:24,280 VARIOUS WAYS AND MORTALITY TO 527 00:23:24,280 --> 00:23:26,760 TRY TO LOOK AT THE DIFFERENT 528 00:23:26,760 --> 00:23:29,560 PATTERNS OF THE AIRWAY DISEASE 529 00:23:29,560 --> 00:23:30,800 AND EMPHYSEMA DISEASE. 530 00:23:30,800 --> 00:23:32,440 THE BLUE DOTS IN THE RIGHT SIDE 531 00:23:32,440 --> 00:23:35,400 OF THE GRAPH ARE INDIVIDUALS 532 00:23:35,400 --> 00:23:37,240 WITH HIGH RISK EMPHYSEMA DISEASE 533 00:23:37,240 --> 00:23:39,360 AND YOU CAN SEE BEGINS AT ZERO 534 00:23:39,360 --> 00:23:41,440 AND PROGRESSES TO THE LEFT UPPER 535 00:23:41,440 --> 00:23:41,800 QUADRANT. 536 00:23:41,800 --> 00:23:44,280 THAT'S IN MARK CONTRAST TO THOSE 537 00:23:44,280 --> 00:23:46,360 WITH AIRWAY DISEASE THE ONES 538 00:23:46,360 --> 00:23:48,240 WITH RED THAT BY THE TIME 539 00:23:48,240 --> 00:23:50,280 THEY'RE HIGH RISK AIRWAY THEY'RE 540 00:23:50,280 --> 00:23:52,760 WELL IN THE PRISM HAVE LOST A 541 00:23:52,760 --> 00:23:57,520 GREAT DEAL OF FEV1 AND CONTINUE 542 00:23:57,520 --> 00:23:58,320 TO 3 AND 4. 543 00:23:58,320 --> 00:24:00,760 BECAUSE AIRWAY DISEASE HAS HIGH 544 00:24:00,760 --> 00:24:02,400 MORTALITY WE CHARACTERIZE THE 545 00:24:02,400 --> 00:24:03,280 MODERATE AIRWAY RISK AS GREEN 546 00:24:03,280 --> 00:24:07,200 AND YOU CAN SEE IT FALLS IN 547 00:24:07,200 --> 00:24:07,440 BETWEEN. 548 00:24:07,440 --> 00:24:08,840 THE SUBTYPES CLEARLY SEPARATE 549 00:24:08,840 --> 00:24:11,480 WHEN WE LOOK AT THE CT PATTERNS 550 00:24:11,480 --> 00:24:13,880 AND PHYSIOLOGIC FUNCTION. 551 00:24:13,880 --> 00:24:15,840 I WANT TO SHOW YOU MORE ABOUT 552 00:24:15,840 --> 00:24:18,480 THE MORTALITY WHICH IS UNLIKE 553 00:24:18,480 --> 00:24:23,240 AND GIVE YOU AN IDEA HOW GO FROM 554 00:24:23,240 --> 00:24:27,040 ZERO TO GOAL 3, 4 WE CAN NOW 555 00:24:27,040 --> 00:24:27,960 FOLLOW OVER 10 YEARS. 556 00:24:27,960 --> 00:24:30,360 THIS IS THE MORTALITY OVER 15 557 00:24:30,360 --> 00:24:32,720 YEARS OF OBSERVATION. 558 00:24:32,720 --> 00:24:34,800 THE TOP GRAY CURVE ARE THE 559 00:24:34,800 --> 00:24:39,560 SUBJECTS THAT HAD NO SIGNIFICANT 560 00:24:39,560 --> 00:24:40,920 AIRWAY OR EMPHYSEMA DISEASE AT 561 00:24:40,920 --> 00:24:41,320 BASELINE. 562 00:24:41,320 --> 00:24:43,840 THE BLUE LINE THOSE THAT HAD 563 00:24:43,840 --> 00:24:46,920 EMPHYSEMA PREDOMINANT DISEASE. 564 00:24:46,920 --> 00:24:50,040 THERE'S A DISTINCT INCREASE IN 565 00:24:50,040 --> 00:24:52,400 MORTALITY BUT KIND OF MILD AND 566 00:24:52,400 --> 00:24:53,480 THEY DEVELOP DISEASE THAT 567 00:24:53,480 --> 00:24:55,480 DOESN'T REALLY PROGRESS. 568 00:24:55,480 --> 00:24:57,200 THE GREEN LINE ARE THOSE WITH 569 00:24:57,200 --> 00:24:58,160 MODERATE AIRWAY DISEASE. 570 00:24:58,160 --> 00:25:00,200 THE NEXT TWO LINES THE RED AND 571 00:25:00,200 --> 00:25:01,800 PURPLE ARE PEOPLE WITH AIRWAY 572 00:25:01,800 --> 00:25:04,000 DISEASE IN RED. 573 00:25:04,000 --> 00:25:07,880 YOU CAN SEE A MARK IN MORTALITY 574 00:25:07,880 --> 00:25:11,600 AND THE PURPLE LINE IS MODERATE 575 00:25:11,600 --> 00:25:13,320 AIRWAY DISEASE PLUS EMPHYSEMA. 576 00:25:13,320 --> 00:25:15,400 THOSE DEVELOP HIGHEST MORTALITY. 577 00:25:15,400 --> 00:25:17,680 THE HIGHEST IS THE YELLOW LINE, 578 00:25:17,680 --> 00:25:23,160 HIGH RISK PEOPLE THAT SHARE HIGH 579 00:25:23,160 --> 00:25:28,640 RISK EMPHYSEMA AND AIRWAY AT 580 00:25:28,640 --> 00:25:33,040 BASELINE. 581 00:25:33,040 --> 00:25:35,400 EMPHYSEMA HIGH MORTALITY AT LATE 582 00:25:35,400 --> 00:25:38,160 STAGE AIRWAY DISEASE AND BY 583 00:25:38,160 --> 00:25:41,800 ITSELF IT'S A HIGH PREDICTOR OF 584 00:25:41,800 --> 00:25:42,360 MORTALITY. 585 00:25:42,360 --> 00:25:46,120 THAT'S TALK ABOUT HOW YOU BECOME 586 00:25:46,120 --> 00:25:48,000 GOLD 3/4. 587 00:25:48,000 --> 00:25:51,160 WE HAD -- WE ARE ABLE TO FIND 588 00:25:51,160 --> 00:25:54,800 157 PEOPLE THAT ARE NEW 589 00:25:54,800 --> 00:25:57,240 INTERESTS OF GOLD 3/4 ABOUT 6% 590 00:25:57,240 --> 00:25:59,080 OF THE POPULATION. 591 00:25:59,080 --> 00:26:01,960 IN BLUE YOU SEE EMPHYSEMA AS A 592 00:26:01,960 --> 00:26:04,400 CLASSIC ONLY ACCOUNTS FOR 14%. 593 00:26:04,400 --> 00:26:06,960 IF YOU ADD THE PURPLE IT'S 594 00:26:06,960 --> 00:26:09,240 ANOTHER 14% AND EMPHYSEMA WITH 595 00:26:09,240 --> 00:26:10,320 AIRWAY DISEASE REMEMBER AT 596 00:26:10,320 --> 00:26:11,520 BASELINE. 597 00:26:11,520 --> 00:26:14,440 THE RED IS HIGH RISK AND BROWN 598 00:26:14,440 --> 00:26:17,840 IS MODERATE AIRWAY RISK. 599 00:26:17,840 --> 00:26:21,800 ABOUT 60% OF OUR SUBJECTS THAT 600 00:26:21,800 --> 00:26:24,960 PROGRESSED SO GOLD 3/4 DON'T 601 00:26:24,960 --> 00:26:26,880 HAVE EMPHYSEMA AT THE BEGINNING 602 00:26:26,880 --> 00:26:28,440 BUT VARIOUS FORMS OF HIGH RISK 603 00:26:28,440 --> 00:26:30,720 OR MODERATE RISK OF AIRWAY 604 00:26:30,720 --> 00:26:30,960 DISEASE. 605 00:26:30,960 --> 00:26:32,680 THIS IS GIVING YOU AN IDEA WHAT 606 00:26:32,680 --> 00:26:35,480 WE CAN LOOK AT AS WE SUBSET AND 607 00:26:35,480 --> 00:26:36,720 FIND THE PATTERNS OF PROGRESSION 608 00:26:36,720 --> 00:26:38,880 AND HOW TO IDENTIFY THE EARLY 609 00:26:38,880 --> 00:26:39,760 ONSET OF DISEASE. 610 00:26:39,760 --> 00:26:49,240 I'LL TURN IT BACK TO ED NOW. 611 00:26:49,240 --> 00:26:52,600 IN 2019 WE DEVELOPED CRITERIA 612 00:26:52,600 --> 00:26:54,720 FOR EXPANDING DIAGNOSE TO BE 613 00:26:54,720 --> 00:26:59,560 COPD RECOGNIZING THE RATIO WAS 614 00:26:59,560 --> 00:27:01,560 INADEQUATE AND HAD EXPOSURE, 615 00:27:01,560 --> 00:27:03,840 SYMPTOMS, IMAGING AND PHYSIOLOGY 616 00:27:03,840 --> 00:27:07,600 INCLUDING A LOW FEV1 WOULD PUT 617 00:27:07,600 --> 00:27:11,760 YOU IN PRISM BELOW THE RATIO AND 618 00:27:11,760 --> 00:27:13,400 WE DON'T TALK ABOUT IMAGING A 619 00:27:13,400 --> 00:27:17,240 LOT IN THE WORKSHOP BUT IT'S A 620 00:27:17,240 --> 00:27:18,760 MAJOR CHARACTERISTIC TO 621 00:27:18,760 --> 00:27:21,000 UNDERSTAND THE SUB TYPES AND 622 00:27:21,000 --> 00:27:21,760 IDENTIFY PATIENTS WITH SEVERE 623 00:27:21,760 --> 00:27:31,880 DISEASE. 624 00:27:32,960 --> 00:27:36,720 >> SOME KEY EARLY FINDINGS 625 00:27:36,720 --> 00:27:38,520 SHOWED INTERSTITIAL LUNG 626 00:27:38,520 --> 00:27:40,960 ABNORMALITIES ASSOCIATED WITH 627 00:27:40,960 --> 00:27:42,200 REDUCED EMPHYSEMA AND LUNG CAST 628 00:27:42,200 --> 00:27:46,720 AND MAY BE PRECURSOR LESIONS TO 629 00:27:46,720 --> 00:27:49,920 PULMONARY FIBROSIS. 630 00:27:49,920 --> 00:27:53,600 AND OTHERS SHOWED AN ELEVATED 631 00:27:53,600 --> 00:27:56,200 PULMONARY RATIO WAS ASSOCIATED 632 00:27:56,200 --> 00:28:00,160 WITH A COPD FREQUENCY. 633 00:28:00,160 --> 00:28:03,120 AND PRISM IS A HETEROGENEOUS 634 00:28:03,120 --> 00:28:05,960 GROUP THAT INCLUDES COPD 635 00:28:05,960 --> 00:28:06,520 SUBJECTS. 636 00:28:06,520 --> 00:28:09,680 IN ADDITION, MANY SMOKERS WITH 637 00:28:09,680 --> 00:28:12,920 SPIROMETRY IN THE NORMAL RANGE 638 00:28:12,920 --> 00:28:17,520 HAD STRUCTURAL IMPAIRMENTS 639 00:28:17,520 --> 00:28:21,840 SHOWING MOST SMOKERS DO NOT 640 00:28:21,840 --> 00:28:26,960 ESCAPE THE NEGATIVE ASSOCIATION 641 00:28:26,960 --> 00:28:29,160 WITH SMOKE AND EMPHYSEMA AT 642 00:28:29,160 --> 00:28:30,280 BASELINE AND MANY SUB TYPING 643 00:28:30,280 --> 00:28:31,440 APPROACHES THAT WERE LOOKED AT 644 00:28:31,440 --> 00:28:33,200 FROM CLUSTER ANALYSIS TO FACTOR 645 00:28:33,200 --> 00:28:38,200 ANALYSIS CONVERGE ON THIS AIRWAY 646 00:28:38,200 --> 00:28:40,440 PREDOMINANT VERSUS US EMPHYSEMA 647 00:28:40,440 --> 00:28:42,200 PREDOMINANT DICHOTOMY AND THERE 648 00:28:42,200 --> 00:28:43,880 WAS A CHARACTERIZATION OF CAUSES 649 00:28:43,880 --> 00:28:46,280 OF DEATH IN COPD FINDING THE 650 00:28:46,280 --> 00:28:48,880 HIGHEST RATE OF LUNG CANCER 651 00:28:48,880 --> 00:28:55,400 DEATHS IN GOLD SPIROMETRY RATES 652 00:28:55,400 --> 00:28:57,560 1-2 AND THOSE IN 3-4. 653 00:28:57,560 --> 00:29:00,240 AND AIRWAY MUCUS PLUGS ARE 654 00:29:00,240 --> 00:29:03,560 ASSOCIATED WITH INCREASED 655 00:29:03,560 --> 00:29:05,160 MORTALITY IN COPD. 656 00:29:05,160 --> 00:29:08,440 WE BUILT A LARGE AND EXPANDING 657 00:29:08,440 --> 00:29:09,680 OMICS DATA RESOURCE IN COPD 658 00:29:09,680 --> 00:29:10,400 GENE. 659 00:29:10,400 --> 00:29:12,840 WE HAVE WHOLE GENOME SEQUENCING 660 00:29:12,840 --> 00:29:15,000 ON ESSENTIALLY THE ENTIRE COHORT 661 00:29:15,000 --> 00:29:16,840 AND STARTED IN EARNEST IN PHASE 662 00:29:16,840 --> 00:29:19,040 2 AND HOPE TO CONTINUE WITH THE 663 00:29:19,040 --> 00:29:26,920 PHASE 3 AND DNA METHYLATION AND 664 00:29:26,920 --> 00:29:29,560 EPIGENETIC MARK AND TOMORROW 665 00:29:29,560 --> 00:29:31,240 YOU'LL HEAR ABOUT THE PROTEOMICS 666 00:29:31,240 --> 00:29:35,560 AND METABOLOMICS IN THE PHASE 2 667 00:29:35,560 --> 00:29:36,680 COPD SAMPLES. 668 00:29:36,680 --> 00:29:39,600 EVEN WITH A RICH OMICS DATA 669 00:29:39,600 --> 00:29:42,120 SOURCE LIKE THIS, IT'S 670 00:29:42,120 --> 00:29:44,320 CHALLENGING TO DISSECT COPD 671 00:29:44,320 --> 00:29:46,240 PATHOGENESIS BECAUSE OF THE 672 00:29:46,240 --> 00:29:49,320 HETEROGENEITY OF THE DISORDER. 673 00:29:49,320 --> 00:29:54,040 IT'S HETEROGENOUS WHERE THEY ARE 674 00:29:54,040 --> 00:29:55,520 EXPOSED TO DIFFERENT 675 00:29:55,520 --> 00:29:56,120 ENVIRONMENTAL EXPOSURES AT 676 00:29:56,120 --> 00:29:57,480 DIFFERENT TIMES. 677 00:29:57,480 --> 00:29:59,120 INFLUENCES IN DEMOGRAPHIC 678 00:29:59,120 --> 00:30:00,920 FACTORS LIKE AGE AND SEX AND THE 679 00:30:00,920 --> 00:30:04,040 IMPACT OF EPIGENETIC MARKS LIKE 680 00:30:04,040 --> 00:30:05,760 DNA METHYLATION AND INTERACTIONS 681 00:30:05,760 --> 00:30:07,280 BETWEEN THE RISK FACTORS. 682 00:30:07,280 --> 00:30:09,000 IN ADDITION THERE'S DISEASE 683 00:30:09,000 --> 00:30:09,360 HETEROGENEITY. 684 00:30:09,360 --> 00:30:13,560 WE TALKED ABOUT THE AIRWAY 685 00:30:13,560 --> 00:30:17,480 VERSUS US EMPHYSEMA DISEASE AND 686 00:30:17,480 --> 00:30:22,160 OTHER CLINICAL OBSERVATIONS LIKE 687 00:30:22,160 --> 00:30:23,480 EXACERBATIONS AND FINDING 688 00:30:23,480 --> 00:30:27,280 SUBTYPES OF PATIENT SHARE A 689 00:30:27,280 --> 00:30:29,680 PATHOPHYSIOLOGICAL MECHANISM FOR 690 00:30:29,680 --> 00:30:33,240 THEIR COPD AND THERE'S 691 00:30:33,240 --> 00:30:34,400 HETEROGENEITY FOR PROGRESSION. 692 00:30:34,400 --> 00:30:36,080 WE MAY CATCH IT AT THE EARLY 693 00:30:36,080 --> 00:30:37,360 STAGE OR END. 694 00:30:37,360 --> 00:30:38,200 INDIVIDUALS CAN HAVE MILD OR 695 00:30:38,200 --> 00:30:44,760 SEARCH -- SEVERE DISEASE AND 696 00:30:44,760 --> 00:30:49,520 TIMES WHERE PEOPLE'S COPD MAY BE 697 00:30:49,520 --> 00:30:52,840 MORE OR LESS ACTIVE THAN OTHERS 698 00:30:52,840 --> 00:30:55,160 BUT IT'S STILL SPECULATIVE AND 699 00:30:55,160 --> 00:30:56,240 THIS IS DONE THROUGH 700 00:30:56,240 --> 00:30:59,560 COLLABORATIVE STUDIES WITH THE 701 00:30:59,560 --> 00:31:00,600 COHORTS WE'LL HEAR FROM TODAY. 702 00:31:00,600 --> 00:31:03,120 USING THE INTERNATIONAL COPD 703 00:31:03,120 --> 00:31:07,760 GENETICS CONSORTIUM AND U.K. BIO 704 00:31:07,760 --> 00:31:10,120 BANK IDENTIFIED 82 REGIONS FOR 705 00:31:10,120 --> 00:31:10,520 COPD. 706 00:31:10,520 --> 00:31:12,480 PARTS OF THE GENOME SOME WORK IN 707 00:31:12,480 --> 00:31:17,800 THAT REGION CONTAINS ONE 708 00:31:17,800 --> 00:31:21,320 SUSCEPTIBILITY FACTOR FOR COPD. 709 00:31:21,320 --> 00:31:26,240 EACH SAY -- IS A SMALL AFFECT 710 00:31:26,240 --> 00:31:27,840 BULTS WITH A RISK SCORE YOU CAN 711 00:31:27,840 --> 00:31:29,520 HAVE REASONABLE PREDICTION OF 712 00:31:29,520 --> 00:31:34,200 RISK ESPECIALLY IN EUROPEAN 713 00:31:34,200 --> 00:31:34,480 PREDICTIONS. 714 00:31:34,480 --> 00:31:37,840 THE PREDICTION WAS LESS OPTIMAL 715 00:31:37,840 --> 00:31:41,720 IN NON-EUROPEAN PREDICTIONS AND 716 00:31:41,720 --> 00:31:43,960 THERE WAS AN ASSOCIATION WITH 717 00:31:43,960 --> 00:31:47,760 MULTIPLE COHORT. 718 00:31:47,760 --> 00:31:52,200 WE'RE USING WHOLE GENOME 719 00:31:52,200 --> 00:31:53,400 SEQUENCING ANALYSIS TO FIND 720 00:31:53,400 --> 00:31:56,280 RELATED PHENOTYPES AND TRYING TO 721 00:31:56,280 --> 00:32:02,040 FIND GENETIC DETERMINATES. 722 00:32:02,040 --> 00:32:04,480 ONCE YOU FIND THEM FROM THE 723 00:32:04,480 --> 00:32:05,520 GENOME WIDE ASSOCIATION STUDIES 724 00:32:05,520 --> 00:32:06,880 IT'S JUST THE BEGINNING. 725 00:32:06,880 --> 00:32:10,200 WE OFTEN LABEL THE REGION OF THE 726 00:32:10,200 --> 00:32:11,760 GENE NAME BUT IT DIDN'T PROVE 727 00:32:11,760 --> 00:32:13,520 IT'S CAUSATIVE IN THAT REGION. 728 00:32:13,520 --> 00:32:14,920 ADDITIONAL WORK NEEDS TO BE 729 00:32:14,920 --> 00:32:15,520 DONE. 730 00:32:15,520 --> 00:32:19,720 THROUGH COLLABORATIVE WORK WITH 731 00:32:19,720 --> 00:32:21,240 SCIENTISTS CAN USE CHROMOSOME 732 00:32:21,240 --> 00:32:22,560 CONFIRMATION CAPTURE TO IDENTIFY 733 00:32:22,560 --> 00:32:26,960 A LONG-RANGE INTERACTION OF UP 734 00:32:26,960 --> 00:32:29,440 STREAM NEAR THE ACTING GENE THAT 735 00:32:29,440 --> 00:32:32,080 CONTAINS A FUNCTIONAL VARIANT. 736 00:32:32,080 --> 00:32:36,200 AND REPORTER ASSAYS TO FIND 737 00:32:36,200 --> 00:32:37,880 FUNCTIONAL VARIANTS AND THERE'S 738 00:32:37,880 --> 00:32:44,440 BEEN MANY MOUSE MODELS FOR COPD 739 00:32:44,440 --> 00:32:45,800 GWAS GENES DONE USING CHRONIC 740 00:32:45,800 --> 00:32:48,240 SMOKE EXPOSURE. 741 00:32:48,240 --> 00:32:50,560 WHAT ARE GENES WE HAVE MOST 742 00:32:50,560 --> 00:32:53,120 CONFIDENCE IN BASED ON THE 743 00:32:53,120 --> 00:32:56,160 FUNCTIONAL CELL-BASED AND ANIMAL 744 00:32:56,160 --> 00:32:56,600 MODELS DONE? 745 00:32:56,600 --> 00:32:58,480 IT DEPENDS WHO YOU TALK TO. 746 00:32:58,480 --> 00:33:01,880 MY OWN LIST OF GENES I HAVE MOST 747 00:33:01,880 --> 00:33:02,960 CONFIDENCE IN ARE THESE THERE 748 00:33:02,960 --> 00:33:05,560 ORDERED IN A SUBJECTIVE WAY 749 00:33:05,560 --> 00:33:07,840 BASED ON THE ONCE I HAVE MOST 750 00:33:07,840 --> 00:33:09,160 CONFIDENCE TO LEAST CONFIDENCE 751 00:33:09,160 --> 00:33:09,360 IN. 752 00:33:09,360 --> 00:33:13,960 THIS IS TOTALLY SUBJECTIVE. 753 00:33:13,960 --> 00:33:24,040 AND THE AGER, PROTEIN D, HIGH 754 00:33:24,040 --> 00:33:28,240 REV 2 AND NPNT AND MMP12 ARE THE 755 00:33:28,240 --> 00:33:30,560 ONES I HAVE THE MOST CONFIDENCE 756 00:33:30,560 --> 00:33:30,720 IN. 757 00:33:30,720 --> 00:33:33,080 YOU WOULD I THINK AGREE MOST OF 758 00:33:33,080 --> 00:33:36,560 THESE GENES DON'T FIT INTO OUR 759 00:33:36,560 --> 00:33:40,880 PRE-GWAS UNDERSTANDING OF COPD 760 00:33:40,880 --> 00:33:44,240 PATHOGENESIS EXCEPT FOR MMP12 761 00:33:44,240 --> 00:33:46,160 AND THEY ARE SMALL IN EFFECT 762 00:33:46,160 --> 00:33:47,320 WISE AND WORK IN NETWORKS TO 763 00:33:47,320 --> 00:33:48,920 INFLUENCE DISEASE RISK. 764 00:33:48,920 --> 00:33:51,920 IN TERMS OF TRANSCRIPTOMICS, KEY 765 00:33:51,920 --> 00:33:53,320 RECENT RESULTS INCLUDE THE 766 00:33:53,320 --> 00:33:55,920 IDENTIFICATION OF THE INTERFERON 767 00:33:55,920 --> 00:33:57,360 AIRWAY DISEASE SIGNATURE THAT 768 00:33:57,360 --> 00:34:01,600 WAS ASSOCIATED WITH PROSPECTIVE 769 00:34:01,600 --> 00:34:03,560 EXACERBATION RISK YOU SEE IN 770 00:34:03,560 --> 00:34:06,200 ADDITION TO ASSOCIATION WITH 771 00:34:06,200 --> 00:34:07,120 EXACERBATION THERE'S AN 772 00:34:07,120 --> 00:34:10,280 ASSOCIATION WITH CHANGE IN FEV1. 773 00:34:10,280 --> 00:34:12,280 THAT ALSO DEVELOPED 774 00:34:12,280 --> 00:34:13,280 TRANSCRIPTOMIC RISK SCORES FOR 775 00:34:13,280 --> 00:34:14,840 COPD THAT GIVE INDEPENDENT 776 00:34:14,840 --> 00:34:19,680 INFORMATION FROM THE POLLEY -- 777 00:34:19,680 --> 00:34:21,920 POLY GENIC RISK SCORE AND GIVE 778 00:34:21,920 --> 00:34:25,480 REASONABLE PREDICTION FOR COPD 779 00:34:25,480 --> 00:34:27,080 AND CURRENTLY WE'RE USING 780 00:34:27,080 --> 00:34:28,160 MACHINE LEARNING APPROACHES TO 781 00:34:28,160 --> 00:34:30,240 IDENTIFY TRANSCRIPTOMICS. 782 00:34:30,240 --> 00:34:31,960 IN TERMS OF PROTEOMICS WE'LL 783 00:34:31,960 --> 00:34:38,280 TALK ABOUT THIS TOMORROW BUT THE 784 00:34:38,280 --> 00:34:40,120 SOMA SCAN 5K PANEL WE'RE TRYING 785 00:34:40,120 --> 00:34:42,560 TO IDENTIFY BIOMARKERS AND 786 00:34:42,560 --> 00:34:44,720 BIOLOGICAL PATHWAYS OF COPD AND 787 00:34:44,720 --> 00:34:45,560 COPD SYMPTOMS. 788 00:34:45,560 --> 00:34:47,760 WE'RE ALSO LOOKING FOR 789 00:34:47,760 --> 00:34:49,440 ASSOCIATIONS OF PROTEOMIC 790 00:34:49,440 --> 00:34:51,520 BIOMARKERS OF PROGRESSION AND 791 00:34:51,520 --> 00:34:58,520 MORTALITY AND TRYING TO DEVELOP 792 00:34:58,520 --> 00:35:01,200 PROTEOMIC RISK SCORES. 793 00:35:01,200 --> 00:35:03,920 TO IDENTIFY THE COPD 794 00:35:03,920 --> 00:35:05,320 PATHOGENESIS WE CAN USE TOP-DOWN 795 00:35:05,320 --> 00:35:09,120 OR BOTTOM-UP APPROACHES. 796 00:35:09,120 --> 00:35:18,160 THE TOP-DOWN IS YOUR PROTEIN AND 797 00:35:18,160 --> 00:35:20,800 PUTTING IT INTO A CORRELATION 798 00:35:20,800 --> 00:35:22,000 NETWORK ANALYSIS MODEL. 799 00:35:22,000 --> 00:35:24,040 GENE REGULATORY NETWORK MODEL 800 00:35:24,040 --> 00:35:25,840 LIKE PANDA FOR PROTEIN 801 00:35:25,840 --> 00:35:30,000 INTERACTION. 802 00:35:30,000 --> 00:35:31,680 WE CAN GO FROM THE BOTTOM-UP AND 803 00:35:31,680 --> 00:35:33,520 FIND THE FUNCTIONAL VARIANTS IN 804 00:35:33,520 --> 00:35:37,600 THE KEY GENES IN THOSE GWAS 805 00:35:37,600 --> 00:35:41,960 REGION AND WHETHER WE'RE GOING 806 00:35:41,960 --> 00:35:43,800 TOP-DOWN OR BOTTOM-UP WE'RE 807 00:35:43,800 --> 00:35:44,840 TRYING TO UNDERSTAND THE 808 00:35:44,840 --> 00:35:48,400 PROTEINS IN NON-CODING REGIONS 809 00:35:48,400 --> 00:35:53,000 AND DEFINE DISEASE PATHOBIOLOGY. 810 00:35:53,000 --> 00:35:56,120 FROM THE BOTTOM-UP WE IDENTIFIED 811 00:35:56,120 --> 00:35:58,600 THE REGION AND THIS IS THE KEY 812 00:35:58,600 --> 00:36:02,160 GENE IN THE GWAS REGION AND THE 813 00:36:02,160 --> 00:36:04,800 CONNECTION. 814 00:36:04,800 --> 00:36:08,120 FROM THE TOP-DOWN WE USED 815 00:36:08,120 --> 00:36:10,840 PROTEIN-PROTEIN CONNECTIONS TO 816 00:36:10,840 --> 00:36:14,240 CONNECT IT TO COPD GWAS GENE 817 00:36:14,240 --> 00:36:15,400 THROUGH AP31. 818 00:36:15,400 --> 00:36:18,200 HOW DO WE KNOW WHEN WE FOUND 819 00:36:18,200 --> 00:36:18,760 SOMETHING IMPORTANT ABOUT 820 00:36:18,760 --> 00:36:20,760 COMPLEX DISEASE PATHOGENESIS 821 00:36:20,760 --> 00:36:24,680 USING THE OMICS DATA TYPES? 822 00:36:24,680 --> 00:36:26,240 IT'S CHALLENGING TO MOVE THE 823 00:36:26,240 --> 00:36:27,480 POPULATION LEVEL OMICS DATA TO 824 00:36:27,480 --> 00:36:31,080 GET INSIGHT TO A COMPLEX DISEASE 825 00:36:31,080 --> 00:36:31,920 LIKE COPD. 826 00:36:31,920 --> 00:36:33,880 THERE'S THINGS WE CAN DO TO 827 00:36:33,880 --> 00:36:35,160 BUILD CONFIDENCE AND BUILD 828 00:36:35,160 --> 00:36:38,360 BIOLOGICAL INSIGHT INTO THE 829 00:36:38,360 --> 00:36:40,280 GENETICS AND OMICS OF COMPLEX 830 00:36:40,280 --> 00:36:40,520 DISEASE. 831 00:36:40,520 --> 00:36:41,960 WE NEED TO REPLICATE FINDINGS IN 832 00:36:41,960 --> 00:36:43,920 OTHER POPULATIONS TO MAKE SURE 833 00:36:43,920 --> 00:36:45,720 THEY'RE REPRODUCIBLE AND REAL. 834 00:36:45,720 --> 00:36:48,720 WE WANT TO LOOK FOR ORTHOGONAL 835 00:36:48,720 --> 00:36:50,360 INFORMATION ON DATA TYPES AND 836 00:36:50,360 --> 00:36:52,680 ANALYTICAL APPROACHES TO ENFORCE 837 00:36:52,680 --> 00:36:54,960 THE CASE THE MOLECULES ARE 838 00:36:54,960 --> 00:36:57,400 IMPORTANT AND FINALLY WE NEED TO 839 00:36:57,400 --> 00:36:59,240 DO FUNCTIONAL VALIDATION IN 840 00:36:59,240 --> 00:37:00,600 CELL-BASED AND ANIMAL MODEL 841 00:37:00,600 --> 00:37:01,680 SYSTEMS THAT IS A KEY THEME OF 842 00:37:01,680 --> 00:37:02,920 THE WORKSHOP. 843 00:37:02,920 --> 00:37:05,280 AS WE THINK ABOUT MAJOR GAPS 844 00:37:05,280 --> 00:37:07,440 BETWEEN THE CLINICAL AND BASIC 845 00:37:07,440 --> 00:37:09,240 SCIENCE RESEARCH IN COPD, WE 846 00:37:09,240 --> 00:37:13,520 THINK WE NEED TO DETERMINE WHICH 847 00:37:13,520 --> 00:37:15,520 POPULATION OMICS ASSOCIATIONS 848 00:37:15,520 --> 00:37:17,920 AND WHICH INVESTIGATION RELEVANT 849 00:37:17,920 --> 00:37:19,720 FOR THE SPECIFIC COMPONENTS OF 850 00:37:19,720 --> 00:37:27,480 THE COPD SYNDROME AND NEED TO 851 00:37:27,480 --> 00:37:30,640 LEVERAGE MULTI-OMICS FOR 852 00:37:30,640 --> 00:37:34,240 RESEARCH AND DEVELOP THROUGHPUT 853 00:37:34,240 --> 00:37:36,320 FUNCTIONAL ASSESSMENTS AND 854 00:37:36,320 --> 00:37:39,960 GENETIC OMICS AND BI-DIRECTIONAL 855 00:37:39,960 --> 00:37:42,080 STUDIES IS CRITICAL AND WHETHER 856 00:37:42,080 --> 00:37:45,000 THE INTEREST IN SINGLE CELL 857 00:37:45,000 --> 00:37:46,440 OMICS COULD BE THE SEE 858 00:37:46,440 --> 00:37:47,320 SCIENTIFIC BRIDGE THAT BRINGS US 859 00:37:47,320 --> 00:37:47,640 ALL TOGETHER. 860 00:37:47,640 --> 00:37:57,960 THANKS VERY MUCH. 861 00:38:02,920 --> 00:38:04,720 >> THANK YOU, DR. SILVERMAN AND 862 00:38:04,720 --> 00:38:05,960 DR. CRAPO. 863 00:38:05,960 --> 00:38:07,560 I DON'T KNOW IF YOU WANT TO 864 00:38:07,560 --> 00:38:09,720 ANSWER THIS ONE QUESTION BECAUSE 865 00:38:09,720 --> 00:38:13,200 WE HAVE A LITTLE OF TIME. 866 00:38:13,200 --> 00:38:18,760 WHAT YOUR THOUGHTS ON WHY AIRWAY 867 00:38:18,760 --> 00:38:20,520 SUB TYPES -- 868 00:38:20,520 --> 00:38:21,000 >> MIGHT AS WELL. 869 00:38:21,000 --> 00:38:22,720 WE STARTED EARLY. 870 00:38:22,720 --> 00:38:27,280 >> COPD IS INFLAMMATION IN MY 871 00:38:27,280 --> 00:38:29,400 OPINION WE CAN SEE IT THE 872 00:38:29,400 --> 00:38:30,760 EMPHYSEMA AND CALLED IT THAT BUT 873 00:38:30,760 --> 00:38:33,600 IN MY OPINION THAT'S A MINOR WAY 874 00:38:33,600 --> 00:38:35,040 OF STARTING AND PROGRESSION BUT 875 00:38:35,040 --> 00:38:38,200 THE BEGINNING IS AIRWAY 876 00:38:38,200 --> 00:38:41,440 INFLAMMATION AND 877 00:38:41,440 --> 00:38:43,720 MICROVASCULATURE INFLAMMATION. 878 00:38:43,720 --> 00:38:45,560 WE DESTROY THE SMALLER AIRWAYS 879 00:38:45,560 --> 00:38:48,960 VERY EARLY AND DON'T EVEN SEE 880 00:38:48,960 --> 00:38:49,120 IT. 881 00:38:49,120 --> 00:38:53,680 ALSO CIGARETTE SMOKE WILL HAVE A 882 00:38:53,680 --> 00:38:55,160 MAJOR SYSTEMIC EFFECT AND A LOT 883 00:38:55,160 --> 00:38:55,960 OF THE DEATHS ARE 884 00:38:55,960 --> 00:38:56,520 CARDIOVASCULAR. 885 00:38:56,520 --> 00:38:58,440 YOU'RE DEALING WITH THE SAME 886 00:38:58,440 --> 00:39:00,880 EVENT OF THE TOXINS OF CIGARETTE 887 00:39:00,880 --> 00:39:04,720 SMOKE IN THE AIRWAYS AND 888 00:39:04,720 --> 00:39:05,920 STIMULATING AN INFLAMMATORY 889 00:39:05,920 --> 00:39:11,560 AFFECT AND THOSE ONE THAT HAVE 890 00:39:11,560 --> 00:39:13,840 THE GREATEST PROGRESS TO PRISM 891 00:39:13,840 --> 00:39:16,240 AND CA GONE TO GOLD 3 AND DIE 892 00:39:16,240 --> 00:39:17,240 AND NEVER DEVELOP EMPHYSEMA OR 893 00:39:17,240 --> 00:39:20,440 DEVELOP IT VERY LATE AND THE 894 00:39:20,440 --> 00:39:21,200 PEOPLE WHO DEVELOP EMPHYSEMA 895 00:39:21,200 --> 00:39:26,280 WITHOUT DEVELOPING AIRWAY 896 00:39:26,280 --> 00:39:28,960 DISEASE WILL CAN STOP AND NOT 897 00:39:28,960 --> 00:39:30,880 HAVE A LOT OF COMPLICATIONS BUT 898 00:39:30,880 --> 00:39:35,400 WHEN THAT PERSON AIRWAY 899 00:39:35,400 --> 00:39:36,960 INFLAMMATION THEY PROGRESS TO 900 00:39:36,960 --> 00:39:37,840 3/4 AND DIE. 901 00:39:37,840 --> 00:39:39,720 THERE'S A FUNDAMENTAL MECHANISM 902 00:39:39,720 --> 00:39:42,400 WE NEED TO ADDRESS AND DEVELOP 903 00:39:42,400 --> 00:39:46,240 THERAPIES FOR. 904 00:39:46,240 --> 00:39:48,760 >> EXCELLENT ANSWER TO A VERY 905 00:39:48,760 --> 00:39:51,040 COMPLEX QUESTION. 906 00:39:51,040 --> 00:39:52,080 WE'LL HAVE A DISCUSSION SECTION 907 00:39:52,080 --> 00:39:53,480 AFTERWARDS FOR ABOUT AN HOUR. 908 00:39:53,480 --> 00:39:58,040 I HOPE TO GAIN MORE KEY INSIGHTS 909 00:39:58,040 --> 00:40:00,720 FROM OUR INVESTIGATORS HERE. 910 00:40:00,720 --> 00:40:04,960 I THINK THE NEXT GROUP WE ARE 911 00:40:04,960 --> 00:40:07,160 GOING TO BE INTRODUCING, THANK 912 00:40:07,160 --> 00:40:09,520 YOU, DR. CRAPO AND SILVERMAN. 913 00:40:09,520 --> 00:40:13,760 IT'S AMAZING ONCE AGAIN TO SEE 914 00:40:13,760 --> 00:40:16,400 THE BREADTH AND DEPTH OF WORK 915 00:40:16,400 --> 00:40:18,160 FROM COPD GENE. 916 00:40:18,160 --> 00:40:20,040 NEXT WE HAVE SPIROMICS AND 917 00:40:20,040 --> 00:40:25,280 SOURCE WHICH IS KIND OF THE 918 00:40:25,280 --> 00:40:35,160 EARLY DISEASE AND MY PLEASURE TO 919 00:40:35,160 --> 00:40:44,920 INTRODUCE DR. MEILENIHAN AND 920 00:40:44,920 --> 00:40:48,200 DR. MARTINEZ FROM UNIVERSITY OF 921 00:40:48,200 --> 00:40:49,040 CORNELL BOTH GREAT FRIENDS OF 922 00:40:49,040 --> 00:40:50,520 MINE I'M INTERESTED TO HEAR 923 00:40:50,520 --> 00:40:57,040 ABOUT SOURCE AND SPIROMICS FROM. 924 00:40:57,040 --> 00:40:58,960 >> IF NIH CAN BRING UP THE 925 00:40:58,960 --> 00:41:01,200 SLIDES. 926 00:41:01,200 --> 00:41:01,920 ACTUALLY, WE WERE HOPING 927 00:41:01,920 --> 00:41:12,440 DR. WOODRUFF WOULD GIVE THE 928 00:41:14,920 --> 00:41:25,200 SPIRO MICS OVERVIEW. 929 00:42:02,720 --> 00:42:04,720 LIKE I SAID I'LL BE PLAYING THE 930 00:42:04,720 --> 00:42:13,360 ROLE OF DR. WOODRUFF AND HAND IT 931 00:42:13,360 --> 00:42:14,920 TO DR. MARTINEZ. 932 00:42:14,920 --> 00:42:17,160 SO SPIROMICS HAS UNDER GONE A 933 00:42:17,160 --> 00:42:19,080 LOT OF CHANGES OVER THE YEARS. 934 00:42:19,080 --> 00:42:26,600 IT WAS ORIGINALLY A CONSORTIA 935 00:42:26,600 --> 00:42:28,280 CONTRACT BETWEEN THE NIH, 936 00:42:28,280 --> 00:42:32,520 FOUNDATION OF THE NIH, FDA AND 937 00:42:32,520 --> 00:42:33,440 INDUSTRY. 938 00:42:33,440 --> 00:42:36,200 THE ORIGINAL GOAL WAS A 939 00:42:36,200 --> 00:42:38,000 THREE-YEAR LONGITUDINAL STUDIES 940 00:42:38,000 --> 00:42:39,840 OF SMOKERS BOTH WITH AND WITHOUT 941 00:42:39,840 --> 00:42:42,040 COPD AND A COHORT OF NEVER 942 00:42:42,040 --> 00:42:44,280 SMOKERS TO IDENTIFY NOVEL 943 00:42:44,280 --> 00:42:46,440 SUBPOPULATIONS OF COPD AND 944 00:42:46,440 --> 00:42:47,520 ULTIMATELY TO DEVELOP BETTER 945 00:42:47,520 --> 00:42:48,640 BIOMARKERS FOR THE DISEASE. 946 00:42:48,640 --> 00:42:53,360 WE ULTIMATELY ENROLLED AROUND 947 00:42:53,360 --> 00:42:55,320 3,000 PARTICIPANTS BETWEEN 2009 948 00:42:55,320 --> 00:43:00,000 AND 2016 AND ENDED UP EXPANDING 949 00:43:00,000 --> 00:43:01,720 TO 12 CLINICAL CENTER. 950 00:43:01,720 --> 00:43:04,040 ONE OF THE WAYS SPIROMICS 951 00:43:04,040 --> 00:43:06,400 DIFFERS FROM COPD GENE IS WITH 952 00:43:06,400 --> 00:43:09,400 RESPECT TO BIOLOGICAL SAMPLE 953 00:43:09,400 --> 00:43:09,680 COLLECTION. 954 00:43:09,680 --> 00:43:15,200 THERE WAS INDUCED SPUTUM AND HAD 955 00:43:15,200 --> 00:43:24,320 BLOOD FROM THE GET GO AND HAD A 956 00:43:24,320 --> 00:43:28,440 BRONCHOSCOPY SUB STUDY WITH 957 00:43:28,440 --> 00:43:28,760 BIOPSIES. 958 00:43:28,760 --> 00:43:34,320 THE SPIROMICS STUDY HAS EXPLODED 959 00:43:34,320 --> 00:43:44,880 AND NOW CONSIDER IT THE SPIROMIC 960 00:43:48,480 --> 00:43:49,720 STUDIES AND SPINOFF INCLUDE THE 961 00:43:49,720 --> 00:43:52,520 RETHINK STUDY WHICH WAS DONE 962 00:43:52,520 --> 00:43:58,600 THROUGH THE NIH PULMONARY TRIALS 963 00:43:58,600 --> 00:43:58,920 CONSORTIUM. 964 00:43:58,920 --> 00:44:02,600 WE IDENTIFIED A SUBSET OF 965 00:44:02,600 --> 00:44:10,800 PATIENTS WITH PRE-COPD WHO WERE 966 00:44:10,800 --> 00:44:11,080 P 967 00:44:11,080 --> 00:44:14,760 PRESYMPTOMATIC AND LOOKED AT IT 968 00:44:14,760 --> 00:44:19,120 WIN A BRONCHO DILATOR AND HAD 969 00:44:19,120 --> 00:44:22,480 THE SPIROMICS HEART FAILURE 970 00:44:22,480 --> 00:44:25,040 STUDY AND DR. BARR WILL BE 971 00:44:25,040 --> 00:44:27,720 SPEAKING LATER ABOUT GETTING 972 00:44:27,720 --> 00:44:30,400 CARDIAC MRIs TO UNDERSTAND 973 00:44:30,400 --> 00:44:34,680 HEART-LUNG INTERACTIONS. 974 00:44:34,680 --> 00:44:38,600 IN SPIROMICS 1 WE LOOKED AT 975 00:44:38,600 --> 00:44:40,400 BASELINE ONE, TWO, AND THREE 976 00:44:40,400 --> 00:44:44,400 YEARS AND CT SCANS THE FIRST TWO 977 00:44:44,400 --> 00:44:46,440 VISITS. 978 00:44:46,440 --> 00:44:48,400 SPUTUM WAS DONE AT THE BASELINE 979 00:44:48,400 --> 00:44:53,120 AND REGULAR PHONE CALLS TO 980 00:44:53,120 --> 00:44:55,520 ASSESS FOR COMORBIDITIES AND 981 00:44:55,520 --> 00:45:00,440 EXACERBATIONS. 982 00:45:00,440 --> 00:45:05,000 WE HAD A BRONCHOSCOPY SUB STUDY 983 00:45:05,000 --> 00:45:07,280 FOCUSSING MORE ON MILDER DISEASE 984 00:45:07,280 --> 00:45:09,400 AND EXACERBATION SUB STUDY WITH 985 00:45:09,400 --> 00:45:12,200 WHERE HE HAD A NUMBER OF 986 00:45:12,200 --> 00:45:13,920 PARTICIPANTS WE BROUGHT IN FOR 987 00:45:13,920 --> 00:45:16,920 ADDITIONAL SAMPLE COLLECTION. 988 00:45:16,920 --> 00:45:24,040 AND THEN IN SPIROMICS 2 FIVE TO 989 00:45:24,040 --> 00:45:25,160 SEVEN YEARS AFTER THE BASELINE 990 00:45:25,160 --> 00:45:25,480 VISIT. 991 00:45:25,480 --> 00:45:28,760 AGAIN WE PERFORMED A SECOND 992 00:45:28,760 --> 00:45:31,000 BRONCHOSCOPY AND HAD A SLIGHTLY 993 00:45:31,000 --> 00:45:33,920 DIFFERENT EXACERBATION. 994 00:45:33,920 --> 00:45:36,280 I WILL SAY BOTH SUB STUDIES WERE 995 00:45:36,280 --> 00:45:38,040 CHALLENGED IN TERMS OF GETTING 996 00:45:38,040 --> 00:45:42,400 PARTICIPANTS IN BUT SPIROMICS 2 997 00:45:42,400 --> 00:45:43,720 DUE TO THE PANDEMIC. 998 00:45:43,720 --> 00:45:45,200 SO THERE ARE A LOT OF THINGS I 999 00:45:45,200 --> 00:45:46,280 COULD HAVE TALKED TO YOU ABOUT 1000 00:45:46,280 --> 00:45:49,000 TODAY THAT WE LEARNED FROM 1001 00:45:49,000 --> 00:45:50,400 SPIROMICS BUT WE HAVE SUCH A 1002 00:45:50,400 --> 00:45:53,160 SHORT AMOUNT OF TIME I DECIDED 1003 00:45:53,160 --> 00:45:57,040 TO STICK WITH ONE SCHEMATIC 1004 00:45:57,040 --> 00:46:00,080 STORY I THINK IS A UNIQUE STORY 1005 00:46:00,080 --> 00:46:01,520 TO TELL HAVING TO DO WITH 1006 00:46:01,520 --> 00:46:08,360 INDIVIDUALS WHO HAVE PRE-COPD. 1007 00:46:08,360 --> 00:46:12,160 IF YOU LOOK AT PATIENT WHO'S ARE 1008 00:46:12,160 --> 00:46:15,720 SYMPTOMATIC DEFINED BY CAT SCORE 1009 00:46:15,720 --> 00:46:17,120 BIGGER THAN 10 EVEN IN THE 1010 00:46:17,120 --> 00:46:19,840 ABSENCE OF AIR FLOW OBSTRUCTION 1011 00:46:19,840 --> 00:46:23,320 HAD INCREASED FREQUENCY OF 1012 00:46:23,320 --> 00:46:25,280 EXACERBATION SIMILAR TO GOLD 1 1013 00:46:25,280 --> 00:46:28,240 AND 2 PATIENTS SYMPTOMATIC 1014 00:46:28,240 --> 00:46:30,400 REGARDLESS OF HOW YOU DEFINE 1015 00:46:30,400 --> 00:46:30,840 EXACERBATIONS. 1016 00:46:30,840 --> 00:46:32,480 SO THAT'S THE GROUP OF PATIENTS 1017 00:46:32,480 --> 00:46:33,480 THAT WE'RE TALKING ABOUT. 1018 00:46:33,480 --> 00:46:35,520 THEY LOOK SIMILAR TO THE FAR 1019 00:46:35,520 --> 00:46:38,080 RIGHT HAND PART OF THE GRAPH AND 1020 00:46:38,080 --> 00:46:40,520 WE KIND OF TOY WITH THE BEST WAY 1021 00:46:40,520 --> 00:46:43,520 TO NAME THESE INDIVIDUALS BUT I 1022 00:46:43,520 --> 00:46:47,560 THINK THIS PAPER WE CALL THEM 1023 00:46:47,560 --> 00:46:48,160 NON-OBSTRUCTIVE CHRONIC AIRWAY 1024 00:46:48,160 --> 00:46:52,200 DISEASE. 1025 00:46:52,200 --> 00:46:54,080 SO ONE OF THE -- TO FOLLOW THE 1026 00:46:54,080 --> 00:46:58,640 THREAT OF THIS STORY, WE HAVE SO 1027 00:46:58,640 --> 00:47:01,440 THE INITIAL PUBLICATION PRESCOTT 1028 00:47:01,440 --> 00:47:02,080 PUBLISHED IN THE NEW ENGLAND 1029 00:47:02,080 --> 00:47:05,880 JOURNAL OF MEDICINE THIS IS A 1030 00:47:05,880 --> 00:47:08,040 FOLLOW-UP PUBLICATION BY UNC 1031 00:47:08,040 --> 00:47:12,840 WHERE IT WAS DEMONSTRATED THAT 1032 00:47:12,840 --> 00:47:14,360 INCREASE IN SCORES WERE 1033 00:47:14,360 --> 00:47:15,520 ASSOCIATED WITH CHARACTERISTICS 1034 00:47:15,520 --> 00:47:17,280 OF COPD. 1035 00:47:17,280 --> 00:47:20,120 IT WAS ASSOCIATED WITH SYMPTOMS 1036 00:47:20,120 --> 00:47:24,520 OF CHRONIC BRONCHITIS. 1037 00:47:24,520 --> 00:47:28,440 AND THIS IS JUST A PICTOGRAM OF 1038 00:47:28,440 --> 00:47:31,520 WHAT WE THINK IS GOING ON WHERE 1039 00:47:31,520 --> 00:47:35,120 IT MAY CONTRIBUTE TO THE 1040 00:47:35,120 --> 00:47:42,240 PATHOGENESIS OF COPD BY LEADING 1041 00:47:42,240 --> 00:47:44,200 TO FOR INSTANCE INCREASED 1042 00:47:44,200 --> 00:47:45,720 BACTERIA AND CELLS. 1043 00:47:45,720 --> 00:47:50,320 WHAT WAS INTERESTING IS WE 1044 00:47:50,320 --> 00:47:57,240 SHOWED MUCIN INCREASES AND IN 1045 00:47:57,240 --> 00:48:04,240 THE SUBSET OF INDIVIDUALS WITH 1046 00:48:04,240 --> 00:48:06,840 NCAD THEY ALSO HAD AN INCREASE 1047 00:48:06,840 --> 00:48:15,560 IN MUCIN SCORE. 1048 00:48:15,560 --> 00:48:18,320 AND THIS FOR ME NAILED THE FACT 1049 00:48:18,320 --> 00:48:20,360 THAT EVEN THESE PATIENTS WITHOUT 1050 00:48:20,360 --> 00:48:22,320 AIR FLOW OBSTRUCTION HAVE THE 1051 00:48:22,320 --> 00:48:26,080 SAME PATHOGENIC PROCESS AS THOSE 1052 00:48:26,080 --> 00:48:27,480 WITH MORE ESTABLISHED AIR FLOW 1053 00:48:27,480 --> 00:48:29,840 OBSTRUCTION AND IT MAY REPRESENT 1054 00:48:29,840 --> 00:48:31,200 A KEY TARGET WHERE WE COULD 1055 00:48:31,200 --> 00:48:41,400 INTERVENE. 1056 00:48:43,240 --> 00:48:46,880 FURTHER DATA SHOWS THE 1057 00:48:46,880 --> 00:48:48,960 CONCENTRATION FROM THE 1058 00:48:48,960 --> 00:48:54,600 CONCENTRATIONS AND SEVERITY. 1059 00:48:54,600 --> 00:48:58,040 THESE ARE ON THE RIGHT-HAND SIDE 1060 00:48:58,040 --> 00:49:03,080 WE LOOKED AT OTHER 1061 00:49:03,080 --> 00:49:07,480 CHARACTERISTICS IN PARTICULAR 1062 00:49:07,480 --> 00:49:12,680 FROM THIS SPUTUM AND SHOWED 1063 00:49:12,680 --> 00:49:14,960 VARIANCES BASED ON DISEASE 1064 00:49:14,960 --> 00:49:15,560 SEVERITY. 1065 00:49:15,560 --> 00:49:18,400 THE NEXT SORT OF FOLLOW-UP ITEM 1066 00:49:18,400 --> 00:49:20,720 LONG THE SAME STORY STILL 1067 00:49:20,720 --> 00:49:24,480 RELATING TO MUCUS IS THE PAPER 1068 00:49:24,480 --> 00:49:26,760 THAT WAS PUBLISHED IN THE BLUE 1069 00:49:26,760 --> 00:49:30,080 JOURNAL IN 2021 THEY SHOWED 1070 00:49:30,080 --> 00:49:34,120 MUCUS AS MANIFESTED BY AIRWAY 1071 00:49:34,120 --> 00:49:36,360 PLUGGING ON CT SCAN WAS ACTUALLY 1072 00:49:36,360 --> 00:49:38,800 NOT NECESSARILY CORRELATED ONE 1073 00:49:38,800 --> 00:49:41,400 TO ONE WITH SYMPTOMS BUT IT WAS 1074 00:49:41,400 --> 00:49:48,240 CORRELATED INDEPENDENTLY WITH 1075 00:49:48,240 --> 00:49:49,000 EXACERBA 1076 00:49:49,000 --> 00:49:49,320 EXACERBATIONS. 1077 00:49:49,320 --> 00:49:50,280 SO INTERESTINGLY AGAIN IN THIS 1078 00:49:50,280 --> 00:49:51,440 PATIENT POPULATION IN GREEN 1079 00:49:51,440 --> 00:49:53,480 WHICH ARE THESE SMOKERS WITH 1080 00:49:53,480 --> 00:49:55,040 PRESERVED LUNG FUNCTION THAT MAY 1081 00:49:55,040 --> 00:50:02,920 HAVE SYMPTOMS, WE DID BEGIN TO 1082 00:50:02,920 --> 00:50:04,440 SEE AN INCREASE IN THE MUCUS 1083 00:50:04,440 --> 00:50:06,640 SCORES AND YOU CAN SEE HOW 1084 00:50:06,640 --> 00:50:07,760 THEY'RE IDENTIFIED. 1085 00:50:07,760 --> 00:50:12,400 THIS JUST KIND OF AGAIN IS 1086 00:50:12,400 --> 00:50:13,400 ANOTHER WAY OF IDENTIFYING 1087 00:50:13,400 --> 00:50:16,560 EXCESS MUCUS IN THE AIRWAYS AND 1088 00:50:16,560 --> 00:50:19,720 THIS DATA AGAIN SUGGESTS IT'S 1089 00:50:19,720 --> 00:50:23,960 PART OF A KEY PATHOLOGIC 1090 00:50:23,960 --> 00:50:25,280 MECHANISM EVEN BEFORE THE 1091 00:50:25,280 --> 00:50:27,720 DEVELOPMENT OF AIRWAY 1092 00:50:27,720 --> 00:50:32,840 OBSTRUCTION. 1093 00:50:32,840 --> 00:50:41,440 THIS JUST HELPS YOU TO SEE WHERE 1094 00:50:41,440 --> 00:50:43,720 I'LL SWITCH IT TO FERNANDO TO 1095 00:50:43,720 --> 00:50:44,560 TALK ABOUT SOURCE. 1096 00:50:44,560 --> 00:50:46,360 >> WE'RE ALL ONE GROUP IN ALL OF 1097 00:50:46,360 --> 00:50:51,360 THIS AS ED SAID ONE THEIR 1098 00:50:51,360 --> 00:50:54,880 ADVANTAGES OF A LOT OF THESE 1099 00:50:54,880 --> 00:50:56,920 EPIDEMIOLOGICAL COHORTS AND 1100 00:50:56,920 --> 00:50:59,320 APOLOGIZE TO MY AUSTRALIAN 1101 00:50:59,320 --> 00:51:00,600 COLLABORATE IT'S A NORTH 1102 00:51:00,600 --> 00:51:03,920 AMERICAN CENTRIC SLIDE AND 1103 00:51:03,920 --> 00:51:05,840 HIGHLIGHTS THE EPIDEMIOLOGICAL 1104 00:51:05,840 --> 00:51:08,560 PROPOSAL OF THE NATURAL HISTORY 1105 00:51:08,560 --> 00:51:11,960 AS PRESENTED BY DR. LAN AND MY 1106 00:51:11,960 --> 00:51:13,520 MENTOR WHO IS A SENIOR AUTHOR OF 1107 00:51:13,520 --> 00:51:15,120 THIS PAPER. 1108 00:51:15,120 --> 00:51:20,360 AND YOU SEE WHERE THE CURRENT 1109 00:51:20,360 --> 00:51:22,960 AGAIN NORTH AMERICAN COHORTS 1110 00:51:22,960 --> 00:51:24,400 WHERE THEY DEFINE AGE RANGES FOR 1111 00:51:24,400 --> 00:51:26,080 INCLUSION. 1112 00:51:26,080 --> 00:51:27,720 AS YOU SEE SOME OF THE DATA FROM 1113 00:51:27,720 --> 00:51:29,600 SOURCE, WHERE WE CURRENTLY 1114 00:51:29,600 --> 00:51:30,240 STAND. 1115 00:51:30,240 --> 00:51:32,360 IF YOU LOOK AT COPD GENE WHICH 1116 00:51:32,360 --> 00:51:35,680 ED AND JAMES HAVE DESCRIBED 1117 00:51:35,680 --> 00:51:38,040 SPIROMICS AS DESCRIBED WE HAVE 1118 00:51:38,040 --> 00:51:41,960 INVESTIGATORS TO FOLLOW. 1119 00:51:41,960 --> 00:51:43,520 THOSE STUDIES WERE GENERALLY IN 1120 00:51:43,520 --> 00:51:45,720 AN OLDER POPULATION WITH MEAN 1121 00:51:45,720 --> 00:51:47,560 AGE IN THE EARLY TO MID 60s. 1122 00:51:47,560 --> 00:51:49,960 TRADITIONAL FOR ANY OF US THAT 1123 00:51:49,960 --> 00:51:50,720 THROUGH THERAPEUTIC TRIALS IN 1124 00:51:50,720 --> 00:51:53,800 COPD THAT'S WHAT WE USUALLY SEE 1125 00:51:53,800 --> 00:51:54,040 IN THOSE. 1126 00:51:54,040 --> 00:51:57,520 SOURCE WAS DESIGNED AS A 1127 00:51:57,520 --> 00:51:59,480 PARALLEL COHORT WHICH WAS 1128 00:51:59,480 --> 00:52:01,720 EMBEDDED WITH SPIROMICS AT THE 1129 00:52:01,720 --> 00:52:04,480 SAME CENTERS USING THE SAME 1130 00:52:04,480 --> 00:52:08,480 APPROACH TO PHENOTYPING AND 1131 00:52:08,480 --> 00:52:09,680 ENDOTYPING THAT MEILAN JUST 1132 00:52:09,680 --> 00:52:11,520 DESCRIBED. 1133 00:52:11,520 --> 00:52:13,360 LEVERAGING THAT LEVEL OF 1134 00:52:13,360 --> 00:52:15,520 EXPERTISE AMONGST SITES IN TERMS 1135 00:52:15,520 --> 00:52:17,360 OF RECRUITMENT AND IN TERMS OF 1136 00:52:17,360 --> 00:52:21,360 THE BIOLOGICAL PROCESSES. 1137 00:52:21,360 --> 00:52:22,800 ALA HEALTH GEORGE WILL DESCRIBE 1138 00:52:22,800 --> 00:52:24,120 FURTHER IS A FURTHER EXTENSION. 1139 00:52:24,120 --> 00:52:28,240 WE WANTED TO ENROLL A POPULATION 1140 00:52:28,240 --> 00:52:29,800 THAT WAS GOING TO BE 1141 00:52:29,800 --> 00:52:32,000 APPROXIMATELY 20 YEARS YOUNGER. 1142 00:52:32,000 --> 00:52:36,680 IT GOES TO SOME COMMENTS IN THE 1143 00:52:36,680 --> 00:52:38,520 CHAT ABOUT THE TIME LINE IN 1144 00:52:38,520 --> 00:52:40,880 DISEASE AND SOURCE IN THAT 1145 00:52:40,880 --> 00:52:41,120 LOCATION. 1146 00:52:41,120 --> 00:52:45,520 THERE'S A SISTER PARALLEL STUDY 1147 00:52:45,520 --> 00:52:49,680 WITH A CO-INVESTIGATOR AND 1148 00:52:49,680 --> 00:52:51,200 MEILAN AND I ARE 1149 00:52:51,200 --> 00:52:52,400 CO-INVESTIGATORS IN THE COHORT. 1150 00:52:52,400 --> 00:52:53,680 WE WERE FOLLOWING IN PART SOME 1151 00:52:53,680 --> 00:52:58,480 OF THE CONCEPTS YOU STATED IN 1152 00:52:58,480 --> 00:53:01,880 THAT TARGET IN THE YOUNGER 1153 00:53:01,880 --> 00:53:03,480 POPULATION THE EARLIEST 1154 00:53:03,480 --> 00:53:06,640 ABNORMALITIES SEEN IN THE SMALL 1155 00:53:06,640 --> 00:53:09,840 AIRWAYS USING METHODOLOGY 1156 00:53:09,840 --> 00:53:11,400 IMAGING AT MICHIGAN MAYBE 15 1157 00:53:11,400 --> 00:53:13,440 YEARS AGO THAT LEVERAGED THE 1158 00:53:13,440 --> 00:53:14,720 EXPERTISE OF THE BROADER 1159 00:53:14,720 --> 00:53:16,160 SPIROMICS GROUP AND THE 1160 00:53:16,160 --> 00:53:17,480 PARTICULARLY THE INVESTIGATORS 1161 00:53:17,480 --> 00:53:21,760 IN UMC WITH MUCUS AND MUCUS 1162 00:53:21,760 --> 00:53:25,960 BIOLOGY MEILAN SHOWED AND WE'RE 1163 00:53:25,960 --> 00:53:27,240 LEVERAGING SPIROMIC DISEASE IN 1164 00:53:27,240 --> 00:53:30,600 POPULATING THE YOUNGER COHORT. 1165 00:53:30,600 --> 00:53:32,920 THE NEXT SLIDE ILLUSTRATES THE 1166 00:53:32,920 --> 00:53:33,840 SPECIFIC AIMS ARE. 1167 00:53:33,840 --> 00:53:35,800 WE SHOW THIS IN PART TO GIVE A 1168 00:53:35,800 --> 00:53:37,840 SENSE OF THE SIDES OF THE COHORT 1169 00:53:37,840 --> 00:53:39,880 AND DATA BEING COLLECTED. 1170 00:53:39,880 --> 00:53:43,920 THE TOTAL COHORT WILL BE 600 AND 1171 00:53:43,920 --> 00:53:45,880 IT WILL UTILIZE A LOT OF THE 1172 00:53:45,880 --> 00:53:48,360 IMAGING EXPERTISE THAT WAS 1173 00:53:48,360 --> 00:53:50,360 INITIALLY DEVELOPED BY COPD GENE 1174 00:53:50,360 --> 00:53:51,560 INVESTIGATORS AND THEN MODIFIED 1175 00:53:51,560 --> 00:53:53,040 AND ADAPTED TO THE SPIROMICS 1176 00:53:53,040 --> 00:53:58,240 INVESTIGATOR GROUP. 1177 00:53:58,240 --> 00:54:01,920 THERE IS A BRONCHO SCOPIC STUDY 1178 00:54:01,920 --> 00:54:05,840 IN SPIROMICS 1 AND 2 THIS IS 1179 00:54:05,840 --> 00:54:08,960 PARALLEL EXTENDING BIOLOGICAL 1180 00:54:08,960 --> 00:54:10,080 SAMPLES TO COLLECTING BIOLOGICAL 1181 00:54:10,080 --> 00:54:11,800 SAMPLES FROM DISTAL AIRWAYS 1182 00:54:11,800 --> 00:54:14,640 USING A METHODOLOGY DEVELOPED 1183 00:54:14,640 --> 00:54:16,840 HERE AT CORNELL AND AGAIN 1184 00:54:16,840 --> 00:54:19,520 LEVERAGED BASELINE AND 1185 00:54:19,520 --> 00:54:21,600 LONGITUDINAL SPUTUM SAMPLES 1186 00:54:21,600 --> 00:54:23,560 USING THE EXPERTISE THAT HAS 1187 00:54:23,560 --> 00:54:26,160 BEEN HIGHLIGHTED BOTH UNC AND 1188 00:54:26,160 --> 00:54:26,360 UCSF. 1189 00:54:26,360 --> 00:54:28,280 THE NEXT SLIDE ILLUSTRATES THE 1190 00:54:28,280 --> 00:54:29,800 GROUPS OF INDIVIDUALS THAT WE 1191 00:54:29,800 --> 00:54:32,160 ARE RECRUITING. 1192 00:54:32,160 --> 00:54:34,160 THEY SPAN FROM GOLD 0 TO GOLD 1 1193 00:54:34,160 --> 00:54:35,400 AND 2. 1194 00:54:35,400 --> 00:54:37,720 REMEMBER, THESE ARE ALL 1195 00:54:37,720 --> 00:54:40,120 INDIVIDUALS YOUNGER IF THEY 1196 00:54:40,120 --> 00:54:42,080 EXHIBIT THE GOLD STAGES 1197 00:54:42,080 --> 00:54:44,080 INCLUDING THE COPD GENE PRISM 1198 00:54:44,080 --> 00:54:45,440 CATEGORY ARE IN PEOPLE 20 YEARS 1199 00:54:45,440 --> 00:54:46,000 YOUNGER. 1200 00:54:46,000 --> 00:54:50,040 THIS IS THE WAY IT'S BEEN 1201 00:54:50,040 --> 00:54:50,440 CONSTRUCTED. 1202 00:54:50,440 --> 00:54:53,840 WE INITIALLY HAD A THRESHOLD FOR 1203 00:54:53,840 --> 00:54:54,840 SYMPTOM REQUIREMENT WITH A CATCH 1204 00:54:54,840 --> 00:54:57,520 AND REMOVED THAT LATER ON TO BE 1205 00:54:57,520 --> 00:54:59,200 ABLE TO PROVIDE ADDITIONAL 1206 00:54:59,200 --> 00:55:00,480 COMPLIMENTARY DATA TO WHAT'S 1207 00:55:00,480 --> 00:55:03,480 BEING RECRUITED IN THE U.K. 1208 00:55:03,480 --> 00:55:05,560 EARLY COPD COHORT SO WE DO NOT 1209 00:55:05,560 --> 00:55:07,840 HAVE A CAT SCORE CRITERIA. 1210 00:55:07,840 --> 00:55:09,560 YOU'LL SEE WHAT THE DATA LOOKED 1211 00:55:09,560 --> 00:55:10,120 LIKE. 1212 00:55:10,120 --> 00:55:12,800 THIS IS A SNAPSHOT AS OF LAST 1213 00:55:12,800 --> 00:55:13,000 WEEK. 1214 00:55:13,000 --> 00:55:14,640 WE ENROLLED 391 PATIENTS AND 1215 00:55:14,640 --> 00:55:17,600 OVER 400 IN THE COHORT. 1216 00:55:17,600 --> 00:55:20,040 DESPITE THE PANDEMIC AND THE 1217 00:55:20,040 --> 00:55:21,240 COVID-19, THE GIFT THAT KEEPS ON 1218 00:55:21,240 --> 00:55:23,760 GIVING, WE'VE BEEN ABLE TO CATCH 1219 00:55:23,760 --> 00:55:25,320 UP IN TERMS OF ENROLLMENT. 1220 00:55:25,320 --> 00:55:26,960 YOU SEE THE DISTRIBUTION OF 1221 00:55:26,960 --> 00:55:29,560 SUBJECTS AS CURRENTLY WE HAVE 1222 00:55:29,560 --> 00:55:29,760 THEM. 1223 00:55:29,760 --> 00:55:30,760 A LITTLE TOO MUCH GOLD 0. 1224 00:55:30,760 --> 00:55:32,640 WE ARE TRYING TO ENHANCE THE 1225 00:55:32,640 --> 00:55:34,520 GOLD 1 AND 2 RIGHT NOW. 1226 00:55:34,520 --> 00:55:39,360 THESE ARE VERY DIFFICULT PATIENT 1227 00:55:39,360 --> 00:55:42,200 TO RECRUIT THE NEXT SLIDE GIVES 1228 00:55:42,200 --> 00:55:44,240 A SENSE WHAT WE WANTED TO 1229 00:55:44,240 --> 00:55:46,720 ACHIEVE PEOPLE IN THEIR MID 40s. 1230 00:55:46,720 --> 00:55:48,400 THESE ARE NOW INDIVIDUALS 20 1231 00:55:48,400 --> 00:55:51,200 YEARS YOUNGER THAN SEEN IN COPD 1232 00:55:51,200 --> 00:55:56,840 GENES SPIROMICS IN CANCOLD AND A 1233 00:55:56,840 --> 00:55:59,880 FAIR AMOUNT OF CIGARETTE 1234 00:55:59,880 --> 00:56:00,280 SMOKING. 1235 00:56:00,280 --> 00:56:03,240 THE COUNT IS ABOUT 11 1/2. 1236 00:56:03,240 --> 00:56:05,960 PEOPLE THAT ARE SYMPTOMATIC AND 1237 00:56:05,960 --> 00:56:07,960 APPROXIMATELY 18% BLACK OR 1238 00:56:07,960 --> 00:56:08,640 AFRICAN AMERICAN INDIVIDUALS. 1239 00:56:08,640 --> 00:56:11,840 THE RECRUITMENT OF THE STUDY WAS 1240 00:56:11,840 --> 00:56:14,360 REALLY ENHANCED IN THE NEXT 1241 00:56:14,360 --> 00:56:17,480 SLIDE THROUGH SOMETHING I WAS 1242 00:56:17,480 --> 00:56:22,040 NAIVE TO WHICH WAS SOCIAL MEDIA, 1243 00:56:22,040 --> 00:56:25,000 I LEVERAGED THE EXPERTISE OF 1244 00:56:25,000 --> 00:56:26,560 MEILAN WHICH IS MORE MEDIA 1245 00:56:26,560 --> 00:56:29,040 FRIENDLY AND WE PARTNERED WITH A 1246 00:56:29,040 --> 00:56:31,360 CANADIAN COMPANY BUMP, WHICH SAY 1247 00:56:31,360 --> 00:56:33,280 DIGITAL MARKETING COMPANY THAT 1248 00:56:33,280 --> 00:56:37,120 HAS PRIOR EXPERTISE IN ENROLLING 1249 00:56:37,120 --> 00:56:37,720 SMOKING-RELATED STUDIES. 1250 00:56:37,720 --> 00:56:43,000 THEY CREATED A WEB-BASED 1251 00:56:43,000 --> 00:56:44,320 PLATFORM PRINCIPALLY THROUGH 1252 00:56:44,320 --> 00:56:46,400 FACEBOOK THAT HAS ALLOWED US TO 1253 00:56:46,400 --> 00:56:49,040 REACH AROUND 30,000 INDIVIDUALS. 1254 00:56:49,040 --> 00:56:51,040 40% OF THOSE PROCEEDED TO A 1255 00:56:51,040 --> 00:56:52,920 PHONE SCREENING. 1256 00:56:52,920 --> 00:56:54,200 THERE'S A WHOLE ALGORITHM USED 1257 00:56:54,200 --> 00:56:56,680 AND MODIFIED IN THE LAST YEAR TO 1258 00:56:56,680 --> 00:56:58,280 BETTER TARGET THIS POPULATION. 1259 00:56:58,280 --> 00:57:00,400 ABOUT A FIFTH OF THOSE 1260 00:57:00,400 --> 00:57:03,040 INDIVIDUALS ARE THEN ASKED TO 1261 00:57:03,040 --> 00:57:03,240 CONSENT. 1262 00:57:03,240 --> 00:57:05,520 ABOUT 20% OF THOSE HAVE AGREED 1263 00:57:05,520 --> 00:57:07,600 TO AND YOU CAN SEE THE BOTTOM 1264 00:57:07,600 --> 00:57:10,000 NUMBER OF INDIVIDUALS THAT HAVE 1265 00:57:10,000 --> 00:57:13,360 BEEN ENROLLED AS OF LAST WEEK 1266 00:57:13,360 --> 00:57:15,320 THE TOTAL AMOUNT OF INVESTMENT 1267 00:57:15,320 --> 00:57:17,120 IS ABOUT 400 YOUNGER INDIVIDUALS 1268 00:57:17,120 --> 00:57:19,680 AS HIGHLIGHTED IN PRIOR SLIDES 1269 00:57:19,680 --> 00:57:21,480 IS $240 PER ENROLLED SUBJECT. 1270 00:57:21,480 --> 00:57:24,280 IT'S AN INTERESTING APPROACH TO 1271 00:57:24,280 --> 00:57:26,440 TRY TO ENROLL A UNIQUE 1272 00:57:26,440 --> 00:57:28,000 POPULATION OF INDIVIDUALS THAT 1273 00:57:28,000 --> 00:57:30,800 ARE WORKING ADULTS TO COME IN 1274 00:57:30,800 --> 00:57:36,680 AND SPEND AN ENTIRE DAY DURING A 1275 00:57:36,680 --> 00:57:38,880 VERY DETAILED ASSESSMENT. 1276 00:57:38,880 --> 00:57:44,960 WITH BOTH CLINICAL IMAGING AND 1277 00:57:44,960 --> 00:57:45,640 BIOLOGICAL SAMPLE COLLECTION AND 1278 00:57:45,640 --> 00:57:49,720 BEFORE I TURN IT OVER TO JEFF 1279 00:57:49,720 --> 00:57:53,520 CURTIS, THE BOTTOM FIGURE IS AN 1280 00:57:53,520 --> 00:57:54,680 ADVANTAGE WE'VE SEEN WITH THIS 1281 00:57:54,680 --> 00:57:56,760 TYPE OF SOCIAL MEDIA APPROACH. 1282 00:57:56,760 --> 00:57:58,520 THE AMOUNT OF FLEXIBILITY IT 1283 00:57:58,520 --> 00:58:01,680 ALLOWS YOU IN BEING ABLE TO 1284 00:58:01,680 --> 00:58:03,200 TARGET SPECIFIC INDIVIDUAL TYPES 1285 00:58:03,200 --> 00:58:05,680 WITHIN EACH OF THE REGIONS 1286 00:58:05,680 --> 00:58:08,920 ACROSS THE SITES BY TAILORING 1287 00:58:08,920 --> 00:58:09,960 THE ADS AND DISTANCE FROM THE 1288 00:58:09,960 --> 00:58:12,680 SITE TO BE ABLE TO ENHANCE THE 1289 00:58:12,680 --> 00:58:14,240 INDIVIDUALS COMING IN HAS BEEN 1290 00:58:14,240 --> 00:58:15,880 VERY INTERESTING TO SEE HOW 1291 00:58:15,880 --> 00:58:19,360 GRANULAR WE CAN GET FROM WEEK TO 1292 00:58:19,360 --> 00:58:21,320 WEEK IN TRYING TO TWEAK THE 1293 00:58:21,320 --> 00:58:22,760 SOCIAL MEDIA APPROACH TO ENROLL. 1294 00:58:22,760 --> 00:58:24,920 THIS APPROACH DOES WORK. 1295 00:58:24,920 --> 00:58:29,320 WE'RE ON SCHEDULE TO ENROLL OUR 1296 00:58:29,320 --> 00:58:31,920 600 SUBJECTS BY THE FOURTH 1297 00:58:31,920 --> 00:58:33,600 QUARTER OF THE YEAR A YEAR 1298 00:58:33,600 --> 00:58:34,960 DELAYED GIVEN THE PANDEMIC WHAT 1299 00:58:34,960 --> 00:58:36,320 WAS ORIGINALLY PLANNED. 1300 00:58:36,320 --> 00:58:38,400 AS ED MENTIONED, A KEY COMPONENT 1301 00:58:38,400 --> 00:58:40,680 I'D LOVE TO SEE COME OUT OF THIS 1302 00:58:40,680 --> 00:58:43,720 ENDEAVOR IS CLOSER INTERACTION 1303 00:58:43,720 --> 00:58:46,080 BETWEEN SOME OF US MORE CLINICAL 1304 00:58:46,080 --> 00:58:46,840 EPIDEMIOLOGICAL INVESTIGATORS 1305 00:58:46,840 --> 00:58:49,080 AND SOME OF ON THE CALL OF 1306 00:58:49,080 --> 00:58:50,240 PARTICIPANTS MUCH MORE AND 1307 00:58:50,240 --> 00:58:53,000 BETTER UNDERSTANDING OF THE 1308 00:58:53,000 --> 00:58:54,520 BIOLOGICAL MECHANISMS AND THE 1309 00:58:54,520 --> 00:58:55,440 TECHNOLOGIES AVAILABLE TO ABLE 1310 00:58:55,440 --> 00:58:57,040 TO ENHANCE THAT. 1311 00:58:57,040 --> 00:58:58,800 I SHOWED YOU ONE EXAMPLE OF HOW 1312 00:58:58,800 --> 00:59:01,600 THIS CAN TAKE PLACE IN THE NEXT 1313 00:59:01,600 --> 00:59:01,800 SLIDE. 1314 00:59:01,800 --> 00:59:06,280 THIS SANE RO1 FUNDED TWO WEEKS 1315 00:59:06,280 --> 00:59:09,200 AGO WHICH IS RUN BY RON CRYSTAL 1316 00:59:09,200 --> 00:59:16,320 AND RON KANER AND LEVERAGING THE 1317 00:59:16,320 --> 00:59:19,040 COHORT DESIGN FOR THIS 1318 00:59:19,040 --> 00:59:19,880 PARTICULAR EARLIER AGE 1319 00:59:19,880 --> 00:59:23,080 INDIVIDUALS AND ARE USING VERY 1320 00:59:23,080 --> 00:59:26,040 ADVANCED METHODOLOGY TO IDENTIFY 1321 00:59:26,040 --> 00:59:29,320 SMALL AIRWAYS FROM DISTAL SMALL 1322 00:59:29,320 --> 00:59:33,280 AIRWAY SAMPLING, BASAL CELLS AND 1323 00:59:33,280 --> 00:59:35,040 AIR LIQUID INTERFACE AND THE 1324 00:59:35,040 --> 00:59:36,320 FUNCTIONAL CHARACTERISTICS OF 1325 00:59:36,320 --> 00:59:39,200 THOSE CELLS AS THEY RELATE TO 1326 00:59:39,200 --> 00:59:41,800 THE DETAILED CLINICAL 1327 00:59:41,800 --> 00:59:42,760 PHENOTYPING DATA COLLECTED 1328 00:59:42,760 --> 00:59:46,080 WITHIN THE BROADER SPIROMICS 1329 00:59:46,080 --> 00:59:50,080 CHARACTERIZATION AS ADAPTED FOR 1330 00:59:50,080 --> 00:59:50,400 SOURCE -- 1331 00:59:50,400 --> 00:59:52,040 >> TWO-MINUTE WARNING. 1332 00:59:52,040 --> 00:59:53,720 >> THIS IS MY LAST SLIDE AND 1333 00:59:53,720 --> 00:59:59,280 THEN I'LL TURN IT OVER TO JEFF 1334 00:59:59,280 --> 01:00:00,320 CURTIS. 1335 01:00:00,320 --> 01:00:03,040 THIS IS HOW WE'D LIKE FOLKS TO 1336 01:00:03,040 --> 01:00:04,640 INTERACT IN THE FASHION WE 1337 01:00:04,640 --> 01:00:04,920 DESCRIBED. 1338 01:00:04,920 --> 01:00:06,480 ED, OVER TO YOU. 1339 01:00:06,480 --> 01:00:07,760 >> THANK YOU. 1340 01:00:07,760 --> 01:00:10,640 AS YOU SEE, WE'VE GOT A VERY 1341 01:00:10,640 --> 01:00:12,520 BROAD RANGE OF SKILLS AMONG THE 1342 01:00:12,520 --> 01:00:14,000 INVESTIGATORS IN THIS SPIROMICS 1343 01:00:14,000 --> 01:00:16,480 FAMILY OF STUDIES WE ONLY SHOWED 1344 01:00:16,480 --> 01:00:20,000 A TINY PART. 1345 01:00:20,000 --> 01:00:21,560 PARTICULARLY SHORT CHANGE AND 1346 01:00:21,560 --> 01:00:22,560 VASCULAR CHANGES. 1347 01:00:22,560 --> 01:00:23,680 IN THE LAST TWO SLIDES WE TAKE 1348 01:00:23,680 --> 01:00:26,280 THE CHARGE TO SAY WHAT WE THINK 1349 01:00:26,280 --> 01:00:29,040 IS THE STATE OF THE SCIENCE IN 1350 01:00:29,040 --> 01:00:31,200 COPD AND THEN THE KNOWLEDGE 1351 01:00:31,200 --> 01:00:31,880 GAPS. 1352 01:00:31,880 --> 01:00:34,920 SO WE BELIEVE WE'VE SHOWN 1353 01:00:34,920 --> 01:00:36,600 CONVINCINGLY AS MEILAN SHOWED 1354 01:00:36,600 --> 01:00:39,560 MANY SMOKERS HAVE SIGNIFICANT 1355 01:00:39,560 --> 01:00:42,360 PULMONARY SYMPTOMS WITHOUT 1356 01:00:42,360 --> 01:00:43,840 AIRWAY OBSTRUCTION AND HOPEFULLY 1357 01:00:43,840 --> 01:00:46,800 IN DATA WE'LL SHOW IT'S 1358 01:00:46,800 --> 01:00:48,360 PERSISTENT OVER A MEAN OF SEVEN 1359 01:00:48,360 --> 01:00:48,560 YEARS. 1360 01:00:48,560 --> 01:00:50,360 SOME OF THOSE SMOKERS 1361 01:00:50,360 --> 01:00:52,400 INDEPENDENT OF AIR FLOW 1362 01:00:52,400 --> 01:00:53,520 OBSTRUCTION MATCHING WHAT 1363 01:00:53,520 --> 01:00:56,680 DR. CRAPO SAID EARLIER WE'RE 1364 01:00:56,680 --> 01:00:59,080 SHOWING DISPLAY REVERSIBLE 1365 01:00:59,080 --> 01:01:01,040 BIOLOGY WE THINK RELATE TO 1366 01:01:01,040 --> 01:01:02,880 PATHOLOGICAL MUCUS AND COULD BE 1367 01:01:02,880 --> 01:01:05,000 A HUGE FOCUS FOR POTENTIAL NEW 1368 01:01:05,000 --> 01:01:05,640 THERAPEUTICS. 1369 01:01:05,640 --> 01:01:09,640 BY INCORPORATING BIO SPECIMEN 1370 01:01:09,640 --> 01:01:11,760 COLLECTION COHORT STUDIES CAN 1371 01:01:11,760 --> 01:01:14,760 BRIDGE THE GAP IN UNDERSTANDING 1372 01:01:14,760 --> 01:01:17,320 BETWEEN HISTOPATHOLOGICAL 1373 01:01:17,320 --> 01:01:22,800 STUDIES RELINING ON SURGICAL OR 1374 01:01:22,800 --> 01:01:24,080 AUTOPSY SPECIMENS AND THE 1375 01:01:24,080 --> 01:01:24,840 MESSAGE TO THE LUNG DIVISION TO 1376 01:01:24,840 --> 01:01:28,520 KEEP FUNDING THE COHORTS. 1377 01:01:28,520 --> 01:01:29,920 FOR THE FINAL SLIDE THE MAJOR 1378 01:01:29,920 --> 01:01:31,760 GAPS WE IDENTIFIED ARE TO DEFINE 1379 01:01:31,760 --> 01:01:34,040 THE PATHOLOGICAL PROCESSES IN 1380 01:01:34,040 --> 01:01:36,080 THE HUMAN LUNG SO WE CAN DEVELOP 1381 01:01:36,080 --> 01:01:39,920 ANIMAL MODELS AND DO THAT ACROSS 1382 01:01:39,920 --> 01:01:41,920 THE TIME FRAME OF COPD 1383 01:01:41,920 --> 01:01:42,200 DEVELOPMENT. 1384 01:01:42,200 --> 01:01:47,000 WE'RE TRYING TO DO THAT WITH 1385 01:01:47,000 --> 01:01:52,960 BRONCHOSCOPY AND THROUGH INDUCED 1386 01:01:52,960 --> 01:01:56,000 SPUTUM AND SAMPLES TO CORRELATE 1387 01:01:56,000 --> 01:01:56,200 THEM. 1388 01:01:56,200 --> 01:01:58,640 WE HOPE TO RELATE THE IMAGING 1389 01:01:58,640 --> 01:02:01,640 STUDIES WITH THE MICROBIOME AND 1390 01:02:01,640 --> 01:02:03,240 MULTI-OMICS OF PARTICULARLY LUNG 1391 01:02:03,240 --> 01:02:05,040 TISSUE BUT OTHER SAMPLES. 1392 01:02:05,040 --> 01:02:06,560 WE THINK IT'S IMPORTANT TO 1393 01:02:06,560 --> 01:02:07,800 DISTINGUISH THE RELATIVE 1394 01:02:07,800 --> 01:02:10,200 IMPORTANCE OF SMALL AIRWAY 1395 01:02:10,200 --> 01:02:15,040 ABNORMALITY VERSUS THE VASCULAR 1396 01:02:15,040 --> 01:02:15,360 PROCESS. 1397 01:02:15,360 --> 01:02:20,920 YOU CAN SEE WE'RE VERY FOCUSSED 1398 01:02:20,920 --> 01:02:26,640 ON CONSIDERING AGE AND START 1399 01:02:26,640 --> 01:02:28,520 PROVIDING MECHANISTIC EXEMPTION 1400 01:02:28,520 --> 01:02:29,600 EARLIER IN THE LIFE SPAN AND 1401 01:02:29,600 --> 01:02:31,320 EXCITED TO PARTNER WITH THE 1402 01:02:31,320 --> 01:02:34,320 YOUNGER COHORTS SUCH AS THE 1403 01:02:34,320 --> 01:02:35,360 AMERICAN LUNG ASSOCIATION HEALTH 1404 01:02:35,360 --> 01:02:37,840 STUDY AND WE THINK IT'S 1405 01:02:37,840 --> 01:02:39,280 IMPORTANT TO EXAMINE THE 1406 01:02:39,280 --> 01:02:39,960 ENVIRONMENTAL EXPOSURES OTHER 1407 01:02:39,960 --> 01:02:41,920 THAN SMOKING WHICH TURN OUT TO 1408 01:02:41,920 --> 01:02:44,400 BE INTIMATELY TIED TO ISSUES OF 1409 01:02:44,400 --> 01:02:44,840 HEALTH DISPARITIES. 1410 01:02:44,840 --> 01:02:53,400 THANK YOU. 1411 01:02:53,400 --> 01:02:56,000 >> THANK YOU, HAN, MARTINEZ AND 1412 01:02:56,000 --> 01:02:58,040 CURTIS ALSO MODERATING. 1413 01:02:58,040 --> 01:03:02,400 LET'S KEEP IT MOVING ALONG. 1414 01:03:02,400 --> 01:03:04,200 AGAIN, IT'S WE'RE WELL AWARE OF 1415 01:03:04,200 --> 01:03:07,840 WHAT SPIROMICS AND SOURCE DO BUT 1416 01:03:07,840 --> 01:03:09,040 GREAT TO SEE IT COME TOGETHER. 1417 01:03:09,040 --> 01:03:11,400 DR. CURTIS, DID YOU WANT TO 1418 01:03:11,400 --> 01:03:13,640 INTRODUCE OUR NEXT GROUP? 1419 01:03:13,640 --> 01:03:14,640 >> I SHOULD IF I HAD THE AGENDA 1420 01:03:14,640 --> 01:03:18,480 UP. 1421 01:03:18,480 --> 01:03:19,640 >> I CAN DO IT. 1422 01:03:19,640 --> 01:03:21,920 >> PLEASE. 1423 01:03:21,920 --> 01:03:26,800 >> THIS IS ANOTHER ONE OF OUR 1424 01:03:26,800 --> 01:03:28,920 COLLEAGUES DR. GRAHAM BARR WHO 1425 01:03:28,920 --> 01:03:30,760 IS GOING TO BE GIVING US AN 1426 01:03:30,760 --> 01:03:36,840 INTRO TO THE MESA LUNG STUDY. 1427 01:03:36,840 --> 01:03:38,480 GRAHAM. 1428 01:03:38,480 --> 01:03:39,800 >> THANK YOU SO MUCH. 1429 01:03:39,800 --> 01:03:41,240 TERRIFIC TALK TO THE EARLIER 1430 01:03:41,240 --> 01:03:42,760 COLLEAGUES. 1431 01:03:42,760 --> 01:03:46,240 SO IT'S MY PLEASURE TO SPEAK ON 1432 01:03:46,240 --> 01:03:46,920 FINDINGS CHALLENGE AND 1433 01:03:46,920 --> 01:03:50,480 OPPORTUNITIES IN THE MESA LUNG 1434 01:03:50,480 --> 01:03:50,880 STUDY. 1435 01:03:50,880 --> 01:03:53,960 I THINK IT'S A FANTASTIC 1436 01:03:53,960 --> 01:03:56,560 SYMPOSIUM I WANT TO QUOTE A LONG 1437 01:03:56,560 --> 01:04:02,320 STANDING CHAIR OF MESA WHO WOULD 1438 01:04:02,320 --> 01:04:03,600 DESCRIBE IT AS A POPULATION 1439 01:04:03,600 --> 01:04:03,920 LABORATORY. 1440 01:04:03,920 --> 01:04:05,240 IT'S A PHENOTYPED GROUP OF 1441 01:04:05,240 --> 01:04:06,400 PEOPLE WE'VE BEEN FOLLOWING FOR 1442 01:04:06,400 --> 01:04:10,200 A VERY LONG TIME NOW. 1443 01:04:10,200 --> 01:04:12,560 WHO HAVE INCREASE LEVEL OF 1444 01:04:12,560 --> 01:04:13,560 GENOTYPING AND ENVIRONMENTAL 1445 01:04:13,560 --> 01:04:15,400 CHARACTERIZATION AND ALLOWS US 1446 01:04:15,400 --> 01:04:17,120 TO ANSWER QUESTIONS PARTICULARLY 1447 01:04:17,120 --> 01:04:21,880 RELATED TO IMAGING PHENOTYPES. 1448 01:04:21,880 --> 01:04:23,760 THIS IS AN UNSELECTED SAMPLE OF 1449 01:04:23,760 --> 01:04:24,880 THE POPULATION THAT CAN 1450 01:04:24,880 --> 01:04:34,800 HOPEFULLY MOVE US FORWARD. 1451 01:04:34,800 --> 01:04:39,440 I'LL GIVE A QUICK OVERVIEW AND 1452 01:04:39,440 --> 01:04:42,600 FINDINGS RELATED TO PULL 1453 01:04:42,600 --> 01:04:49,480 MONETARY VASCULATURE WE FOCUSSED 1454 01:04:49,480 --> 01:04:52,480 ON. 1455 01:04:52,480 --> 01:04:58,960 DYSANAPSIS AND MESA LUNG IS A 1456 01:04:58,960 --> 01:05:06,560 POPULATION-BASED COHORT AND COPD 1457 01:05:06,560 --> 01:05:09,440 AND OTHER RELATED PHENOTYPES AND 1458 01:05:09,440 --> 01:05:11,400 TALK ABOUT RESEARCH GAPS AND 1459 01:05:11,400 --> 01:05:17,080 OPPORTUNITIES IN MESA LUNG WHICH 1460 01:05:17,080 --> 01:05:26,480 IS MULTIETHNIC AND MULTIOMIC AND 1461 01:05:26,480 --> 01:05:32,600 ANALYSIS FOR OTHER SYMPTOMS. 1462 01:05:32,600 --> 01:05:37,720 MESA MULTIETHNIC STUDIES OF 1463 01:05:37,720 --> 01:05:39,320 ATHEROSCLEROSIS IS A COHORT 1464 01:05:39,320 --> 01:05:41,400 ORIGINALLY FUNDED AS MY KIDS 1465 01:05:41,400 --> 01:05:44,040 WOULD SAY IN THE 1900s. 1466 01:05:44,040 --> 01:05:46,920 THE INITIAL EXAMINE WAS IN 2000 1467 01:05:46,920 --> 01:05:48,200 THROUGH 2002. 1468 01:05:48,200 --> 01:05:58,840 THERE WERE FOLLOW-UP EXAMINES 1469 01:06:08,320 --> 01:06:10,080 AND THERE WERE PARTICIPANTS 1470 01:06:10,080 --> 01:06:15,200 RECRUITED AT SIX SITES. 1471 01:06:15,200 --> 01:06:19,040 MEANING BACK IN THE DAY AND 1472 01:06:19,040 --> 01:06:19,720 NEIGHBORHOODS AROUND THE MAIN 1473 01:06:19,720 --> 01:06:23,000 SITES IN A TARGETED WAY AND WE 1474 01:06:23,000 --> 01:06:25,520 WERE EXPLICITLY NOT RECRUITING 1475 01:06:25,520 --> 01:06:27,440 PATIENTS WITH DISEASE OR 1476 01:06:27,440 --> 01:06:29,480 PATIENTS COMING INTO MEDICAL 1477 01:06:29,480 --> 01:06:29,840 CENTER. 1478 01:06:29,840 --> 01:06:31,640 IT'S A POPULATION-BASED DESIGN 1479 01:06:31,640 --> 01:06:33,560 WHICH LETS US LOOK AT WHAT'S 1480 01:06:33,560 --> 01:06:34,680 GOING ON IN THE GENERAL 1481 01:06:34,680 --> 01:06:36,480 POPULATION AND IS A LITTLE BIT 1482 01:06:36,480 --> 01:06:37,960 EASIER TO INFERENCE FOR THESE 1483 01:06:37,960 --> 01:06:42,520 REASONS. 1484 01:06:42,520 --> 01:06:53,200 MESA RECRUIT ED AND LOOK AT 1485 01:07:01,760 --> 01:07:02,320 MEASURES OF CARDIOVASCULAR 1486 01:07:02,320 --> 01:07:07,400 DISEASE AND WHETHER THEY PREDICT 1487 01:07:07,400 --> 01:07:10,080 CLINICAL CARDIOVASCULAR DISEASE 1488 01:07:10,080 --> 01:07:13,240 AND THE IMPORTANT ONES WAS 1489 01:07:13,240 --> 01:07:15,920 PULMONARY CALCIUM THE WHITE 1490 01:07:15,920 --> 01:07:19,400 STUFF WITH THE ARROWS WHICH IS 1491 01:07:19,400 --> 01:07:22,360 HARD CALCIFIED PLAQUE IN THE 1492 01:07:22,360 --> 01:07:22,760 ARTERIES. 1493 01:07:22,760 --> 01:07:25,160 THE ADVANTAGES WE TOOK ADVANTAGE 1494 01:07:25,160 --> 01:07:30,000 OF THE LUNGS SHOWN ON THE CTs. 1495 01:07:30,000 --> 01:07:31,400 WE ARE FORTUNATE ENOUGH TO AT 1496 01:07:31,400 --> 01:07:36,880 THE MESA LUNG STUDY FUNDED BACK 1497 01:07:36,880 --> 01:07:41,640 IN 2014, 2004, EXCUSE ME WHEN WE 1498 01:07:41,640 --> 01:07:50,880 ORIGINAL MEASURED SPIROMETRY 1499 01:07:50,880 --> 01:07:53,560 EXAMINE IN THE FOURTH MESA 1500 01:07:53,560 --> 01:07:58,720 EXAMINE AND TOOK THE CT SCANS 1501 01:07:58,720 --> 01:08:06,800 FOR CALCIUM AND THIS IS 1502 01:08:06,800 --> 01:08:08,960 RECONSTRUCTION IF 2000 AND GET 1503 01:08:08,960 --> 01:08:14,240 LUNG MEASURES AND VALIDATED 1504 01:08:14,240 --> 01:08:17,840 THESE PREVIOUSLY. 1505 01:08:17,840 --> 01:08:20,720 AND WE CO-REGISTERED THE IMAGES 1506 01:08:20,720 --> 01:08:22,960 AND SEE THE LUNG PROGRESSION AT 1507 01:08:22,960 --> 01:08:24,800 A REGIONAL LEVEL. 1508 01:08:24,800 --> 01:08:28,320 IN 2017, 2018, GIVE CONTRAST TO 1509 01:08:28,320 --> 01:08:32,560 ABOUT 750 PEOPLE TO MEASURE 1510 01:08:32,560 --> 01:08:37,560 PULMONARY BLOOD VOLUME AND 1511 01:08:37,560 --> 01:08:38,160 MICROVASCULATURE ENERGY AND 1512 01:08:38,160 --> 01:08:41,040 WE'RE CURRENTLY REPEATING THE 1513 01:08:41,040 --> 01:08:45,320 FULL LUNG CTs AS REQUIRED A FEW 1514 01:08:45,320 --> 01:08:47,760 YEARS AGO IN THE CURRENT 1515 01:08:47,760 --> 01:08:48,360 EXAMINE. 1516 01:08:48,360 --> 01:08:52,320 IT GIVES FOUR MEASURES OF 1517 01:08:52,320 --> 01:08:58,120 SPIROMETRY OVER 17 YEARS AND SIX 1518 01:08:58,120 --> 01:08:59,920 MEASURES OF CT IN EMPHYSEMA 1519 01:08:59,920 --> 01:09:04,520 RELATED MEASURES OVER 22 YEARS. 1520 01:09:04,520 --> 01:09:06,400 MESA HAS A LOT OF CARDIOVASCULAR 1521 01:09:06,400 --> 01:09:08,240 PHENOTYPING AS A CARDIOVASCULAR 1522 01:09:08,240 --> 01:09:08,480 COHORT. 1523 01:09:08,480 --> 01:09:11,400 AND WE'VE TAKEN ADVANTAGE OF 1524 01:09:11,400 --> 01:09:17,480 THAT TO LOOK AT CARDIO PULMONARY 1525 01:09:17,480 --> 01:09:19,440 INTERACTIONS AND THESE SHOW A 1526 01:09:19,440 --> 01:09:21,720 LINEAR RELATIONSHIP BETWEEN THE 1527 01:09:21,720 --> 01:09:27,240 HEART AND LUNG, MEASURED 1528 01:09:27,240 --> 01:09:28,800 QUANTITATIVELY BETWEEN EMPHYSEMA 1529 01:09:28,800 --> 01:09:31,280 AND THE STROKE MEASURED ON MRI 1530 01:09:31,280 --> 01:09:36,960 AND FOCUS ON TRYING TO ASSESS 1531 01:09:36,960 --> 01:09:45,080 THE PULMONARY VASCULATURE USING 1532 01:09:45,080 --> 01:09:47,080 MRI AND OTHER MEASURES OF CT. 1533 01:09:47,080 --> 01:09:54,440 IN SMITH AND COLLEAGUES LOOKED 1534 01:09:54,440 --> 01:10:04,840 AT DYSANAPSIS AND HIGH 1535 01:10:09,360 --> 01:10:11,560 VARIABILITY IN THE LUNG 1536 01:10:11,560 --> 01:10:22,040 POPULATION IN THE AND AS THE 1537 01:10:28,880 --> 01:10:30,440 DEVELOPMENT AND THERE'S FURTHER 1538 01:10:30,440 --> 01:10:39,880 WORK IN DETAIL. 1539 01:10:39,880 --> 01:10:44,400 AND NOT RELATED TO COPD AND 1540 01:10:44,400 --> 01:10:44,960 HIGHLIGHTS THE DIFFERENCE 1541 01:10:44,960 --> 01:10:46,800 BETWEEN RISK AND PREVENTION AND 1542 01:10:46,800 --> 01:10:48,600 SECONDARY PREVENTION AMONG 1543 01:10:48,600 --> 01:10:53,440 PATIENTS WITH COPD. 1544 01:10:53,440 --> 01:11:00,680 IT'S A LONG STANDING ISSUE IN 1545 01:11:00,680 --> 01:11:02,440 THE CARDIOVASCULAR ARENA AND 1546 01:11:02,440 --> 01:11:04,120 SOMETHING WE NEED TO APPRECIATE 1547 01:11:04,120 --> 01:11:06,560 IN THE PULMONARY ARENA AND THE 1548 01:11:06,560 --> 01:11:07,960 PAPER SHOWS WHERE YOU MAY NOT 1549 01:11:07,960 --> 01:11:13,400 WANT TO RANDOMIZE PATIENTS WITH 1550 01:11:13,400 --> 01:11:15,320 DYSANAPSIS TO A CLINICAL TRIAL. 1551 01:11:15,320 --> 01:11:16,080 MESA ALSO PROVIDE THE 1552 01:11:16,080 --> 01:11:21,160 OPPORTUNITY TO LOOK AT THE 1553 01:11:21,160 --> 01:11:22,960 GENERAL POPULATION AND THERE'S A 1554 01:11:22,960 --> 01:11:26,840 MAY IS LUNG SAMPLE OF ABOUT 2400 1555 01:11:26,840 --> 01:11:27,400 PARTICIPANTS. 1556 01:11:27,400 --> 01:11:31,680 10% HAVE COPD BY STANDARDS BIO 1557 01:11:31,680 --> 01:11:33,480 METRIC CRITERIA. 1558 01:11:33,480 --> 01:11:36,240 NOT SURPRISINGLY THERE'S SOME 1559 01:11:36,240 --> 01:11:39,360 OVERLAP WITH ASTHMA AND SOME 1560 01:11:39,360 --> 01:11:41,320 OVERLAP WITH CHRONIC BRONCHITIS 1561 01:11:41,320 --> 01:11:44,320 SHOWN FOR A LONG TIME AND IN THE 1562 01:11:44,320 --> 01:11:51,120 VEN DIAGRAM WE SEE OVERLAP WITH 1563 01:11:51,120 --> 01:11:56,000 EMPHYSEMA BUT MOST DO NOT IN 1564 01:11:56,000 --> 01:12:00,960 FACT HAVE COPD SPIROMETRIC 1565 01:12:00,960 --> 01:12:03,120 DEFINED AND AS WE LOOK IN THE 1566 01:12:03,120 --> 01:12:03,800 GENERAL POPULATION THE 1567 01:12:03,800 --> 01:12:05,080 PHENOTYPES GET SPREAD OUT AND 1568 01:12:05,080 --> 01:12:07,480 IT'S IMPORTANT FROM AN MODELLING 1569 01:12:07,480 --> 01:12:09,680 SPECIFIC AND ANIMAL MODEL TO 1570 01:12:09,680 --> 01:12:10,720 KNOW WHICH OF THESE QUADRANTS 1571 01:12:10,720 --> 01:12:20,920 YOU'RE IN. 1572 01:12:47,000 --> 01:12:49,080 AND OTHER SUBTYPES ARE EQUALLY 1573 01:12:49,080 --> 01:12:53,280 COMMON IN MESA LUNG WHICH IS 1574 01:12:53,280 --> 01:12:54,760 POPULATION-BASED WITH MUCH MORE 1575 01:12:54,760 --> 01:12:56,160 SMOKING EXPOSURE. 1576 01:12:56,160 --> 01:12:57,920 THESE ARE I WOULD ARGUE 1577 01:12:57,920 --> 01:12:59,560 DIFFERENT DISEASES IN DIFFERENT 1578 01:12:59,560 --> 01:13:00,400 PEOPLE WITH DIFFERENT RISK 1579 01:13:00,400 --> 01:13:02,400 FACTORS. 1580 01:13:02,400 --> 01:13:04,600 THIS IS NOT A NEW CONCEPT. 1581 01:13:04,600 --> 01:13:08,840 WE'VE LINED OUT SIX OF THESE NOT 1582 01:13:08,840 --> 01:13:10,200 SMOKING RELATED EMPHYSEMA SUB 1583 01:13:10,200 --> 01:13:12,160 TYPES AND THE OTHER THREE THAT 1584 01:13:12,160 --> 01:13:15,880 ARE SMOKING RELATED AND SOME ARE 1585 01:13:15,880 --> 01:13:17,240 CLEARLY COPD SUBPHENOTYPES. 1586 01:13:17,240 --> 01:13:20,600 THIS IS AN OLD CONCEPT GOING 1587 01:13:20,600 --> 01:13:23,080 BACK MORE OR LESS HALF A CENTURY 1588 01:13:23,080 --> 01:13:28,680 TO ORIGINAL PAPER SHOWING THE 1589 01:13:28,680 --> 01:13:29,400 DISSEMIN 1590 01:13:29,400 --> 01:13:30,520 DISSEMINATED EMPHYSEMA IS NOT 1591 01:13:30,520 --> 01:13:32,080 RELATED TO SMOKING. 1592 01:13:32,080 --> 01:13:35,040 MESA HAS A LARGE AMOUNT OF 1593 01:13:35,040 --> 01:13:35,800 ENVIRONMENTAL CHARACTERIZATION 1594 01:13:35,800 --> 01:13:39,000 AND WE RECENTLY PUBLISHED THE 1595 01:13:39,000 --> 01:13:42,040 AMBIENT OZONE EXPOSURE AND MANY 1596 01:13:42,040 --> 01:13:44,520 OF US HAD PARTICULAR EXPOSURES 1597 01:13:44,520 --> 01:13:46,520 IN THE EAST COAST RECENTLY. 1598 01:13:46,520 --> 01:13:49,640 THIS IS SHOWING 10 TO 18-YEAR 1599 01:13:49,640 --> 01:13:52,240 OZONE EXPERIENCE GROUND LEVEL IN 1600 01:13:52,240 --> 01:13:53,920 PROGRESSION OF EMPHYSEMA. 1601 01:13:53,920 --> 01:13:55,720 IT'S ONE EXAMPLE OF A NUMBER OF 1602 01:13:55,720 --> 01:13:57,480 AIR POLLUTION STUDIES WE'RE 1603 01:13:57,480 --> 01:14:05,800 GOING AND USING OZONE AS A MODEL 1604 01:14:05,800 --> 01:14:08,720 THAT WAS STANDARD AND THERE'S A 1605 01:14:08,720 --> 01:14:09,920 LOT OF OPPORTUNITIES IN MESA TO 1606 01:14:09,920 --> 01:14:11,080 MOVE FORWARD. 1607 01:14:11,080 --> 01:14:13,640 SOME RESEARCH GAPS WILL HELP IN 1608 01:14:13,640 --> 01:14:15,720 OUR INVOLVING INFORMATION OF 1609 01:14:15,720 --> 01:14:17,360 COPD RELATED PHENOTYPES IN THE 1610 01:14:17,360 --> 01:14:20,520 GENERAL POPULATION AND I THINK 1611 01:14:20,520 --> 01:14:23,120 THIS GOES BEYOND PRE-COPD 1612 01:14:23,120 --> 01:14:24,080 BECAUSE A LOT OF THESE 1613 01:14:24,080 --> 01:14:25,640 PARTICIPANTS HAVE ILLNESSES WE 1614 01:14:25,640 --> 01:14:30,920 FOUND IN SPIROMICS AND MESA 1615 01:14:30,920 --> 01:14:31,720 WHICH DOES NOT NECESSARILY 1616 01:14:31,720 --> 01:14:33,960 PROGRESS AND FIND A LIMITED 1617 01:14:33,960 --> 01:14:35,560 UNDERSTANDING OF COPD PHENOTYPES 1618 01:14:35,560 --> 01:14:37,120 AMONG INDIVIDUALS WITHOUT 1619 01:14:37,120 --> 01:14:39,400 SMOKING EXPOSURE AND SOME OF THE 1620 01:14:39,400 --> 01:14:41,080 SUBSEQUENT COHORTS WE TALKED 1621 01:14:41,080 --> 01:14:43,560 ABOUT AND IT'S IMPORTANT TO 1622 01:14:43,560 --> 01:14:45,240 STUDY THIS IN THE GENERAL 1623 01:14:45,240 --> 01:14:47,440 POPULATION AND THERE'S LIMITED 1624 01:14:47,440 --> 01:14:50,440 MULTI-ETHNIC STUDIES OF ADEQUATE 1625 01:14:50,440 --> 01:14:52,240 POWER WHICH ARE PARTICULARLY 1626 01:14:52,240 --> 01:14:54,640 IMPORTANT GIVEN IN THE U.S. WE 1627 01:14:54,640 --> 01:14:57,400 LIVE IN MULTI-ETHNIC COUNTRY AND 1628 01:14:57,400 --> 01:14:59,080 MUCH OF WHAT WE NEED TO 1629 01:14:59,080 --> 01:15:03,240 RECOGNIZE THE MEDICALIZATION OF 1630 01:15:03,240 --> 01:15:05,920 ASPECTS RELATING TO 1631 01:15:05,920 --> 01:15:09,040 MULTI-ETHNICITY IN ASPECTS OF 1632 01:15:09,040 --> 01:15:09,480 MULTI-ENVIRONMENT 1633 01:15:09,480 --> 01:15:15,000 CHARACTERIZATION BEYOND THE 1634 01:15:15,000 --> 01:15:16,120 GENETIC CHARACTERIZATION. 1635 01:15:16,120 --> 01:15:18,960 SOME CHALLENGES WORKING IN MESA 1636 01:15:18,960 --> 01:15:21,000 IS THESE ARE COMPLEX DATA AND 1637 01:15:21,000 --> 01:15:23,240 LONGITUDINAL REPEATED NEARBY AND 1638 01:15:23,240 --> 01:15:27,120 THE ANCILLARY STUDIES AND THE 1639 01:15:27,120 --> 01:15:27,800 ANALYTICAL EFFORT AND EXPERTISE 1640 01:15:27,800 --> 01:15:29,240 IS CHALLENGING. 1641 01:15:29,240 --> 01:15:33,320 WE WANT TO HELP AND WOULD BE 1642 01:15:33,320 --> 01:15:34,800 DELIGHTED TO SET UP SUBSEQUENT 1643 01:15:34,800 --> 01:15:36,360 SEMINARS IF PEOPLE ARE 1644 01:15:36,360 --> 01:15:38,720 INTERESTED BUT AGAIN A HIGHLY 1645 01:15:38,720 --> 01:15:41,080 CHARACTERIZED POPULATION-BASED 1646 01:15:41,080 --> 01:15:42,560 SAMPLE WHERE MOST PEOPLE HAVING 1647 01:15:42,560 --> 01:15:47,960 SMOKED A LOT AND REFLECTS OF THE 1648 01:15:47,960 --> 01:15:50,320 REALITY OF PEOPLE WITH LUNG 1649 01:15:50,320 --> 01:15:52,640 DISEASE AND THE MULTIETHNIC 1650 01:15:52,640 --> 01:15:59,760 DESIGN FOR CONFOUNDING AND 1651 01:15:59,760 --> 01:16:02,080 ELEMENT 23 YEARS OF FOLLOW-UP 1652 01:16:02,080 --> 01:16:02,840 AND BEFORE THEY DEVELOP LUNG 1653 01:16:02,840 --> 01:16:06,440 DISEASE TO UNDERSTANDING THE 1654 01:16:06,440 --> 01:16:07,640 LUNG DISEASE. 1655 01:16:07,640 --> 01:16:09,400 THERE'S A LOT OF OPPORTUNITIES 1656 01:16:09,400 --> 01:16:13,040 IN MESA WITH TOPMED. 1657 01:16:13,040 --> 01:16:16,880 I'M ONLY SHOWING THE TOPMED 1658 01:16:16,880 --> 01:16:19,560 MULTIOMIC DATA BUT ESSENTIALLY 1659 01:16:19,560 --> 01:16:22,080 THE WHOLE COHORT HAS WHOLE 1660 01:16:22,080 --> 01:16:26,320 GENOME SEQUENCING AS METHYLATION 1661 01:16:26,320 --> 01:16:31,760 AND TRANSCRIPTOMICS AND 1662 01:16:31,760 --> 01:16:42,240 PROTEOMICS AND METABOLOMICS. 1663 01:16:42,560 --> 01:16:43,920 AND WE'RE EXTENDING THIS 1664 01:16:43,920 --> 01:16:45,840 CURRENTLY GIVEN MOST THE WORK IS 1665 01:16:45,840 --> 01:16:48,400 IN BLOOD WHEREAS WE KNOW WE'RE 1666 01:16:48,400 --> 01:16:50,280 NOT ACCESSING THE LUNGS SO WELL 1667 01:16:50,280 --> 01:16:53,400 SO WE'RE CURRENTLY COLLECTING 1668 01:16:53,400 --> 01:16:56,280 AND HAVE ALMOST 1,000 1669 01:16:56,280 --> 01:16:58,360 PARTICIPANTS IN THE EXAMINE WITH 1670 01:16:58,360 --> 01:17:03,840 AIR FOLLICLES AND NASAL EPIT 1671 01:17:03,840 --> 01:17:08,480 EPITHELIAL SAMPLING. 1672 01:17:08,480 --> 01:17:10,560 IN CONCLUSION THE MESA LUNG 1673 01:17:10,560 --> 01:17:16,480 STUDY IS A UNIQUE MULTIETHNIC 1674 01:17:16,480 --> 01:17:19,160 STUDIES AND HIGH LEVEL OF 1675 01:17:19,160 --> 01:17:20,960 ENVIRONMENTAL AND MULTI-OMIC 1676 01:17:20,960 --> 01:17:23,760 CHARACTERIZATION WHICH SETS UP 1677 01:17:23,760 --> 01:17:26,720 TRANSLATION IN TERMS OF IMAGING 1678 01:17:26,720 --> 01:17:29,000 AND MULTIOMIC CHARACTERIZATION 1679 01:17:29,000 --> 01:17:31,200 WITH LAB STUDIES AND OPEN TO 1680 01:17:31,200 --> 01:17:31,680 COLLABORATION. 1681 01:17:31,680 --> 01:17:35,520 DETAILS IN THE MESA WEBSITE 1682 01:17:35,520 --> 01:17:40,720 SHOWN HERE AND MESA DATA AND 1683 01:17:40,720 --> 01:17:42,160 ANALYSIS COMMENTS AND BIODATA 1684 01:17:42,160 --> 01:17:47,520 CATALYST AND A WANT TO THANK THE 1685 01:17:47,520 --> 01:17:48,280 CURRENT COLLABORATORS INCLUDING 1686 01:17:48,280 --> 01:17:51,720 ERIC HOFFMAN AND MANY OTHERS AND 1687 01:17:51,720 --> 01:17:53,320 PARTICULARLY THE NUMBER OF 1688 01:17:53,320 --> 01:17:54,920 COLLABORATORS WE WORKED WITH 1689 01:17:54,920 --> 01:18:00,000 OVER THE YEARS TO SET THIS STUDY 1690 01:18:00,000 --> 01:18:01,800 UP INCLUDING SENIOR 1691 01:18:01,800 --> 01:18:03,480 CARDIOVASCULAR EPIDEMIOLOGISTS 1692 01:18:03,480 --> 01:18:06,360 WHO HELPED JUNIOR FACULTY 1693 01:18:06,360 --> 01:18:07,720 MEMBERS 20 YEARS AGO TO GET MESA 1694 01:18:07,720 --> 01:18:08,000 LOCKED UP. 1695 01:18:08,000 --> 01:18:18,160 THANK YOU. 1696 01:18:26,960 --> 01:18:32,840 >> NEXT IS SPEAKER IS IS 1697 01:18:32,840 --> 01:18:42,240 DR. WASHKO AN AT HARVARD AND 1698 01:18:42,240 --> 01:18:43,480 COLLABORATOR OF QUANTITATIVE 1699 01:18:43,480 --> 01:18:44,040 IMAGING SOLUTION. 1700 01:18:44,040 --> 01:18:46,840 >> THREW FOR THE INVITATION TO 1701 01:18:46,840 --> 01:18:48,440 BE HERE TODAY TO BE A 1702 01:18:48,440 --> 01:18:50,080 PARTICIPANT AND TO SHARE IN A 1703 01:18:50,080 --> 01:18:51,880 LOT OF THESE GREAT COHORTS. 1704 01:18:51,880 --> 01:18:54,720 I ENJOYED THE TALKS SO FAR. 1705 01:18:54,720 --> 01:18:56,920 WHAT I'LL BE DOING NEXT IS 1706 01:18:56,920 --> 01:18:59,160 TALKING THROUGH CARDIA AND THE 1707 01:18:59,160 --> 01:18:59,800 AMERICAN LUNG ASSOCIATION LUNG 1708 01:18:59,800 --> 01:19:03,960 HEALTH COHORT. 1709 01:19:03,960 --> 01:19:10,280 GETTING STARTED, CARDIA IS A 1710 01:19:10,280 --> 01:19:10,920 PROSPECTIVE COMMUNITY-BASED 1711 01:19:10,920 --> 01:19:13,440 POPULATION STUDY FOCUSSED ON THE 1712 01:19:13,440 --> 01:19:14,120 EVOLUTION OF CARDIOVASCULAR 1713 01:19:14,120 --> 01:19:17,040 DISEASE FROM YOUNG ADULTHOOD. 1714 01:19:17,040 --> 01:19:20,040 IT STARTED IN 1985 WHEN A LITTLE 1715 01:19:20,040 --> 01:19:22,840 OVER 5,000 BLACK AND WHITE 1716 01:19:22,840 --> 01:19:24,720 INDIVIDUALS AGE 18 TO 30 WERE 1717 01:19:24,720 --> 01:19:25,920 RECRUITED FROM THE FOUR SITES 1718 01:19:25,920 --> 01:19:27,400 YOU SEE LISTED THERE. 1719 01:19:27,400 --> 01:19:29,440 EACH SITE HAT AN EQUAL NUMBER OF 1720 01:19:29,440 --> 01:19:32,160 RACE, SEX AND EDUCATIONAL 1721 01:19:32,160 --> 01:19:32,480 ATTAINMENT. 1722 01:19:32,480 --> 01:19:34,920 A NICE BALANCE AND 50% OF THE 1723 01:19:34,920 --> 01:19:36,440 INVITED INDIVIDUALS WERE 1724 01:19:36,440 --> 01:19:39,520 ULTIMATELY EXAMINED AND ENROLLED 1725 01:19:39,520 --> 01:19:43,800 IN CARDIA. 1726 01:19:43,800 --> 01:19:44,480 RE-EXAMINATIONS HAVE OCCURRED 1727 01:19:44,480 --> 01:19:46,760 AND AT THE YEAR, 30 YEAR THE 1728 01:19:46,760 --> 01:19:49,840 MEAN AGE OF 55 OVER 70% OF THE 1729 01:19:49,840 --> 01:19:54,320 SURVIVING COHORT RETURNED FOR 1730 01:19:54,320 --> 01:20:00,840 THE EXAMINATION AND WE'RE 1731 01:20:00,840 --> 01:20:04,120 COMPLETING AN EXAMINATION AND 1732 01:20:04,120 --> 01:20:09,280 WITHIN CARDIA IS CARDIA LUNG 1733 01:20:09,280 --> 01:20:12,160 WITH A CARDIOLOGIST AND WE 1734 01:20:12,160 --> 01:20:15,000 LOOKED AT SMOKING HISTORY, 1735 01:20:15,000 --> 01:20:18,960 EXPOSURE, LUNG FUNCTION AT THE 1736 01:20:18,960 --> 01:20:20,880 DAYS WE SEE AND CT SCANS 1737 01:20:20,880 --> 01:20:24,400 OBTAINED AT YEAR 15, 20, 25 AND 1738 01:20:24,400 --> 01:20:26,640 35. 1739 01:20:26,640 --> 01:20:28,680 AND THE CT SCANS -- IF YOU CAN 1740 01:20:28,680 --> 01:20:29,960 GO BACK. 1741 01:20:29,960 --> 01:20:34,480 THE CT SCANS AT YEAR 15, 20 AND 1742 01:20:34,480 --> 01:20:39,960 25 WERE THE CARDIAC SCANS 1743 01:20:39,960 --> 01:20:45,320 SIMILAR TO MESA AND YEAR 35 IS A 1744 01:20:45,320 --> 01:20:46,920 VOLUMETRIC LUNG SCAN WE'RE JUST 1745 01:20:46,920 --> 01:20:47,200 COMPLETING. 1746 01:20:47,200 --> 01:20:49,400 I WANT TO SPEND THE NEXT FEW 1747 01:20:49,400 --> 01:20:51,560 MINUTES TALKING ABOUT THE DATA 1748 01:20:51,560 --> 01:20:54,680 COMING FROM CARDIA. 1749 01:20:54,680 --> 01:20:56,320 I'LL FOCUS ON THE ADULT LIFE 1750 01:20:56,320 --> 01:20:56,840 COURSE MEASURES OF LUNG 1751 01:20:56,840 --> 01:20:59,440 FUNCTION. 1752 01:20:59,440 --> 01:21:02,440 SO WE PUT TOGETHER THESE 1753 01:21:02,440 --> 01:21:03,880 TRAJECTORIES, IF YOU WILL, OF 1754 01:21:03,880 --> 01:21:07,480 LUNG FUNCTION FROM MEAN AGE 25 1755 01:21:07,480 --> 01:21:08,800 SPANNING TO MEAN AGE 55. 1756 01:21:08,800 --> 01:21:15,000 I'M SHOWING ON THE LEFT THE FEV1 1757 01:21:15,000 --> 01:21:17,480 EXPRESSED AND FOUND FIVE UNIQUE 1758 01:21:17,480 --> 01:21:18,680 TRAJECTORIES FROM THE PRESERVED 1759 01:21:18,680 --> 01:21:21,360 IDEAL LUNG HEALTH AT THE TOP IN 1760 01:21:21,360 --> 01:21:27,120 THE BLUE TO THE WORSENING LUNG 1761 01:21:27,120 --> 01:21:28,440 HEALTH IN RED AND POOR LUNG 1762 01:21:28,440 --> 01:21:33,640 HEALTH IN THE BOTTOM. 1763 01:21:33,640 --> 01:21:38,480 THIS IS THE PREVALENCE OF RATIO 1764 01:21:38,480 --> 01:21:41,280 OF LESS THAN 0.7. 1765 01:21:41,280 --> 01:21:42,920 AT BASELINE THIS IS AGAIN THE 1766 01:21:42,920 --> 01:21:46,520 MEAN AGE OF 25, ALMOST 30% OF 1767 01:21:46,520 --> 01:21:50,840 PEOPLE IN THAT PERSISTENTLY POOR 1768 01:21:50,840 --> 01:21:52,680 HEALTH GROUP HAD OBSTRUCTION AND 1769 01:21:52,680 --> 01:21:54,320 THAT CLIMBED TO ALMOST 60% OF 1770 01:21:54,320 --> 01:21:57,320 PEOPLE IN THAT TRAJECTORY BY THE 1771 01:21:57,320 --> 01:22:07,880 YEAR 30 OR MEAN AGE 55 EXAMINE. 1772 01:22:09,640 --> 01:22:12,280 WE DID A VISUAL INSPECTION OF 1773 01:22:12,280 --> 01:22:16,880 THE EARLIER SERIAL CT SCANS AT 1774 01:22:16,880 --> 01:22:21,960 15, 20 AND 25 AND CARDIAC CT 1775 01:22:21,960 --> 01:22:30,440 SCANS AND LOOK FOR EMPHYSEMA OR 1776 01:22:30,440 --> 01:22:35,120 PARASEPTAL DISEASE AND A 8% OF 1777 01:22:35,120 --> 01:22:37,920 THOSE PEOPLE OF PERSISTENTLY 1778 01:22:37,920 --> 01:22:39,520 POOR HEALTH HAD SOME FORM OF 1779 01:22:39,520 --> 01:22:47,120 COPD A MEAN AGE OF 40 ANG 20% OF 1780 01:22:47,120 --> 01:22:49,120 THE PEOPLE IN THE WORSENING LUNG 1781 01:22:49,120 --> 01:22:51,400 HEALTH TRAJECTORY AND 1782 01:22:51,400 --> 01:22:55,120 PERSISTENTLY POOR HEALTH 1783 01:22:55,120 --> 01:22:59,280 TRAJECTORY HAD A FORM OF 1784 01:22:59,280 --> 01:23:01,560 EMPHYSEMA ON THEIR CT SCANS. 1785 01:23:01,560 --> 01:23:04,800 WE WENT BACK TO THE EARLIER 1786 01:23:04,800 --> 01:23:08,800 COLLECTION AND RESPIRATORY 1787 01:23:08,800 --> 01:23:10,120 SYMPTOMS TO BE CONSIDERED 1788 01:23:10,120 --> 01:23:10,400 POSITIVE. 1789 01:23:10,400 --> 01:23:15,320 A PERSON HAD TO INDEPENDENTLY 1790 01:23:15,320 --> 01:23:19,960 REPORT AT YEAR ZERO AND AT YEAR 1791 01:23:19,960 --> 01:23:20,600 TWO. 1792 01:23:20,600 --> 01:23:22,920 YOU SEE THE RESPIRATORY SYMPTOMS 1793 01:23:22,920 --> 01:23:24,800 ON THE LEFT COLUMN OF THE PANEL. 1794 01:23:24,800 --> 01:23:26,800 WE THEN LOOKED AT THE SUBSEQUENT 1795 01:23:26,800 --> 01:23:28,960 DECLINE IN LUNG FUNCTION FROM 1796 01:23:28,960 --> 01:23:30,800 YEAR FIVE TO YEAR 30. 1797 01:23:30,800 --> 01:23:34,000 AND YOU CAN SEE THAT ANY SYMPTOM 1798 01:23:34,000 --> 01:23:35,160 AS WELL AS THE SUBTYPES OF 1799 01:23:35,160 --> 01:23:38,720 SYMPTOMS WERE GENERALLY ALL 1800 01:23:38,720 --> 01:23:41,480 RELATED TO AN ACCELERATED LOSS 1801 01:23:41,480 --> 01:23:50,680 OF THE FEV1 AS WELL AS THE FEV1, 1802 01:23:50,680 --> 01:23:52,520 FEC AND ANNUALIZED DECLINE THE 1803 01:23:52,520 --> 01:23:54,760 BASELINE PRESENTATION AND 1804 01:23:54,760 --> 01:23:55,920 SYMPTOMATIC MANIFESTATION WAS 1805 01:23:55,920 --> 01:23:59,520 RELATED TO THE SUBSEQUENT LOSS 1806 01:23:59,520 --> 01:24:07,040 OF LUNG FUNCTION. 1807 01:24:07,040 --> 01:24:09,600 WE LOOKED AT THE SYMPTOMS AND 1808 01:24:09,600 --> 01:24:17,400 THE SUBSEQUENT DEVELOPMENT OF 1809 01:24:17,400 --> 01:24:23,280 EMPHYSEMA AND IF YOU LOOK AT 1810 01:24:23,280 --> 01:24:24,480 COUGH-RELATED SYMPTOMS AND CHESS 1811 01:24:24,480 --> 01:24:28,720 ILLNESS AND WHEEZE THEY'RE 1812 01:24:28,720 --> 01:24:31,520 ASSOCIATED WITH CENTRAL 1813 01:24:31,520 --> 01:24:38,960 EMPHYSEMA AND ANY FORM OF VISUAL 1814 01:24:38,960 --> 01:24:40,000 EMPHYSEMA SYMPTOMS PREDICT 1815 01:24:40,000 --> 01:24:42,400 DISEASE SOME 25 YEARS LATER. 1816 01:24:42,400 --> 01:24:44,280 THEN IF WE STEP OUTSIDE THE 1817 01:24:44,280 --> 01:24:47,000 LUNG, THESE ARE DATA NOW 1818 01:24:47,000 --> 01:24:50,640 PUBLISHED SIX YEARS AGO LOOKING 1819 01:24:50,640 --> 01:24:51,760 AT BASELINE MEASURES OF LUNG 1820 01:24:51,760 --> 01:24:55,560 FUNCTION AND THE SUBSEQUENT 1821 01:24:55,560 --> 01:24:58,280 DEVELOPMENT OF EXTRA PULMONARY 1822 01:24:58,280 --> 01:24:59,120 COMORBIDITIES LOOK AT THE LINK 1823 01:24:59,120 --> 01:25:00,400 BETWEEN THE LUNG AND THE REST OF 1824 01:25:00,400 --> 01:25:03,480 THE BODY. 1825 01:25:03,480 --> 01:25:07,320 AND WHAT THEY FOUND WAS LUNG 1826 01:25:07,320 --> 01:25:08,720 FUNCTION PREDICTED THE 1827 01:25:08,720 --> 01:25:10,280 DEVELOPMENT OF COMORBIDITIES. 1828 01:25:10,280 --> 01:25:11,440 IF YOU LOOK AT THE PANEL ON THE 1829 01:25:11,440 --> 01:25:14,240 LEFT FOR THOSE WHO HAD A FEV1 1830 01:25:14,240 --> 01:25:17,920 GREATER OR EQUAL TO 80% 1831 01:25:17,920 --> 01:25:19,200 PREDICTED AT THE BASELINE 1832 01:25:19,200 --> 01:25:21,400 EXAMINE THE MEAN AGE DIAGNOSED 1833 01:25:21,400 --> 01:25:25,000 WITH THE FIRST COMORBIDITY WAS 1834 01:25:25,000 --> 01:25:29,640 48 TO 49 YEARS WHEREAS IF YOU 1835 01:25:29,640 --> 01:25:32,760 LOOK TO THE RIGHT WITH THOSE 1836 01:25:32,760 --> 01:25:35,560 WITH LUNG FUNCTION IT WAS LESS 1837 01:25:35,560 --> 01:25:36,440 THAN 40 YEARS OF AGE. 1838 01:25:36,440 --> 01:25:39,520 IT'S EXCITING AND WE'RE NOW 1839 01:25:39,520 --> 01:25:41,200 TRYING TO UNDERSTAND THE LINK 1840 01:25:41,200 --> 01:25:42,120 BETWEEN THE LUNG AND THE REST OF 1841 01:25:42,120 --> 01:25:52,280 THE BODY. 1842 01:25:54,600 --> 01:25:57,000 AND CARDIA HAS GIVEN GREAT 1843 01:25:57,000 --> 01:25:59,240 INSIGHT THAT THE OLD IR LIFE 1844 01:25:59,240 --> 01:26:00,120 SPAN. 1845 01:26:00,120 --> 01:26:03,960 IT WAS STARTED AT SPECIALLY THE 1846 01:26:03,960 --> 01:26:07,440 YOUNG ADULT AND DATA ARE NOT AT 1847 01:26:07,440 --> 01:26:07,720 RICH. 1848 01:26:07,720 --> 01:26:10,240 WHAT WE SOUGHT TO DO IS DEFINE A 1849 01:26:10,240 --> 01:26:13,400 NEW COHORT TO EXPLORE THE 1850 01:26:13,400 --> 01:26:16,160 INITIAL STEPS OR PATHWAYS THAT 1851 01:26:16,160 --> 01:26:19,080 LEAD TO THE DIVERGENCE FROM PEAK 1852 01:26:19,080 --> 01:26:23,600 HEALTH TO PARALLEL HEALTH TO 1853 01:26:23,600 --> 01:26:24,880 DISEASE THAT ARE DESCRIBED IN 1854 01:26:24,880 --> 01:26:29,480 MULTIPLE COHORTS TODAY. 1855 01:26:29,480 --> 01:26:32,040 SO TO DO THIS WE EMBRACED THE 1856 01:26:32,040 --> 01:26:33,640 CONCEPT IDEAL LUNG HEALTH IS 1857 01:26:33,640 --> 01:26:35,680 MORE THAN THE ABSENCE OF LUNG 1858 01:26:35,680 --> 01:26:37,120 DISEASE AND ASSOCIATED WITH 1859 01:26:37,120 --> 01:26:39,880 ADVERSE CONSEQUENCES AS SHOWN IN 1860 01:26:39,880 --> 01:26:41,880 SOME OF THE PREVIOUS SLIDES. 1861 01:26:41,880 --> 01:26:45,120 AND DISEASE-FOCUS STUDIES WITH 1862 01:26:45,120 --> 01:26:47,080 DISEASE DO NOT NUMBER LUNG 1863 01:26:47,080 --> 01:26:48,720 HEALTH OF THE PREVENTION 1864 01:26:48,720 --> 01:26:50,080 STRATEGIES AND THE PREVENTION OF 1865 01:26:50,080 --> 01:26:53,040 LUNG HEALTH IS NOT SOLELY 1866 01:26:53,040 --> 01:26:54,200 PREDICATED ON THE CIGARETTE 1867 01:26:54,200 --> 01:26:57,960 SMOKE BUT UNDERSTANDING THE FULL 1868 01:26:57,960 --> 01:26:59,560 EXPOSOME RELATED TO THAT LOSS OF 1869 01:26:59,560 --> 01:27:00,760 LUNG HEALTH. 1870 01:27:00,760 --> 01:27:03,920 AND IF WE LOOK TO THE HEART AND 1871 01:27:03,920 --> 01:27:06,080 CARDIOVASCULAR DISEASE 1872 01:27:06,080 --> 01:27:07,560 PREVENTION HAVE BEEN ATTRIBUTED 1873 01:27:07,560 --> 01:27:10,280 TO HEALTH PROMOTION AND THE 1874 01:27:10,280 --> 01:27:13,040 ABSENCE OF A DISEASE AGNOSTIC 1875 01:27:13,040 --> 01:27:14,920 COHORT IN THE U.S. HAS HINDERED 1876 01:27:14,920 --> 01:27:17,280 OUR EFFORTS AT PREVENTION OF 1877 01:27:17,280 --> 01:27:17,760 LUNG DISEASE. 1878 01:27:17,760 --> 01:27:21,280 WE LACK THE FRAMINGHAM HEART 1879 01:27:21,280 --> 01:27:22,960 STUDY FOR THE LUNG. 1880 01:27:22,960 --> 01:27:27,160 THIS IS REALLY THE KEY POINT IS 1881 01:27:27,160 --> 01:27:29,160 WE LACK THE CHOLESTEROL. 1882 01:27:29,160 --> 01:27:30,600 THE AMERICAN LUNG ASSOCIATION 1883 01:27:30,600 --> 01:27:33,040 LUNG HEALTH COHORT IS A 1884 01:27:33,040 --> 01:27:34,400 PROSPECTIVE COMMUNITY-BASED 1885 01:27:34,400 --> 01:27:41,400 COHORT STUDY CONDUCT THROUGH THE 1886 01:27:41,400 --> 01:27:41,600 ACRC. 1887 01:27:41,600 --> 01:27:45,080 IT'S A CONSORTIUM OF 1888 01:27:45,080 --> 01:27:45,880 INVESTIGATIVE SCIENCE CHAPERONED 1889 01:27:45,880 --> 01:27:47,800 AND SORTED BY THE AMERICAN LUNG 1890 01:27:47,800 --> 01:27:49,240 ASSOCIATION AND THE RESEARCH 1891 01:27:49,240 --> 01:27:52,040 CENTER ARE CENTERS OF EXCELLENCE 1892 01:27:52,040 --> 01:27:53,320 FOR CLINICAL TRANSLATIONAL 1893 01:27:53,320 --> 01:27:53,640 INVESTIGATION. 1894 01:27:53,640 --> 01:27:56,040 THE GOAL OF THE ALA LUNG HEALTH 1895 01:27:56,040 --> 01:27:59,640 COHORT IS TO RECRUIT 4,000 1896 01:27:59,640 --> 01:28:01,440 PATIENTS, THAT'S ABOUT 235 PER 1897 01:28:01,440 --> 01:28:06,440 CENTER AT A BASELINE AGE OF 25 1898 01:28:06,440 --> 01:28:08,120 TO 35 YEARS OLD. 1899 01:28:08,120 --> 01:28:09,560 IT IS DISEASE AGNOSTIC AND 1900 01:28:09,560 --> 01:28:12,240 FOCUSSED ON THE CONCEPT OF 1901 01:28:12,240 --> 01:28:14,080 RESPIRATORY HEALTH AND THE 1902 01:28:14,080 --> 01:28:16,040 CURRENT FUNDING CYCLE SUPPORTS 1903 01:28:16,040 --> 01:28:20,080 THE RECRUITMENT IN A SINGLE 1904 01:28:20,080 --> 01:28:25,520 INITIAL-BASELINE PERSON 1905 01:28:25,520 --> 01:28:26,120 EXEMPT 1906 01:28:26,120 --> 01:28:27,600 EXAMINATION AND WE WANT TO MAKE 1907 01:28:27,600 --> 01:28:31,920 THIS ESSENTIALLY THE FRAMINGHAM 1908 01:28:31,920 --> 01:28:37,120 ANALOG OR FRAMINGHAM LUNG STUDY. 1909 01:28:37,120 --> 01:28:40,600 THE OVER ARCHING GOALS ARE THE 1910 01:28:40,600 --> 01:28:41,360 DIVERGENCE BETWEEN HEALTH AND 1911 01:28:41,360 --> 01:28:42,640 DISEASE OVER THE LIFE SPAN. 1912 01:28:42,640 --> 01:28:44,440 IN THE NEAR TERM WE WANT TO 1913 01:28:44,440 --> 01:28:47,480 EXPOSE THE RELATIONSHIP BETWEEN 1914 01:28:47,480 --> 01:28:48,960 EXPOSURES, BEHAVIORS, BIOMARKERS 1915 01:28:48,960 --> 01:28:50,560 AND RESPIRATORY HEALTH AND 1916 01:28:50,560 --> 01:28:52,480 MEDIUM AND LONG-TERM TO 1917 01:28:52,480 --> 01:28:53,800 DETERMINE FACTORS IN THE 1918 01:28:53,800 --> 01:28:55,320 BIOLOGICAL PATHWAYS THAT 1919 01:28:55,320 --> 01:28:57,760 INFLUENCE THE DIVERGENCE FROM 1920 01:28:57,760 --> 01:29:01,080 IDEAL TO PARALLEL HEALTH AND TO 1921 01:29:01,080 --> 01:29:02,560 CHRONIC LUNG DISEASE ACROSS THE 1922 01:29:02,560 --> 01:29:03,920 ADULT LIFE SPAN. 1923 01:29:03,920 --> 01:29:09,120 WE WANT TO FIND THAT 1924 01:29:09,120 --> 01:29:10,240 CHOLESTEROL. 1925 01:29:10,240 --> 01:29:17,120 THE PROTOCOL FOR INCLUDES 1926 01:29:17,120 --> 01:29:20,680 QUESTIONNAIRES, SPIROMETRY AND 1927 01:29:20,680 --> 01:29:24,000 BIO BANKING AND HAVE A SCAN 1928 01:29:24,000 --> 01:29:25,520 HARMONIZED WITH COPD GENE AND 1929 01:29:25,520 --> 01:29:29,120 THE TASMANIAN LONGITUDINAL 1930 01:29:29,120 --> 01:29:31,840 HEALTH STUDY YOU'LL HEAR ABOUT 1931 01:29:31,840 --> 01:29:33,280 TO HAVE DIRECT COMPARISONS OF 1932 01:29:33,280 --> 01:29:42,440 THE RADIO LOGIC FEATURES AND 1933 01:29:42,440 --> 01:29:45,120 COLLECTING SPIROMETRY AND KEY 1934 01:29:45,120 --> 01:29:47,000 ISSUES INCLUDE HOW TO RECRUIT A 1935 01:29:47,000 --> 01:29:49,320 REPRESENTATIVE COHORT OF THE 1936 01:29:49,320 --> 01:29:50,880 U.S. POPULATION OF 25 TO 1937 01:29:50,880 --> 01:29:51,440 35-YEAR-OLDS. 1938 01:29:51,440 --> 01:29:55,240 WE WANT TO MAKE SURE IT'S 1939 01:29:55,240 --> 01:29:56,560 REPRESENTATIVE IN TERM OF RISK 1940 01:29:56,560 --> 01:29:58,880 FACTORS AND HOW DO WE ENGAGE THE 1941 01:29:58,880 --> 01:30:00,240 SAME GROUP OF PARTICIPANTS 1942 01:30:00,240 --> 01:30:02,320 INCREASINGLY MOBILE. 1943 01:30:02,320 --> 01:30:03,520 WE WANT TO MAKE SURE THEY FEEL 1944 01:30:03,520 --> 01:30:06,160 LIKE THEY'RE PART OF SOMETHING 1945 01:30:06,160 --> 01:30:11,520 AND WILLING TO PARTICIPATE. 1946 01:30:11,520 --> 01:30:13,520 WITH CURRENTLY HAVE A LITTLE 1947 01:30:13,520 --> 01:30:15,960 OVER 1,000 PEOPLE ENROLLED. 1948 01:30:15,960 --> 01:30:19,400 AS DR. MARTINEZ ALLUDED TO WE'RE 1949 01:30:19,400 --> 01:30:20,560 ADAPTING TO THE POST-COVID 1950 01:30:20,560 --> 01:30:20,760 WORLD. 1951 01:30:20,760 --> 01:30:23,760 ONE THING THAT CAME OUT IS OUR 1952 01:30:23,760 --> 01:30:25,840 PIVOT AND FOCUS ON HOME 1953 01:30:25,840 --> 01:30:28,920 SPIROMETRY AND WE'VE BEEN 1954 01:30:28,920 --> 01:30:30,280 GETTING GREAT ADAPT ARGUING FOR 1955 01:30:30,280 --> 01:30:31,880 THIS TYPE OF WORK AND PRESENTED 1956 01:30:31,880 --> 01:30:34,720 THE DATA AT THE RECENT AMERICAN 1957 01:30:34,720 --> 01:30:36,160 THORACIC SOCIETY CONFERENCE. 1958 01:30:36,160 --> 01:30:38,920 THE DATA IS ONGOING AND WE'RE 1959 01:30:38,920 --> 01:30:42,440 PREPARING OUR FIRST BATCH OF BIO 1960 01:30:42,440 --> 01:30:46,200 SPECIMENS FOR PROCESS. 1961 01:30:46,200 --> 01:30:49,080 WITH THAT I WANT TO CLOSE BY 1962 01:30:49,080 --> 01:30:52,640 ACKNOWLEDGING REALLY THE 1963 01:30:52,640 --> 01:30:55,400 MULTITUDE PEOPLE INVOLVED IN 1964 01:30:55,400 --> 01:30:57,040 SUPPORTING CARDIOVASCULAR LUNG 1965 01:30:57,040 --> 01:30:57,280 COHORT. 1966 01:30:57,280 --> 01:31:00,440 DR. CALLAHAN IS THE P.I. OF 1967 01:31:00,440 --> 01:31:03,600 CARDIA LUNG AND THE OVER ALL 1968 01:31:03,600 --> 01:31:06,040 P.I. OF THE LUNG HEALTH COHORT 1969 01:31:06,040 --> 01:31:10,440 AND HAS A TEAM THAT INCLUDES 1970 01:31:10,440 --> 01:31:10,680 MYSELF. 1971 01:31:10,680 --> 01:31:14,240 I WANT TO THANK ALL THE CARDIA 1972 01:31:14,240 --> 01:31:17,240 SITES AND THE EXECUTIVE 1973 01:31:17,240 --> 01:31:19,120 COMMITTEE AND THE SCIENCE 1974 01:31:19,120 --> 01:31:21,240 INVESTIGATORS AND ME AMERICAN 1975 01:31:21,240 --> 01:31:23,080 LUNG ASSOCIATION WHO HAS BEEN 1976 01:31:23,080 --> 01:31:26,320 PARTNERING WITH THE NHLBI AND 1977 01:31:26,320 --> 01:31:27,360 SUPPORTING THIS WORK AND 1978 01:31:27,360 --> 01:31:28,840 EVERYONE BEHIND THIS HAS BEEN 1979 01:31:28,840 --> 01:31:30,800 SUPPORTIVE IN THIS AND CERTAINLY 1980 01:31:30,800 --> 01:31:32,680 THE NIH AND NHLBI FOR ALL THEIR 1981 01:31:32,680 --> 01:31:35,000 SCIENTIFIC ENGAGEMENT AND 1982 01:31:35,000 --> 01:31:37,440 SUPPORT FOR THE COMPLETION OF 1983 01:31:37,440 --> 01:31:39,520 BOTH THESE METHODS. 1984 01:31:39,520 --> 01:31:47,880 THANK YOU. 1985 01:31:47,880 --> 01:31:54,000 [POOR AUDIO] 1986 01:31:54,000 --> 01:32:04,480 >> YOU'RE BREAKING UP A BIT. 1987 01:32:08,800 --> 01:32:10,480 >> JEFF, DO YOU WANT TO TAKE 1988 01:32:10,480 --> 01:32:10,880 OVER? 1989 01:32:10,880 --> 01:32:14,040 >> I'LL TAKE THE NEXT ONE THEN. 1990 01:32:14,040 --> 01:32:16,480 GREAT, SO THE NEXT PRESENTATION 1991 01:32:16,480 --> 01:32:21,680 IS GOING TO DESCRIBE THE CANCOLD 1992 01:32:21,680 --> 01:32:23,560 COHORT FROM WAN-CHENG TAN 1993 01:32:23,560 --> 01:32:29,920 PROFESSOR OF MEDICINE AT UBC AND 1994 01:32:29,920 --> 01:32:34,440 JEAN BOURBEAU IN CANADA. 1995 01:32:34,440 --> 01:32:35,600 OVER TO YOU, DR. TAN. 1996 01:32:35,600 --> 01:32:39,840 >> THANK YOU FOR INVITING US. 1997 01:32:39,840 --> 01:32:42,960 DR. BOURBEAU SPEAKING. 1998 01:32:42,960 --> 01:32:47,760 I'LL DO THE PRESENTATION ON 1999 01:32:47,760 --> 01:32:51,680 BEHALF AS CO-P.I. 2000 01:32:51,680 --> 01:32:57,000 IT'S ALREADY BEEN MENTIONED ALL 2001 01:32:57,000 --> 01:33:00,040 THEE COHORT AND THE VILLAGE OF 2002 01:33:00,040 --> 01:33:03,200 PEOPLE WITH DIFFERENT EXPERTISE. 2003 01:33:03,200 --> 01:33:06,440 WE'RE VERY LUCKY TO CO-LEAD THIS 2004 01:33:06,440 --> 01:33:16,800 CANADIAN INITIATIVE. 2005 01:33:28,360 --> 01:33:30,160 WHILE THE SLIDES ARE COMING UP 2006 01:33:30,160 --> 01:33:34,600 AS LONG AS SOMEONE IS WORK ON 2007 01:33:34,600 --> 01:33:38,120 THE SLIDE PRESENTATION AND WE 2008 01:33:38,120 --> 01:33:39,680 HAVE A CANADIAN CO-OBSTRUCTIVE 2009 01:33:39,680 --> 01:33:40,600 LUNG DISEASE. 2010 01:33:40,600 --> 01:33:44,280 IT'S A POPULATION-BASED COHORT. 2011 01:33:44,280 --> 01:33:45,520 I'M GOING FIRST PRESENT THE 2012 01:33:45,520 --> 01:33:48,880 DESIGN OF THE STUDY AND WHERE DO 2013 01:33:48,880 --> 01:33:59,320 WE STAND WITH THE STUDY. 2014 01:34:06,520 --> 01:34:08,400 THE FOCUS IS GOING TO BE FOR 2015 01:34:08,400 --> 01:34:13,120 THIS SESSION CONSIDERING THE 2016 01:34:13,120 --> 01:34:15,680 TOPIC THERE'S BEEN A LOT OF 2017 01:34:15,680 --> 01:34:16,160 PUBLICATION. 2018 01:34:16,160 --> 01:34:18,960 IT'S RELATIVELY A SMALL COHORT 2019 01:34:18,960 --> 01:34:20,760 BUT VERY MUCH KEY DETAIL AND IN 2020 01:34:20,760 --> 01:34:23,080 TERMS OF THE CHARACTERIZATION OF 2021 01:34:23,080 --> 01:34:24,880 IT AND WE HAVE CLOSE TO ONE OF 2022 01:34:24,880 --> 01:34:27,880 THE STUDIES BUT I DECIDED TO 2023 01:34:27,880 --> 01:34:30,200 FOCUS ON THE NEW KNOWLEDGE AND 2024 01:34:30,200 --> 01:34:33,240 RISK FACTOR TO GIVE EXAMPLE OF 2025 01:34:33,240 --> 01:34:35,960 WHAT POTENTIAL FOR PATHOGENESIS 2026 01:34:35,960 --> 01:34:38,880 OF COPD AND SOME OF THE CURRENT 2027 01:34:38,880 --> 01:34:39,840 INITIATIVE GIVING A HIGHLIGHT ON 2028 01:34:39,840 --> 01:34:44,040 THE CT IMAGING AND SOME OF THE 2029 01:34:44,040 --> 01:34:46,000 EARLY WORK IN UNDERSTANDING OF 2030 01:34:46,000 --> 01:34:49,640 THE PATHOPHYSIOLOGY AND NOT TO 2031 01:34:49,640 --> 01:34:52,560 SAY I'M AN EXPERT IN EITHER AREA 2032 01:34:52,560 --> 01:34:57,040 BUT MORE FOR PEOPLE TO SEE THE 2033 01:34:57,040 --> 01:34:58,960 APPROACHES NOW AND TO COME AND 2034 01:34:58,960 --> 01:35:03,520 END IT ON THE FUTURE RESEARCH. 2035 01:35:03,520 --> 01:35:05,880 AND THE OVERVIEW OF THE STUDY 2036 01:35:05,880 --> 01:35:07,720 IT'S BEEN A LONG JOURNEY. 2037 01:35:07,720 --> 01:35:11,560 PEOPLE HAVE TO KNOW IT STARTED 2038 01:35:11,560 --> 01:35:13,160 FROM BOLD WHERE VANCOUVER WAS 2039 01:35:13,160 --> 01:35:19,560 PART OF A PREVALENT STUDY AND 2040 01:35:19,560 --> 01:35:22,840 THEN WE STARTED BUILDING WITH 2041 01:35:22,840 --> 01:35:28,520 FIVE SIDE AND WHEN I REACHED 2042 01:35:28,520 --> 01:35:30,360 DR. WAN TAN TO BUILD ON THE 2043 01:35:30,360 --> 01:35:36,280 COHORT WE EXTENDED THE PREVALENT 2044 01:35:36,280 --> 01:35:38,360 STUDY OF FIVE TO NINE CANADIAN 2045 01:35:38,360 --> 01:35:41,400 SIDE OVER 6,500 SUBJECTS HAD 2046 01:35:41,400 --> 01:35:47,200 BEEN STUDIED IN COLD AND THEN 2047 01:35:47,200 --> 01:35:57,000 INVITED THE COPD SUBJECT AND TO 2048 01:35:57,000 --> 01:35:59,400 PARTICIPATE AND MATCHING A 2049 01:35:59,400 --> 01:36:05,520 SMOKER WITH NORMAL SPIROMETRY 2050 01:36:05,520 --> 01:36:11,160 AND A NEVER SMOKER AND 2051 01:36:11,160 --> 01:36:11,520 SPIROMETRY. 2052 01:36:11,520 --> 01:36:18,720 AND TO IDENTIFY THE POTENTIAL 2053 01:36:18,720 --> 01:36:22,840 MODIFIABLE FACTOR BEYOND SMOKING 2054 01:36:22,840 --> 01:36:25,880 FOR THE PATHOGENESIS OF COPD AND 2055 01:36:25,880 --> 01:36:27,400 TO A WORLD WHERE DIFFERENT 2056 01:36:27,400 --> 01:36:34,440 EXPOSURES HAVE BEEN CHANGING. 2057 01:36:34,440 --> 01:36:36,000 AND A PLATFORM OF THE 2058 01:36:36,000 --> 01:36:38,200 POSSIBILITY OF GENERATING NEW 2059 01:36:38,200 --> 01:36:43,200 RESEARCH QUESTIONS USING SOME OF 2060 01:36:43,200 --> 01:36:44,080 THE TECHNOLOGY THAT WE'RE 2061 01:36:44,080 --> 01:36:47,520 LOOKING AT FROM THE 2062 01:36:47,520 --> 01:36:49,360 CROSS-SECTIONAL DATA AND 2063 01:36:49,360 --> 01:36:49,960 LONGITUDINAL DATA. 2064 01:36:49,960 --> 01:36:53,240 IT'S ASSEMBLED FROM THE GENERAL 2065 01:36:53,240 --> 01:36:55,600 POPULATION AND RANDOM DIGIT 2066 01:36:55,600 --> 01:37:00,000 DIALING WHERE PEOPLE WERE 2067 01:37:00,000 --> 01:37:02,240 INVITED NOT IN CONSIDERATION OF 2068 01:37:02,240 --> 01:37:03,840 THE EXPOSURE WITH SMOKING BUT 2069 01:37:03,840 --> 01:37:07,080 THE AGE, 40 YEARS OF AGE OR MORE 2070 01:37:07,080 --> 01:37:13,640 AND NOT BEING INSTITUTIONALIZED. 2071 01:37:13,640 --> 01:37:22,800 AND THEN USING THE MATCH GROUP 2072 01:37:22,800 --> 01:37:23,400 INDIVIDUAL AND POPULATION 2073 01:37:23,400 --> 01:37:27,160 WITHOUT COPD EXPOSED TO SMOKING 2074 01:37:27,160 --> 01:37:29,000 OR NOT-EXPOSED TO SMOKING. 2075 01:37:29,000 --> 01:37:32,800 THE EVALUATION TO NOW HAD BEEN 2076 01:37:32,800 --> 01:37:35,400 THE FIRST EVALUATION OF COLD TO 2077 01:37:35,400 --> 01:37:39,880 THE BASELINE WHICH IS A MEDIAN 2078 01:37:39,880 --> 01:37:41,480 FOLLOW-UP OF THREE YEARS AND 2079 01:37:41,480 --> 01:37:46,680 ANOTHER FOLLOW-UP AT 18 MONTHS 2080 01:37:46,680 --> 01:37:48,320 THAT WAS NOT COMPLETED BECAUSE 2081 01:37:48,320 --> 01:37:51,400 OF LACK OF FUNDING AND THREE 2082 01:37:51,400 --> 01:37:53,000 YEAR AND WE'RE PROCESS NOW AND 2083 01:37:53,000 --> 01:37:54,760 DEALING WITH COVID AS MANY OF 2084 01:37:54,760 --> 01:38:02,440 OUR STUDY AND PRESENT ED WE'RE 2085 01:38:02,440 --> 01:38:05,120 ABOUT TO DO 10 TO 12 YEARS AT 2086 01:38:05,120 --> 01:38:06,680 MEDIAN FOLLOW-UP AND WE'RE 2087 01:38:06,680 --> 01:38:08,560 HALFWAY THROUGH THE EVALUATION 2088 01:38:08,560 --> 01:38:13,960 AND THAT SHOULD END IN 2024. 2089 01:38:13,960 --> 01:38:17,160 THE EVALUATION INCLUDES A 2090 01:38:17,160 --> 01:38:26,040 QUESTIONNAIRE IN DIET AND 2091 01:38:26,040 --> 01:38:30,560 DEMOGRAPHIC, SMOKING, BIO MASS 2092 01:38:30,560 --> 01:38:34,360 EXPOSURE, MARIJUANA EXPOSURE AND 2093 01:38:34,360 --> 01:38:40,080 QUALITY OF LIFE AND ALSO 2094 01:38:40,080 --> 01:38:41,520 CARDIOVASCULAR PULMONARY 2095 01:38:41,520 --> 01:38:44,040 EXERCISE TEST, CT SCAN USING THE 2096 01:38:44,040 --> 01:38:49,640 SAME METHODOLOGY THE COPD GENE 2097 01:38:49,640 --> 01:38:53,320 AND BLOOD BANKING WE HAVE AT 2098 01:38:53,320 --> 01:38:54,120 EACH VISIT. 2099 01:38:54,120 --> 01:38:56,680 IT HAD BEEN DONE AT THE BASELINE 2100 01:38:56,680 --> 01:38:58,520 OF TEN FOLD. 2101 01:38:58,520 --> 01:39:02,160 IT'S BEEN REPEATED AT THREE 2102 01:39:02,160 --> 01:39:05,160 YEARS AT RISK AND COPD AND IT'S 2103 01:39:05,160 --> 01:39:09,320 GOING TO BE REPEATED AT VISIT 12 2104 01:39:09,320 --> 01:39:13,400 AND 10, 12 YEARS INCLUDING WHAT 2105 01:39:13,400 --> 01:39:16,240 WE CALL THE HEALTHY SUBJECT 2106 01:39:16,240 --> 01:39:21,360 REFERENCE GROUP FOLLOWED WE'LL 2107 01:39:21,360 --> 01:39:26,880 HAVE COPD AND CT SCAN AS WELL 2108 01:39:26,880 --> 01:39:30,320 AND PROSPECTIVE EXACERBATION. 2109 01:39:30,320 --> 01:39:33,560 WE HAVE A 10 TO 8 YEAR MEDIAN 2110 01:39:33,560 --> 01:39:37,760 FOLLOW-UP AND WE'RE ABOUT TO 2111 01:39:37,760 --> 01:39:39,800 ACCESS THE DATABASE LINKAGE IN 2112 01:39:39,800 --> 01:39:40,400 CANADA. 2113 01:39:40,400 --> 01:39:43,680 THERE'S AN ISSUE BECAUSE IT'S 2114 01:39:43,680 --> 01:39:45,080 MANAGED THROUGH DIFFERENT 2115 01:39:45,080 --> 01:39:45,360 PROVINCES. 2116 01:39:45,360 --> 01:39:47,040 WE'LL HAVE THE POSSIBILITY OF 2117 01:39:47,040 --> 01:39:52,440 HAVING ACCESS AT THE CANADIAN 2118 01:39:52,440 --> 01:39:57,480 LEVEL TO AND STARTED LINKABLE 2119 01:39:57,480 --> 01:39:58,760 WITH ENVIRONMENTAL EXPOSURE. 2120 01:39:58,760 --> 01:40:01,240 YOU CAN SEE THE NINE SIDES 2121 01:40:01,240 --> 01:40:06,400 ACROSS SIX PROVINCES IN CANADA. 2122 01:40:06,400 --> 01:40:08,680 THIS IS WHERE AS A FLOW CHART WE 2123 01:40:08,680 --> 01:40:10,240 START FROM THE BEGINNING WITH 2124 01:40:10,240 --> 01:40:14,800 THE COPREVALENT STUDY 6,500 AND 2125 01:40:14,800 --> 01:40:17,680 WE INVITED AND VISITED ONE TO 2126 01:40:17,680 --> 01:40:18,000 PARTICIPATE. 2127 01:40:18,000 --> 01:40:21,640 WE HAVE 1,500 SUBJECTS AND AT 2128 01:40:21,640 --> 01:40:30,080 VISIT THREE WE HAD THE 78% OF 2129 01:40:30,080 --> 01:40:31,680 PEOPLE WITH 330 PARTICIPANTS 2130 01:40:31,680 --> 01:40:33,880 LOST AT FOLLOW-UP AND WE'RE IN 2131 01:40:33,880 --> 01:40:38,000 THE PROCESS OF DOING VISIT FOUR 2132 01:40:38,000 --> 01:40:41,880 WHICH IS REPRESENTING A 10, 12 2133 01:40:41,880 --> 01:40:42,640 YEAR FOLLOW-UP. 2134 01:40:42,640 --> 01:40:49,560 YOU HAVE A PAPER TALKING ABOUT 2135 01:40:49,560 --> 01:40:50,800 THE LONGITUDINAL COHORT. 2136 01:40:50,800 --> 01:40:53,960 I'D LIKE TO GIVE YOU AN OVERVIEW 2137 01:40:53,960 --> 01:40:57,000 OF THE RISK FACTOR AND SOME OF 2138 01:40:57,000 --> 01:41:02,480 THE NEW KNOWLEDGE PEOPLE CAN SEE 2139 01:41:02,480 --> 01:41:04,480 PROBABLY WE HAVE BAUD IT'S OPEN 2140 01:41:04,480 --> 01:41:06,240 TO PEOPLE NOT ONLY IN CANADA AND 2141 01:41:06,240 --> 01:41:08,320 INVITE PEOPLE TO VISIT THE 2142 01:41:08,320 --> 01:41:11,520 WEBSITE AND CALL AND SEE WHAT WE 2143 01:41:11,520 --> 01:41:17,680 HAVE. 2144 01:41:17,680 --> 01:41:19,520 AND FROM THE STUDY YOU CAN SEE 2145 01:41:19,520 --> 01:41:24,240 THE DISTRIBUTION OF THE NON-COPD 2146 01:41:24,240 --> 01:41:29,520 IN THE OTHER -- ORIGINAL 2147 01:41:29,520 --> 01:41:31,160 PREVALENT STUDY TO GOLD 1 2148 01:41:31,160 --> 01:41:36,800 THROUGH 4 AND OTHER THAN SEX 2149 01:41:36,800 --> 01:41:39,680 THAT IS IN THE COHORT WE HAVE 2150 01:41:39,680 --> 01:41:42,880 THE POSSIBILITY OF THE COPD. 2151 01:41:42,880 --> 01:41:45,600 THE PHYSICIAN THAT HAVE NOT 2152 01:41:45,600 --> 01:41:47,280 REQUIRED PEOPLE HAD COPD THEN 2153 01:41:47,280 --> 01:41:48,800 HAVING THE POSSIBILITY OF 2154 01:41:48,800 --> 01:41:49,400 FOLLOWING PEOPLE WITH MILD 2155 01:41:49,400 --> 01:41:53,840 DISEASE FROM THE BEGINNING. 2156 01:41:53,840 --> 01:41:57,000 THIS IS WHERE IF YOU START FROM 2157 01:41:57,000 --> 01:42:00,600 THE END RIGHT SIDE OF THE TABLE 2158 01:42:00,600 --> 01:42:04,240 THAT BUILDS THE GOLD 3 PLUS 2159 01:42:04,240 --> 01:42:07,520 WHICH IS THE SAMPLING OF THE 2160 01:42:07,520 --> 01:42:11,520 POPULATION HERE WE'RE VERY 2161 01:42:11,520 --> 01:42:12,960 SKEWED TOWARDS GOLD 1 AND 2 AND 2162 01:42:12,960 --> 01:42:18,360 HAVE THE GROUP OF PRISM THAT 2163 01:42:18,360 --> 01:42:23,680 HAVE B 2164 01:42:23,680 --> 01:42:26,560 HAVE BEEN AND WE HAVE THE EVER 2165 01:42:26,560 --> 01:42:30,200 SMOKER AND WE HAVE THE NEVER 2166 01:42:30,200 --> 01:42:35,520 SMOKER AS WELL IN THE COHORT. 2167 01:42:35,520 --> 01:42:45,880 >> TWO-MINUTE WARNING. 2168 01:42:46,880 --> 01:42:47,640 >> THAT MEANS I TALKED FOR -- 2169 01:42:47,640 --> 01:42:49,920 OKAY. 2170 01:42:49,920 --> 01:42:52,800 LET'S MOVE ON TO THE TRADITIONAL 2171 01:42:52,800 --> 01:42:54,440 RISK FACTOR. 2172 01:42:54,440 --> 01:42:57,320 MOVE ON, PLEASE. 2173 01:42:57,320 --> 01:42:58,960 THEN WE AGAIN GIVING SOME 2174 01:42:58,960 --> 01:43:00,560 INTEREST ON THE NEVER-SMOKER 2175 01:43:00,560 --> 01:43:10,960 MOVE ON IN THE FEATURE. 2176 01:43:23,640 --> 01:43:25,040 THERE'S SOME INTEREST IN 2177 01:43:25,040 --> 01:43:28,800 MARIJUANA AND MORE MODERN 2178 01:43:28,800 --> 01:43:30,760 EXPOSURE AND ALSO BLOOD IN THE 2179 01:43:30,760 --> 01:43:33,440 FIELD AS A PROGNOSTIC BIOMARKER 2180 01:43:33,440 --> 01:43:40,760 AND THE DECLINE IN FEV1. 2181 01:43:40,760 --> 01:43:44,640 THERE'S ALREADY BEEN SPIROMIC 2182 01:43:44,640 --> 01:43:51,040 ON THE DYSANAPSIS AND A 2183 01:43:51,040 --> 01:43:57,560 COLLABORATION BETWEEN COHORT 2184 01:43:57,560 --> 01:44:08,120 STUDY AND WE'RE PLANNING TO LOOK 2185 01:44:14,160 --> 01:44:14,960 AT THE LONGITUDE DATA IN THE 2186 01:44:14,960 --> 01:44:17,640 NEXT YEAR TO COME. 2187 01:44:17,640 --> 01:44:18,920 SOME ON CT IMAGING. 2188 01:44:18,920 --> 01:44:22,480 THIS IS NOT MY AREA OF EXPERTISE 2189 01:44:22,480 --> 01:44:27,880 BUT TO SHOW THERE'S WORK DONE ON 2190 01:44:27,880 --> 01:44:33,320 THE VASCULAR PRUNING AND TRACHEA 2191 01:44:33,320 --> 01:44:42,000 ABNORMALITIES AND PECTORAL 2192 01:44:42,000 --> 01:44:43,880 MUSCLE AND THERE'S NEW BIOMARKER 2193 01:44:43,880 --> 01:44:47,200 WORK AND SOME WORK ALSO THAT HAD 2194 01:44:47,200 --> 01:44:48,840 BEEN COMPLIMENTARY TO THE 2195 01:44:48,840 --> 01:44:50,720 CANNABIS USE IN ASSOCIATION NOT 2196 01:44:50,720 --> 01:44:54,440 ONLY WITH PHYSIOLOGICAL CHANGE 2197 01:44:54,440 --> 01:44:56,920 BUT WITH CT MEASURE. 2198 01:44:56,920 --> 01:45:00,360 AND AN AREA OF GREAT INTEREST IS 2199 01:45:00,360 --> 01:45:04,920 THE PHYSIOLOGY MEASURE AND THE 2200 01:45:04,920 --> 01:45:06,720 CARDIO PULMONARY STRESS AND SOME 2201 01:45:06,720 --> 01:45:09,920 PEOPLE HAVE ALLUDED TO THE QUIET 2202 01:45:09,920 --> 01:45:14,720 ZONE WHERE THERE'S BEEN PREVIOUS 2203 01:45:14,720 --> 01:45:17,000 WORK DONE AND RECENTLY IN THE 2204 01:45:17,000 --> 01:45:19,080 LAST DECADE SHOWING THE 2205 01:45:19,080 --> 01:45:24,200 NARROWING AND REDUCED NUMBER OF 2206 01:45:24,200 --> 01:45:28,240 TERMINAL BRONCHIAL THAT PRECEDES 2207 01:45:28,240 --> 01:45:28,480 EMPHYSEMA. 2208 01:45:28,480 --> 01:45:31,560 WE'RE LOOKING AT THE VASCULAR 2209 01:45:31,560 --> 01:45:37,520 CENTRIC PORTION OF COPD. 2210 01:45:37,520 --> 01:45:39,920 TO START TO BE INTERESTED IN 2211 01:45:39,920 --> 01:45:44,360 SOME OF THE PHYSIOLOGY FEATURES 2212 01:45:44,360 --> 01:45:48,160 OF AND THE PRESENCE OF THE MILD 2213 01:45:48,160 --> 01:45:51,400 COPD COHORT AND THE RELATIONSHIP 2214 01:45:51,400 --> 01:45:56,520 BETWEEN SOME CLINICAL OUTCOME 2215 01:45:56,520 --> 01:46:00,840 SUCH AS DYSAPNEA AND RELATED 2216 01:46:00,840 --> 01:46:02,000 ACTIVITY. 2217 01:46:02,000 --> 01:46:06,160 WHERE THE MICROVASCULATURE 2218 01:46:06,160 --> 01:46:07,880 DYSFUNCTION AND YARD YO 2219 01:46:07,880 --> 01:46:08,960 PULMONARY EXERCISE TEST. 2220 01:46:08,960 --> 01:46:11,120 WE DO BELIEVE THERE'S INDICATION 2221 01:46:11,120 --> 01:46:14,160 THAT COULD PRECEDE THE LEVEL OF 2222 01:46:14,160 --> 01:46:16,840 DETECTION BY THE CT SCAN AND 2223 01:46:16,840 --> 01:46:19,760 THERE IS ALSO WHEN IT IS 2224 01:46:19,760 --> 01:46:23,080 DETECTED EARLY ON THE VASCULAR 2225 01:46:23,080 --> 01:46:26,080 DYSFUNCTION IN COPD HAS BEEN 2226 01:46:26,080 --> 01:46:29,720 SHOWN TO BE REVERSIBLE USING THE 2227 01:46:29,720 --> 01:46:34,680 NITRIC OXIDE EFFECT YOU CAN SEE 2228 01:46:34,680 --> 01:46:39,720 ON THE PANEL. 2229 01:46:39,720 --> 01:46:46,560 WE HAVE DETERMINED ALSO ON 2230 01:46:46,560 --> 01:46:49,840 EXERCISE THE EFFICIENCY MEASURED 2231 01:46:49,840 --> 01:46:55,200 BY V CO2 AND REFERENCE 2232 01:46:55,200 --> 01:46:58,400 POPULATION THERE'S BEEN A 2233 01:46:58,400 --> 01:47:00,280 PUBLICATION ON THAT. 2234 01:47:00,280 --> 01:47:02,520 THERE ARE NOW CORRELATION WITH A 2235 01:47:02,520 --> 01:47:05,760 TEST THAT WOULD BE EASIER TO 2236 01:47:05,760 --> 01:47:08,400 MEASURE AND SOME IMAGING ALSO 2237 01:47:08,400 --> 01:47:12,440 AND THAT IS QUITE IMPORTANT 2238 01:47:12,440 --> 01:47:19,520 BECAUSE THE CVO2 ASSOCIATED WITH 2239 01:47:19,520 --> 01:47:25,520 THE PEAK WORK HAS BEEN PRESENT 2240 01:47:25,520 --> 01:47:30,320 IN A QUARTER OF THE COPD 2241 01:47:30,320 --> 01:47:31,280 REGARDLESS OF THE GOLD STATE AND 2242 01:47:31,280 --> 01:47:34,480 THIS IS WHERE THE LONGITUDINAL 2243 01:47:34,480 --> 01:47:36,640 DATA WILL BE IMPORTANT THAT 2244 01:47:36,640 --> 01:47:40,560 IMPAIRED EV EFFICIENCY WOULD BE 2245 01:47:40,560 --> 01:47:44,880 A POTENTIAL CONTRIBUTOR TO 2246 01:47:44,880 --> 01:47:45,160 DYSAPNEA. 2247 01:47:45,160 --> 01:47:50,480 WE HAVE INITIATED SOME WORK IN 2248 01:47:50,480 --> 01:47:50,680 PRISM. 2249 01:47:50,680 --> 01:47:55,240 THIS IS A PUBLICATION IN PRESS 2250 01:47:55,240 --> 01:47:56,960 ON THE CARDIOVASCULAR RISK AND 2251 01:47:56,960 --> 01:47:58,160 PRESENCE OF THE PRISM. 2252 01:47:58,160 --> 01:48:00,440 THE TOP PANEL BEING THE 2253 01:48:00,440 --> 01:48:02,000 PREVALENCE AND THE LOWER PANEL 2254 01:48:02,000 --> 01:48:04,080 BEING THE INCIDENTS ON 2255 01:48:04,080 --> 01:48:05,640 THREE-YEAR WHERE WE ATTEMPT TO 2256 01:48:05,640 --> 01:48:08,440 LOOK OVER A LONGER PERIOD OF 2257 01:48:08,440 --> 01:48:12,920 TIME AND THIS IS INDEPENDENT OF 2258 01:48:12,920 --> 01:48:15,760 THE KNOWN RISK FACTOR, AGE, SEX, 2259 01:48:15,760 --> 01:48:18,000 SMOKING AND HYPERTENSION AND 2260 01:48:18,000 --> 01:48:18,480 THOSE WHO DIDN'T HAVE 2261 01:48:18,480 --> 01:48:23,720 CARDIOVASCULAR DISEASE TO START. 2262 01:48:23,720 --> 01:48:34,240 THEN THERE IS MORE GOING ON ALSO 2263 01:48:38,520 --> 01:48:41,520 COMPARING PRISM TO COPD AND 2264 01:48:41,520 --> 01:48:43,720 CONTROL AND WORK AND PREPARATION 2265 01:48:43,720 --> 01:48:49,040 TO SHOW REDUCED LIMIT FOR VOLUME 2266 01:48:49,040 --> 01:48:53,080 EXPANSION WITH AN ACCELERATED 2267 01:48:53,080 --> 01:48:57,520 ACHIEVEMENT WITH VT ON IC IN 2268 01:48:57,520 --> 01:49:03,760 ABOUT 70% OF PATIENTS WITH 2269 01:49:03,760 --> 01:49:04,120 PRISM. 2270 01:49:04,120 --> 01:49:09,920 AND THIS IS MAINLY A FEATURE 2271 01:49:09,920 --> 01:49:14,560 THAT REDUCES OPERATING LIMIT. 2272 01:49:14,560 --> 01:49:18,440 WE THINK THAT CANCOLD HAS A 2273 01:49:18,440 --> 01:49:20,280 FUTURE IN TERMS OF RESEARCH AND 2274 01:49:20,280 --> 01:49:23,480 IMPLEMENTING COHORT AND IN TERMS 2275 01:49:23,480 --> 01:49:25,280 OF DETERMINATES OF DISEASE 2276 01:49:25,280 --> 01:49:28,280 PROGRESSION FOR USING THE 2277 01:49:28,280 --> 01:49:31,000 LONGITUDINAL EVALUATION I THINK 2278 01:49:31,000 --> 01:49:35,800 OUR EFFORT SHOULD BE UNDERTAKEN 2279 01:49:35,800 --> 01:49:37,160 FROM NOT ONLY THE MAIN AND KNOWN 2280 01:49:37,160 --> 01:49:40,640 RISK FACTOR BUT LOOKING AT THE 2281 01:49:40,640 --> 01:49:42,200 NEW RISK FACTOR AND 2282 01:49:42,200 --> 01:49:43,920 CHARACTERIZING THE POPULATION 2283 01:49:43,920 --> 01:49:45,840 BETTER AND HAVE GWAS 2284 01:49:45,840 --> 01:49:49,680 CHARACTERIZATION AND OLD 2285 01:49:49,680 --> 01:49:51,280 CHEMICAL POPULATION FOR EXAMPLE 2286 01:49:51,280 --> 01:49:52,920 AND LOOKING AT THE MODERN 2287 01:49:52,920 --> 01:49:54,040 SOCIETY EXPOSURE SUCH AS 2288 01:49:54,040 --> 01:49:55,520 POLLUTION, WILDFIRE. 2289 01:49:55,520 --> 01:50:00,480 WE HAVE A PROJECT GOING ON RIGHT 2290 01:50:00,480 --> 01:50:04,040 NOW ON THIS AND WITH THE 10 TO 2291 01:50:04,040 --> 01:50:05,840 12 YEAR MEDIAN FOLLOW-UP AND 2292 01:50:05,840 --> 01:50:08,120 THINK THE DATA WILL BRING INTO 2293 01:50:08,120 --> 01:50:09,720 OUR UNDERSTANDING OF THE 2294 01:50:09,720 --> 01:50:11,440 PATHOGENESIS AND RISK FACTOR. 2295 01:50:11,440 --> 01:50:15,280 ALSO A BETTER UNDERSTANDING OF 2296 01:50:15,280 --> 01:50:16,760 HETEROGENEITY AND 2297 01:50:16,760 --> 01:50:18,120 INTERRELATIONSHIP BETWEEN 2298 01:50:18,120 --> 01:50:22,160 MEASURABLE STRUCTURAL FROM THE 2299 01:50:22,160 --> 01:50:25,760 CT SCAN WITH THE NEW BIOMARKER 2300 01:50:25,760 --> 01:50:28,720 AND FUNCTIONAL ABNORMALITY FROM 2301 01:50:28,720 --> 01:50:30,680 THE FUNCTION TEST AND DURING 2302 01:50:30,680 --> 01:50:32,920 EXERCISE AND ALSO CLINICAL 2303 01:50:32,920 --> 01:50:34,240 OUTCOME IN PATIENTS WITH MILD 2304 01:50:34,240 --> 01:50:34,520 DISEASE. 2305 01:50:34,520 --> 01:50:36,400 WE THINK MILD DISEASE IS THE KEY 2306 01:50:36,400 --> 01:50:40,120 HERE OPPOSED TO WORKING WITH 2307 01:50:40,120 --> 01:50:41,400 DISEASE THAT IS ALREADY WELL 2308 01:50:41,400 --> 01:50:43,560 WHERE THE DAMAGE IS ALREADY IN 2309 01:50:43,560 --> 01:50:46,440 PLACE WHERE WE CAN LOOK AT 2310 01:50:46,440 --> 01:50:52,360 DISTINCT PHYSIOLOGICAL DISEASE 2311 01:50:52,360 --> 01:50:56,120 MICROVASCULATURE DYSFUNCTION AND 2312 01:50:56,120 --> 01:51:00,840 PHYSIOLOGY FROM CT SCAN IMAGING 2313 01:51:00,840 --> 01:51:05,240 TO SEE IF IT WILL BETTER HELP US 2314 01:51:05,240 --> 01:51:08,040 PREDICT DISEASE PROGRESSION AND 2315 01:51:08,040 --> 01:51:12,640 THINK SPECIFIC 2316 01:51:12,640 --> 01:51:15,080 PATHOPHYSIOLOGICAL PHENOTYPE MAY 2317 01:51:15,080 --> 01:51:18,440 HAVE BIOLOGICAL SIGNATURE 2318 01:51:18,440 --> 01:51:19,560 UNDERSTANDING THE HETEROGENEITY. 2319 01:51:19,560 --> 01:51:22,560 I THINK THERE'S NICE 2320 01:51:22,560 --> 01:51:25,160 COLLABORATION ON THE BIOLOGICAL 2321 01:51:25,160 --> 01:51:26,280 DETERMINATES AND GENETIC 2322 01:51:26,280 --> 01:51:28,000 SIGNATURE AND ALSO LOOKING AT 2323 01:51:28,000 --> 01:51:33,240 THE PROGNOSTIC AND COMORBIDITY 2324 01:51:33,240 --> 01:51:36,480 IN PARTICULAR CARDIOVASCULAR 2325 01:51:36,480 --> 01:51:38,440 COMORBIDITY AND LOOKING AT THE 2326 01:51:38,440 --> 01:51:39,880 STRUCTURAL FINDING AND CLINICAL 2327 01:51:39,880 --> 01:51:44,520 OUTCOME BASED ON ESTABLISHING A 2328 01:51:44,520 --> 01:51:47,000 NEW RISK FACTOR AND COPD 2329 01:51:47,000 --> 01:51:49,040 ENDOTYPE AND OFFER TRANSLATIONAL 2330 01:51:49,040 --> 01:51:54,440 RESEARCH AND FINAL 2331 01:51:54,440 --> 01:51:55,160 ACKNOWLEDGEMENT AS I SAID 2332 01:51:55,160 --> 01:51:59,360 THERE'S A HUGE AMOUNT OF PEOPLE 2333 01:51:59,360 --> 01:52:00,560 THAT DOESN'T SHOW ON THE SLIDE 2334 01:52:00,560 --> 01:52:03,680 BUT IT'S IMPORTANT TO REALIZE 2335 01:52:03,680 --> 01:52:06,280 THERE'S A SITE INVESTIGATOR 2336 01:52:06,280 --> 01:52:07,120 ACROSS CANADA FROM WHOM THIS 2337 01:52:07,120 --> 01:52:09,840 WOULD NOT HAVE BEEN POSSIBLE. 2338 01:52:09,840 --> 01:52:17,120 FINANCIAL PARTNER THAT INCLUDES 2339 01:52:17,120 --> 01:52:19,840 CLINIC RESEARCH RESPIRATORY 2340 01:52:19,840 --> 01:52:24,360 NETWORK AND SOME OF OUR OWN 2341 01:52:24,360 --> 01:52:26,360 INSTITUTIONS FROM THE TWO 2342 01:52:26,360 --> 01:52:30,840 CO-P.I. AND UCB AND MYSELF IN 2343 01:52:30,840 --> 01:52:33,560 THE McGILL UNIVERSITY AND THE 2344 01:52:33,560 --> 01:52:34,920 PRIVATE SECTOR THAT HAS BEEN 2345 01:52:34,920 --> 01:52:40,440 VERY GENEROUS GIVING MONEY TO 2346 01:52:40,440 --> 01:52:42,280 SUPPORT THIS WITHOUT HAVING ANY 2347 01:52:42,280 --> 01:52:44,680 WORD TO SAY IN THE DEVELOPMENT 2348 01:52:44,680 --> 01:52:48,320 OF THIS COHORT THAT IS ABOUT 2349 01:52:48,320 --> 01:52:50,320 PATHOGENESIS AND PATHOPHYSIOLOGY 2350 01:52:50,320 --> 01:52:51,720 OF THE DISEASE. 2351 01:52:51,720 --> 01:52:54,520 AND THANK YOU FOR YOUR TIME AND 2352 01:52:54,520 --> 01:52:55,160 GIVING ME THE OPPORTUNITY TO BE 2353 01:52:55,160 --> 01:53:00,840 HERE THIS MORNING. 2354 01:53:00,840 --> 01:53:08,440 >> THANK YOU. 2355 01:53:08,440 --> 01:53:10,640 >> THANK YOU SO MUCH. 2356 01:53:10,640 --> 01:53:13,360 THAT WAS A GREAT TO HEAR FROM 2357 01:53:13,360 --> 01:53:18,480 OUR CANADIAN COLLEAGUES. 2358 01:53:18,480 --> 01:53:23,080 NOW WE'RE GOING FURTHER THE 2359 01:53:23,080 --> 01:53:24,200 FURTHEST ZOOM IN YOUR PRIZE IS 2360 01:53:24,200 --> 01:53:26,520 BEING UP IN THE MIDDLE OF THE 2361 01:53:26,520 --> 01:53:26,720 NIGHT. 2362 01:53:26,720 --> 01:53:28,040 THANK YOU FOR JOINING US FROM 2363 01:53:28,040 --> 01:53:32,600 THE TASMANIAN LONGITUDINAL 2364 01:53:32,600 --> 01:53:35,800 CENTER DR. SHYAMALI DHARMAGE AND 2365 01:53:35,800 --> 01:53:44,600 DR. BUI FROM THE MELBOURNE 2366 01:53:44,600 --> 01:53:49,720 POPULATION AND GLOBAL HEALTH. 2367 01:53:49,720 --> 01:53:50,560 TAKE IT AWAY. 2368 01:54:01,720 --> 01:54:03,920 >> THANK YOU SO MUCH. 2369 01:54:03,920 --> 01:54:05,240 I'M SHYAMALI DHARMAGE. 2370 01:54:05,240 --> 01:54:11,560 THE CURRENT P.I. OF THE 2371 01:54:11,560 --> 01:54:12,840 TASMANIAN LONGITUDINAL HEALTH 2372 01:54:12,840 --> 01:54:14,480 STUDY WITH DR. BUI WHO HAS DUB A 2373 01:54:14,480 --> 01:54:17,840 LOT OF WORK WITHIN THE STUDY. 2374 01:54:17,840 --> 01:54:22,360 SO THIS IS THE STRUCTURE OF THE 2375 01:54:22,360 --> 01:54:23,520 PRESENTATION. 2376 01:54:23,520 --> 01:54:27,440 FIRST, I'LL BRIEFLY TALK ABOUT 2377 01:54:27,440 --> 01:54:30,120 THE TASK OF THE TASMANIAN 2378 01:54:30,120 --> 01:54:31,520 LONGITUDINAL HEALTH STUDY AND 2379 01:54:31,520 --> 01:54:34,520 WHAT DATA HAVE BEEN COLLECTED. 2380 01:54:34,520 --> 01:54:39,000 THEN WE'LL TALK A LITTLE BIT 2381 01:54:39,000 --> 01:54:41,000 MORE ABOUT HOW TAHS HAS 2382 01:54:41,000 --> 01:54:42,360 CONTRIBUTED TO THE FIELD OF 2383 01:54:42,360 --> 01:54:43,400 COPD. 2384 01:54:43,400 --> 01:54:45,320 WE FOCUS MAINLY ON THE UNIQUE 2385 01:54:45,320 --> 01:54:48,800 FINDINGS OF THE TAHS RATHER THAN 2386 01:54:48,800 --> 01:54:51,520 EVERYTHING WE HAVE DONE. 2387 01:54:51,520 --> 01:54:53,280 AND FINALLY I'LL TALK ABOUT WHAT 2388 01:54:53,280 --> 01:55:00,760 IS NEXT IN TAHS AND BEYOND. 2389 01:55:00,760 --> 01:55:04,320 THOSE WHO HAVEN'T BEEN TO OUR 2390 01:55:04,320 --> 01:55:10,280 AUSTRALIA WE HAVE A BEAUTIFUL 2391 01:55:10,280 --> 01:55:14,560 UNIVERSITY WITH VERY OLD 2392 01:55:14,560 --> 01:55:15,480 BEAUTIFUL BUILDINGS. 2393 01:55:15,480 --> 01:55:21,240 ALSO MODERN BUILDINGS SUCH AS 2394 01:55:21,240 --> 01:55:24,600 THIS. 2395 01:55:24,600 --> 01:55:27,440 IF YOU'D LIKE TO WELCOME US 2396 01:55:27,440 --> 01:55:28,800 YOU'RE WELCOME TO VISIT US AS 2397 01:55:28,800 --> 01:55:29,320 WELL. 2398 01:55:29,320 --> 01:55:36,280 NOW TO TALK ABOUT THE TASMANIAN 2399 01:55:36,280 --> 01:55:37,320 HEALTH STUDY. 2400 01:55:37,320 --> 01:55:41,400 TAHS WE STARTED BACK IN 1961. 2401 01:55:41,400 --> 01:55:42,680 I'M OLD BUT NOT THAT OLD. 2402 01:55:42,680 --> 01:55:45,160 I TOOK OVER THE STUDY AS THE 2403 01:55:45,160 --> 01:55:47,320 P.I. IN 2000. 2404 01:55:47,320 --> 01:55:53,400 SO WHEN TAHS STARTED IN 1968, IT 2405 01:55:53,400 --> 01:55:59,520 STARTED IN 1968 BY INVESTIGATING 2406 01:55:59,520 --> 01:56:04,640 ALL 7-YEAR-OLD SCHOOL CHILDREN 2407 01:56:04,640 --> 01:56:08,800 IN TASMANIA THAT INCLUDED 8,000 2408 01:56:08,800 --> 01:56:11,680 OR SO CHILDREN AND PARENTS IN 2409 01:56:11,680 --> 01:56:15,680 TOTAL 45,600. 2410 01:56:15,680 --> 01:56:17,680 THE 7-YEAR OLD SCHOOL CHILDREN 2411 01:56:17,680 --> 01:56:22,720 HAD LUNG FUNCTION DONE. 2412 01:56:22,720 --> 01:56:24,200 EVERYONE ELSE INCLUDING THIS HAD 2413 01:56:24,200 --> 01:56:29,960 FIELD QUESTIONNAIRES ON THEIR 2414 01:56:29,960 --> 01:56:31,240 HEALTH STATUS AND DR. WASHKO 2415 01:56:31,240 --> 01:56:34,720 TALKED ABOUT THE LUNG STUDY 2416 01:56:34,720 --> 01:56:36,480 FOCUSSED ON RESPIRATIVE HEALTH 2417 01:56:36,480 --> 01:56:42,280 AND THAT'S WHAT THEY DID AT THE 2418 01:56:42,280 --> 01:56:45,960 TIME. 2419 01:56:45,960 --> 01:56:48,760 I'LL ACKNOWLEDGE THOSE WHO STUDY 2420 01:56:48,760 --> 01:56:55,240 THE STUDY HEATHER GIBSON AND 2421 01:56:55,240 --> 01:56:57,520 PUBLIC HEALTH PHYSICIAN AND 2422 01:56:57,520 --> 01:56:57,840 STATISTICIAN. 2423 01:56:57,840 --> 01:56:59,120 THREE GREAT PEOPLE STARTED THE 2424 01:56:59,120 --> 01:57:01,680 STUDY AND HAD A GREAT MISSION AT 2425 01:57:01,680 --> 01:57:03,320 THE TIME AND COLLECTED A HUGE 2426 01:57:03,320 --> 01:57:04,840 AMOUNT OF DATA AND WE ARE LUCKY 2427 01:57:04,840 --> 01:57:14,800 TO HAVE THIS STUDY. 2428 01:57:14,800 --> 01:57:16,320 HOWEVER, WE HAVE THIS HISTORICAL 2429 01:57:16,320 --> 01:57:19,840 STUDY STARTED IN 1968. 2430 01:57:19,840 --> 01:57:21,120 NOT A LOT OF MODERN MEASUREMENTS 2431 01:57:21,120 --> 01:57:21,960 HAD BEEN DONE AT THE TIME AND 2432 01:57:21,960 --> 01:57:25,560 THAT'S THE LIMITATION. 2433 01:57:25,560 --> 01:57:27,480 TO GO BACK TO THE FOLLOW-UPS 2434 01:57:27,480 --> 01:57:30,440 THAT HAVE HAPPENED SINCE IT 2435 01:57:30,440 --> 01:57:33,240 STARTED. 2436 01:57:33,240 --> 01:57:35,680 THE 7-YEAR-OLD SCHOOL CHILDREN 2437 01:57:35,680 --> 01:57:37,280 COHORT HAVE BEEN FOLLOWED UP 2438 01:57:37,280 --> 01:57:41,040 EVERY DECADE AND WE HAVE JUST 2439 01:57:41,040 --> 01:57:42,280 STARTED TO START THE SEVENTH 2440 01:57:42,280 --> 01:57:44,320 DECADE FOLLOW-UP. 2441 01:57:44,320 --> 01:57:45,960 THE PARENTS AND THE SIBLINGS 2442 01:57:45,960 --> 01:57:51,440 WERE ALSO FOLLOWED UP RECENTLY 2443 01:57:51,440 --> 01:57:56,160 AND SIBLINGS TEST AND PARENTS 2444 01:57:56,160 --> 01:57:56,520 QUESTIONNAIRES. 2445 01:57:56,520 --> 01:58:02,960 SINCE I TOOK OVER AT THE P.I. IN 2446 01:58:02,960 --> 01:58:04,640 2000 WE HAVE DONE FIVE MAJOR 2447 01:58:04,640 --> 01:58:07,960 FOLLOW-UPS AND ARE DOING THE 2448 01:58:07,960 --> 01:58:09,600 CURRENT FOLLOW-UP. 2449 01:58:09,600 --> 01:58:11,880 THAT'S WHAT ARE COMPLETING SINCE 2450 01:58:11,880 --> 01:58:22,000 2000. 2451 01:58:25,360 --> 01:58:27,560 AND THERE'S DOMAINS. 2452 01:58:27,560 --> 01:58:30,920 THERE'S LIFESTYLE AND GENETIC 2453 01:58:30,920 --> 01:58:31,680 FACTORS AND COMPLEX LUNG 2454 01:58:31,680 --> 01:58:35,200 FUNCTION TESTS, ENVIRONMENT 2455 01:58:35,200 --> 01:58:36,480 OCCUPATION AND CLINICAL DATA AND 2456 01:58:36,480 --> 01:58:37,800 BLOOD SAMPLES AND BIOMARKERS 2457 01:58:37,800 --> 01:58:42,480 HAVE BEEN DONE AND WE HAVE 2458 01:58:42,480 --> 01:58:49,040 COLLECTED COMORBIDITIES. 2459 01:58:49,040 --> 01:58:50,920 THIS TABLE SUMMARIZES THE DATA 2460 01:58:50,920 --> 01:58:51,240 COLLECTION. 2461 01:58:51,240 --> 01:58:53,520 THE FIRST THREE FOLLOW-UPS FOCUS 2462 01:58:53,520 --> 01:58:56,480 ON SERVICE AND LUNG FUNCTION. 2463 01:58:56,480 --> 01:58:59,520 BUT SINCE 2000 WE HAVE FOCUSSED 2464 01:58:59,520 --> 01:59:03,720 ON A NUMBER OF OUTCOMES AND 2465 01:59:03,720 --> 01:59:07,360 COLLECTED BLOOD SPECIMENS AND 2466 01:59:07,360 --> 01:59:09,160 JUST DONE THE EXOME SEQUENCING 2467 01:59:09,160 --> 01:59:11,880 OF 600 PEOPLE AND HAVE DONE A 2468 01:59:11,880 --> 01:59:16,960 NUMBER OF BIOMARKERS. 2469 01:59:16,960 --> 01:59:22,440 WE HAVE DONE EPI GENGENOMICS AN 2470 01:59:22,440 --> 01:59:27,640 PROTEOMICS ON SMALLER SAM AND 2471 01:59:27,640 --> 01:59:34,400 THERE'S AN A STUDY FROM 2472 01:59:34,400 --> 01:59:36,280 DR. WASHKO AND HAN AND WE'RE 2473 01:59:36,280 --> 01:59:38,240 LUCKY TO HAVE THEM JOIN THE 2474 01:59:38,240 --> 01:59:38,520 STUDY. 2475 01:59:38,520 --> 01:59:41,840 NEXT TO THE CHANGING LANDSCAPE 2476 01:59:41,840 --> 01:59:46,360 OF COPD AND HOW IT'S 2477 01:59:46,360 --> 01:59:49,200 CONTRIBUTED, AS WE KNOW, THERE 2478 01:59:49,200 --> 01:59:50,800 HAVE BEEN A NUMBER OF CHANGES IN 2479 01:59:50,800 --> 01:59:53,640 THE WAY THAT COPD HAS BEEN 2480 01:59:53,640 --> 01:59:55,400 VIEWED AND I DON'T HAVE TO 2481 01:59:55,400 --> 02:00:02,640 EXPLAIN THESE THINGS TO THIS 2482 02:00:02,640 --> 02:00:03,120 AUDIENCE. 2483 02:00:03,120 --> 02:00:05,720 WE KNOW IT'S A SINGLE ENTITY 2484 02:00:05,720 --> 02:00:07,680 RELATED TO FUNCTION DECLINE AND 2485 02:00:07,680 --> 02:00:12,560 SMOKERS DISEASE. 2486 02:00:12,560 --> 02:00:21,120 NOW WE KNOW THERE ARE DIFFERENT 2487 02:00:21,120 --> 02:00:23,880 LUNG FUNCTION PATHWAYS AND 2488 02:00:23,880 --> 02:00:25,800 MULTIPLE RISKS THAT INTERACT 2489 02:00:25,800 --> 02:00:27,760 WITH EACH OTHER NOT JUST 2490 02:00:27,760 --> 02:00:28,000 SMOKING. 2491 02:00:28,000 --> 02:00:31,520 MORE IMPORTANTLY, WE KNOW IT HAS 2492 02:00:31,520 --> 02:00:34,120 EARLY ORIGINS. 2493 02:00:34,120 --> 02:00:35,720 MORE THAN 80% OF COPD ORIGINATES 2494 02:00:35,720 --> 02:00:37,400 IN EARLY LIFE. 2495 02:00:37,400 --> 02:00:38,720 AND THEY CAN ACCENTUATE RISK 2496 02:00:38,720 --> 02:00:48,880 FACTORS. 2497 02:00:50,880 --> 02:00:52,880 IF WE FOCUS ON WHAT WE HAVE DONE 2498 02:00:52,880 --> 02:00:58,040 ON COPD AND TESTS LOOK AT OTHER 2499 02:00:58,040 --> 02:01:00,120 OUTCOMES. 2500 02:01:00,120 --> 02:01:01,000 THESE ARE THE THEMES WITHIN 2501 02:01:01,000 --> 02:01:01,400 TAHS. 2502 02:01:01,400 --> 02:01:03,080 AS I SAID BEFORE, WE ARE GOING 2503 02:01:03,080 --> 02:01:07,360 TO JUST FOCUS ON EARLY LIFE 2504 02:01:07,360 --> 02:01:08,840 RISKS AND WITHOUT RISK. 2505 02:01:08,840 --> 02:01:10,200 LUNG FUNCTION TRAJECTORIES IS 2506 02:01:10,200 --> 02:01:15,320 ONE OF OUR STRENGTHS AND THEN 2507 02:01:15,320 --> 02:01:23,120 PREDICTION AND DETECTION 2508 02:01:23,120 --> 02:01:25,240 ALGORITHMS WE'RE LOOKING AT AND 2509 02:01:25,240 --> 02:01:33,480 I'LL HAND IT OVER TO DINH. 2510 02:01:33,480 --> 02:01:36,840 >> WE LOOKED AT KEY FINDINGS FOR 2511 02:01:36,840 --> 02:01:37,520 THE AREA. 2512 02:01:37,520 --> 02:01:41,120 EARLY LIFE DETERMINATES IS A KEY 2513 02:01:41,120 --> 02:01:46,360 AREA WITH RICH DATA WITH EARLY 2514 02:01:46,360 --> 02:01:48,520 LIFE AND IT INCREASED THE RISK 2515 02:01:48,520 --> 02:01:54,840 OF COPD AND LOW BIRTH WEIGHT IS 2516 02:01:54,840 --> 02:01:58,760 ASSOCIATED WITH LUNG FUNCTION 2517 02:01:58,760 --> 02:02:01,520 DEFICIT AND NOW THE IMPACT OF 2518 02:02:01,520 --> 02:02:04,680 PRETERM AND THE COPD. 2519 02:02:04,680 --> 02:02:07,400 IN FACT COPD RELATED TO PRETERM 2520 02:02:07,400 --> 02:02:09,680 BIRTH IS CONSIDERED A SUB TYPE 2521 02:02:09,680 --> 02:02:19,920 IN THE RESEARCH. 2522 02:02:23,760 --> 02:02:27,160 LOOKING AT RATIO AT SEVEN YEARS 2523 02:02:27,160 --> 02:02:30,120 WAS ASSOCIATED WITH INCREASED 2524 02:02:30,120 --> 02:02:33,040 RISK OF COPD AND 45 YEARS. 2525 02:02:33,040 --> 02:02:38,880 AS YOU CAN SEE THE COPD GROUPS 2526 02:02:38,880 --> 02:02:43,320 HAVE A LOWER LUNG FUNCTION. 2527 02:02:43,320 --> 02:02:45,480 WE ARE PAPERS ON THE IMPACT OF 2528 02:02:45,480 --> 02:02:49,480 EARLY LIFE INFECTIONS AND 2529 02:02:49,480 --> 02:02:51,320 SMOKING EXPOSOME. 2530 02:02:51,320 --> 02:02:55,120 AND SMOKING ASSOCIATED WITH 2531 02:02:55,120 --> 02:02:59,560 BRONCHITIS ASSOCIATED WITH 2532 02:02:59,560 --> 02:03:01,920 OBSTRUCTIVE LUNG DISEASE. 2533 02:03:01,920 --> 02:03:03,000 INTERESTI 2534 02:03:03,000 --> 02:03:04,400 INTERESTINGLY LUNG FUNCTION 2535 02:03:04,400 --> 02:03:06,480 DEFICIT WAS ASSOCIATED WITH 2536 02:03:06,480 --> 02:03:10,600 SMALLER LUNGS IN MIDDLE AGE. 2537 02:03:10,600 --> 02:03:12,360 WE THEN INVESTIGATED PROFILES OF 2538 02:03:12,360 --> 02:03:16,880 EARLY LIFE RISK FACTS AND IMPACT 2539 02:03:16,880 --> 02:03:19,800 OF COPD AND IDENTIFIED SIX 2540 02:03:19,800 --> 02:03:21,840 DISTINCT PROFILES OF RISK 2541 02:03:21,840 --> 02:03:23,920 FACTORS USING ANALYSIS. 2542 02:03:23,920 --> 02:03:27,520 THIS HEAT MAP SHOWS PROBABILITY 2543 02:03:27,520 --> 02:03:29,640 ACROSS SIX PROFILES. 2544 02:03:29,640 --> 02:03:31,360 OVER ALL THE PROFILES HAVE 2545 02:03:31,360 --> 02:03:36,280 DIFFERENT IMPACTS ON COPD AND 2546 02:03:36,280 --> 02:03:38,160 THE PROFILE WITH FREQUENT CHILD 2547 02:03:38,160 --> 02:03:39,600 ASTHMA HAVE THE HIGHEST RISK OF 2548 02:03:39,600 --> 02:03:48,480 COPD IN MIDDLE AGE. 2549 02:03:48,480 --> 02:03:50,240 ALSO WE INVESTIGATED THE 2550 02:03:50,240 --> 02:03:54,800 INTERACTION BETWEEN LIFE TIME 2551 02:03:54,800 --> 02:03:58,760 RISK FACTORS FOR EXAMPLE LOOKING 2552 02:03:58,760 --> 02:04:02,080 AT RISK FOR THE RISK OF AIR FLOW 2553 02:04:02,080 --> 02:04:08,240 OBSTRUCTION IN MIDDLE AGE AND 2554 02:04:08,240 --> 02:04:10,360 ASTHMA WERE INDEPENDENTLY 2555 02:04:10,360 --> 02:04:12,520 ASSOCIATED HOWEVER, THE 2556 02:04:12,520 --> 02:04:15,440 REDUCTION IN THE RATIO IN PEOPLE 2557 02:04:15,440 --> 02:04:22,920 WITH BOTH ASTHMA AND SMOKING 2558 02:04:22,920 --> 02:04:28,200 SHOWS EFFECT. 2559 02:04:28,200 --> 02:04:31,240 AND LOOKED AT THE IMPACT OF 2560 02:04:31,240 --> 02:04:32,960 SMOKING AND OCCUPATIONAL 2561 02:04:32,960 --> 02:04:40,560 EXPOSOME IN MIDDLE AGE. 2562 02:04:40,560 --> 02:04:41,920 AUTO SMOKING INCREASING LUNG 2563 02:04:41,920 --> 02:04:46,000 FUNCTION DECLINE RATES. 2564 02:04:46,000 --> 02:04:49,560 AND OBSERVED INTERACTION BETWEEN 2565 02:04:49,560 --> 02:04:52,400 PRE TERM BIRTH AND SMOKING ON 2566 02:04:52,400 --> 02:04:55,880 MIDDLE AGE AND INCREASED THE 2567 02:04:55,880 --> 02:05:00,040 RISK OF COPD AND APPARENT 2568 02:05:00,040 --> 02:05:04,120 AMONGST SMOKERS AND LOOKED 2569 02:05:04,120 --> 02:05:08,360 ACROSS PRETERM GROUPS AND 2570 02:05:08,360 --> 02:05:14,480 STRATIFIED BY SMOKING STATUS AND 2571 02:05:14,480 --> 02:05:19,400 YOU SEE THE GROUPS MUCK SMOKERS 2572 02:05:19,400 --> 02:05:21,320 AND REPEATED LUNG FUNCTION WHICH 2573 02:05:21,320 --> 02:05:25,800 ALLOW US TO INVESTIGATE THE 2574 02:05:25,800 --> 02:05:27,520 PATHWAYS OF COPD. 2575 02:05:27,520 --> 02:05:31,320 WHILE THE STUDY LOOKED AT WHAT 2576 02:05:31,320 --> 02:05:35,400 HAPPENED IN LIFE OR CHILDHOOD WE 2577 02:05:35,400 --> 02:05:41,440 LOOKED AT THE GROUPS AND 2578 02:05:41,440 --> 02:05:47,160 IDENTIFIED SIX TRAJECTORIES. 2579 02:05:47,160 --> 02:05:52,480 AND IT'S IN THIS TRAJECTORY AND 2580 02:05:52,480 --> 02:05:56,080 LOOKING AT EARLY LOW AND NORMAL 2581 02:05:56,080 --> 02:05:58,360 DECLINE, AVERAGE, EARLY MIDDLE 2582 02:05:58,360 --> 02:06:01,560 AVERAGE AND RAPID DECLINE. 2583 02:06:01,560 --> 02:06:03,680 WE IDENTIFIED DIFFERENT 2584 02:06:03,680 --> 02:06:08,960 TRAJECTORIES OF RISK OF COPD 2585 02:06:08,960 --> 02:06:14,800 INCLUDING THE DECLINE AND ADDED 2586 02:06:14,800 --> 02:06:17,840 TRAJECTORIES LOW AND THE BELOW 2587 02:06:17,840 --> 02:06:18,200 AVERAGE. 2588 02:06:18,200 --> 02:06:28,760 ALSO ASSOCIATED WITH COPD THEY 2589 02:06:33,440 --> 02:06:35,720 TECHNOLOGY CONTRIBUTED TO 75% OF 2590 02:06:35,720 --> 02:06:38,760 COPD AND LOOKED AT OBSTRUCTION 2591 02:06:38,760 --> 02:06:44,320 BASED ON THE LIFE TIME ON RATIO 2592 02:06:44,320 --> 02:06:51,280 AND WE IDENTIFIED TRAJECTORIES 2593 02:06:51,280 --> 02:06:53,440 AND CLASSIFIED PEOPLE WITH LOW 2594 02:06:53,440 --> 02:07:00,560 RATIO TRAJECTORIES AND THOSE 2595 02:07:00,560 --> 02:07:05,560 WITH THE LOW FEC AND NORMAL FEV1 2596 02:07:05,560 --> 02:07:07,560 RATIO TRAJECTORIES HAD 2597 02:07:07,560 --> 02:07:12,000 RESTRICTED PATTERN. 2598 02:07:12,000 --> 02:07:15,240 AND THOSE WITH LOW RATIO BUT 2599 02:07:15,240 --> 02:07:18,480 NORMAL TRAJECTORIES AS 2600 02:07:18,480 --> 02:07:23,560 OBSTRUCTIVE PATTERNS AND NORMAL 2601 02:07:23,560 --> 02:07:25,440 FOR BOTH TRAJECTORIES. 2602 02:07:25,440 --> 02:07:28,240 AND THIS IS THE HIGHEST RISK OF 2603 02:07:28,240 --> 02:07:30,600 COPD AND THE STRONGEST 2604 02:07:30,600 --> 02:07:35,280 ASSOCIATED WITH RISK FACTOR IT'S 2605 02:07:35,280 --> 02:07:37,400 ALSO GOES TO MENTAL HEALTH 2606 02:07:37,400 --> 02:07:38,880 DISORDERS. 2607 02:07:38,880 --> 02:07:41,640 AND THE PATTERN HAS THE SECOND 2608 02:07:41,640 --> 02:07:43,720 HIGHEST RISK OF COPD. 2609 02:07:43,720 --> 02:07:46,760 THE RESTRICTIVE PATTERN HAS 2610 02:07:46,760 --> 02:07:50,000 EVIDENCE OF LUNG RESTRICTION 2611 02:07:50,000 --> 02:07:53,880 WITH LOWER LUNG CAPACITY AND HAS 2612 02:07:53,880 --> 02:07:57,240 PREVALENCE AND AT RISK OF 2613 02:07:57,240 --> 02:08:01,960 MULTIPLE MORBIDITIES INCLUDING 2614 02:08:01,960 --> 02:08:03,240 OBESITY, DIABETES, 2615 02:08:03,240 --> 02:08:05,200 CARDIOVASCULAR ISSUES, 2616 02:08:05,200 --> 02:08:07,920 HYPERTENSION AND SLEEP APNEA. 2617 02:08:07,920 --> 02:08:11,080 AND THE LIFE TIME RISK FACTORS 2618 02:08:11,080 --> 02:08:15,040 LEADING TO COPD WE MOVE TO 2619 02:08:15,040 --> 02:08:16,480 PREVENTION AND PREDICTION. 2620 02:08:16,480 --> 02:08:18,880 ONE KEY QUESTION IS TO IDENTIFY 2621 02:08:18,880 --> 02:08:24,520 WHAT IS THE LIFE TIME FUNCTION 2622 02:08:24,520 --> 02:08:31,440 TRAJECTORIES IN COPD PATIENT AND 2623 02:08:31,440 --> 02:08:37,200 USING BIOMEDIARKERS IS A POTENT 2624 02:08:37,200 --> 02:08:42,760 WAY AND THE RATE MAY BE 2625 02:08:42,760 --> 02:08:44,040 DIFFERENCE BETWEEN COPD FROM THE 2626 02:08:44,040 --> 02:08:47,040 FUNCTION DECLINE TRAJECTORY AND 2627 02:08:47,040 --> 02:08:49,840 THE COPD WITH NORMAL LUNG 2628 02:08:49,840 --> 02:08:53,520 FUNCTION DECLINE AND WE HAVE 2629 02:08:53,520 --> 02:08:55,800 FUNDING AND DOING MORE 2630 02:08:55,800 --> 02:08:57,320 BIOMARKERS. 2631 02:08:57,320 --> 02:09:00,360 WE HAVE DEVELOPED A MODEL TO 2632 02:09:00,360 --> 02:09:05,480 PREDICT AIR FLOW OBSTRUCTION 2633 02:09:05,480 --> 02:09:12,200 BASED ON THE CHARACTERISTIC 2634 02:09:12,200 --> 02:09:13,840 USING THE STUDY AND WE'RE 2635 02:09:13,840 --> 02:09:18,240 LOOKING AT OTHER COHORTS AND WE 2636 02:09:18,240 --> 02:09:28,760 ARE DEVELOPING ON ONLINE TOOL. 2637 02:09:31,680 --> 02:09:33,600 >> WE HAVE INVESTIGATING FACTORS 2638 02:09:33,600 --> 02:09:36,320 THAT CAN AFFECT LUNG FUNCTION 2639 02:09:36,320 --> 02:09:42,560 AND COPD AND THESE FACTORS SPAN 2640 02:09:42,560 --> 02:09:46,200 FROM PRECONCEPTION TO NEWBORN, 2641 02:09:46,200 --> 02:09:47,200 CHILDHOOD AND ADULTHOOD. 2642 02:09:47,200 --> 02:09:50,320 HERE'S A SUMMARY OF LIFE TIME 2643 02:09:50,320 --> 02:09:54,440 RISK FACTORS THAT CAN INCREASE 2644 02:09:54,440 --> 02:09:58,200 THE RISK OF COPD. 2645 02:09:58,200 --> 02:10:00,320 WE HAVE INVESTIGATED MOST OF 2646 02:10:00,320 --> 02:10:01,320 THESE FACTORS. 2647 02:10:01,320 --> 02:10:02,640 AND THIS KNOWLEDGE IS CRITICAL 2648 02:10:02,640 --> 02:10:08,320 FOR DEVELOPING PREVENTIVE 2649 02:10:08,320 --> 02:10:09,920 STRATEGIES FOR DEVELOPING 2650 02:10:09,920 --> 02:10:10,920 CLINICAL RISK OF COPD. 2651 02:10:10,920 --> 02:10:13,760 OUR FINDINGS HAVE INFORMED THE 2652 02:10:13,760 --> 02:10:15,520 NOVEL COPD CLASSIFICATION 2653 02:10:15,520 --> 02:10:20,480 ACCORDING TO MAJOR RISK FACTORS 2654 02:10:20,480 --> 02:10:30,320 IN THE LAST CONSORTIUM. 2655 02:10:30,320 --> 02:10:33,280 CAN WE HAVE AN OPTIMISTIC 2656 02:10:33,280 --> 02:10:35,360 FUNCTION FOR COPD AND CAN WE 2657 02:10:35,360 --> 02:10:36,000 CURE PEOPLE? 2658 02:10:36,000 --> 02:10:40,440 IF SO, THERE'S NO QUESTION WE 2659 02:10:40,440 --> 02:10:44,760 NEED TO FOCUS ON PRE-COPD AND 2660 02:10:44,760 --> 02:10:45,800 COLLABORATIONS WITH RESEARCHERS 2661 02:10:45,800 --> 02:10:50,280 AND ONE OF THEM WILL BE 2662 02:10:50,280 --> 02:10:52,280 PRESENTING HERE TODAY 2663 02:10:52,280 --> 02:10:54,760 DR. HANSBRO FROM SYDNEY AND HAVE 2664 02:10:54,760 --> 02:10:56,360 A PROBLEM TO PREVENT COPD BY 2665 02:10:56,360 --> 02:11:00,680 EARLY DETECTION AND MANAGEMENT. 2666 02:11:00,680 --> 02:11:02,120 WE IDENTIFIED SO MANY RISK 2667 02:11:02,120 --> 02:11:05,040 FACTORS THAT COULD BE USED TO 2668 02:11:05,040 --> 02:11:07,720 INFORM THE PREVENTION BUT IT IS 2669 02:11:07,720 --> 02:11:09,280 BEYOND AN INDIVIDUAL'S CONTROL 2670 02:11:09,280 --> 02:11:11,520 SOME RISK FACTORS. 2671 02:11:11,520 --> 02:11:14,520 IN THAT CASE IN ORDER TO CURE 2672 02:11:14,520 --> 02:11:16,640 COPD CAN WE DETECT COPD EARLY 2673 02:11:16,640 --> 02:11:19,800 AND MANAGE THEM SO IT IS NOT 2674 02:11:19,800 --> 02:11:22,600 SYMPTOMATIC MANAGEMENT. 2675 02:11:22,600 --> 02:11:24,360 WE CAN CURE. 2676 02:11:24,360 --> 02:11:27,560 IN ORDER TO DO THAT WE LOOKED AT 2677 02:11:27,560 --> 02:11:29,680 BASIC MECHANISMS THROUGH 2678 02:11:29,680 --> 02:11:31,800 EXPERIMENTAL RESEARCH USING 2679 02:11:31,800 --> 02:11:33,240 CELLULAR RESEARCH AS WELL AS 2680 02:11:33,240 --> 02:11:37,080 ANIMAL STUDIES. 2681 02:11:37,080 --> 02:11:38,280 CELLULAR RESEARCH COULD INCLUDE 2682 02:11:38,280 --> 02:11:42,480 THINGS LIKE ORGANOIDS AND HAVE 2683 02:11:42,480 --> 02:11:43,200 WORK FOR FUNDING. 2684 02:11:43,200 --> 02:11:45,880 WE HAVE ALSO PROPOSED A SERIES 2685 02:11:45,880 --> 02:11:48,120 OF CLINICAL TRIALS ON COPD. 2686 02:11:48,120 --> 02:11:51,440 >> TWO-MINUTE WARNING. 2687 02:11:51,440 --> 02:11:52,640 >> THE DIAGRAM SUMMARIZES THE 2688 02:11:52,640 --> 02:11:58,160 PROGRAM WE HAVE PROPOSED. 2689 02:11:58,160 --> 02:11:59,800 AND YESTERDAY WE SUBMITTED A 2690 02:11:59,800 --> 02:12:03,000 GRANT PROPOSAL TO DO A 2691 02:12:03,000 --> 02:12:05,200 RANDOMIZED CONTROL TRIALS ON 2692 02:12:05,200 --> 02:12:08,760 FUNCTION TRAJECTORIES. 2693 02:12:08,760 --> 02:12:13,320 FIRST HOW TO GET BIOLOGY THROUGH 2694 02:12:13,320 --> 02:12:15,040 MULTI-OMICS AND THERAPEUTICS 2695 02:12:15,040 --> 02:12:15,880 THROUGH EXPERIMENTAL RESEARCH 2696 02:12:15,880 --> 02:12:17,080 AND TESTING INTERVENTIONS. 2697 02:12:17,080 --> 02:12:19,360 THESE ARE THE STEPS WE HAVE TO 2698 02:12:19,360 --> 02:12:20,400 TAKE IF WE WANT TO FIND A CURE 2699 02:12:20,400 --> 02:12:30,600 FOR COPD. 2700 02:12:31,800 --> 02:12:38,040 IT'S A BIG TEAM AND BIG STUDY 2701 02:12:38,040 --> 02:12:38,600 TO ACHIEVE THAT. 2702 02:12:38,600 --> 02:12:39,640 THANK YOU VERY MUCH FOR INVITING 2703 02:12:39,640 --> 02:12:44,880 US AND LISTENING TO US. 2704 02:12:44,880 --> 02:12:47,520 >> HE'D LIKE TO THANK THE 2705 02:12:47,520 --> 02:12:48,240 SPEAKERS FOR A WONDERFUL 2706 02:12:48,240 --> 02:12:50,800 OVERVIEW OF THE COHORTS. 2707 02:12:50,800 --> 02:12:51,720 AND FOCUS POTENTIAL 2708 02:12:51,720 --> 02:12:55,680 COLLABORATIONS BETWEEN THE 2709 02:12:55,680 --> 02:12:57,560 COHORTS OR HELPFULLY THOSE OTHER 2710 02:12:57,560 --> 02:12:59,400 SCIENTISTS ON HERE. 2711 02:12:59,400 --> 02:13:01,200 WE'D LIKE TO ASK QUESTIONS 2712 02:13:01,200 --> 02:13:02,320 STEPHANIE'S GOING TO GIVE IN A 2713 02:13:02,320 --> 02:13:07,800 SECOND TO EACH OF THE COHORTS 2714 02:13:07,800 --> 02:13:09,280 STARTING IN THE ORDER YOU 2715 02:13:09,280 --> 02:13:09,560 PRESENTED. 2716 02:13:09,560 --> 02:13:11,720 TWO MINUTES PER PERSON AND ONE 2717 02:13:11,720 --> 02:13:14,480 RESPONDER PER COHORT. 2718 02:13:14,480 --> 02:13:19,240 DR. CHRISTENSON. 2719 02:13:19,240 --> 02:13:22,920 >> WE'LL COLLATE OTHER PEOPLE'S 2720 02:13:22,920 --> 02:13:23,920 QUESTIONS IN THE CHATS AS THE 2721 02:13:23,920 --> 02:13:25,640 P.I.s ANSWER. 2722 02:13:25,640 --> 02:13:31,280 WE HAD ONE OVER ARCHING 2723 02:13:31,280 --> 02:13:31,560 QUESTION. 2724 02:13:31,560 --> 02:13:34,240 THAT IS WE'RE HEARING FROM GREAT 2725 02:13:34,240 --> 02:13:37,000 COHORTS AND I WANTED IDEAS FROM 2726 02:13:37,000 --> 02:13:40,800 THE P.I.s YOU BRAIN STORM ON 2727 02:13:40,800 --> 02:13:43,320 WAYS IN WHICH WE CAN INCREASE 2728 02:13:43,320 --> 02:13:44,800 COLLABORATION ACROSS THE COHORT 2729 02:13:44,800 --> 02:13:47,720 AND WITH BASIC SCIENTISTS TO 2730 02:13:47,720 --> 02:13:51,520 FURTHER OUR UNDERSTANDING OF 2731 02:13:51,520 --> 02:13:55,160 COPD PATHOPHYSIOLOGY AND 2732 02:13:55,160 --> 02:13:57,880 QUESTION 1A IS HOW DO 2733 02:13:57,880 --> 02:13:59,000 RESEARCHERS WHO ARE NOT 2734 02:13:59,000 --> 02:14:01,240 CURRENTLY PARTICIPATING IN THOSE 2735 02:14:01,240 --> 02:14:05,800 COHORTS HOW DO THEY CONNECT WITH 2736 02:14:05,800 --> 02:14:11,320 YOU TO POTENTIALLY START 2737 02:14:11,320 --> 02:14:11,640 COLLABORATING. 2738 02:14:11,640 --> 02:14:14,720 MAYBE WE'LL START WITH THE COPD 2739 02:14:14,720 --> 02:14:16,560 COHORT AND IN TWO MINUTES MAYBE 2740 02:14:16,560 --> 02:14:21,800 ONE P.I. PER STUDY. 2741 02:14:21,800 --> 02:14:24,480 >> THE ISSUE'S AROUND 2742 02:14:24,480 --> 02:14:25,760 COLLABORATION. 2743 02:14:25,760 --> 02:14:27,080 WE TRIED TO HAVE 2744 02:14:27,080 --> 02:14:30,320 COLLABORATIONTOWN THE COHORTS 2745 02:14:30,320 --> 02:14:33,640 AND -- COLLABORATION BETWEEN THE 2746 02:14:33,640 --> 02:14:34,520 COHORTS AND THERE'S BEEN 2747 02:14:34,520 --> 02:14:36,040 COLLABORATION BETWEEN THE 2748 02:14:36,040 --> 02:14:36,280 COHORTS. 2749 02:14:36,280 --> 02:14:37,960 MANY ARE GETTING THEIR OMICS 2750 02:14:37,960 --> 02:14:39,960 DATA THROUGH TOP MED AND THE TOP 2751 02:14:39,960 --> 02:14:42,760 MED LUNG WORKING GROUP AND COPD 2752 02:14:42,760 --> 02:14:45,400 WORKING GROUP AND PULMONARY 2753 02:14:45,400 --> 02:14:47,720 FUNCTION WORKING GROUP AND IT'S 2754 02:14:47,720 --> 02:14:51,120 BEEN A NICE PLATFORM AND THE WAY 2755 02:14:51,120 --> 02:14:52,480 IS TO GET THE INVESTIGATORS AND 2756 02:14:52,480 --> 02:14:53,640 BASIC SCIENTISTS WORKING 2757 02:14:53,640 --> 02:14:55,320 TOGETHER AND THE COLLABORATIONS 2758 02:14:55,320 --> 02:14:57,200 HAVE GROWN ORGANICALLY BUT I 2759 02:14:57,200 --> 02:14:59,280 THINK THE OPPORTUNITY TO 2760 02:14:59,280 --> 02:15:01,280 PARTICIPATE IN WORKING GROUPS IS 2761 02:15:01,280 --> 02:15:02,320 AVAILABLE IN COPD. 2762 02:15:02,320 --> 02:15:06,320 I KNOW IT IS IN OTHER COHORTS AS 2763 02:15:06,320 --> 02:15:07,160 WELL PARTICIPATING IN OTHER 2764 02:15:07,160 --> 02:15:08,520 WORKING GROUPS IS AN OPTION. 2765 02:15:08,520 --> 02:15:10,760 THE BEST APPROACH WOULD BE TO 2766 02:15:10,760 --> 02:15:16,040 THINK ABOUT REACHING OUT TO 2767 02:15:16,040 --> 02:15:16,560 INDIVIDUAL INVESTIGATORS. 2768 02:15:16,560 --> 02:15:27,120 JAMES AND I WOULD BE HAPPY TAKE 2769 02:15:27,520 --> 02:15:29,840 INQUIRIES AND THEY ASK ABOUT A 2770 02:15:29,840 --> 02:15:33,160 GENE RELATED TO THE PROTEOMICS 2771 02:15:33,160 --> 02:15:34,880 OR TRANSCRIPTOMICS AND WE LOOKED 2772 02:15:34,880 --> 02:15:37,080 UP STUDIES IN THE PAST AND 2773 02:15:37,080 --> 02:15:38,320 THINKING OF MORE DURABLE AND 2774 02:15:38,320 --> 02:15:40,160 DEEPER COLLABORATION TO SAY HOW 2775 02:15:40,160 --> 02:15:43,120 CAN WE INVESTIGATE THE IMPACT OF 2776 02:15:43,120 --> 02:15:46,600 THE COPD GENETIC RISK PROFILE ON 2777 02:15:46,600 --> 02:15:47,960 MY MODEL SYSTEM WOULD BE THINGS 2778 02:15:47,960 --> 02:15:50,240 I'M HAPPY TO DISCUSS AS WELL. 2779 02:15:50,240 --> 02:15:52,400 DID YOU WANT TO ADD ANYTHING? 2780 02:15:52,400 --> 02:15:54,440 >> JUST WE ENCOURAGE 2781 02:15:54,440 --> 02:15:54,800 COLLABORATION. 2782 02:15:54,800 --> 02:15:58,840 WE HAVE A STUDIES COMMITTEE AND 2783 02:15:58,840 --> 02:16:01,120 WELCOME ANYBODY TO INTERACT AND 2784 02:16:01,120 --> 02:16:05,760 GATHER DATA OR SHARE IDEAS. 2785 02:16:05,760 --> 02:16:06,480 >> MEILAN, SAME QUESTION, 2786 02:16:06,480 --> 02:16:13,520 PLEASE. 2787 02:16:13,520 --> 02:16:14,400 >> SORRY. 2788 02:16:14,400 --> 02:16:17,120 THE SPIROMICS WEBSITE IS A GOOD 2789 02:16:17,120 --> 02:16:20,480 SOURCE OF INFORMATION. 2790 02:16:20,480 --> 02:16:22,040 WE'VE BEEN TRYING TO HARMONIZE 2791 02:16:22,040 --> 02:16:24,440 THE DATA ACCESS AND REQUEST 2792 02:16:24,440 --> 02:16:25,960 PROCESS TO BE SIMILAR TO COPD 2793 02:16:25,960 --> 02:16:29,600 GENE IT MAKE IT EASIER FOR 2794 02:16:29,600 --> 02:16:29,960 EVERYONE. 2795 02:16:29,960 --> 02:16:31,880 IF YOU GO TO THIS I THINK TYPE 2796 02:16:31,880 --> 02:16:36,440 IN THE WORD SPIROMICS IF YOU GO 2797 02:16:36,440 --> 02:16:38,080 TO THE WEBSITE YOU'LL PULL UP 2798 02:16:38,080 --> 02:16:39,280 PUBLIC INFORMATION ABOUT WHAT 2799 02:16:39,280 --> 02:16:44,160 DATA SETS ARE AVAILABLE AND THEN 2800 02:16:44,160 --> 02:16:49,800 YOU CAN SUBMIT A REQUEST FOR 2801 02:16:49,800 --> 02:16:50,840 MANUSCRIPT PROJECT AND REQUEST 2802 02:16:50,840 --> 02:16:52,600 FOR ANCILLARY STUDIES AND FOR 2803 02:16:52,600 --> 02:16:54,000 THE DATA. 2804 02:16:54,000 --> 02:16:55,440 THERE'S A DATA USE AGREEMENT AS 2805 02:16:55,440 --> 02:16:55,880 WELL. 2806 02:16:55,880 --> 02:16:59,720 WE TRIED TO HARMONIZE THE FORMS 2807 02:16:59,720 --> 02:17:01,920 TO TAKE EITHER VERSION BUT HAVE 2808 02:17:01,920 --> 02:17:03,920 SIMILAR DATA ON IT. 2809 02:17:03,920 --> 02:17:06,360 WE TRIED TO TO MAKE IT EASIER 2810 02:17:06,360 --> 02:17:07,400 FOR PEOPLE. 2811 02:17:07,400 --> 02:17:09,240 >> WE CO-CHAIR THE ANCILLARY 2812 02:17:09,240 --> 02:17:11,400 COMMITTEE FOR THE SPIROMICS 2813 02:17:11,400 --> 02:17:13,080 FAMILY OF STUDIES AND WE'D BE 2814 02:17:13,080 --> 02:17:15,400 HAPPY TO TALK TO PEOPLE WITH 2815 02:17:15,400 --> 02:17:23,120 JUST IDEAS FOR PRE-INQUIRPRE-IN. 2816 02:17:23,120 --> 02:17:24,520 >> I WANT TO SAY THAT TO THE 2817 02:17:24,520 --> 02:17:26,920 BASIC SCIENTISTS THERE'S A LOT 2818 02:17:26,920 --> 02:17:30,320 OF PEOPLE WHO DO MORE 2819 02:17:30,320 --> 02:17:31,280 TRANSLATIONAL RESEARCH IN A LOT 2820 02:17:31,280 --> 02:17:33,800 OF THE COHORTS THAT ARE VERY 2821 02:17:33,800 --> 02:17:36,040 WILLING TO WORK WITH PEOPLE WHO 2822 02:17:36,040 --> 02:17:37,520 ARE DOING MORE BASIC RESEARCH 2823 02:17:37,520 --> 02:17:39,560 WHO KNOW THE COHORTS VERY WELL 2824 02:17:39,560 --> 02:17:41,960 AND COULD POTENTIALLY HELP YOU 2825 02:17:41,960 --> 02:17:45,480 SO YOU'RE NOT JUST LOADED WITH 2826 02:17:45,480 --> 02:17:46,480 CLINICAL DATA YOU DON'T KNOW HOW 2827 02:17:46,480 --> 02:17:47,760 TO USE. 2828 02:17:47,760 --> 02:17:49,920 WE'RE WILLING TO COLLABORATE AND 2829 02:17:49,920 --> 02:17:54,560 TRY TO MAKE THAT DATA EASIER. 2830 02:17:54,560 --> 02:17:57,280 IT'S A MUCH MORE COLLABORATIVE 2831 02:17:57,280 --> 02:17:58,560 PROCESS THAN BASIC LABS WHICH 2832 02:17:58,560 --> 02:18:03,560 ARE LAB FOCUSSED. 2833 02:18:03,560 --> 02:18:05,240 SO WE'RE MAKING SURE PEOPLE 2834 02:18:05,240 --> 02:18:06,440 UNDERSTAND THAT. 2835 02:18:06,440 --> 02:18:11,960 IS GRAHAM ON. 2836 02:18:11,960 --> 02:18:17,200 >> YEAH, I CAN'T TURN MY VIDEO 2837 02:18:17,200 --> 02:18:17,360 ON. 2838 02:18:17,360 --> 02:18:23,520 >> THIS IS DR. BERIMO. 2839 02:18:23,520 --> 02:18:26,200 THESE ARE INTERESTING STUDIES 2840 02:18:26,200 --> 02:18:27,320 AND THERE ARE OPPORTUNITIES NOW 2841 02:18:27,320 --> 02:18:29,120 TO INVESTIGATE WHAT'S GOING ON 2842 02:18:29,120 --> 02:18:33,160 AT THE TISSUE LEVEL OF THE LUNG. 2843 02:18:33,160 --> 02:18:35,560 DURING THESE VARIOUS TYPES OF 2844 02:18:35,560 --> 02:18:38,600 CLINICAL PRESENTATIONS. 2845 02:18:38,600 --> 02:18:40,480 THE BIOMARKER HAS PROVEN MORE 2846 02:18:40,480 --> 02:18:43,480 AND MORE RELIABLE AND REFLECTING 2847 02:18:43,480 --> 02:18:46,240 WHAT'S GOING ON WITH THE 2848 02:18:46,240 --> 02:18:47,560 DISEASE. 2849 02:18:47,560 --> 02:18:50,000 IT DETECTS ELASTIC TISSUE 2850 02:18:50,000 --> 02:18:50,840 BREAKDOWN AND APPEARS WITH TIME 2851 02:18:50,840 --> 02:18:56,160 GOING ON WITH THE STUDIES 2852 02:18:56,160 --> 02:18:59,360 ELASTIC TISSUE BREAKDOWN IS 2853 02:18:59,360 --> 02:19:00,920 STILL A FUNDAMENTAL MECHANISM IN 2854 02:19:00,920 --> 02:19:03,120 COPD AND HERE YOU HAVE VARIOUS 2855 02:19:03,120 --> 02:19:05,360 PHASES IN THE DISEASE AND EARLY 2856 02:19:05,360 --> 02:19:08,200 STAGES AND LATE STAGES AND SO ON 2857 02:19:08,200 --> 02:19:09,880 AND BIOMARKER RESULTS 2858 02:19:09,880 --> 02:19:11,200 PARTICULARLY WITH REGARD TO 2859 02:19:11,200 --> 02:19:14,800 ELASTIC DEGRADATION WOULD BE I 2860 02:19:14,800 --> 02:19:16,720 THINK VERY SIGNIFICANT IN TRYING 2861 02:19:16,720 --> 02:19:19,360 TO UNDERSTAND WHAT'S GOING ON 2862 02:19:19,360 --> 02:19:23,880 WITH THE DISEASE AT THESE 2863 02:19:23,880 --> 02:19:27,680 VARIOUS STAGES OF LIFE. 2864 02:19:27,680 --> 02:19:29,080 THERE'S MORE RELIABLE BIOMEDICAL 2865 02:19:29,080 --> 02:19:30,520 WE HAVE AND URGE YOU TO INCLUDE 2866 02:19:30,520 --> 02:19:33,080 IT IN YOUR STUDIES. 2867 02:19:33,080 --> 02:19:37,160 >> THANK YOU. 2868 02:19:37,160 --> 02:19:38,320 >> ANOTHER GOOD POTENTIAL AREA 2869 02:19:38,320 --> 02:19:39,520 OF COLLABORATION. 2870 02:19:39,520 --> 02:19:42,040 IF PEOPLE HAVE SPECIFIC IDEAS I 2871 02:19:42,040 --> 02:19:43,560 THERE WERE SOME AROUND OR 2872 02:19:43,560 --> 02:19:47,680 QUESTIONS AROUND AIRWAY DISEASE, 2873 02:19:47,680 --> 02:19:48,600 AROUND OTHER EXPOSURES BUT 2874 02:19:48,600 --> 02:19:49,800 GRAHAM WOULD YOU MIND ANSWERING 2875 02:19:49,800 --> 02:19:51,920 FOR US YOUR IDEAS ON 2876 02:19:51,920 --> 02:19:54,440 COLLABORATION AND HOW PEOPLE CAN 2877 02:19:54,440 --> 02:19:55,440 USE YOUR DATA? 2878 02:19:55,440 --> 02:19:58,080 >> YEAH, SURE. 2879 02:19:58,080 --> 02:20:00,680 I AGREE WITH EARLIER COMMENTS I 2880 02:20:00,680 --> 02:20:02,960 THINK GETTING IN TOUCH WITH 2881 02:20:02,960 --> 02:20:04,560 NASCENT INVESTIGATORS AND 2882 02:20:04,560 --> 02:20:08,600 JOINING THE CLUB, SHALL WE SAY, 2883 02:20:08,600 --> 02:20:10,960 IS A GOOD WAY TO GO BECAUSE THE 2884 02:20:10,960 --> 02:20:12,800 DEA DATA IS COMPLEX AND HARD TO 2885 02:20:12,800 --> 02:20:14,280 DOWNLOAD AND DEAL WITH IT. 2886 02:20:14,280 --> 02:20:17,080 MESA STARTED AS A FEW HUNDRED 2887 02:20:17,080 --> 02:20:17,400 INVESTIGATORS. 2888 02:20:17,400 --> 02:20:20,400 IT'S NOW A FEW THOUSAND 2889 02:20:20,400 --> 02:20:20,760 INVESTIGATORS. 2890 02:20:20,760 --> 02:20:25,560 ANYBODY CAN JOIN. 2891 02:20:25,560 --> 02:20:28,280 THERE'S NO PARTICULAR AND WE 2892 02:20:28,280 --> 02:20:29,600 CONTINUE TO DO TO WHEN WE START 2893 02:20:29,600 --> 02:20:33,160 ON THE MULTI-OMICS WE NEED TO 2894 02:20:33,160 --> 02:20:35,480 UNDERSTAND EVERYTHING. 2895 02:20:35,480 --> 02:20:38,120 THE OTHER COMMENT IS THAT 2896 02:20:38,120 --> 02:20:39,920 THERE'S INCREASING EFFORTS FOR 2897 02:20:39,920 --> 02:20:42,560 HARMONIZATION ACROSS THE STUDIES 2898 02:20:42,560 --> 02:20:44,040 WHICH WILL MAKE THINGS A BIT 2899 02:20:44,040 --> 02:20:49,560 EASIER AND SOME OF THOSE WERE 2900 02:20:49,560 --> 02:20:51,280 ALLUDED TO ALREADY. 2901 02:20:51,280 --> 02:20:56,600 AND WE ARE ALSO THERE'S A 2902 02:20:56,600 --> 02:21:03,320 COLLABORATION FOR COHORTS ACROSS 2903 02:21:03,320 --> 02:21:04,640 RESEARCH THAT IS NOT LUNG 2904 02:21:04,640 --> 02:21:07,320 FOCUSSED BUT HAS A FAIR AMOUNT 2905 02:21:07,320 --> 02:21:09,480 OF LUNG PHENOTYPING THAT WILL 2906 02:21:09,480 --> 02:21:11,840 INCREASINGLY BE HARMONIZED AND 2907 02:21:11,840 --> 02:21:14,160 HOPEFULLY AVAILABLE IN A CENTRAL 2908 02:21:14,160 --> 02:21:15,320 SOURCE VIA THE NIH. 2909 02:21:15,320 --> 02:21:19,400 THAT'S ALSO ONE WAY TO GET 2910 02:21:19,400 --> 02:21:19,960 INVOLVED WITH MULTIPLE WORK. 2911 02:21:19,960 --> 02:21:27,240 THANK YOU. 2912 02:21:27,240 --> 02:21:27,800 >> THANK YOU. 2913 02:21:27,800 --> 02:21:32,800 DR. WASHKO CAN YOU TELL US ABOUT 2914 02:21:32,800 --> 02:21:34,120 ALA AND CARDIA. 2915 02:21:34,120 --> 02:21:35,920 >> I WOULD ECHO WHAT EVERYONE 2916 02:21:35,920 --> 02:21:36,120 SAID. 2917 02:21:36,120 --> 02:21:38,280 I AGREE THAT IF WE LOOK AT 2918 02:21:38,280 --> 02:21:40,880 CARDIA BECAUSE IT'S BEEN SUCH A 2919 02:21:40,880 --> 02:21:42,600 TRUE LIFE COURSE STUDIED IT'S 2920 02:21:42,600 --> 02:21:44,680 LIKE SECRETS HIDDEN IN PLAIN 2921 02:21:44,680 --> 02:21:45,880 SITE. 2922 02:21:45,880 --> 02:21:48,080 THE NAVIGATION OF THE DATA OF 2923 02:21:48,080 --> 02:21:53,360 TOP MED IS VERY INTIMIDATING. 2924 02:21:53,360 --> 02:21:54,960 REACH OUT TO US AND HAPPY TO 2925 02:21:54,960 --> 02:21:55,720 GUIDE THINGS. 2926 02:21:55,720 --> 02:21:57,440 BEING ON THE INSIDE IS 2927 02:21:57,440 --> 02:22:01,480 CONSIDERED A CARDIA PERSON OR A 2928 02:22:01,480 --> 02:22:06,520 LUNG HEALTH PERSON EVEN NAVIGATE 2929 02:22:06,520 --> 02:22:08,480 THOSE DATA. 2930 02:22:08,480 --> 02:22:10,320 ALA JUST GETTING GOING. 2931 02:22:10,320 --> 02:22:13,800 WE'RE OPEN TO ALL FORMS OF 2932 02:22:13,800 --> 02:22:14,680 COLLABORATION AND BUILDING 2933 02:22:14,680 --> 02:22:16,120 BRIDGES WITH OTHER COHORTS AND 2934 02:22:16,120 --> 02:22:20,760 WE'VE BEEN INTENTIONAL IN 2935 02:22:20,760 --> 02:22:22,080 HARMONIZING A LOT OF THE DATA 2936 02:22:22,080 --> 02:22:24,480 WITH THE LONG OBSERVATIONAL 2937 02:22:24,480 --> 02:22:27,080 STUDIES TO ACTUALLY ENHANCE 2938 02:22:27,080 --> 02:22:27,680 COMMUNICATION. 2939 02:22:27,680 --> 02:22:29,360 SO IF PEOPLE FIND SOMETHING THEY 2940 02:22:29,360 --> 02:22:30,600 CAN DIRECTLY COME OVER TO 2941 02:22:30,600 --> 02:22:32,200 ANOTHER COHORT. 2942 02:22:32,200 --> 02:22:34,320 THAT IS BY DESIGN WITH THE GOAL 2943 02:22:34,320 --> 02:22:35,320 AND HOPE THAT PEOPLE START 2944 02:22:35,320 --> 02:22:36,000 WORKING WITH ALL THE DATA THAT 2945 02:22:36,000 --> 02:22:42,600 WE HAVE. 2946 02:22:42,600 --> 02:22:44,880 >> PROFESSOR BOURBEAU. 2947 02:22:44,880 --> 02:22:47,920 >> I AGREE WITH WHAT'S BEEN SAID 2948 02:22:47,920 --> 02:22:49,160 THE EASIEST QUESTION IS ANSWER 2949 02:22:49,160 --> 02:22:51,240 IS THE SECOND ONE AND THE NEEDS 2950 02:22:51,240 --> 02:22:53,240 AND THE EASIEST WAY TO ACCESS US 2951 02:22:53,240 --> 02:22:55,400 IS THROUGH THE WEBSITE. 2952 02:22:55,400 --> 02:22:56,920 WE HAVE DONE QUITE A BIT OF WORK 2953 02:22:56,920 --> 02:23:02,080 IN THE LAST COUPLE YEARS WHERE 2954 02:23:02,080 --> 02:23:06,400 YOU CAN ACCESS WHAT IS 2955 02:23:06,400 --> 02:23:06,720 ACCESSIBLE. 2956 02:23:06,720 --> 02:23:09,320 WE HAVE NOW A SYSTEM THAT 2957 02:23:09,320 --> 02:23:10,920 ALLOWED PEOPLE TO APPLY TO THE 2958 02:23:10,920 --> 02:23:13,360 WEBSITE WHERE THERE IS A FORM TO 2959 02:23:13,360 --> 02:23:14,560 APPLY AND WE HAVE A COMMITTEE IN 2960 02:23:14,560 --> 02:23:17,480 PLACE TO REVIEW THE PROPOSAL AND 2961 02:23:17,480 --> 02:23:18,680 THE POSSIBILITY FOR PEOPLE 2962 02:23:18,680 --> 02:23:21,000 OUTSIDE CANADA TO DO THE 2963 02:23:21,000 --> 02:23:26,120 ANALYSIS WHERE EVERYTHING IS ON 2964 02:23:26,120 --> 02:23:29,560 THE CENTRAL PLATFORM AND WORK TO 2965 02:23:29,560 --> 02:23:32,520 HAVE THAT APPROVED AND HAVE THAT 2966 02:23:32,520 --> 02:23:33,360 IN PLACE. 2967 02:23:33,360 --> 02:23:34,480 I WOULD RECOMMEND PEOPLE TO GO 2968 02:23:34,480 --> 02:23:38,400 ON THE WEBSITE AND SEE WHAT WE 2969 02:23:38,400 --> 02:23:41,080 HAVE ALREADY DONE AND SUMMARY 2970 02:23:41,080 --> 02:23:44,400 KEY MESSAGES AND WHAT WOULD BE 2971 02:23:44,400 --> 02:23:49,640 ACCESSIBLE NOW AND WHAT IS 2972 02:23:49,640 --> 02:23:51,560 COMING WITH THE FOLLOWING 2973 02:23:51,560 --> 02:23:51,880 VISUAL. 2974 02:23:51,880 --> 02:23:57,360 I WOULD PROBABLY END BY THE 2975 02:23:57,360 --> 02:24:02,320 FIRST QUESTION IS AND THERE'S AN 2976 02:24:02,320 --> 02:24:04,200 ART AND BEYOND THAT I WOULD SAY 2977 02:24:04,200 --> 02:24:08,840 IF WE REALLY WANT TO GO TAKE 2978 02:24:08,840 --> 02:24:11,800 HUGE ADVANTAGE OF TAKING ALL THE 2979 02:24:11,800 --> 02:24:21,640 COHORT WITH THE SIMILARITY, 2980 02:24:21,640 --> 02:24:22,440 DIFFERENCES AND COMPLEMENTARTY 2981 02:24:22,440 --> 02:24:25,280 AND THERE'S HARMONIZATION. 2982 02:24:25,280 --> 02:24:27,760 THAT'S SOMETHING THE NHLBI, NIH 2983 02:24:27,760 --> 02:24:31,720 WOULD LIKE TO THINK ABOUT AT 2984 02:24:31,720 --> 02:24:33,560 LEAST TO RECEIVE OR HAVE FUNDING 2985 02:24:33,560 --> 02:24:35,520 WE CAN PUT TOGETHER A PROPOSAL 2986 02:24:35,520 --> 02:24:38,520 AND WHAT WOULD IT TAKE TO REALLY 2987 02:24:38,520 --> 02:24:39,160 GET TOGETHER. 2988 02:24:39,160 --> 02:24:44,360 EVERYTHING HAS TO DO WITH 2989 02:24:44,360 --> 02:24:48,440 RESEARCH QUESTION AND OTHER 2990 02:24:48,440 --> 02:24:49,880 THING IS MAY BE MORE COMPLICATED 2991 02:24:49,880 --> 02:24:53,880 BUT AT THE END OF THE DAY IT 2992 02:24:53,880 --> 02:24:57,120 NEEDS A PROJECT WHERE THERE 2993 02:24:57,120 --> 02:25:00,120 WOULD BE MORE THAN ONLY MUTUAL 2994 02:25:00,120 --> 02:25:01,920 INTEREST BUT SOMETHING WE CAN 2995 02:25:01,920 --> 02:25:04,320 PLAN OVER THE YEAR THAT WOULD 2996 02:25:04,320 --> 02:25:10,600 REALLY -- IT'S BEEN DONE IN THE 2997 02:25:10,600 --> 02:25:11,840 CARDIOLOGY COHORT WHERE THERE'S 2998 02:25:11,840 --> 02:25:15,520 BEEN HARMON AND A GROUP IN 2999 02:25:15,520 --> 02:25:17,280 COLOMBIA HAS DONE WORK WHERE WE 3000 02:25:17,280 --> 02:25:22,520 CAN LEARN FROM OTHERS AS WELL IN 3001 02:25:22,520 --> 02:25:22,720 THIS. 3002 02:25:22,720 --> 02:25:25,120 IT NEEDS TO BE HARMONIZED AND 3003 02:25:25,120 --> 02:25:35,560 NOT ONLY LOCAL INITIATIVE. 3004 02:25:35,880 --> 02:25:42,200 THE LAST FROM THE HEALTH STUDY 3005 02:25:42,200 --> 02:25:52,680 AND WAYS TO COLLABORATE AND 3006 02:25:56,480 --> 02:26:01,840 THERE WAS AN INVESTIGATOR COHORT 3007 02:26:01,840 --> 02:26:04,560 AND IT WAS A SMALL NUMBER OF 3008 02:26:04,560 --> 02:26:04,880 INVESTIGATORS. 3009 02:26:04,880 --> 02:26:09,520 SINCE I HAVE TAKEN OVER AND 3010 02:26:09,520 --> 02:26:10,920 EXPANDED COLLABORATIONS BECAUSE 3011 02:26:10,920 --> 02:26:12,320 I WOULD LOOK FOR COLLABORATION 3012 02:26:12,320 --> 02:26:19,040 TO MAKE OUR WORK BETTER. 3013 02:26:19,040 --> 02:26:22,920 HOWEVER, UNLIKE THE MESA COHORT 3014 02:26:22,920 --> 02:26:25,800 IT'S NOT LIKE HUNDREDS BUT IT IS 3015 02:26:25,800 --> 02:26:27,000 A BIT CLOSE TO TASK BUT WE DO 3016 02:26:27,000 --> 02:26:29,880 HAVE A WEBSITE. 3017 02:26:29,880 --> 02:26:36,040 WE HAVE A WAY OF APPLYING FOR 3018 02:26:36,040 --> 02:26:38,040 DATA THERE ARE DATA ON THE 3019 02:26:38,040 --> 02:26:40,760 WEBSITE YOU HAVE TO CUT AND 3020 02:26:40,760 --> 02:26:42,480 PASTE ON THE DATA REQUEST FORM 3021 02:26:42,480 --> 02:26:44,640 AN IT GETS AUTOMATICALLY SENT TO 3022 02:26:44,640 --> 02:26:45,800 THE DATABASE MANAGER BUT THE 3023 02:26:45,800 --> 02:26:49,040 PROPOSAL HAS TO BE APPROVED BY 3024 02:26:49,040 --> 02:26:49,920 THE TEST TABLE COMMITTEE. 3025 02:26:49,920 --> 02:26:54,520 SO THERE'S A PROCESS BUT WE ALSO 3026 02:26:54,520 --> 02:27:01,440 HAVE POLICIES AROUND HOW WE LOOK 3027 02:27:01,440 --> 02:27:05,920 AT PAPERS AND THE POLICY IS ON 3028 02:27:05,920 --> 02:27:07,120 THE WEBSITE. 3029 02:27:07,120 --> 02:27:09,040 THE FIRST QUESTION ABOUT 3030 02:27:09,040 --> 02:27:14,120 COLLABORATIONS I TOTALLY AGREE 3031 02:27:14,120 --> 02:27:16,080 WITH THE FACT THAT IT'S NOT JUST 3032 02:27:16,080 --> 02:27:17,560 GETTING TOGETHER AND TALKING 3033 02:27:17,560 --> 02:27:18,120 ABOUT IT BUT HAS TO BE A 3034 02:27:18,120 --> 02:27:22,880 PROJECT. 3035 02:27:22,880 --> 02:27:24,480 THE TASK HAS COLLABORATED WITH 3036 02:27:24,480 --> 02:27:29,560 EUROPEAN COHORTS AND IT'S CALLED 3037 02:27:29,560 --> 02:27:34,080 AGING LUNG COHORT AND WE HAVE A 3038 02:27:34,080 --> 02:27:36,560 CONSORTIUM AND THAT EXPIRED IN 3039 02:27:36,560 --> 02:27:36,760 2020. 3040 02:27:36,760 --> 02:27:41,720 WE BROUGHT SIMILAR COHORTS 3041 02:27:41,720 --> 02:27:42,880 TOGETHER AND CROSS SECTIONAL 3042 02:27:42,880 --> 02:27:45,080 STUDIES AND THAT WORKED WELL. 3043 02:27:45,080 --> 02:27:54,200 WE HAD WORK PACKAGES AND WE 3044 02:27:54,200 --> 02:27:56,600 STARTED A COLLABORATION AND 3045 02:27:56,600 --> 02:27:58,120 STARTED IT THROUGH DR. WASHKO 3046 02:27:58,120 --> 02:28:00,240 AND IT'S CALLED AUSTRALIAN 3047 02:28:00,240 --> 02:28:07,000 U.S. COHORT COLLABORATION. 3048 02:28:07,000 --> 02:28:08,400 THAT'S ONE COHORT TOGETHER BUT 3049 02:28:08,400 --> 02:28:15,880 IF YOU WANT TO HAVE A CONSORTIA 3050 02:28:15,880 --> 02:28:17,480 IT HAS TO BE FUNDED BUT THAT'S 3051 02:28:17,480 --> 02:28:19,000 THE WAY FORWARD BECAUSE 3052 02:28:19,000 --> 02:28:19,680 INDIVIDUALLY THERE'S SO MUCH WE 3053 02:28:19,680 --> 02:28:27,720 CAN TWO -- DO AND IF WE THINK 3054 02:28:27,720 --> 02:28:29,880 OF MECHANISTIC STUDIES THEY HAVE 3055 02:28:29,880 --> 02:28:32,240 TO BE REPLICATED AND WE ALWAYS 3056 02:28:32,240 --> 02:28:40,800 ASK FOR REPLICATIONS NOW. 3057 02:28:40,800 --> 02:28:46,320 WE SHOULD COME TOGETHER AS A 3058 02:28:46,320 --> 02:28:48,200 CONSORTIUM AND I THINK IT NEEDS 3059 02:28:48,200 --> 02:28:49,520 TO BE A PROJECT CAN'T BE JUST 3060 02:28:49,520 --> 02:28:49,800 INTEREST. 3061 02:28:49,800 --> 02:28:58,000 I FULLY AGREE. 3062 02:28:58,000 --> 02:29:04,400 >> WOULD YOU ALLOW ME TO ADD 3063 02:29:04,400 --> 02:29:04,720 SOMETHING? 3064 02:29:04,720 --> 02:29:07,560 >> PLEASE. 3065 02:29:07,560 --> 02:29:11,160 TO REINFORCE IT'S NOT ONLY ABOUT 3066 02:29:11,160 --> 02:29:16,440 THE EPIDEMIOLOGY STUDY AND 3067 02:29:16,440 --> 02:29:18,040 ANSWER QUESTION AND 3068 02:29:18,040 --> 02:29:19,760 HARMONIZATION OF THE COHORT BUT 3069 02:29:19,760 --> 02:29:22,800 DO LEAD YOUR PROJECT AND THAT'S 3070 02:29:22,800 --> 02:29:24,480 THE REASON WHY WE'RE HERE FOR 3071 02:29:24,480 --> 02:29:28,320 TWO DAYS AND TO THE FUNDAMENTAL 3072 02:29:28,320 --> 02:29:30,920 RESEARCH BECAUSE THIS WOULD BE 3073 02:29:30,920 --> 02:29:33,600 EXTREMELY POWERFUL IF WE WERE 3074 02:29:33,600 --> 02:29:34,960 WORKING TOGETHER IN THE 3075 02:29:34,960 --> 02:29:36,320 HARMONIZATION OF THE COHORT NOT 3076 02:29:36,320 --> 02:29:39,920 ONLY DEFINING THE QUESTION YOU 3077 02:29:39,920 --> 02:29:43,920 CAN ANSWER BETTER FROM AN 3078 02:29:43,920 --> 02:29:44,800 EPIDEMIOLOGY POINT OF VIEW AND 3079 02:29:44,800 --> 02:29:48,320 THE MECHANISTIC DIFFERENT WAY OF 3080 02:29:48,320 --> 02:29:54,920 LOOKING AT MECHANISTIC FROM 3081 02:29:54,920 --> 02:29:56,680 BIOLOGICAL ETCETERA AND FROM 3082 02:29:56,680 --> 02:30:00,280 WHERE ALL THE FUNDAMENTAL 3083 02:30:00,280 --> 02:30:01,600 QUESTION COULD LEAD STO THE 3084 02:30:01,600 --> 02:30:07,160 GROUP OF RESEARCH AND RESEARCHER 3085 02:30:07,160 --> 02:30:09,080 TO BE PART OF THAT CONSORTIUM 3086 02:30:09,080 --> 02:30:13,960 AND WOULD BE POWERFUL ACROSS THE 3087 02:30:13,960 --> 02:30:16,760 SPECTRUM AND BENEFICIAL NOT ONLY 3088 02:30:16,760 --> 02:30:18,160 FROM A COHORT POINT OF VIEW BUT 3089 02:30:18,160 --> 02:30:20,040 ACCESS TO NEW RESEARCH QUESTION 3090 02:30:20,040 --> 02:30:21,600 AND DEVELOPING MORE FUNDAMENTAL 3091 02:30:21,600 --> 02:30:29,720 RESEARCH. 3092 02:30:29,720 --> 02:30:30,240 >> THANK YOU. 3093 02:30:30,240 --> 02:30:31,280 VERY USEFUL. 3094 02:30:31,280 --> 02:30:32,880 I THINK YOU'RE TOUCHING ON WHAT 3095 02:30:32,880 --> 02:30:36,680 SOME OF THESE OTHER QUESTIONS 3096 02:30:36,680 --> 02:30:38,720 THE FOLLOW-UP QUESTION TO THIS 3097 02:30:38,720 --> 02:30:43,320 QUESTION AND I WILL SAY STARTING 3098 02:30:43,320 --> 02:30:46,920 WITH WE'RE HEARING HOW DO WE 3099 02:30:46,920 --> 02:30:50,000 TOUCH BASE WITH SOME OF THESE 3100 02:30:50,000 --> 02:30:51,360 COHORTS BUT DOES ANYBODY HAVE 3101 02:30:51,360 --> 02:30:56,440 OUT OF THE BOX IDEAS HOW TO 3102 02:30:56,440 --> 02:31:01,600 POTENTIALLY IMPROVE CROSS-COHORT 3103 02:31:01,600 --> 02:31:02,440 COLLABORATION AND WE TALKED 3104 02:31:02,440 --> 02:31:04,720 ABOUT PUB MED AS ONE WAY BUT 3105 02:31:04,720 --> 02:31:09,360 DOES ANYBODY HAVE IDEAS HOW TO 3106 02:31:09,360 --> 02:31:11,520 PUSH THIS FORWARD BECAUSE THERE 3107 02:31:11,520 --> 02:31:22,040 ARE SUBSTANTIAL BARRIERS HERE. 3108 02:31:24,320 --> 02:31:27,280 >> I THINK THERE COULD BE A REAL 3109 02:31:27,280 --> 02:31:27,560 CATALYST. 3110 02:31:27,560 --> 02:31:32,600 BECAUSE WE HAVE TO HAVE OUR DATA 3111 02:31:32,600 --> 02:31:34,800 THAT COMES FROM TOP MED INTO THE 3112 02:31:34,800 --> 02:31:35,040 CATALYST. 3113 02:31:35,040 --> 02:31:39,440 >> WOULD YOU MIND SAYING WHAT IT 3114 02:31:39,440 --> 02:31:39,600 IS. 3115 02:31:39,600 --> 02:31:43,360 >> NHLBI REPOSITORY OF A 3116 02:31:43,360 --> 02:31:48,000 PLATFORM ALL THE OMICS DATA GOES 3117 02:31:48,000 --> 02:31:50,240 SUBMITTED ARE COPD AND CT SCANS 3118 02:31:50,240 --> 02:31:51,360 THERE AS WELL AS AND OTHER 3119 02:31:51,360 --> 02:31:54,880 EFFORTS TO GET ADDITIONAL 3120 02:31:54,880 --> 02:31:57,720 IMAGING DATA AND PHENOTYPE DATA 3121 02:31:57,720 --> 02:32:00,560 AND MY UNDERSTANDING IS THE TOP 3122 02:32:00,560 --> 02:32:03,200 MED THE C4R WILL GO THERE. 3123 02:32:03,200 --> 02:32:04,360 RATHER THAN TRYING TO CREATE A 3124 02:32:04,360 --> 02:32:08,280 NEW CLOUD ENVIRONMENT I THINK WE 3125 02:32:08,280 --> 02:32:10,880 SHOULD REDOUBLE OUR EFFORTS TO 3126 02:32:10,880 --> 02:32:14,240 GET DATA IN THE MOST HARMONIZED 3127 02:32:14,240 --> 02:32:16,440 FORMAT WE CAN INTO THE CATALYST 3128 02:32:16,440 --> 02:32:18,440 SO INVESTIGATORS CAN GET ACCESS 3129 02:32:18,440 --> 02:32:19,080 TO IT. 3130 02:32:19,080 --> 02:32:20,760 >> CAN I ASK ANYONE WHO MIGHT 3131 02:32:20,760 --> 02:32:22,720 KNOW THIS, IS IT POSSIBLE TO PUT 3132 02:32:22,720 --> 02:32:25,480 THE NON-AMERICAN COHORTS INTO 3133 02:32:25,480 --> 02:32:25,760 THE SITE? 3134 02:32:25,760 --> 02:32:35,320 GRAHAM, YOU'RE NODDING. 3135 02:32:35,320 --> 02:32:41,840 >> SO THE QUICK ANSWER IS YES. 3136 02:32:41,840 --> 02:32:48,200 THERE ARE DIFFERENT AREAS WITHIN 3137 02:32:48,200 --> 02:32:49,280 BIO DATA CATALYST. 3138 02:32:49,280 --> 02:32:53,520 I WAS GOING TO ADD IN TERMS OF I 3139 02:32:53,520 --> 02:32:59,160 PUT IN THE CHAT A COLLABORATIVE 3140 02:32:59,160 --> 02:33:04,840 COHORT OF RESEARCH IS IN PROCESS 3141 02:33:04,840 --> 02:33:15,360 OF HARMONIZING COHORTS THOSE 3142 02:33:16,280 --> 02:33:17,680 MENTIONED TODAY AND THAT'S 3143 02:33:17,680 --> 02:33:18,560 INITIALLY FOR COVID RESEARCH BUT 3144 02:33:18,560 --> 02:33:22,360 WE'RE WORKING TO EXPAND IT. 3145 02:33:22,360 --> 02:33:28,760 ONE OF THE NICE THINGS IS 3146 02:33:28,760 --> 02:33:32,560 BETWEEN EPIDEMIOLOGIC ANALYSES 3147 02:33:32,560 --> 02:33:34,960 THE COMPUTE POWER IS LESS 3148 02:33:34,960 --> 02:33:35,760 BURDENSOME IN THE CLOUD THAN 3149 02:33:35,760 --> 02:33:38,800 LARGE SCALE OMIC ANALYSES. 3150 02:33:38,800 --> 02:33:44,640 THAT THEN THE DATA IS IN ONE 3151 02:33:44,640 --> 02:33:50,080 PLACE AND YOU ANALYZE THERE'S AN 3152 02:33:50,080 --> 02:33:56,520 A VARIETY OF WAYS TO WORK THIS 3153 02:33:56,520 --> 02:33:56,680 OUT. 3154 02:33:56,680 --> 02:34:03,160 THIS IS MOVING WELL. 3155 02:34:03,160 --> 02:34:06,280 YOU HAD A COMMENT. 3156 02:34:06,280 --> 02:34:09,800 >> THIS COULD BE GOOD IF THE 3157 02:34:09,800 --> 02:34:12,000 P.I.s CAN GET TOGETHER AND TALK 3158 02:34:12,000 --> 02:34:12,400 ABOUT THIS. 3159 02:34:12,400 --> 02:34:15,720 WE ARE ALL BUSY WE DON'T WANT 3160 02:34:15,720 --> 02:34:17,040 ANOTHER MEETING. 3161 02:34:17,040 --> 02:34:19,840 I THINK SOME DOWNGOING 3162 02:34:19,840 --> 02:34:21,680 DISCUSSIONS IS NEEDED BECAUSE IT 3163 02:34:21,680 --> 02:34:32,120 CAN'T HAPPEN OVERNIGHT. 3164 02:34:36,120 --> 02:34:41,960 >> FERNANDO DO YOU HAVE 3165 02:34:41,960 --> 02:34:42,960 SOMETHING ON THE CATSELT. 3166 02:34:42,960 --> 02:34:47,800 >> IT'S FUNDED BY THE ERS THAT 3167 02:34:47,800 --> 02:34:50,840 HAS BASKETBALL ABLE TO DO THIS 3168 02:34:50,840 --> 02:34:53,240 FOR EARLY LUNGS FUNCTION AND 3169 02:34:53,240 --> 02:34:55,880 COPD AND THEY ORGANIZED COHORTS 3170 02:34:55,880 --> 02:34:58,000 ACROSS EUROPEAN COMPONENTS AND 3171 02:34:58,000 --> 02:35:08,520 THAT'S BEEN HIGHLY SUCCESSFUL. 3172 02:35:15,600 --> 02:35:15,960 AC 3173 02:35:15,960 --> 02:35:17,800 >> WHAT ARE THE RESOURCES THAT 3174 02:35:17,800 --> 02:35:27,800 CAME UP IN THE CHAT IS BIO LINK. 3175 02:35:27,800 --> 02:35:29,560 ANDESE OF USING THAT AND 3176 02:35:29,560 --> 02:35:40,000 HARMONIZING THE DATA SETS. 3177 02:35:42,920 --> 02:35:45,560 THERE ARE OBSTACLES AND BETWEEN 3178 02:35:45,560 --> 02:35:47,560 COUNTRIES THINGS CAN GET MORE 3179 02:35:47,560 --> 02:35:49,040 COMPLICATED. 3180 02:35:49,040 --> 02:35:51,360 THAT'S WHY IF YOU WANT TO DO 3181 02:35:51,360 --> 02:35:52,440 THAT FROM A USA POINT OF VIEW 3182 02:35:52,440 --> 02:35:55,320 THAT MAY BE KIND OF EASIER. 3183 02:35:55,320 --> 02:35:56,320 YOU ALREADY HAVE SOME INITIATIVE 3184 02:35:56,320 --> 02:35:59,840 GOING ON. 3185 02:35:59,840 --> 02:36:01,400 IF YOU WANT TO LOOK AT THE 3186 02:36:01,400 --> 02:36:02,840 LARGER PERSPECTIVE, THEN I THINK 3187 02:36:02,840 --> 02:36:05,880 THIS GROUP WOULD BE A STARTING 3188 02:36:05,880 --> 02:36:07,360 POINT AND THAT COULD EVOLVE OVER 3189 02:36:07,360 --> 02:36:11,400 TIME WHERE OTHER COHORTS COULD 3190 02:36:11,400 --> 02:36:12,960 BE HARMONIZED. 3191 02:36:12,960 --> 02:36:16,880 THERE'S A LEGAL ISSUE ALSO. 3192 02:36:16,880 --> 02:36:23,000 AS A RESEARCHER YOU THINK DOING 3193 02:36:23,000 --> 02:36:24,560 THAT WITH VERY GOOD INTENTION 3194 02:36:24,560 --> 02:36:27,520 BUT WHEN IT COMES TO IMPLEMENT 3195 02:36:27,520 --> 02:36:33,720 ANY OF THIS IT IS SO COMPLICATED 3196 02:36:33,720 --> 02:36:38,120 FROM A LEGAL POINT OF VIEW 3197 02:36:38,120 --> 02:36:39,840 SHARING TISSUE AND DATA AND 3198 02:36:39,840 --> 02:36:42,880 THINGS LIKE THAT IS NOT 3199 02:36:42,880 --> 02:36:43,880 SOMETHING EASY. 3200 02:36:43,880 --> 02:36:45,800 THAT'S WHY IT NEEDS TO BE 3201 02:36:45,800 --> 02:36:49,920 ORGANIZED FROM THE POINT OF VIEW 3202 02:36:49,920 --> 02:36:52,720 THAT WE CAN SHARE GOOD 3203 02:36:52,720 --> 02:36:54,160 EXPERIENCE AND FERNANDO 3204 02:36:54,160 --> 02:36:56,360 MENTIONED OTHER COUNTRIES AND WE 3205 02:36:56,360 --> 02:36:57,880 CAN WORK ON HARMONIZATION AND WE 3206 02:36:57,880 --> 02:37:04,640 HAVE TO COME UP WITH A PLAN AND 3207 02:37:04,640 --> 02:37:07,240 THAT NEEDS TO BE DONE TO THE 3208 02:37:07,240 --> 02:37:11,400 FUNDING AND HAVING A GOOD PLAN 3209 02:37:11,400 --> 02:37:16,480 AND TOGETHER GET AND TRY TO 3210 02:37:16,480 --> 02:37:21,000 DISCUSS THAT. 3211 02:37:21,000 --> 02:37:22,320 EVERYTHING HAS TO START WITH A 3212 02:37:22,320 --> 02:37:23,960 PROJECT AND THINGS THAT ARE 3213 02:37:23,960 --> 02:37:28,120 CONCRETE AND ADDRESS A RESEARCH 3214 02:37:28,120 --> 02:37:29,760 QUESTION PEOPLE CAN SHARE AND 3215 02:37:29,760 --> 02:37:37,080 PUT THIS IN PLACE AND SEE IT IS 3216 02:37:37,080 --> 02:37:37,600 FOOE 3217 02:37:37,600 --> 02:37:43,560 FEASIBLE AND WORKING. 3218 02:37:43,560 --> 02:37:45,560 >> THE CHALLENGES OF 3219 02:37:45,560 --> 02:37:46,440 INTERNATIONAL COLLABORATION ARE 3220 02:37:46,440 --> 02:37:48,280 REAL AND IMPORTANT AND I THINK 3221 02:37:48,280 --> 02:37:51,120 THIS IS WHERE SOME OF THESE 3222 02:37:51,120 --> 02:37:53,480 MODELS OF FED RATED DATA 3223 02:37:53,480 --> 02:37:54,640 ANALYSIS HAVE BEEN DEVELOPED IN 3224 02:37:54,640 --> 02:37:56,040 EUROPE BECAUSE OF THE EFFORTS TO 3225 02:37:56,040 --> 02:37:58,920 WORK AROUND THE GDPR ARE WORTH 3226 02:37:58,920 --> 02:38:00,880 CONSIDERING AND IT STAYS AT THE 3227 02:38:00,880 --> 02:38:04,320 LOCAL INSTITUTION BUT THE 3228 02:38:04,320 --> 02:38:05,880 ANALYSIS IS DONE IN A FEDERATED 3229 02:38:05,880 --> 02:38:07,440 AND COLLABORATIVE WAY IS 3230 02:38:07,440 --> 02:38:09,000 SOMETHING WE COULD THINK ABOUT 3231 02:38:09,000 --> 02:38:10,200 TO EXTEND THE REACH OF THE 3232 02:38:10,200 --> 02:38:20,640 COHORTS BEYOND THE U.S. 3233 02:38:21,280 --> 02:38:23,560 WHAT I'M STRIKE IS THE CAT SAN 3234 02:38:23,560 --> 02:38:26,600 MODEL IS WHAT THEY'VE DONE 3235 02:38:26,600 --> 02:38:27,120 SUCCESSFULLY. 3236 02:38:27,120 --> 02:38:28,960 THEY'RE INTERESTED IN PARTNERING 3237 02:38:28,960 --> 02:38:32,240 TO DO SOMETHING SIMILAR IN THE 3238 02:38:32,240 --> 02:38:34,560 U.S. AND WOULD BE HIGHLY 3239 02:38:34,560 --> 02:38:36,120 FRUITFUL. 3240 02:38:36,120 --> 02:38:38,000 I'M ON THE STEERING COMMITTEE 3241 02:38:38,000 --> 02:38:44,320 AND I NOW AT THE LAST ERS THERE 3242 02:38:44,320 --> 02:38:46,840 WAS SOMETHING SIMILAR AND 3243 02:38:46,840 --> 02:38:49,840 BRINGING IN JOB COHORTS. 3244 02:38:49,840 --> 02:38:51,160 ERS MAY BE THE NEXT OPPORTUNITY 3245 02:38:51,160 --> 02:38:53,440 MANY OF US CAN GET TOGETHER TO 3246 02:38:53,440 --> 02:39:03,840 OFFLINE TALK ABOUT THIS. 3247 02:39:04,960 --> 02:39:07,480 >> OUTSIDE THE MEETING YOU MAY 3248 02:39:07,480 --> 02:39:09,960 NEED MORE MEETINGS. 3249 02:39:09,960 --> 02:39:13,600 >> IT WAS FUNDED UNDER CRC. 3250 02:39:13,600 --> 02:39:21,400 ARE YOU ELIGIBLE FOR CRC FUNDING 3251 02:39:21,400 --> 02:39:27,920 OR ONLY EUROPEANS? 3252 02:39:27,920 --> 02:39:29,880 >> 3253 02:39:29,880 --> 02:39:32,240 >> THE LAST MEETING THE QUESTION 3254 02:39:32,240 --> 02:39:33,360 WAS WHETHER SOMETHING SIMILAR 3255 02:39:33,360 --> 02:39:34,120 COULD BE DONE. 3256 02:39:34,120 --> 02:39:39,560 IT WAS A MODEST AMOUNT OF 3257 02:39:39,560 --> 02:39:42,520 FUNDING PROVIDED VIA THEIR 3258 02:39:42,520 --> 02:39:47,960 COLLABORATION MECHANISM. 3259 02:39:47,960 --> 02:39:48,800 >> I THINK THEY HAVE INDUSTRY 3260 02:39:48,800 --> 02:39:53,960 FUNDING. 3261 02:39:53,960 --> 02:39:59,200 >> TO EXPAND ON THE COMMENT THE 3262 02:39:59,200 --> 02:40:01,400 COLLABORATION BETWEEN CARDIA AND 3263 02:40:01,400 --> 02:40:03,920 TAHS WAS BORN OUT OF I DON'T 3264 02:40:03,920 --> 02:40:07,360 KNOW HOW MANY MEETINGS OF 3265 02:40:07,360 --> 02:40:10,000 GETTING TOGETHER OVER A SPAN OF 3266 02:40:10,000 --> 02:40:11,960 MAYBE TWO YEARS AND GROWING AND 3267 02:40:11,960 --> 02:40:17,080 SHAPING AND I THINK TO ECHO 3268 02:40:17,080 --> 02:40:23,800 DR. BOURBEAU IT CHRIS -- 3269 02:40:23,800 --> 02:40:25,360 CRYSTALIZES AND WE HAD TO 3270 02:40:25,360 --> 02:40:27,920 REALIGN TRAJECTORIES, REBUILD 3271 02:40:27,920 --> 02:40:29,760 ALL THESE AND BUI HAS DONE A LOT 3272 02:40:29,760 --> 02:40:32,200 OF THAT WORK. 3273 02:40:32,200 --> 02:40:34,080 IT'S ALL POSSIBLE BUT IT IS A 3274 02:40:34,080 --> 02:40:38,320 TRMENT AMOUNT OF WORK. 3275 02:40:38,320 --> 02:40:40,360 IT'S NOT JUST A COMMON ACCESS 3276 02:40:40,360 --> 02:40:48,360 POINT YOU DOWNLOAD DATA FROM. 3277 02:40:48,360 --> 02:40:50,280 >> SEEMS THERE'S SEVERAL 3278 02:40:50,280 --> 02:40:51,720 QUESTIONS IN THE CHAT ABOUT BIO 3279 02:40:51,720 --> 02:40:53,240 SPECIMEN ACCESS PARTICULARLY 3280 02:40:53,240 --> 02:40:55,800 THOSE COMING FROM THE LUNG. 3281 02:40:55,800 --> 02:41:01,440 HOWEVER, REALLY BIO SPECIMEN 3282 02:41:01,440 --> 02:41:04,440 ACCESS IN GENERAL THEY WANT TO 3283 02:41:04,440 --> 02:41:07,240 KNOW HOW WE ACCESS SOME OF THE 3284 02:41:07,240 --> 02:41:07,480 DATA. 3285 02:41:07,480 --> 02:41:08,360 THERE'S AN INCREDIBLE AMOUNT OF 3286 02:41:08,360 --> 02:41:11,920 WORK THAT GOES IN THE STAM PALS 3287 02:41:11,920 --> 02:41:14,120 BUT HOW DO WE MAKE IT EASY FOR 3288 02:41:14,120 --> 02:41:16,320 SO ONE HOW DO WE MAKE IT EASY 3289 02:41:16,320 --> 02:41:17,880 FOR BASIC SCIENTIST TO ACCESS 3290 02:41:17,880 --> 02:41:23,480 THESE OR CAN YOU TOUCH ON HOW 3291 02:41:23,480 --> 02:41:26,600 SCIENTISTS ACCESS THE BIO 3292 02:41:26,600 --> 02:41:29,440 SPECIMENS AND CAN WE TOUCH UPON 3293 02:41:29,440 --> 02:41:36,560 WHO ACTUALLY HAS SAM SAMPLING 3294 02:41:36,560 --> 02:41:37,800 THE LUNG. 3295 02:41:37,800 --> 02:41:40,480 IT'S OKAY IT RAISE YOUR HAND OR 3296 02:41:40,480 --> 02:41:41,000 SPEAK UP. 3297 02:41:41,000 --> 02:41:46,560 >> JEFF, I THINK YOU'RE ME BEST 3298 02:41:46,560 --> 02:41:49,280 PERSON TO ANSWER THIS INVOLVED 3299 02:41:49,280 --> 02:41:52,680 IN THE CONSORTIUM AND COPD AND 3300 02:41:52,680 --> 02:41:53,360 SPIROMICS. 3301 02:41:53,360 --> 02:41:54,560 I THINK YOU UNDERSTAND THIS AS 3302 02:41:54,560 --> 02:41:58,040 WELL AS ANYBODY DOES. 3303 02:41:58,040 --> 02:42:01,080 >> I THINK FOR COPD GENES THEY 3304 02:42:01,080 --> 02:42:03,640 BOTH HAVE FAIRLY ROBUST AND NOW 3305 02:42:03,640 --> 02:42:05,760 INCREASINGLY HARMONIZED 3306 02:42:05,760 --> 02:42:07,160 MECHANISMS TO SOLICIT OR SUBMIT 3307 02:42:07,160 --> 02:42:11,720 ANCILLARIES. 3308 02:42:11,720 --> 02:42:17,480 KINDS OF CONTACTS ARE WAN DA AND 3309 02:42:17,480 --> 02:42:17,720 MYSELF. 3310 02:42:17,720 --> 02:42:21,600 I'M ON BOTH SPIROMICS AND COPD 3311 02:42:21,600 --> 02:42:23,520 GENE AND KENNY SAY GOOD PERSON 3312 02:42:23,520 --> 02:42:25,240 TO TALK TO. 3313 02:42:25,240 --> 02:42:26,360 THE QUESTION I SAW IN THE CHAT 3314 02:42:26,360 --> 02:42:31,240 WAS WHAT ABOUT SOME OF THE OTHER 3315 02:42:31,240 --> 02:42:37,480 COHORTS THAT I THINK GRAHAM SAID 3316 02:42:37,480 --> 02:42:40,840 MESA HAS SOME BIO SPECIMENS BUT 3317 02:42:40,840 --> 02:42:46,080 CAN YOU ELABORATE. 3318 02:42:46,080 --> 02:42:51,720 >> MESA HAS HAD A LOT OF BLOOD 3319 02:42:51,720 --> 02:42:55,080 FOR A LONG TIME AND OTHERS ARE 3320 02:42:55,080 --> 02:42:58,400 COLLECTING NASAL SAMPLING ON THE 3321 02:42:58,400 --> 02:43:05,160 COHORT AND HAIR FOLLICLES. 3322 02:43:05,160 --> 02:43:11,120 >> RUSS, DO YOU WANT TO JUMP IN 3323 02:43:11,120 --> 02:43:11,320 THERE? 3324 02:43:11,320 --> 02:43:16,960 >> THIS IS FROM A FEW MINUTES 3325 02:43:16,960 --> 02:43:17,360 AGO. 3326 02:43:17,360 --> 02:43:18,480 AND THERE'S A POTENTIAL OPTION 3327 02:43:18,480 --> 02:43:19,480 FOR COLLABORATION. 3328 02:43:19,480 --> 02:43:25,920 WE USE IT A LOT FOR OMICS DATA. 3329 02:43:25,920 --> 02:43:28,160 AND EVEN DATA NOT IN TOP MED. 3330 02:43:28,160 --> 02:43:30,640 YOU CAN PUT NON-TOP MED DATA 3331 02:43:30,640 --> 02:43:31,520 INTO DATA CATALYST TO MAKE IT 3332 02:43:31,520 --> 02:43:36,040 CLEAR TO EVERYBODY. 3333 02:43:36,040 --> 02:43:39,200 THERE'S NO SUBSTITUTE FOR 3334 02:43:39,200 --> 02:43:40,000 IN-PERSON MEETING AND THE OTHER 3335 02:43:40,000 --> 02:43:43,520 MODEL I THINK I WOULD LOVE TO 3336 02:43:43,520 --> 02:43:46,800 EMULATE IS THE CHARGE MODEL AN 3337 02:43:46,800 --> 02:43:48,200 IN-PERSON MEETINGS THAT ARE 3338 02:43:48,200 --> 02:43:48,440 WONDERFUL. 3339 02:43:48,440 --> 02:43:51,400 IT'S GROWN FROM MY UNDERSTANDING 3340 02:43:51,400 --> 02:43:52,760 IN THE LAST DECADE. 3341 02:43:52,760 --> 02:43:55,200 BUT I FEEL WE NEED SOMETHING 3342 02:43:55,200 --> 02:43:57,960 LIKE CHARGE THAT HAS IN-PERSON 3343 02:43:57,960 --> 02:43:59,120 MEETINGS WITH ONE COHORT SUCH AS 3344 02:43:59,120 --> 02:44:09,520 THE ONES ON THE CALL. 3345 02:44:15,520 --> 02:44:17,960 >> I'M SEEING IN THE CHAT FROM 3346 02:44:17,960 --> 02:44:22,360 DR. NOEL SOMETHING THAT SUGGESTS 3347 02:44:22,360 --> 02:44:25,080 WE BRING UP AGAIN ENVIRONMENTAL 3348 02:44:25,080 --> 02:44:27,920 EXPOSURES OTHER THAN SMOKING ARE 3349 02:44:27,920 --> 02:44:29,040 INCREASINGLY BEING RECOGNIZED TO 3350 02:44:29,040 --> 02:44:34,920 BE IMPORTANT AND POSSIBLY 3351 02:44:34,920 --> 02:44:38,120 ADDITIVE OR BUT IT'S NOT CLEAR 3352 02:44:38,120 --> 02:44:42,880 TO THE PEOPLE IN THE COHORTS 3353 02:44:42,880 --> 02:44:46,000 WHAT EPIDEMLOGIC DATA IS 3354 02:44:46,000 --> 02:44:50,320 AVAILABLE IN THE COHORTS. 3355 02:44:50,320 --> 02:44:53,440 AND STARTING WITH DR. SHYAMALI 3356 02:44:53,440 --> 02:44:53,720 DHARMAGE. 3357 02:44:53,720 --> 02:45:01,800 >> YES, WE HAVE A LOT OF 3358 02:45:01,800 --> 02:45:04,280 ENVIRONMENTAL EXPOSURES AND 3359 02:45:04,280 --> 02:45:07,760 GIVEN THE LIMITED TIME WE HAVE 3360 02:45:07,760 --> 02:45:13,960 AIR POLLUTION DATA AND 3361 02:45:13,960 --> 02:45:16,480 OCCUPATIONAL HISTORY DATA THAT 3362 02:45:16,480 --> 02:45:23,200 HAS BEEN QUOTED USING METRIXES 3363 02:45:23,200 --> 02:45:25,720 AND WE HAVE ENVIRONMENTAL DATA 3364 02:45:25,720 --> 02:45:27,240 THAT HAVE BEEN BEEN EXTRACTED 3365 02:45:27,240 --> 02:45:32,560 FROM DIFFERENT DATABASES BECAUSE 3366 02:45:32,560 --> 02:45:34,480 WE KNOW WHERE THEY LINK. 3367 02:45:34,480 --> 02:45:36,400 AND WE HAVE CAPTURED THE 3368 02:45:36,400 --> 02:45:38,200 ENVIRONMENTAL DATA. 3369 02:45:38,200 --> 02:45:40,480 WE HAVE GONE BACK AND COLLECTED 3370 02:45:40,480 --> 02:45:41,680 THE WORK. 3371 02:45:41,680 --> 02:45:47,840 THERE'S MODELS THAT GENERATE AIR 3372 02:45:47,840 --> 02:45:52,120 POLLUTION AND THAT WHAT WE HAVE 3373 02:45:52,120 --> 02:45:56,920 DONE IS WE HAVE NOT ONLY 3374 02:45:56,920 --> 02:45:59,560 COLLECTED ENVIRONMENTAL DATA 3375 02:45:59,560 --> 02:46:05,240 SINCE 2000 WE GOT ENVIRONMENTAL 3376 02:46:05,240 --> 02:46:05,640 DATA. 3377 02:46:05,640 --> 02:46:12,720 WE HAVE COLLECTED DATA THAT WAY. 3378 02:46:12,720 --> 02:46:18,520 WE'VE WORKED WITH THE CONSORTIUM 3379 02:46:18,520 --> 02:46:21,520 FOR THE DATA FROM THE 3380 02:46:21,520 --> 02:46:24,920 PARTICIPANT SIX-DIGIT 3381 02:46:24,920 --> 02:46:26,640 RESIDENTIAL POSTAL CODE AT 3382 02:46:26,640 --> 02:46:27,960 BASELINE ASSESSMENT. 3383 02:46:27,960 --> 02:46:30,920 WE'RE LOOKING IN CANADA THERE'S 3384 02:46:30,920 --> 02:46:32,840 NOT AS MUCH AS MOVEMENT IN TERMS 3385 02:46:32,840 --> 02:46:34,240 OF THE POPULATION MOVING WITHIN 3386 02:46:34,240 --> 02:46:34,840 THE COUNTRY OR OUTSIDE THE 3387 02:46:34,840 --> 02:46:38,440 COUNTRY. 3388 02:46:38,440 --> 02:46:41,880 THIS IS A FRACTURE AND AGAIN 3389 02:46:41,880 --> 02:46:44,560 WE'VE BEEN WORKING FROM AVERAGE 3390 02:46:44,560 --> 02:46:47,520 AGE OF FOR EXAMPLE, THE BM2.5 3391 02:46:47,520 --> 02:46:48,680 CONCENTRATION ASSESSED ON THE 3392 02:46:48,680 --> 02:46:54,760 ONE BY ONE KILOMETER AND ON THE 3393 02:46:54,760 --> 02:46:56,120 GRID COVERING THE NORTH AMERICA 3394 02:46:56,120 --> 02:46:57,680 SOLUTION IN AGING AND THERE'S A 3395 02:46:57,680 --> 02:47:02,600 LOT OF THINGS VERY WELL KNOWN. 3396 02:47:02,600 --> 02:47:03,760 THERE'S AN EXPERT IN THE FIELD 3397 02:47:03,760 --> 02:47:06,720 BY ITSELF AND WE DEVELOPED 3398 02:47:06,720 --> 02:47:06,960 MODELS. 3399 02:47:06,960 --> 02:47:07,800 WE'RE VERY MUCH INTERESTED IN 3400 02:47:07,800 --> 02:47:10,240 THE ACUTE AFFECT OF THE 3401 02:47:10,240 --> 02:47:11,040 POLLUTION. 3402 02:47:11,040 --> 02:47:16,600 WE HAVE HAD SOME DUPLICATION. 3403 02:47:16,600 --> 02:47:21,000 ONE IS WE'RE INTERESTED 3404 02:47:21,000 --> 02:47:23,720 WILDFIRES AND EQUATIONS CAN 3405 02:47:23,720 --> 02:47:27,840 PREDICT YOUR EXPOSURE LONG-TERM 3406 02:47:27,840 --> 02:47:29,480 AND AT THIS WILDFIRE WE'RE MORE 3407 02:47:29,480 --> 02:47:33,320 AND MORE INTERESTED IN THE ACUTE 3408 02:47:33,320 --> 02:47:35,520 AFFECT BUT IN THE LONG-TERM 3409 02:47:35,520 --> 02:47:35,760 AFFECT. 3410 02:47:35,760 --> 02:47:37,480 IT'S A BIT MORE COMPLICATED THAN 3411 02:47:37,480 --> 02:47:40,360 THAT IN THE AREA YOU HAVE TO 3412 02:47:40,360 --> 02:47:45,840 TAKE INTO ACCOUNT TEMPERATURE, 3413 02:47:45,840 --> 02:47:47,160 COLD, WARM AND THE OTHER FACTOR 3414 02:47:47,160 --> 02:47:49,080 YOU HAVE TO TAKE INTO 3415 02:47:49,080 --> 02:47:49,560 CONSIDERATION. 3416 02:47:49,560 --> 02:47:54,800 AND THIS NEEDS TO BE WORK WITH 3417 02:47:54,800 --> 02:47:58,080 AN EXPERT GROUP THAT CAN PUT 3418 02:47:58,080 --> 02:47:59,560 INTO THIS AND IT'S A REAL 3419 02:47:59,560 --> 02:48:03,360 COLLABORATION AND PARTNERSHIP. 3420 02:48:03,360 --> 02:48:04,760 I THINK WE'RE GETTING BETTER IN 3421 02:48:04,760 --> 02:48:06,240 TERMS OF THE MEASUREMENT OF THIS 3422 02:48:06,240 --> 02:48:09,000 ALSO AND BETTER IN TERMS OF 3423 02:48:09,000 --> 02:48:15,920 TRYING TO INDIVIDUALIZE THE AND 3424 02:48:15,920 --> 02:48:18,240 LONG-TERM EXPOSURE WITH ALL THE 3425 02:48:18,240 --> 02:48:19,520 FACTORS THAT HAVE IMPORTANCE IN 3426 02:48:19,520 --> 02:48:29,800 GLOBAL WARMING. 3427 02:48:32,560 --> 02:48:34,040 >> THERE'S A RICH DATA WITH ARD 3428 02:48:34,040 --> 02:48:36,520 YA AND A QUESTIONNAIRE DATA I 3429 02:48:36,520 --> 02:48:39,040 THINK IS HARMONIZED WITH OTHER 3430 02:48:39,040 --> 02:48:42,520 COHORTS IN THE AND GEOLOCATED 3431 02:48:42,520 --> 02:48:42,720 DATA. 3432 02:48:42,720 --> 02:48:49,160 WE HAVE BOTH SES AND 3433 02:48:49,160 --> 02:48:50,240 NEIGHBORHOOD DEPRIVATION 3434 02:48:50,240 --> 02:48:56,080 PROXIMITY TO GREEN SPACE. 3435 02:48:56,080 --> 02:49:04,040 AS THE OTHER INHALED EXPOSURES. 3436 02:49:04,040 --> 02:49:05,600 IF WE LOOK TO THE LUNG/HEART 3437 02:49:05,600 --> 02:49:08,040 COHORT THEY'RE REFLECTING TRUE 3438 02:49:08,040 --> 02:49:09,320 LIFE COURSE ADDRESS HISTORY AND 3439 02:49:09,320 --> 02:49:10,720 THE GOOD NEWS IS BECAUSE THESE 3440 02:49:10,720 --> 02:49:12,120 PEOPLE ARE YOUNG WE HAVE 3441 02:49:12,120 --> 02:49:14,120 SATELLITE DATA DATING BACK TO 3442 02:49:14,120 --> 02:49:18,520 ESSENTIALLY THEIR BIRTH. 3443 02:49:18,520 --> 02:49:20,200 WE'LL KNOW WHERE THEY LIVED AND 3444 02:49:20,200 --> 02:49:22,320 HAVE HIGH RESOLUTION ESTIMATES 3445 02:49:22,320 --> 02:49:24,200 OF PARTICULATE EXPOSURE IN 3446 02:49:24,200 --> 02:49:26,400 ADDITION TO MORE STANDARD 3447 02:49:26,400 --> 02:49:26,880 ASSESSMENTS. 3448 02:49:26,880 --> 02:49:29,280 AND DR. RICE IS LEADING THOSE 3449 02:49:29,280 --> 02:49:30,840 EFFORTS WITHIN THE LUNG HEALTH 3450 02:49:30,840 --> 02:49:31,080 COHORT. 3451 02:49:31,080 --> 02:49:32,200 I'D ENCOURAGE PEOPLE IF THEY 3452 02:49:32,200 --> 02:49:36,840 WANT MORE DETAILS TO REACH OUT 3453 02:49:36,840 --> 02:49:40,360 DIRECTLY TO MARRY AND I CAN HELP 3454 02:49:40,360 --> 02:49:44,960 CONNECT PEOPLE BUT THERE'S MORE 3455 02:49:44,960 --> 02:49:45,400 DATA. 3456 02:49:45,400 --> 02:49:45,720 >> 3457 02:49:45,720 --> 02:49:49,920 >> JOE COFFMAN LEFT THE LARGEST 3458 02:49:49,920 --> 02:49:51,640 STUDY SINCE THE STUDIES THAT WAS 3459 02:49:51,640 --> 02:49:55,480 THE BASIS FOR THE CLEAN AIR ACT 3460 02:49:55,480 --> 02:49:58,120 AND PRESENTED ON OZONE AND 3461 02:49:58,120 --> 02:50:01,480 EMPHYSEMA DATA FROM THAT. 3462 02:50:01,480 --> 02:50:02,200 THERE'S A LOT OF CARDIOVASCULAR 3463 02:50:02,200 --> 02:50:08,560 PAPERS AND BASICALLY MODELS AND 3464 02:50:08,560 --> 02:50:10,760 VALIDATED EXPOSURES FROM 3465 02:50:10,760 --> 02:50:15,760 POLLUTANTS FROM 1990 THROUGH THE 3466 02:50:15,760 --> 02:50:17,560 END OF THE CURRENT EXAM. 3467 02:50:17,560 --> 02:50:23,720 IT'S EXTENSIVE AND BEYOND THAT 3468 02:50:23,720 --> 02:50:29,080 BEYOND THAT COLLABORATIONS OVER 3469 02:50:29,080 --> 02:50:35,440 THE YEARS AND THERE'S FACTORS 3470 02:50:35,440 --> 02:50:39,000 WHICH ARE PRODUCING STATE OF THE 3471 02:50:39,000 --> 02:50:44,640 ART MEASURES AS DESCRIBED, 3472 02:50:44,640 --> 02:50:45,840 ETCETERA. 3473 02:50:45,840 --> 02:50:48,480 >> MEILAN PERHAPS YOU CAN 3474 02:50:48,480 --> 02:50:50,480 DESCRIBE SPIROMICS 3475 02:50:50,480 --> 02:50:52,920 >> I THINK WE HAVE NARA ON THE 3476 02:50:52,920 --> 02:50:53,360 CALL. 3477 02:50:53,360 --> 02:50:53,920 >> THAT'S A BETTER PERSON. 3478 02:50:53,920 --> 02:50:59,840 ARE YOU ON? 3479 02:50:59,840 --> 02:51:05,040 >> I KNOW SPIROMICS ORIGINALLY 3480 02:51:05,040 --> 02:51:09,360 WAS LOOKING AT LARGELY AMBIENT 3481 02:51:09,360 --> 02:51:17,720 AIR POLLUTION THAT WAS BASED ON 3482 02:51:17,720 --> 02:51:20,640 LOCATION INFORMATION. 3483 02:51:20,640 --> 02:51:23,480 AND USED SOME BASIC COMPLICATED 3484 02:51:23,480 --> 02:51:24,160 MODELLING TO UNDERSTAND THE 3485 02:51:24,160 --> 02:51:24,800 HISTORICAL EXPOSURES OVER THE 3486 02:51:24,800 --> 02:51:28,000 PAST DECADE OR SO. 3487 02:51:28,000 --> 02:51:30,800 THERE'S A LIMITED AMOUNT OF 3488 02:51:30,800 --> 02:51:31,960 INDOOR AIR POLLUTION DATA THAT 3489 02:51:31,960 --> 02:51:40,240 WAS INCORPORATED AS WELL. 3490 02:51:40,240 --> 02:51:44,840 AND IT'S A SPIROMICS 1 VISIT AND 3491 02:51:44,840 --> 02:51:47,720 NOT ABLE TO BE WELL EXTRAPOLATED 3492 02:51:47,720 --> 02:51:55,400 FOR BEYOND SPIROMICS FINDINGS. 3493 02:51:55,400 --> 02:51:59,200 >> WE HAVE LONGITUDINAL 3494 02:51:59,200 --> 02:52:01,360 QUESTIONNAIRE DATA ON TOBACCO 3495 02:52:01,360 --> 02:52:04,960 AND VAPING AND OCCUPATIONAL DATA 3496 02:52:04,960 --> 02:52:09,040 AND SOCIO ECONOMIC STATUS AND 3497 02:52:09,040 --> 02:52:10,720 GIS CODING TO LINK TO 3498 02:52:10,720 --> 02:52:13,840 RESIDENTIAL ADDRESSES TO AIR 3499 02:52:13,840 --> 02:52:15,520 POLLUTION AND QUESTIONNAIRES ON 3500 02:52:15,520 --> 02:52:17,680 A SUBSET OF THE COHORT. 3501 02:52:17,680 --> 02:52:22,160 ONE THING TO POINT OUT IS THE 3502 02:52:22,160 --> 02:52:25,040 METABOLOMICS MASS SPEC DATA TO 3503 02:52:25,040 --> 02:52:26,440 BE A VALUABLE TOOL FOR STUDIES 3504 02:52:26,440 --> 02:52:28,160 AND IF CHEMICALS COULD BE 3505 02:52:28,160 --> 02:52:30,320 IDENTIFIED ARE BEING MEASURED IN 3506 02:52:30,320 --> 02:52:35,040 THAT METABOLOMICS DATA. 3507 02:52:35,040 --> 02:52:37,400 AND IF YOU HAVE THE RIGHT DATA 3508 02:52:37,400 --> 02:52:39,000 TO IDENTIFY THE MASS SPEC 3509 02:52:39,000 --> 02:52:39,920 PROFILES AND THERE ARE 3510 02:52:39,920 --> 02:52:41,640 INVESTIGATORS WHO SPECIALIZE IN 3511 02:52:41,640 --> 02:52:43,680 THIS COULD LEAD TO THE 3512 02:52:43,680 --> 02:52:46,040 IDENTIFICATION OF THOUSANDS OF 3513 02:52:46,040 --> 02:52:46,280 CHEMICALS. 3514 02:52:46,280 --> 02:52:47,520 IT'S SOMETHING WE SHOULD THINK 3515 02:52:47,520 --> 02:52:58,080 ABOUT FOR MANY OF THESE COHORTS. 3516 02:52:59,200 --> 02:53:00,560 >> THERE'S EXPOSURE 3517 02:53:00,560 --> 02:53:04,240 HARMONIZATION TO YOUR MEETING 3518 02:53:04,240 --> 02:53:06,640 COULD BE A GOOD AIM OF YOUR 3519 02:53:06,640 --> 02:53:06,880 MEETING. 3520 02:53:06,880 --> 02:53:09,920 I DON'T KNOW IF YOU HAD 3521 02:53:09,920 --> 02:53:10,400 ADDITIONAL QUESTIONS. 3522 02:53:10,400 --> 02:53:14,120 ONE OF THE THINGS I WAS SEEING 3523 02:53:14,120 --> 02:53:15,840 IN THE CHAT WITH AROUND LOOKING 3524 02:53:15,840 --> 02:53:19,040 AT AIRWAY CENTRIC DISEASE VERSUS 3525 02:53:19,040 --> 02:53:22,880 EMPHYSEMA AND THOUGHT IT MIGHT 3526 02:53:22,880 --> 02:53:24,680 BE A GOOD -- GEORGE WAS TALKING 3527 02:53:24,680 --> 02:53:26,440 ABOUT THIS EARLIER WE WEREN'T 3528 02:53:26,440 --> 02:53:28,160 FOCUSSING ON RADIO DRAFK 3529 02:53:28,160 --> 02:53:30,800 MEASURES IN THIS MEETING BUT IT 3530 02:53:30,800 --> 02:53:36,560 MIGHT BE A NICE PLACE TO GIVE A 3531 02:53:36,560 --> 02:53:40,200 LITTLE PLACE WHERE PEOPLE CAN 3532 02:53:40,200 --> 02:53:43,440 LOOK AT THE RADIO GRAPHIC 3533 02:53:43,440 --> 02:53:44,520 MEASURES AND HOW TO HELP EARTH 3534 02:53:44,520 --> 02:53:47,120 THE QUESTIONS OR USE IN 3535 02:53:47,120 --> 02:53:51,240 CONJUNCTION WITH THE BIO 3536 02:53:51,240 --> 02:53:53,800 SPESMANS TO LOOK AT AIRWAY 3537 02:53:53,800 --> 02:53:54,400 DISEASE VERSUS LUNG TISSUE 3538 02:53:54,400 --> 02:53:59,720 OBSTRUCTION. 3539 02:53:59,720 --> 02:54:01,560 >> THE IMAGING WORKING GROUPS 3540 02:54:01,560 --> 02:54:04,800 FOR A LOT OF THE COHORTS ARE 3541 02:54:04,800 --> 02:54:07,440 INCREDIBLY ACTIVE AND THERE'S 3542 02:54:07,440 --> 02:54:09,000 ALREADY A LOT OF CROSS 3543 02:54:09,000 --> 02:54:11,160 FERTILIZATION BETWEEN 3544 02:54:11,160 --> 02:54:12,600 INDIVIDUALS LIKE DAVID LYNCH AND 3545 02:54:12,600 --> 02:54:15,720 ERIC HOFFMAN INVOLVED IN THE CPG 3546 02:54:15,720 --> 02:54:17,800 AND SPIROMIC STUDIES. 3547 02:54:17,800 --> 02:54:19,640 GEORGE HAS BEEN ACTIVELY WORKING 3548 02:54:19,640 --> 02:54:26,440 WITH THEM TO IN RESPECT TO LHC 3549 02:54:26,440 --> 02:54:28,560 AND I THINK THE IMAGING GROUP 3550 02:54:28,560 --> 02:54:30,280 HAS A LIFE OF THEIR OWN AND IT'S 3551 02:54:30,280 --> 02:54:34,120 IMPORTANT FOR HELPING DEFINE 3552 02:54:34,120 --> 02:54:35,480 SPECIFIC PHENOTYPES LIKE VEEP 3553 02:54:35,480 --> 02:54:36,720 THE INDIVIDUAL ANALYSIS WITH THE 3554 02:54:36,720 --> 02:54:42,800 MUCUS PLUGGING IS NOW A VERY HOT 3555 02:54:42,800 --> 02:54:45,560 AREA IN COPD AND PEOPLE ARE 3556 02:54:45,560 --> 02:54:47,080 TRYING TO DEVELOP WAYS TO 3557 02:54:47,080 --> 02:54:48,520 ANALYZE THAT IN A MORE 3558 02:54:48,520 --> 02:54:58,880 QUANTITATIVE FASHION. 3559 02:54:59,600 --> 02:55:00,520 >> IF THERE'S SOMEONE INTERESTED 3560 02:55:00,520 --> 02:55:02,320 I THINK YOU CAN HOP ON TO ANY 3561 02:55:02,320 --> 02:55:04,960 ONE OF THE WORKING GROUPS AND 3562 02:55:04,960 --> 02:55:08,320 THE CPG MAY BE ONE OF THE MORE 3563 02:55:08,320 --> 02:55:10,080 BROAD ONES AND WILL GIVE A NICE 3564 02:55:10,080 --> 02:55:10,720 INTRODUCTION TO WHAT'S GOING ON 3565 02:55:10,720 --> 02:55:16,200 IN THE SPACE IN PARTICULAR. 3566 02:55:16,200 --> 02:55:18,920 >> AS A TRANSLATIONAL RESEARCHER 3567 02:55:18,920 --> 02:55:25,280 SOME RADIO GRAPHIC FINDINGS THE 3568 02:55:25,280 --> 02:55:26,560 OBJECTIVE MEASURES OF EMPHYSEMA 3569 02:55:26,560 --> 02:55:31,800 OR AIRWAY WALL THICKENING, 3570 02:55:31,800 --> 02:55:33,040 PULMONARY DISEASE CAN BE HIGHLY 3571 02:55:33,040 --> 02:55:38,840 RELATED TO FINDINGS IN BIO 3572 02:55:38,840 --> 02:55:39,280 SPECIMENS. 3573 02:55:39,280 --> 02:55:41,120 JUST THINKING ABOUT OF THOSE 3574 02:55:41,120 --> 02:55:41,920 THINGS BEYOND LUNG FUNCTION 3575 02:55:41,920 --> 02:55:44,680 EXPOSURES WE HAVE A LOT OF THESE 3576 02:55:44,680 --> 02:55:47,280 OTHER MEASURES IN SOME OF THE 3577 02:55:47,280 --> 02:55:50,680 STUDIES AND I'M SURE THE PEOPLE, 3578 02:55:50,680 --> 02:55:52,160 GRAHAM AND GEORGE, HAVE BEEN 3579 02:55:52,160 --> 02:55:54,640 WORKING ON THIS A LOT AND MAYBE 3580 02:55:54,640 --> 02:56:00,680 CAN COMMENT FURTHER. 3581 02:56:00,680 --> 02:56:06,880 >> I COMPLETELY AGREE. 3582 02:56:06,880 --> 02:56:08,280 THERE ARE TO MY PERSPECTIVE 3583 02:56:08,280 --> 02:56:11,600 DIFFERENT DISEASES WE END UP 3584 02:56:11,600 --> 02:56:12,920 WITH DIFFERENT CHANGES IN 3585 02:56:12,920 --> 02:56:13,960 STRUCTURE. 3586 02:56:13,960 --> 02:56:15,360 AS I SHOWED IN THE GENERAL 3587 02:56:15,360 --> 02:56:15,960 POPULATION THERE'S DIFFERENT 3588 02:56:15,960 --> 02:56:17,000 PEOPLE WITH DIFFERENT THINGS 3589 02:56:17,000 --> 02:56:19,200 GOING ON IN THE LUNGS AND DON'T 3590 02:56:19,200 --> 02:56:23,760 NECESSARILY COALESCE WITH SPIRO 3591 02:56:23,760 --> 02:56:26,720 METRIC COPD AND OFTEN I THINK 3592 02:56:26,720 --> 02:56:30,120 EASIER TO GET BIOLOGICAL 3593 02:56:30,120 --> 02:56:35,240 SIGNATURES FOR THE EVEN SMALLER 3594 02:56:35,240 --> 02:56:36,000 SAMPLES. 3595 02:56:36,000 --> 02:56:39,120 ONE OF THE AREAS IS IN THE 3596 02:56:39,120 --> 02:56:42,080 ENDOTHELIUM AND WE CAN IMAGINE 3597 02:56:42,080 --> 02:56:44,040 IN TERMS OF THE YARD YO 3598 02:56:44,040 --> 02:56:45,720 VASCULATURE AND THE SPECIMENS IN 3599 02:56:45,720 --> 02:56:49,880 THE COHORTS ARE BLOOD. 3600 02:56:49,880 --> 02:56:51,120 THE BLOOD OBVIOUSLY USED 3601 02:56:51,120 --> 02:56:54,400 DIRECTLY BUT ASPECTS OF THE 3602 02:56:54,400 --> 02:57:02,160 BLOOD AND ENDOTHELIUM AND WE CAN 3603 02:57:02,160 --> 02:57:04,000 SUGGEST MORE DIRECTLY 3604 02:57:04,000 --> 02:57:04,280 PHENOTYPES. 3605 02:57:04,280 --> 02:57:06,600 >> THE CONCEPT OF MANY OF OUR 3606 02:57:06,600 --> 02:57:08,880 BASIC SCIENCE INVESTIGATORS MAY 3607 02:57:08,880 --> 02:57:10,440 OBTAIN BIO SPECIMENS FROM THEIR 3608 02:57:10,440 --> 02:57:12,720 OWN INSTITUTIONS RATHER FROM AN 3609 02:57:12,720 --> 02:57:15,520 EXISTING BIO BANK WHICH GIVES 3610 02:57:15,520 --> 02:57:17,360 ADVANTAGES TO FRESH SAMPLES BUT 3611 02:57:17,360 --> 02:57:18,360 WHEN DO YOU THAT YOU SHOULD GET 3612 02:57:18,360 --> 02:57:21,640 THE IMAGING ON THE BIO SAMPLE 3613 02:57:21,640 --> 02:57:24,320 AND USE ONE OF OUR IMAGING 3614 02:57:24,320 --> 02:57:26,600 GROUPS AND TO TELL YOU HOW TO 3615 02:57:26,600 --> 02:57:31,560 INTERPRET THE SMALLER IMAGES AND 3616 02:57:31,560 --> 02:57:35,520 WHERE THE SUBTYPES ARE. 3617 02:57:35,520 --> 02:57:37,840 YOU CAN GET GOOD QUALITY CT 3618 02:57:37,840 --> 02:57:40,440 IMAGING AND SHARE THAT WITH THE 3619 02:57:40,440 --> 02:57:42,840 GRUP TO CHARACTERIZE IT. 3620 02:57:42,840 --> 02:57:44,120 >> I THINK GEORGE WILL GET THE 3621 02:57:44,120 --> 02:57:45,560 LAST WORD DOWN TO TWO MINUTES. 3622 02:57:45,560 --> 02:57:47,840 >> FABULOUS COMMENT. 3623 02:57:47,840 --> 02:57:49,680 THANK YOU. 3624 02:57:49,680 --> 02:57:52,160 >> ONE FINAL PLUG FOR THE 3625 02:57:52,160 --> 02:57:53,720 IMAGING IT'S ALMOST A RENEWABLE 3626 02:57:53,720 --> 02:57:54,080 RESOURCE. 3627 02:57:54,080 --> 02:57:57,120 YOU CAN MAKE DIGITAL COPIES AND 3628 02:57:57,120 --> 02:57:58,400 HAND THEM UP UNLIKE BIO 3629 02:57:58,400 --> 02:57:59,640 SPECIMENS THAT ARE CONSUMED. 3630 02:57:59,640 --> 02:58:03,560 WE ENCOURAGE PEOPLE TO REACH OUT 3631 02:58:03,560 --> 02:58:05,840 TO ALL THE TEAMS AND GET COPIES 3632 02:58:05,840 --> 02:58:07,760 OF THE DATA AND WE CAN ALL HELP 3633 02:58:07,760 --> 02:58:12,160 YOU WORK WITH IT. 3634 02:58:12,160 --> 02:58:12,520 >> THANK YOU. 3635 02:58:12,520 --> 02:58:13,560 I THINK WE'VE DONE IT. 3636 02:58:13,560 --> 02:58:17,480 >> YES. 3637 02:58:17,480 --> 02:58:20,160 I THINK WE'RE TWO MINUTES BEFORE 3638 02:58:20,160 --> 02:58:20,840 OUR TIME. 3639 02:58:20,840 --> 02:58:23,800 SO I THINK IT'S TIME FOR A BREAK 3640 02:58:23,800 --> 02:58:30,160 AND I REALLY THANK YOU ALL FOR 3641 02:58:30,160 --> 02:58:34,120 ALL THE SPEAKERS AND THERE'S A 3642 02:58:34,120 --> 02:58:36,000 LOT OF WORK AHEAD OF US BUT 3643 02:58:36,000 --> 02:58:36,680 THERE ARE A LOT OF OPPORTUNITIES 3644 02:58:36,680 --> 02:58:38,080 FOR COLLABORATION I HOPE 3645 02:58:38,080 --> 02:58:39,840 EVERYBODY ON THE CALL IS 3646 02:58:39,840 --> 02:58:41,400 STARTING TO REALIZE THAT MAYBE 3647 02:58:41,400 --> 02:58:44,240 IT MAKES IT A LITTLE BIT LESS OF 3648 02:58:44,240 --> 02:58:45,960 A BARRIER TO WORKING WITH SOME 3649 02:58:45,960 --> 02:58:46,600 OF THE GROUPS SEEING WHAT THEY 3650 02:58:46,600 --> 02:58:50,800 HAVE. 3651 02:58:50,800 --> 02:58:54,080 ANY LAST WORDS, JEF? 3652 02:58:54,080 --> 02:58:55,320 >> NOPE. 3653 02:58:55,320 --> 02:59:02,920 EVERYBODY BE BACK AT 1:30. 3654 02:59:02,920 --> 02:59:06,560 >> WE'RE BACK AT 1:30 EASTERN. 3655 02:59:06,560 --> 02:59:06,880 >> THANK YOU. 3656 02:59:06,880 --> 02:59:13,080 THANKS, EVERYBODY. 3657 02:59:13,080 --> 02:59:17,760 >> ON BEHALF OF MY ORGANIZERS 3658 02:59:17,760 --> 02:59:21,880 AND MY CO-CHAIR I'M HAPPY TO 3659 02:59:21,880 --> 02:59:23,920 INVITE TO YOU DAY ONE OF THE 3660 02:59:23,920 --> 02:59:25,520 PATHOGENESIS OF COPD. 3661 02:59:25,520 --> 02:59:29,240 WE HAVE SIX OUTSTANDING SPEAKERS 3662 02:59:29,240 --> 02:59:32,920 FOR THIS SESSION AND I THINK IT 3663 02:59:32,920 --> 02:59:34,400 WILL GIVE US A BROAD SWATH OF 3664 02:59:34,400 --> 02:59:40,160 THE UNDERSTANDING OF THE UNIQUE 3665 02:59:40,160 --> 02:59:43,080 BIOLOGY THAT IS BEING STUDIED IN 3666 02:59:43,080 --> 02:59:43,440 THIS DISEASE. 3667 02:59:43,440 --> 02:59:47,280 I'LL TURN IT OVER TO DR. HUANG. 3668 02:59:47,280 --> 02:59:47,680 >> THANK YOU. 3669 02:59:47,680 --> 02:59:48,880 I'M PERSONALLY LOOKING FORWARD 3670 02:59:48,880 --> 02:59:52,880 TO THE SESSION AS A 3671 02:59:52,880 --> 02:59:53,720 TRANSLATIONAL SCIENTISTS. 3672 02:59:53,720 --> 02:59:58,360 IT'S MY PLEASURE TO INTRODUCE 3673 02:59:58,360 --> 03:00:06,400 DR. KRISTOPHER GAGGAR TALKING 3674 03:00:06,400 --> 03:00:08,080 ABOUT EXOMES AND COPD. 3675 03:00:08,080 --> 03:00:14,040 >> CAN YOU SEE MY SLIDES? 3676 03:00:14,040 --> 03:00:18,240 >> I THINK IT NEEDS TO BE 3677 03:00:18,240 --> 03:00:18,480 ADVANCED. 3678 03:00:18,480 --> 03:00:20,360 >> ARE YOU SHARING YOUR OWN 3679 03:00:20,360 --> 03:00:20,880 SLIDES? 3680 03:00:20,880 --> 03:00:23,120 >> I GOT THEM. 3681 03:00:23,120 --> 03:00:23,880 I'M SHARING NOW. 3682 03:00:23,880 --> 03:00:24,480 >> YOU'RE CURRENTLY NOT SHARING 3683 03:00:24,480 --> 03:00:28,720 NOW. 3684 03:00:28,720 --> 03:00:30,720 I'LL STOP SHARING AND YOU CAN 3685 03:00:30,720 --> 03:00:31,600 PUT YOUR SLIDES. 3686 03:00:31,600 --> 03:00:33,640 >> FIRST OFF I'D LIKE TO SAY I'M 3687 03:00:33,640 --> 03:00:34,800 VERY HONORED TO BE A PART OF 3688 03:00:34,800 --> 03:00:35,720 THIS EVENT. 3689 03:00:35,720 --> 03:00:36,680 I'D LIKE TO THANK EVERYONE FOR 3690 03:00:36,680 --> 03:00:42,200 THE OPPORTUNITY TO GIVE A TALK 3691 03:00:42,200 --> 03:00:43,400 TODAY. 3692 03:00:43,400 --> 03:00:53,920 I'M KRISTOPHER GENSCMER AND THE 3693 03:01:01,520 --> 03:01:06,680 AFFECT OF PROTEASES ON COPD. 3694 03:01:06,680 --> 03:01:08,760 THEY'RE DERIVED FROM MOST CELL 3695 03:01:08,760 --> 03:01:10,320 TYPES AND EXTRA CELLULAR 3696 03:01:10,320 --> 03:01:11,560 VESICLES HAVE BEEN DIVIDED INTO 3697 03:01:11,560 --> 03:01:13,560 THREE CATEGORIES AND THEY CHANGE 3698 03:01:13,560 --> 03:01:15,160 OVER TIME AS MORE 3699 03:01:15,160 --> 03:01:17,360 CLASSIFICATIONS OF EVs GET 3700 03:01:17,360 --> 03:01:18,400 DISCUSSED. 3701 03:01:18,400 --> 03:01:19,360 THEY'RE ALL VERY SMALL. 3702 03:01:19,360 --> 03:01:21,440 THIS GRAPHIC ILLUSTRATES SOME OF 3703 03:01:21,440 --> 03:01:23,040 THE COMPLEX PROCESSES I WON'T 3704 03:01:23,040 --> 03:01:26,680 GET INTO TODAY FOR TIME THAT ARE 3705 03:01:26,680 --> 03:01:28,640 REQUIRED FOR EXTRA CELLULAR 3706 03:01:28,640 --> 03:01:29,880 VESICLE RELEASE. 3707 03:01:29,880 --> 03:01:32,080 THE SMALLER VESICLES ARE 3708 03:01:32,080 --> 03:01:33,720 GENERATED THROUGH THIS BODY 3709 03:01:33,720 --> 03:01:36,760 PATHWAY RELEASED. 3710 03:01:36,760 --> 03:01:39,480 THEY CONTAIN NUCLEIC ACIDS AND 3711 03:01:39,480 --> 03:01:45,000 EXPOSED PROTEASES. 3712 03:01:45,000 --> 03:01:47,200 VESICLES ARE BUDDING FROM THE 3713 03:01:47,200 --> 03:01:50,840 CELL MEMBRANE 3,000 TO 1,000 NAN 3714 03:01:50,840 --> 03:01:56,280 YO OMETERS IN SIZE AND THEY 3715 03:01:56,280 --> 03:01:59,600 RESULT FROM THE APOPTOSIS OF 3716 03:01:59,600 --> 03:01:59,800 CELLS. 3717 03:01:59,800 --> 03:02:02,680 I'LL BE REFERRING TO EXOSOMES 3718 03:02:02,680 --> 03:02:06,480 SIZE EVs WHEN I REFER TO EXTRA 3719 03:02:06,480 --> 03:02:11,080 CELLULAR VESICLES. 3720 03:02:11,080 --> 03:02:12,920 SOME HAVE BEEN DISCOVERED IN 3721 03:02:12,920 --> 03:02:15,760 EXTRA CELLULAR VESICLES FROM 3722 03:02:15,760 --> 03:02:18,800 MATRIX DEGRADATION LIKE 3723 03:02:18,800 --> 03:02:22,120 ELASTASES TO THE GENERATION OF 3724 03:02:22,120 --> 03:02:24,200 PRO-INFLAMMATORY SIGNALS LIKE 3725 03:02:24,200 --> 03:02:30,200 GENERATION OF PGP FOUND IN EVs 3726 03:02:30,200 --> 03:02:35,560 AS WELL AS THE LGPT4. 3727 03:02:35,560 --> 03:02:37,680 WE'LL FIND RIDGE REGARD TO 3728 03:02:37,680 --> 03:02:39,440 ELASTASE THE ASSOCIATION WITH 3729 03:02:39,440 --> 03:02:41,360 SOME PROTEASES ON THE EV SURFACE 3730 03:02:41,360 --> 03:02:44,120 RENDERS THEM RESISTANCE TO THEIR 3731 03:02:44,120 --> 03:02:45,760 PROTEASE INHIBITION FACILITATING 3732 03:02:45,760 --> 03:02:49,360 THE DISRUPTION OF THE PROTEASE, 3733 03:02:49,360 --> 03:02:50,520 ANTI-PROTEASE BALANCE. 3734 03:02:50,520 --> 03:02:57,400 A LOT OF THE PROTEASE WORK SIN 3735 03:02:57,400 --> 03:03:01,320 RESISTANCE TO THE ENDOGENOUS 3736 03:03:01,320 --> 03:03:03,720 PROTEASE AND SHOW YOU THE EXTRA 3737 03:03:03,720 --> 03:03:06,800 VESICLES FROM NEUTROPHILS. 3738 03:03:06,800 --> 03:03:13,080 PANEL A RELEASE THE SKOE 3739 03:03:13,080 --> 03:03:15,640 CENTIMETERS AND WHEN THE 3740 03:03:15,640 --> 03:03:17,800 NEUTROPHILS GET ACTIVATE AND 3741 03:03:17,800 --> 03:03:20,760 RELEASE THEIR GRANULES THEY CAN 3742 03:03:20,760 --> 03:03:23,240 BIND BACK TO THE SURFACE OF THE 3743 03:03:23,240 --> 03:03:25,840 EXTRA CELLULAR VESICLE THUS 3744 03:03:25,840 --> 03:03:29,760 KEEPING THE ALPHA 1 ALPHA 3745 03:03:29,760 --> 03:03:32,840 TRIPSON INCAPABLE BEING SOCKET 3746 03:03:32,840 --> 03:03:37,280 ED -- ASSOCIATED WITH THE 3747 03:03:37,280 --> 03:03:38,680 VESICLE AND IF YOU CAN DISRUPT 3748 03:03:38,680 --> 03:03:40,120 THIS YOU CAN ALLOW IT TO BE 3749 03:03:40,120 --> 03:03:43,200 CAPABLE OF BEING INHIBITED BY 3750 03:03:43,200 --> 03:03:48,480 ALPHA 1 ANTI-TRIPSON AGAIN AND 3751 03:03:48,480 --> 03:03:52,360 YOU TAKE NEUTROPHILS FROM 3752 03:03:52,360 --> 03:03:58,400 PERIPHERAL BLOOD AND YOU 3753 03:03:58,400 --> 03:03:59,960 STIMULATE DEGRANULATION YOU'LL 3754 03:03:59,960 --> 03:04:03,120 GENERATE TWO COHORTS OF EXTRA 3755 03:04:03,120 --> 03:04:03,560 CELLULAR VESICLES. 3756 03:04:03,560 --> 03:04:06,760 THE EVs ISOLATED FROM EACH OTHER 3757 03:04:06,760 --> 03:04:08,000 SHOW TWO SEPARATE CONDITIONS BUT 3758 03:04:08,000 --> 03:04:11,040 NO DIFFERENCE IN SIZE OR SHAPE 3759 03:04:11,040 --> 03:04:14,400 WHEN LOOKED AT UNDER THE 3760 03:04:14,400 --> 03:04:15,880 MICROGRAPH AND UNDER FLOW 3761 03:04:15,880 --> 03:04:17,720 CYTOMETRY YOU'LL SEE MORE 3762 03:04:17,720 --> 03:04:19,120 SURFACE ELASTASE ON THE SURFACE 3763 03:04:19,120 --> 03:04:21,720 OF THE EXTRA CELLULAR VESICLES 3764 03:04:21,720 --> 03:04:24,440 FROM ACTIVATED NEUTROPHILS FROM 3765 03:04:24,440 --> 03:04:25,880 THEY 3766 03:04:28,800 --> 03:04:34,320 -- THE QUIESCENT AND IS THIS 3767 03:04:34,320 --> 03:04:36,240 PROTEOLYTICALLY ACTED VATED. 3768 03:04:36,240 --> 03:04:38,960 THESE EVs ASSOCIATE WITH KOL 3769 03:04:38,960 --> 03:04:42,200 AGAIN FIBRILS. 3770 03:04:42,200 --> 03:04:47,080 WE GOT A MICROGRAPH OF THEM BY 3771 03:04:47,080 --> 03:04:49,520 THEMSELVES AND QUIESCENT ALONG 3772 03:04:49,520 --> 03:04:52,240 WITH THE FIBRILS AT TIMES ZERO. 3773 03:04:52,240 --> 03:04:55,320 IF YOU LOOK AT THE SAME FIBRILS 3774 03:04:55,320 --> 03:04:59,480 24 HOURS LATER YOU SEE A MORE 3775 03:04:59,480 --> 03:05:02,200 DRASTIC CHANGE IN THE PHENOTYPE 3776 03:05:02,200 --> 03:05:05,000 AND QUIESCENT NEUTROPHILS DO NO 3777 03:05:05,000 --> 03:05:11,280 DAMAGE AND THOSE INCUBATE FROM 3778 03:05:11,280 --> 03:05:11,920 DEGRANULATED NEUTROPHILS SHOW 3779 03:05:11,920 --> 03:05:13,840 THE FIBRILS IN THE PROCESS AND 3780 03:05:13,840 --> 03:05:18,280 PANEL F SHOWS A BLOWUP OF THE 3781 03:05:18,280 --> 03:05:21,480 ACTIVATED EXTRA CELLULAR VESICLE 3782 03:05:21,480 --> 03:05:26,720 NEAR POINT OF DEGRADATION. 3783 03:05:26,720 --> 03:05:36,320 THEY HAVE PROTEOLYTICALLY 3784 03:05:36,320 --> 03:05:42,400 ACTIVATED CELLS. 3785 03:05:42,400 --> 03:05:42,920 WHAT WE DO IS YOU 3786 03:05:42,920 --> 03:05:45,480 THE EXTRA CELLULAR VESICLES IN 3787 03:05:45,480 --> 03:05:48,440 THE MOUSE MODEL INTRATRACHEALLY 3788 03:05:48,440 --> 03:05:54,080 TO OBSERVE ENLARGEMENT IN THE 3789 03:05:54,080 --> 03:05:57,160 EMPHYSEMA PANEL AND YOU SEE THE 3790 03:05:57,160 --> 03:05:59,160 NORMAL LUNG AND THOSE WITH 3791 03:05:59,160 --> 03:06:04,760 QUIESCENT NEUTROPHILS SHOW NO 3792 03:06:04,760 --> 03:06:10,960 CHANGE SHOWING XENO TROPIC 3793 03:06:10,960 --> 03:06:15,360 AFFECT AND THE ACTIVATED 3794 03:06:15,360 --> 03:06:16,440 NEUTROPHILS INCREASES THE 3795 03:06:16,440 --> 03:06:19,640 ALVEOLAR ENLARGEMENT AND PANEL B 3796 03:06:19,640 --> 03:06:23,280 IS A MEASUREMENT OF THE 3797 03:06:23,280 --> 03:06:24,320 INTERCEMENT IN THE RED COLUMN 3798 03:06:24,320 --> 03:06:26,800 YOU SEE THE INCREASE IN SIZE AND 3799 03:06:26,800 --> 03:06:29,800 PANEL C IS PULMONARY FUNCTION 3800 03:06:29,800 --> 03:06:31,280 TEST AND SEE IN INCREASE IN 3801 03:06:31,280 --> 03:06:34,680 AIRWAY RESISTANCE WHEN GIVEN THE 3802 03:06:34,680 --> 03:06:39,880 ACTIVATED EXTRA CELLULAR 3803 03:06:39,880 --> 03:06:43,920 VESICLES AND IN B THE HALLMARK 3804 03:06:43,920 --> 03:06:46,440 OF THE EMPHYSEMA MODEL. 3805 03:06:46,440 --> 03:06:48,760 NEUTROPHIL ELASTASE GOES TO THE 3806 03:06:48,760 --> 03:06:52,640 SURFACE VIA IONIC CHARGE AND 3807 03:06:52,640 --> 03:06:55,840 INCUBATING THEM FROM AN 3808 03:06:55,840 --> 03:07:00,240 ACTIVATED NEUTROPHIL SUCH AS 3809 03:07:00,240 --> 03:07:02,480 WITH SULPHATE YOU CAN REMOVE THE 3810 03:07:02,480 --> 03:07:04,360 ELASTASE FROM THE SURFACE 3811 03:07:04,360 --> 03:07:07,720 ALLOWING IT TO BE INHIBITED BY 3812 03:07:07,720 --> 03:07:11,800 THE ALPHA TRIPSAN. 3813 03:07:11,800 --> 03:07:15,080 YOU SEE THE EXOSOME POPULATION 3814 03:07:15,080 --> 03:07:23,880 AND IN GREEN YOU SEE ALPHA 3815 03:07:23,880 --> 03:07:27,880 TRIPSAN WITH THE EXTRA CELLULAR 3816 03:07:27,880 --> 03:07:34,640 VESICLES IN THE BLUE WITH NO 3817 03:07:34,640 --> 03:07:36,840 TRIPSAN SHO SHOW NO TRIPSAN TO 3818 03:07:36,840 --> 03:07:37,880 INHIBIT THE ELASTASE. 3819 03:07:37,880 --> 03:07:47,760 IN TEAL AT THE BOUGTTOM IF YOU 3820 03:07:47,760 --> 03:07:49,480 ACTIVATE AND USE THE INHIBITOR 3821 03:07:49,480 --> 03:07:54,960 YOU SEE THE RECOVERABILITY TO 3822 03:07:54,960 --> 03:07:55,560 INHIBIT THE ELASTASE IN THE 3823 03:07:55,560 --> 03:07:59,240 MODEL. 3824 03:07:59,240 --> 03:08:03,440 THE IN VIVO AFFECTS THE 3825 03:08:03,440 --> 03:08:06,040 NEUTROPHIL ELASTASE THROUGHOUT 3826 03:08:06,040 --> 03:08:08,280 THE INTERACTION YOU CAN SEE AS 3827 03:08:08,280 --> 03:08:09,880 IN THE SAME MODEL PREVIOUSLY. 3828 03:08:09,880 --> 03:08:13,640 THE ACTIVATED NEUTROPHILS AND IN 3829 03:08:13,640 --> 03:08:20,080 THE MIDDLE SHOW THE ALVEOLAR 3830 03:08:20,080 --> 03:08:24,840 ENLARGEMENT AND YOU INDICATE THE 3831 03:08:24,840 --> 03:08:29,560 IT'S ABLE TO INHIBIT ALL THE 3832 03:08:29,560 --> 03:08:36,920 UNFOUND NEUTROPHIL ELASTASE AND 3833 03:08:36,920 --> 03:08:38,440 THIS SHOWS AIRWAY RESISTANCE AND 3834 03:08:38,440 --> 03:08:41,840 THAT IS DECREASED WITH THE EXTRA 3835 03:08:41,840 --> 03:08:48,040 CELLULAR VESS KICLES STRS TREAT 3836 03:08:48,040 --> 03:08:55,560 YOU GET A DECREASE IN ACTIVATE 3837 03:08:55,840 --> 03:08:57,200 EXOSOMES BUT NOT THOSE TREATED 3838 03:08:57,200 --> 03:08:59,160 WITH THE SULPHATE. 3839 03:08:59,160 --> 03:09:02,600 AND BRINGS TO THE MOUSE MODEL. 3840 03:09:02,600 --> 03:09:05,880 IN THE LEFT EXTRA CELLULAR 3841 03:09:05,880 --> 03:09:12,040 VESICLES RESISTANCE TO THE 3842 03:09:12,040 --> 03:09:14,800 ANTITRIPSAN AND THEY CAUSE 3843 03:09:14,800 --> 03:09:17,200 DAMAGE TO COLLAGEN. 3844 03:09:17,200 --> 03:09:19,920 IF YOU ERROR TO TREAT THEM THE 3845 03:09:19,920 --> 03:09:26,240 SULPHATE YOU RELEASE THE 3846 03:09:26,240 --> 03:09:30,000 ELASTASE INHIBIT THE DEGREDATION 3847 03:09:30,000 --> 03:09:31,560 AND REDUCED AIRWAY DAMAGE. 3848 03:09:31,560 --> 03:09:33,840 BRINGS US TO THE POINT OF THE 3849 03:09:33,840 --> 03:09:36,440 QUESTION REMAINING ARE THE EVs 3850 03:09:36,440 --> 03:09:38,800 GENERATED FROM ACTIVATED 3851 03:09:38,800 --> 03:09:41,880 NEUTROPHILS CAN THEY BE FOUND IN 3852 03:09:41,880 --> 03:09:43,240 THE COPD PATIENTS GIVEN THE 3853 03:09:43,240 --> 03:09:43,520 PHENOTYPE. 3854 03:09:43,520 --> 03:09:45,440 IT'S IMPORTANT BECAUSE THE 3855 03:09:45,440 --> 03:09:51,280 PRESENCE OF THESE EXTRA CELLULAR 3856 03:09:51,280 --> 03:09:54,920 VESICL 3857 03:09:54,920 --> 03:09:57,120 VESICLES DEFICIENCY AND YOU SEE 3858 03:09:57,120 --> 03:10:00,080 THE EVs THOSE FROM ACTIVATED 3859 03:10:00,080 --> 03:10:01,520 NEUTROPHILS AND INCREASE IN 3860 03:10:01,520 --> 03:10:03,440 NEUTROPHIL ELASTASE AND FIND A 3861 03:10:03,440 --> 03:10:06,360 HIGHER PERCENTAGE OF ELASTASE 3862 03:10:06,360 --> 03:10:08,600 POSITIVE EXTRA CELLULAR VESICLES 3863 03:10:08,600 --> 03:10:09,200 BETWEEN THE COPD AND NEVER 3864 03:10:09,200 --> 03:10:19,480 SMOKING PATIENT. 3865 03:10:31,240 --> 03:10:33,440 IS AND THOSE ON THE RIGHT SHOW 3866 03:10:33,440 --> 03:10:36,320 NO APPRECIABLE CHANGE IN THE 3867 03:10:36,320 --> 03:10:38,160 ALVEOLAR SIZE BUT IF YOU GIVE 3868 03:10:38,160 --> 03:10:40,200 THEM RECOVERED FROM COPD 3869 03:10:40,200 --> 03:10:42,000 PATIENTS YOU SHOW DRASTIC 3870 03:10:42,000 --> 03:10:43,080 DEGRADATION AND DAMAGE IN THE 3871 03:10:43,080 --> 03:10:46,400 LUNG ARCHITECTURE AND THE 3872 03:10:46,400 --> 03:10:49,640 ALVEOLAR ENLARGEMENT AND SINCE 3873 03:10:49,640 --> 03:10:51,840 IT'S EXOSOMES TO ILLUSTRATE THE 3874 03:10:51,840 --> 03:10:54,280 CONTRIBUTION THE ACTIVITY YOU'RE 3875 03:10:54,280 --> 03:10:58,440 SEEING DUE TO NEUTROPHIL AND 3876 03:10:58,440 --> 03:11:04,040 LOOK AT THE ELASTASE INHIBITOR 3877 03:11:04,040 --> 03:11:10,000 CAUSED BY THE NEUTROSOME AND 3878 03:11:10,000 --> 03:11:14,200 LOOKING AT THE COHORT OF VARIOUS 3879 03:11:14,200 --> 03:11:16,720 SMOKING DEGREES AND DISEASE 3880 03:11:16,720 --> 03:11:19,200 PATHO 3881 03:11:19,200 --> 03:11:29,320 PATHO 3882 03:11:35,120 --> 03:11:35,360 PATHOGENICITY. 3883 03:11:35,360 --> 03:11:36,840 YOU CAN SEE COPD PATIENT WHO'S 3884 03:11:36,840 --> 03:11:40,400 ARE CURRENT SMOKERS TENDED TO 3885 03:11:40,400 --> 03:11:46,400 POSSESS EXTRA CELLULAR VESICLES 3886 03:11:46,400 --> 03:11:49,560 MOST PATHOGENIC AND COPD PATIENT 3887 03:11:49,560 --> 03:11:51,440 WHO'S DECREASED DECREASED THE 3888 03:11:51,440 --> 03:11:52,840 SMOKING EFFECT BUT WERE STILL 3889 03:11:52,840 --> 03:11:54,320 HIGHER THAN THE NEVER SMOKERERS. 3890 03:11:54,320 --> 03:11:56,440 THEY NEVER RETURNED BACK TO 3891 03:11:56,440 --> 03:11:57,200 NORMAL. 3892 03:11:57,200 --> 03:11:58,880 INTERESTINGLY, CURRENT SMOKERS 3893 03:11:58,880 --> 03:12:01,480 WHO DID NOT HAVE COPD THEY'RE 3894 03:12:01,480 --> 03:12:03,800 EXTRA CELLULAR VESICLES WERE 3895 03:12:03,800 --> 03:12:06,200 ABLE TO CAUSE ALVEOLAR 3896 03:12:06,200 --> 03:12:11,560 ENLARGEMENT SIMILAR TO THOSE WHO 3897 03:12:11,560 --> 03:12:15,600 HAD COPD BUT SHOWING THE 3898 03:12:15,600 --> 03:12:20,200 PATHOGENICITY OF THE VESICLES. 3899 03:12:20,200 --> 03:12:22,320 PEOPLE WHO QUIT SMOKING 3900 03:12:22,320 --> 03:12:23,600 DECREASED THE EXTRA CELLULAR 3901 03:12:23,600 --> 03:12:26,000 VESICLES BUT DID NOT RETURN BACK 3902 03:12:26,000 --> 03:12:28,600 TO THE BASELINE THE MEDIAN OF 3903 03:12:28,600 --> 03:12:33,000 THE NEVER SMOKERS. 3904 03:12:33,000 --> 03:12:34,360 THERE'S AN THAT NEEDS TO BE 3905 03:12:34,360 --> 03:12:36,280 EXAMINED FURTHER. 3906 03:12:36,280 --> 03:12:39,080 AND THAT BRINGS ME TO WHERE WE 3907 03:12:39,080 --> 03:12:41,520 GO WITH THE VESICLES. 3908 03:12:41,520 --> 03:12:42,640 ALL THE PATIENT DATA WE'VE SEEN 3909 03:12:42,640 --> 03:12:44,960 SO FAR TO THIS POINT WERE SINGLE 3910 03:12:44,960 --> 03:12:45,560 SNAPSHOTS IN TIME. 3911 03:12:45,560 --> 03:12:48,160 IT'S VERY IMPORTANT TO 3912 03:12:48,160 --> 03:12:49,760 CHARACTERIZE THESE PATIENT EXTRA 3913 03:12:49,760 --> 03:12:53,560 CELLULAR VESICLES 3914 03:12:53,560 --> 03:12:54,080 LONGITUDINALLY. 3915 03:12:54,080 --> 03:12:55,680 DOES THIS CONTINUE WITH DISEASE 3916 03:12:55,680 --> 03:12:56,560 OR DURATION. 3917 03:12:56,560 --> 03:12:58,400 IF YOU QUICK SMOKING WOULD YOU 3918 03:12:58,400 --> 03:13:00,840 RETURN BACK TO A BASELINE OR 3919 03:13:00,840 --> 03:13:02,160 BEGIN TO SEE A CHANGE OF THOSE 3920 03:13:02,160 --> 03:13:06,040 THAT WILL GO ON TO DEVELOP COPD 3921 03:13:06,040 --> 03:13:07,880 AND THOSE WHO WILL SORT OF 3922 03:13:07,880 --> 03:13:08,760 DECREASE DOWN THE BASELINE. 3923 03:13:08,760 --> 03:13:11,160 IT'S ALSO IMPORTANT TO LOOK AT 3924 03:13:11,160 --> 03:13:15,480 PRO VERSUS ANTI-INFLAMMATORY 3925 03:13:15,480 --> 03:13:17,160 SOURCES. 3926 03:13:17,160 --> 03:13:20,200 NEUTROPHIL THE MACROPHAGES AND 3927 03:13:20,200 --> 03:13:23,640 MONOCYTES AND EPITHELIAL CELLS 3928 03:13:23,640 --> 03:13:26,200 WHICH PROVIDE ANTI-CELLULAR 3929 03:13:26,200 --> 03:13:27,000 VESICLES. 3930 03:13:27,000 --> 03:13:28,600 CELLULAR SENESCENCE IS IMPORTANT 3931 03:13:28,600 --> 03:13:31,560 TO LOOK AT THE HALLMARK OF COPD 3932 03:13:31,560 --> 03:13:38,080 WITH SENESCENCE THEY'RE 3933 03:13:38,080 --> 03:13:39,640 PHENOTYPICALLY DIFFERENT AND 3934 03:13:39,640 --> 03:13:41,200 UNDERSTANDING HOW THAT 3935 03:13:41,200 --> 03:13:43,400 CONTRIBUTES TO COPD PATHOGENESIS 3936 03:13:43,400 --> 03:13:45,920 IS IMPORTANT AS WELL AND LOOKING 3937 03:13:45,920 --> 03:13:50,320 AT SINGULAR VESICLES UP TO THIS 3938 03:13:50,320 --> 03:13:52,920 POINT EVERYTHING IS LARGE 3939 03:13:52,920 --> 03:13:54,720 QUANTITIES OF EVs AND TO 3940 03:13:54,720 --> 03:13:56,360 IDENTIFY THE CHARACTERIZATIONS 3941 03:13:56,360 --> 03:13:59,280 WITH REGARDS TO CARGO AND CELL 3942 03:13:59,280 --> 03:14:00,000 SIGNALLING WILL BE MORE USEFUL 3943 03:14:00,000 --> 03:14:00,600 DOWN THE ROAD. 3944 03:14:00,600 --> 03:14:04,960 I'D LIKE TO THANK OUR GROUP AT 3945 03:14:04,960 --> 03:14:12,080 UAB THAT HAS DONE A LOT OF THE 3946 03:14:12,080 --> 03:14:19,120 WORK THANK YOU. 3947 03:14:19,120 --> 03:14:20,760 >> THANK YOU, KRIS. 3948 03:14:20,760 --> 03:14:24,240 TO REMIND OUR SPEAKERS, WE ARE 3949 03:14:24,240 --> 03:14:25,360 LOOKING AT 15-MINUTE TALKS. 3950 03:14:25,360 --> 03:14:29,360 WE'LL GET A TWO-MINUTE WARNING. 3951 03:14:29,360 --> 03:14:31,760 I FORGOT TO MENTION THIS UP 3952 03:14:31,760 --> 03:14:35,320 FRONT, MY APOLOGY. 3953 03:14:35,320 --> 03:14:36,720 QUESTIONS PUT IN THE CHAT, 3954 03:14:36,720 --> 03:14:36,960 PLEASE. 3955 03:14:36,960 --> 03:14:40,200 WE WON'T HAVE A QUESTION ANSWER 3956 03:14:40,200 --> 03:14:44,600 SESSION BETWEEN TALKS. 3957 03:14:44,600 --> 03:14:50,480 OUR NEXT TALK IS FARRAH 3958 03:14:50,480 --> 03:14:52,800 KHERADMAND FROM BAYLOR COLLEGE 3959 03:14:52,800 --> 03:14:54,920 OF MEDICINE AT YUM CELL 3960 03:14:54,920 --> 03:15:05,240 DYSFUNCTION IN COPD. 3961 03:15:09,360 --> 03:15:11,600 >>I WANT TO THANK THE ORGANIZERS 3962 03:15:11,600 --> 03:15:13,920 FOR THE OPPORTUNITY TO TALK. 3963 03:15:13,920 --> 03:15:15,560 I WANT TO THANK KRIS FOR 3964 03:15:15,560 --> 03:15:17,400 BRINGING US BACK TO THE LEVEL 3965 03:15:17,400 --> 03:15:23,040 I'M PROBABLY GOING TO BE ALSO 3966 03:15:23,040 --> 03:15:27,920 TALKING TO YOU NOT THE LEVEL WE 3967 03:15:27,920 --> 03:15:38,400 LEARNED EARLIER TODAY AND WE 3968 03:15:48,440 --> 03:15:50,040 STARTED LOOKING AT THE ADAPTIVE 3969 03:15:50,040 --> 03:15:51,960 RESPONSE TO SMOKING AND THE TWO 3970 03:15:51,960 --> 03:15:53,280 STORIES, THE FIRST PART OF WHICH 3971 03:15:53,280 --> 03:15:53,960 IS PUBLISHED. 3972 03:15:53,960 --> 03:15:58,280 I'M GOING TO USE THAT AS A WHY 3973 03:15:58,280 --> 03:16:00,920 WE'RE MOVING IN THE DIRECTION 3974 03:16:00,920 --> 03:16:02,280 WE'RE GOING BUT THEY'RE 3975 03:16:02,280 --> 03:16:03,920 INTERRELATES. 3976 03:16:03,920 --> 03:16:12,960 WHAT I'D LIKE TO DO IS AND THE 3977 03:16:12,960 --> 03:16:17,800 IDEA THE NEUTROPHILS IS DRIVING 3978 03:16:17,800 --> 03:16:19,840 THE DISEASE AND WE'RE FOCUSSING 3979 03:16:19,840 --> 03:16:22,440 ON A PARTICULAR CYTOKINE AND 3980 03:16:22,440 --> 03:16:24,560 IL17A KNOWN TO BE CRITICAL IN 3981 03:16:24,560 --> 03:16:28,000 DRIVING NEUTROPHILS INTO THE 3982 03:16:28,000 --> 03:16:28,680 LUNGS. 3983 03:16:28,680 --> 03:16:34,640 LET ME START TELLING YOU PART 1 3984 03:16:34,640 --> 03:16:39,880 OF THE STORY WHICH START FROM 3985 03:16:39,880 --> 03:16:50,400 WORK IT STARTED FROM A STUDENT 3986 03:16:52,120 --> 03:16:55,720 WHO CAME TO MY OFFICE AND IF YOU 3987 03:16:55,720 --> 03:16:57,320 EXPOSED MICE TO A PROLONGED 3988 03:16:57,320 --> 03:16:58,880 PERIOD OF CIGARETTE SMOKE YOU 3989 03:16:58,880 --> 03:17:04,600 SEE A DEFINITIVE CHANGE IN THEIR 3990 03:17:04,600 --> 03:17:08,040 IL17 ADAPT IMMUNE CELLS CHANGES 3991 03:17:08,040 --> 03:17:11,920 YOU WOULD SEE AND THAT'S MARK BY 3992 03:17:11,920 --> 03:17:19,520 INCREASE IN IL17 IN THE T CELLS 3993 03:17:19,520 --> 03:17:24,560 AND THAT WAS OBVIOUSLY FOLLOWED 3994 03:17:24,560 --> 03:17:27,400 BY SOME QUANTITATIVE DATA WE 3995 03:17:27,400 --> 03:17:29,280 SHOWED THAT BOTH VOLUME AND 3996 03:17:29,280 --> 03:17:31,040 DENSITY, THESE ARE THINGS THAT 3997 03:17:31,040 --> 03:17:35,080 WE LEARNED ABOUT TODAY IN THE 3998 03:17:35,080 --> 03:17:37,360 COPD COHORT STUDIES THE VOLUME 3999 03:17:37,360 --> 03:17:39,120 GOES UP AND THE DENSITY GOES 4000 03:17:39,120 --> 03:17:43,360 DOWN IN MICE THAT ARE EXPRESSING 4001 03:17:43,360 --> 03:17:46,920 PROFOUND IL17A PRODUCTION IB 4002 03:17:46,920 --> 03:17:47,440 THEIR CD 3. 4003 03:17:47,440 --> 03:17:58,000 WE WENT ON TO SHOW IN FACT THE 4004 03:17:59,960 --> 03:18:03,920 IL17A THE DEFICIENCY ADVOCATED 4005 03:18:03,920 --> 03:18:07,720 IN MICE AND IF YOU EXPOSE MICE 4006 03:18:07,720 --> 03:18:12,120 GLOBALLY DEFICIENT IN IL17 FOR A 4007 03:18:12,120 --> 03:18:14,680 PROLONGED PERIOD OF TIME FOR 4008 03:18:14,680 --> 03:18:17,000 CIGARETTE SMOKE THEY HAVE 4009 03:18:17,000 --> 03:18:21,400 ATTENUATED RESPONSE AND SHOWN IN 4010 03:18:21,400 --> 03:18:26,320 THE HISTOLOGY WHERE THE IL17 4011 03:18:26,320 --> 03:18:34,120 DEFICIENT MICE HAVE ATTENUATED 4012 03:18:34,120 --> 03:18:38,000 EMPHYSEMA AND IT WAS ALLUDED TO 4013 03:18:38,000 --> 03:18:39,360 DURING THE MORNING SESSION HOW 4014 03:18:39,360 --> 03:18:43,200 MUCH OF INFECTION PART OF THE 4015 03:18:43,200 --> 03:18:44,400 DISEASE THAT WE KNOW ABOUT AND 4016 03:18:44,400 --> 03:18:46,720 AS CLINICIANS TAKE CARE OF IS 4017 03:18:46,720 --> 03:18:49,760 ACTUALLY MAYBE DRIVING THE 4018 03:18:49,760 --> 03:18:50,000 DISEASE. 4019 03:18:50,000 --> 03:18:51,200 SO IN ORDER TO GET TO THE SECOND 4020 03:18:51,200 --> 03:18:53,600 PART OF THIS AND AGAIN THIS IS 4021 03:18:53,600 --> 03:18:56,560 PUBLISHED WORK I'LL GO OVER 4022 03:18:56,560 --> 03:18:58,280 QUICKLY WE TOOK TWO COHORTS OF 4023 03:18:58,280 --> 03:19:01,560 MICE EXPOSED THEM TO AIR OR 4024 03:19:01,560 --> 03:19:03,360 CIGARETTE SMOKE FOR THREE MONTHS 4025 03:19:03,360 --> 03:19:05,000 AND EXPOSED THEM TO INFLUENZA 4026 03:19:05,000 --> 03:19:14,640 VIRUS AND THE HUMAN ISOLATES THE 4027 03:19:14,640 --> 03:19:18,280 MICE AND EUTHANIZED THEM AND 4028 03:19:18,280 --> 03:19:20,600 AFTER EMULATING WHAT HAPPENS IN 4029 03:19:20,600 --> 03:19:22,480 CLINICS NOT SURPRISINGLY WE 4030 03:19:22,480 --> 03:19:25,920 FOUND MICE EXPOSED TO CIGARETTE 4031 03:19:25,920 --> 03:19:27,520 SMOKE AND INFLUENZA IN FACT MOST 4032 03:19:27,520 --> 03:19:33,760 OF WHICH SUCCUMB TO THEIR DEATH 4033 03:19:33,760 --> 03:19:36,240 AND WE EUTHANIZE THEM AT THE END 4034 03:19:36,240 --> 03:19:37,800 OF TWO WEEKS AND MICE EXPOSED TO 4035 03:19:37,800 --> 03:19:40,800 THE AIR AND WERE INFECTED WITH 4036 03:19:40,800 --> 03:19:46,440 INFLUENZA STARTED RECOVERING TWO 4037 03:19:46,440 --> 03:19:46,760 WEEKS. 4038 03:19:46,760 --> 03:19:54,520 SOMETHING WE DO SEE IN HUMANS 4039 03:19:54,520 --> 03:19:56,920 AND THE NEUTROPHILS WAS 4040 03:19:56,920 --> 03:19:58,720 INCREASED SIGNIFICANTLY IN MICE 4041 03:19:58,720 --> 03:20:01,760 EXPOSED TO CIGARETTE SMOKE AND 4042 03:20:01,760 --> 03:20:02,040 INFLUENZA. 4043 03:20:02,040 --> 03:20:03,200 THIS IS SOMETHING THAT I WANTED 4044 03:20:03,200 --> 03:20:06,600 TO SHARE WITH YOU WHICH IS VERY 4045 03:20:06,600 --> 03:20:11,200 TELLING THAT WE KNOW TERTIARY 4046 03:20:11,200 --> 03:20:13,800 LYMPHOID STRUCTURES ARE MADE IN 4047 03:20:13,800 --> 03:20:16,640 THE LUNG AFTER INFECTION AFTER 4048 03:20:16,640 --> 03:20:18,240 TRYING TO HEAL FROM THE 4049 03:20:18,240 --> 03:20:19,240 INFECTION I'LL GET TO IN THE 4050 03:20:19,240 --> 03:20:21,280 SECOND PART OF MY TALK AND I'LL 4051 03:20:21,280 --> 03:20:25,160 SHARE UNPUBLISHED WORK BUT THAT 4052 03:20:25,160 --> 03:20:28,200 INFLAMMATION IS REALLY MORE 4053 03:20:28,200 --> 03:20:38,760 DISORGANIZED AND THROUGHOUT THE 4054 03:20:42,040 --> 03:20:47,080 LUNG AND DOES NOT FORM THE 4055 03:20:47,080 --> 03:20:48,120 STRUCTURES. 4056 03:20:48,120 --> 03:20:49,760 AND TO HAVE A FEW CRITICAL DATA 4057 03:20:49,760 --> 03:20:53,400 I WANTED TO SHOW THE T CELL HERE 4058 03:20:53,400 --> 03:20:59,920 SPECIFIC TYPE OF ADAPTIVE IMMUNE 4059 03:20:59,920 --> 03:21:03,400 CELLS TO THE MUCOSAL LINING 4060 03:21:03,400 --> 03:21:05,320 THEY'RE NORMALLY EXPRESSING 4061 03:21:05,320 --> 03:21:06,920 IL17. 4062 03:21:06,920 --> 03:21:08,520 WE DON'T KNOW WHY BUT MAYBE PART 4063 03:21:08,520 --> 03:21:10,160 OF WHY THEY'RE THERE AND WHEN 4064 03:21:10,160 --> 03:21:11,240 MICE ARE EXPOSED TO INFLUENZA 4065 03:21:11,240 --> 03:21:15,840 THE AMOUNT OF THE IL17 4066 03:21:15,840 --> 03:21:17,240 SIGNIFICANTLY GOES DOWN IN GAMMA 4067 03:21:17,240 --> 03:21:19,880 DELTA T CELLS AND THOSE EXPOSED 4068 03:21:19,880 --> 03:21:21,440 TO CIGARETTES WERE INCAPABLE OF 4069 03:21:21,440 --> 03:21:24,400 SWITCHING THE PHENOTYPE. 4070 03:21:24,400 --> 03:21:27,160 IF YOU LOOK AT THE SAME T CELLS 4071 03:21:27,160 --> 03:21:29,080 PRODUCING INTERFERON GAMMA AND 4072 03:21:29,080 --> 03:21:30,920 FOR MOST WHO KNOW ABOUT THE 4073 03:21:30,920 --> 03:21:34,080 DISEASE OR INFECTION YOU NEED 4074 03:21:34,080 --> 03:21:36,800 THIS IN ORDER TO RECOVER FROM A 4075 03:21:36,800 --> 03:21:39,520 VIRAL INFECTION, THESE MICE ARE 4076 03:21:39,520 --> 03:21:42,640 INCAPABLE TO PRODUCE INTERFERON 4077 03:21:42,640 --> 03:21:45,800 GAMMA AT THE MUCOSAL LEVEL AND 4078 03:21:45,800 --> 03:21:46,080 SYSTEMIC. 4079 03:21:46,080 --> 03:21:47,280 INTERESTINGLY WE DIDN'T FIND A 4080 03:21:47,280 --> 03:21:48,680 SIGNAL IN THE CD8 T CELL WHICH 4081 03:21:48,680 --> 03:21:51,840 IS IS ANOTHER STORY I'LL SHARE 4082 03:21:51,840 --> 03:21:53,440 AT SOME OTHER TIME. 4083 03:21:53,440 --> 03:21:56,400 IMPORTANTLY WHILE WE FOUND 4084 03:21:56,400 --> 03:21:59,280 THERE'S QUITE A BIT OF 4085 03:21:59,280 --> 03:22:00,920 IMMUNOGLOBULIN PRODUCED IN THE 4086 03:22:00,920 --> 03:22:05,920 CIGARETTE SMOKE OR FLU INFECTED 4087 03:22:05,920 --> 03:22:08,280 COHORT, THE ANTIGEN SPECIFICITY 4088 03:22:08,280 --> 03:22:12,080 WHEN THE B CELLS LEARN ABOUT THE 4089 03:22:12,080 --> 03:22:14,560 ANTIGEN AND GO ABOUT CHANGING 4090 03:22:14,560 --> 03:22:17,080 THEIR PHENOTYPE THERE'S A 4091 03:22:17,080 --> 03:22:20,080 HYPERMUTATION HAPPENING TO MAKE 4092 03:22:20,080 --> 03:22:21,280 ANTIGEN SPECIFIC NEUTRALIZING 4093 03:22:21,280 --> 03:22:24,320 ANTIBODY ARE REDUCED IN THE MICE 4094 03:22:24,320 --> 03:22:27,880 IN THE AIRWAY AS WELL AS 4095 03:22:27,880 --> 03:22:28,240 SYSTEMICALLY. 4096 03:22:28,240 --> 03:22:33,160 INDICATING THAT THERE'S A 4097 03:22:33,160 --> 03:22:38,600 SIGNIFICANT REDUCTION IN THE 4098 03:22:38,600 --> 03:22:40,520 ANTIVIRAL IMMUNITY AND STILL 4099 03:22:40,520 --> 03:22:45,520 TRANSLATES TO TRANS 4100 03:22:45,520 --> 03:22:46,400 TRANSCRIPTIONAL FACTOR SOMETHING 4101 03:22:46,400 --> 03:22:48,320 TO PAY ATTENTION TO INTERFERON 4102 03:22:48,320 --> 03:22:53,400 RESPONSE IN THE IR7 AND IF3. 4103 03:22:53,400 --> 03:22:54,560 TWO OF THE IMPORTANT 4104 03:22:54,560 --> 03:22:56,800 TRANSCRIPTION FACTORS CRITICAL 4105 03:22:56,800 --> 03:22:58,920 FOR INDUCING ANTIVIRAL IMMUNITY 4106 03:22:58,920 --> 03:23:00,200 ARE REDUCED. 4107 03:23:00,200 --> 03:23:01,840 AGAIN, TO FINISH THIS PART OF 4108 03:23:01,840 --> 03:23:06,320 THE STORY, WE AGAIN WENT TO IL17 4109 03:23:06,320 --> 03:23:08,480 GLOBAL DEFICIENT MICE AND DID 4110 03:23:08,480 --> 03:23:11,080 WILD TYPE MICE AND IL17 4111 03:23:11,080 --> 03:23:12,200 DEFICIENT AND EXPOSED THEM TO 4112 03:23:12,200 --> 03:23:15,640 AIR OR CIGARETTE SMOKE AND FOUND 4113 03:23:15,640 --> 03:23:18,160 WHILE WILD TYPE SMOKE INFECTED 4114 03:23:18,160 --> 03:23:21,160 MICE SIGNIFICANTLY SUCCUMB TO 4115 03:23:21,160 --> 03:23:24,520 THEIR DISEASE THE LACK OF IL17 4116 03:23:24,520 --> 03:23:27,120 FROM THE GET GO PROTECT THE 4117 03:23:27,120 --> 03:23:27,400 MICE. 4118 03:23:27,400 --> 03:23:30,000 THAT IS SORT OF WHAT WANT TO DO 4119 03:23:30,000 --> 03:23:32,440 IS SUMMARIZE THIS PART OF THE 4120 03:23:32,440 --> 03:23:33,640 PRECLINICAL DATA THAT MICE WILL 4121 03:23:33,640 --> 03:23:39,880 DIE WHEN INFECTED WITH LETHAL 4122 03:23:39,880 --> 03:23:43,480 DOSES OF INFLUENZA AND LOWER 4123 03:23:43,480 --> 03:23:44,720 TITERS OF NEUTRALIZING 4124 03:23:44,720 --> 03:23:47,840 ANTIBODIES PRESENCE IN THE LUNG 4125 03:23:47,840 --> 03:23:51,520 AND GLOBAL DEFICIENCY WHICH HAS 4126 03:23:51,520 --> 03:23:53,720 SOME CLINICAL IMPORTANCE BUT IN 4127 03:23:53,720 --> 03:23:57,840 HUMANS WOULD BE PROTECTIVE IN 4128 03:23:57,840 --> 03:23:58,120 INFLUENZA. 4129 03:23:58,120 --> 03:24:00,840 IN THE LAST FEW MINUTES I WANT 4130 03:24:00,840 --> 03:24:02,880 TO SHARE WITH YOU SOME OF THE 4131 03:24:02,880 --> 03:24:04,880 WHY AND HOW AS PART OF THIS 4132 03:24:04,880 --> 03:24:07,600 STORY THAT IS NOT PUBLISHED. 4133 03:24:07,600 --> 03:24:13,480 TO GAIN INSIGHT INTO HOW THE 4134 03:24:13,480 --> 03:24:19,720 CIGARETTE SMOKE ALTERS 4135 03:24:19,720 --> 03:24:22,680 NEUTRALIZING ANTIBODY WE MINED 4136 03:24:22,680 --> 03:24:24,920 THE B CELL TRANSCRIPTOMIC 4137 03:24:24,920 --> 03:24:27,400 SIGNATURES AND FOUND THE B CELL 4138 03:24:27,400 --> 03:24:32,160 RECEPTOR SIGNALLING PATHWAYS AND 4139 03:24:32,160 --> 03:24:34,920 KINASE ARE ALTERED IN A COHORT 4140 03:24:34,920 --> 03:24:37,920 OF ABOUT 40 PATIENTS WHO NEVER 4141 03:24:37,920 --> 03:24:39,440 SMOKED COMPARED TO THOSE WHO 4142 03:24:39,440 --> 03:24:39,680 SMOKED. 4143 03:24:39,680 --> 03:24:45,360 THESE ARE NOT INFECTED PEOPLE. 4144 03:24:45,360 --> 03:24:51,000 THESE ARE POPULATION STUDIES AND 4145 03:24:51,000 --> 03:24:52,920 SIGNALLING IS ALTERED WHEN THEY 4146 03:24:52,920 --> 03:24:53,240 SMOKE. 4147 03:24:53,240 --> 03:24:55,120 TO ADDRESS THE QUESTION, HOW 4148 03:24:55,120 --> 03:24:57,840 DOES SMOKING REDUCE B CELL 4149 03:24:57,840 --> 03:24:58,960 RESPONSE IN INFLUENZA INFECTION. 4150 03:24:58,960 --> 03:25:03,360 WE GO BACK TO OUR ANIMAL MODEL 4151 03:25:03,360 --> 03:25:04,720 AND EXPOSED MICE TO CIGARETTE 4152 03:25:04,720 --> 03:25:08,120 SMOKE AND INFECTED THEM WITH 4153 03:25:08,120 --> 03:25:10,600 INFLUENZA AND EUTHANIZED MICE TO 4154 03:25:10,600 --> 03:25:13,640 LOOK AT THE LUNG AND DRAINING 4155 03:25:13,640 --> 03:25:15,240 LYMPH NODE POPULATION AND INDEED 4156 03:25:15,240 --> 03:25:18,280 WE FOUND MEMORY B CELLS WITHIN 4157 03:25:18,280 --> 03:25:22,600 THE LUNG ARE SIGNIFICANTLY 4158 03:25:22,600 --> 03:25:27,920 REDUCED AS SHOWN HERE AND AS 4159 03:25:27,920 --> 03:25:29,880 SUMMARIZED IN THE QUANTITATIVE 4160 03:25:29,880 --> 03:25:35,320 THAT IT REDUCES B CELLS IN THE 4161 03:25:35,320 --> 03:25:36,680 LUNG AND LOOKED AT WHAT HAPPENED 4162 03:25:36,680 --> 03:25:38,240 WITHIN THE B CELLS AND WHAT WE 4163 03:25:38,240 --> 03:25:44,400 FOUND IS THAT CIGARETTE SMOKE 4164 03:25:44,400 --> 03:25:46,040 REDUCES THE INFLUENZA SPECIFIC B 4165 03:25:46,040 --> 03:25:49,040 CELL CENTERS IN THE LUNG AS WELL 4166 03:25:49,040 --> 03:25:54,600 AS IDENTIFIED THAT AGAIN THROUGH 4167 03:25:54,600 --> 03:25:56,240 SPECIFIC STUDIES. 4168 03:25:56,240 --> 03:26:06,960 WE WENT ON IT LOOK AT THE LT CEL 4169 03:26:08,440 --> 03:26:13,160 HELPER CELLS TO GO THROUGH 4170 03:26:13,160 --> 03:26:14,080 SOMATIC HYPERMUTATION AND 4171 03:26:14,080 --> 03:26:18,480 THERE'S A REDUCTION IN THE T 4172 03:26:18,480 --> 03:26:22,960 CELLS AND WE AGAIN SHOWED THAT 4173 03:26:22,960 --> 03:26:25,320 AND IN THE LAST PART OF THE TALK 4174 03:26:25,320 --> 03:26:27,880 WE THEN WANTED TO PUT THE 4175 03:26:27,880 --> 03:26:29,760 CIGARETTE SMOKE ASIDE. 4176 03:26:29,760 --> 03:26:33,600 LET'S FOCUS ON IL17. 4177 03:26:33,600 --> 03:26:38,320 IT'S SOMETHING THAT WE HAVE 4178 03:26:38,320 --> 03:26:42,160 ANTIBODIES AGAINST SO CAN WE 4179 03:26:42,160 --> 03:26:43,560 RECAPITULATE WHAT HAPPENS WITH 4180 03:26:43,560 --> 03:26:46,800 CIGARETTE SMOKE IN A MODEL 4181 03:26:46,800 --> 03:26:47,440 LOOKING AT THE POPULATION AND B 4182 03:26:47,440 --> 03:26:49,400 CELL FORMATION. 4183 03:26:49,400 --> 03:26:51,200 AND SO THIS TIME THERE'S A 4184 03:26:51,200 --> 03:26:52,520 COHORT OF MICE WERE NEVER 4185 03:26:52,520 --> 03:26:53,920 EXPOSED TO CIGARETTE SMOKE, 4186 03:26:53,920 --> 03:26:55,240 HOWEVER, THE DAY BEFORE THEY 4187 03:26:55,240 --> 03:27:00,280 WERE INFECTED THEY WERE GIVEN 4188 03:27:00,280 --> 03:27:01,920 IL17A IN ONE DOSE FOLLOWED BY 4189 03:27:01,920 --> 03:27:03,720 THREE DOSES. 4190 03:27:03,720 --> 03:27:05,040 EMULATING WHAT CIGARETTE SMOKE 4191 03:27:05,040 --> 03:27:06,720 MAY BE DOING IN THE LUNG AND THE 4192 03:27:06,720 --> 03:27:09,080 MICE SIX DAYS AFTER INFECTION 4193 03:27:09,080 --> 03:27:11,760 WERE EUTHANIZED AND INDEED WE 4194 03:27:11,760 --> 03:27:17,080 FOUND THAT BOTH ALPHA BETA T 4195 03:27:17,080 --> 03:27:21,000 CELLS WERE SIGNIFICANTLY REDUCED 4196 03:27:21,000 --> 03:27:25,600 WHEN MICE RECEIVED IL17A WITH 4197 03:27:25,600 --> 03:27:27,440 INFLUENZA. 4198 03:27:27,440 --> 03:27:31,880 INTRANASALLY IL17 ALSO REDUCES 4199 03:27:31,880 --> 03:27:39,880 GERMINAL CENTER CELLS AND 4200 03:27:39,880 --> 03:27:42,200 FINALLY WE FOUND THAT THE 4201 03:27:42,200 --> 03:27:48,000 INTRANASAL IL17 CAN REDUCE 4202 03:27:48,000 --> 03:27:53,840 HELPER CELLS USING NUCLEAR 4203 03:27:53,840 --> 03:27:57,240 TETRAMERS WE OBTAINED. 4204 03:27:57,240 --> 03:28:02,120 I WANTED TO TAKE A MINUTE TO 4205 03:28:02,120 --> 03:28:05,000 TELL YOU THAT ACTIVE SMOKING 4206 03:28:05,000 --> 03:28:06,840 INCREASES IL17 IN THE LUNGS. 4207 03:28:06,840 --> 03:28:08,320 AS KRIS MENTIONED THE 4208 03:28:08,320 --> 03:28:09,840 NEUTROPHILS COME IN THE LUNG. 4209 03:28:09,840 --> 03:28:14,720 WELL, IL17 IS CRITICAL FOR THE 4210 03:28:14,720 --> 03:28:15,040 NEUTROPHILS. 4211 03:28:15,040 --> 03:28:18,400 IN ADDITION IL17 REDUCES 4212 03:28:18,400 --> 03:28:19,600 NEUTRALIZING ANTIBODIES AGAINST 4213 03:28:19,600 --> 03:28:21,520 VIRUSES. 4214 03:28:21,520 --> 03:28:25,440 SMOKING REDUCES ACTIVATION IN 4215 03:28:25,440 --> 03:28:27,400 THE LUNG DRAINING LYMPH NODE AS 4216 03:28:27,400 --> 03:28:30,560 WELL AS ABLE TO RECAPITULATE THE 4217 03:28:30,560 --> 03:28:31,520 INFECTIONS WE SEE. 4218 03:28:31,520 --> 03:28:34,360 SOME OF THE EFFECTS OF CIGARETTE 4219 03:28:34,360 --> 03:28:38,400 SMOKE AND JUST GETTING IL17 WE 4220 03:28:38,400 --> 03:28:43,560 SHOWED THE PHENOCOPY OF THE 4221 03:28:43,560 --> 03:28:44,920 ALPHA B CELLS. 4222 03:28:44,920 --> 03:28:46,920 I WANT TO ADVERTISE FOR A 4223 03:28:46,920 --> 03:28:48,280 COMPREHENSIVE REVIEW OF THE 4224 03:28:48,280 --> 03:28:52,960 TOPIC WE JUST PUBLISHED IN 4225 03:28:52,960 --> 03:28:54,800 PHYSIOLOGICAL REVIEWS AND YOU 4226 03:28:54,800 --> 03:28:56,000 WANT TO FOLLOW-UP ON THE 4227 03:28:56,000 --> 03:28:56,360 STORIES. 4228 03:28:56,360 --> 03:28:59,920 THANK YOU FOR THE TIME AND I'M 4229 03:28:59,920 --> 03:29:02,800 HAPPY TO STOP. 4230 03:29:02,800 --> 03:29:03,800 >> 4231 03:29:03,800 --> 03:29:05,840 >> WONDERFUL. 4232 03:29:05,840 --> 03:29:08,840 WE ARE SPOT ON AND DOING GREAT 4233 03:29:08,840 --> 03:29:11,880 ON TIME IN SUMMARIZING DATA IN A 4234 03:29:11,880 --> 03:29:15,480 SHORT FASHION. 4235 03:29:15,480 --> 03:29:23,720 NEXT IS DR. RENAT SHAYKHIEV TO 4236 03:29:23,720 --> 03:29:27,920 TALK ABOUT THE SMALL AIRWAY 4237 03:29:27,920 --> 03:29:29,960 PROGENITOR CELL DYSFUNCTION. 4238 03:29:29,960 --> 03:29:34,480 >> MY FOCUS OF MY LAB IS DISTAL 4239 03:29:34,480 --> 03:29:36,120 AIRWAYS BECAUSE OF THEIR 4240 03:29:36,120 --> 03:29:37,720 POSITION IN THE AIRWAY BRIDGING 4241 03:29:37,720 --> 03:29:37,960 SYSTEM. 4242 03:29:37,960 --> 03:29:40,240 THESE ARE THE LAST BRIDGES OF 4243 03:29:40,240 --> 03:29:42,960 THE AIRWAY WHERE COPD IS THOUGHT 4244 03:29:42,960 --> 03:29:51,880 TO BEGIN. 4245 03:29:51,880 --> 03:29:55,840 THEY GO TO RESPIRATORY 4246 03:29:55,840 --> 03:29:58,120 BRONCHIOLES AND THIS IS THE AXIS 4247 03:29:58,120 --> 03:30:00,360 WHICH THE DISEASE EVOLVES AND WE 4248 03:30:00,360 --> 03:30:02,880 FOCUS ON THIS PARTICULAR AREA. 4249 03:30:02,880 --> 03:30:06,960 THERE'S A LOT OF EVIDENCE 4250 03:30:06,960 --> 03:30:08,560 SUGGESTING THOSE CHANGES 4251 03:30:08,560 --> 03:30:12,080 HAPPENING IN DISTAL AIRWAYS 4252 03:30:12,080 --> 03:30:15,240 INCLUDING NARROWING OF LUMEN AND 4253 03:30:15,240 --> 03:30:16,800 DISAPPEARANCE OF THE NORMAL 4254 03:30:16,800 --> 03:30:20,280 STRUCTURE ORGANIZED TERMINAL AND 4255 03:30:20,280 --> 03:30:22,680 PRE-TERMAL BRONCHIOLES AND AIR 4256 03:30:22,680 --> 03:30:24,200 TRADING CAN BE SEEN IN 4257 03:30:24,200 --> 03:30:25,960 INDIVIDUALS NOT ONLY WITH COPD 4258 03:30:25,960 --> 03:30:31,000 BUT ALSO IN PEOPLE AT RISK ALL 4259 03:30:31,000 --> 03:30:32,120 THE SUBJECTS WITHOUT COPD. 4260 03:30:32,120 --> 03:30:33,960 AS DISEASE PROGRESSES YOU CAN 4261 03:30:33,960 --> 03:30:37,000 SEE PROGRESSION OF ANATOMICAL 4262 03:30:37,000 --> 03:30:40,760 CHANGES GOING MORE DISTALLY LIKE 4263 03:30:40,760 --> 03:30:44,160 CHANGES IN THE RESPIRATORY 4264 03:30:44,160 --> 03:30:45,680 BRONCHIOLES CONTRIBUTING TO 4265 03:30:45,680 --> 03:30:46,840 EMPHYSEMA AND IT'S POORLY 4266 03:30:46,840 --> 03:30:50,040 STUDIED AND IT'S HARD TO SAY 4267 03:30:50,040 --> 03:30:51,320 WHAT STARTS FIRST. 4268 03:30:51,320 --> 03:30:54,960 RESPIRATORY BRONCHIOLES GIVEN 4269 03:30:54,960 --> 03:30:56,440 TERMINAL BRONCHIOLES AND HARD TO 4270 03:30:56,440 --> 03:30:58,880 DETECT THE EARLIEST CHANGES IN 4271 03:30:58,880 --> 03:31:00,120 THIS TRANSITIONAL REGION IS 4272 03:31:00,120 --> 03:31:01,080 CHALLENGING. 4273 03:31:01,080 --> 03:31:03,200 AT THE MOMENT I'LL SAY IF 4274 03:31:03,200 --> 03:31:11,160 CHANGES HAPPEN IN RESPIRATORY 4275 03:31:11,160 --> 03:31:13,200 BRONCHIOLES AND EMPHYSEMA 4276 03:31:13,200 --> 03:31:17,520 BECOMES MORE DIFFUSED AND 4277 03:31:17,520 --> 03:31:17,800 DETECTABLE. 4278 03:31:17,800 --> 03:31:19,440 AND TO UNDERSTAND THE BIOLOGY OF 4279 03:31:19,440 --> 03:31:21,360 THE REGION WITHOUT DISEASE AND 4280 03:31:21,360 --> 03:31:25,040 HOW IT CHANGES TO COPD AT SINGLE 4281 03:31:25,040 --> 03:31:25,680 CELL LEVEL AND EQUATION SPECIFIC 4282 03:31:25,680 --> 03:31:28,680 LEVEL. 4283 03:31:28,680 --> 03:31:32,920 AND HOW TO MODEL THE CHANGES AND 4284 03:31:32,920 --> 03:31:34,400 FIND MAPS WE CAN TARGET AND 4285 03:31:34,400 --> 03:31:36,920 THERE ARE MAJOR BARRIERS I WANT 4286 03:31:36,920 --> 03:31:39,160 TO SHARE WITH YOU WHICH I AM 4287 03:31:39,160 --> 03:31:41,640 DEALING WITH EVERY DAY. 4288 03:31:41,640 --> 03:31:45,520 THE AIRWAYS TO ACCESS THROUGH 4289 03:31:45,520 --> 03:31:46,080 CONVENTIONAL WAYS. 4290 03:31:46,080 --> 03:31:48,320 YOU CANNOT REACH THEM THROUGH 4291 03:31:48,320 --> 03:31:50,800 REGULAR MICROSCOPY. 4292 03:31:50,800 --> 03:31:52,800 THE REGION CANNOT BE 4293 03:31:52,800 --> 03:31:54,280 RECAPITULATED IN MOUSE AND 4294 03:31:54,280 --> 03:31:57,000 LOOKING AT CELLULAR ELEMENTS ARE 4295 03:31:57,000 --> 03:31:59,600 NOT PRESENT IN THE MOUSE LAB AND 4296 03:31:59,600 --> 03:32:02,240 ALMOST NEVER GET RO1 TO STUDY 4297 03:32:02,240 --> 03:32:07,720 THE REGION YOU NEED TO KNOW THE 4298 03:32:07,720 --> 03:32:09,760 QUESTION BEFORE YOU KNOW 4299 03:32:09,760 --> 03:32:11,320 ORGANIZATIONAL AND WHAT IS THE 4300 03:32:11,320 --> 03:32:12,840 BIGGER PICTURE OF CHANGES IN 4301 03:32:12,840 --> 03:32:15,680 COPD. 4302 03:32:15,680 --> 03:32:19,400 WE FOUND ANOTHER ROUTE BECAUSE 4303 03:32:19,400 --> 03:32:23,680 WE COULDN'T START AND WE FOUND A 4304 03:32:23,680 --> 03:32:24,840 WAY OF STARTING. 4305 03:32:24,840 --> 03:32:30,000 BY FOCUSSING ON AGING OF DISTAL 4306 03:32:30,000 --> 03:32:32,120 AIRWAYS MANY CHANGE IN DISTAL 4307 03:32:32,120 --> 03:32:34,320 AIRWAYS ALSO HAPPEN IN OLDER 4308 03:32:34,320 --> 03:32:39,400 SUBJECTS WITHOUT DISEASE. 4309 03:32:39,400 --> 03:32:41,480 SO WE INSTITUTES NHLBI A 4310 03:32:41,480 --> 03:32:43,520 CO-FUNDED PROGRAM IN WHICH WE 4311 03:32:43,520 --> 03:32:46,760 WANTED TO ESTABLISH METHODOLOGY 4312 03:32:46,760 --> 03:32:49,400 TO DISSECT THE SMALL RANGES AND 4313 03:32:49,400 --> 03:32:51,360 SEE HOW BIOLOGY OF THE RANGES 4314 03:32:51,360 --> 03:32:53,800 CHANGE IN INDIVIDUALS WITH 4315 03:32:53,800 --> 03:32:56,600 DIFFERENT AGE AND ALSO AS LATE 4316 03:32:56,600 --> 03:32:58,200 TRANSITION TO COPD AND INCREASE 4317 03:32:58,200 --> 03:33:00,600 COLLABORATION TO GET NORMAL LUNG 4318 03:33:00,600 --> 03:33:03,440 TISSUE AND TO GET SAMPLES FROM 4319 03:33:03,440 --> 03:33:07,080 PEOPLE WITH AGING-RELATED LUNG 4320 03:33:07,080 --> 03:33:09,680 DISEASE AND BY COMPARING 4321 03:33:09,680 --> 03:33:10,560 DIFFERENT PATHOLOGIES TO SEE 4322 03:33:10,560 --> 03:33:13,880 WHAT IS UNIQUE WITH COPD. 4323 03:33:13,880 --> 03:33:19,920 THIS IS THE LOBULE AND THE UNIT 4324 03:33:19,920 --> 03:33:21,960 WHERE ALL THE CHANGES HAPPEN AND 4325 03:33:21,960 --> 03:33:23,880 THE LUNG DISEASE. 4326 03:33:23,880 --> 03:33:25,120 THIS IS THE LAST VISIBLE AIRWAYS 4327 03:33:25,120 --> 03:33:30,080 YOU CAN SEE. 4328 03:33:30,080 --> 03:33:36,200 HOW TO CONNECT THEM IN A PRECISE 4329 03:33:36,200 --> 03:33:39,680 WAY AND THE APPROACH BY WHICH 4330 03:33:39,680 --> 03:33:42,440 INJECTING AIR TO THE LAST 4331 03:33:42,440 --> 03:33:45,040 VISIBLE AIRWAY WE CAN DELINEATE 4332 03:33:45,040 --> 03:33:47,880 THE PATHWAY THAT AIR TRAVELS TO 4333 03:33:47,880 --> 03:33:51,120 THE LOBULES AND NOW WE CAN 4334 03:33:51,120 --> 03:33:53,560 DISSECT THE PATHWAY AND GET TO 4335 03:33:53,560 --> 03:33:56,000 THE LAST VISIBLE AIRWAY AND THE 4336 03:33:56,000 --> 03:34:03,880 LAST VISIBLE AIRWAY WOULD BE THE 4337 03:34:03,880 --> 03:34:06,760 PRETERMINAL BRONCHIOLE AND WE 4338 03:34:06,760 --> 03:34:12,120 REACHED THE LEVEL OF WHERE THE 4339 03:34:12,120 --> 03:34:16,680 TRANSITION TO THE LOBULE AND THE 4340 03:34:16,680 --> 03:34:19,760 PRETERMINAL BRONCHIOLES LEADING 4341 03:34:19,760 --> 03:34:22,560 TO THE ENRICHED TISSUE GOING TO 4342 03:34:22,560 --> 03:34:27,760 THE RESPIRATORY REGION AND BY 4343 03:34:27,760 --> 03:34:30,720 INJECT INK IN THE AIRWAY WE CAN 4344 03:34:30,720 --> 03:34:36,440 DISSECT THE UNIT OF THE LAST 4345 03:34:36,440 --> 03:34:38,880 PRE-BRONCHIOLE WHERE ALL THE 4346 03:34:38,880 --> 03:34:42,080 DISEASE-RELATED BIOLOGY HAPPENS. 4347 03:34:42,080 --> 03:34:44,520 AND SO THIS IS ANOTHER EXAMPLE 4348 03:34:44,520 --> 03:34:46,040 SHOWING WE CAN VISUALIZE AIR 4349 03:34:46,040 --> 03:34:48,600 TRANSPORT THROUGH THE AIRWAYS 4350 03:34:48,600 --> 03:34:52,400 AND THIS TRACKING IN THE AREA OF 4351 03:34:52,400 --> 03:34:53,800 BIFURCATION WHERE IT'S HARD FOR 4352 03:34:53,800 --> 03:34:58,920 AIR BUBBLES TO MOVE AND THIS IS 4353 03:34:58,920 --> 03:35:02,120 THE ALVEOLAR REGION AND YOU SEE 4354 03:35:02,120 --> 03:35:03,720 THE ALVEOLI AND THE AIR BUBBLES 4355 03:35:03,720 --> 03:35:06,040 WHICH END UP IN THE ALVEOLI 4356 03:35:06,040 --> 03:35:09,880 AFTER THE INJECTION OF AIR WHICH 4357 03:35:09,880 --> 03:35:10,840 I SHOWED. 4358 03:35:10,840 --> 03:35:12,440 AND THERE'S DIFFERENT LEVELS OF 4359 03:35:12,440 --> 03:35:15,280 AIRWAYS FROM THE SAME PATIENT WE 4360 03:35:15,280 --> 03:35:17,640 CAN FOLLOW THE WHOLE SYSTEM UP 4361 03:35:17,640 --> 03:35:22,040 TO OPEN THE BRONCHIOLES TO THE 4362 03:35:22,040 --> 03:35:25,480 RESPIRATORY REGION WHERE WITH A 4363 03:35:25,480 --> 03:35:28,120 MULTI-MARK ING APPROACH AND 4364 03:35:28,120 --> 03:35:29,720 IDENTIFY UNIQUE BIOLOGY AND WHAT 4365 03:35:29,720 --> 03:35:33,880 WE FOUND IS THERE'S A BRIDGE 4366 03:35:33,880 --> 03:35:37,560 CELL POPULATION GOING TO THE 4367 03:35:37,560 --> 03:35:39,000 CLINICAL AND BASIC SCIENCE AND 4368 03:35:39,000 --> 03:35:42,680 BRIDGES THIS WITH THE ALVEOLAR 4369 03:35:42,680 --> 03:35:46,680 EPITHELIUM AND THESE ARE IN THE 4370 03:35:46,680 --> 03:35:49,320 CELL POPULATION SECRETORY CELLS 4371 03:35:49,320 --> 03:35:51,120 IN THE AREA OF TRANSITION FROM 4372 03:35:51,120 --> 03:35:54,480 TERMINAL TO RESPIRATORY 4373 03:35:54,480 --> 03:35:56,000 BRONCHIOLES THESE ARE RED CELLS. 4374 03:35:56,000 --> 03:35:57,680 WE WERE ABLE TO USE DIFFERENT 4375 03:35:57,680 --> 03:36:01,720 MARKERS TO SHOW DIFFERENT FROM 4376 03:36:01,720 --> 03:36:08,600 CLASSICAL POETIC -- 4377 03:36:08,600 --> 03:36:09,560 HEMATOPOIETIC CELLS AND THEY 4378 03:36:09,560 --> 03:36:12,400 TRANSITION TO THE DISTAL REGION. 4379 03:36:12,400 --> 03:36:17,840 AND WE FOUND IN ADDITION TO THE 4380 03:36:17,840 --> 03:36:21,400 TASK LONG THE PROXIMAL DISTAL 4381 03:36:21,400 --> 03:36:25,400 AXIS AND WE CALL THEM SECRETORY 4382 03:36:25,400 --> 03:36:28,920 CELLS AND THEY WERE LOST AND THE 4383 03:36:28,920 --> 03:36:32,360 CELL POPULATION WHICH WE KNOW 4384 03:36:32,360 --> 03:36:37,320 LITTLE ABOUT SIMILAR TO 4385 03:36:37,320 --> 03:36:38,920 ARROCYTES WHICH MAKE THE 4386 03:36:38,920 --> 03:36:48,400 CAPILLARY INTERFACE IN THE AL 4387 03:36:48,400 --> 03:36:48,800 ALVEOLI. 4388 03:36:48,800 --> 03:36:55,360 AND THESE ARE THE CAPILLARIES OF 4389 03:36:55,360 --> 03:36:59,440 THE CELLS OF THE ALVEOLI IN THE 4390 03:36:59,440 --> 03:37:00,800 REGION OF TRANSMISSION WHERE THE 4391 03:37:00,800 --> 03:37:01,600 BIOLOGY HAPPENS. 4392 03:37:01,600 --> 03:37:03,920 IT'S NOT UNIQUE TO CHANGES TO 4393 03:37:03,920 --> 03:37:04,200 COPD. 4394 03:37:04,200 --> 03:37:06,920 WHEN WE LOOKED AT THE SAME 4395 03:37:06,920 --> 03:37:08,480 SINGLE-CELL DATA OF ALL THE 4396 03:37:08,480 --> 03:37:11,400 INDIVIDUALS OLDER THAN 60 YEARS 4397 03:37:11,400 --> 03:37:13,680 OLD WE SAW THE SAME CHANGES AND 4398 03:37:13,680 --> 03:37:15,760 THE CAPILLARY CELL POPULATION 4399 03:37:15,760 --> 03:37:17,680 SUGGESTING THAT MAYBE SOME KIND 4400 03:37:17,680 --> 03:37:20,120 OF REGION SPECIFIC NEEDS 4401 03:37:20,120 --> 03:37:22,240 COMPOSED TO REGION SPECIFIC 4402 03:37:22,240 --> 03:37:27,840 CAPILLARIES AND SMOOMAL CELLS A 4403 03:37:27,840 --> 03:37:30,000 CELLS WHICH REGENERATE IN THE 4404 03:37:30,000 --> 03:37:34,080 PRESENCE OF THIS UNIQUE REGION 4405 03:37:34,080 --> 03:37:35,240 SPECIFIC EPITHELIAL CELL 4406 03:37:35,240 --> 03:37:38,360 POPULATION AND THE BRONCHIOLES 4407 03:37:38,360 --> 03:37:40,640 ABSENT IN MICE AND THE TB-RB 4408 03:37:40,640 --> 03:37:45,120 JUNCTION ABSENT IN MICE AND 4409 03:37:45,120 --> 03:37:48,160 SUGGESTING THE UNIQUE BIOLOGY IS 4410 03:37:48,160 --> 03:37:49,120 HAPPENING IN THE TRANSITIONAL 4411 03:37:49,120 --> 03:37:52,560 REGION AND HOW IT CHANGES IS 4412 03:37:52,560 --> 03:37:55,880 IMPOSSIBLE TO MIMIC RECAPITULATE 4413 03:37:55,880 --> 03:37:57,880 USING MOUSE SO WHAT WE NEED TO 4414 03:37:57,880 --> 03:38:01,280 DO IS ESTABLISH A HUMAN-BASED 4415 03:38:01,280 --> 03:38:04,440 MODEL AND HOW DO WE IDENTIFY THE 4416 03:38:04,440 --> 03:38:04,680 AIRWAYS? 4417 03:38:04,680 --> 03:38:06,040 WE SEPARATED BASAL SELLS FROM 4418 03:38:06,040 --> 03:38:09,360 THE BRONCHIOLES FROM THE SAME 4419 03:38:09,360 --> 03:38:14,640 PATIENTS FROM PROXIMAL AIRWAYS 4420 03:38:14,640 --> 03:38:17,440 AND WHEN WE DIFFERENTIATE THE 4421 03:38:17,440 --> 03:38:21,600 CELLS WE WERE ABLE TO 4422 03:38:21,600 --> 03:38:22,960 RECAPITULATE THE CELLS WITH ALL 4423 03:38:22,960 --> 03:38:27,880 THE MARKERS OF TASKS AND FOCUS 4424 03:38:27,880 --> 03:38:32,520 ON A2 TRANSCRIPTION FACTOR. 4425 03:38:32,520 --> 03:38:33,800 AND AT THE SINGLE CELL LEVEL 4426 03:38:33,800 --> 03:38:36,600 THERE ARE TWO SAMPLES ONE WHICH 4427 03:38:36,600 --> 03:38:39,880 WAS SUCCESSFUL HAVING THE MEMORY 4428 03:38:39,880 --> 03:38:41,640 TO REGENERATE TASKS IN VITRO 4429 03:38:41,640 --> 03:38:46,440 DATA AND THE TASKS ARE THE SAME 4430 03:38:46,440 --> 03:38:50,560 WE SEE IN EXPRESSING THE CELLS 4431 03:38:50,560 --> 03:38:52,640 AND 32 ALSO. 4432 03:38:52,640 --> 03:38:54,520 WHAT IS THE MEMORY IN STEM CELLS 4433 03:38:54,520 --> 03:38:57,560 WHICH ALLOWS THE STEM CELLS TO 4434 03:38:57,560 --> 03:39:01,760 REGENERATE IN THE ABSENCE OF IN 4435 03:39:01,760 --> 03:39:09,240 VIVO IN NICHE AND WE SAW THE 4436 03:39:09,240 --> 03:39:12,360 BASAL CELLS EXPRESSED MARKERS 4437 03:39:12,360 --> 03:39:16,440 AND TRANSCRIPT FACTOR. 4438 03:39:16,440 --> 03:39:22,680 WE WENT TO CHROMATIN LEVEL AND 4439 03:39:22,680 --> 03:39:25,920 WE FOUND IN DISTAL AIRWAYS THE 4440 03:39:25,920 --> 03:39:31,320 RED COLORS ENRICHED 4441 03:39:31,320 --> 03:39:33,600 TRANSCRIPTION FACTORS IN DISTAL 4442 03:39:33,600 --> 03:39:36,760 AIRWAY BASAL CELLS RELATED TO 4443 03:39:36,760 --> 03:39:39,560 THE TRANSCRIPTION FACTORS I 4444 03:39:39,560 --> 03:39:42,160 DIDN'T SHOW ALL OF THEM BUT IF 4445 03:39:42,160 --> 03:39:44,720 YOU WANT TRANSCRIPTION FACTORS 4446 03:39:44,720 --> 03:39:46,880 MOST SPECIFIC TO PROXIMAL 4447 03:39:46,880 --> 03:39:48,800 AIRWAYS AND PIONEERED FACTORS 4448 03:39:48,800 --> 03:39:50,480 AND ARE IMPORTANT FOR 4449 03:39:50,480 --> 03:39:54,480 MAINTAINING DIFFERENT TYPE OF 4450 03:39:54,480 --> 03:39:54,800 MEMORY. 4451 03:39:54,800 --> 03:39:56,720 AND DIFFERENT MEMORY 4452 03:39:56,720 --> 03:39:58,120 TRANSCRIPTION FACTORS TO 4453 03:39:58,120 --> 03:40:00,600 PROXIMAL AND DISTAL AIRWAYS AND 4454 03:40:00,600 --> 03:40:03,080 ENRICHED IN BASAL AND 4455 03:40:03,080 --> 03:40:05,080 INTERMEDIATE CELLS IN THE 4456 03:40:05,080 --> 03:40:06,000 PROXIMAL AIRWAYS. 4457 03:40:06,000 --> 03:40:08,120 AND ACTUALLY THAT WAS FUNDED BY 4458 03:40:08,120 --> 03:40:10,640 NIH THAT'S WHY I SHOWED THE 4459 03:40:10,640 --> 03:40:11,120 SLIDE. 4460 03:40:11,120 --> 03:40:12,200 MANY THINGS YOU'RE GOING TO DO 4461 03:40:12,200 --> 03:40:14,720 BASED ON YOUR ENTHUSIASM IF NOT 4462 03:40:14,720 --> 03:40:17,600 SUPPORTED BY THE STUDY SECTION 4463 03:40:17,600 --> 03:40:17,920 OPINIONS. 4464 03:40:17,920 --> 03:40:20,880 AND THIS IS THE ENRICHMENT OF 4465 03:40:20,880 --> 03:40:26,000 THE DISTAL MEMORY IN THE AREA 4466 03:40:26,000 --> 03:40:26,760 WHERE BRONCHIOLES TRANSITION AND 4467 03:40:26,760 --> 03:40:29,840 WHEN WE LOOKED AT THE INITIAL 4468 03:40:29,840 --> 03:40:32,280 DATA OF COPD WE ALSO LOOKED AT 4469 03:40:32,280 --> 03:40:35,880 THIS DETECTABLE FEATURE OF 4470 03:40:35,880 --> 03:40:46,120 BROTHER -- BRONCHIOLES IN THE 4471 03:40:46,120 --> 03:40:47,280 SURROUNDING CELLS. 4472 03:40:47,280 --> 03:40:50,120 WHAT HAPPENS WHEN THE BASAL 4473 03:40:50,120 --> 03:40:50,640 CELLS PROGRESS? 4474 03:40:50,640 --> 03:40:55,720 THAT'S ANOTHER SAMPLE. 4475 03:40:55,720 --> 03:41:05,000 THIS COULDN'T MAKE SQUAMOUS CELL 4476 03:41:05,000 --> 03:41:07,160 FACTORS FOR THE DISTAL AIRWAYS. 4477 03:41:07,160 --> 03:41:10,720 THE CELLS BECOME SQUAMOUS AND 4478 03:41:10,720 --> 03:41:14,000 SENESCENT AND HAVE SENESCENT 4479 03:41:14,000 --> 03:41:14,640 MARKERS AND EXPRESSION OF GAMMA 4480 03:41:14,640 --> 03:41:16,360 RECEPTOR. 4481 03:41:16,360 --> 03:41:18,600 AND THAT'S A CONNECTION TO THE 4482 03:41:18,600 --> 03:41:20,800 NEW SYSTEM BECAUSE WE FOUND IN 4483 03:41:20,800 --> 03:41:22,840 COPD AND ALSO IN ALL THE 4484 03:41:22,840 --> 03:41:25,080 SUBJECTS THERE'S INCREASED 4485 03:41:25,080 --> 03:41:29,960 FREQUENCY OF INTERFERON GAMMA 4486 03:41:29,960 --> 03:41:31,880 HIGHLY EXPRESSING T CELLS. 4487 03:41:31,880 --> 03:41:36,920 SUGGESTING A NUMBER OF T CELLS 4488 03:41:36,920 --> 03:41:37,720 RECEPTORS MAY INCREASE CELLS 4489 03:41:37,720 --> 03:41:40,600 WITH MEMORY OF REGIONAL 4490 03:41:40,600 --> 03:41:41,120 DIFFERENTIATION. 4491 03:41:41,120 --> 03:41:42,960 AND THAT CD 8 CELLS RIGHT NEXT 4492 03:41:42,960 --> 03:41:45,840 TO BASAL CELLS AND THESE ARE THE 4493 03:41:45,840 --> 03:41:46,920 TASKS. 4494 03:41:46,920 --> 03:41:48,200 EVERYTHING HAPPENS IN THIS 4495 03:41:48,200 --> 03:41:48,560 NICHE. 4496 03:41:48,560 --> 03:41:51,000 WE SHOWED THE DATA IN REGIONS OF 4497 03:41:51,000 --> 03:41:57,000 CD 8 POSITIVE CELLS IN THE COPD 4498 03:41:57,000 --> 03:41:58,520 AND I WON'T GO INTO FOCUS BUT 4499 03:41:58,520 --> 03:42:02,720 WHAT I WANT TO END WITH IS 4500 03:42:02,720 --> 03:42:05,520 BRIDGING THE GAP IN NHLBI 4501 03:42:05,520 --> 03:42:05,800 PROPOSES. 4502 03:42:05,800 --> 03:42:08,760 BY SEEING INCREASED PATHOLOGY WE 4503 03:42:08,760 --> 03:42:10,320 SEE INTERNAL BRONCHIOLES THERE'S 4504 03:42:10,320 --> 03:42:15,520 IN WAY TO IMAGE THAT. 4505 03:42:15,520 --> 03:42:17,480 IS THERE THE PATHOLOGY IN THE 4506 03:42:17,480 --> 03:42:25,200 PROXIMAL AIRWAYS AND THIS 4507 03:42:25,200 --> 03:42:30,440 CULMINATES IN THE BRONCHIOLES. 4508 03:42:30,440 --> 03:42:33,600 I MET ALL THESE PEOPLE AND 4509 03:42:33,600 --> 03:42:39,640 LOOKED AT SPIROMETER DATA AND 4510 03:42:39,640 --> 03:42:44,320 BRONCHOSCOPY SAMPLES AND THE 4511 03:42:44,320 --> 03:42:50,760 SCORE OF DISTAL ENRICHMENT WAS 4512 03:42:50,760 --> 03:42:52,280 REGULATED IN SMOKERS AND FORMER 4513 03:42:52,280 --> 03:42:54,760 SMOKERS WHO DON'T HAVE AIRWAY 4514 03:42:54,760 --> 03:42:56,240 OBSTRUCTION SUGGESTING NOT ONLY 4515 03:42:56,240 --> 03:42:58,920 THE GENES ARE DETECTABLE AND 4516 03:42:58,920 --> 03:43:03,640 MEMORY IS BEGINNING TO BE 4517 03:43:03,640 --> 03:43:04,280 ACQUIRED. 4518 03:43:04,280 --> 03:43:06,200 AND DIFFERENTIATION IS LOST 4519 03:43:06,200 --> 03:43:07,160 SMOKERS WITHOUT LUNG DISEASE AND 4520 03:43:07,160 --> 03:43:09,960 OTHER MARKERS WHICH ARE MARKERS 4521 03:43:09,960 --> 03:43:11,680 OF DISTAL AIRWAY MEMORY. 4522 03:43:11,680 --> 03:43:14,360 AND THOSE SMOKERS WHO HAVE 4523 03:43:14,360 --> 03:43:17,520 DRAMATIC LOSS OF MEMORY HAVE 4524 03:43:17,520 --> 03:43:20,440 HIGHEST LEVEL OF SYMPTOMS WHICH 4525 03:43:20,440 --> 03:43:21,480 DEFINES PRE-COPD PEOPLE WHO 4526 03:43:21,480 --> 03:43:26,280 DON'T HAVE AIRWAY OBSTRUCTION 4527 03:43:26,280 --> 03:43:30,440 BUT HAVE COPD AND BY BIOLOGICAL 4528 03:43:30,440 --> 03:43:32,680 OBSTRUCTION WE CAN USE 4529 03:43:32,680 --> 03:43:36,240 LONGITUDINAL NATURE OF SPIROMICS 4530 03:43:36,240 --> 03:43:40,880 TO SEE IF IT'S TRUE IN PATIENTS 4531 03:43:40,880 --> 03:43:44,840 AND THERAPY COULD BE RESTORATION 4532 03:43:44,840 --> 03:43:46,680 OF THE DID I DISTAL REGION AND 4533 03:43:46,680 --> 03:43:49,480 RESTORING GOOD MEMORIES WHICH IS 4534 03:43:49,480 --> 03:43:52,840 STORED IN THE PROGENITOR CELLS 4535 03:43:52,840 --> 03:43:56,360 AND BECAUSE OF AGING OR 4536 03:43:56,360 --> 03:43:57,360 PROCESSES SPECIFIC TO 4537 03:43:57,360 --> 03:43:59,880 DEVELOPMENT OF COPD. 4538 03:43:59,880 --> 03:44:06,200 THANK YOU. 4539 03:44:06,200 --> 03:44:10,440 >> EXCELLENT TALK AND WORK. 4540 03:44:10,440 --> 03:44:14,360 NEXT TALK WILL BE FROM THE ROLE 4541 03:44:14,360 --> 03:44:19,480 OF PULMONARY MODELLING IN THE 4542 03:44:19,480 --> 03:44:21,760 MECHANISMS OF COPD FROM IRINA 4543 03:44:21,760 --> 03:44:22,040 PETRACHE. 4544 03:44:22,040 --> 03:44:23,880 >> THANK YOU FOR INVITING ME TO 4545 03:44:23,880 --> 03:44:26,920 PRESENT BRIEF OVERVIEW OF HOW TO 4546 03:44:26,920 --> 03:44:30,960 THE LING ENDOTHELIUM MAY 4547 03:44:30,960 --> 03:44:35,920 CONTRIBUTE TO COPD AND DIFFERENT 4548 03:44:35,920 --> 03:44:36,200 PHENOTYPE. 4549 03:44:36,200 --> 03:44:37,840 I'LL REMIND YOU OF THE 4550 03:44:37,840 --> 03:44:40,120 IMPORTANCE OF THE LOCATION AND 4551 03:44:40,120 --> 03:44:43,400 FUNCTION OF VARIOUS ENDOTHELIAL 4552 03:44:43,400 --> 03:44:45,720 CELLS THE OTHER LUNG STRUCTURES 4553 03:44:45,720 --> 03:44:51,120 AND CELLS AND HOW CAN BE A DOOR 4554 03:44:51,120 --> 03:44:55,320 TO SYSTEMIC PATHOGENESIS OF COPD 4555 03:44:55,320 --> 03:44:57,480 AND HOW IMPORTANT THE 4556 03:44:57,480 --> 03:44:58,480 HETEROGENEITY IS IN DISEASE 4557 03:44:58,480 --> 03:45:01,160 DEVELOPMENT AND GO OVER ACUTE 4558 03:45:01,160 --> 03:45:03,360 VERSUS ADAPTIVE CHANGES TO 4559 03:45:03,360 --> 03:45:05,600 CIGARETTE SMOKE AND HOW THEY MAY 4560 03:45:05,600 --> 03:45:09,040 INFLUENCE VARIOUS DISEASE 4561 03:45:09,040 --> 03:45:09,880 PHENOTYPES. 4562 03:45:09,880 --> 03:45:13,240 SUCH AS CAPILLARY DROP OUTS AND 4563 03:45:13,240 --> 03:45:16,080 PRESENT IN EMPHYSEMA IN THE PULL 4564 03:45:16,080 --> 03:45:17,280 MONET 4565 03:45:17,280 --> 03:45:18,960 MONET 4566 03:45:18,960 --> 03:45:23,120 MONETARY HYPERTENSION AND REMIND 4567 03:45:23,120 --> 03:45:26,320 YOU ENDOTHELIAL CELLS ARE 4568 03:45:26,320 --> 03:45:28,640 CRUCIAL FOR THE DEVELOPMENT OF 4569 03:45:28,640 --> 03:45:31,520 INFLAMMATION AND AIR SPACE 4570 03:45:31,520 --> 03:45:36,320 REMODELLING AND REMODELLING SUCH 4571 03:45:36,320 --> 03:45:37,680 AS VASCULAR WALL. 4572 03:45:37,680 --> 03:45:39,240 AS THE PREVIOUS SPEAKERS I'LL 4573 03:45:39,240 --> 03:45:42,720 FOCUS ON THE DISTAL AIRWAY 4574 03:45:42,720 --> 03:45:44,680 FOLLOWING ON THE OBSERVATIONS 4575 03:45:44,680 --> 03:45:48,800 THAT IN EARLY OR PRE-COPD OR 4576 03:45:48,800 --> 03:45:52,360 EARLY DISEASE, THIS IS A SIGN OF 4577 03:45:52,360 --> 03:45:55,520 MAJOR CHANGES. 4578 03:45:55,520 --> 03:45:57,160 REMINDING YOU THAT THE DISTAL 4579 03:45:57,160 --> 03:46:01,880 LUNG IS ENRICHED IN PULMONARY 4580 03:46:01,880 --> 03:46:07,040 CAPITAL CELLS AND FORM A NETWORK 4581 03:46:07,040 --> 03:46:13,040 OF SHORT VESSELS LIKE CAPILLARY 4582 03:46:13,040 --> 03:46:14,280 POSTS AND CONSTITUTE 32% OF THE 4583 03:46:14,280 --> 03:46:17,200 MASS OF THE ALVEOLI. 4584 03:46:17,200 --> 03:46:20,160 AND REMIND YOU IT'S DIFFICULT TO 4585 03:46:20,160 --> 03:46:23,720 VISUALIZE THE PULMONARY VASCULAR 4586 03:46:23,720 --> 03:46:26,360 SYSTEM IN CROSS-SECTIONAL LUNG 4587 03:46:26,360 --> 03:46:29,120 TISSUE WE PRIMARILY USE TO 4588 03:46:29,120 --> 03:46:30,520 INVESTIGATE THE LUNGS. 4589 03:46:30,520 --> 03:46:37,720 WE HOPE TO ADD ANOTHER LAYER OF 4590 03:46:37,720 --> 03:46:39,040 SOPHISTICATION AND UNDERSTANDING 4591 03:46:39,040 --> 03:46:42,400 TO THE TWO-DIMENSIONAL 4592 03:46:42,400 --> 03:46:43,400 VISUALIZATION OF THE VESSELS. 4593 03:46:43,400 --> 03:46:47,560 UNLIKE THE AIRWAYS THE VESSELS 4594 03:46:47,560 --> 03:46:51,600 DO NOT BRANCH IN A DICHOTOMOUS 4595 03:46:51,600 --> 03:46:54,400 FASHION AND THEY CAN FORM FROM 4596 03:46:54,400 --> 03:46:56,880 LARGER VESSELS RATHER THAN A 4597 03:46:56,880 --> 03:46:59,880 LOGICAL EXTENSION OF THE 4598 03:46:59,880 --> 03:47:00,280 MICROVASCULATURE. 4599 03:47:00,280 --> 03:47:01,760 AND VARIOUS INVESTIGATORS HAVE 4600 03:47:01,760 --> 03:47:03,600 TRIED TO CLASSIFY THE VESSELS 4601 03:47:03,600 --> 03:47:08,600 AND YOU'LL SEE IN THE LITERATURE 4602 03:47:08,600 --> 03:47:14,040 VARIOUS NOMENCLATURE WE HAVE TO 4603 03:47:14,040 --> 03:47:18,960 PAY ATTENTION TO AS WE DESCRIBE 4604 03:47:18,960 --> 03:47:19,160 COPD. 4605 03:47:19,160 --> 03:47:24,960 I WANTED TO HIGHLIGHT THE WORK 4606 03:47:24,960 --> 03:47:27,240 OF OUTSTANDING VISUALIZATION OF 4607 03:47:27,240 --> 03:47:33,000 THE HISTOLOGY REMINDS US THE 4608 03:47:33,000 --> 03:47:34,280 ENDOTHELIAL CELLS IN VASCULATURE 4609 03:47:34,280 --> 03:47:36,600 IS NOT ISOLATED. 4610 03:47:36,600 --> 03:47:41,720 IT'S IN CLOSE CONTACT WITH THE 4611 03:47:41,720 --> 03:47:42,960 SMOOTH MUSCLE LAYER AS WELL AS 4612 03:47:42,960 --> 03:47:47,880 TO ALVEOLI DIRECTLY IN THE 4613 03:47:47,880 --> 03:47:48,360 STRUCTURE OF THE LUNG. 4614 03:47:48,360 --> 03:47:50,080 AND AGAIN HERE PULMONARY AND 4615 03:47:50,080 --> 03:47:52,240 LARGE ARTERY IN ENDOTHELIAL CELL 4616 03:47:52,240 --> 03:47:58,760 CAN BE CLOSE TO A LARGE AIRWAY 4617 03:47:58,760 --> 03:48:04,440 AS WELL AS CELLS FROM THE DISTAL 4618 03:48:04,440 --> 03:48:04,840 LUNG. 4619 03:48:04,840 --> 03:48:10,360 THE ENDOTHELIAL CELLS HAVE A 4620 03:48:10,360 --> 03:48:12,960 DIFFERENT TRANSCRIPTOME AND 4621 03:48:12,960 --> 03:48:15,520 THESE ARE TRANSCRIPTOMIC 4622 03:48:15,520 --> 03:48:18,960 ANALYSIS VERSUS SYSTEMIC 4623 03:48:18,960 --> 03:48:23,840 ENDOTHELIAL CELLS. 4624 03:48:23,840 --> 03:48:27,880 THROUGH WORK DONE BY DR 4625 03:48:27,880 --> 03:48:30,120 DR. STEPHANS AND COLLEAGUES THE 4626 03:48:30,120 --> 03:48:37,640 LARGE ARTERY ENDOTHELIAL CELLS 4627 03:48:37,640 --> 03:48:38,400 HAVE A HIGHER PROGENITOR 4628 03:48:38,400 --> 03:48:44,840 CAPACITY. 4629 03:48:44,840 --> 03:48:48,600 MORE SO RECENT RNA SEQ SHOWS TWO 4630 03:48:48,600 --> 03:48:54,680 TYPES OF EPITHELIAL CELLS OF THE 4631 03:48:54,680 --> 03:48:57,560 MICROVASCULATURE WITH THE SUB 4632 03:48:57,560 --> 03:49:01,480 TYPE BEING PARTNERS TYPE 1 CELLS 4633 03:49:01,480 --> 03:49:07,200 IN GAS EXCHANGE AND WITH THE 4634 03:49:07,200 --> 03:49:14,760 MORE AND G CAP OR GENERAL 4635 03:49:14,760 --> 03:49:16,240 CAPILLARY ENDOTHELIAL CELLS 4636 03:49:16,240 --> 03:49:17,280 PARTICIPATING IN THE CROSS TALK 4637 03:49:17,280 --> 03:49:22,680 AND IN THE PROGENITOR CELL 4638 03:49:22,680 --> 03:49:26,440 FUNCTION FOR THE AEROCYTE. 4639 03:49:26,440 --> 03:49:29,480 THERE'S PLENTY OF WORK I DON'T 4640 03:49:29,480 --> 03:49:31,160 HAVE TIME TO GO TO HOW IMPORTANT 4641 03:49:31,160 --> 03:49:33,360 THEY ARE IN THE REGENERATION OF 4642 03:49:33,360 --> 03:49:36,200 THE LIST TAL LUNG STRUCTURE. 4643 03:49:36,200 --> 03:49:37,680 -- DISTAL LUNG STRUCTURE. 4644 03:49:37,680 --> 03:49:40,160 HOW DO WE UNDERSTAND THE 4645 03:49:40,160 --> 03:49:43,080 IMPORTANCE OF ENDO THELIUM TO 4646 03:49:43,080 --> 03:49:44,840 THE THREE MAJOR PHENOTYPES OF 4647 03:49:44,840 --> 03:49:47,680 EMPHASIZE WE'VE BEEN TALKING 4648 03:49:47,680 --> 03:49:50,280 ABOUT SINCE THE MORNING WHERE IN 4649 03:49:50,280 --> 03:49:53,280 THE CHRONIC BRONCHITIS AIRWAY 4650 03:49:53,280 --> 03:49:56,720 THICKENING AND INFLAMMATION IS 4651 03:49:56,720 --> 03:50:07,240 CONTRIBUTING TO BY LEAKY BRONCHO 4652 03:50:08,560 --> 03:50:09,800 THELIAL CELLS AND HAVE TO DEAL 4653 03:50:09,800 --> 03:50:11,800 WITH THE PATHOGENESIS AND 4654 03:50:11,800 --> 03:50:15,640 THERE'S LITTLE WORK THERE WHERE 4655 03:50:15,640 --> 03:50:21,240 WE UNDERSTAND THE SIMILARITY 4656 03:50:21,240 --> 03:50:24,760 WITH COPD AND MANY DIFFERENCES. 4657 03:50:24,760 --> 03:50:27,480 WE POSE THE LUNG ENDOTHELIAL 4658 03:50:27,480 --> 03:50:29,880 CELLS RESPONSE TO CIGARETTE 4659 03:50:29,880 --> 03:50:31,120 SMOKE AND OTHER EXPOSOME WE 4660 03:50:31,120 --> 03:50:35,960 STILL HAVE TO STUDY MAY 4661 03:50:35,960 --> 03:50:36,960 DETERMINE THE DISEASE PHENOTYPE. 4662 03:50:36,960 --> 03:50:39,920 I WANT TO REMIND THE AUDIENCE 4663 03:50:39,920 --> 03:50:41,800 ESPECIALLY THE CLINICIANS THOUGH 4664 03:50:41,800 --> 03:50:44,080 THE AIRWAY AND THE EPITHELIAL 4665 03:50:44,080 --> 03:50:49,240 CELLS IS FIRST SEEING THE 4666 03:50:49,240 --> 03:50:52,800 CIGARETTE SMOKE 2,000 COMPOUNDS 4667 03:50:52,800 --> 03:50:54,840 THE ENDOTHELIUM QUICKLY IS 4668 03:50:54,840 --> 03:50:56,680 EXPOSED TO THE SAME THROUGH 4669 03:50:56,680 --> 03:51:02,280 ABSORPTION OF THE TOXIC 4670 03:51:02,280 --> 03:51:02,560 CHEMICALS. 4671 03:51:02,560 --> 03:51:05,280 SO WE HAVE SHOWN WITH EXPOSURE 4672 03:51:05,280 --> 03:51:08,840 VIA THE INHALATION THERE'S 4673 03:51:08,840 --> 03:51:12,480 LEUKOCYTES AND DECREASED FLOW 4674 03:51:12,480 --> 03:51:19,000 AND THIS MAY BE IMPACTED BY 4675 03:51:19,000 --> 03:51:24,240 MULTIPLE SUSCEPTIBILITY FACTORS 4676 03:51:24,240 --> 03:51:27,600 SUCH AS LOSS OF CFTR SEEN IN THE 4677 03:51:27,600 --> 03:51:30,160 MOUSE WHEN THEY GO THROUGH THE 4678 03:51:30,160 --> 03:51:32,200 ACUTE CHANGES IN SMOKE 4679 03:51:32,200 --> 03:51:32,480 INHALATION. 4680 03:51:32,480 --> 03:51:34,120 HERE WE'RE MOSTLY INTERESTED IN 4681 03:51:34,120 --> 03:51:35,120 SEEING WHAT HAPPENS AFTER 4682 03:51:35,120 --> 03:51:36,400 DECADES OF SMOKING. 4683 03:51:36,400 --> 03:51:46,400 THIS WAS A SEMINOLE PAPER THAT 4684 03:51:46,400 --> 03:51:48,480 SHOWS ENDOTHELIAL CELL APOPTOSIS 4685 03:51:48,480 --> 03:51:51,280 IS DIRECTLY CAUSATIVE OF 4686 03:51:51,280 --> 03:51:53,120 EMPHYSEMA IN THE ALVEOLAR CELL 4687 03:51:53,120 --> 03:51:55,720 LOSS AND WE HAVE IDENTIFIED THE 4688 03:51:55,720 --> 03:51:59,040 IMPORTANCE OF SINGLE LIPID 4689 03:51:59,040 --> 03:52:03,880 SIGNALLING IN THE POST 4690 03:52:03,880 --> 03:52:06,040 TRANSCRIPTIONAL AFFECT OF 4691 03:52:06,040 --> 03:52:08,600 SMOKING AND BLOCKADE IN THE 4692 03:52:08,600 --> 03:52:11,600 SPACE AND USING COLLABORATIVE 4693 03:52:11,600 --> 03:52:13,880 WORK WITH SAMPLES FROM THE COPD 4694 03:52:13,880 --> 03:52:17,040 GENE AND OTHER COHORTS, WE HAVE 4695 03:52:17,040 --> 03:52:20,040 IDENTIFY A PERIPHERAL BLOOD 4696 03:52:20,040 --> 03:52:23,160 SIGNATURE USING METABOLOMICS AND 4697 03:52:23,160 --> 03:52:25,960 EVENTUALLY GENOMICS OF AN 4698 03:52:25,960 --> 03:52:29,520 ALTERED SINGLE-LIPID METABOLISM 4699 03:52:29,520 --> 03:52:34,280 IN COPD AND SIGNAL FOR A 4700 03:52:34,280 --> 03:52:38,120 PHOSPHATE SIGNALLING IN THE 4701 03:52:38,120 --> 03:52:42,680 COHORT OF EMPHYSEMA OF COPD 4702 03:52:42,680 --> 03:52:43,160 ASKER BASES. 4703 03:52:43,160 --> 03:52:48,120 THIS WAS -- EXACERBATION AND 4704 03:52:48,120 --> 03:52:49,960 THIS CAME FROM DONOR LUNGS OF 4705 03:52:49,960 --> 03:52:52,160 SMOKERS VERSUS NON-SMOKERS WHERE 4706 03:52:52,160 --> 03:52:57,160 WE SAW AGAIN SIGNAL FOR A LOW 4707 03:52:57,160 --> 03:52:59,160 S1P ENVIRONMENT AND TO REMIND 4708 03:52:59,160 --> 03:53:04,560 EVERYONE, S1P AND THE RECEPTOR 4709 03:53:04,560 --> 03:53:06,120 S1P1 IS IMPORTANT FOR THE 4710 03:53:06,120 --> 03:53:10,560 MAINTENANCE OF VESSELS AND FOR 4711 03:53:10,560 --> 03:53:11,440 REPAIR. 4712 03:53:11,440 --> 03:53:13,960 AGAIN, THERE'S THE UNBIASSED 4713 03:53:13,960 --> 03:53:15,320 SIGNALS CONFIRMED BY OTHER 4714 03:53:15,320 --> 03:53:18,360 STUDIES INCLUDING IN MICE, WE 4715 03:53:18,360 --> 03:53:21,520 THINK BOTH SINGLE LIPID 4716 03:53:21,520 --> 03:53:23,920 METABOLISM MAY BE IMPORTANT IN 4717 03:53:23,920 --> 03:53:24,840 THE SIGNAL TOWARDS DISTAL CELL 4718 03:53:24,840 --> 03:53:29,800 LOSS AND INJURY. 4719 03:53:29,800 --> 03:53:32,760 TO MAKE HUNDREDS OF PAPERS FROM 4720 03:53:32,760 --> 03:53:34,880 OTHER LABS AND AS WELL AS OUR 4721 03:53:34,880 --> 03:53:36,400 CONTRIBUTIONS TO THE IMPORTANCE 4722 03:53:36,400 --> 03:53:41,680 OF THE ENDOTHELIAL CELLS IN 4723 03:53:41,680 --> 03:53:45,040 EMPHASIZE PATHOGENESIS I'M 4724 03:53:45,040 --> 03:53:48,240 HIGHLIGHTING IN PINK WHERE THE 4725 03:53:48,240 --> 03:53:51,120 PATHOGENIC MECHANISMS THAT HAVE 4726 03:53:51,120 --> 03:53:53,280 BEEN SHOWN IN OTHER CELL TYPES 4727 03:53:53,280 --> 03:53:55,360 TO BE IMPORTANT AND MANY OF YOU 4728 03:53:55,360 --> 03:53:57,360 WILL TALK ABOUT THEM TODAY, THEY 4729 03:53:57,360 --> 03:54:00,360 HAVE ALSO BEEN SHOWN TO BE 4730 03:54:00,360 --> 03:54:03,640 PERTINENT IN THE ENDOTHELIAL 4731 03:54:03,640 --> 03:54:05,200 CELLS IN RESPONSE TO CIGARETTE 4732 03:54:05,200 --> 03:54:06,280 SMOKE DAMAGE. 4733 03:54:06,280 --> 03:54:12,360 AND OUR LAB HAS FOCUSSED ON 4734 03:54:12,360 --> 03:54:22,840 THESE POTENTIAL TARGETS AND 4735 03:54:23,320 --> 03:54:26,960 SERAMIDE HAS BEEN INVOLVED IN 4736 03:54:26,960 --> 03:54:30,920 INFLAMMATORY AND THE REPAIR AND 4737 03:54:30,920 --> 03:54:35,880 THEN VERY WELL KNOWN 4738 03:54:35,880 --> 03:54:38,320 SUSCEPTIBILITY FACTOR IN 4739 03:54:38,320 --> 03:54:41,640 FUNCTION AS WELL AS LOSS OF CFTR 4740 03:54:41,640 --> 03:54:44,080 FUNCTION HAVE BEEN SHOWN TO BE 4741 03:54:44,080 --> 03:54:49,720 DAMAGING TO THE ENDOTHELIAL 4742 03:54:49,720 --> 03:54:54,680 CELLS IN THE LUNG. 4743 03:54:54,680 --> 03:54:59,880 AND SHOWS THEY'RE IMPORTANT IN 4744 03:54:59,880 --> 03:55:04,480 DEVELOPMENT AND CONTINUE TO 4745 03:55:04,480 --> 03:55:06,760 STUDY THE HYPERTENSION PHENOTYPE 4746 03:55:06,760 --> 03:55:09,600 BECAUSE IT ACCOUNTS FOR A LOT OF 4747 03:55:09,600 --> 03:55:11,880 MORTALITY AS WELL AS INCREASES 4748 03:55:11,880 --> 03:55:15,480 THE RISK OF EXACERBATIONS AND TO 4749 03:55:15,480 --> 03:55:17,240 POINT TO THERE'S A PHENOTYPE 4750 03:55:17,240 --> 03:55:20,040 THAT'S OUT OF PROPORTION. 4751 03:55:20,040 --> 03:55:23,440 THE PULMONARY HYPERTENSION IS 4752 03:55:23,440 --> 03:55:25,240 OUT OF PROPORTION TO THE LUNG 4753 03:55:25,240 --> 03:55:27,920 DYSFUNCTION AND WE KNOW VERY 4754 03:55:27,920 --> 03:55:31,880 LITTLE AS TO HOW THAT OCCURS. 4755 03:55:31,880 --> 03:55:33,520 THERE'S PROPOSED MECHANISM THAT 4756 03:55:33,520 --> 03:55:36,160 HAVE TO DO WITH MECHANICS, 4757 03:55:36,160 --> 03:55:37,200 HYPOXIA AND REMODELLING. 4758 03:55:37,200 --> 03:55:38,840 I'M GOING TO FOCUS ON SOME OF 4759 03:55:38,840 --> 03:55:40,480 THE WORK THAT WE AND OTHERS ARE 4760 03:55:40,480 --> 03:55:42,640 DOING TO BETTER UNDERSTAND THE 4761 03:55:42,640 --> 03:55:45,200 PATHOGENESIS OF THESE. 4762 03:55:45,200 --> 03:55:47,000 I WANTED TO HIGHLIGHT ONE OF THE 4763 03:55:47,000 --> 03:55:53,240 FIRST PAPERS THAT POINTED TO THE 4764 03:55:53,240 --> 03:55:54,760 CULPRIT FOR BOTH EMPHYSEMA 4765 03:55:54,760 --> 03:55:58,240 REMODELLING IN MICE AND TO 4766 03:55:58,240 --> 03:55:59,240 MENTION THAT THE MODELLING IS 4767 03:55:59,240 --> 03:56:05,360 STILL UNCLEAR AS TO WHERE IT 4768 03:56:05,360 --> 03:56:05,600 OCCURS. 4769 03:56:05,600 --> 03:56:10,960 WE TOOK THAT ON WITH A 4770 03:56:10,960 --> 03:56:21,480 COLLABORATION AND THERE WAS A 4771 03:56:23,320 --> 03:56:27,240 COHORT AND HAVE ADVANCED LUNG 4772 03:56:27,240 --> 03:56:27,880 DISEASE AND UNDERGOING LUNG 4773 03:56:27,880 --> 03:56:30,600 TRANSPLANTATION AND FEW SAMPLES 4774 03:56:30,600 --> 03:56:32,280 BUT WE LOOKED AT THE REMODELLING 4775 03:56:32,280 --> 03:56:36,080 AND WHERE DOES IT OCCUR IN 4776 03:56:36,080 --> 03:56:40,120 ESTABLISHED CONFIRMED COPD PH 4777 03:56:40,120 --> 03:56:42,280 AND ALL HONOREES OF THE CLASSES 4778 03:56:42,280 --> 03:56:43,920 I DEFINED PREVIOUSLY HAVE 4779 03:56:43,920 --> 03:56:49,200 EVIDENCE OF REMODELLING THAT 4780 03:56:49,200 --> 03:56:52,080 DON'T CORRELATE WITH THE MEAN 4781 03:56:52,080 --> 03:56:54,800 PRESSURE IN THE COPD AND COPD 4782 03:56:54,800 --> 03:56:54,960 PH. 4783 03:56:54,960 --> 03:56:58,400 WE THEN LOOKED AT ENDOTHELIAL 4784 03:56:58,400 --> 03:57:01,360 CELLS WITHIN THE LARGER VESSELS 4785 03:57:01,360 --> 03:57:04,760 OR MICROVASCULATURE AREAS AND 4786 03:57:04,760 --> 03:57:14,600 SAW A CHANGE AT THE LATE STAGE 4787 03:57:14,600 --> 03:57:17,560 OF DISEASE AND HE HEMODYNAMIC 4788 03:57:17,560 --> 03:57:24,120 CHANGES OF M -- PH. 4789 03:57:24,120 --> 03:57:29,800 IT'S ADAPTATION OF THE 4790 03:57:29,800 --> 03:57:32,560 ENDOTHELIUM AFTER THEY SEE 4791 03:57:32,560 --> 03:57:34,760 CERAMIDE AND IN RESPONSE TO 4792 03:57:34,760 --> 03:57:38,240 CHRONIC SMOKING ENDOTHELIAL 4793 03:57:38,240 --> 03:57:48,760 CELLS ADAPT AND LESS APOPTIC 4794 03:57:49,280 --> 03:57:50,760 THAN OTHER CELLS AND THINK IT 4795 03:57:50,760 --> 03:57:53,360 MAY HAVE TO DO WITH ADAPTATION 4796 03:57:53,360 --> 03:57:59,800 IN MICRORNA CONTENT. 4797 03:58:07,800 --> 03:58:12,240 AND THEY'RE RICH IN THE NEURON 4798 03:58:12,240 --> 03:58:17,960 26 BUT THERE WAS A NET LOSS IN 4799 03:58:17,960 --> 03:58:20,720 ENDOTHELIAL CELL CENTRIC RNA AND 4800 03:58:20,720 --> 03:58:23,880 THIS IS CONSISTENT WITH THE LUNG 4801 03:58:23,880 --> 03:58:30,720 OF MICE EXPOSED TO SMOKE IN COPD 4802 03:58:30,720 --> 03:58:33,760 LUNG TISSUE AS WELL AS IN HUMAN 4803 03:58:33,760 --> 03:58:34,800 LUNG TISSUE WE EXPLORED. 4804 03:58:34,800 --> 03:58:38,280 TO MAKE A LONG STORY SHORT SINCE 4805 03:58:38,280 --> 03:58:42,200 WE PUBLISHED THERE'S A DIFFERENT 4806 03:58:42,200 --> 03:58:45,520 FUNCTION IN LARGER ENDOTHELIAL 4807 03:58:45,520 --> 03:58:47,680 CELLS SUCH AS SYSTEMIC 4808 03:58:47,680 --> 03:58:51,440 VASCULATURE COMPARED TO SMALL 4809 03:58:51,440 --> 03:58:54,960 ENDOTHELIAL CELLS WHERE WE HAVE 4810 03:58:54,960 --> 03:58:58,560 SHOWN MECHANISTICALLY THEY'RE 4811 03:58:58,560 --> 03:59:00,360 REFLECT DECREASED PROLIFERATION. 4812 03:59:00,360 --> 03:59:01,680 IN THE INTEREST OF TIME I'LL 4813 03:59:01,680 --> 03:59:05,800 SKIP TO THE SCHEMATIC TO POINT 4814 03:59:05,800 --> 03:59:09,040 TO YOU THE SAME MICRO-RNA HAS A 4815 03:59:09,040 --> 03:59:11,240 DIFFERENT FUNCTION IN 4816 03:59:11,240 --> 03:59:14,200 ENDOTHELIAL CELLS COMPARED TO 4817 03:59:14,200 --> 03:59:19,040 SMALL ENDOTHELIAL CELLS AND MAY 4818 03:59:19,040 --> 03:59:23,120 BE RELEVANT TO PULMONARY 4819 03:59:23,120 --> 03:59:25,600 HYPERTENSION IN COPD TO SMALL 4820 03:59:25,600 --> 03:59:29,600 AND LARGE VESSELS DIFFERENTIALLY 4821 03:59:29,600 --> 03:59:32,560 AND ADAM 9 IS A TARGET SHOWING 4822 03:59:32,560 --> 03:59:35,680 INCREASE IN SMOKE AND COPD LUNGS 4823 03:59:35,680 --> 03:59:39,600 AND FOUND IT INCREASING THE 4824 03:59:39,600 --> 03:59:41,480 VESSELS OF THE COPD AND COPD PH 4825 03:59:41,480 --> 03:59:45,760 TISSUES AVAILABLE. 4826 03:59:45,760 --> 03:59:47,720 I THINK THE BETTER DISEASE 4827 03:59:47,720 --> 03:59:49,880 MODELS THAT MAKE US MORE NIMBLE 4828 03:59:49,880 --> 03:59:55,680 TO TEST THE HYPOTHESIS COMING 4829 03:59:55,680 --> 03:59:59,040 FROM OUR COLLEAGUES WITH HE 4830 03:59:59,040 --> 04:00:00,960 CLINICAL RESEARCH AND NEED 4831 04:00:00,960 --> 04:00:03,320 BETTER COHORTS AND DO THE 4832 04:00:03,320 --> 04:00:05,520 COMPLEXITY AND I THINK WE'RE 4833 04:00:05,520 --> 04:00:08,200 RIPE FOR THAT AND THE CLUE FOR 4834 04:00:08,200 --> 04:00:11,800 WHO AFTER SMOKING OR OTHER 4835 04:00:11,800 --> 04:00:22,280 EXPOSURES DEVELOPS PULMONARY 4836 04:00:24,560 --> 04:00:29,160 HYPERTENSION OR CHRONIC 4837 04:00:29,160 --> 04:00:30,760 BRONCHITIS AND OTHER INFLUENCES 4838 04:00:30,760 --> 04:00:31,520 AND THANK YOU FOR THE 4839 04:00:31,520 --> 04:00:34,240 OPPORTUNITY AND FOR THE FUNDING 4840 04:00:34,240 --> 04:00:42,800 AGENCIES WHO SUPPORT OUR WORK. 4841 04:00:42,800 --> 04:00:43,200 INCLUDE NHLBI. 4842 04:00:43,200 --> 04:00:46,400 THANK YOU. 4843 04:00:46,400 --> 04:00:47,880 >> WE'RE DOING WELL ON TIME I'M 4844 04:00:47,880 --> 04:00:50,800 HOPEFUL WE'LL HAVE A GREAT HOUR 4845 04:00:50,800 --> 04:00:52,280 OF DISCUSSION. 4846 04:00:52,280 --> 04:00:54,320 NEXT IS PHIL HANSBRO FROM 4847 04:00:54,320 --> 04:00:56,240 UNIVERSITY OF SYDNEY. 4848 04:00:56,240 --> 04:00:57,240 I'M SURE IT'S EARLY IN THE 4849 04:00:57,240 --> 04:00:57,520 MORNING. 4850 04:00:57,520 --> 04:00:58,960 HE'LL TALK TO US ABOUT THE 4851 04:00:58,960 --> 04:01:09,160 MICROBIOME. 4852 04:01:14,520 --> 04:01:19,880 >> THANK YOU TO THE ORGANIZERS. 4853 04:01:19,880 --> 04:01:21,600 IT'S ABOUT 3:00 IN THE MORNING 4854 04:01:21,600 --> 04:01:24,960 AND HERE'S MY DISCLOSURES. 4855 04:01:24,960 --> 04:01:28,640 NOTHING RELEVANT TO TODAY. 4856 04:01:28,640 --> 04:01:33,520 I'LL TALK ABOUT MICROBIOME IN 4857 04:01:33,520 --> 04:01:39,600 COPD AND COMPONENTS SUCH AS LPS 4858 04:01:39,600 --> 04:01:43,640 AND COMPONENTS CAN IMPACT IMMUNE 4859 04:01:43,640 --> 04:01:45,200 CELLS AND DRIVE INFLAMMATION 4860 04:01:45,200 --> 04:01:49,400 WITH MODIFYING T CELLS AND MACRO 4861 04:01:49,400 --> 04:01:50,640 PHAGES AND INCREASING IMMUNE 4862 04:01:50,640 --> 04:01:54,160 DISEASE ALL OF WHICH CAN HAVE 4863 04:01:54,160 --> 04:01:57,520 BENEFICIAL EFFECTS AND CREATE 4864 04:01:57,520 --> 04:01:59,640 FATTY ACIDS THAT CAUSE IMMUNE 4865 04:01:59,640 --> 04:02:02,360 SUPPRESSION AND SUPPRESS THE 4866 04:02:02,360 --> 04:02:08,120 INFLAMMATORY RESPONSES OF 4867 04:02:08,120 --> 04:02:11,120 MACROPHAGES AND NEUTROPHILS AND 4868 04:02:11,120 --> 04:02:12,600 HAVE DELETERIOUS AFFECTS IN THE 4869 04:02:12,600 --> 04:02:15,880 LUNG BUT CAN BE DERIVED FROM THE 4870 04:02:15,880 --> 04:02:22,920 LUNG OR GUT. 4871 04:02:22,920 --> 04:02:24,680 SEQUENCE ADVANCES HAVE BEEN ABLE 4872 04:02:24,680 --> 04:02:29,800 TO HELP US AND THERE'S VARIOUS 4873 04:02:29,800 --> 04:02:33,440 WAYS TO ANALYZE THE MICROBIOME 4874 04:02:33,440 --> 04:02:34,600 TELLING US WHAT BACTERIA IS 4875 04:02:34,600 --> 04:02:39,480 THERE AN METAGENOMIC TO SKRNS 4876 04:02:39,480 --> 04:02:40,880 THE MICROBIAL DNA TO IDENTIFY 4877 04:02:40,880 --> 04:02:43,840 THE SPECIES AND FUNCTIONS OF DNA 4878 04:02:43,840 --> 04:02:45,840 IN A PARTICULAR SAMPLE. 4879 04:02:45,840 --> 04:02:50,720 THIS ENABLES TO US TO IDENTIFY 4880 04:02:50,720 --> 04:02:53,720 THE SPECIES THAT ARE PRESENT AND 4881 04:02:53,720 --> 04:02:55,560 ASSOCIATE WITH DISEASE FEATURES 4882 04:02:55,560 --> 04:02:56,680 AND ALSO HOW THEY MIGHT BE 4883 04:02:56,680 --> 04:02:58,720 DRIVING THE DISEASE FEATURES AND 4884 04:02:58,720 --> 04:03:01,800 HELPS US WORK OUT WHAT THE ROLES 4885 04:03:01,800 --> 04:03:04,200 OF THE BACTERIA ARE IN HEATH AND 4886 04:03:04,200 --> 04:03:05,640 DISEASE. 4887 04:03:05,640 --> 04:03:07,200 -- HEALTH AND TODAY. 4888 04:03:07,200 --> 04:03:09,880 ONE CHALLENGES IN THE MICROBIOME 4889 04:03:09,880 --> 04:03:12,480 SPACE IS WORKING OUT CAUSE AND 4890 04:03:12,480 --> 04:03:12,680 EFFECT. 4891 04:03:12,680 --> 04:03:17,240 THE VAST MAJORITY OF STUDIES ARE 4892 04:03:17,240 --> 04:03:20,000 ASSOCIATIONAL STUDIES IN HUMAN 4893 04:03:20,000 --> 04:03:20,240 SAMPLES. 4894 04:03:20,240 --> 04:03:24,320 THERE'S A PLETHORA AND FOR THE 4895 04:03:24,320 --> 04:03:26,200 FIELD TO DEFINE THE CAUSE AND 4896 04:03:26,200 --> 04:03:27,320 EFFECT IN MICROBIOME. 4897 04:03:27,320 --> 04:03:30,720 A GOOD WAY FORWARD IS TO 4898 04:03:30,720 --> 04:03:34,200 CHARACTERIZE THE MICROBIOME, USE 4899 04:03:34,200 --> 04:03:39,880 INTEGRATED OMIC TO WORK OUT M 4900 04:03:39,880 --> 04:03:44,960 METAGENOMICS TO DEFINE HOW THE 4901 04:03:44,960 --> 04:03:49,520 MICROBIOTA ARE IMPACTING THE 4902 04:03:49,520 --> 04:03:51,120 BIOLOGICAL PROCESSES AND USE 4903 04:03:51,120 --> 04:03:52,320 ANIMAL MODEL TO WORK OUT CAUSE 4904 04:03:52,320 --> 04:03:54,520 AND EFFECT AND TRANSLATE THE 4905 04:03:54,520 --> 04:03:55,320 FINDINGS TO HUMAN DISEASE IN 4906 04:03:55,320 --> 04:03:58,880 COPD. 4907 04:03:58,880 --> 04:04:01,560 THERE'S BEEN NUMEROUS STUDIES OF 4908 04:04:01,560 --> 04:04:03,760 THE LUNG MICROBIOME IN COPD. 4909 04:04:03,760 --> 04:04:07,080 THERE'S LOTS OF STUDIES AND 4910 04:04:07,080 --> 04:04:17,640 THERE'S AN INCREASE IN MICROBIAL 4911 04:04:21,040 --> 04:04:21,720 INFLUENCES. 4912 04:04:21,720 --> 04:04:26,120 AND WHAT STUDYS HAVE SHOWN 4913 04:04:26,120 --> 04:04:29,000 DIFFERENT METABOLITES AND AFFECT 4914 04:04:29,000 --> 04:04:31,920 ON CELLULAR PROCESSES THAT 4915 04:04:31,920 --> 04:04:40,880 IMPACT ON THE COPD PHENOTYPE. 4916 04:04:40,880 --> 04:04:45,480 AND THE MOST RECENT STUDIES 4917 04:04:45,480 --> 04:04:47,880 PROFILE THE MICROBIOME AND 4918 04:04:47,880 --> 04:04:49,080 METABOLITE CHANGES AND NEED TO 4919 04:04:49,080 --> 04:04:51,880 MOVE TO CAUSE AND EFFECT HERE. 4920 04:04:51,880 --> 04:04:54,280 IN THE GUT, THERE'S BEEN LESS 4921 04:04:54,280 --> 04:04:54,680 STUDIES. 4922 04:04:54,680 --> 04:04:55,600 ONLY A FEW. 4923 04:04:55,600 --> 04:04:57,240 THEY'VE IDENTIFIED DIFFERENCES 4924 04:04:57,240 --> 04:05:03,360 IN HEALTHY SMOKERS AS WELL AS IN 4925 04:05:03,360 --> 04:05:13,600 COPD AND START TO USE ANIMAL 4926 04:05:13,600 --> 04:05:18,840 MODELS ON THE MICROBIOME AND HOW 4927 04:05:18,840 --> 04:05:20,720 AFFECT ON COPD TO MODIFY THE 4928 04:05:20,720 --> 04:05:21,240 DISEASE COURSE. 4929 04:05:21,240 --> 04:05:26,680 YOU CAN MODIFY THE DIET TO 4930 04:05:26,680 --> 04:05:27,680 INCREASE SOME FACTORS LIKE 4931 04:05:27,680 --> 04:05:32,760 TRYPTOPHAN OR WHATEVER TO 4932 04:05:32,760 --> 04:05:35,320 IMPROVE COPD SYMPTOMS IN MICE WE 4933 04:05:35,320 --> 04:05:39,280 CAN REDUCE DELETERIOUS BACTERIA 4934 04:05:39,280 --> 04:05:42,760 AND HAVE BENEFICIAL AFFECTS ON 4935 04:05:42,760 --> 04:05:48,400 PATHOGENESIS AND USE FECAL 4936 04:05:48,400 --> 04:05:51,600 TRANSFERS AND HIGH FIBER DIET TO 4937 04:05:51,600 --> 04:05:53,640 REDUCE THE COPD FEATURES IN 4938 04:05:53,640 --> 04:05:53,840 MICE. 4939 04:05:53,840 --> 04:05:55,920 THERE'S WAYS TO MODIFY THE 4940 04:05:55,920 --> 04:05:56,280 MICROBIOME. 4941 04:05:56,280 --> 04:05:58,280 THIS IS THE CRUCIAL PATHWAY WE 4942 04:05:58,280 --> 04:06:00,080 CAN LOOK AT IN TERMS OF 4943 04:06:00,080 --> 04:06:00,840 MODIFYING THE MICROBIOME IN 4944 04:06:00,840 --> 04:06:07,720 COPD. 4945 04:06:07,720 --> 04:06:10,720 WE CAN INTERVENE TO HAVE AN 4946 04:06:10,720 --> 04:06:11,800 IMPACT ON THE DISEASE PROCESS. 4947 04:06:11,800 --> 04:06:16,240 WE CAN USE DIETS AND MODIFYING 4948 04:06:16,240 --> 04:06:20,400 THE DIET TO ALTER THE GOOD 4949 04:06:20,400 --> 04:06:22,000 MICROBIOTA AND CHANGE THE 4950 04:06:22,000 --> 04:06:25,920 MICROBIOTA AND METABOLITES THEY 4951 04:06:25,920 --> 04:06:26,920 PRODUCE TO AFFECT INFLAMMATION 4952 04:06:26,920 --> 04:06:33,280 AND IMMUNE RESPONSES AND MAY 4953 04:06:33,280 --> 04:06:35,480 IMPACT COPD. 4954 04:06:35,480 --> 04:06:40,120 ONCE WE KNOW THE MOLECULAR 4955 04:06:40,120 --> 04:06:43,320 MAKEUP WE CAN USE MOLECULARLY 4956 04:06:43,320 --> 04:06:44,360 TARGETED DIETS TO REVERSE THE 4957 04:06:44,360 --> 04:06:51,000 CHANGES IN THE GUT. 4958 04:06:51,000 --> 04:06:54,640 WE CAN ALSO USE MICROBIOME 4959 04:06:54,640 --> 04:06:57,080 INTERVENTIONS AND USE BENEFICIAL 4960 04:06:57,080 --> 04:06:59,200 BACTERIA TO REVERSE THE DISEASE 4961 04:06:59,200 --> 04:07:04,360 FEATURES AS WELL. 4962 04:07:04,360 --> 04:07:06,040 WE NEED TO USE MICROBIOLOGY AND 4963 04:07:06,040 --> 04:07:08,120 CAUSE AND EFFECT STUDIES TO WORK 4964 04:07:08,120 --> 04:07:10,040 OUT CAUSE AND EFFECT OF THE 4965 04:07:10,040 --> 04:07:11,560 BACTERIA AND HOW THEY'RE 4966 04:07:11,560 --> 04:07:12,000 INFLUENCING DISEASE. 4967 04:07:12,000 --> 04:07:14,320 JUST SOME EXAMPLES OF HOW WE 4968 04:07:14,320 --> 04:07:15,160 MIGHT DO THIS. 4969 04:07:15,160 --> 04:07:19,720 SO THIS IS UNWPUBLISHED DATA 4970 04:07:19,720 --> 04:07:22,120 TAKING COHORTS OF COPD PATIENTS 4971 04:07:22,120 --> 04:07:24,160 VERSUS HEALTHY CONTROLS AND HAVE 4972 04:07:24,160 --> 04:07:26,000 DONE AN ANALYSIS OF THEIR DIET. 4973 04:07:26,000 --> 04:07:30,520 WHAT WE CAN SEE IS COPD PATIENTS 4974 04:07:30,520 --> 04:07:32,080 HAVE A LOWER FIBER DENSITY IN 4975 04:07:32,080 --> 04:07:34,600 THEIR DIET COMPARED TO HEALTHY 4976 04:07:34,600 --> 04:07:38,200 PEOPLE AND IF WE STRATIFY COPD 4977 04:07:38,200 --> 04:07:39,680 PATIENTS ACCORDING TO HOW MUCH 4978 04:07:39,680 --> 04:07:42,240 FIBER THEY TAKE IN, THOSE THAT 4979 04:07:42,240 --> 04:07:44,040 TAKE ON MORE FIBER HAVE GOT A 4980 04:07:44,040 --> 04:07:47,840 BETTER LUNG FUNCTION. 4981 04:07:47,840 --> 04:07:50,320 THEN WE CAN PROFILE THE GUT AND 4982 04:07:50,320 --> 04:07:51,240 LUNG MICROBIOME. 4983 04:07:51,240 --> 04:07:59,880 THIS IS PUBLISHED WORK WE CAN 4984 04:07:59,880 --> 04:08:08,360 PERFORM METAGENE I'MICS -- 4985 04:08:08,360 --> 04:08:10,560 METAGENOMICS AND SEE DIFFERENCES 4986 04:08:10,560 --> 04:08:11,680 AND CORRELATE THE SPECIFIC 4987 04:08:11,680 --> 04:08:16,520 BACTERIA WITH THE SPECIFIC 4988 04:08:16,520 --> 04:08:19,120 DISEASE FEATURES AS WELL AS AND 4989 04:08:19,120 --> 04:08:22,560 PERFORM METABOLOMICS ON THE GUT 4990 04:08:22,560 --> 04:08:24,000 SAMPLES AND CORRELATE THE 4991 04:08:24,000 --> 04:08:26,160 DIFFERENT BACTERIA, THE GENES 4992 04:08:26,160 --> 04:08:28,680 THEY ARE PRODUCING WITH THE 4993 04:08:28,680 --> 04:08:31,000 METABOLITES THEY PRODUCE WITH 4994 04:08:31,000 --> 04:08:34,200 DISEASE FEATURES IN PEOPLE. 4995 04:08:34,200 --> 04:08:37,480 WE CAN GENERATE THE NETWORK 4996 04:08:37,480 --> 04:08:40,600 PROCESSES AND LINK THESE 4997 04:08:40,600 --> 04:08:41,880 MICROBIOMES THE METABOLITES WITH 4998 04:08:41,880 --> 04:08:44,960 DISEASE FEATURES. 4999 04:08:44,960 --> 04:08:46,280 THAT'S REALLY CLOSED TO GETTING 5000 04:08:46,280 --> 04:08:48,480 THE BEST WE CAN DO TO A CERTAIN 5001 04:08:48,480 --> 04:08:52,280 EXTENT IN HUMAN SAMPLES. 5002 04:08:52,280 --> 04:08:54,920 WE CAN THEN USE ANIMAL MODELS TO 5003 04:08:54,920 --> 04:08:57,880 TRANSLATE THESE FINDINGS INTO 5004 04:08:57,880 --> 04:08:58,560 CAUSE AND EFFECT. 5005 04:08:58,560 --> 04:09:00,480 THE BENEFIT OF ANIMAL MODELS IS 5006 04:09:00,480 --> 04:09:05,960 THAT WE CAN COLLECT ALL THE 5007 04:09:05,960 --> 04:09:14,200 SAMPLES AND COPD THAT HAVE BEEN 5008 04:09:14,200 --> 04:09:16,160 PRODUCED AND WHOLE BODY 5009 04:09:16,160 --> 04:09:18,400 EXPOSURES AND EXACERBATIONS AND 5010 04:09:18,400 --> 04:09:26,280 USE GERM-FREE MICE WHICH IS 5011 04:09:26,280 --> 04:09:28,000 TOOLS AND DEFINE CAUSE AND 5012 04:09:28,000 --> 04:09:37,840 EFFECT AND CAN TEST BACTERIAL 5013 04:09:37,840 --> 04:09:40,880 TRANSFERS AS POTENTIAL 5014 04:09:40,880 --> 04:09:42,320 INTERFERENCE IN COPD AND THE 5015 04:09:42,320 --> 04:09:43,280 BACTERIA IS DIFFERENT BETWEEN 5016 04:09:43,280 --> 04:09:45,400 MICE AND HUMANS. 5017 04:09:45,400 --> 04:09:50,160 WE CAN SEE HERE DIFFERENTSES IN 5018 04:09:50,160 --> 04:09:51,680 MAJOR FAMILIES AND MAJOR 5019 04:09:51,680 --> 04:09:54,960 GENERATE BETWEEN MOUSE AND 5020 04:09:54,960 --> 04:09:57,600 HUMANS. 5021 04:09:57,600 --> 04:10:01,360 OVERALL THE FUNCTION AL BACTERIL 5022 04:10:01,360 --> 04:10:04,440 POPULATIONS ARE SIMILAR BETWEEN 5023 04:10:04,440 --> 04:10:06,560 MOUSE AND HUMANS AND PRODUCE 5024 04:10:06,560 --> 04:10:09,000 SIMILAR LEVELS OF METABOLITES. 5025 04:10:09,000 --> 04:10:13,800 IF WE LOOK AT THE FUNCTIONAL 5026 04:10:13,800 --> 04:10:15,080 COHORTS OF BACTERIA ARE SIMILAR 5027 04:10:15,080 --> 04:10:18,440 BETWEEN HUMANS AND MICE AND 5028 04:10:18,440 --> 04:10:21,880 GIVES CONFIDENCE TO GIVE ANIMAL 5029 04:10:21,880 --> 04:10:24,280 MODELS TO STUDY COPD AND LOOK AT 5030 04:10:24,280 --> 04:10:26,680 THE CHANGES IN THE GUT 5031 04:10:26,680 --> 04:10:32,200 MICROBIOMES IN COPD MICE 5032 04:10:32,200 --> 04:10:35,840 COMPARED TO HUMANS ALSO TAKE 5033 04:10:35,840 --> 04:10:39,200 BACTERIA AND METABOLITES AND POP 5034 04:10:39,200 --> 04:10:41,240 THEM IN ANIMAL MODELS TO LOOK AT 5035 04:10:41,240 --> 04:10:43,280 THE IMPACT OF DISEASE FEATURES. 5036 04:10:43,280 --> 04:10:45,480 WE CAN GO BOTH WAYS. 5037 04:10:45,480 --> 04:10:51,880 THESE ARE ANIMAL MODELS 5038 04:10:51,880 --> 04:10:55,440 CIGARETTE SMOKE EXPOSURE AND 5039 04:10:55,440 --> 04:10:58,120 INFLAMMATION WITH CELLS AND 5040 04:10:58,120 --> 04:11:07,400 CYTOKINES AND KENOKINES AND 5041 04:11:07,400 --> 04:11:08,880 EMPHYSEMA AND LOOK AT IMPAIRMENT 5042 04:11:08,880 --> 04:11:14,160 OF GAS EXCHANGE AS WE SEE IN 5043 04:11:14,160 --> 04:11:18,560 PEOPLE EXACERBATE THE INFECTION 5044 04:11:18,560 --> 04:11:20,480 WITH STREP PNEUMONIA OR 5045 04:11:20,480 --> 04:11:20,760 INFLUENZA. 5046 04:11:20,760 --> 04:11:23,880 WE CAN LOOK AT THE GUT 5047 04:11:23,880 --> 04:11:26,920 MICROBIOME IN THE COPD MODEL AND 5048 04:11:26,920 --> 04:11:27,680 LINK WE FIND TO SPECIFIC DISEASE 5049 04:11:27,680 --> 04:11:36,920 FEATURES. 5050 04:11:36,920 --> 04:11:42,200 WE FIND THIS LINK TO 5051 04:11:42,200 --> 04:11:46,040 INFLAMMATION AND EMPHYSEMA AND 5052 04:11:46,040 --> 04:11:48,960 AKKERMANSIA IN RESPONSES IN TLR 5053 04:11:48,960 --> 04:11:59,640 AND LACHONSPIRACEA IMPROVES LUNG 5054 04:11:59,640 --> 04:12:01,240 FUNCTION AND WE SEE THE CHANGES 5055 04:12:01,240 --> 04:12:02,880 THAT OCCURRED IN THE MODELS WE 5056 04:12:02,880 --> 04:12:07,880 CAN THEN USE INTERVENTIONS WITH 5057 04:12:07,880 --> 04:12:11,600 DIETS OR MICROBIOMES. 5058 04:12:11,600 --> 04:12:14,200 THIS IS HIGH FIBER DIETS AS A 5059 04:12:14,200 --> 04:12:15,480 POTENTIAL THERAPY. 5060 04:12:15,480 --> 04:12:19,120 IF WE LOOK AT SMOKING MICE WE 5061 04:12:19,120 --> 04:12:23,000 SEE REDUCTION IN THE SHORT CHAIN 5062 04:12:23,000 --> 04:12:27,000 FATTY ACIDS BUT WITH A HIGH 5063 04:12:27,000 --> 04:12:28,640 FIBER ACID AS THEY COME BACK TO 5064 04:12:28,640 --> 04:12:28,920 BASELINE. 5065 04:12:28,920 --> 04:12:30,480 AND THEN WE CAN HAVE A LOOK AT 5066 04:12:30,480 --> 04:12:35,040 WHAT HAPPENS TO THE DISEASE 5067 04:12:35,040 --> 04:12:38,240 FEATURES AND THE HIGH FIBER DIET 5068 04:12:38,240 --> 04:12:43,200 OR SHORT CHAIN FATTY ACIDS 5069 04:12:43,200 --> 04:12:45,280 SUPPRESS COLLAGEN AND EMPHASIZE 5070 04:12:45,280 --> 04:12:47,880 IN THE MOUSE MODELS AND IMPROVE 5071 04:12:47,880 --> 04:12:55,880 LUNG FUNCTION. 5072 04:12:55,880 --> 04:12:58,280 THIS IS WHERE WE USED MICROBIOME 5073 04:12:58,280 --> 04:13:04,080 TRA 5074 04:13:04,080 --> 04:13:04,560 TRA 5075 04:13:04,560 --> 04:13:05,320 TRANSFERS AS A POTENTIAL 5076 04:13:05,320 --> 04:13:07,000 TREATMENT AND PERFORMED 5077 04:13:07,000 --> 04:13:09,200 TRANSFERRED TO MODIFY THE GUT 5078 04:13:09,200 --> 04:13:11,880 MICROBIOMES IN THE MICE AND CAN 5079 04:13:11,880 --> 04:13:15,040 SEE REDUCED AIRWAY INFLAMMATION 5080 04:13:15,040 --> 04:13:18,520 MACRO PHAGES, COLLAGEN AND LUNG 5081 04:13:18,520 --> 04:13:20,120 EMPHYSEMA AND CHANGES AS WELL 5082 04:13:20,120 --> 04:13:23,520 AND PERFORM THE MICROBIOME 5083 04:13:23,520 --> 04:13:25,160 ANALYSIS AND SHOW THE DIFFERENCE 5084 04:13:25,160 --> 04:13:27,880 BETWEEN COPD AND HEALTH AND 5085 04:13:27,880 --> 04:13:30,040 NON-SMOKING AND IF WE DO THE 5086 04:13:30,040 --> 04:13:32,200 MICROBIOME TRANSFERS THIS 5087 04:13:32,200 --> 04:13:41,000 NORMALIZES THE MICROBIOMES AND 5088 04:13:41,000 --> 04:13:42,720 IDENTIFY THE SPECIES ALTERED IN 5089 04:13:42,720 --> 04:13:44,800 COPD AND HOW TO REVERSE THEM 5090 04:13:44,800 --> 04:13:52,640 USING THE MICROBIOME TRANSFERS. 5091 04:13:52,640 --> 04:13:55,360 NOW WE'VE ESTABLISHED A PIPELINE 5092 04:13:55,360 --> 04:14:00,560 AND THIS SAY FIVE-YEAR GRANT 5093 04:14:00,560 --> 04:14:06,120 WE'RE DOING WHERE WE CAN DEFINE 5094 04:14:06,120 --> 04:14:08,240 THE CHANGES IN IMMUNITY AND TEST 5095 04:14:08,240 --> 04:14:10,680 THE DIETARY INTERVENTIONS IN 5096 04:14:10,680 --> 04:14:12,840 ANIMALS AND PUT THEM STRAIGHT 5097 04:14:12,840 --> 04:14:14,400 INTO AN ADAPTIVE CLINICAL TRIAL 5098 04:14:14,400 --> 04:14:16,640 IN COPD PATIENTS. 5099 04:14:16,640 --> 04:14:17,960 I THINK THIS IS A GOOD 5100 04:14:17,960 --> 04:14:23,280 OPPORTUNITY FOR US ALL TO WORK 5101 04:14:23,280 --> 04:14:27,640 TOGETHER TO HARNESS THE CHANGES 5102 04:14:27,640 --> 04:14:30,120 IN MICROBIOME AND ANALYZE THEM 5103 04:14:30,120 --> 04:14:32,600 IN DISEASE AND IDENTIFIED 5104 04:14:32,600 --> 04:14:34,480 DIFFERENCES IN DISEASE AND USE 5105 04:14:34,480 --> 04:14:38,520 ANIMAL MODELS TO DEFINE HOW HE 5106 04:14:38,520 --> 04:14:40,040 MICROBIOME CHANGES OCCUR IN THE 5107 04:14:40,040 --> 04:14:43,160 DEVELOPMENT AND PROGRESSION AND 5108 04:14:43,160 --> 04:14:44,840 EXACERBATIONS OF COPD AND 5109 04:14:44,840 --> 04:14:46,440 IDENTIFY THE SPECIFIC FACTORS 5110 04:14:46,440 --> 04:14:50,600 AND PROCESSES THAT REVOLVED AND 5111 04:14:50,600 --> 04:14:53,480 COMBINE WITH MULTIOMICS AND DO 5112 04:14:53,480 --> 04:14:56,200 INTERVENTION STUDIES TO DEFINE 5113 04:14:56,200 --> 04:14:58,920 CAUSE AND AFFECT AND OFFICIALLY 5114 04:14:58,920 --> 04:15:00,600 IDENTIFIED THERAPIES AND 5115 04:15:00,600 --> 04:15:02,440 TRANSLATE THESE USING HUMAN 5116 04:15:02,440 --> 04:15:04,440 CELLS AND TISSUE ANALYSIS LIKE 5117 04:15:04,440 --> 04:15:06,520 WE ARE HEARING ABOUT IN THE 5118 04:15:06,520 --> 04:15:11,040 WORKSHOP AND THEN TAKE THESE IN 5119 04:15:11,040 --> 04:15:13,000 TO CLINICAL TRIALS AS POTENTIAL 5120 04:15:13,000 --> 04:15:13,280 TREATMENTS. 5121 04:15:13,280 --> 04:15:17,120 I WANT TO HIGHLIGHT SOME OF THE 5122 04:15:17,120 --> 04:15:19,160 IMPORTANT RECENT PUBLICATIONS 5123 04:15:19,160 --> 04:15:22,760 FOR MANY PEOPLE IN THE 5124 04:15:22,760 --> 04:15:23,960 CONSORTIUM AND ENHANCE WHAT 5125 04:15:23,960 --> 04:15:24,680 WE'RE TALKING ABOUT IN THE 5126 04:15:24,680 --> 04:15:28,560 WORKSHOPS. 5127 04:15:28,560 --> 04:15:29,000 I'LL LEAVE IT THERE. 5128 04:15:29,000 --> 04:15:30,240 THANKS. 5129 04:15:30,240 --> 04:15:35,960 >> THANK YOU, PHIL FOR A GREAT 5130 04:15:35,960 --> 04:15:44,280 TALK AND GET SOME COFFEE. 5131 04:15:44,280 --> 04:15:45,520 THANK YOU TO THE SPEAKERS FOR 5132 04:15:45,520 --> 04:15:48,040 CONSIDERATION OF OUR SCHEDULE. 5133 04:15:48,040 --> 04:15:51,200 OUR LAST SPEAKER AND I ALSO 5134 04:15:51,200 --> 04:15:52,640 APPRECIATE ALL THE DISCUSSIONS 5135 04:15:52,640 --> 04:15:54,440 GOING ON IN THE CHAT AS WELL. 5136 04:15:54,440 --> 04:15:56,800 THERE'S GREAT QUESTIONS BEING 5137 04:15:56,800 --> 04:16:01,000 ASKED SHOULD LEAD IT A LIVELY 5138 04:16:01,000 --> 04:16:01,400 OPEN DISCUSSION. 5139 04:16:01,400 --> 04:16:06,480 THE LAST SPEAKER IS AUGUSTINE 5140 04:16:06,480 --> 04:16:08,720 CHOI AT FROM CORNELL AND TALK 5141 04:16:08,720 --> 04:16:11,040 ABOUT SENESCENCE AND CELL DEATH 5142 04:16:11,040 --> 04:16:12,360 AND MITOCHONDRIAL DYSFUNCTION. 5143 04:16:12,360 --> 04:16:13,760 GREAT TO SEE YOU AND THE FLOOR 5144 04:16:13,760 --> 04:16:14,320 IS YOURS. 5145 04:16:14,320 --> 04:16:14,920 >> THANK YOU VERY MUCH. 5146 04:16:14,920 --> 04:16:16,800 CAN YOU HEAR ME OKAY? 5147 04:16:16,800 --> 04:16:20,200 >> ABSOLUTELY. 5148 04:16:20,200 --> 04:16:23,240 >> THANK YOU AND ED WIN FOR THE 5149 04:16:23,240 --> 04:16:25,840 INVITATION AND ORGANIZING 5150 04:16:25,840 --> 04:16:27,480 COMMITTEE AND THE LUNG DIVISION 5151 04:16:27,480 --> 04:16:29,000 AT NHLBI AND I THANK ALL THE 5152 04:16:29,000 --> 04:16:34,640 SPEAKERS AND ATTENDEES FOR THEIR 5153 04:16:34,640 --> 04:16:41,640 COMMITMENT TO COMBAT COPD. 5154 04:16:41,640 --> 04:16:47,160 SO BEFORE I GET INTO ROLE OF 5155 04:16:47,160 --> 04:16:49,000 COPD, LET ME ANIMATE THE REST OF 5156 04:16:49,000 --> 04:16:51,360 THE ANIMATION HERE. 5157 04:16:51,360 --> 04:16:53,400 IN TERMS OF PATHOGENESIS OF COPD 5158 04:16:53,400 --> 04:16:58,640 IN THE LAST DECADES, SO THIS IS 5159 04:16:58,640 --> 04:17:02,080 NOT INCLUSIVE LIST BUT I THINK 5160 04:17:02,080 --> 04:17:05,160 ALL OF US AGREE INFLAMMATION 5161 04:17:05,160 --> 04:17:12,520 CELL DEATH AND ANTIOXIDANT AND 5162 04:17:12,520 --> 04:17:14,160 PROTEASE AND ARE PROCESSES 5163 04:17:14,160 --> 04:17:16,400 REPORTED TO PLAY AN IMPORTANT 5164 04:17:16,400 --> 04:17:18,160 ROLE IN PATHOGENESIS OF COPD. 5165 04:17:18,160 --> 04:17:20,480 I WANT TO SHARE A COUPLE SLIDES 5166 04:17:20,480 --> 04:17:26,360 HOW WE STUMBLED INTO THE ROLE OF 5167 04:17:26,360 --> 04:17:26,680 MITOCHONDRIA. 5168 04:17:26,680 --> 04:17:32,800 WE WERE NOT A MITOCHONDRIAL LAB. 5169 04:17:32,800 --> 04:17:36,480 WE WITNESSED AUTOPHAGY AND IN A 5170 04:17:36,480 --> 04:17:40,480 SERIES OF REPORTS REPORTED SMOKE 5171 04:17:40,480 --> 04:17:43,120 INDUCED AN OXIDATIVE STRESS 5172 04:17:43,120 --> 04:17:46,160 CAUSING AN IMBALANCE OF ROS 5173 04:17:46,160 --> 04:17:48,040 ACTIVATING H STACK MOLECULES AND 5174 04:17:48,040 --> 04:17:54,960 TURNED OUT THE H STACK IS 5175 04:17:54,960 --> 04:17:57,520 REGULATED AND ACTIVATES 5176 04:17:57,520 --> 04:18:01,400 AUTOPHAGY PROCESSES THE LCB 5177 04:18:01,400 --> 04:18:05,960 PROTEIN AND INSTEAD OF THE USUAL 5178 04:18:05,960 --> 04:18:09,280 PROSURVIVAL EFFECT OF AUTOPHAGY 5179 04:18:09,280 --> 04:18:11,880 TOO MUCH AUTOPHAGY WAS 5180 04:18:11,880 --> 04:18:15,520 DELETERIOUS IN SMOKE INDUCED 5181 04:18:15,520 --> 04:18:15,800 EMPHYSEMA. 5182 04:18:15,800 --> 04:18:20,240 IT'S NOT A SURPRISE AND TOO MUCH 5183 04:18:20,240 --> 04:18:21,240 AUTOPHAGY CAN BE A BAD PLAYER 5184 04:18:21,240 --> 04:18:21,840 FOR YOU. 5185 04:18:21,840 --> 04:18:23,160 THIS IS HOW WE GOT STARTED IN 5186 04:18:23,160 --> 04:18:27,680 THE ROLE OF AUTOPHAGY AND 5187 04:18:27,680 --> 04:18:27,960 EMPHYSEMA. 5188 04:18:27,960 --> 04:18:30,360 AND BEYOND THE STUDIES WE WENT 5189 04:18:30,360 --> 04:18:33,000 INTO STUDYING SELECTIVE 5190 04:18:33,000 --> 04:18:35,560 AUTOPHAGY AND THIS IS STUDIES 5191 04:18:35,560 --> 04:18:37,320 DONE BY A GRADUATE STUDENT AT 5192 04:18:37,320 --> 04:18:41,040 THE TIME AT PITTSBURGH AND 5193 04:18:41,040 --> 04:18:44,040 BRIGHAM AND SUSAN CLUNIN WHO 5194 04:18:44,040 --> 04:18:46,040 JOINTLY DID A STUDY SHOWING THE 5195 04:18:46,040 --> 04:18:51,720 ROLE OF SELECTIVE AUTOPHAGY HOW 5196 04:18:51,720 --> 04:18:55,520 CIGARETTE SMOKE DYSFUNCTION IS 5197 04:18:55,520 --> 04:19:01,320 REGULATED BY CILIA PHAGY AND 5198 04:19:01,320 --> 04:19:07,080 SELECTIVE AUTOPHAGY WE GOT 5199 04:19:07,080 --> 04:19:17,640 INTERESTED IN MITOPHAGY IN THE 5200 04:19:20,760 --> 04:19:22,840 EXPERIMENTAL MODEL OF EMPHYSEMA 5201 04:19:22,840 --> 04:19:31,600 AND LINKED THE PROCESS TO A MOTE 5202 04:19:31,600 --> 04:19:42,120 OF NECROP TOSIS AND THEY WERE 5203 04:19:45,040 --> 04:19:48,120 LOOKING AT MODELS OF SEPSIS. 5204 04:19:48,120 --> 04:19:56,040 AND STUMBLED INTO AN INTERESTING 5205 04:19:56,040 --> 04:20:01,800 FINDING WITH MITOCHONDRIAL 5206 04:20:01,800 --> 04:20:04,360 HOMEOSTASIS AND DEFICIENT MICE 5207 04:20:04,360 --> 04:20:07,200 IN MACROPHAGES. 5208 04:20:07,200 --> 04:20:11,720 THEY DERIVED FROM THE LC 5209 04:20:16,680 --> 04:20:18,680 B KNOCKOUT MICE AND THERE WERE 5210 04:20:18,680 --> 04:20:20,000 ENLARGED MITOCHONDRIA. 5211 04:20:20,000 --> 04:20:23,800 ONE OF THE EFFECTS OF 5212 04:20:23,800 --> 04:20:26,080 MITOCHONDRIAL DYSFUNCTION 5213 04:20:26,080 --> 04:20:26,440 MORPHOLOGICALLY. 5214 04:20:26,440 --> 04:20:29,960 WITH THAT THERE WAS A PAPER 5215 04:20:29,960 --> 04:20:32,320 LINKING THE IMMUNE RESPONSES 5216 04:20:32,320 --> 04:20:35,360 AUTOPHAGY BY INHIBITING 5217 04:20:35,360 --> 04:20:38,400 MITOCHONDRIAL DNA RELEASE 5218 04:20:38,400 --> 04:20:40,880 MEDIATED BY THE INFLAMMASOME. 5219 04:20:40,880 --> 04:20:44,400 SO THIS IS ABOUT 10 YEARS AGO 5220 04:20:44,400 --> 04:20:48,160 AND HOW WE GOT INTERESTED IN 5221 04:20:48,160 --> 04:20:49,640 MITOCHONDRIA. 5222 04:20:49,640 --> 04:20:55,880 ICONIC AND PIONEER IN THIS FIELD 5223 04:20:55,880 --> 04:20:59,920 DR. SHARP WHO TRAGICALLY PASSED 5224 04:20:59,920 --> 04:21:04,200 AWAY FOUND MITOCHONDRIA WAS 5225 04:21:04,200 --> 04:21:14,720 IMPORTANT IN THE INFLAMMASOME. 5226 04:21:36,320 --> 04:21:40,280 IT'S A SECOND MESSENGER 5227 04:21:40,280 --> 04:21:45,600 ORGANELLE AND WITH SECOND 5228 04:21:45,600 --> 04:21:50,200 IMPORTANT MESSENGERS AND MORE TO 5229 04:21:50,200 --> 04:21:53,240 COME IN THE FUTURE. 5230 04:21:53,240 --> 04:21:57,440 AROUND THAT TIME WE WERE JOINED 5231 04:21:57,440 --> 04:21:59,880 AS A POST-DOCTORAL FELLOW AND 5232 04:21:59,880 --> 04:22:02,120 THERE'S A PROFESSOR AT TRINITY 5233 04:22:02,120 --> 04:22:05,040 COLLEGE IN DUBLIN WHO WAS IN OUR 5234 04:22:05,040 --> 04:22:08,120 PROGRAM PROJECT WITH THE BOSTON 5235 04:22:08,120 --> 04:22:10,200 GROUP WITH ED SILVERMAN AND 5236 04:22:10,200 --> 04:22:14,880 OTHERS AND OUR JOB WAS TO 5237 04:22:14,880 --> 04:22:16,640 DELINEATE THE MECHANISM OF ONE 5238 04:22:16,640 --> 04:22:23,000 OF THE GWAS -- CAN YOU ANIMATE 5239 04:22:23,000 --> 04:22:23,640 IT, PLEASE. 5240 04:22:23,640 --> 04:22:30,920 THE TOP GWAS AND OUR JOB 5241 04:22:30,920 --> 04:22:33,520 DELINEATE THE MECHANISM HOW IT 5242 04:22:33,520 --> 04:22:36,960 COULD MEDIATE PATHOGENESIS OF 5243 04:22:36,960 --> 04:22:38,480 SMOKING AND EMPHYSEMA. 5244 04:22:38,480 --> 04:22:42,320 AS A SUMMARY USING IN VITRO 5245 04:22:42,320 --> 04:22:43,920 MODELS AND TARGETED MICE AND 5246 04:22:43,920 --> 04:22:46,120 SOME HUMAN SAMPLES, SUSAN WAS 5247 04:22:46,120 --> 04:22:47,840 ABLE TO SHOW THIS INDEED WAS 5248 04:22:47,840 --> 04:22:53,240 VERY IMPORTANT IN THE 5249 04:22:53,240 --> 04:22:56,360 PATHOGENESIS OF EMPHYSEMA AND 5250 04:22:56,360 --> 04:22:58,040 IRON METABOLISM INCLUDING 5251 04:22:58,040 --> 04:22:59,600 MITOCHONDRIAL RN WAS IMPORTANT 5252 04:22:59,600 --> 04:23:06,560 IN THE PATH AGAIN -- 5253 04:23:06,560 --> 04:23:07,600 PATHOGENESIS. 5254 04:23:07,600 --> 04:23:12,080 MITOCHONDRIA CAN RELEASE SIGNALS 5255 04:23:12,080 --> 04:23:13,880 FROM DAMAGED MITOCHONDRIA AND 5256 04:23:13,880 --> 04:23:18,960 WE'LL FOCUS ON MITOCHONDRIAL DNA 5257 04:23:18,960 --> 04:23:29,200 FOR THE TALK. 5258 04:23:38,440 --> 04:23:47,840 AND WE THANK THE COHORT AND 5259 04:23:47,840 --> 04:23:50,440 FERNANDO FOR HIS SAMPLES OF 5260 04:23:50,440 --> 04:23:53,040 PLASMA AND LOOKING AT PROOF OF 5261 04:23:53,040 --> 04:23:55,720 CONCEPT, CAN WE DETECT CELL-FREE 5262 04:23:55,720 --> 04:23:59,760 MITOCHONDRIAL DNA IN THE PLASMA 5263 04:23:59,760 --> 04:24:04,280 OF PATIENTS WHO ARE SMOKERS AND 5264 04:24:04,280 --> 04:24:05,200 CLASSIFY THEM TO DIFFERENT 5265 04:24:05,200 --> 04:24:06,280 SEVERITY OF COPD. 5266 04:24:06,280 --> 04:24:12,240 WE WERE INTRIGUED BY THE 5267 04:24:12,240 --> 04:24:13,840 OBSERVATION HERE YOU SEE THE 5268 04:24:13,840 --> 04:24:16,000 COPY NUMBER AS YOU PROGRESS FROM 5269 04:24:16,000 --> 04:24:24,120 MILD TO MODERATE TO SEVERE COPD. 5270 04:24:24,120 --> 04:24:24,600 WE W 5271 04:24:24,600 --> 04:24:28,080 WE WERE A BIT DISAPPOINT WHEN WE 5272 04:24:28,080 --> 04:24:29,240 DOESN'T SEE ASSOCIATION BETWEEN 5273 04:24:29,240 --> 04:24:31,280 THE PLASMA COPD AND OUTCOME AND 5274 04:24:31,280 --> 04:24:35,880 WE LOOKED AT A VARIETY OF 5275 04:24:35,880 --> 04:24:36,520 EXTENSIVE LIST OF CLINICAL COPD 5276 04:24:36,520 --> 04:24:40,360 OUTCOMES. 5277 04:24:40,360 --> 04:24:41,080 INTERESTINGLY, THEY WERE 5278 04:24:41,080 --> 04:24:43,480 INTERESTED IN THE ROLE OF KIDNEY 5279 04:24:43,480 --> 04:24:45,040 DYSFUNCTION AND MITOCHONDRIAL 5280 04:24:45,040 --> 04:24:47,880 DYSFUNCTION AND KIDNEYS IN 5281 04:24:47,880 --> 04:24:49,840 SMOKING EMPHYSEMA AND WE WERE 5282 04:24:49,840 --> 04:24:52,920 ABLE TO OBTAIN AGAIN FROM 5283 04:24:52,920 --> 04:24:58,880 SPIROMICS COHORT THE SAME PAL -- 5284 04:24:58,880 --> 04:25:02,960 SAMPLES FROM THE DATA AND THE 5285 04:25:02,960 --> 04:25:04,560 MITOCHONDRIAL DNA WITH EXERCISE 5286 04:25:04,560 --> 04:25:06,760 TOLERANCE AND SYMPTOM BURDEN OF 5287 04:25:06,760 --> 04:25:08,320 SMOKERS WITHOUT AIRWAY 5288 04:25:08,320 --> 04:25:13,000 OBSTRUCTION IN THIS STUDY. 5289 04:25:13,000 --> 04:25:20,440 SO IN PURSUING THIS WE FOCUSSED 5290 04:25:20,440 --> 04:25:25,680 ON THE MITOCHONDRIAL DYNAMICS 5291 04:25:25,680 --> 04:25:27,640 AND PLAYING A ROLE IN 5292 04:25:27,640 --> 04:25:29,240 PATHOGENESIS OF COPD. 5293 04:25:29,240 --> 04:25:32,520 WE'LL ALLOW DETAILS AND 5294 04:25:32,520 --> 04:25:35,200 MITOCHONDRIAL HOMEOSTASIS 5295 04:25:35,200 --> 04:25:36,960 DEPENDENT ON FUSION, VISION OR 5296 04:25:36,960 --> 04:25:37,880 BIO GENESIS. 5297 04:25:37,880 --> 04:25:41,280 WE'LL FOCUS ON THE TALK THE ROLE 5298 04:25:41,280 --> 04:25:47,120 OF DIFFUSION AND THE OUTER 5299 04:25:47,120 --> 04:25:52,600 MEMBRANE FUSION MITOFUSION 1 AND 5300 04:25:52,600 --> 04:25:56,640 2 AND LOOKED AT THE MICE FROM 5301 04:25:56,640 --> 04:25:59,360 MITOFUSIN 1 AND 2 AND DOUBLE 5302 04:25:59,360 --> 04:26:05,520 KNOCKOUTS AND HAVE DONE 5303 04:26:05,520 --> 04:26:07,280 EXPERIMENTS IN THE PULMONARY 5304 04:26:07,280 --> 04:26:09,440 FIBROSIS MODEL AND COPD AND WE 5305 04:26:09,440 --> 04:26:12,960 REPOR 5306 04:26:12,960 --> 04:26:21,440 REPORTED THAT IT MEDIATE THE 5307 04:26:21,440 --> 04:26:24,440 LUNG FIBROSIS IN A MODEL AND 5308 04:26:24,440 --> 04:26:29,120 THERE'S ANOTHER REPORT HOW 5309 04:26:29,120 --> 04:26:32,600 CRITICAL MITO FUSIN 2 SUPPRESSES 5310 04:26:32,600 --> 04:26:35,280 ENDOTHELIAL CELL VIA MODULATION 5311 04:26:35,280 --> 04:26:40,600 OF THE BETA 10 SIGNAL. 5312 04:26:40,600 --> 04:26:42,400 WITH STARTED TO DO STUDIES IN 5313 04:26:42,400 --> 04:26:46,520 THE MODEL OF SMOKE-INDUCED 5314 04:26:46,520 --> 04:26:47,320 EMPHYSEMA. 5315 04:26:47,320 --> 04:26:49,320 THIS IS PART OF THE PROGRAM 5316 04:26:49,320 --> 04:26:51,840 PROJECT WITH THE CORNELL AND 5317 04:26:51,840 --> 04:26:55,040 BOSTON COLLEAGUES AND MITOFUSIN 5318 04:26:55,040 --> 04:26:57,640 1 BUT NOT 2 IS PROTECTIVE FOR 5319 04:26:57,640 --> 04:27:02,960 SMOKE INDUCED LUNG INJURY. 5320 04:27:02,960 --> 04:27:07,600 SO I DO WANT TO FINISH THE NEXT 5321 04:27:07,600 --> 04:27:14,920 TWO OR THREE MINUTES ON AN ANGLE 5322 04:27:14,920 --> 04:27:20,080 WITH A BIOLOGIST AND THIS IS A 5323 04:27:20,080 --> 04:27:25,320 PAPER FROM A RESEARCH SCHOLAR 5324 04:27:25,320 --> 04:27:35,440 FROM JAPAN AND OTHERS AND 5325 04:27:35,440 --> 04:27:35,920 REVERSING THE MODEL BY 5326 04:27:35,920 --> 04:27:38,880 PROGENITOR CELLS ISOLATED FROM 5327 04:27:38,880 --> 04:27:40,520 THE LUNG. 5328 04:27:40,520 --> 04:27:41,720 THIS PAPER SHOWED THAT AND ONE 5329 04:27:41,720 --> 04:27:44,800 PAPER I WANT TO SHARE WITH YOU 5330 04:27:44,800 --> 04:27:45,800 AND WE DON'T HAVE COMPELLING 5331 04:27:45,800 --> 04:27:48,320 EVIDENCE YET THAT MITOCHONDRIAL 5332 04:27:48,320 --> 04:27:49,960 DYSFUNCTION PLAYS A ROLE BUT 5333 04:27:49,960 --> 04:27:54,840 THIS IS USING ELASTIS MODEL 5334 04:27:54,840 --> 04:27:57,960 SHOWING DELIVERY OF SPECIALIZED 5335 04:27:57,960 --> 04:28:00,360 LUNG ENDOTHELIAL CELLS 5336 04:28:00,360 --> 04:28:04,480 PROGENITOR CELLS MITIGATED THE 5337 04:28:04,480 --> 04:28:06,560 DEVELOPMENT OF EMPHYSEMA 5338 04:28:06,560 --> 04:28:10,560 FOLLOWING ELASTASE BY MLI AND 5339 04:28:10,560 --> 04:28:14,400 HISTOLOGICAL SLIDES. 5340 04:28:14,400 --> 04:28:16,240 THE MECHANISM OF THAT COULD BE 5341 04:28:16,240 --> 04:28:22,640 FURTHER LOSS OF ENDOTHELIAL CELL 5342 04:28:22,640 --> 04:28:27,920 PROTECT FROM THE EMPHYSEMA 5343 04:28:27,920 --> 04:28:30,240 PHENOTYPE AND SHOWING AGAIN THAT 5344 04:28:30,240 --> 04:28:33,560 YOU HAVE AFFECTS. 5345 04:28:33,560 --> 04:28:36,000 THAT IS THE SLIDES AND THIS IS 5346 04:28:36,000 --> 04:28:37,440 MY LAST SLIDE SHOWING YOU WHAT 5347 04:28:37,440 --> 04:28:39,640 THE FUTURE STUDIES HERE ARE 5348 04:28:39,640 --> 04:28:43,640 LOOKING AT SMOKING INDUCED 5349 04:28:43,640 --> 04:28:48,200 EMPHYSEMA AND FIBROSIS AND LOOK 5350 04:28:48,200 --> 04:28:52,200 AT THE ROLE OF AUTOPHAGY AND 5351 04:28:52,200 --> 04:28:55,360 DYSFUNCTION AND GETTING IN THE 5352 04:28:55,360 --> 04:28:57,160 MITOCHONDRIAL DNA MUTATIONS IN 5353 04:28:57,160 --> 04:29:01,000 THE CELL-FREE PLASMA AND URINE 5354 04:29:01,000 --> 04:29:10,320 FROM PATIENTS WITH SPIROMICS 5355 04:29:10,320 --> 04:29:11,880 COHORT. 5356 04:29:11,880 --> 04:29:21,080 THANK YOU FOR YOUR ATTENTION. 5357 04:29:21,080 --> 04:29:26,000 >> WONDERFUL SUMMARY. 5358 04:29:26,000 --> 04:29:27,720 WE FINISHED RIGHT ON TOP OF THE 5359 04:29:27,720 --> 04:29:28,080 HOUR. 5360 04:29:28,080 --> 04:29:29,240 I'M IMPRESSED. 5361 04:29:29,240 --> 04:29:33,440 WE WERE THINKING HOW TO KICK OFF 5362 04:29:33,440 --> 04:29:35,480 THE DISCUSSION, IN CASE 5363 04:29:35,480 --> 04:29:37,800 INDIVIDUAL NOT PRESENT THIS 5364 04:29:37,800 --> 04:29:38,840 MORNING FOR DISCUSSION SO WHERE 5365 04:29:38,840 --> 04:29:40,480 WE LEFT OFF BEFORE THE LUNCH 5366 04:29:40,480 --> 04:29:43,000 HOUR WAS TALKING ABOUT SORT OF 5367 04:29:43,000 --> 04:29:45,800 THE AMAZING RESOURCES OF DATA 5368 04:29:45,800 --> 04:29:47,280 AND POTENTIAL SAMPLES AVAILABLE 5369 04:29:47,280 --> 04:29:50,160 FOR KLIN CALICO HORTS AND 5370 04:29:50,160 --> 04:29:51,280 DOVETAILED INTO DISCUSSION OF 5371 04:29:51,280 --> 04:29:53,600 ACCESS AND LIMITATIONS OF THAT. 5372 04:29:53,600 --> 04:29:54,960 WE THOUGHT FOR EACH OF THE 5373 04:29:54,960 --> 04:29:56,960 SPEAKERS WE'D START BY ASKING 5374 04:29:56,960 --> 04:29:58,880 YOU NOT REALLY A SIMPLE QUESTION 5375 04:29:58,880 --> 04:30:02,640 BUT I THINK WE SAW EXAMPLES FROM 5376 04:30:02,640 --> 04:30:04,680 VARIOUS SPEAKERS OF POTENTIAL 5377 04:30:04,680 --> 04:30:08,320 SUCCESSES IN LEVERAGING COHORTS 5378 04:30:08,320 --> 04:30:17,720 AND SAMPLES AND THE QUESTION IF 5379 04:30:17,720 --> 04:30:19,360 HAVE ONE SPECIFIC DESIRE OR NEED 5380 04:30:19,360 --> 04:30:20,760 FOR YOUR LINE OF INVESTIGATION 5381 04:30:20,760 --> 04:30:23,040 YOU'D LIKE TO HAVE FULFILLED 5382 04:30:23,040 --> 04:30:25,760 FROM ACCESS TO CLINICAL COHORTS 5383 04:30:25,760 --> 04:30:27,120 FROM DATA OR BIO MATERIAL WHAT 5384 04:30:27,120 --> 04:30:28,200 WOULD THAT BE OR MAYBE 5385 04:30:28,200 --> 04:30:30,080 HIGHLIGHTING FOR THE AUDIENCE 5386 04:30:30,080 --> 04:30:33,000 AND DISCUSSANTS AND STAKEHOLDERS 5387 04:30:33,000 --> 04:30:33,760 BARRIERS YOU'D LIKE TO SEE 5388 04:30:33,760 --> 04:30:39,880 ADDRESSED AND OVERCOME TO MOVE 5389 04:30:39,880 --> 04:30:40,360 TOWARDS TRANSLATION. 5390 04:30:40,360 --> 04:30:45,800 I THINK WHY DON'T WE START WITH 5391 04:30:45,800 --> 04:30:56,360 OUR FIRST SPEAKER DR. GENSCHMER 5392 04:31:00,880 --> 04:31:06,400 AND IF YOU HAVE ONE COHORT IN 5393 04:31:06,400 --> 04:31:12,080 TERMS OF BIO SPECIMENS WHAT 5394 04:31:12,080 --> 04:31:12,760 WORLD IT BE? 5395 04:31:12,760 --> 04:31:23,320 >> AND I'M VERY EXCITED TO LOOK 5396 04:31:24,120 --> 04:31:25,920 INTO THAT. 5397 04:31:25,920 --> 04:31:28,360 AND ANY COHORT OVERTIME WITH THE 5398 04:31:28,360 --> 04:31:29,560 SAME PATIENT MULTIPLE TIME 5399 04:31:29,560 --> 04:31:40,120 POINTS IS IDEAL FOR MY STUDIES. 5400 04:31:53,920 --> 04:31:57,520 >> CAN WE SPECIFY PEOPLE WHAT 5401 04:31:57,520 --> 04:32:03,880 THEY NEED IF IT'S BLOOD IT'S 5402 04:32:03,880 --> 04:32:05,760 SIMPLE FOR US AND OTHERS MAY 5403 04:32:05,760 --> 04:32:06,640 REQUIRE ADDITIONAL WORK BECAUSE 5404 04:32:06,640 --> 04:32:07,960 THEY MAY NOT HAVE BEEN 5405 04:32:07,960 --> 04:32:08,360 COLLECTED. 5406 04:32:08,360 --> 04:32:12,320 >> I'LL GO BACK TO ONE. 5407 04:32:12,320 --> 04:32:15,920 I'M CURRENTLY LOOKING MOSTLY AT 5408 04:32:15,920 --> 04:32:19,000 THE FLUIDS OF PATIENTS. 5409 04:32:19,000 --> 04:32:22,760 I'VE BEGUN LOOKING AT SPUTUM AND 5410 04:32:22,760 --> 04:32:26,800 IF I WAS ABLE TO FIND A SIMILAR 5411 04:32:26,800 --> 04:32:27,800 BIOMARKER OR PHENOTYPE WITHIN 5412 04:32:27,800 --> 04:32:29,880 THOSE SAMPLES THEN THAT WOULD 5413 04:32:29,880 --> 04:32:30,600 DEFINITELY BE SOMETHING I'D WANT 5414 04:32:30,600 --> 04:32:38,480 TO LOOK INTO. 5415 04:32:38,480 --> 04:32:40,880 >> YOU BRING UP A GREAT POINT OF 5416 04:32:40,880 --> 04:32:42,800 WHAT'S AVAILABLE AND MAY NOT BE 5417 04:32:42,800 --> 04:32:44,600 SURMOUNTABLE FOR THE 5418 04:32:44,600 --> 04:32:49,120 LONGER-STANDING COHORTS. 5419 04:32:49,120 --> 04:32:51,280 DR. FARRAH KHERADMAND. 5420 04:32:51,280 --> 04:32:52,960 >> SO I THINK WHAT YOU'RE 5421 04:32:52,960 --> 04:32:57,200 GETTING AT IS HOW DO WE 5422 04:32:57,200 --> 04:33:00,080 INTEGRATE WHAT WE DO IN THE LAB 5423 04:33:00,080 --> 04:33:04,000 WITH THE COHORT STUDIES. 5424 04:33:04,000 --> 04:33:05,560 I THINK MANY PEOPLE OBVIOUSLY 5425 04:33:05,560 --> 04:33:08,640 NOTED AND IT'S BEEN PUBLISHED 5426 04:33:08,640 --> 04:33:14,160 MANY TIMES OVER THAT YOU HAVE A 5427 04:33:14,160 --> 04:33:15,840 HETEROGENOUS POPULATION AND THEY 5428 04:33:15,840 --> 04:33:17,800 HAVE INVARIABLY COME ACROSS A 5429 04:33:17,800 --> 04:33:19,440 LOT OF INFECTION WHICH IS SORT 5430 04:33:19,440 --> 04:33:22,280 OF MISSING IN THE ANIMAL MODELS 5431 04:33:22,280 --> 04:33:24,160 WHERE WE ACTUALLY JUST EXPOSE 5432 04:33:24,160 --> 04:33:26,880 MICE TO A VERY STERILE 5433 04:33:26,880 --> 04:33:27,160 ENVIRONMENT. 5434 04:33:27,160 --> 04:33:32,120 WHAT I WANT TO POINT OUT IS THAT 5435 04:33:32,120 --> 04:33:35,360 EVEN THOUGH IT SEEMS 5436 04:33:35,360 --> 04:33:36,800 ARTIFACTUALLY UNREAL FROM WHAT 5437 04:33:36,800 --> 04:33:39,240 HAPPENS IN A HUMAN POPULATION 5438 04:33:39,240 --> 04:33:44,120 AND WE DON'T SIT IN A CAGE IN A 5439 04:33:44,120 --> 04:33:45,200 STERILE ENVIRONMENT UNTIL WE 5440 04:33:45,200 --> 04:33:47,480 DIE, WE RUN AROUND AND GET 5441 04:33:47,480 --> 04:33:48,520 INFECTIONS. 5442 04:33:48,520 --> 04:33:51,080 IT ADDS A LEVEL OF COMPLEXITY TO 5443 04:33:51,080 --> 04:33:53,320 THE DISEASE IN ITSELF. 5444 04:33:53,320 --> 04:33:56,360 IT IS IMPORTANT FOR COHORT 5445 04:33:56,360 --> 04:33:58,520 STUDIES TO TAKE INTO ACCOUNT NOT 5446 04:33:58,520 --> 04:34:05,440 JUST COPD EXACERBATION BUT TO 5447 04:34:05,440 --> 04:34:07,680 THE BIOMARKERS AND TRY TO 5448 04:34:07,680 --> 04:34:10,640 COLLECT TO UNDERSTAND IS IT FOR 5449 04:34:10,640 --> 04:34:15,560 INSTANCE THAT WHEN WE IMMUNIZE 5450 04:34:15,560 --> 04:34:17,720 PEOPLE, ARE THE RESPONSE TO THE 5451 04:34:17,720 --> 04:34:19,960 IMMUNOGEN, THAT BEING THE FLU OR 5452 04:34:19,960 --> 04:34:23,480 COVID VACCINE, GOD FORBID, IS 5453 04:34:23,480 --> 04:34:25,760 THEIR IMMUNE RESPONSE THE SAME 5454 04:34:25,760 --> 04:34:26,880 AS IF YOU WERE NOT AN ACTIVE 5455 04:34:26,880 --> 04:34:28,600 SMOKER. 5456 04:34:28,600 --> 04:34:31,040 I CAN TELL YOU THAT I THINK SOME 5457 04:34:31,040 --> 04:34:36,440 OF THE FUNDAMENTAL QUESTIONS CAN 5458 04:34:36,440 --> 04:34:38,200 BE ADDRESSED IN A COHORT STUDY 5459 04:34:38,200 --> 04:34:38,800 PEOPLE WERE TALKING ABOUT THIS 5460 04:34:38,800 --> 04:34:44,840 MORNING, 7,000, 10,000, 4,000, I 5461 04:34:44,840 --> 04:34:45,640 THINK THAT'S COLLECTIVE 5462 04:34:45,640 --> 04:34:48,560 INFORMATION THAT NEEDS TO BE PUT 5463 04:34:48,560 --> 04:34:52,400 TOGETHER TO TRY TO DECIPHER WHAT 5464 04:34:52,400 --> 04:34:56,080 IS IT ABOUT CIGARETTE SMOKING 5465 04:34:56,080 --> 04:34:56,720 AND IMMUNE RESPONSE. 5466 04:34:56,720 --> 04:34:57,920 DOES THAT ANSWER YOUR QUESTION? 5467 04:34:57,920 --> 04:34:59,320 >> I THINK IT DOES. 5468 04:34:59,320 --> 04:35:02,840 I THINK THERE'S MESSAGES IN THE 5469 04:35:02,840 --> 04:35:04,600 CHAT SPRING BOARDING OFF THAT 5470 04:35:04,600 --> 04:35:06,640 AND CLARIFYING WHAT WE CAN DO 5471 04:35:06,640 --> 04:35:08,480 WITH EXISTING DATA FROM THE 5472 04:35:08,480 --> 04:35:11,640 COHORTS GIVEN THEIR LARGE SAMPLE 5473 04:35:11,640 --> 04:35:13,000 SIZE DOVETAILING THAT WITH WHAT 5474 04:35:13,000 --> 04:35:16,120 YOU'RE SEEING IN THE MECHANISTIC 5475 04:35:16,120 --> 04:35:17,720 STUDIES AND STILL ROOM TO GROW 5476 04:35:17,720 --> 04:35:24,640 AND EXPAND THAT SPACE. 5477 04:35:24,640 --> 04:35:29,640 >> YOU DOVETAILED IT NICELY WITH 5478 04:35:29,640 --> 04:35:31,120 THE LUNG SPACE. 5479 04:35:31,120 --> 04:35:33,320 ANY THOUGHTS OR ORTHOGONAL IDEAS 5480 04:35:33,320 --> 04:35:34,480 YOU'D LIKE TO SHARE AND BRING UP 5481 04:35:34,480 --> 04:35:35,400 FOR DISCUSSION? 5482 04:35:35,400 --> 04:35:38,160 >> I THINK THE OVER ALL 5483 04:35:38,160 --> 04:35:44,400 CONCEPTUAL DEPTH IS NOT JUST 5484 04:35:44,400 --> 04:35:46,800 PEOPLE WHO STUDY BIOLOGICAL 5485 04:35:46,800 --> 04:35:49,360 CREATIONS BUT PROPORTIONAL TO 5486 04:35:49,360 --> 04:35:51,320 THE ANATOMICAL DISTANCE BETWEEN 5487 04:35:51,320 --> 04:35:53,840 THINGS THAT HAPPEN AND WHICH WE 5488 04:35:53,840 --> 04:35:54,040 STUDY. 5489 04:35:54,040 --> 04:35:58,200 I THINK THE CLOSER WE GET TO THE 5490 04:35:58,200 --> 04:36:02,480 APPROACH IN WHICH WE FIND SOME 5491 04:36:02,480 --> 04:36:05,120 BIOLOGICAL MARKERS OR SOME 5492 04:36:05,120 --> 04:36:08,320 BIOLOGICAL FEATURES WHICH SIGNAL 5493 04:36:08,320 --> 04:36:10,800 ABOUT WHAT'S HAPPENING IN THE 5494 04:36:10,800 --> 04:36:12,720 PARTICULAR AREA OF DISEASE 5495 04:36:12,720 --> 04:36:15,120 DEVELOPMENT YOU CAN DEFINE WHAT 5496 04:36:15,120 --> 04:36:16,560 INJURY IS. 5497 04:36:16,560 --> 04:36:18,720 WHAT IS INJURY AND WHAT IS THE 5498 04:36:18,720 --> 04:36:20,520 INITIAL EVENT AND HOW IT 5499 04:36:20,520 --> 04:36:23,400 CORRESPONDS TO SYSTEMIC MARKERS 5500 04:36:23,400 --> 04:36:25,320 AND PHYSIOLOGICAL FEATURES WHICH 5501 04:36:25,320 --> 04:36:27,560 WE CAN MEASURE IN PATIENTS. 5502 04:36:27,560 --> 04:36:29,600 I THINK THAT IS MOST INFORMATIVE 5503 04:36:29,600 --> 04:36:33,360 IN TERMS OF GUIDING CLINICAL 5504 04:36:33,360 --> 04:36:34,960 STUDIES AND FUTURE INTERVENTIONS 5505 04:36:34,960 --> 04:36:36,800 BECAUSE THEY'LL INFORM US ABOUT 5506 04:36:36,800 --> 04:36:39,440 CHANGES HAPPENING IN TERMS OF 5507 04:36:39,440 --> 04:36:40,320 DISEASE DRIVING PROCESS INTO 5508 04:36:40,320 --> 04:36:45,560 DISEASE AND MY EXAMPLE WAS ONE 5509 04:36:45,560 --> 04:36:48,440 OF THEM IN WHICH WITH YOU CAB 5510 04:36:48,440 --> 04:36:51,440 TRY TO SWITCH FROM TERMINAL 5511 04:36:51,440 --> 04:36:55,040 BRONCHIOLES TO THE AIRWAYS AND 5512 04:36:55,040 --> 04:37:00,160 SPIROMICS CAN DO BRONCHIAL 5513 04:37:00,160 --> 04:37:04,320 AIRWAYS AND PROXIMAL AIRWAY AND 5514 04:37:04,320 --> 04:37:07,880 SURE SIGNATURES CAN BE FOUND BY 5515 04:37:07,880 --> 04:37:11,920 ANALYZING THE LONGITUDINAL DATA 5516 04:37:11,920 --> 04:37:12,120 SETS. 5517 04:37:12,120 --> 04:37:14,240 >> THANK YOU. 5518 04:37:14,240 --> 04:37:19,480 I'LL HIGHLIGHT WONDERFUL 5519 04:37:19,480 --> 04:37:21,760 EXAMPLES FROM DEEP STUDIES AND 5520 04:37:21,760 --> 04:37:22,600 TO GO BACK TO THE INITIAL 5521 04:37:22,600 --> 04:37:24,360 COMMENT OF THE SECTION THAT MAY 5522 04:37:24,360 --> 04:37:26,720 NOT BE POSSIBLE FOR OTHER 5523 04:37:26,720 --> 04:37:27,000 COHORTS. 5524 04:37:27,000 --> 04:37:29,080 COLLECTIVELY IT WOULD BE NICE TO 5525 04:37:29,080 --> 04:37:31,280 DOVETAIL IT AS WE MOVE FORWARD 5526 04:37:31,280 --> 04:37:33,520 TO WHAT OPPORTUNITIES ARE THERE 5527 04:37:33,520 --> 04:37:35,560 TO EITHER ADD THAT OR LEVERAGE 5528 04:37:35,560 --> 04:37:40,280 OTHER TECHNIQUES TO ASSAY THE 5529 04:37:40,280 --> 04:37:41,680 INACCESSIBLE OR SPACES BECAUSE 5530 04:37:41,680 --> 04:37:44,120 WE DON'T WANT TO LIMIT TO ONE 5531 04:37:44,120 --> 04:37:48,200 COHORT GIVEN THE HETEROGENEITY 5532 04:37:48,200 --> 04:37:58,720 OF COHORTS WE HAVE ACCESS TO. 5533 04:38:00,560 --> 04:38:01,400 IRINA PETRACHE. 5534 04:38:01,400 --> 04:38:05,440 >> I LIKE THE ANSWERS GIVEN. 5535 04:38:05,440 --> 04:38:06,840 INSTEAD OF LISTING THE 5536 04:38:06,840 --> 04:38:11,880 APPRECIATION RESOURCE HAVE NOT 5537 04:38:11,880 --> 04:38:14,960 BEEN COLLECTED YET IN THE CROSS 5538 04:38:14,960 --> 04:38:17,320 SECTIONAL STUDIES WE HAD, I 5539 04:38:17,320 --> 04:38:21,320 WANTED TO POSE A POTENTIAL 5540 04:38:21,320 --> 04:38:22,920 APPROACH OR OPPORTUNITY WE HAVE 5541 04:38:22,920 --> 04:38:24,560 ON THE BASIC SCIENCE THERE'S 5542 04:38:24,560 --> 04:38:27,080 BEEN QUITE A RICH AMOUNT OF DATA 5543 04:38:27,080 --> 04:38:31,200 THAT IS COMING THROUGH WITH 5544 04:38:31,200 --> 04:38:32,560 POTENTIAL TARGETS. 5545 04:38:32,560 --> 04:38:35,480 AND PERHAPS THE LACK OF 5546 04:38:35,480 --> 04:38:40,280 ENTHUSIASM OF MOVING THEM TO 5547 04:38:40,280 --> 04:38:42,160 BEDSIDE IS RELATED TO THE FACT 5548 04:38:42,160 --> 04:38:44,360 THAT TESTING FOR THE RELEVANCE 5549 04:38:44,360 --> 04:38:49,840 FROM THE MOUSE OR CELL CULTURE 5550 04:38:49,840 --> 04:38:57,320 OR INTO COHORTS AND LOOKING FOR 5551 04:38:57,320 --> 04:38:58,920 A SIGNAL LIKE NEEDLE IN A 5552 04:38:58,920 --> 04:39:03,040 HAYSTACK IS NOT ONLYING BUT OF 5553 04:39:03,040 --> 04:39:05,520 THE -- ONLY DAUNTING BUT 5554 04:39:05,520 --> 04:39:09,000 RESULTS IN NEGATIVE DATA AND MAY 5555 04:39:09,000 --> 04:39:10,440 DIMINISH THE ENTHUSIASM OF 5556 04:39:10,440 --> 04:39:15,840 FUNDING AGENCIES OR BIG PHARMA 5557 04:39:15,840 --> 04:39:23,920 TO REALLY LEAVE OR MOVE IT 5558 04:39:23,920 --> 04:39:27,800 FORWARD SUCH AS COPD. 5559 04:39:27,800 --> 04:39:31,640 AND I THINK THE OPPORTUNITY FOR 5560 04:39:31,640 --> 04:39:36,360 THE SUBPHENOTYPING LIKE 5561 04:39:36,360 --> 04:39:40,240 IDENTIFYING AND COUPLE 5562 04:39:40,240 --> 04:39:44,240 INDEPENDENTLY VALIDATED TARGETS 5563 04:39:44,240 --> 04:39:47,720 CAN WE LEVERAGE THE WEALTH OF 5564 04:39:47,720 --> 04:39:51,800 THE CLINICAL DATA AND BIOMARKER 5565 04:39:51,800 --> 04:39:55,640 DATA TO UNDERSTAND IN WHICH 5566 04:39:55,640 --> 04:39:58,320 INDIVIDUAL AND WHICH EXPOSURE 5567 04:39:58,320 --> 04:39:59,760 AND MICROBIOME AND DIET IS THAT 5568 04:39:59,760 --> 04:40:01,160 TARGET RELEVANT. 5569 04:40:01,160 --> 04:40:02,720 AND PUTTING THOSE TOGETHER I 5570 04:40:02,720 --> 04:40:07,320 THINK WITH THE ADVENT OF LARGE 5571 04:40:07,320 --> 04:40:08,040 INFORMATIC CAPABILITIES WE CAN 5572 04:40:08,040 --> 04:40:15,760 GET THERE. 5573 04:40:15,760 --> 04:40:18,200 >> I AGREE WITH WHAT THEY'RE 5574 04:40:18,200 --> 04:40:19,880 CHATTING ABOUT MAKING WHAT WE 5575 04:40:19,880 --> 04:40:23,840 KNOW FROM THE BASIC SCIENCE AND 5576 04:40:23,840 --> 04:40:26,320 COULD WE POTENTIALLY RECLASSIFY 5577 04:40:26,320 --> 04:40:26,640 PHENOTYPES. 5578 04:40:26,640 --> 04:40:28,920 IT'S SOMETHING WE HAD IN THE 5579 04:40:28,920 --> 04:40:31,040 LAST QUESTION AND MAYBE WE'LL 5580 04:40:31,040 --> 04:40:31,400 GET THERE. 5581 04:40:31,400 --> 04:40:40,120 PHIL, THOUGHTS? 5582 04:40:40,120 --> 04:40:42,240 >> YOU'RE GOING TO HATE ME FOR 5583 04:40:42,240 --> 04:40:45,160 THIS ABOUT WHAT WE NEED FROM 5584 04:40:45,160 --> 04:40:51,160 MICROBIOMES TO THIS BECAUSE IF 5585 04:40:51,160 --> 04:40:52,880 YOU COULD GO TO THE SUPER MARKET 5586 04:40:52,880 --> 04:40:56,840 AND GET SAMPLES YOU WANTED OFF 5587 04:40:56,840 --> 04:40:57,760 THE SHELF WE'D GET STABLE 5588 04:40:57,760 --> 04:41:00,080 DISEASE AND EXACERBATIONS AND 5589 04:41:00,080 --> 04:41:05,480 WANT GUT, LUNG AND BLOOD SAMPLES 5590 04:41:05,480 --> 04:41:08,120 THAT MATCH FROM THE SAME 5591 04:41:08,120 --> 04:41:15,520 PATIENTS AND GUT BIOPSIES TO DO 5592 04:41:15,520 --> 04:41:26,040 THE FULL METABOLOMICS AND LOOK 5593 04:41:28,600 --> 04:41:31,440 AT THE FACTORS OF PATHOGENESIS. 5594 04:41:31,440 --> 04:41:33,280 WHERE WE NEED TO COME TO AS A 5595 04:41:33,280 --> 04:41:43,760 FIELD IS THIS IS WHAT WE NEED 5596 04:41:44,920 --> 04:41:46,800 THIS IS WHAT'S POSSIBLE AND WHAT 5597 04:41:46,800 --> 04:41:49,080 WE CAN GET TO BETTER UNDERSTAND 5598 04:41:49,080 --> 04:41:59,440 THE DISEASE. 5599 04:41:59,440 --> 04:42:01,560 >> THERE WAS A COMMENT ABOUT THE 5600 04:42:01,560 --> 04:42:06,280 ONE MECHANISM APPROACH WE ALL 5601 04:42:06,280 --> 04:42:15,400 ASPIRE TO BECAUSE THAT CHALLENGE 5602 04:42:15,400 --> 04:42:18,560 I THINK WAS OUTLINED AND THERE'S 5603 04:42:18,560 --> 04:42:23,880 NHLBI HERE HOW TO SUPPORT THE 5604 04:42:23,880 --> 04:42:31,000 COMMUNITY IN NOVEL COLLABOR 5605 04:42:31,000 --> 04:42:36,320 COLLABORATIONS AND LOOKING AT 5606 04:42:36,320 --> 04:42:40,280 LINES RELATED TO SAY THE DISEASE 5607 04:42:40,280 --> 04:42:45,480 PHENOTYPE ASSOCIATED WITH COPD 5608 04:42:45,480 --> 04:42:49,440 PROGRESSION AND VASCULATURE 5609 04:42:49,440 --> 04:42:50,840 RELATED TO EMPHYSEMA AND 5610 04:42:50,840 --> 04:42:51,360 CORRELATIONS. 5611 04:42:51,360 --> 04:42:55,560 I THINK THAT WOULD BE NICE ALSO 5612 04:42:55,560 --> 04:42:56,680 TOE TALK ABOUT STRATEGIES TO 5613 04:42:56,680 --> 04:42:59,800 MOVE FORWARD IN TERMS OF 5614 04:42:59,800 --> 04:43:00,080 FUNDING. 5615 04:43:00,080 --> 04:43:03,200 IN THE U.S. SIDE THERE'S 5616 04:43:03,200 --> 04:43:05,200 CHALLENGES IN BRINGING FORWARD 5617 04:43:05,200 --> 04:43:11,280 THE BIGGER, BROADER IDEAS AND 5618 04:43:11,280 --> 04:43:12,880 FRANKLY FUNDAMENTAL TO ADDRESS 5619 04:43:12,880 --> 04:43:14,280 THE NEWER LINES OF INVESTIGATION 5620 04:43:14,280 --> 04:43:15,120 WHERE WE'D LIKE TO KNOW 5621 04:43:15,120 --> 04:43:22,560 TECHNOLOGIES AND IDEAS. 5622 04:43:22,560 --> 04:43:28,360 ORE TO AMIT. 5623 04:43:28,360 --> 04:43:30,760 >> THANK YOU AND THERE'S 5624 04:43:30,760 --> 04:43:31,640 THOUGHTFUL ANSWERS THERE. 5625 04:43:31,640 --> 04:43:35,200 I WANT TO JUMP BACK TO WHAT 5626 04:43:35,200 --> 04:43:37,800 IRENA SAID AND I THINK IT'S 5627 04:43:37,800 --> 04:43:38,360 SHOWING UP IN THE CHAT. 5628 04:43:38,360 --> 04:43:39,600 IT'S GOING TO BE HIGHLY RELEVANT 5629 04:43:39,600 --> 04:43:44,360 TO EVERYBODY I THINK ON THE 5630 04:43:44,360 --> 04:43:46,040 CALL. 5631 04:43:46,040 --> 04:43:53,560 THE IDEA OF THE DISEASE OF COPD 5632 04:43:53,560 --> 04:43:55,840 AND IT'S POSSIBLY SO MANY 5633 04:43:55,840 --> 04:43:58,320 LITTLER DISEASES AND ENDOTYPING 5634 04:43:58,320 --> 04:43:59,360 AND USING CF AS AN EXAMPLE 5635 04:43:59,360 --> 04:44:01,360 BECAUSE IT'S A SPACE I KNOW. 5636 04:44:01,360 --> 04:44:06,800 AS A MONOGENIC DISEASE IT WAS 5637 04:44:06,800 --> 04:44:10,120 FOCUSSED ON THE DEVELOPING 5638 04:44:10,120 --> 04:44:11,240 THERAPIES AGAIN THE GENE THERAPY 5639 04:44:11,240 --> 04:44:16,800 AND WHAT IT LOOKED LIKE IS 5640 04:44:16,800 --> 04:44:20,240 THAT'S HARDER WHILE THE PATHWAY 5641 04:44:20,240 --> 04:44:25,720 WORKS THE THERO TYPING IS MORE 5642 04:44:25,720 --> 04:44:28,200 DIFFICULT AND NOT JUST ONE DRUG 5643 04:44:28,200 --> 04:44:29,320 OR GENE. 5644 04:44:29,320 --> 04:44:29,960 IT'S A BIT MORE COMPLICATED THAN 5645 04:44:29,960 --> 04:44:34,080 THAT. 5646 04:44:34,080 --> 04:44:35,920 KNOW TAKING A COMPLICATED 5647 04:44:35,920 --> 04:44:37,280 DISEASE LIKE COPD HOW DO YOU GO 5648 04:44:37,280 --> 04:44:39,160 TO THE MECHANISTIC QUESTIONS. 5649 04:44:39,160 --> 04:44:40,600 ARE THE MECHANISMS WE'RE SEEING 5650 04:44:40,600 --> 04:44:44,480 ARE THEY PREVALENT IN ALL TYPES 5651 04:44:44,480 --> 04:44:47,240 OF COPD OR WILL THEY NEED TO BE 5652 04:44:47,240 --> 04:44:51,320 REALLY -- WILL THE MECHANISTIC 5653 04:44:51,320 --> 04:44:53,560 ENDOTYPING PUT US IN DIFFERENT 5654 04:44:53,560 --> 04:44:55,320 CLASSES OF COPD OR OTHER 5655 04:44:55,320 --> 04:44:58,000 FEATURES THAT WILL DRIVE US INTO 5656 04:44:58,000 --> 04:45:00,960 ENDOTYPING PROPERLY AND HOW DO 5657 04:45:00,960 --> 04:45:04,040 YOU TAKE THAT TO A THEROTYPE? 5658 04:45:04,040 --> 04:45:04,880 IT'S A LOADED QUESTION. 5659 04:45:04,880 --> 04:45:06,200 I DON'T KNOW WHO WANTS TO TAKE 5660 04:45:06,200 --> 04:45:09,920 THE FIRST SHOT ON IT BUT IF 5661 04:45:09,920 --> 04:45:11,760 ANYBODY IN THE PARTICIPANTS 5662 04:45:11,760 --> 04:45:15,440 WOULD LIKE TO ADD TO THE CHAT, 5663 04:45:15,440 --> 04:45:15,800 PLEASE DO. 5664 04:45:15,800 --> 04:45:19,040 IT'S WHAT WE'RE ALL GETTING AT 5665 04:45:19,040 --> 04:45:19,640 IS THAT. 5666 04:45:19,640 --> 04:45:22,080 I'LL BE QUIET AND LET YOU GUYS 5667 04:45:22,080 --> 04:45:22,800 WHOEVER WANTS TO TAKE A SHOT 5668 04:45:22,800 --> 04:45:32,920 FIRST. 5669 04:45:36,880 --> 04:45:38,800 PHIL, YOU'RE UNMUTED SO YOU'RE 5670 04:45:38,800 --> 04:45:39,480 GOING FIRST. 5671 04:45:39,480 --> 04:45:43,040 >> IT'S A GREAT QUESTION AND 5672 04:45:43,040 --> 04:45:51,240 RAISES IMPORTANT POINTS. 5673 04:45:51,240 --> 04:45:55,280 AS TRANSLATIONAL PEOPLE WE NEED 5674 04:45:55,280 --> 04:45:57,040 TO KNOW WHAT WE'RE TRYING TO 5675 04:45:57,040 --> 04:45:57,240 TREAT. 5676 04:45:57,240 --> 04:46:03,640 WITH ASTHMA IT'S A BIT MORE 5677 04:46:03,640 --> 04:46:05,320 DEFINED. 5678 04:46:05,320 --> 04:46:08,760 YOU HAVE NEUTROPHILIC ASTHMA AND 5679 04:46:08,760 --> 04:46:09,960 PUT IT INTO DIFFERENT COHORTS OF 5680 04:46:09,960 --> 04:46:13,880 PEOPLE AND TRY TO BREAK IT DOWN 5681 04:46:13,880 --> 04:46:15,800 AS YOU SAID INTO DIFFERENT 5682 04:46:15,800 --> 04:46:19,360 POPULATIONS THAT MIGHT BENEFIT 5683 04:46:19,360 --> 04:46:21,000 FROM SPECIFIC TARGETED 5684 04:46:21,000 --> 04:46:21,240 THERAPIES. 5685 04:46:21,240 --> 04:46:23,800 HOW DO WE DO THAT IN COPD? 5686 04:46:23,800 --> 04:46:28,720 WE ALL LEARNED THAT -- WE ALL 5687 04:46:28,720 --> 04:46:32,720 HEARD ABOUT THAT WHEN WE HEARD 5688 04:46:32,720 --> 04:46:35,720 OF TYPES OF COPD. 5689 04:46:35,720 --> 04:46:41,840 HOW ELSE CAN WE BREAK DOWN COPD 5690 04:46:41,840 --> 04:46:45,400 POPULATIONS AND TRY TO MODEL 5691 04:46:45,400 --> 04:46:51,560 THOSE TYPE TO IDENTIFY SPECIFIC 5692 04:46:51,560 --> 04:46:53,880 THERAPIES FOR SPECIFIC GROUPS OF 5693 04:46:53,880 --> 04:46:54,120 PEOPLE. 5694 04:46:54,120 --> 04:46:55,040 THAT'S A GREAT QUESTION. 5695 04:46:55,040 --> 04:46:57,080 HOW DO WE DO THAT AND HOW CAN WE 5696 04:46:57,080 --> 04:46:58,280 MODEL IT TO COME UP WITH BETTER 5697 04:46:58,280 --> 04:47:08,480 SOLUTIONS? 5698 04:47:15,320 --> 04:47:16,880 >> ANYBODY ELSE WANT TO TAKE A 5699 04:47:16,880 --> 04:47:19,040 SHOT ON GOAL? 5700 04:47:19,040 --> 04:47:21,480 >> WHAT PHIL BRINGS UP IS 5701 04:47:21,480 --> 04:47:24,400 CRITICAL BORROWING FROM OTHER 5702 04:47:24,400 --> 04:47:26,360 DISEASES AND TALKING TO 5703 04:47:26,360 --> 04:47:28,640 CARDIOLOGISTS THEY WANT TO KNOW 5704 04:47:28,640 --> 04:47:34,840 IF IT'S HALF GRAPH OR WHATEVER 5705 04:47:34,840 --> 04:47:40,200 THEY'RE DISCUSSING WHEREAS WE 5706 04:47:40,200 --> 04:47:46,920 CALL EVERYONE COPD AND AND 5707 04:47:46,920 --> 04:47:52,400 THERE'S THE TRAJECTORY OF THE 5708 04:47:52,400 --> 04:47:52,760 DISEASE. 5709 04:47:52,760 --> 04:47:57,080 WE KNOW THERE'S EXTRA ONES 5710 04:47:57,080 --> 04:47:59,200 IDENTIFIED AND WE DON'T ALL HAVE 5711 04:47:59,200 --> 04:48:00,040 THE SNIPS AND THEY DON'T ALL 5712 04:48:00,040 --> 04:48:03,600 HAVE IT. 5713 04:48:03,600 --> 04:48:08,240 A LITTLE BIT BITS ALONG WITH 5714 04:48:08,240 --> 04:48:14,840 LIVING IN THE CITY WHERE IT'S 5715 04:48:14,840 --> 04:48:21,760 POLLUTED AND SMOKING. 5716 04:48:21,760 --> 04:48:23,320 UNLESS WE START LOOKING AT THE 5717 04:48:23,320 --> 04:48:26,160 DISEASE IN A DETAIL, ORIENTED 5718 04:48:26,160 --> 04:48:27,160 MANNER I THINK MOST CLINICAL 5719 04:48:27,160 --> 04:48:27,800 TRIALS WILL FAIL AS THEY HAVE IN 5720 04:48:27,800 --> 04:48:36,600 THE PAST. 5721 04:48:36,600 --> 04:48:37,920 >> WOULD A TRIALIST LIKE TO 5722 04:48:37,920 --> 04:48:48,400 SPEAK UP ABOUT THAT QUICKLY? 5723 04:48:51,080 --> 04:48:53,680 >> THERE WAS A BIG DOCUMENT IN 5724 04:48:53,680 --> 04:48:58,760 LANCET WITH THE COPD COMMISSION 5725 04:48:58,760 --> 04:49:00,960 AND LOOKED AT THE TAXONOMY OF 5726 04:49:00,960 --> 04:49:03,760 COPD AND SHOULD WE FIRST APPLY 5727 04:49:03,760 --> 04:49:07,040 THIS IDEA OF ETIOTYPES AS ONE 5728 04:49:07,040 --> 04:49:10,600 WAY OF BETTER CHARACTERIZING THE 5729 04:49:10,600 --> 04:49:12,120 HETEROGENEITY OF DISEASE AND 5730 04:49:12,120 --> 04:49:14,040 DISCUSSION AROUND PRO-COPD AND 5731 04:49:14,040 --> 04:49:20,120 HOW WE CHARACTERIZE THAT AND A 5732 04:49:20,120 --> 04:49:23,880 SEPARATE DISCUSSION ABOUT 5733 04:49:23,880 --> 04:49:25,120 ENDOTYPES AND PHENOTYPES WITH 5734 04:49:25,120 --> 04:49:27,720 RESPECT TO DRUG DEVELOPMENT 5735 04:49:27,720 --> 04:49:29,120 THERE'S NEWER DRUGS TARGETING 5736 04:49:29,120 --> 04:49:33,440 SPECIFIC PATHWAYS LIKE L33, TYPE 5737 04:49:33,440 --> 04:49:38,320 2 INFLAMMATION. 5738 04:49:38,320 --> 04:49:41,840 THE CHALLENGE WE HAVE IS THAT WE 5739 04:49:41,840 --> 04:49:43,720 DON'T HAVE GOOD WAYS OF 5740 04:49:43,720 --> 04:49:45,840 PHENOTYPING THEM IN CLINIC. 5741 04:49:45,840 --> 04:49:47,880 WE DON'T GET LUNG FUNCTION WE 5742 04:49:47,880 --> 04:49:51,280 DON'T EVEN KNOW THE RAPID P 5743 04:49:51,280 --> 04:49:53,920 PROGRESSERS AND HAVE DRUGS TO 5744 04:49:53,920 --> 04:49:56,080 MATCH IT UP. 5745 04:49:56,080 --> 04:50:00,760 THERE'S NOT HUGE I MPETUS TO DO 5746 04:50:00,760 --> 04:50:05,400 THAT AND AS WE GET NEWER DRUGS 5747 04:50:05,400 --> 04:50:06,720 FOR INSTANCE THE DATA LOOKING 5748 04:50:06,720 --> 04:50:07,560 POTENTIALLY PROMISING. 5749 04:50:07,560 --> 04:50:14,920 WE MAY HAVE MORE DRUGS FOR TYPE 5750 04:50:14,920 --> 04:50:18,640 2 INFLAMMATION AND I THINK 5751 04:50:18,640 --> 04:50:19,880 HOPEFULLY THE CLINIC WILL CATCH 5752 04:50:19,880 --> 04:50:22,040 UP BUT HOW DO WE IDENTIFY THE 5753 04:50:22,040 --> 04:50:23,160 UNIQUE SUBTYPES OF PATIENTS IN 5754 04:50:23,160 --> 04:50:33,040 REAL LIFE. 5755 04:50:33,040 --> 04:50:38,760 >> YOU MADE GREAT POINTS AND 5756 04:50:38,760 --> 04:50:49,280 YOUR THOUGHTS ABOUT THE DEVE 5757 04:50:55,960 --> 04:51:03,880 DEVE -- DEFILLA MAB AND THEN YOU 5758 04:51:03,880 --> 04:51:10,520 HAD A DRUG THAT CAN TARGET THE 5759 04:51:10,520 --> 04:51:14,800 ORIGINAL MECHANISM. 5760 04:51:14,800 --> 04:51:15,880 YOU HAVE TO PROVE IT AND YOU 5761 04:51:15,880 --> 04:51:17,560 HAVE TO PROVE THE MECHANISM 5762 04:51:17,560 --> 04:51:23,000 YOU'RE TARGETING IS REAL AND NOT 5763 04:51:23,000 --> 04:51:25,880 A CONSEQUENCE OF YOU LOOKING FOR 5764 04:51:25,880 --> 04:51:27,360 THE MECHANISM INSIDE THE STUDY 5765 04:51:27,360 --> 04:51:28,640 AND HOW DO YOU FIND THE 5766 04:51:28,640 --> 04:51:30,840 BIOMARKER AND CONSISTENTLY SHOW 5767 04:51:30,840 --> 04:51:33,720 OVER AND OVER AGAIN IN MULTIPLE 5768 04:51:33,720 --> 04:51:35,800 COHORT IT'S A READ OUT OF A 5769 04:51:35,800 --> 04:51:37,080 PROCESS THAT CAN BE TARGETED 5770 04:51:37,080 --> 04:51:40,400 SUCCESSFULLY? 5771 04:51:40,400 --> 04:51:43,320 >> EXCELLENT. 5772 04:51:43,320 --> 04:51:48,680 ANY OTHER TAKES ON THE GENERAL 5773 04:51:48,680 --> 04:51:49,040 QUESTION? 5774 04:51:49,040 --> 04:51:51,360 I THINK TOMORROW THERE WILL BE A 5775 04:51:51,360 --> 04:51:54,520 LONG SESSION TO COVER THIS TOPIC 5776 04:51:54,520 --> 04:51:56,320 SO I DON'T BELABOR IT THAT MUCH 5777 04:51:56,320 --> 04:51:57,880 LONGER BUT I'D LIKE TO PIVOT TO 5778 04:51:57,880 --> 04:51:58,800 ONE MORE QUESTION. 5779 04:51:58,800 --> 04:52:00,760 FOR THE SPEAKERS AND ANYBODY 5780 04:52:00,760 --> 04:52:08,560 ELSE WHO MIGHT BE INTERESTED, 5781 04:52:08,560 --> 04:52:12,440 WHAT'S EXCITING TO YOU AND WHAT 5782 04:52:12,440 --> 04:52:15,880 ARE YOU SEEING IN THE WORLD OF 5783 04:52:15,880 --> 04:52:19,000 LUNG DISEASE OR CANCER? 5784 04:52:19,000 --> 04:52:21,400 MAYBE IN YOUR OWN RESEARCH YOU 5785 04:52:21,400 --> 04:52:24,800 THINK IS UNIQUE IN UNDERSTANDING 5786 04:52:24,800 --> 04:52:29,680 THE BIOLOGY OF COPD EVEN BETTER? 5787 04:52:29,680 --> 04:52:32,560 I'VE BEEN EXCITED ABOUT THE 5788 04:52:32,560 --> 04:52:34,200 DEVELOPMENT OF SPATIAL 5789 04:52:34,200 --> 04:52:36,280 TRANSCRIPTOMICS AS AN AREA OF 5790 04:52:36,280 --> 04:52:39,560 LEARNING A BIT MORE ABOUT WHAT 5791 04:52:39,560 --> 04:52:42,360 MIGHT BE GOING ON IN SPECIFIC 5792 04:52:42,360 --> 04:52:44,160 MISSIONS VERSUS THE WHOLE 5793 04:52:44,160 --> 04:52:44,480 DIGESTIONS. 5794 04:52:44,480 --> 04:52:49,720 IS THERE ANYTHING ELSE RIGHT NOW 5795 04:52:49,720 --> 04:52:53,600 YOU GUYS ARE SEEING IN COPD OR 5796 04:52:53,600 --> 04:52:54,440 UNRELATED DISEASE THAT'S 5797 04:52:54,440 --> 04:52:57,040 EXCITING AND SHOULD BE INVESTED 5798 04:52:57,040 --> 04:52:59,520 OR CONSIDERED AS WE MOVE FORWARD 5799 04:52:59,520 --> 04:52:59,760 IN COPD. 5800 04:52:59,760 --> 04:53:09,880 ANYBODY? 5801 04:53:14,360 --> 04:53:16,200 PHIL, YOU'RE UNMUTED SO YOU GO 5802 04:53:16,200 --> 04:53:16,840 FIRST AGAIN. 5803 04:53:16,840 --> 04:53:22,640 >> NOW I KNOW HOW TO GET MY 5804 04:53:22,640 --> 04:53:23,080 RESPONSES IN. 5805 04:53:23,080 --> 04:53:26,320 SO I THINK THE NEW OMIC 5806 04:53:26,320 --> 04:53:29,240 TECHNOLOGY IS EXCITING. 5807 04:53:29,240 --> 04:53:32,080 YOU MENTIONED SPATIAL 5808 04:53:32,080 --> 04:53:33,600 TRANSCRIPTOMICS AND SPATIAL 5809 04:53:33,600 --> 04:53:35,040 PROTEOMICS AND WE START TO LOOK 5810 04:53:35,040 --> 04:53:36,920 AT AND I THINK WE HAVE TO DO IT 5811 04:53:36,920 --> 04:53:39,520 THIS WAY, WE START TO LOOK AT 5812 04:53:39,520 --> 04:53:43,200 EACH ONE OF THESE OMICS 5813 04:53:43,200 --> 04:53:46,680 INDIVIDUALLY. 5814 04:53:46,680 --> 04:53:48,920 WE HAVE TO BECAUSE THEY'RE 5815 04:53:48,920 --> 04:53:49,880 COMPLICATED AND NEED TO MAXIMIZE 5816 04:53:49,880 --> 04:53:51,160 WHAT WE GET FROM EACH ONE AND 5817 04:53:51,160 --> 04:54:01,720 OVER TIME WE NEED TO WORK OUT WE 5818 04:54:03,040 --> 04:54:05,520 NEED TO WORK OUT HOW WE 5819 04:54:05,520 --> 04:54:07,480 INTEGRATE A LOT OF THESE 5820 04:54:07,480 --> 04:54:11,880 FINDINGS TO MORE HOLISTICALLY 5821 04:54:11,880 --> 04:54:13,040 UNDERSTAND DISEASE. 5822 04:54:13,040 --> 04:54:15,440 ONCE WE DO THAT WE CAN FIND 5823 04:54:15,440 --> 04:54:18,080 POTENTIALLY NEW TARGETS THAT 5824 04:54:18,080 --> 04:54:21,720 CONTROL ENTIRE DISEASE PATHWAYS 5825 04:54:21,720 --> 04:54:23,960 WE'VE NOT DISCOVERED YET. 5826 04:54:23,960 --> 04:54:25,240 THAT BE ONE WAY. 5827 04:54:25,240 --> 04:54:31,760 MAYBE THAT'S PIE IN THE SKY. 5828 04:54:31,760 --> 04:54:33,120 NEVERTHELESS I THINK MAXIMIZING 5829 04:54:33,120 --> 04:54:35,960 THE USE OF THE GENOMIC AND 5830 04:54:35,960 --> 04:54:40,080 SPATIAL TRANSCRIPTOMIC AND NOW 5831 04:54:40,080 --> 04:54:44,200 PROTEOMICS WILL ALLOW TO US 5832 04:54:44,200 --> 04:54:44,440 PROGRESS. 5833 04:54:44,440 --> 04:54:46,960 YOU MENTIONED ALL THE FAILS BUT 5834 04:54:46,960 --> 04:54:57,480 ONE PRESENTATION AT ATS ABOUT 5835 04:55:01,600 --> 04:55:02,320 BRONCHIECSTASIS THAT PREDICTED 5836 04:55:02,320 --> 04:55:09,680 DISEASE PROGRESSION. 5837 04:55:09,680 --> 04:55:11,200 THAT'S HOW TO USE THE 5838 04:55:11,200 --> 04:55:11,760 TECHNOLOGIES AND BETTER 5839 04:55:11,760 --> 04:55:13,760 UNDERSTAND DISEASE AND COME UP 5840 04:55:13,760 --> 04:55:16,200 WITH BETTER DIAGNOSTICS AND 5841 04:55:16,200 --> 04:55:26,400 TREATMENTS. 5842 04:55:28,520 --> 04:55:31,280 >> I WANT TO BE AS AWAKE AS PHIL 5843 04:55:31,280 --> 04:55:31,680 IS. 5844 04:55:31,680 --> 04:55:35,240 I WANT TO KNOW HIS MICROBIOME. 5845 04:55:35,240 --> 04:55:37,120 I HAVE BEEN INVOLVED IN ADVANCES 5846 04:55:37,120 --> 04:55:39,720 IN THREE DISEASES AND WE TALKED 5847 04:55:39,720 --> 04:55:40,800 ABOUT CF. 5848 04:55:40,800 --> 04:55:45,000 THE SUCCESS IN CF IS AMAZING AND 5849 04:55:45,000 --> 04:55:46,560 I THINK WE HAVE SO MUCH TO LEARN 5850 04:55:46,560 --> 04:55:48,760 FROM THAT AND I'M NOT GOING TO 5851 04:55:48,760 --> 04:55:53,520 REPEAT WHAT WAS SAID. 5852 04:55:53,520 --> 04:55:54,760 THE SECOND IS LUNG CANCER. 5853 04:55:54,760 --> 04:55:56,720 YOU ARE TAKE THE MOST FATAL 5854 04:55:56,720 --> 04:55:59,280 CANCER OF ALL AND WE'RE MAKE 5855 04:55:59,280 --> 04:56:04,480 SUCH GREAT IMPACT BECAUSE OF 5856 04:56:04,480 --> 04:56:08,160 PERSONALIZATION AND EARLY 5857 04:56:08,160 --> 04:56:08,440 DETECTION. 5858 04:56:08,440 --> 04:56:10,720 MOVING THE EARLY DETECTION AND 5859 04:56:10,720 --> 04:56:16,600 IMPROVING THE DEFECTION OF COPD, 5860 04:56:16,600 --> 04:56:20,640 IMPROVING OUR METHODOLOGIES 5861 04:56:20,640 --> 04:56:23,560 BEFORE FEB1 MAY BE A CLUE. 5862 04:56:23,560 --> 04:56:28,080 AND FINALLY IN CARDIOVASCULAR 5863 04:56:28,080 --> 04:56:33,320 DISEASE THEIR IMPROVING ON THE 5864 04:56:33,320 --> 04:56:35,360 CHOLESTEROL AND ON TRAPONIN. 5865 04:56:35,360 --> 04:56:38,520 IF YOU LOOK AT BAD VERSUS GOOD 5866 04:56:38,520 --> 04:56:42,960 CERAMIDE RATIO AND MAJOR ADVERSE 5867 04:56:42,960 --> 04:56:44,080 CARDIOVASCULAR EVENTS IT'S A 5868 04:56:44,080 --> 04:56:49,920 HUGE REFINEMENT BROUGHT TO YOU 5869 04:56:49,920 --> 04:56:51,920 CURTSY OF TARGETED METABOLOMICS 5870 04:56:51,920 --> 04:57:01,000 AND NEVER GIVING UP ON THE 5871 04:57:01,000 --> 04:57:01,920 METHODS YOU HAVE AND I'M HAPPY 5872 04:57:01,920 --> 04:57:11,920 TO BE PART OF THIS. 5873 04:57:11,920 --> 04:57:12,800 >> ANYBODY ELSE? 5874 04:57:12,800 --> 04:57:19,640 >> I LOVE THE QUESTION. 5875 04:57:19,640 --> 04:57:21,920 ANOTHER IRISH IN COPD AND MAYBE 5876 04:57:21,920 --> 04:57:26,840 ANY OTHER LUNG DISEASE PEOPLE 5877 04:57:26,840 --> 04:57:29,320 WHO STUDY ONE INDIVIDUAL LUNG 5878 04:57:29,320 --> 04:57:33,000 DISEASE LIKE THE IDEA OF BIOLOGY 5879 04:57:33,000 --> 04:57:36,320 MANY DON'T STUDY THE SAME 5880 04:57:36,320 --> 04:57:38,160 ANATOMICAL STRUCTURE AND SAME 5881 04:57:38,160 --> 04:57:43,360 ALVEOLI AND CELLS IN COPD AND 5882 04:57:43,360 --> 04:57:47,080 SAME IN LUNG CANCER NOT ONLY IN 5883 04:57:47,080 --> 04:57:52,680 TERMS OF CLINICAL STUDIES BUT 5884 04:57:52,680 --> 04:57:55,480 BIOLOGY. 5885 04:57:55,480 --> 04:57:59,120 AND LOOKING HOW THEY'RE SIMILAR 5886 04:57:59,120 --> 04:58:05,840 IN COPD, OR WHAT I BELIEVE AND 5887 04:58:05,840 --> 04:58:10,520 DIFFERENT PATHWAYS AND BIOLOGY. 5888 04:58:10,520 --> 04:58:12,080 IN FACT IT'S LIKE COMPETITION 5889 04:58:12,080 --> 04:58:14,880 FOR THE SAME CELL TYPE AND 5890 04:58:14,880 --> 04:58:15,920 DIVIDING THEM NOT COMPARING OR 5891 04:58:15,920 --> 04:58:17,440 UNDERSTANDING THE PRINCIPLES BUT 5892 04:58:17,440 --> 04:58:21,200 WHAT ARE THE UNIVERSAL KINDS OF 5893 04:58:21,200 --> 04:58:23,000 MECHANISMS OR PATHWAYS WHICH ARE 5894 04:58:23,000 --> 04:58:26,520 OF INTEREST FOR ALL THE 5895 04:58:26,520 --> 04:58:26,840 PATHOLOGISTS. 5896 04:58:26,840 --> 04:58:30,800 THAT MAY HOLD IMPORTANT VALUE 5897 04:58:30,800 --> 04:58:32,800 FOR UNDERSTANDING THE MECHANISM 5898 04:58:32,800 --> 04:58:36,760 LEADING TO DIFFERENT CLINICAL 5899 04:58:36,760 --> 04:58:37,080 FEATURES. 5900 04:58:37,080 --> 04:58:41,160 I THINK HAVING THE INTEGRATED 5901 04:58:41,160 --> 04:58:41,800 APPROACH NOT BY DIVIDING INTO 5902 04:58:41,800 --> 04:58:43,520 DIFFERENT PATHOLOGIES BUT TRYING 5903 04:58:43,520 --> 04:58:45,960 TO INTEGRATE THE KNOWLEDGE IN 5904 04:58:45,960 --> 04:58:49,680 DIFFERENT LUNG DISEASES. 5905 04:58:49,680 --> 04:58:52,040 THAT WOULD BE ONE OF THE 5906 04:58:52,040 --> 04:58:59,120 DIRECTIONS TO FIND AN ANSWER. 5907 04:58:59,120 --> 04:59:09,600 >> AND CAN I SAY SOMETHING, 5908 04:59:16,480 --> 04:59:20,280 WE'RE AN INTIMATE GROUP OF 200 5909 04:59:20,280 --> 04:59:24,080 PEOPLE OR SO, WHAT I'VE SEEN 5910 04:59:24,080 --> 04:59:25,400 OVER THE LAST 20 YEARS IN THE 5911 04:59:25,400 --> 04:59:27,080 FIELD IS THAT THERE'S LESS AND 5912 04:59:27,080 --> 04:59:34,080 LESS INTEREST IN IMMUNOLOGY IN 5913 04:59:34,080 --> 04:59:36,440 PARTICULAR AND THE MOST ADVANCES 5914 04:59:36,440 --> 04:59:40,160 MADE IN TREATMENT OF LUNG CANCER 5915 04:59:40,160 --> 04:59:45,440 IS IMMUNE CHECKPOINT INHIBITORS 5916 04:59:45,440 --> 04:59:47,960 AS A RESULT OF UNDERSTANDING HOW 5917 04:59:47,960 --> 04:59:49,840 IMMUNE CELLS CAN BE HARNESSED IN 5918 04:59:49,840 --> 04:59:54,880 ORDER TO TREAT CANCER. 5919 04:59:54,880 --> 04:59:57,840 SO CAN WE DO REVERSE ENGINEERING 5920 04:59:57,840 --> 05:00:01,080 UNDERSTANDING HOW IMMUNE CELLS 5921 05:00:01,080 --> 05:00:05,760 ARE TRYING TO DO REVERSE 5922 05:00:05,760 --> 05:00:06,080 ENGINEERING. 5923 05:00:06,080 --> 05:00:09,360 WE KNOW CELLS DIE AND THERE IS 5924 05:00:09,360 --> 05:00:12,440 AUTOPHAGY AND ALL KINDS OF 5925 05:00:12,440 --> 05:00:15,400 THINGS AND WHAT I'M NOT HEARING 5926 05:00:15,400 --> 05:00:17,520 IS THAT WE KNOW THERE IS A 5927 05:00:17,520 --> 05:00:20,560 DESTRUCTION OF THE LUNG. 5928 05:00:20,560 --> 05:00:23,720 WE KNOW IT IS SYSTEMIC AND 5929 05:00:23,720 --> 05:00:25,440 CARDIOVASCULAR'S INVOLVED AND 5930 05:00:25,440 --> 05:00:32,560 MULTIPLE ORGANS ARE INVOLVED AND 5931 05:00:32,560 --> 05:00:35,080 WE KNOW THERE'S A SYSTEMIC 5932 05:00:35,080 --> 05:00:37,520 RESPONSE TO CIGARETTE SMOKING 5933 05:00:37,520 --> 05:00:39,760 BUT NOT LOOKING AT THE 800 POUND 5934 05:00:39,760 --> 05:00:41,840 GORILLA IN THE ROOM BECAUSE LESS 5935 05:00:41,840 --> 05:00:43,880 PEOPLE ARE INTERESTED IN 5936 05:00:43,880 --> 05:00:45,080 UNDERSTANDING IMMUNOLOGY OF COPD 5937 05:00:45,080 --> 05:00:48,520 AND MORE INTERESTED IN FINDING 5938 05:00:48,520 --> 05:00:48,800 BIOMARKERS. 5939 05:00:48,800 --> 05:00:50,760 NOT THAT THERE'S ANYTHING LONG 5940 05:00:50,760 --> 05:00:51,880 WITH UNDERSTANDING BIOMARKERS 5941 05:00:51,880 --> 05:00:58,680 NEED TO FUNDAMENTALLY GET TO 5942 05:00:58,680 --> 05:01:01,480 WHAT IS IT THAT AFFECTS OTHER 5943 05:01:01,480 --> 05:01:03,280 SYSTEMIC ORGANS. 5944 05:01:03,280 --> 05:01:07,520 >> I THOUGHT ABOUT WHETHER OR 5945 05:01:07,520 --> 05:01:08,160 NOT SOMETHING LIKE WHAT MARK 5946 05:01:08,160 --> 05:01:10,640 DAVIS HAS BEEN TALKING ABOUT 5947 05:01:10,640 --> 05:01:13,360 ABOUT A SYSTEMS IMMUNOLOGY AND 5948 05:01:13,360 --> 05:01:15,120 SPATIAL IMMUNOLOGY APPROACH 5949 05:01:15,120 --> 05:01:20,200 MIGHT OFFER US MORE TO BE SAID 5950 05:01:20,200 --> 05:01:23,320 THEN JUST SAYING WE MEASURED T 5951 05:01:23,320 --> 05:01:23,520 CELLS. 5952 05:01:23,520 --> 05:01:25,800 THIS GIVES A NICHE -- THE 5953 05:01:25,800 --> 05:01:33,480 SPATIAL NICHE AND AN IDEA OF THE 5954 05:01:33,480 --> 05:01:34,160 SPATIAL OMICS. 5955 05:01:34,160 --> 05:01:36,760 I DON'T KNOW HOW CLOSE THAT IS 5956 05:01:36,760 --> 05:01:38,920 TO REALITY BUT I KNOW THEY'VE 5957 05:01:38,920 --> 05:01:40,720 DONE IT IN OTHER DISEASES. 5958 05:01:40,720 --> 05:01:48,440 >> TO FOLLOW-UP ON THAT I THINK 5959 05:01:48,440 --> 05:01:50,520 WE CAN HAVE MORE DATA TO WHAT 5960 05:01:50,520 --> 05:01:52,080 I'M SAYING. 5961 05:01:52,080 --> 05:01:54,360 EVEN WITHIN THE CD 8 AND 4 5962 05:01:54,360 --> 05:01:55,600 POPULATION THERE'S SO MANY 5963 05:01:55,600 --> 05:01:58,640 SUBSETS OF T CELLS WITHIN THAT 5964 05:01:58,640 --> 05:01:58,960 POPULATION. 5965 05:01:58,960 --> 05:02:04,520 THE SINGLE CELL OMIC STUDIES CAN 5966 05:02:04,520 --> 05:02:07,240 INFORM US AND TELL US WHY 5967 05:02:07,240 --> 05:02:10,760 SOMEONE WHO SMOKES HAVE THEIR 5968 05:02:10,760 --> 05:02:11,600 MUCOSAL IMMUNITY ACT SO 5969 05:02:11,600 --> 05:02:14,360 DIFFERENT FROM THEIR SYSTEMIC 5970 05:02:14,360 --> 05:02:15,640 AND VICE VERSA. 5971 05:02:15,640 --> 05:02:17,560 THEY'RE ALL IMPORTANT QUESTIONS. 5972 05:02:17,560 --> 05:02:20,240 WE CAN'T LOOK AT A CD4 5973 05:02:20,240 --> 05:02:24,160 POPULATION AND SAY THEY'RE ALL 5974 05:02:24,160 --> 05:02:24,320 CD4. 5975 05:02:24,320 --> 05:02:26,640 SAME WITH MACROPHAGES. 5976 05:02:26,640 --> 05:02:28,840 THERE'S SO MANY TYPES THAT REACT 5977 05:02:28,840 --> 05:02:30,120 DIFFERENTLY IN THE LUNG IN 5978 05:02:30,120 --> 05:02:34,480 RESPONSE TO ENVIRONMENTAL 5979 05:02:34,480 --> 05:02:36,640 ANTIGENS AND CALL THEM 5980 05:02:36,640 --> 05:02:36,920 MACROPHAGES. 5981 05:02:36,920 --> 05:02:42,280 UNTIL WE GET INTO SUBSET OF 5982 05:02:42,280 --> 05:02:45,720 CELLS AND UNDERSTAND THE 5983 05:02:45,720 --> 05:02:46,520 INDIVIDUAL CONTRIBUTION I DON'T 5984 05:02:46,520 --> 05:02:49,840 THINK WE'LL UNDERSTAND MUCH 5985 05:02:49,840 --> 05:02:52,560 ABOUT THIS DISEASE PAT 5986 05:02:52,560 --> 05:02:53,480 PATHOPHYSI 5987 05:02:53,480 --> 05:02:53,840 PATHOPHYSIOLOGY. 5988 05:02:53,840 --> 05:02:55,640 >> TO BROADEN ON WHAT YOU SAID, 5989 05:02:55,640 --> 05:03:01,040 WHAT DR. CRAPO SAID THIS MORNING 5990 05:03:01,040 --> 05:03:05,200 I TEND TO AGREE WITH THE 5991 05:03:05,200 --> 05:03:10,360 IMPORTANCE OF FLVRMENT -- 5992 05:03:10,360 --> 05:03:11,960 INFLAMMATION A LOT OF THIS AND 5993 05:03:11,960 --> 05:03:13,240 THE ROOT OF INFLAMMATION IS 5994 05:03:13,240 --> 05:03:16,160 GENERALLY CELLS OF IMMUNE 5995 05:03:16,160 --> 05:03:20,120 SYSTEM. 5996 05:03:20,120 --> 05:03:25,920 I'D ECHO THE SENTIMENT HE HAD. 5997 05:03:25,920 --> 05:03:28,080 >> AND INVOLVING THE TECHNOLOGY 5998 05:03:28,080 --> 05:03:30,360 POSED ABOUT SYSTEMS IMMUNOLOGY 5999 05:03:30,360 --> 05:03:32,000 AND SPATIAL TRANSCRIPTOMICS. 6000 05:03:32,000 --> 05:03:34,120 AS A TRANSLATIONAL PERSON I'M 6001 05:03:34,120 --> 05:03:37,200 THINKING HOW DO YOU SCALE THAT 6002 05:03:37,200 --> 05:03:39,440 UP AND DEPLOY THAT INTO A 6003 05:03:39,440 --> 05:03:43,680 CLINICAL COHORT AND THERE'S A 6004 05:03:43,680 --> 05:03:44,760 RECURRENT THEME ON THE CONVERSE 6005 05:03:44,760 --> 05:03:46,360 AND HOW YOU POTENTIALLY 6006 05:03:46,360 --> 05:03:48,480 INTRODUCE THE TECHNIQUES TO 6007 05:03:48,480 --> 05:03:50,080 BETTER CHARACTERIZE THE PATIENTS 6008 05:03:50,080 --> 05:03:55,280 AND COHORTS AND THE PHENOTYPES 6009 05:03:55,280 --> 05:03:57,520 BASED ON LARGER BIOMARKERS AND 6010 05:03:57,520 --> 05:04:00,000 TRANSLATE THAT TO BETTER MODELS 6011 05:04:00,000 --> 05:04:03,360 CAN BE MADE FOR THE PHENOTYPES 6012 05:04:03,360 --> 05:04:05,480 DEFINED FOR OUTCOME TRAJECTORIES 6013 05:04:05,480 --> 05:04:07,080 AND THERE'S DISCUSSION WITH 6014 05:04:07,080 --> 05:04:11,600 FERNANDO AND OTHERS ABOUT HOW TO 6015 05:04:11,600 --> 05:04:13,280 TAKE THAT INFORMATION. 6016 05:04:13,280 --> 05:04:20,320 DO WE NEED TO DEFINE IMMUNOLOGIC 6017 05:04:20,320 --> 05:04:22,200 DATA OR GENE EXPRESSION DATA TO 6018 05:04:22,200 --> 05:04:27,680 BETTER HONE IN ON POSSIBLE 6019 05:04:27,680 --> 05:04:29,960 MECHANISMS THAT SMARTER THAN ME 6020 05:04:29,960 --> 05:04:31,440 CAN DEVELOP. 6021 05:04:31,440 --> 05:04:37,320 HOW DO WE ACTUATE THE 6022 05:04:37,320 --> 05:04:38,240 IMPROVEME 6023 05:04:38,240 --> 05:04:40,920 IMPROVEMENTS AND TAKE CLINICAL 6024 05:04:40,920 --> 05:04:42,120 FINDINGS AND MARRY IT. 6025 05:04:42,120 --> 05:04:44,120 >> I'LL SAY I THINK WE'RE IN THE 6026 05:04:44,120 --> 05:04:46,440 WALKING STAGE OF THIS RIGHT NOW. 6027 05:04:46,440 --> 05:04:52,240 WE'RE NOT QUITE AT THE RUNNING 6028 05:04:52,240 --> 05:04:52,640 STAGE. 6029 05:04:52,640 --> 05:04:55,880 BUT I DO LIKE THAT WE'RE 6030 05:04:55,880 --> 05:05:00,160 STARTING TO WALK. 6031 05:05:00,160 --> 05:05:01,520 THAT'S AT LEAST SOMETHING TO BE 6032 05:05:01,520 --> 05:05:02,160 SAID FOR THAT. 6033 05:05:02,160 --> 05:05:12,880 I WANT TO HEAR FROM YOU AS WELL. 6034 05:05:12,880 --> 05:05:16,560 >> IN RESPONSE TO FARRAH ANOTHER 6035 05:05:16,560 --> 05:05:18,720 LEVEL OF COMPARTMENTIZATION AND 6036 05:05:18,720 --> 05:05:22,840 PEOPLE IN RESPONSES OF 6037 05:05:22,840 --> 05:05:28,360 INFLAMMATION BARELY ATTACH THEIR 6038 05:05:28,360 --> 05:05:33,880 LEVEL OF WHAT A PARTICULAR CELL 6039 05:05:33,880 --> 05:05:39,520 TYPES WITHIN THE DISEASE 6040 05:05:39,520 --> 05:05:40,360 PATHOLOGICAL REGION WITH THE 6041 05:05:40,360 --> 05:05:47,520 IMMUNE SIGNALS. 6042 05:05:47,520 --> 05:05:50,000 THOSE STUDIES ARE NEEDED FOR 6043 05:05:50,000 --> 05:05:51,600 HUGE AMOUNT OF INFORMATION WE 6044 05:05:51,600 --> 05:05:52,240 KNOW ABOUT INFLAMMATORY AND 6045 05:05:52,240 --> 05:05:54,440 IMMUNITY AND LINK IT TO THOSE 6046 05:05:54,440 --> 05:05:58,680 SPECIFIC PATHOLOGICAL CHANGES 6047 05:05:58,680 --> 05:06:01,040 AND STRUCTURAL AND EPITHELIAL 6048 05:06:01,040 --> 05:06:03,160 CELLS AND STROMAL CELLS AND 6049 05:06:03,160 --> 05:06:04,480 FIBROBLASTS AND SO ON AND SEE 6050 05:06:04,480 --> 05:06:09,520 HOW THE DIFFERENT CELL TYPES 6051 05:06:09,520 --> 05:06:19,640 XHBLTH 6052 05:06:48,800 --> 05:06:51,520 >> I MISSED PART OF THE 6053 05:06:51,520 --> 05:06:51,800 DISCUSSION. 6054 05:06:51,800 --> 05:06:52,960 THE ADVANTAGE OF BEING REMOTE 6055 05:06:52,960 --> 05:06:55,360 AND I GOT A CALL FOR A PATIENT. 6056 05:06:55,360 --> 05:06:57,400 WHAT I'M HEARING I LIKE VERY 6057 05:06:57,400 --> 05:06:58,520 MUCH WHAT I'M HEARING. 6058 05:06:58,520 --> 05:06:59,800 BUT I THINK WHAT YVONNE IS 6059 05:06:59,800 --> 05:07:08,920 SAYING IS QUITE IMPORTANT. 6060 05:07:08,920 --> 05:07:10,240 WE HAVE TO TRY TO TAKE ADVANTAGE 6061 05:07:10,240 --> 05:07:12,680 OF THE LARGE COHORT AND AGAIN 6062 05:07:12,680 --> 05:07:17,880 NOT TO SAY EVERYTHING HAS TO BE 6063 05:07:17,880 --> 05:07:24,400 DONE WAS WORK HAS TO BE DONE IN 6064 05:07:24,400 --> 05:07:25,920 VITRO, IN VIVO, I DON'T THINK 6065 05:07:25,920 --> 05:07:27,200 WE'RE TAKING FULL ADVANTAGE OF 6066 05:07:27,200 --> 05:07:29,320 THE POTENTIAL WE HAVE HERE. 6067 05:07:29,320 --> 05:07:30,600 AND SOME OF THESE THERE'S MANY 6068 05:07:30,600 --> 05:07:34,440 FROM WHAT WE HEARD THIS MORNING 6069 05:07:34,440 --> 05:07:41,920 THAT ARE TO A CERTAIN LEVEL 6070 05:07:41,920 --> 05:07:45,400 MAT 6071 05:07:45,400 --> 05:07:45,920 MATURE AND THERE'S BEEN 6072 05:07:45,920 --> 05:07:46,440 CHARACTERIZED QUITE A BIT. 6073 05:07:46,440 --> 05:07:47,080 THAT MAY STILL REQUIRE THE FIRST 6074 05:07:47,080 --> 05:07:48,760 QUESTION WE HAVE TO ASK 6075 05:07:48,760 --> 05:07:54,120 OURSELVES IS WHAT CAN WE DO WITH 6076 05:07:54,120 --> 05:07:58,520 WHAT WE HAVE BECAUSE WITH YOU 6077 05:07:58,520 --> 05:08:00,800 MAY NOT HAVE THE RIGHT BIO 6078 05:08:00,800 --> 05:08:03,000 SPECIMEN AND OFTEN THE TISSUE IS 6079 05:08:03,000 --> 05:08:08,080 MISSING EXCEPT FOR BLOOD AND 6080 05:08:08,080 --> 05:08:17,040 SOMETIMES BRONCHOSCOPY WITH 6081 05:08:17,040 --> 05:08:19,720 LAVAGE BUT WE CANNOT ADD THROUGH 6082 05:08:19,720 --> 05:08:22,120 ANCILLARY STUDY BECAUSE IN MANY 6083 05:08:22,120 --> 05:08:24,480 COHORT WE WOULD HAVE THE 6084 05:08:24,480 --> 05:08:29,680 POSSIBILITY OF DOING ADDITIONAL 6085 05:08:29,680 --> 05:08:34,480 MESH URASUREMENT AND THE MORE 6086 05:08:34,480 --> 05:08:36,040 COMPLICATED BUT I'D START WITH 6087 05:08:36,040 --> 05:08:37,720 ASKING MYSELF WITH WHAT CAN WE 6088 05:08:37,720 --> 05:08:42,960 DO WITH WHAT WE HAVE BETTER AND 6089 05:08:42,960 --> 05:08:45,840 WITH YOUR EXPERTISE AND ANYONE 6090 05:08:45,840 --> 05:08:47,840 WHO DOES OUTCOME RESEARCH LIKE 6091 05:08:47,840 --> 05:08:50,080 MYSELF AND IF THERE IS ANY 6092 05:08:50,080 --> 05:08:51,840 ADDITIONAL NEED AND HOW CAN WE 6093 05:08:51,840 --> 05:08:57,400 WORK THAT TOGETHER THAT THERE IS 6094 05:08:57,400 --> 05:09:00,560 PLACE FOR ANCILLARY STUDY WHERE 6095 05:09:00,560 --> 05:09:03,360 IN THE SAMPLE OF OUR COHORT WE 6096 05:09:03,360 --> 05:09:04,520 CAN BUILD A SUBPROJECT THAT 6097 05:09:04,520 --> 05:09:07,080 WOULD ALLOW US TO MOVE AHEAD? 6098 05:09:07,080 --> 05:09:11,800 I THINK THE PROBLEM IN COPD AS 6099 05:09:11,800 --> 05:09:12,920 LUNG WE CAN'T DEVELOP THE 6100 05:09:12,920 --> 05:09:14,520 UNDERSTANDING OF THE MECHANISTIC 6101 05:09:14,520 --> 05:09:15,880 POINT OF VIEW. 6102 05:09:15,880 --> 05:09:20,160 IT'S GOING TO BE VERY DIFFICULT 6103 05:09:20,160 --> 05:09:23,440 TO HAVE NEW TARGETS FOR NEW 6104 05:09:23,440 --> 05:09:25,360 TREATMENT AND WE'RE TALKING 6105 05:09:25,360 --> 05:09:27,320 TREATABLE BUT IT'S VERY MUCH 6106 05:09:27,320 --> 05:09:30,760 CLINICAL AND/OR A BASE TO 6107 05:09:30,760 --> 05:09:31,840 LIMITED UNDERSTANDING WE HAVE 6108 05:09:31,840 --> 05:09:37,560 SOME TIME BY ACCIDENT AND THE T2 6109 05:09:37,560 --> 05:09:39,120 INFLAMMATORY PROCESS BEEN 6110 05:09:39,120 --> 05:09:44,080 DISCOVERED MORE LATELY AND THE 6111 05:09:44,080 --> 05:09:47,080 BIOLOGICAL ITL5 ARE NOT COMING 6112 05:09:47,080 --> 05:09:49,800 FROM A GOOD UNDERSTANDING OF 6113 05:09:49,800 --> 05:09:51,800 MECHANISM IN THE FIRST PLACE. 6114 05:09:51,800 --> 05:09:54,720 NOW WE'RE KIND OF GOING 6115 05:09:54,720 --> 05:09:57,080 BACKWARDS AND SAME IMMUNOLOGY 6116 05:09:57,080 --> 05:09:58,760 AND WHAT FARRAH WAS PROPOSING 6117 05:09:58,760 --> 05:10:03,000 THAT SEEMS TO ME VERY APPEALING. 6118 05:10:03,000 --> 05:10:07,120 HOW CAN WE THAT BETTER WITH WHAT 6119 05:10:07,120 --> 05:10:12,600 WE HAVE RIGHT NOW. 6120 05:10:12,600 --> 05:10:15,880 >> ANY ADDITIONAL COMMENTS? 6121 05:10:15,880 --> 05:10:24,240 I THINK THAT WAS A THOUGHTFUL 6122 05:10:24,240 --> 05:10:27,080 STATEMENT BY DR. BOURBEAU. 6123 05:10:27,080 --> 05:10:27,920 ONE THING THAT'S IMPORTANT AND 6124 05:10:27,920 --> 05:10:30,920 GOES BACK TO OUR DISCUSSIONS 6125 05:10:30,920 --> 05:10:39,320 FROM EARLIER TODAY, I THINK 6126 05:10:39,320 --> 05:10:41,080 THERE'S GREAT INTEREST FROM 6127 05:10:41,080 --> 05:10:42,680 INVESTIGATORS TO USE THE SAMPLE 6128 05:10:42,680 --> 05:10:48,600 GIVEN AND THE KEY IS TO TAKE THE 6129 05:10:48,600 --> 05:10:51,360 SAMPLES AND UTILIZE THEM TO NEW 6130 05:10:51,360 --> 05:10:54,520 TECHNOLOGIES OR AS AN EXAMPLE, 6131 05:10:54,520 --> 05:10:56,040 LUNG BIOPSIES THAT MAY BE STORED 6132 05:10:56,040 --> 05:11:03,120 FOR A CERTAINLY COHORT FOR 6133 05:11:03,120 --> 05:11:03,560 SPATIAL. 6134 05:11:03,560 --> 05:11:05,240 IT'S IMPORTANT AND THE MORE 6135 05:11:05,240 --> 05:11:07,480 BASIC SCIENTISTS MAY NOT KNOW 6136 05:11:07,480 --> 05:11:11,520 IT'S FROM A TERTIARY OR DISTAL 6137 05:11:11,520 --> 05:11:15,520 AIRWAY OR AREA WITH HIGH 6138 05:11:15,520 --> 05:11:15,800 EMPHYSEMA. 6139 05:11:15,800 --> 05:11:17,280 IT'S VERY IMPORTANT THAT 6140 05:11:17,280 --> 05:11:22,640 COMMUNICATION IS MADE, THE 6141 05:11:22,640 --> 05:11:24,200 HANDOFF IS MADE. 6142 05:11:24,200 --> 05:11:26,040 THE CLINICAL IMPLICATIONS ARE 6143 05:11:26,040 --> 05:11:27,600 MORE CLEAR. 6144 05:11:27,600 --> 05:11:28,320 TO SAY AGAIN IT'S A 6145 05:11:28,320 --> 05:11:30,160 COMMUNICATION THING. 6146 05:11:30,160 --> 05:11:33,000 I DON'T THINK WE ALL ANTICIPATE 6147 05:11:33,000 --> 05:11:36,560 WE'LL GET A WHOLE BANK OF 6148 05:11:36,560 --> 05:11:37,800 SAMPLES. 6149 05:11:37,800 --> 05:11:38,640 MAYBE THAT. 6150 05:11:38,640 --> 05:11:41,320 THAT'S WHAT A THOUGHT COULD BE 6151 05:11:41,320 --> 05:11:42,720 AS WELL. 6152 05:11:42,720 --> 05:11:44,520 >> I'M NOT SURE AND IT'S WHAT I 6153 05:11:44,520 --> 05:11:45,320 WAS TRYING TO SAY. 6154 05:11:45,320 --> 05:11:50,760 HOW CAN WE LINK THIS BETTER 6155 05:11:50,760 --> 05:11:53,400 BECAUSE THERE'S A GROUP DOING 6156 05:11:53,400 --> 05:11:58,600 QUITE WELL IN CHARACTERIZING IT 6157 05:11:58,600 --> 05:12:00,560 AND AT THE SAME TIME THREES 6158 05:12:00,560 --> 05:12:02,040 ANOTHER GROUP THAT HAS THE 6159 05:12:02,040 --> 05:12:06,840 EXPERTISE IS AND SOME TECHNOLOGY 6160 05:12:06,840 --> 05:12:08,240 THAT COULD BE USED HOW DO WE PUT 6161 05:12:08,240 --> 05:12:09,200 THAT TOGETHER. 6162 05:12:09,200 --> 05:12:14,800 I WAS LISTENING EARLIER ON. 6163 05:12:14,800 --> 05:12:19,200 WE HAVE AN OUR QUESTIONNAIRE AND 6164 05:12:19,200 --> 05:12:21,280 THE FORMATION HAD NOT BEENIZED 6165 05:12:21,280 --> 05:12:26,000 AT ALL. 6166 05:12:26,000 --> 05:12:29,000 IT WAS GOOD THERE WAS GOOD 6167 05:12:29,000 --> 05:12:30,880 INTENTION AND HYPOTHESIS WHEN WE 6168 05:12:30,880 --> 05:12:33,440 STARTED THE COHORT BUT HOW CAN 6169 05:12:33,440 --> 05:12:37,120 WE PUT THAT TO BETTER USE IN 6170 05:12:37,120 --> 05:12:38,680 LIGHT OF YOUR PRESENTATION AND 6171 05:12:38,680 --> 05:12:40,720 SOME OTHER MEASUREMENT AND CAN 6172 05:12:40,720 --> 05:12:46,720 WE SEE AND BE ABLE TO TEST AND 6173 05:12:46,720 --> 05:12:48,320 WE'LL BE ABLE TO SEE OVER 12 6174 05:12:48,320 --> 05:12:50,520 YEARS AND A CHANGE IN COPD. 6175 05:12:50,520 --> 05:12:53,720 THIS IS THE KIND OF THING THAT 6176 05:12:53,720 --> 05:12:55,760 JOINING THOSE TOGETHER WOULD 6177 05:12:55,760 --> 05:13:05,400 ALLOW US TO VALIDATE SOME OF 6178 05:13:05,400 --> 05:13:06,800 THESE HYPOTHESIS. 6179 05:13:06,800 --> 05:13:17,240 >> CAN I RESPOND TO THAT? 6180 05:13:21,040 --> 05:13:24,720 WE WAN GUT, LUNG, BLOOD SAMPLES 6181 05:13:24,720 --> 05:13:26,760 BUT IF IT'S NOT POSSIBLE YOU 6182 05:13:26,760 --> 05:13:29,240 WILL STILL BE ABLE TO DO 6183 05:13:29,240 --> 05:13:34,520 METABOLOMICS ON BLOOD SAMPLES 6184 05:13:34,520 --> 05:13:36,920 COLLECTED AND LINK THE 6185 05:13:36,920 --> 05:13:39,440 QUESTIONNAIRES AND BE ABLE TO 6186 05:13:39,440 --> 05:13:40,640 IDENTIFY FOR EXAMPLE HOW MUCH 6187 05:13:40,640 --> 05:13:45,680 FIBER PEOPLE WERE EATING AND 6188 05:13:45,680 --> 05:13:49,080 THEN MATCH THAT TO METABOLOMICS 6189 05:13:49,080 --> 05:13:55,120 AND DISEASE FEATURES. 6190 05:13:55,120 --> 05:13:56,920 IF YOU HAVE SAMPLES FOR 6191 05:13:56,920 --> 05:13:58,320 MICROBIOMES THERE'S MORE POWER 6192 05:13:58,320 --> 05:14:03,400 TO THE SAMPLES YOU'VE ALREADY 6193 05:14:03,400 --> 05:14:03,560 GOT. 6194 05:14:03,560 --> 05:14:04,400 YOU'RE RIGHT THERE'S A LOT OF 6195 05:14:04,400 --> 05:14:06,440 THINGS WE CAN DO WITH SAMPLES 6196 05:14:06,440 --> 05:14:08,040 ALREADY COLLECTED AND DATA 6197 05:14:08,040 --> 05:14:09,200 ALREADY COLLECTED. 6198 05:14:09,200 --> 05:14:11,880 THAT'S BEEN A MASSIVE EFFORT BY 6199 05:14:11,880 --> 05:14:15,400 PEOPLE. 6200 05:14:15,400 --> 05:14:15,840 >> 6201 05:14:15,840 --> 05:14:20,480 >> WE'VE BEEN TALKING AND HAVE 6202 05:14:20,480 --> 05:14:22,640 GOT SAMPLE AND BLOOD SAMPLES. 6203 05:14:22,640 --> 05:14:26,680 ANOTHER WAY TO ADD ON TO THAT IS 6204 05:14:26,680 --> 05:14:35,480 LEVERAGING OTHER COHORTS FOR 6205 05:14:35,480 --> 05:14:35,760 VALIDATION. 6206 05:14:35,760 --> 05:14:44,600 IF JEAN HAS METABOLOMICS AND 6207 05:14:44,600 --> 05:14:47,320 VALIDATE AND THERE WAS A 6208 05:14:47,320 --> 05:14:52,920 QUESTION A WHILE BACK I WANTED 6209 05:14:52,920 --> 05:14:57,640 TO BRING FORWARD AND IT HAS TO 6210 05:14:57,640 --> 05:15:01,840 DO INCREASING SAMPLE SIZE OF 6211 05:15:01,840 --> 05:15:08,400 HUNDREDS TO THOUSANDS OF 6212 05:15:08,400 --> 05:15:10,440 OBSERVATIONS AND WE HEAR ABOUT 6213 05:15:10,440 --> 05:15:14,320 THE LIMITATIONS OF SINGLE-CELL 6214 05:15:14,320 --> 05:15:17,800 DATA AT THE MOMENT AND NF3 OR 10 6215 05:15:17,800 --> 05:15:22,040 AND I WANT TO BRING THAT 6216 05:15:22,040 --> 05:15:23,880 QUESTION FORWARD AND HEAR THE 6217 05:15:23,880 --> 05:15:34,400 THOUGHTS FROM THE PANEL HERE. 6218 05:15:35,520 --> 05:15:37,040 IS IT POSSIBLE DO SINGLE CELL 6219 05:15:37,040 --> 05:15:39,400 OVER A POPULATION AND WOULD THAT 6220 05:15:39,400 --> 05:15:43,120 BE USEFUL WOULD WE UNCOVER OTHER 6221 05:15:43,120 --> 05:15:43,920 HETEROGENEITY AND MECHANISMS 6222 05:15:43,920 --> 05:15:47,840 BEYOND WHAT WE SEE FROM THE 6223 05:15:47,840 --> 05:15:49,920 HANDFULS OF LUNG TISSUE AND FEEL 6224 05:15:49,920 --> 05:15:51,000 FREE TO CHIME IN. 6225 05:15:51,000 --> 05:15:52,400 I KNOW YOU'VE DONE WORK IN THE 6226 05:15:52,400 --> 05:15:53,080 SPACE AS WELL. 6227 05:15:53,080 --> 05:15:55,240 >> IT'S POSSIBLE, HE SAYS. 6228 05:15:55,240 --> 05:15:56,960 NOT SURE IF IT'S USEFUL YET. 6229 05:15:56,960 --> 05:15:59,160 >> ADDS WE MOVE FORWARD THAT'S 6230 05:15:59,160 --> 05:16:02,520 GOING TO BE VALUABLE. 6231 05:16:02,520 --> 05:16:04,920 AND THE MORE WE GET THE MORE 6232 05:16:04,920 --> 05:16:15,360 POWERFUL THE DATA BECOMES. 6233 05:16:16,200 --> 05:16:21,880 >> IT'S IMPORTANT FOR PEOPLE TO 6234 05:16:21,880 --> 05:16:26,720 REALIZE THAT SAMPLING OF A WELL 6235 05:16:26,720 --> 05:16:27,800 PHENOTYPED COHORT DOESN'T HAVE 6236 05:16:27,800 --> 05:16:34,520 TO BE THE ENTIRE SAMPLE. 6237 05:16:34,520 --> 05:16:37,560 LIKE WITH FLOW CYTOMETRY WITHIN 6238 05:16:37,560 --> 05:16:43,200 MINUTES WE CAN TELL WHAT'S GOING 6239 05:16:43,200 --> 05:16:43,640 ON. 6240 05:16:43,640 --> 05:16:46,240 WE SAY FOR AN EXTRA MINUTE TO DO 6241 05:16:46,240 --> 05:16:48,000 100,000 BUT YOU DON'T NEED 6242 05:16:48,000 --> 05:16:49,480 100,000 OR 10,000 YOU CAN DO 6243 05:16:49,480 --> 05:16:51,920 WHAT IS COMMONLY DONE IS EXTREME 6244 05:16:51,920 --> 05:16:53,000 PHENOTYPING. 6245 05:16:53,000 --> 05:16:55,440 YOU TAKE A COHORT WITH AN 6246 05:16:55,440 --> 05:16:59,880 EXTREME PHENOTYPE AND TRY TO 6247 05:16:59,880 --> 05:17:01,640 LEVERAGE ONE AGAINST THE OTHER 6248 05:17:01,640 --> 05:17:03,640 AND DECIPHER WHAT IS ABOUT ONE 6249 05:17:03,640 --> 05:17:06,200 PHENOTYPE STARTING AT AGE 40 AND 6250 05:17:06,200 --> 05:17:08,840 START GOING DOWN THE SLIPPERY 6251 05:17:08,840 --> 05:17:12,320 PATH OF DEVELOPING LATE-STAGE 6252 05:17:12,320 --> 05:17:14,720 EMPHYSEMA VERSUS SOMEONE WHO 6253 05:17:14,720 --> 05:17:19,320 BARELY GETS EMPHYSEMA AND LIVES 6254 05:17:19,320 --> 05:17:21,920 FOR 100 YEARS AND THERE'S THINGS 6255 05:17:21,920 --> 05:17:24,480 THAT CAN BE DONE AND DOESN'T 6256 05:17:24,480 --> 05:17:25,360 HAVE TO BE DIDN'T ON EVERY 6257 05:17:25,360 --> 05:17:25,920 SINGLE ONE. 6258 05:17:25,920 --> 05:17:27,720 IF YOU HAVE A GENEROUS COHORT 6259 05:17:27,720 --> 05:17:31,120 YOU CAN IDENTIFY THE EXTREME AND 6260 05:17:31,120 --> 05:17:41,320 STUDY THOSE. 6261 05:17:41,640 --> 05:17:43,640 >> I'D LIKE TO ADVOCATE FOR THE 6262 05:17:43,640 --> 05:17:47,160 NUMBER OF SINGLE-CELL STUDIES 6263 05:17:47,160 --> 05:17:50,200 AND YOU CAN LOOK AT THE OMIC 6264 05:17:50,200 --> 05:17:51,000 DETERMINATES OF SING OF SINGLE 6265 05:17:51,000 --> 05:17:55,160 CELL PARAMETERS YOU CONDITAN'T 6266 05:17:55,160 --> 05:17:56,360 FROM CELLS IF A FEW PEOPLE. 6267 05:17:56,360 --> 05:18:00,120 IF YOU CAN DO A CELL-BASED MOUSE 6268 05:18:00,120 --> 05:18:02,600 STUDY IN THE LAB WOULD HAVE 6269 05:18:02,600 --> 05:18:07,680 HUNDREDS OF OBSERVATIONS CHANGE 6270 05:18:07,680 --> 05:18:11,440 YOUR APPROACH? 6271 05:18:11,440 --> 05:18:15,760 THEY WERE LOOKING AT 6272 05:18:15,760 --> 05:18:17,800 REPRODUCIBILITY OF STUDIES AND 6273 05:18:17,800 --> 05:18:19,600 HOW MUCH IT IMPROVED OF THE 6274 05:18:19,600 --> 05:18:21,760 SAMPLE SIZE AND YOU HAD A LOT OF 6275 05:18:21,760 --> 05:18:26,960 FALSE POSITIVES AND YOU HAD A 6276 05:18:26,960 --> 05:18:28,360 POINT WHERE YOU PROBABLY AREN'T 6277 05:18:28,360 --> 05:18:30,240 GETTING MORE. 6278 05:18:30,240 --> 05:18:33,080 IS THERE SOMETHING FROM THE 6279 05:18:33,080 --> 05:18:35,880 HETEROGENEITY OF THE STUDIES YOU 6280 05:18:35,880 --> 05:18:44,880 CAN LEARN FROM? 6281 05:18:44,880 --> 05:18:48,200 >> AN ISSUE IS THE MICE ARE 6282 05:18:48,200 --> 05:18:51,080 INBRED MICE AND SUM LAR AND ONE 6283 05:18:51,080 --> 05:18:54,120 OF THE ISSUES HAS ALWAYS BEEN 6284 05:18:54,120 --> 05:18:57,600 HOW REPRESENTATIVE ARE THE 6285 05:18:57,600 --> 05:19:00,080 ANIMAL MODELS BUT MICE 6286 05:19:00,080 --> 05:19:03,080 THEMSELVES AND THERE'S BEEN 6287 05:19:03,080 --> 05:19:07,840 INTEREST IN MODELS OF OUT BRED 6288 05:19:07,840 --> 05:19:14,240 MICE AND SEE IF YOU GET A MORE 6289 05:19:14,240 --> 05:19:16,160 REPRESENTATIVE PHENOTYPE FOR THE 6290 05:19:16,160 --> 05:19:18,080 MODEL WITH AN OUTBRED MICE THAN 6291 05:19:18,080 --> 05:19:19,520 VARIATION YOU SEE IN HUMANS. 6292 05:19:19,520 --> 05:19:21,800 I'M NOT IN EXPERT IN THAT SPACE. 6293 05:19:21,800 --> 05:19:24,920 I JUST KNOW THE MODELS 6294 05:19:24,920 --> 05:19:26,320 THEMSELVES AND REPEATING A 6295 05:19:26,320 --> 05:19:28,720 THOUSAND MEASUREMENTS ON A MODEL 6296 05:19:28,720 --> 05:19:30,800 THAT DOESN'T REALLY CAPITULATE 6297 05:19:30,800 --> 05:19:32,560 THE DISEASE YOU THINK IS 6298 05:19:32,560 --> 05:19:36,040 IMPORTANT MAY NOT BE SUPER 6299 05:19:36,040 --> 05:19:37,760 HELPFUL BUT IF IT'S CAPITULATING 6300 05:19:37,760 --> 05:19:43,080 A PART OF A DISEASE YOU THINK IS 6301 05:19:43,080 --> 05:19:44,880 VERY IMPORTANT THEN IT MAY BE 6302 05:19:44,880 --> 05:19:46,320 HELPFUL TO HAVE MORE 6303 05:19:46,320 --> 05:19:46,640 OBSERVATION. 6304 05:19:46,640 --> 05:19:49,080 I'LL LEAVE IT AT THAT AS A BROAD 6305 05:19:49,080 --> 05:19:51,880 STATEMENT BUT WOULD LOVE OTHER 6306 05:19:51,880 --> 05:20:02,200 PEOPLE TO COMMENT. 6307 05:20:08,080 --> 05:20:10,120 >> I THINK ON FOCUSSING 6308 05:20:10,120 --> 05:20:11,560 HETEROGENEITY IS IMPORTANT FOR 6309 05:20:11,560 --> 05:20:19,600 COPD AND ANY KIND OF DISEASE. 6310 05:20:19,600 --> 05:20:22,760 AND WHAT IS COMMON FOR ALL 6311 05:20:22,760 --> 05:20:23,600 PATIENTS IN COPD AND BY 6312 05:20:23,600 --> 05:20:28,320 COMPARING FEWER SAMPLES FROM 6313 05:20:28,320 --> 05:20:30,400 PATIENTS TO THOSE WHO DON'T HAVE 6314 05:20:30,400 --> 05:20:32,520 DISEASE, WHAT ARE THOSE 6315 05:20:32,520 --> 05:20:37,920 UNIVERSAL FEATURES WE CAN 6316 05:20:37,920 --> 05:20:38,520 CAPTURE? 6317 05:20:38,520 --> 05:20:42,760 I THINK YOU GUIDE THE PRINCIPLE 6318 05:20:42,760 --> 05:20:46,040 FEATURES WHICH CAN BE DETECTED 6319 05:20:46,040 --> 05:20:48,560 AND THEN MAYBE USED AS A BASIS 6320 05:20:48,560 --> 05:20:50,200 FOR NEXT-LEVEL STUDIES FOCUSSING 6321 05:20:50,200 --> 05:20:58,840 ON HETEROGENEITY. 6322 05:20:58,840 --> 05:21:01,520 DO YOU HEAR ME? 6323 05:21:01,520 --> 05:21:02,120 >> YES. 6324 05:21:02,120 --> 05:21:03,200 >> AND CREATING DIFFERENT TYPES 6325 05:21:03,200 --> 05:21:06,280 OF SAMPLES FROM TRE SAME PATIENT 6326 05:21:06,280 --> 05:21:11,920 IN WHICH WE DON'T NEED TOO MANY 6327 05:21:11,920 --> 05:21:14,600 DIFFERENT SAMPLES BUT AND WHAT 6328 05:21:14,600 --> 05:21:16,760 WE SEE IN TERMS OF PHYSIOLOGY OR 6329 05:21:16,760 --> 05:21:18,960 BLOOD OR BLOOD FUNCTION OR OTHER 6330 05:21:18,960 --> 05:21:19,360 PARAMETERS. 6331 05:21:19,360 --> 05:21:22,320 IT MAY BE IMPORTANT IN DEALING 6332 05:21:22,320 --> 05:21:24,200 WITH HETEROGENEITY AND THERE'S 6333 05:21:24,200 --> 05:21:26,800 ONE OR TWO SAMPLES WHICH CAN 6334 05:21:26,800 --> 05:21:29,440 GIVE INTERESTING DATA BUT DON'T 6335 05:21:29,440 --> 05:21:31,440 GO TO THE GROUP WHICH CAN GIVE 6336 05:21:31,440 --> 05:21:33,880 STATISTICS AND PHENOTYPES YOU 6337 05:21:33,880 --> 05:21:34,640 MAY NOT ABLE TO CAPTURE 6338 05:21:34,640 --> 05:21:42,200 STATISTICALLY. 6339 05:21:42,200 --> 05:21:47,880 >> I AGREE. 6340 05:21:47,880 --> 05:21:52,960 I CONCUR AND AGREE WITH ED'S 6341 05:21:52,960 --> 05:21:54,320 COMMENT AND WHEN IS A CONFIDENCE 6342 05:21:54,320 --> 05:21:57,400 LEVEL GOOD ENOUGH TO PURSUE A 6343 05:21:57,400 --> 05:21:58,200 CERTAIN TARGET OR CERTAIN 6344 05:21:58,200 --> 05:22:03,640 MECHANISM. 6345 05:22:03,640 --> 05:22:06,160 THAT GOES FOR ANY SAMPLES, IN 6346 05:22:06,160 --> 05:22:07,560 MICE, IN PRIMARY CELLS FROM 6347 05:22:07,560 --> 05:22:12,000 DIFFERENT DONORS, ETCETERA. 6348 05:22:12,000 --> 05:22:16,720 AND I THINK I'VE BEEN EXCITED TO 6349 05:22:16,720 --> 05:22:21,440 LEARN ABOUT NEW METHODOLOGY TO 6350 05:22:21,440 --> 05:22:27,200 SCALE UP REDUCE COST AND SOME 6351 05:22:27,200 --> 05:22:29,320 EXPERIMENTS WE DO AND TAG EACH 6352 05:22:29,320 --> 05:22:31,120 CELL AND SAMPLE. 6353 05:22:31,120 --> 05:22:36,800 USING THE TECHNOLOGY FOR SINGLE 6354 05:22:36,800 --> 05:22:42,640 CELL RNA SEQ FOR SCALING UP 6355 05:22:42,640 --> 05:22:44,960 HOMOGENOUS POPULATIONS AN 6356 05:22:44,960 --> 05:22:46,640 REPRODUCIBILITY AND WHAT'S 6357 05:22:46,640 --> 05:22:50,200 ADAPTIVE AND WHAT MAY NOT BE 6358 05:22:50,200 --> 05:22:50,480 ADAPTIVE. 6359 05:22:50,480 --> 05:22:52,200 I WILL LOOK AT THE REFERENCE I'M 6360 05:22:52,200 --> 05:22:55,120 TALKING ABOUT AND PUT IT IN THE 6361 05:22:55,120 --> 05:23:04,520 CHAT SHORTLY. 6362 05:23:04,520 --> 05:23:06,360 >> WE'RE COMING UP TO THE END OF 6363 05:23:06,360 --> 05:23:06,840 THE HOUR. 6364 05:23:06,840 --> 05:23:08,640 ANY FINAL QUESTIONS OR POINTS 6365 05:23:08,640 --> 05:23:11,440 ANY OF THE SPEAKERS WOULD LIKE 6366 05:23:11,440 --> 05:23:13,480 TO MAKE IN TERM OF ANYTHING YOU 6367 05:23:13,480 --> 05:23:19,080 WANT TO ADD ON TO TO FROM THIS 6368 05:23:19,080 --> 05:23:24,360 VERY ROBUST DISCUSSION. 6369 05:23:24,360 --> 05:23:27,480 IT'S BEEN WONDERFUL. 6370 05:23:27,480 --> 05:23:30,760 AND I THINK MORE CREATIVELY ON 6371 05:23:30,760 --> 05:23:32,800 MORE THOUGHTFUL STUDY SECTIONS 6372 05:23:32,800 --> 05:23:34,440 WHICH INCLUDE PEOPLE INTERESTED 6373 05:23:34,440 --> 05:23:39,320 IN HUMANS AND INTERESTED IN 6374 05:23:39,320 --> 05:23:42,800 DISEASE NOT ONLY MOUSE BUT 6375 05:23:42,800 --> 05:23:45,800 BIOLOGISTS INTERESTED IN 6376 05:23:45,800 --> 05:23:48,280 UNDERSTANDING DISEASE IN HUMAN 6377 05:23:48,280 --> 05:23:58,080 MODELS WHICH MAY NOT BE ONE 6378 05:23:58,080 --> 05:24:03,880 HYPOTHESIS BUT A BIGGER SCOPE 6379 05:24:03,880 --> 05:24:08,320 APPROACH AND PRODUCING HIGH BOTH 6380 05:24:08,320 --> 05:24:09,840 SIS FOR THE FIELD. 6381 05:24:09,840 --> 05:24:12,800 -- HYPOTHESIS FOR THE FIELD. 6382 05:24:12,800 --> 05:24:15,440 >> SOMETHING THAT COULD CAPTURE 6383 05:24:15,440 --> 05:24:18,480 A LOT OF WHAT WE'VE BEEN TALKING 6384 05:24:18,480 --> 05:24:21,160 ABOUT IS INTEGRATING PEOPLE WITH 6385 05:24:21,160 --> 05:24:22,240 ANIMAL MODELS. 6386 05:24:22,240 --> 05:24:26,920 WE KNOW WHAT THE DISEASE 6387 05:24:26,920 --> 05:24:28,760 FEATURES ARE IN ANIMAL MODELS 6388 05:24:28,760 --> 05:24:30,400 AND MATCH THE OMICS DATA FROM 6389 05:24:30,400 --> 05:24:36,160 THE ANIMAL MODELS TO HUMAN 6390 05:24:36,160 --> 05:24:41,080 DISEASE THAT WILL SHOWS THE 6391 05:24:41,080 --> 05:24:42,120 DISEASE FEATURES AND THE 6392 05:24:42,120 --> 05:24:47,200 PATHWAYS THE MOUSE MODELS 6393 05:24:47,200 --> 05:24:49,280 REPRESENT IN HUMAN DISEASE AND 6394 05:24:49,280 --> 05:24:51,080 UNDERSTAND MECHANISMS OF 6395 05:24:51,080 --> 05:24:58,800 INDIVIDUAL DISEASE FEATURES AND 6396 05:24:58,800 --> 05:25:01,600 IDENTIFY TARGETS FOR THE DISEASE 6397 05:25:01,600 --> 05:25:04,400 FEATURE CONTRIBUTING TO THE 6398 05:25:04,400 --> 05:25:05,800 ENDOTYPING DISCUSSION WE HAD AS 6399 05:25:05,800 --> 05:25:06,120 WELL. 6400 05:25:06,120 --> 05:25:12,000 >> I WANT TO ECHO SOMETHING ON 6401 05:25:12,000 --> 05:25:13,800 THE TALK WHICH IS ONLY WHETHER 6402 05:25:13,800 --> 05:25:15,880 WE TALKED ABOUT AND THE ABILITY 6403 05:25:15,880 --> 05:25:21,440 TO GET ACCESS TO THE INDIVIDUAL 6404 05:25:21,440 --> 05:25:22,640 MODELS IN MANY CASES EXPOSURE 6405 05:25:22,640 --> 05:25:27,520 SYSTEMS AND TISSUES FROM THE 6406 05:25:27,520 --> 05:25:30,080 ANIMALS OR MODELS WOULD BE 6407 05:25:30,080 --> 05:25:30,920 IMPORTANT THROUGH INVESTIGATORS 6408 05:25:30,920 --> 05:25:37,080 OR COHORTS OR NIH, THROUGH I 6409 05:25:37,080 --> 05:25:40,640 DON'T KNOW HOW INVESTIGATORS MAY 6410 05:25:40,640 --> 05:25:46,200 GET ACCESS TO UNIQUE MODELS AND 6411 05:25:46,200 --> 05:25:46,440 TISSUES. 6412 05:25:46,440 --> 05:25:48,840 AND I WANT TO CAPTURE THE 6413 05:25:48,840 --> 05:25:49,920 ESSENCE OF WHAT YOUR SAYING. 6414 05:25:49,920 --> 05:25:58,040 >> ABSOLUTELY A STREAMLINE WAY 6415 05:25:58,040 --> 05:25:59,640 TO COLLABORATE WITH THESE 6416 05:25:59,640 --> 05:26:02,080 TISSUES AND PHIL YOU'RE VERY 6417 05:26:02,080 --> 05:26:03,320 GENEROUS BUT THERE'S DIFFERENT 6418 05:26:03,320 --> 05:26:06,960 EXPOSURE SYSTEMS, DIFFERENT 6419 05:26:06,960 --> 05:26:09,400 MODELS AND THAT COULD BE ONE WAY 6420 05:26:09,400 --> 05:26:12,120 TO INCREASE AS MENTIONED BEFORE 6421 05:26:12,120 --> 05:26:13,360 WITHOUT EACH INDIVIDUAL PERSON 6422 05:26:13,360 --> 05:26:15,280 SITTING THERE AND TRYING TO 6423 05:26:15,280 --> 05:26:20,280 EXPOSE 350 MICE. 6424 05:26:20,280 --> 05:26:22,120 >> YVONNE, DO YOU HAVE ANYTHING 6425 05:26:22,120 --> 05:26:23,880 ELSE YOU'D LIKE TO ADD? 6426 05:26:23,880 --> 05:26:24,360 >> I DON'T. 6427 05:26:24,360 --> 05:26:29,040 I THINK IT'S BEEN A GREAT 57 6428 05:26:29,040 --> 05:26:31,520 MINUTES OF DISCUSSION. 6429 05:26:31,520 --> 05:26:33,400 MEILAN, ANY OTHER THOUGHTS? 6430 05:26:33,400 --> 05:26:37,760 >> A MASTERFUL JOB OF TRYING TO 6431 05:26:37,760 --> 05:26:44,560 MANAGE OVER 100 VERY ACTIVE 6432 05:26:44,560 --> 05:26:46,240 PARTICIPANTS ON ZOOM AND CHAT. 6433 05:26:46,240 --> 05:26:47,120 I'VE BEEN TRYING TO KEEP UP WITH 6434 05:26:47,120 --> 05:26:52,960 BOTH. 6435 05:26:52,960 --> 05:26:54,480 QUITE IMPRESSIVE YOU'RE DOING A 6436 05:26:54,480 --> 05:26:55,400 BETTER JOB THAN I AM. 6437 05:26:55,400 --> 05:26:59,880 I WANT TO THANK EVERYONE. 6438 05:26:59,880 --> 05:27:01,800 I HAVEN'T HAD AN OPPORTUNITY TO 6439 05:27:01,800 --> 05:27:02,880 PARTICIPATE IN A WORKSHOP THIS 6440 05:27:02,880 --> 05:27:04,000 LARGE OR IN SCOPE BEFORE. 6441 05:27:04,000 --> 05:27:05,760 IT'S KIND OF FUN FOR ME AND I 6442 05:27:05,760 --> 05:27:07,800 HAVE A CHANCE TO INTERACT WITH 6443 05:27:07,800 --> 05:27:11,880 PEOPLE FROM ACROSS THE WORLD IS 6444 05:27:11,880 --> 05:27:14,520 ALSO A REAL TREAT. 6445 05:27:14,520 --> 05:27:16,320 ED, DID YOU WANT TO SAY ANYTHING 6446 05:27:16,320 --> 05:27:17,520 OR NIH COLLEAGUES? 6447 05:27:17,520 --> 05:27:19,600 >> I WOULD ECHO WHAT YOU SAY AND 6448 05:27:19,600 --> 05:27:21,960 SAY I'M PLEASED WITH THE WAY THE 6449 05:27:21,960 --> 05:27:27,960 FIRST DAY'S GONE AND PUCTUALITY 6450 05:27:27,960 --> 05:27:30,680 OF THE SPEAKERS AND LEAVING 6451 05:27:30,680 --> 05:27:31,680 SUFFICIENT TIME TO HAVE GREAT 6452 05:27:31,680 --> 05:27:33,840 DISCUSSIONS FOR BOTH SESSIONS. 6453 05:27:33,840 --> 05:27:34,400 HOPEFULLY WE'LL REPEAT THIS 6454 05:27:34,400 --> 05:27:42,280 TOMORROW. 6455 05:27:42,280 --> 05:27:47,360 >> I THINK TODAY'S A GREAT DAY. 6456 05:27:47,360 --> 05:27:52,680 THANK EVERYONE FOR THE 6457 05:27:52,680 --> 05:27:53,320 PARTICIPATION. 6458 05:27:53,320 --> 05:27:54,680 WE LOOK FORWARD TO ANOTHER 6459 05:27:54,680 --> 05:27:55,520 EXCELLENT DAY. 6460 05:27:55,520 --> 05:28:03,760 EVERYBODY HAVE A GREAT EVENING. 6461 05:28:03,760 --> 05:28:07,120 >> WE'LL LET PHIL GO TO GET SOME 6462 05:28:07,120 --> 05:28:09,480 SLEEP. 6463 05:28:09,480 --> 05:28:10,960 >> THANK YOU. 6464 05:28:10,960 --> 05:28:21,320 >> SEE YOU TOMORROW.