>> I'M DR. QUING LU WITH THE
NATIONAL HEART, LUNG AND BLOOD
INSTITUTE.
I'M HAPPY TO REPORT WE HAVE 274
PEOPLE HAVE SIGNED UP FOR THIS
WORKSHOP.
AND I KNOW EVERYBODY HAS BUSY
SCHEDULE AND TOTAL WE HAVE 274
SIGNED UP.
I'M SO HAPPY TO SEE YOU ALL HERE
VIRTUALLY.
AS YOU MAY KNOW, OUR DIVISION
DIRECTOR DR. JAMES KEIGHLEY
WOULD LIKE TO BE HERE TO WELCOME
YOU HOWEVER, HE IS HAVING
ANOTHER MEETING RIGHT NOW AND HE
CANNOT ESCAPE.
HE WILL JOIN AT A LATER TIME.
I ALSO HEARD THE NHLBI DIRECTOR,
DR. GIBBONS MAY DROP IN DURING
THE WORKSHOP WHICH IS VERY
EXCITING.
I WOULD LIKE TO INTRODUCE OUR
DEPUTY DIRECTOR, DR
DRDR
DR. MATUTE-BELLO HE WAS
PROFESSOR OF MEDICINE AT THE
UNIVERSITY OF WASHINGTON AND
PHYSICIAN AT THE V.A. HEALTH
CARE SYSTEMS.
HE RECEIVED HIS M.D. DEGREE FROM
THE CENTRAL UNIVERSITY OF
VENEZUELA AND COMPLETED HIS
INTERNAL MEDICINE INTERNSHIP AND
RESIDENCY AT THE ALBERT EINSTEIN
MEDICAL CENTER IN PHILADELPHIA
AND PULMONARY FELLOWSHIP IN
SEATTLE.
HE HAS BOOKS AND IS THE PRIMARY
INTEREST IN LUNG TRANSPLANT AND
YOU MAY OPEN THE WORKSHOP.
>> I'M PLEASED TO SEE MORE THAN
270 PARTICIPANTS HAVE SIGNED ON
TO THE WORKSHOP.
THEY COME FROM ACROSS THE UNITED
STATES, EUROPE, CANADA,
AUSTRALIA.
AND I THINK THIS LEVEL OF
INTEREST IN ENTHUSIASM HIGHLIGHT
THE INTEREST IN THE TOPIC.
WELCOME TO NHLBI.
THE NHLBI MISSION IS TO PROVIDE
GLOBAL LEADERSHIP FOR RESEARCH,
TRAINING AND EDUCATION PROGRAMS
THAT PROMOTE THE PREVENTION AND
TREATMENT OF HEART, LUNG AND
BLOOD DISEASES AND ENHANCE THE
HEALTH OF ALL INDIVIDUALS.
SO THEY CAN LIVE LONGER AND MORE
FULFILLING LIVES.
OUR GOALS ARE TO UNDERSTAND
HUMAN BIOLOGY, REDUCE HUMAN
DISEASE, DEVELOP WORKFORCE
RESOURCES AND ADVANCE
TRANSLATIONAL RESEARCH.
AT THE DIVISION OF LUNG DISEASES
WE ARE RESPONSIBLE FOR
MONITORING THE LATEST RESEARCH
DEVELOPMENTS IN THE SCIENTIFIC
COMMUNITY AS WELL AS IDENTIFYING
RESEARCH GAPS AND NEEDS
OBTAINING ADVICE FROM EXPERTS IN
THE FIELD AND IMPLEMENTING
PROGRAMS TO ADDRESS NEW
OPPORTUNITIES.
THIS WORKSHOP BRIDGING THE GAP
BETWEEN CLINICAL AND BASIC
RESEARCH TO UNDERSTAND COPD
MECHANISMS IS HIGHLY RELEVANT TO
THESE GOALS.
I DON'T HAVE TO TELL THIS
AUDIENCE THAT COPD IS THE THIRD
LEADING CAUSE OF DEATH IN THE
UNITED STATES ALONE AND COSTS UP
TO $55 BILLION PER YEAR.
SMOKING CESSATION AND OTHER
CURRENT THERAPIES CAN REDUCE
SYMPTOMS BUT DO NO REVERSE
DISEASE PROGRESSION.
THE MAJOR REASON IS WE LACK
FUNDAMENTAL UNDERSTANDING OF
COPD MECHANISMS.
NOW, AS YOU KNOW, MAJOR
LONGITUDINAL OBSERVATIONAL
COHORT STUDIES OF COPD PATIENTS
HAVE COLLECTED ENORMOUS CLINICAL
IMAGING GENETIC AND OTHER
MULTIOMICS THAT INCREASED THE
UNDERSTANDING OF PATHOPHYSIOLOGY
AND PATHOGENESIS OF COPD IN
PARALLEL SIGNIFICANT PROGRESS
HAS ALSO BEEN MADE IN THE BASIC
SCIENCE PHASE.
NOVEL AND PROMISING HYPOTHESISES
HAVE BEEN RAISED AND TESTS FOR
COPD ONSET AND PROGRESSION AND
THIS IS EXCITING AND
ENCOURAGING.
HOWEVER, THE FINDINGS OF COPD
CLINICAL RESEARCH HAVE NOT
READILY MAPPED TO RESEARCH AND
THERE'S A GAP IN RESEARCH IN
COPD.
THE PURPOSE OF THE WORKSHOP IS
TO BRING TOGETHER CLINICAL AND
BASIC SCIENTISTS IN COPD TO
IDENTIFY THE CURRENT STATE OF
SCIENCE, CRITICAL KNOWLEDGE
GAPS, KEY CHALLENGES AND
BARRIERS AND OPPORTUNITIES IN
UNDERSTANDING COPD PATHOBIOLOGY
AND PATHOGENESIS.
IT IS ANTICIPATED SPEAKERS AND
PARTICIPANTS WILL DISCUSS HOW TO
TRANSLATE THE KNOWLEDGE GAINED
FROM MAJOR CLINICAL
OBSERVATIONAL STUDIES TO KEY
QUESTIONS THAT CAN BE ADDRESSED
BY BASIC MECHANISTIC RESEARCH.
WE PROBABLY CAN DO THAT BY
TAKING ADVANTAGE OF NEW
TECHNOLOGY AND MODEL SYSTEMS.
IT IS OUR HOPE THAT THIS
WORKSHOP WILL HELP SHAPE A
RESEARCH VISION AND AGENDA ON
HOW TO MOVE COPD RESEARCH
FORWARD FOR MECHANISTIC STUDIES.
WE FURTHER HOPE THAT A DEEPER
UNDERSTANDING OF COPD PATHOGENIC
MECHANISMS WILL LEAD TO
DISCOVERY OF THERAPEUTIC
STRATEGIES BEYOND TREATMENT
SYSTEM AND DISEASE MODIFYING
APPROACHES.
I BELIEVE THIS WORKSHOP IS
NECESSARY AND TIMELY.
I AM HAPPY TO SEE A VERY DIVERSE
AND INCLUSIVE PANEL OF EXPERTS
AND PARTICIPANTS.
THANK YOU AGAIN FOR YOUR
PARTICIPATION.
I AM LOOKING FORWARD TO A
SUCCESSFUL AND PRODUCTIVE
WORKSHOP AND WORK WITH YOU IN
THE FUTURE TO PROMOTE LUNG AND
SLEEP HEALTH.
THANK YOU, DR. MATUTE-BELLO.
I'D LIKE TO THANK OUR CO-CHAIRS
DR. HUANG AND BLALOCK FOR THEIR
CONCEPTION AND PLANNING AND
EXPRESS OUR GRATITUDE TO ALL
SECTION CO-CHAIRS, SPEAKERS,
PANELISTS, DISCUSSANTS AND ALL
OF YOU FOR WORKING HARD DAY AND
NIGHT TO ADVANCE COPD RESEARCH
AND IMPROVE THE QUALITY OF LIFE
WITH INDIVIDUALS WITH COPD OR
OTHER LUNG DISEASE.
WE THANK YOU FOR YOUR INSIGHT
AND YOU CONTRIBUTION TO THIS
WORKSHOP.
I WOULD ALSO PARTICULARLY LIKE
TO THANK MANY COLLEAGUES FROM
THE DIFFERENT PARTS OF THE GLOBE
WHO HAVE TO OVERCOME SIGNIFICANT
TIME ZONE DIFFERENCES AND
SACRIFICE THEIR SLEEP TO
PARTICIPATE IN THIS WORKSHOP.
I KNOW THIS IS PROBABLY MIDNIGHT
IN YOUR TIME.
THANK YOU.
THE NHLBI DIVISION OF LUNG
DISEASE WOULD ALSO LIKE TO THANK
ALL PEOPLE WITH OR WITHOUT COPD
WHO HAVE PARTICIPATED IN THE
RESEARCH DISCUSSED TODAY AND
TOMORROW.
WITHOUT THEIR PARTICIPATION WE
COULD NOT MOVE THE FIELD
FORWARD.
WE ARE GRATEFUL TO DR. WRIGHT
FROM THE COPD FOUNDATION WHO
JOINED WITH US AND PROVIDE
INSIGHT FROM THE PATIENT
PERSPECTIVES.
AND IT WOULD NOT BE ABLE TO
ORGANIZE WITHOUT THE TEAM'S HELP
AND LAST BUT NOT LEAST I WOULD
LIKE TO THANK THE DOD LEADERSHIP
AND DR. PUNTURIERI FOR THEIR
SUGGESTIONS.
AND THE PURPOSE OF THIS WORKSHOP
IS TO BRING TOGETHER CLINIC AND
BASIC SCIENCE AND IDENTIFY THE
CURRENT STATE OF SCIENCE,
CRITICAL KNOWLEDGE GABZ, KEY
CHALLENGES AND THE BARRIERS AND
OPPORTUNITY IN UNDERSTANDING OF
COPD PATHOPHYSIOLOGY AND
PATHOGENESIS.
WE LOOK FORWARD TO YOUR
ACTIONABLE AND IMPLEMENTABLE
IDEAS AND RECOMMENDATION.
THANK YOU AGAIN FOR YOUR
PARTICIPATION.
I LOOK FORWARD TO A SUCCESSFUL
AND PRODUCTIVE WORKSHOP AND
WORKING WITH YOU IN THE FUTURE
TO PROMOTE LUNG AND SLEEP
HEALTH.
NEXT I WOULD LIKE TO SAY A FEW
THINGS ABOUT THE MEETING
LOGISTIC.
THE WORKSHOP IS VIDEOCAST AND
LIVE STREAMED.
THE RECORDING WILL BE AVAILABLE
IN THE NIH VIDEOCAST PAST EVENT
APPROXIMATELY ONE WEEK FROM THE
EVENT.
SECOND, TIME IS GIVEN TO EACH
PRESENTATIONS.
AND AT THE END OF THE 90 MINUTE
PRESENTATION SECTION THERE WILL
BE A 60-MINUTE DISCUSSION.
SO AUDIENCE, PLEASE HOLD YOUR
QUESTIONS TO THE OPEN
DISCUSSIONS.
AUDIENCE YOU CAN ALSO USE THE
CHAT BOX TO ASK QUESTIONS DURING
THE PRESENTATIONS.
THE CO-CHAIR AND PROGRAM STAFF
WILL MONITOR CHAT TO MAKE SURE
ALL QUESTIONS GET ADDRESSED AND
PRESENTERS ARE ENCOURAGED TO
ANSWER IN THE CHAT THE TECHNICAL
QUESTIONS AND QUESTIONS
ADDRESSED IN THE OPEN DISCUSSION
SECTION.
DISCUSSANTS AND PANELISTS ARE
ENCOURAGED TO USE RAISING HAND
FUNCTION AND OPEN CAMERA WITH
THE TALK.
IF A SPEAKER DOES NOT HAVE A
DISCLOSURE SLIDE YOU CAN
PRESENTATION IT BEFORE YOUR
PRESENTATIONS.
WE DIDN'T EMPHASIZE IT IN DRY
RUN BUT IT'S OKAY IF YOU DO NOT
HAVE SLIGHT BUT STATE IF YOU
HAVE FINANCIAL AD OR NOT.
AND OUR SUPPORT TEAM ALREADY
SAID TO SAVE THE BANDWIDTH,
PLEASE KEEP CAMERA OFF OR AUDIO
MUTES WHEN NOT TALKING.
THE SUPPORT STAFF TEAM WILL BE
HERE TO RESPOND TO TECHNICAL
QUESTIONS OR QUESTIONS DURING
THE WORKSHOP.
NOW, I WOULD LIKE TO INTRODUCE
OUR CO-CHAIRS, DR. HAN FROM THE
UNIVERSITY OF MICHIGAN AND
DRDR
DR. BLALOCK FROM THE UNIVERSITY
OF BIRMINGHAM.
DR. HAN AND DR. BLALOCK THE
FLOOR IS YOURS.
>> I'D LIKE TO WELCOME ALL
PARTICIPATING IN THE MEETING AND
GIVE A PARTICULAR THANKS TO THE
INVITEES.
WHEN WE STARTED WORKING ON THIS
PROJECT I THOUGHT SCHEDULING WAS
GOING TO BE BE AN ABSOLUTE
NIGHTMARE.
BECAUSE OF THE ENTHUSIASM AND
ACCOMMODATING NATURE OF ALL THE
PEOPLE WE INVITED IT TURNED OUT
TO BE VERY EASY.
FOR THAT I THANK YOU.
I BELIEVE MEILAN WANTS TO GIVE
THE CHARGE.
>> MOST HAVE PARTICIPATED IN
WORKSHOP AND THOSE TRADITIONALLY
HAVE ALWAYS BEEN AMAZING
EXPERIENCES AND WE WISH WE COULD
HAVE OFFERED THIS IN PERSON BUT
AS IT IS THIS IS THE MOST IDEAL
FORMAT.
ON THE UPSIDE, I DO NOT REMEMBER
AN IN-PERSON WORKSHOP WHERE WE
HAD OVER 250 PEOPLE THAT WERE
ABLE TO PARTICIPATE AND I SEE
RIGHT NOW OUR PARTICIPANTS ARE
HOVERING AROUND 130.
THAT'S EXCITING TO ME AND I'LL
ECHO WHAT ED SAID IN THAT WE'RE
JUST HONORED THAT SO MANY PEOPLE
WERE ENTHUSIASTIC ABOUT
PARTICIPATING AND JUST FROM A
PERSONAL PERSPECTIVE WE'VE BEEN
HOPING FOR BREAKTHROUGHS IN COPD
FOR A LONG TIME AND I THINK
WE'RE STARTING TO GET A LOT OF
INFORMATION COMING OUT IN THE
LAST FEW YEARS THAT I THINK
POISES FOR BREAKTHROUGHS AND TO
PROVIDE OVERVIEW FOR THE
WORKSHOP, AS YOU PROBABLY
ALREADY SAW FROM THE AGENDA
WE'RE ACTUALLY BROKEN INTO FOUR
DISTINCT SECTIONS.
TWO THAT WILL OCCUR TODAY AND
TWO THAT WILL OCCUR TOMORROW
WITH THE LAST SESSION REALLY
BEING FOCUSSING PRIMARILY ON
DISCUSSION AND WRAP UP.
ONE OF THE GOALS OF THIS
WORKSHOP IS TO BRING CLINICAL
RESEARCHERS AND BASIC SCIENTISTS
TOGETHER.
YOU'LL SEE FROM EVEN THE CHAIRS
MORE OF A CLINICAL RESEARCHER
AND ED IS MORE OF A BASIC
SCIENCE RESEARCHER IN COPD AND
THAT'S REALLY THE THEME FOR
TODAY IS TO BRING BOTH GROUPS
TOGETHER TO SEE HOW WE CAN
TRANSLATE THE SCIENCE AND
RESEARCH CHALLENGES TO
UNDERSTAND WHAT THE
OPPORTUNITIES ARE FOR COPD
PARTICULARLY WITH RESPECT TO
PATHOBIOLOGY AND PATHOGENESIS.
WE REALIZE WE ARE NOT ABLE TO
COVER EVERY TOPIC BUT STILL WE
BROUGHT A LOT PEOPLE TOGETHER
AND CAN BRING THIS FORWARD WITH
RESPECT TO PATHOGENESIS.
IN THIS MORNING'S SESSION YOU'LL
SEE INFORMATION FROM SOME OF THE
MAJOR COPD COHORTS OR WE'RE
HONORED TO HAVE OUR COLLEAGUES
FROM AUSTRALIA TO ABOUT THE
TASMANIAN COHORT AS WELL AND HOW
EPIDEMIOLOGIC STUDIES
CONTRIBUTED TO THE DISEASE AND
WE'LL HAVE A SECTION ON MODELS
FOR STUDYING COPD AND THIS IS
MOVED BEYOND THE TRADITIONAL
ANIMAL MODELS AND NOW INCLUDES
MORE SOPHISTICATED SYSTEMS LIKE
ORGANOID SYSTEMS AND I'M EXCITED
FOR THAT SESSION AS WELL AND
THEN WE HAVE A SESSION TOMORROW
DEDICATED TO UNDERSTANDING SOME
OF THE DIFFERENT MECHANISMS
BEHIND INJURY IN COPD.
NOW, OBVIOUSLY WE CAN'T COVER
EVERY SINGLE POTENTIAL PATHWAY
THAT MIGHT BE IMPLICATED BUT WE
WILL DO OUR BEST TO GET A BROAD
OVERVIEW AND THEN AT THE END
WE'RE JUST GOING TO WRAP
EVERYTHING UP BY TRYING TO
UNDERSTAND WHERE WE NEED TO MOVE
FORWARD.
WHAT ARE THE IMPORTANT TESTABLE
HYPOTHESES WE AS A RESEARCH
COMMUNITY SHOULD BE DOING NEXT.
HOW COULD WE BETTER COLLABORATE
TOGETHER.
I WOULD HOPE THAT'S A MAJOR
OUTPUT OF THIS WORKSHOP.
I THINK WE'RE ALSO ENVISIONING
THERE BE AN EXECUTIVE SUMMARY
PEOPLE WILL HELP PARTICIPATE ON
WITH RESPECT TO AUTHORSHIP.
I BELIEVE WE'VE BEEN SLOTTED
UNTIL 10:30 FOR THIS BUT I DON'T
KNOW THAT WE NEED TO KEEP GOING.
IT MAY BE BEST JUST TO GO AHEAD
AND JUMP INTO OUR FIRST SESSION
UNLESS ED OR ANYONE FROM THE NIH
HAD ANY OTHER COMMENTS BEFORE WE
JUMP INTO OUR FIRST SESSION.
>> YEAH, YOU ARE CHAIR.
>> OKAY.
I HAVE A FUNNY FEELING WE'LL
WISH FOR EXTRA TIME ON THE BACK
END SO I'LL TAKE THE CHAIR'S
PREROGATIVE AND MOVE US FORWARD.
THIS FIRST SECTION IS GOING TO
BE CO-CHAIRED BY DR. JEFFERY
CURTIS A PROFESSOR OF INTERNAL
MEDICINE IN CRITICAL CARE HERE
IN ANN ARBOR AT THE V.A. MEDICAL
CENTER AND STEPHANIE CHRISTENSON
PROFESSOR OF MEDICINE
UNIVERSITY, SAN FRANCISCO AND
LOOK AT THE COHORTS INCLUDING
COPD, SPIROMICS, MESA HEALTH
STUDY AND THE TASMANIAN HEALTH
STUDIES.
WE HAVE A LOT OF PRESENTERS FROM
ALL OVER THE WORLD AND THEY'LL
BE HELPING UNDERSTAND WHAT WE
CAN TAKEAWAY FROM THIS.
I'LL TURN THIS OVER TO OUR
CO-CHAIRS DR. CURTIS AND
DR. CHRISTENSON.
>> THANK YOU SO MUCH.
>> THANK YOU FOR BEING HERE.
JUST TO GIVE A LAYOUT TO THIS
SESSION, WE HAVE SEVERAL COHORTS
TO GET THROUGH IN THE FIRST HOUR
AND A HALF AND THEN THERE'S AN
HOUR FOR DISCUSSION AFTERWORDS.
UNLESS YOU HAVE FURTHER COMMENTS
I THINK WE WANTED TO HEAR FROM
THE P.I.'S OF THE COHORTS ON
WHAT THEY THINK OF THE STATE OF
CLINICAL RESEARCH.
DID YOU WANT TO INTRODUCE COPD
GENE, JEF?
>> THAT'S WHAT I WAS TYPING.
PLEASED TO INTRODUCE DR. ED
SILVERMAN AND DR. CRAPO.
>> IT'S A PLEASURE TO BE HERE TO
TALK ABOUT THIS LONGITUDINAL
STUDY TO UNDERSTAND
SUSCEPTIBILITY AND PROGRESSION
OF COPD.
THIS SLIDE SUMMARIZES OUR
PERSONAL FINANCIAL RELATIONSHIP.
SO COPD GENE HAS A NUMBER OF
GOALS.
WE WANT TO TRY TO IDENTIFY NEW
GENETIC LOCI THAT INFLUENCE
SUSCEPTIBILITY FOR AND COPD AND
RELATED PHENOTYPES.
WE WOULD LIKE TO RECLASSIFY THE
SYNDROME INTO SUBTYPES THAT
SHARE A COMMON PATHOGENESIS,
GENETICS, BIOMARKERS PROGRESS
AND RESPONSE TO THERAPY AND
WOULD LIKE TO CHARACTERIZE THE
PATTERNS OF DISEASE PROGRESSION
AND ULTIMATE WE WANT THIS WORK
TO LEAD TO IMPROVED CLINIC
PRACTICE WITH EARLIER
IDENTIFICATION OF COPD PATIENTS
AND IDENTIFY THERAPIES AND
APPROACH TO DISEASE PREVENTION.
JAMES WILL TALK ABOUT THE
COHORT.
>> THE COHORT IS OVER 10,000
PEOPLE WHOSE PRIMARY CRITERIA
FOR COMING IN IS THEY SMOKED AND
45 TO 80 AND 455 NON-SMOKING
CONTROLS.
WE LOOKED AT THEM DETAILED AT
BASELINE AT FIVE YEAR AND
10-YEAR FOLLOW-UP.
IN MONTHS WE'LL START A 15-YEAR
FOLLOW-UP.
THIS IS THE DISTRIBUTION OF MORE
THAN 10,000 PEOPLE IN OUR
COHORT.
AND IT'S IMPORTANT THAT MORE
THAN HALF OF THEM DID NOT HAVE
COPD AS DEFINED BY LOW F EV1
RATIO AND THERE'S ABOUT 40% OF
THE COHORT IN THE UPPER LEFT
QUADRANT IS THE QUADRANT WE CALL
PRISM PRESERVED RACIAL IMPAIRED
SPIROMETRY.
WE FOUND A GREAT DEAL OF DISEASE
IN THESE QUADRANTS.
SEVERE DISEASE.
WE FOUND UNIQUE PATTERNS OF
PROGRESSION.
SO THE BEGINNING OF THE DISEASE
WE THINK IS IN THE RIGHT UPPER
QUADRANT WE NEED TO UNDERSTAND
AND SHOULD BE A MAJOR TOPIC OF
DISCUSSIONS IN THIS COHORT.
THIS COHORT IS ABOUT TWO-THIRDS
NON-HISPANIC WHITE, ONE-THIRD
AFRICAN AMERICAN AND DISTRIBUTED
BETWEEN MALE AND FEMALE.
ONE OF OUR QUESTIONS IS HOW DO
PEOPLE PROGRESS FROM SO-CALLED
NORMAL TO REACH THE LOWER LEFT
QUADRANT WITH HIGH MORBIDITY AND
MORTALITY AND SOMETHING WE'LL
TALK ABOUT.
WE IDENTIFY THIS IS NOT ONE
DISEASE.
IT'S A PATTERN OF MANY DISEASE.
WE'RE EMPHASIZES ONE DOESN'T
HAVE MUCH EMPHYSEMA IN THE LATE
IN THE PROCESS AND THERE'S A LOT
OF AIRWAY WALL THICKENING YOU
CAN PICK UP ON CT.
AND THIS IS IN CONTRAST WITH OUR
EMPHYSEMA DISEASE CLASSIC WITH
PATTERNS IN EMPHYSEMA HAS LITTLE
AIRWAY DISEASE SO TWO SEPARATE
GROUPS.
THE POINT IS WE DON'T CONSIDER
COPD 1 DISEASE AND CT IS A MAJOR
FACTOR IN HELPING UNDERSTAND THE
DIFFERENCES.
THIS IS -- WE USED A.I. IN
VARIOUS WAYS AND MORTALITY TO
TRY TO LOOK AT THE DIFFERENT
PATTERNS OF THE AIRWAY DISEASE
AND EMPHYSEMA DISEASE.
THE BLUE DOTS IN THE RIGHT SIDE
OF THE GRAPH ARE INDIVIDUALS
WITH HIGH RISK EMPHYSEMA DISEASE
AND YOU CAN SEE BEGINS AT ZERO
AND PROGRESSES TO THE LEFT UPPER
QUADRANT.
THAT'S IN MARK CONTRAST TO THOSE
WITH AIRWAY DISEASE THE ONES
WITH RED THAT BY THE TIME
THEY'RE HIGH RISK AIRWAY THEY'RE
WELL IN THE PRISM HAVE LOST A
GREAT DEAL OF FEV1 AND CONTINUE
TO 3 AND 4.
BECAUSE AIRWAY DISEASE HAS HIGH
MORTALITY WE CHARACTERIZE THE
MODERATE AIRWAY RISK AS GREEN
AND YOU CAN SEE IT FALLS IN
BETWEEN.
THE SUBTYPES CLEARLY SEPARATE
WHEN WE LOOK AT THE CT PATTERNS
AND PHYSIOLOGIC FUNCTION.
I WANT TO SHOW YOU MORE ABOUT
THE MORTALITY WHICH IS UNLIKE
AND GIVE YOU AN IDEA HOW GO FROM
ZERO TO GOAL 3, 4 WE CAN NOW
FOLLOW OVER 10 YEARS.
THIS IS THE MORTALITY OVER 15
YEARS OF OBSERVATION.
THE TOP GRAY CURVE ARE THE
SUBJECTS THAT HAD NO SIGNIFICANT
AIRWAY OR EMPHYSEMA DISEASE AT
BASELINE.
THE BLUE LINE THOSE THAT HAD
EMPHYSEMA PREDOMINANT DISEASE.
THERE'S A DISTINCT INCREASE IN
MORTALITY BUT KIND OF MILD AND
THEY DEVELOP DISEASE THAT
DOESN'T REALLY PROGRESS.
THE GREEN LINE ARE THOSE WITH
MODERATE AIRWAY DISEASE.
THE NEXT TWO LINES THE RED AND
PURPLE ARE PEOPLE WITH AIRWAY
DISEASE IN RED.
YOU CAN SEE A MARK IN MORTALITY
AND THE PURPLE LINE IS MODERATE
AIRWAY DISEASE PLUS EMPHYSEMA.
THOSE DEVELOP HIGHEST MORTALITY.
THE HIGHEST IS THE YELLOW LINE,
HIGH RISK PEOPLE THAT SHARE HIGH
RISK EMPHYSEMA AND AIRWAY AT
BASELINE.
EMPHYSEMA HIGH MORTALITY AT LATE
STAGE AIRWAY DISEASE AND BY
ITSELF IT'S A HIGH PREDICTOR OF
MORTALITY.
THAT'S TALK ABOUT HOW YOU BECOME
GOLD 3/4.
WE HAD -- WE ARE ABLE TO FIND
157 PEOPLE THAT ARE NEW
INTERESTS OF GOLD 3/4 ABOUT 6%
OF THE POPULATION.
IN BLUE YOU SEE EMPHYSEMA AS A
CLASSIC ONLY ACCOUNTS FOR 14%.
IF YOU ADD THE PURPLE IT'S
ANOTHER 14% AND EMPHYSEMA WITH
AIRWAY DISEASE REMEMBER AT
BASELINE.
THE RED IS HIGH RISK AND BROWN
IS MODERATE AIRWAY RISK.
ABOUT 60% OF OUR SUBJECTS THAT
PROGRESSED SO GOLD 3/4 DON'T
HAVE EMPHYSEMA AT THE BEGINNING
BUT VARIOUS FORMS OF HIGH RISK
OR MODERATE RISK OF AIRWAY
DISEASE.
THIS IS GIVING YOU AN IDEA WHAT
WE CAN LOOK AT AS WE SUBSET AND
FIND THE PATTERNS OF PROGRESSION
AND HOW TO IDENTIFY THE EARLY
ONSET OF DISEASE.
I'LL TURN IT BACK TO ED NOW.
IN 2019 WE DEVELOPED CRITERIA
FOR EXPANDING DIAGNOSE TO BE
COPD RECOGNIZING THE RATIO WAS
INADEQUATE AND HAD EXPOSURE,
SYMPTOMS, IMAGING AND PHYSIOLOGY
INCLUDING A LOW FEV1 WOULD PUT
YOU IN PRISM BELOW THE RATIO AND
WE DON'T TALK ABOUT IMAGING A
LOT IN THE WORKSHOP BUT IT'S A
MAJOR CHARACTERISTIC TO
UNDERSTAND THE SUB TYPES AND
IDENTIFY PATIENTS WITH SEVERE
DISEASE.
>> SOME KEY EARLY FINDINGS
SHOWED INTERSTITIAL LUNG
ABNORMALITIES ASSOCIATED WITH
REDUCED EMPHYSEMA AND LUNG CAST
AND MAY BE PRECURSOR LESIONS TO
PULMONARY FIBROSIS.
AND OTHERS SHOWED AN ELEVATED
PULMONARY RATIO WAS ASSOCIATED
WITH A COPD FREQUENCY.
AND PRISM IS A HETEROGENEOUS
GROUP THAT INCLUDES COPD
SUBJECTS.
IN ADDITION, MANY SMOKERS WITH
SPIROMETRY IN THE NORMAL RANGE
HAD STRUCTURAL IMPAIRMENTS
SHOWING MOST SMOKERS DO NOT
ESCAPE THE NEGATIVE ASSOCIATION
WITH SMOKE AND EMPHYSEMA AT
BASELINE AND MANY SUB TYPING
APPROACHES THAT WERE LOOKED AT
FROM CLUSTER ANALYSIS TO FACTOR
ANALYSIS CONVERGE ON THIS AIRWAY
PREDOMINANT VERSUS US EMPHYSEMA
PREDOMINANT DICHOTOMY AND THERE
WAS A CHARACTERIZATION OF CAUSES
OF DEATH IN COPD FINDING THE
HIGHEST RATE OF LUNG CANCER
DEATHS IN GOLD SPIROMETRY RATES
1-2 AND THOSE IN 3-4.
AND AIRWAY MUCUS PLUGS ARE
ASSOCIATED WITH INCREASED
MORTALITY IN COPD.
WE BUILT A LARGE AND EXPANDING
OMICS DATA RESOURCE IN COPD
GENE.
WE HAVE WHOLE GENOME SEQUENCING
ON ESSENTIALLY THE ENTIRE COHORT
AND STARTED IN EARNEST IN PHASE
2 AND HOPE TO CONTINUE WITH THE
PHASE 3 AND DNA METHYLATION AND
EPIGENETIC MARK AND TOMORROW
YOU'LL HEAR ABOUT THE PROTEOMICS
AND METABOLOMICS IN THE PHASE 2
COPD SAMPLES.
EVEN WITH A RICH OMICS DATA
SOURCE LIKE THIS, IT'S
CHALLENGING TO DISSECT COPD
PATHOGENESIS BECAUSE OF THE
HETEROGENEITY OF THE DISORDER.
IT'S HETEROGENOUS WHERE THEY ARE
EXPOSED TO DIFFERENT
ENVIRONMENTAL EXPOSURES AT
DIFFERENT TIMES.
INFLUENCES IN DEMOGRAPHIC
FACTORS LIKE AGE AND SEX AND THE
IMPACT OF EPIGENETIC MARKS LIKE
DNA METHYLATION AND INTERACTIONS
BETWEEN THE RISK FACTORS.
IN ADDITION THERE'S DISEASE
HETEROGENEITY.
WE TALKED ABOUT THE AIRWAY
VERSUS US EMPHYSEMA DISEASE AND
OTHER CLINICAL OBSERVATIONS LIKE
EXACERBATIONS AND FINDING
SUBTYPES OF PATIENT SHARE A
PATHOPHYSIOLOGICAL MECHANISM FOR
THEIR COPD AND THERE'S
HETEROGENEITY FOR PROGRESSION.
WE MAY CATCH IT AT THE EARLY
STAGE OR END.
INDIVIDUALS CAN HAVE MILD OR
SEARCH -- SEVERE DISEASE AND
TIMES WHERE PEOPLE'S COPD MAY BE
MORE OR LESS ACTIVE THAN OTHERS
BUT IT'S STILL SPECULATIVE AND
THIS IS DONE THROUGH
COLLABORATIVE STUDIES WITH THE
COHORTS WE'LL HEAR FROM TODAY.
USING THE INTERNATIONAL COPD
GENETICS CONSORTIUM AND U.K. BIO
BANK IDENTIFIED 82 REGIONS FOR
COPD.
PARTS OF THE GENOME SOME WORK IN
THAT REGION CONTAINS ONE
SUSCEPTIBILITY FACTOR FOR COPD.
EACH SAY -- IS A SMALL AFFECT
BULTS WITH A RISK SCORE YOU CAN
HAVE REASONABLE PREDICTION OF
RISK ESPECIALLY IN EUROPEAN
PREDICTIONS.
THE PREDICTION WAS LESS OPTIMAL
IN NON-EUROPEAN PREDICTIONS AND
THERE WAS AN ASSOCIATION WITH
MULTIPLE COHORT.
WE'RE USING WHOLE GENOME
SEQUENCING ANALYSIS TO FIND
RELATED PHENOTYPES AND TRYING TO
FIND GENETIC DETERMINATES.
ONCE YOU FIND THEM FROM THE
GENOME WIDE ASSOCIATION STUDIES
IT'S JUST THE BEGINNING.
WE OFTEN LABEL THE REGION OF THE
GENE NAME BUT IT DIDN'T PROVE
IT'S CAUSATIVE IN THAT REGION.
ADDITIONAL WORK NEEDS TO BE
DONE.
THROUGH COLLABORATIVE WORK WITH
SCIENTISTS CAN USE CHROMOSOME
CONFIRMATION CAPTURE TO IDENTIFY
A LONG-RANGE INTERACTION OF UP
STREAM NEAR THE ACTING GENE THAT
CONTAINS A FUNCTIONAL VARIANT.
AND REPORTER ASSAYS TO FIND
FUNCTIONAL VARIANTS AND THERE'S
BEEN MANY MOUSE MODELS FOR COPD
GWAS GENES DONE USING CHRONIC
SMOKE EXPOSURE.
WHAT ARE GENES WE HAVE MOST
CONFIDENCE IN BASED ON THE
FUNCTIONAL CELL-BASED AND ANIMAL
MODELS DONE?
IT DEPENDS WHO YOU TALK TO.
MY OWN LIST OF GENES I HAVE MOST
CONFIDENCE IN ARE THESE THERE
ORDERED IN A SUBJECTIVE WAY
BASED ON THE ONCE I HAVE MOST
CONFIDENCE TO LEAST CONFIDENCE
IN.
THIS IS TOTALLY SUBJECTIVE.
AND THE AGER, PROTEIN D, HIGH
REV 2 AND NPNT AND MMP12 ARE THE
ONES I HAVE THE MOST CONFIDENCE
IN.
YOU WOULD I THINK AGREE MOST OF
THESE GENES DON'T FIT INTO OUR
PRE-GWAS UNDERSTANDING OF COPD
PATHOGENESIS EXCEPT FOR MMP12
AND THEY ARE SMALL IN EFFECT
WISE AND WORK IN NETWORKS TO
INFLUENCE DISEASE RISK.
IN TERMS OF TRANSCRIPTOMICS, KEY
RECENT RESULTS INCLUDE THE
IDENTIFICATION OF THE INTERFERON
AIRWAY DISEASE SIGNATURE THAT
WAS ASSOCIATED WITH PROSPECTIVE
EXACERBATION RISK YOU SEE IN
ADDITION TO ASSOCIATION WITH
EXACERBATION THERE'S AN
ASSOCIATION WITH CHANGE IN FEV1.
THAT ALSO DEVELOPED
TRANSCRIPTOMIC RISK SCORES FOR
COPD THAT GIVE INDEPENDENT
INFORMATION FROM THE POLLEY --
POLY GENIC RISK SCORE AND GIVE
REASONABLE PREDICTION FOR COPD
AND CURRENTLY WE'RE USING
MACHINE LEARNING APPROACHES TO
IDENTIFY TRANSCRIPTOMICS.
IN TERMS OF PROTEOMICS WE'LL
TALK ABOUT THIS TOMORROW BUT THE
SOMA SCAN 5K PANEL WE'RE TRYING
TO IDENTIFY BIOMARKERS AND
BIOLOGICAL PATHWAYS OF COPD AND
COPD SYMPTOMS.
WE'RE ALSO LOOKING FOR
ASSOCIATIONS OF PROTEOMIC
BIOMARKERS OF PROGRESSION AND
MORTALITY AND TRYING TO DEVELOP
PROTEOMIC RISK SCORES.
TO IDENTIFY THE COPD
PATHOGENESIS WE CAN USE TOP-DOWN
OR BOTTOM-UP APPROACHES.
THE TOP-DOWN IS YOUR PROTEIN AND
PUTTING IT INTO A CORRELATION
NETWORK ANALYSIS MODEL.
GENE REGULATORY NETWORK MODEL
LIKE PANDA FOR PROTEIN
INTERACTION.
WE CAN GO FROM THE BOTTOM-UP AND
FIND THE FUNCTIONAL VARIANTS IN
THE KEY GENES IN THOSE GWAS
REGION AND WHETHER WE'RE GOING
TOP-DOWN OR BOTTOM-UP WE'RE
TRYING TO UNDERSTAND THE
PROTEINS IN NON-CODING REGIONS
AND DEFINE DISEASE PATHOBIOLOGY.
FROM THE BOTTOM-UP WE IDENTIFIED
THE REGION AND THIS IS THE KEY
GENE IN THE GWAS REGION AND THE
CONNECTION.
FROM THE TOP-DOWN WE USED
PROTEIN-PROTEIN CONNECTIONS TO
CONNECT IT TO COPD GWAS GENE
THROUGH AP31.
HOW DO WE KNOW WHEN WE FOUND
SOMETHING IMPORTANT ABOUT
COMPLEX DISEASE PATHOGENESIS
USING THE OMICS DATA TYPES?
IT'S CHALLENGING TO MOVE THE
POPULATION LEVEL OMICS DATA TO
GET INSIGHT TO A COMPLEX DISEASE
LIKE COPD.
THERE'S THINGS WE CAN DO TO
BUILD CONFIDENCE AND BUILD
BIOLOGICAL INSIGHT INTO THE
GENETICS AND OMICS OF COMPLEX
DISEASE.
WE NEED TO REPLICATE FINDINGS IN
OTHER POPULATIONS TO MAKE SURE
THEY'RE REPRODUCIBLE AND REAL.
WE WANT TO LOOK FOR ORTHOGONAL
INFORMATION ON DATA TYPES AND
ANALYTICAL APPROACHES TO ENFORCE
THE CASE THE MOLECULES ARE
IMPORTANT AND FINALLY WE NEED TO
DO FUNCTIONAL VALIDATION IN
CELL-BASED AND ANIMAL MODEL
SYSTEMS THAT IS A KEY THEME OF
THE WORKSHOP.
AS WE THINK ABOUT MAJOR GAPS
BETWEEN THE CLINICAL AND BASIC
SCIENCE RESEARCH IN COPD, WE
THINK WE NEED TO DETERMINE WHICH
POPULATION OMICS ASSOCIATIONS
AND WHICH INVESTIGATION RELEVANT
FOR THE SPECIFIC COMPONENTS OF
THE COPD SYNDROME AND NEED TO
LEVERAGE MULTI-OMICS FOR
RESEARCH AND DEVELOP THROUGHPUT
FUNCTIONAL ASSESSMENTS AND
GENETIC OMICS AND BI-DIRECTIONAL
STUDIES IS CRITICAL AND WHETHER
THE INTEREST IN SINGLE CELL
OMICS COULD BE THE SEE
SCIENTIFIC BRIDGE THAT BRINGS US
ALL TOGETHER.
THANKS VERY MUCH.
>> THANK YOU, DR. SILVERMAN AND
DR. CRAPO.
I DON'T KNOW IF YOU WANT TO
ANSWER THIS ONE QUESTION BECAUSE
WE HAVE A LITTLE OF TIME.
WHAT YOUR THOUGHTS ON WHY AIRWAY
SUB TYPES --
>> MIGHT AS WELL.
WE STARTED EARLY.
>> COPD IS INFLAMMATION IN MY
OPINION WE CAN SEE IT THE
EMPHYSEMA AND CALLED IT THAT BUT
IN MY OPINION THAT'S A MINOR WAY
OF STARTING AND PROGRESSION BUT
THE BEGINNING IS AIRWAY
INFLAMMATION AND
MICROVASCULATURE INFLAMMATION.
WE DESTROY THE SMALLER AIRWAYS
VERY EARLY AND DON'T EVEN SEE
IT.
ALSO CIGARETTE SMOKE WILL HAVE A
MAJOR SYSTEMIC EFFECT AND A LOT
OF THE DEATHS ARE
CARDIOVASCULAR.
YOU'RE DEALING WITH THE SAME
EVENT OF THE TOXINS OF CIGARETTE
SMOKE IN THE AIRWAYS AND
STIMULATING AN INFLAMMATORY
AFFECT AND THOSE ONE THAT HAVE
THE GREATEST PROGRESS TO PRISM
AND CA GONE TO GOLD 3 AND DIE
AND NEVER DEVELOP EMPHYSEMA OR
DEVELOP IT VERY LATE AND THE
PEOPLE WHO DEVELOP EMPHYSEMA
WITHOUT DEVELOPING AIRWAY
DISEASE WILL CAN STOP AND NOT
HAVE A LOT OF COMPLICATIONS BUT
WHEN THAT PERSON AIRWAY
INFLAMMATION THEY PROGRESS TO
3/4 AND DIE.
THERE'S A FUNDAMENTAL MECHANISM
WE NEED TO ADDRESS AND DEVELOP
THERAPIES FOR.
>> EXCELLENT ANSWER TO A VERY
COMPLEX QUESTION.
WE'LL HAVE A DISCUSSION SECTION
AFTERWARDS FOR ABOUT AN HOUR.
I HOPE TO GAIN MORE KEY INSIGHTS
FROM OUR INVESTIGATORS HERE.
I THINK THE NEXT GROUP WE ARE
GOING TO BE INTRODUCING, THANK
YOU, DR. CRAPO AND SILVERMAN.
IT'S AMAZING ONCE AGAIN TO SEE
THE BREADTH AND DEPTH OF WORK
FROM COPD GENE.
NEXT WE HAVE SPIROMICS AND
SOURCE WHICH IS KIND OF THE
EARLY DISEASE AND MY PLEASURE TO
INTRODUCE DR. MEILENIHAN AND
DR. MARTINEZ FROM UNIVERSITY OF
CORNELL BOTH GREAT FRIENDS OF
MINE I'M INTERESTED TO HEAR
ABOUT SOURCE AND SPIROMICS FROM.
>> IF NIH CAN BRING UP THE
SLIDES.
ACTUALLY, WE WERE HOPING
DR. WOODRUFF WOULD GIVE THE
SPIRO MICS OVERVIEW.
LIKE I SAID I'LL BE PLAYING THE
ROLE OF DR. WOODRUFF AND HAND IT
TO DR. MARTINEZ.
SO SPIROMICS HAS UNDER GONE A
LOT OF CHANGES OVER THE YEARS.
IT WAS ORIGINALLY A CONSORTIA
CONTRACT BETWEEN THE NIH,
FOUNDATION OF THE NIH, FDA AND
INDUSTRY.
THE ORIGINAL GOAL WAS A
THREE-YEAR LONGITUDINAL STUDIES
OF SMOKERS BOTH WITH AND WITHOUT
COPD AND A COHORT OF NEVER
SMOKERS TO IDENTIFY NOVEL
SUBPOPULATIONS OF COPD AND
ULTIMATELY TO DEVELOP BETTER
BIOMARKERS FOR THE DISEASE.
WE ULTIMATELY ENROLLED AROUND
3,000 PARTICIPANTS BETWEEN 2009
AND 2016 AND ENDED UP EXPANDING
TO 12 CLINICAL CENTER.
ONE OF THE WAYS SPIROMICS
DIFFERS FROM COPD GENE IS WITH
RESPECT TO BIOLOGICAL SAMPLE
COLLECTION.
THERE WAS INDUCED SPUTUM AND HAD
BLOOD FROM THE GET GO AND HAD A
BRONCHOSCOPY SUB STUDY WITH
BIOPSIES.
THE SPIROMICS STUDY HAS EXPLODED
AND NOW CONSIDER IT THE SPIROMIC
STUDIES AND SPINOFF INCLUDE THE
RETHINK STUDY WHICH WAS DONE
THROUGH THE NIH PULMONARY TRIALS
CONSORTIUM.
WE IDENTIFIED A SUBSET OF
PATIENTS WITH PRE-COPD WHO WERE
P
PRESYMPTOMATIC AND LOOKED AT IT
WIN A BRONCHO DILATOR AND HAD
THE SPIROMICS HEART FAILURE
STUDY AND DR. BARR WILL BE
SPEAKING LATER ABOUT GETTING
CARDIAC MRIs TO UNDERSTAND
HEART-LUNG INTERACTIONS.
IN SPIROMICS 1 WE LOOKED AT
BASELINE ONE, TWO, AND THREE
YEARS AND CT SCANS THE FIRST TWO
VISITS.
SPUTUM WAS DONE AT THE BASELINE
AND REGULAR PHONE CALLS TO
ASSESS FOR COMORBIDITIES AND
EXACERBATIONS.
WE HAD A BRONCHOSCOPY SUB STUDY
FOCUSSING MORE ON MILDER DISEASE
AND EXACERBATION SUB STUDY WITH
WHERE HE HAD A NUMBER OF
PARTICIPANTS WE BROUGHT IN FOR
ADDITIONAL SAMPLE COLLECTION.
AND THEN IN SPIROMICS 2 FIVE TO
SEVEN YEARS AFTER THE BASELINE
VISIT.
AGAIN WE PERFORMED A SECOND
BRONCHOSCOPY AND HAD A SLIGHTLY
DIFFERENT EXACERBATION.
I WILL SAY BOTH SUB STUDIES WERE
CHALLENGED IN TERMS OF GETTING
PARTICIPANTS IN BUT SPIROMICS 2
DUE TO THE PANDEMIC.
SO THERE ARE A LOT OF THINGS I
COULD HAVE TALKED TO YOU ABOUT
TODAY THAT WE LEARNED FROM
SPIROMICS BUT WE HAVE SUCH A
SHORT AMOUNT OF TIME I DECIDED
TO STICK WITH ONE SCHEMATIC
STORY I THINK IS A UNIQUE STORY
TO TELL HAVING TO DO WITH
INDIVIDUALS WHO HAVE PRE-COPD.
IF YOU LOOK AT PATIENT WHO'S ARE
SYMPTOMATIC DEFINED BY CAT SCORE
BIGGER THAN 10 EVEN IN THE
ABSENCE OF AIR FLOW OBSTRUCTION
HAD INCREASED FREQUENCY OF
EXACERBATION SIMILAR TO GOLD 1
AND 2 PATIENTS SYMPTOMATIC
REGARDLESS OF HOW YOU DEFINE
EXACERBATIONS.
SO THAT'S THE GROUP OF PATIENTS
THAT WE'RE TALKING ABOUT.
THEY LOOK SIMILAR TO THE FAR
RIGHT HAND PART OF THE GRAPH AND
WE KIND OF TOY WITH THE BEST WAY
TO NAME THESE INDIVIDUALS BUT I
THINK THIS PAPER WE CALL THEM
NON-OBSTRUCTIVE CHRONIC AIRWAY
DISEASE.
SO ONE OF THE -- TO FOLLOW THE
THREAT OF THIS STORY, WE HAVE SO
THE INITIAL PUBLICATION PRESCOTT
PUBLISHED IN THE NEW ENGLAND
JOURNAL OF MEDICINE THIS IS A
FOLLOW-UP PUBLICATION BY UNC
WHERE IT WAS DEMONSTRATED THAT
INCREASE IN SCORES WERE
ASSOCIATED WITH CHARACTERISTICS
OF COPD.
IT WAS ASSOCIATED WITH SYMPTOMS
OF CHRONIC BRONCHITIS.
AND THIS IS JUST A PICTOGRAM OF
WHAT WE THINK IS GOING ON WHERE
IT MAY CONTRIBUTE TO THE
PATHOGENESIS OF COPD BY LEADING
TO FOR INSTANCE INCREASED
BACTERIA AND CELLS.
WHAT WAS INTERESTING IS WE
SHOWED MUCIN INCREASES AND IN
THE SUBSET OF INDIVIDUALS WITH
NCAD THEY ALSO HAD AN INCREASE
IN MUCIN SCORE.
AND THIS FOR ME NAILED THE FACT
THAT EVEN THESE PATIENTS WITHOUT
AIR FLOW OBSTRUCTION HAVE THE
SAME PATHOGENIC PROCESS AS THOSE
WITH MORE ESTABLISHED AIR FLOW
OBSTRUCTION AND IT MAY REPRESENT
A KEY TARGET WHERE WE COULD
INTERVENE.
FURTHER DATA SHOWS THE
CONCENTRATION FROM THE
CONCENTRATIONS AND SEVERITY.
THESE ARE ON THE RIGHT-HAND SIDE
WE LOOKED AT OTHER
CHARACTERISTICS IN PARTICULAR
FROM THIS SPUTUM AND SHOWED
VARIANCES BASED ON DISEASE
SEVERITY.
THE NEXT SORT OF FOLLOW-UP ITEM
LONG THE SAME STORY STILL
RELATING TO MUCUS IS THE PAPER
THAT WAS PUBLISHED IN THE BLUE
JOURNAL IN 2021 THEY SHOWED
MUCUS AS MANIFESTED BY AIRWAY
PLUGGING ON CT SCAN WAS ACTUALLY
NOT NECESSARILY CORRELATED ONE
TO ONE WITH SYMPTOMS BUT IT WAS
CORRELATED INDEPENDENTLY WITH
EXACERBA
EXACERBATIONS.
SO INTERESTINGLY AGAIN IN THIS
PATIENT POPULATION IN GREEN
WHICH ARE THESE SMOKERS WITH
PRESERVED LUNG FUNCTION THAT MAY
HAVE SYMPTOMS, WE DID BEGIN TO
SEE AN INCREASE IN THE MUCUS
SCORES AND YOU CAN SEE HOW
THEY'RE IDENTIFIED.
THIS JUST KIND OF AGAIN IS
ANOTHER WAY OF IDENTIFYING
EXCESS MUCUS IN THE AIRWAYS AND
THIS DATA AGAIN SUGGESTS IT'S
PART OF A KEY PATHOLOGIC
MECHANISM EVEN BEFORE THE
DEVELOPMENT OF AIRWAY
OBSTRUCTION.
THIS JUST HELPS YOU TO SEE WHERE
I'LL SWITCH IT TO FERNANDO TO
TALK ABOUT SOURCE.
>> WE'RE ALL ONE GROUP IN ALL OF
THIS AS ED SAID ONE THEIR
ADVANTAGES OF A LOT OF THESE
EPIDEMIOLOGICAL COHORTS AND
APOLOGIZE TO MY AUSTRALIAN
COLLABORATE IT'S A NORTH
AMERICAN CENTRIC SLIDE AND
HIGHLIGHTS THE EPIDEMIOLOGICAL
PROPOSAL OF THE NATURAL HISTORY
AS PRESENTED BY DR. LAN AND MY
MENTOR WHO IS A SENIOR AUTHOR OF
THIS PAPER.
AND YOU SEE WHERE THE CURRENT
AGAIN NORTH AMERICAN COHORTS
WHERE THEY DEFINE AGE RANGES FOR
INCLUSION.
AS YOU SEE SOME OF THE DATA FROM
SOURCE, WHERE WE CURRENTLY
STAND.
IF YOU LOOK AT COPD GENE WHICH
ED AND JAMES HAVE DESCRIBED
SPIROMICS AS DESCRIBED WE HAVE
INVESTIGATORS TO FOLLOW.
THOSE STUDIES WERE GENERALLY IN
AN OLDER POPULATION WITH MEAN
AGE IN THE EARLY TO MID 60s.
TRADITIONAL FOR ANY OF US THAT
THROUGH THERAPEUTIC TRIALS IN
COPD THAT'S WHAT WE USUALLY SEE
IN THOSE.
SOURCE WAS DESIGNED AS A
PARALLEL COHORT WHICH WAS
EMBEDDED WITH SPIROMICS AT THE
SAME CENTERS USING THE SAME
APPROACH TO PHENOTYPING AND
ENDOTYPING THAT MEILAN JUST
DESCRIBED.
LEVERAGING THAT LEVEL OF
EXPERTISE AMONGST SITES IN TERMS
OF RECRUITMENT AND IN TERMS OF
THE BIOLOGICAL PROCESSES.
ALA HEALTH GEORGE WILL DESCRIBE
FURTHER IS A FURTHER EXTENSION.
WE WANTED TO ENROLL A POPULATION
THAT WAS GOING TO BE
APPROXIMATELY 20 YEARS YOUNGER.
IT GOES TO SOME COMMENTS IN THE
CHAT ABOUT THE TIME LINE IN
DISEASE AND SOURCE IN THAT
LOCATION.
THERE'S A SISTER PARALLEL STUDY
WITH A CO-INVESTIGATOR AND
MEILAN AND I ARE
CO-INVESTIGATORS IN THE COHORT.
WE WERE FOLLOWING IN PART SOME
OF THE CONCEPTS YOU STATED IN
THAT TARGET IN THE YOUNGER
POPULATION THE EARLIEST
ABNORMALITIES SEEN IN THE SMALL
AIRWAYS USING METHODOLOGY
IMAGING AT MICHIGAN MAYBE 15
YEARS AGO THAT LEVERAGED THE
EXPERTISE OF THE BROADER
SPIROMICS GROUP AND THE
PARTICULARLY THE INVESTIGATORS
IN UMC WITH MUCUS AND MUCUS
BIOLOGY MEILAN SHOWED AND WE'RE
LEVERAGING SPIROMIC DISEASE IN
POPULATING THE YOUNGER COHORT.
THE NEXT SLIDE ILLUSTRATES THE
SPECIFIC AIMS ARE.
WE SHOW THIS IN PART TO GIVE A
SENSE OF THE SIDES OF THE COHORT
AND DATA BEING COLLECTED.
THE TOTAL COHORT WILL BE 600 AND
IT WILL UTILIZE A LOT OF THE
IMAGING EXPERTISE THAT WAS
INITIALLY DEVELOPED BY COPD GENE
INVESTIGATORS AND THEN MODIFIED
AND ADAPTED TO THE SPIROMICS
INVESTIGATOR GROUP.
THERE IS A BRONCHO SCOPIC STUDY
IN SPIROMICS 1 AND 2 THIS IS
PARALLEL EXTENDING BIOLOGICAL
SAMPLES TO COLLECTING BIOLOGICAL
SAMPLES FROM DISTAL AIRWAYS
USING A METHODOLOGY DEVELOPED
HERE AT CORNELL AND AGAIN
LEVERAGED BASELINE AND
LONGITUDINAL SPUTUM SAMPLES
USING THE EXPERTISE THAT HAS
BEEN HIGHLIGHTED BOTH UNC AND
UCSF.
THE NEXT SLIDE ILLUSTRATES THE
GROUPS OF INDIVIDUALS THAT WE
ARE RECRUITING.
THEY SPAN FROM GOLD 0 TO GOLD 1
AND 2.
REMEMBER, THESE ARE ALL
INDIVIDUALS YOUNGER IF THEY
EXHIBIT THE GOLD STAGES
INCLUDING THE COPD GENE PRISM
CATEGORY ARE IN PEOPLE 20 YEARS
YOUNGER.
THIS IS THE WAY IT'S BEEN
CONSTRUCTED.
WE INITIALLY HAD A THRESHOLD FOR
SYMPTOM REQUIREMENT WITH A CATCH
AND REMOVED THAT LATER ON TO BE
ABLE TO PROVIDE ADDITIONAL
COMPLIMENTARY DATA TO WHAT'S
BEING RECRUITED IN THE U.K.
EARLY COPD COHORT SO WE DO NOT
HAVE A CAT SCORE CRITERIA.
YOU'LL SEE WHAT THE DATA LOOKED
LIKE.
THIS IS A SNAPSHOT AS OF LAST
WEEK.
WE ENROLLED 391 PATIENTS AND
OVER 400 IN THE COHORT.
DESPITE THE PANDEMIC AND THE
COVID-19, THE GIFT THAT KEEPS ON
GIVING, WE'VE BEEN ABLE TO CATCH
UP IN TERMS OF ENROLLMENT.
YOU SEE THE DISTRIBUTION OF
SUBJECTS AS CURRENTLY WE HAVE
THEM.
A LITTLE TOO MUCH GOLD 0.
WE ARE TRYING TO ENHANCE THE
GOLD 1 AND 2 RIGHT NOW.
THESE ARE VERY DIFFICULT PATIENT
TO RECRUIT THE NEXT SLIDE GIVES
A SENSE WHAT WE WANTED TO
ACHIEVE PEOPLE IN THEIR MID 40s.
THESE ARE NOW INDIVIDUALS 20
YEARS YOUNGER THAN SEEN IN COPD
GENES SPIROMICS IN CANCOLD AND A
FAIR AMOUNT OF CIGARETTE
SMOKING.
THE COUNT IS ABOUT 11 1/2.
PEOPLE THAT ARE SYMPTOMATIC AND
APPROXIMATELY 18% BLACK OR
AFRICAN AMERICAN INDIVIDUALS.
THE RECRUITMENT OF THE STUDY WAS
REALLY ENHANCED IN THE NEXT
SLIDE THROUGH SOMETHING I WAS
NAIVE TO WHICH WAS SOCIAL MEDIA,
I LEVERAGED THE EXPERTISE OF
MEILAN WHICH IS MORE MEDIA
FRIENDLY AND WE PARTNERED WITH A
CANADIAN COMPANY BUMP, WHICH SAY
DIGITAL MARKETING COMPANY THAT
HAS PRIOR EXPERTISE IN ENROLLING
SMOKING-RELATED STUDIES.
THEY CREATED A WEB-BASED
PLATFORM PRINCIPALLY THROUGH
FACEBOOK THAT HAS ALLOWED US TO
REACH AROUND 30,000 INDIVIDUALS.
40% OF THOSE PROCEEDED TO A
PHONE SCREENING.
THERE'S A WHOLE ALGORITHM USED
AND MODIFIED IN THE LAST YEAR TO
BETTER TARGET THIS POPULATION.
ABOUT A FIFTH OF THOSE
INDIVIDUALS ARE THEN ASKED TO
CONSENT.
ABOUT 20% OF THOSE HAVE AGREED
TO AND YOU CAN SEE THE BOTTOM
NUMBER OF INDIVIDUALS THAT HAVE
BEEN ENROLLED AS OF LAST WEEK
THE TOTAL AMOUNT OF INVESTMENT
IS ABOUT 400 YOUNGER INDIVIDUALS
AS HIGHLIGHTED IN PRIOR SLIDES
IS $240 PER ENROLLED SUBJECT.
IT'S AN INTERESTING APPROACH TO
TRY TO ENROLL A UNIQUE
POPULATION OF INDIVIDUALS THAT
ARE WORKING ADULTS TO COME IN
AND SPEND AN ENTIRE DAY DURING A
VERY DETAILED ASSESSMENT.
WITH BOTH CLINICAL IMAGING AND
BIOLOGICAL SAMPLE COLLECTION AND
BEFORE I TURN IT OVER TO JEFF
CURTIS, THE BOTTOM FIGURE IS AN
ADVANTAGE WE'VE SEEN WITH THIS
TYPE OF SOCIAL MEDIA APPROACH.
THE AMOUNT OF FLEXIBILITY IT
ALLOWS YOU IN BEING ABLE TO
TARGET SPECIFIC INDIVIDUAL TYPES
WITHIN EACH OF THE REGIONS
ACROSS THE SITES BY TAILORING
THE ADS AND DISTANCE FROM THE
SITE TO BE ABLE TO ENHANCE THE
INDIVIDUALS COMING IN HAS BEEN
VERY INTERESTING TO SEE HOW
GRANULAR WE CAN GET FROM WEEK TO
WEEK IN TRYING TO TWEAK THE
SOCIAL MEDIA APPROACH TO ENROLL.
THIS APPROACH DOES WORK.
WE'RE ON SCHEDULE TO ENROLL OUR
600 SUBJECTS BY THE FOURTH
QUARTER OF THE YEAR A YEAR
DELAYED GIVEN THE PANDEMIC WHAT
WAS ORIGINALLY PLANNED.
AS ED MENTIONED, A KEY COMPONENT
I'D LOVE TO SEE COME OUT OF THIS
ENDEAVOR IS CLOSER INTERACTION
BETWEEN SOME OF US MORE CLINICAL
EPIDEMIOLOGICAL INVESTIGATORS
AND SOME OF ON THE CALL OF
PARTICIPANTS MUCH MORE AND
BETTER UNDERSTANDING OF THE
BIOLOGICAL MECHANISMS AND THE
TECHNOLOGIES AVAILABLE TO ABLE
TO ENHANCE THAT.
I SHOWED YOU ONE EXAMPLE OF HOW
THIS CAN TAKE PLACE IN THE NEXT
SLIDE.
THIS SANE RO1 FUNDED TWO WEEKS
AGO WHICH IS RUN BY RON CRYSTAL
AND RON KANER AND LEVERAGING THE
COHORT DESIGN FOR THIS
PARTICULAR EARLIER AGE
INDIVIDUALS AND ARE USING VERY
ADVANCED METHODOLOGY TO IDENTIFY
SMALL AIRWAYS FROM DISTAL SMALL
AIRWAY SAMPLING, BASAL CELLS AND
AIR LIQUID INTERFACE AND THE
FUNCTIONAL CHARACTERISTICS OF
THOSE CELLS AS THEY RELATE TO
THE DETAILED CLINICAL
PHENOTYPING DATA COLLECTED
WITHIN THE BROADER SPIROMICS
CHARACTERIZATION AS ADAPTED FOR
SOURCE --
>> TWO-MINUTE WARNING.
>> THIS IS MY LAST SLIDE AND
THEN I'LL TURN IT OVER TO JEFF
CURTIS.
THIS IS HOW WE'D LIKE FOLKS TO
INTERACT IN THE FASHION WE
DESCRIBED.
ED, OVER TO YOU.
>> THANK YOU.
AS YOU SEE, WE'VE GOT A VERY
BROAD RANGE OF SKILLS AMONG THE
INVESTIGATORS IN THIS SPIROMICS
FAMILY OF STUDIES WE ONLY SHOWED
A TINY PART.
PARTICULARLY SHORT CHANGE AND
VASCULAR CHANGES.
IN THE LAST TWO SLIDES WE TAKE
THE CHARGE TO SAY WHAT WE THINK
IS THE STATE OF THE SCIENCE IN
COPD AND THEN THE KNOWLEDGE
GAPS.
SO WE BELIEVE WE'VE SHOWN
CONVINCINGLY AS MEILAN SHOWED
MANY SMOKERS HAVE SIGNIFICANT
PULMONARY SYMPTOMS WITHOUT
AIRWAY OBSTRUCTION AND HOPEFULLY
IN DATA WE'LL SHOW IT'S
PERSISTENT OVER A MEAN OF SEVEN
YEARS.
SOME OF THOSE SMOKERS
INDEPENDENT OF AIR FLOW
OBSTRUCTION MATCHING WHAT
DR. CRAPO SAID EARLIER WE'RE
SHOWING DISPLAY REVERSIBLE
BIOLOGY WE THINK RELATE TO
PATHOLOGICAL MUCUS AND COULD BE
A HUGE FOCUS FOR POTENTIAL NEW
THERAPEUTICS.
BY INCORPORATING BIO SPECIMEN
COLLECTION COHORT STUDIES CAN
BRIDGE THE GAP IN UNDERSTANDING
BETWEEN HISTOPATHOLOGICAL
STUDIES RELINING ON SURGICAL OR
AUTOPSY SPECIMENS AND THE
MESSAGE TO THE LUNG DIVISION TO
KEEP FUNDING THE COHORTS.
FOR THE FINAL SLIDE THE MAJOR
GAPS WE IDENTIFIED ARE TO DEFINE
THE PATHOLOGICAL PROCESSES IN
THE HUMAN LUNG SO WE CAN DEVELOP
ANIMAL MODELS AND DO THAT ACROSS
THE TIME FRAME OF COPD
DEVELOPMENT.
WE'RE TRYING TO DO THAT WITH
BRONCHOSCOPY AND THROUGH INDUCED
SPUTUM AND SAMPLES TO CORRELATE
THEM.
WE HOPE TO RELATE THE IMAGING
STUDIES WITH THE MICROBIOME AND
MULTI-OMICS OF PARTICULARLY LUNG
TISSUE BUT OTHER SAMPLES.
WE THINK IT'S IMPORTANT TO
DISTINGUISH THE RELATIVE
IMPORTANCE OF SMALL AIRWAY
ABNORMALITY VERSUS THE VASCULAR
PROCESS.
YOU CAN SEE WE'RE VERY FOCUSSED
ON CONSIDERING AGE AND START
PROVIDING MECHANISTIC EXEMPTION
EARLIER IN THE LIFE SPAN AND
EXCITED TO PARTNER WITH THE
YOUNGER COHORTS SUCH AS THE
AMERICAN LUNG ASSOCIATION HEALTH
STUDY AND WE THINK IT'S
IMPORTANT TO EXAMINE THE
ENVIRONMENTAL EXPOSURES OTHER
THAN SMOKING WHICH TURN OUT TO
BE INTIMATELY TIED TO ISSUES OF
HEALTH DISPARITIES.
THANK YOU.
>> THANK YOU, HAN, MARTINEZ AND
CURTIS ALSO MODERATING.
LET'S KEEP IT MOVING ALONG.
AGAIN, IT'S WE'RE WELL AWARE OF
WHAT SPIROMICS AND SOURCE DO BUT
GREAT TO SEE IT COME TOGETHER.
DR. CURTIS, DID YOU WANT TO
INTRODUCE OUR NEXT GROUP?
>> I SHOULD IF I HAD THE AGENDA
UP.
>> I CAN DO IT.
>> PLEASE.
>> THIS IS ANOTHER ONE OF OUR
COLLEAGUES DR. GRAHAM BARR WHO
IS GOING TO BE GIVING US AN
INTRO TO THE MESA LUNG STUDY.
GRAHAM.
>> THANK YOU SO MUCH.
TERRIFIC TALK TO THE EARLIER
COLLEAGUES.
SO IT'S MY PLEASURE TO SPEAK ON
FINDINGS CHALLENGE AND
OPPORTUNITIES IN THE MESA LUNG
STUDY.
I THINK IT'S A FANTASTIC
SYMPOSIUM I WANT TO QUOTE A LONG
STANDING CHAIR OF MESA WHO WOULD
DESCRIBE IT AS A POPULATION
LABORATORY.
IT'S A PHENOTYPED GROUP OF
PEOPLE WE'VE BEEN FOLLOWING FOR
A VERY LONG TIME NOW.
WHO HAVE INCREASE LEVEL OF
GENOTYPING AND ENVIRONMENTAL
CHARACTERIZATION AND ALLOWS US
TO ANSWER QUESTIONS PARTICULARLY
RELATED TO IMAGING PHENOTYPES.
THIS IS AN UNSELECTED SAMPLE OF
THE POPULATION THAT CAN
HOPEFULLY MOVE US FORWARD.
I'LL GIVE A QUICK OVERVIEW AND
FINDINGS RELATED TO PULL
MONETARY VASCULATURE WE FOCUSSED
ON.
DYSANAPSIS AND MESA LUNG IS A
POPULATION-BASED COHORT AND COPD
AND OTHER RELATED PHENOTYPES AND
TALK ABOUT RESEARCH GAPS AND
OPPORTUNITIES IN MESA LUNG WHICH
IS MULTIETHNIC AND MULTIOMIC AND
ANALYSIS FOR OTHER SYMPTOMS.
MESA MULTIETHNIC STUDIES OF
ATHEROSCLEROSIS IS A COHORT
ORIGINALLY FUNDED AS MY KIDS
WOULD SAY IN THE 1900s.
THE INITIAL EXAMINE WAS IN 2000
THROUGH 2002.
THERE WERE FOLLOW-UP EXAMINES
AND THERE WERE PARTICIPANTS
RECRUITED AT SIX SITES.
MEANING BACK IN THE DAY AND
NEIGHBORHOODS AROUND THE MAIN
SITES IN A TARGETED WAY AND WE
WERE EXPLICITLY NOT RECRUITING
PATIENTS WITH DISEASE OR
PATIENTS COMING INTO MEDICAL
CENTER.
IT'S A POPULATION-BASED DESIGN
WHICH LETS US LOOK AT WHAT'S
GOING ON IN THE GENERAL
POPULATION AND IS A LITTLE BIT
EASIER TO INFERENCE FOR THESE
REASONS.
MESA RECRUIT ED AND LOOK AT
MEASURES OF CARDIOVASCULAR
DISEASE AND WHETHER THEY PREDICT
CLINICAL CARDIOVASCULAR DISEASE
AND THE IMPORTANT ONES WAS
PULMONARY CALCIUM THE WHITE
STUFF WITH THE ARROWS WHICH IS
HARD CALCIFIED PLAQUE IN THE
ARTERIES.
THE ADVANTAGES WE TOOK ADVANTAGE
OF THE LUNGS SHOWN ON THE CTs.
WE ARE FORTUNATE ENOUGH TO AT
THE MESA LUNG STUDY FUNDED BACK
IN 2014, 2004, EXCUSE ME WHEN WE
ORIGINAL MEASURED SPIROMETRY
EXAMINE IN THE FOURTH MESA
EXAMINE AND TOOK THE CT SCANS
FOR CALCIUM AND THIS IS
RECONSTRUCTION IF 2000 AND GET
LUNG MEASURES AND VALIDATED
THESE PREVIOUSLY.
AND WE CO-REGISTERED THE IMAGES
AND SEE THE LUNG PROGRESSION AT
A REGIONAL LEVEL.
IN 2017, 2018, GIVE CONTRAST TO
ABOUT 750 PEOPLE TO MEASURE
PULMONARY BLOOD VOLUME AND
MICROVASCULATURE ENERGY AND
WE'RE CURRENTLY REPEATING THE
FULL LUNG CTs AS REQUIRED A FEW
YEARS AGO IN THE CURRENT
EXAMINE.
IT GIVES FOUR MEASURES OF
SPIROMETRY OVER 17 YEARS AND SIX
MEASURES OF CT IN EMPHYSEMA
RELATED MEASURES OVER 22 YEARS.
MESA HAS A LOT OF CARDIOVASCULAR
PHENOTYPING AS A CARDIOVASCULAR
COHORT.
AND WE'VE TAKEN ADVANTAGE OF
THAT TO LOOK AT CARDIO PULMONARY
INTERACTIONS AND THESE SHOW A
LINEAR RELATIONSHIP BETWEEN THE
HEART AND LUNG, MEASURED
QUANTITATIVELY BETWEEN EMPHYSEMA
AND THE STROKE MEASURED ON MRI
AND FOCUS ON TRYING TO ASSESS
THE PULMONARY VASCULATURE USING
MRI AND OTHER MEASURES OF CT.
IN SMITH AND COLLEAGUES LOOKED
AT DYSANAPSIS AND HIGH
VARIABILITY IN THE LUNG
POPULATION IN THE AND AS THE
DEVELOPMENT AND THERE'S FURTHER
WORK IN DETAIL.
AND NOT RELATED TO COPD AND
HIGHLIGHTS THE DIFFERENCE
BETWEEN RISK AND PREVENTION AND
SECONDARY PREVENTION AMONG
PATIENTS WITH COPD.
IT'S A LONG STANDING ISSUE IN
THE CARDIOVASCULAR ARENA AND
SOMETHING WE NEED TO APPRECIATE
IN THE PULMONARY ARENA AND THE
PAPER SHOWS WHERE YOU MAY NOT
WANT TO RANDOMIZE PATIENTS WITH
DYSANAPSIS TO A CLINICAL TRIAL.
MESA ALSO PROVIDE THE
OPPORTUNITY TO LOOK AT THE
GENERAL POPULATION AND THERE'S A
MAY IS LUNG SAMPLE OF ABOUT 2400
PARTICIPANTS.
10% HAVE COPD BY STANDARDS BIO
METRIC CRITERIA.
NOT SURPRISINGLY THERE'S SOME
OVERLAP WITH ASTHMA AND SOME
OVERLAP WITH CHRONIC BRONCHITIS
SHOWN FOR A LONG TIME AND IN THE
VEN DIAGRAM WE SEE OVERLAP WITH
EMPHYSEMA BUT MOST DO NOT IN
FACT HAVE COPD SPIROMETRIC
DEFINED AND AS WE LOOK IN THE
GENERAL POPULATION THE
PHENOTYPES GET SPREAD OUT AND
IT'S IMPORTANT FROM AN MODELLING
SPECIFIC AND ANIMAL MODEL TO
KNOW WHICH OF THESE QUADRANTS
YOU'RE IN.
AND OTHER SUBTYPES ARE EQUALLY
COMMON IN MESA LUNG WHICH IS
POPULATION-BASED WITH MUCH MORE
SMOKING EXPOSURE.
THESE ARE I WOULD ARGUE
DIFFERENT DISEASES IN DIFFERENT
PEOPLE WITH DIFFERENT RISK
FACTORS.
THIS IS NOT A NEW CONCEPT.
WE'VE LINED OUT SIX OF THESE NOT
SMOKING RELATED EMPHYSEMA SUB
TYPES AND THE OTHER THREE THAT
ARE SMOKING RELATED AND SOME ARE
CLEARLY COPD SUBPHENOTYPES.
THIS IS AN OLD CONCEPT GOING
BACK MORE OR LESS HALF A CENTURY
TO ORIGINAL PAPER SHOWING THE
DISSEMIN
DISSEMINATED EMPHYSEMA IS NOT
RELATED TO SMOKING.
MESA HAS A LARGE AMOUNT OF
ENVIRONMENTAL CHARACTERIZATION
AND WE RECENTLY PUBLISHED THE
AMBIENT OZONE EXPOSURE AND MANY
OF US HAD PARTICULAR EXPOSURES
IN THE EAST COAST RECENTLY.
THIS IS SHOWING 10 TO 18-YEAR
OZONE EXPERIENCE GROUND LEVEL IN
PROGRESSION OF EMPHYSEMA.
IT'S ONE EXAMPLE OF A NUMBER OF
AIR POLLUTION STUDIES WE'RE
GOING AND USING OZONE AS A MODEL
THAT WAS STANDARD AND THERE'S A
LOT OF OPPORTUNITIES IN MESA TO
MOVE FORWARD.
SOME RESEARCH GAPS WILL HELP IN
OUR INVOLVING INFORMATION OF
COPD RELATED PHENOTYPES IN THE
GENERAL POPULATION AND I THINK
THIS GOES BEYOND PRE-COPD
BECAUSE A LOT OF THESE
PARTICIPANTS HAVE ILLNESSES WE
FOUND IN SPIROMICS AND MESA
WHICH DOES NOT NECESSARILY
PROGRESS AND FIND A LIMITED
UNDERSTANDING OF COPD PHENOTYPES
AMONG INDIVIDUALS WITHOUT
SMOKING EXPOSURE AND SOME OF THE
SUBSEQUENT COHORTS WE TALKED
ABOUT AND IT'S IMPORTANT TO
STUDY THIS IN THE GENERAL
POPULATION AND THERE'S LIMITED
MULTI-ETHNIC STUDIES OF ADEQUATE
POWER WHICH ARE PARTICULARLY
IMPORTANT GIVEN IN THE U.S. WE
LIVE IN MULTI-ETHNIC COUNTRY AND
MUCH OF WHAT WE NEED TO
RECOGNIZE THE MEDICALIZATION OF
ASPECTS RELATING TO
MULTI-ETHNICITY IN ASPECTS OF
MULTI-ENVIRONMENT
CHARACTERIZATION BEYOND THE
GENETIC CHARACTERIZATION.
SOME CHALLENGES WORKING IN MESA
IS THESE ARE COMPLEX DATA AND
LONGITUDINAL REPEATED NEARBY AND
THE ANCILLARY STUDIES AND THE
ANALYTICAL EFFORT AND EXPERTISE
IS CHALLENGING.
WE WANT TO HELP AND WOULD BE
DELIGHTED TO SET UP SUBSEQUENT
SEMINARS IF PEOPLE ARE
INTERESTED BUT AGAIN A HIGHLY
CHARACTERIZED POPULATION-BASED
SAMPLE WHERE MOST PEOPLE HAVING
SMOKED A LOT AND REFLECTS OF THE
REALITY OF PEOPLE WITH LUNG
DISEASE AND THE MULTIETHNIC
DESIGN FOR CONFOUNDING AND
ELEMENT 23 YEARS OF FOLLOW-UP
AND BEFORE THEY DEVELOP LUNG
DISEASE TO UNDERSTANDING THE
LUNG DISEASE.
THERE'S A LOT OF OPPORTUNITIES
IN MESA WITH TOPMED.
I'M ONLY SHOWING THE TOPMED
MULTIOMIC DATA BUT ESSENTIALLY
THE WHOLE COHORT HAS WHOLE
GENOME SEQUENCING AS METHYLATION
AND TRANSCRIPTOMICS AND
PROTEOMICS AND METABOLOMICS.
AND WE'RE EXTENDING THIS
CURRENTLY GIVEN MOST THE WORK IS
IN BLOOD WHEREAS WE KNOW WE'RE
NOT ACCESSING THE LUNGS SO WELL
SO WE'RE CURRENTLY COLLECTING
AND HAVE ALMOST 1,000
PARTICIPANTS IN THE EXAMINE WITH
AIR FOLLICLES AND NASAL EPIT
EPITHELIAL SAMPLING.
IN CONCLUSION THE MESA LUNG
STUDY IS A UNIQUE MULTIETHNIC
STUDIES AND HIGH LEVEL OF
ENVIRONMENTAL AND MULTI-OMIC
CHARACTERIZATION WHICH SETS UP
TRANSLATION IN TERMS OF IMAGING
AND MULTIOMIC CHARACTERIZATION
WITH LAB STUDIES AND OPEN TO
COLLABORATION.
DETAILS IN THE MESA WEBSITE
SHOWN HERE AND MESA DATA AND
ANALYSIS COMMENTS AND BIODATA
CATALYST AND A WANT TO THANK THE
CURRENT COLLABORATORS INCLUDING
ERIC HOFFMAN AND MANY OTHERS AND
PARTICULARLY THE NUMBER OF
COLLABORATORS WE WORKED WITH
OVER THE YEARS TO SET THIS STUDY
UP INCLUDING SENIOR
CARDIOVASCULAR EPIDEMIOLOGISTS
WHO HELPED JUNIOR FACULTY
MEMBERS 20 YEARS AGO TO GET MESA
LOCKED UP.
THANK YOU.
>> NEXT IS SPEAKER IS IS
DR. WASHKO AN AT HARVARD AND
COLLABORATOR OF QUANTITATIVE
IMAGING SOLUTION.
>> THREW FOR THE INVITATION TO
BE HERE TODAY TO BE A
PARTICIPANT AND TO SHARE IN A
LOT OF THESE GREAT COHORTS.
I ENJOYED THE TALKS SO FAR.
WHAT I'LL BE DOING NEXT IS
TALKING THROUGH CARDIA AND THE
AMERICAN LUNG ASSOCIATION LUNG
HEALTH COHORT.
GETTING STARTED, CARDIA IS A
PROSPECTIVE COMMUNITY-BASED
POPULATION STUDY FOCUSSED ON THE
EVOLUTION OF CARDIOVASCULAR
DISEASE FROM YOUNG ADULTHOOD.
IT STARTED IN 1985 WHEN A LITTLE
OVER 5,000 BLACK AND WHITE
INDIVIDUALS AGE 18 TO 30 WERE
RECRUITED FROM THE FOUR SITES
YOU SEE LISTED THERE.
EACH SITE HAT AN EQUAL NUMBER OF
RACE, SEX AND EDUCATIONAL
ATTAINMENT.
A NICE BALANCE AND 50% OF THE
INVITED INDIVIDUALS WERE
ULTIMATELY EXAMINED AND ENROLLED
IN CARDIA.
RE-EXAMINATIONS HAVE OCCURRED
AND AT THE YEAR, 30 YEAR THE
MEAN AGE OF 55 OVER 70% OF THE
SURVIVING COHORT RETURNED FOR
THE EXAMINATION AND WE'RE
COMPLETING AN EXAMINATION AND
WITHIN CARDIA IS CARDIA LUNG
WITH A CARDIOLOGIST AND WE
LOOKED AT SMOKING HISTORY,
EXPOSURE, LUNG FUNCTION AT THE
DAYS WE SEE AND CT SCANS
OBTAINED AT YEAR 15, 20, 25 AND
35.
AND THE CT SCANS -- IF YOU CAN
GO BACK.
THE CT SCANS AT YEAR 15, 20 AND
25 WERE THE CARDIAC SCANS
SIMILAR TO MESA AND YEAR 35 IS A
VOLUMETRIC LUNG SCAN WE'RE JUST
COMPLETING.
I WANT TO SPEND THE NEXT FEW
MINUTES TALKING ABOUT THE DATA
COMING FROM CARDIA.
I'LL FOCUS ON THE ADULT LIFE
COURSE MEASURES OF LUNG
FUNCTION.
SO WE PUT TOGETHER THESE
TRAJECTORIES, IF YOU WILL, OF
LUNG FUNCTION FROM MEAN AGE 25
SPANNING TO MEAN AGE 55.
I'M SHOWING ON THE LEFT THE FEV1
EXPRESSED AND FOUND FIVE UNIQUE
TRAJECTORIES FROM THE PRESERVED
IDEAL LUNG HEALTH AT THE TOP IN
THE BLUE TO THE WORSENING LUNG
HEALTH IN RED AND POOR LUNG
HEALTH IN THE BOTTOM.
THIS IS THE PREVALENCE OF RATIO
OF LESS THAN 0.7.
AT BASELINE THIS IS AGAIN THE
MEAN AGE OF 25, ALMOST 30% OF
PEOPLE IN THAT PERSISTENTLY POOR
HEALTH GROUP HAD OBSTRUCTION AND
THAT CLIMBED TO ALMOST 60% OF
PEOPLE IN THAT TRAJECTORY BY THE
YEAR 30 OR MEAN AGE 55 EXAMINE.
WE DID A VISUAL INSPECTION OF
THE EARLIER SERIAL CT SCANS AT
15, 20 AND 25 AND CARDIAC CT
SCANS AND LOOK FOR EMPHYSEMA OR
PARASEPTAL DISEASE AND A 8% OF
THOSE PEOPLE OF PERSISTENTLY
POOR HEALTH HAD SOME FORM OF
COPD A MEAN AGE OF 40 ANG 20% OF
THE PEOPLE IN THE WORSENING LUNG
HEALTH TRAJECTORY AND
PERSISTENTLY POOR HEALTH
TRAJECTORY HAD A FORM OF
EMPHYSEMA ON THEIR CT SCANS.
WE WENT BACK TO THE EARLIER
COLLECTION AND RESPIRATORY
SYMPTOMS TO BE CONSIDERED
POSITIVE.
A PERSON HAD TO INDEPENDENTLY
REPORT AT YEAR ZERO AND AT YEAR
TWO.
YOU SEE THE RESPIRATORY SYMPTOMS
ON THE LEFT COLUMN OF THE PANEL.
WE THEN LOOKED AT THE SUBSEQUENT
DECLINE IN LUNG FUNCTION FROM
YEAR FIVE TO YEAR 30.
AND YOU CAN SEE THAT ANY SYMPTOM
AS WELL AS THE SUBTYPES OF
SYMPTOMS WERE GENERALLY ALL
RELATED TO AN ACCELERATED LOSS
OF THE FEV1 AS WELL AS THE FEV1,
FEC AND ANNUALIZED DECLINE THE
BASELINE PRESENTATION AND
SYMPTOMATIC MANIFESTATION WAS
RELATED TO THE SUBSEQUENT LOSS
OF LUNG FUNCTION.
WE LOOKED AT THE SYMPTOMS AND
THE SUBSEQUENT DEVELOPMENT OF
EMPHYSEMA AND IF YOU LOOK AT
COUGH-RELATED SYMPTOMS AND CHESS
ILLNESS AND WHEEZE THEY'RE
ASSOCIATED WITH CENTRAL
EMPHYSEMA AND ANY FORM OF VISUAL
EMPHYSEMA SYMPTOMS PREDICT
DISEASE SOME 25 YEARS LATER.
THEN IF WE STEP OUTSIDE THE
LUNG, THESE ARE DATA NOW
PUBLISHED SIX YEARS AGO LOOKING
AT BASELINE MEASURES OF LUNG
FUNCTION AND THE SUBSEQUENT
DEVELOPMENT OF EXTRA PULMONARY
COMORBIDITIES LOOK AT THE LINK
BETWEEN THE LUNG AND THE REST OF
THE BODY.
AND WHAT THEY FOUND WAS LUNG
FUNCTION PREDICTED THE
DEVELOPMENT OF COMORBIDITIES.
IF YOU LOOK AT THE PANEL ON THE
LEFT FOR THOSE WHO HAD A FEV1
GREATER OR EQUAL TO 80%
PREDICTED AT THE BASELINE
EXAMINE THE MEAN AGE DIAGNOSED
WITH THE FIRST COMORBIDITY WAS
48 TO 49 YEARS WHEREAS IF YOU
LOOK TO THE RIGHT WITH THOSE
WITH LUNG FUNCTION IT WAS LESS
THAN 40 YEARS OF AGE.
IT'S EXCITING AND WE'RE NOW
TRYING TO UNDERSTAND THE LINK
BETWEEN THE LUNG AND THE REST OF
THE BODY.
AND CARDIA HAS GIVEN GREAT
INSIGHT THAT THE OLD IR LIFE
SPAN.
IT WAS STARTED AT SPECIALLY THE
YOUNG ADULT AND DATA ARE NOT AT
RICH.
WHAT WE SOUGHT TO DO IS DEFINE A
NEW COHORT TO EXPLORE THE
INITIAL STEPS OR PATHWAYS THAT
LEAD TO THE DIVERGENCE FROM PEAK
HEALTH TO PARALLEL HEALTH TO
DISEASE THAT ARE DESCRIBED IN
MULTIPLE COHORTS TODAY.
SO TO DO THIS WE EMBRACED THE
CONCEPT IDEAL LUNG HEALTH IS
MORE THAN THE ABSENCE OF LUNG
DISEASE AND ASSOCIATED WITH
ADVERSE CONSEQUENCES AS SHOWN IN
SOME OF THE PREVIOUS SLIDES.
AND DISEASE-FOCUS STUDIES WITH
DISEASE DO NOT NUMBER LUNG
HEALTH OF THE PREVENTION
STRATEGIES AND THE PREVENTION OF
LUNG HEALTH IS NOT SOLELY
PREDICATED ON THE CIGARETTE
SMOKE BUT UNDERSTANDING THE FULL
EXPOSOME RELATED TO THAT LOSS OF
LUNG HEALTH.
AND IF WE LOOK TO THE HEART AND
CARDIOVASCULAR DISEASE
PREVENTION HAVE BEEN ATTRIBUTED
TO HEALTH PROMOTION AND THE
ABSENCE OF A DISEASE AGNOSTIC
COHORT IN THE U.S. HAS HINDERED
OUR EFFORTS AT PREVENTION OF
LUNG DISEASE.
WE LACK THE FRAMINGHAM HEART
STUDY FOR THE LUNG.
THIS IS REALLY THE KEY POINT IS
WE LACK THE CHOLESTEROL.
THE AMERICAN LUNG ASSOCIATION
LUNG HEALTH COHORT IS A
PROSPECTIVE COMMUNITY-BASED
COHORT STUDY CONDUCT THROUGH THE
ACRC.
IT'S A CONSORTIUM OF
INVESTIGATIVE SCIENCE CHAPERONED
AND SORTED BY THE AMERICAN LUNG
ASSOCIATION AND THE RESEARCH
CENTER ARE CENTERS OF EXCELLENCE
FOR CLINICAL TRANSLATIONAL
INVESTIGATION.
THE GOAL OF THE ALA LUNG HEALTH
COHORT IS TO RECRUIT 4,000
PATIENTS, THAT'S ABOUT 235 PER
CENTER AT A BASELINE AGE OF 25
TO 35 YEARS OLD.
IT IS DISEASE AGNOSTIC AND
FOCUSSED ON THE CONCEPT OF
RESPIRATORY HEALTH AND THE
CURRENT FUNDING CYCLE SUPPORTS
THE RECRUITMENT IN A SINGLE
INITIAL-BASELINE PERSON
EXEMPT
EXAMINATION AND WE WANT TO MAKE
THIS ESSENTIALLY THE FRAMINGHAM
ANALOG OR FRAMINGHAM LUNG STUDY.
THE OVER ARCHING GOALS ARE THE
DIVERGENCE BETWEEN HEALTH AND
DISEASE OVER THE LIFE SPAN.
IN THE NEAR TERM WE WANT TO
EXPOSE THE RELATIONSHIP BETWEEN
EXPOSURES, BEHAVIORS, BIOMARKERS
AND RESPIRATORY HEALTH AND
MEDIUM AND LONG-TERM TO
DETERMINE FACTORS IN THE
BIOLOGICAL PATHWAYS THAT
INFLUENCE THE DIVERGENCE FROM
IDEAL TO PARALLEL HEALTH AND TO
CHRONIC LUNG DISEASE ACROSS THE
ADULT LIFE SPAN.
WE WANT TO FIND THAT
CHOLESTEROL.
THE PROTOCOL FOR INCLUDES
QUESTIONNAIRES, SPIROMETRY AND
BIO BANKING AND HAVE A SCAN
HARMONIZED WITH COPD GENE AND
THE TASMANIAN LONGITUDINAL
HEALTH STUDY YOU'LL HEAR ABOUT
TO HAVE DIRECT COMPARISONS OF
THE RADIO LOGIC FEATURES AND
COLLECTING SPIROMETRY AND KEY
ISSUES INCLUDE HOW TO RECRUIT A
REPRESENTATIVE COHORT OF THE
U.S. POPULATION OF 25 TO
35-YEAR-OLDS.
WE WANT TO MAKE SURE IT'S
REPRESENTATIVE IN TERM OF RISK
FACTORS AND HOW DO WE ENGAGE THE
SAME GROUP OF PARTICIPANTS
INCREASINGLY MOBILE.
WE WANT TO MAKE SURE THEY FEEL
LIKE THEY'RE PART OF SOMETHING
AND WILLING TO PARTICIPATE.
WITH CURRENTLY HAVE A LITTLE
OVER 1,000 PEOPLE ENROLLED.
AS DR. MARTINEZ ALLUDED TO WE'RE
ADAPTING TO THE POST-COVID
WORLD.
ONE THING THAT CAME OUT IS OUR
PIVOT AND FOCUS ON HOME
SPIROMETRY AND WE'VE BEEN
GETTING GREAT ADAPT ARGUING FOR
THIS TYPE OF WORK AND PRESENTED
THE DATA AT THE RECENT AMERICAN
THORACIC SOCIETY CONFERENCE.
THE DATA IS ONGOING AND WE'RE
PREPARING OUR FIRST BATCH OF BIO
SPECIMENS FOR PROCESS.
WITH THAT I WANT TO CLOSE BY
ACKNOWLEDGING REALLY THE
MULTITUDE PEOPLE INVOLVED IN
SUPPORTING CARDIOVASCULAR LUNG
COHORT.
DR. CALLAHAN IS THE P.I. OF
CARDIA LUNG AND THE OVER ALL
P.I. OF THE LUNG HEALTH COHORT
AND HAS A TEAM THAT INCLUDES
MYSELF.
I WANT TO THANK ALL THE CARDIA
SITES AND THE EXECUTIVE
COMMITTEE AND THE SCIENCE
INVESTIGATORS AND ME AMERICAN
LUNG ASSOCIATION WHO HAS BEEN
PARTNERING WITH THE NHLBI AND
SUPPORTING THIS WORK AND
EVERYONE BEHIND THIS HAS BEEN
SUPPORTIVE IN THIS AND CERTAINLY
THE NIH AND NHLBI FOR ALL THEIR
SCIENTIFIC ENGAGEMENT AND
SUPPORT FOR THE COMPLETION OF
BOTH THESE METHODS.
THANK YOU.
[POOR AUDIO]
>> YOU'RE BREAKING UP A BIT.
>> JEFF, DO YOU WANT TO TAKE
OVER?
>> I'LL TAKE THE NEXT ONE THEN.
GREAT, SO THE NEXT PRESENTATION
IS GOING TO DESCRIBE THE CANCOLD
COHORT FROM WAN-CHENG TAN
PROFESSOR OF MEDICINE AT UBC AND
JEAN BOURBEAU IN CANADA.
OVER TO YOU, DR. TAN.
>> THANK YOU FOR INVITING US.
DR. BOURBEAU SPEAKING.
I'LL DO THE PRESENTATION ON
BEHALF AS CO-P.I.
IT'S ALREADY BEEN MENTIONED ALL
THEE COHORT AND THE VILLAGE OF
PEOPLE WITH DIFFERENT EXPERTISE.
WE'RE VERY LUCKY TO CO-LEAD THIS
CANADIAN INITIATIVE.
WHILE THE SLIDES ARE COMING UP
AS LONG AS SOMEONE IS WORK ON
THE SLIDE PRESENTATION AND WE
HAVE A CANADIAN CO-OBSTRUCTIVE
LUNG DISEASE.
IT'S A POPULATION-BASED COHORT.
I'M GOING FIRST PRESENT THE
DESIGN OF THE STUDY AND WHERE DO
WE STAND WITH THE STUDY.
THE FOCUS IS GOING TO BE FOR
THIS SESSION CONSIDERING THE
TOPIC THERE'S BEEN A LOT OF
PUBLICATION.
IT'S RELATIVELY A SMALL COHORT
BUT VERY MUCH KEY DETAIL AND IN
TERMS OF THE CHARACTERIZATION OF
IT AND WE HAVE CLOSE TO ONE OF
THE STUDIES BUT I DECIDED TO
FOCUS ON THE NEW KNOWLEDGE AND
RISK FACTOR TO GIVE EXAMPLE OF
WHAT POTENTIAL FOR PATHOGENESIS
OF COPD AND SOME OF THE CURRENT
INITIATIVE GIVING A HIGHLIGHT ON
THE CT IMAGING AND SOME OF THE
EARLY WORK IN UNDERSTANDING OF
THE PATHOPHYSIOLOGY AND NOT TO
SAY I'M AN EXPERT IN EITHER AREA
BUT MORE FOR PEOPLE TO SEE THE
APPROACHES NOW AND TO COME AND
END IT ON THE FUTURE RESEARCH.
AND THE OVERVIEW OF THE STUDY
IT'S BEEN A LONG JOURNEY.
PEOPLE HAVE TO KNOW IT STARTED
FROM BOLD WHERE VANCOUVER WAS
PART OF A PREVALENT STUDY AND
THEN WE STARTED BUILDING WITH
FIVE SIDE AND WHEN I REACHED
DR. WAN TAN TO BUILD ON THE
COHORT WE EXTENDED THE PREVALENT
STUDY OF FIVE TO NINE CANADIAN
SIDE OVER 6,500 SUBJECTS HAD
BEEN STUDIED IN COLD AND THEN
INVITED THE COPD SUBJECT AND TO
PARTICIPATE AND MATCHING A
SMOKER WITH NORMAL SPIROMETRY
AND A NEVER SMOKER AND
SPIROMETRY.
AND TO IDENTIFY THE POTENTIAL
MODIFIABLE FACTOR BEYOND SMOKING
FOR THE PATHOGENESIS OF COPD AND
TO A WORLD WHERE DIFFERENT
EXPOSURES HAVE BEEN CHANGING.
AND A PLATFORM OF THE
POSSIBILITY OF GENERATING NEW
RESEARCH QUESTIONS USING SOME OF
THE TECHNOLOGY THAT WE'RE
LOOKING AT FROM THE
CROSS-SECTIONAL DATA AND
LONGITUDINAL DATA.
IT'S ASSEMBLED FROM THE GENERAL
POPULATION AND RANDOM DIGIT
DIALING WHERE PEOPLE WERE
INVITED NOT IN CONSIDERATION OF
THE EXPOSURE WITH SMOKING BUT
THE AGE, 40 YEARS OF AGE OR MORE
AND NOT BEING INSTITUTIONALIZED.
AND THEN USING THE MATCH GROUP
INDIVIDUAL AND POPULATION
WITHOUT COPD EXPOSED TO SMOKING
OR NOT-EXPOSED TO SMOKING.
THE EVALUATION TO NOW HAD BEEN
THE FIRST EVALUATION OF COLD TO
THE BASELINE WHICH IS A MEDIAN
FOLLOW-UP OF THREE YEARS AND
ANOTHER FOLLOW-UP AT 18 MONTHS
THAT WAS NOT COMPLETED BECAUSE
OF LACK OF FUNDING AND THREE
YEAR AND WE'RE PROCESS NOW AND
DEALING WITH COVID AS MANY OF
OUR STUDY AND PRESENT ED WE'RE
ABOUT TO DO 10 TO 12 YEARS AT
MEDIAN FOLLOW-UP AND WE'RE
HALFWAY THROUGH THE EVALUATION
AND THAT SHOULD END IN 2024.
THE EVALUATION INCLUDES A
QUESTIONNAIRE IN DIET AND
DEMOGRAPHIC, SMOKING, BIO MASS
EXPOSURE, MARIJUANA EXPOSURE AND
QUALITY OF LIFE AND ALSO
CARDIOVASCULAR PULMONARY
EXERCISE TEST, CT SCAN USING THE
SAME METHODOLOGY THE COPD GENE
AND BLOOD BANKING WE HAVE AT
EACH VISIT.
IT HAD BEEN DONE AT THE BASELINE
OF TEN FOLD.
IT'S BEEN REPEATED AT THREE
YEARS AT RISK AND COPD AND IT'S
GOING TO BE REPEATED AT VISIT 12
AND 10, 12 YEARS INCLUDING WHAT
WE CALL THE HEALTHY SUBJECT
REFERENCE GROUP FOLLOWED WE'LL
HAVE COPD AND CT SCAN AS WELL
AND PROSPECTIVE EXACERBATION.
WE HAVE A 10 TO 8 YEAR MEDIAN
FOLLOW-UP AND WE'RE ABOUT TO
ACCESS THE DATABASE LINKAGE IN
CANADA.
THERE'S AN ISSUE BECAUSE IT'S
MANAGED THROUGH DIFFERENT
PROVINCES.
WE'LL HAVE THE POSSIBILITY OF
HAVING ACCESS AT THE CANADIAN
LEVEL TO AND STARTED LINKABLE
WITH ENVIRONMENTAL EXPOSURE.
YOU CAN SEE THE NINE SIDES
ACROSS SIX PROVINCES IN CANADA.
THIS IS WHERE AS A FLOW CHART WE
START FROM THE BEGINNING WITH
THE COPREVALENT STUDY 6,500 AND
WE INVITED AND VISITED ONE TO
PARTICIPATE.
WE HAVE 1,500 SUBJECTS AND AT
VISIT THREE WE HAD THE 78% OF
PEOPLE WITH 330 PARTICIPANTS
LOST AT FOLLOW-UP AND WE'RE IN
THE PROCESS OF DOING VISIT FOUR
WHICH IS REPRESENTING A 10, 12
YEAR FOLLOW-UP.
YOU HAVE A PAPER TALKING ABOUT
THE LONGITUDINAL COHORT.
I'D LIKE TO GIVE YOU AN OVERVIEW
OF THE RISK FACTOR AND SOME OF
THE NEW KNOWLEDGE PEOPLE CAN SEE
PROBABLY WE HAVE BAUD IT'S OPEN
TO PEOPLE NOT ONLY IN CANADA AND
INVITE PEOPLE TO VISIT THE
WEBSITE AND CALL AND SEE WHAT WE
HAVE.
AND FROM THE STUDY YOU CAN SEE
THE DISTRIBUTION OF THE NON-COPD
IN THE OTHER -- ORIGINAL
PREVALENT STUDY TO GOLD 1
THROUGH 4 AND OTHER THAN SEX
THAT IS IN THE COHORT WE HAVE
THE POSSIBILITY OF THE COPD.
THE PHYSICIAN THAT HAVE NOT
REQUIRED PEOPLE HAD COPD THEN
HAVING THE POSSIBILITY OF
FOLLOWING PEOPLE WITH MILD
DISEASE FROM THE BEGINNING.
THIS IS WHERE IF YOU START FROM
THE END RIGHT SIDE OF THE TABLE
THAT BUILDS THE GOLD 3 PLUS
WHICH IS THE SAMPLING OF THE
POPULATION HERE WE'RE VERY
SKEWED TOWARDS GOLD 1 AND 2 AND
HAVE THE GROUP OF PRISM THAT
HAVE B
HAVE BEEN AND WE HAVE THE EVER
SMOKER AND WE HAVE THE NEVER
SMOKER AS WELL IN THE COHORT.
>> TWO-MINUTE WARNING.
>> THAT MEANS I TALKED FOR --
OKAY.
LET'S MOVE ON TO THE TRADITIONAL
RISK FACTOR.
MOVE ON, PLEASE.
THEN WE AGAIN GIVING SOME
INTEREST ON THE NEVER-SMOKER
MOVE ON IN THE FEATURE.
THERE'S SOME INTEREST IN
MARIJUANA AND MORE MODERN
EXPOSURE AND ALSO BLOOD IN THE
FIELD AS A PROGNOSTIC BIOMARKER
AND THE DECLINE IN FEV1.
THERE'S ALREADY BEEN SPIROMIC
ON THE DYSANAPSIS AND A
COLLABORATION BETWEEN COHORT
STUDY AND WE'RE PLANNING TO LOOK
AT THE LONGITUDE DATA IN THE
NEXT YEAR TO COME.
SOME ON CT IMAGING.
THIS IS NOT MY AREA OF EXPERTISE
BUT TO SHOW THERE'S WORK DONE ON
THE VASCULAR PRUNING AND TRACHEA
ABNORMALITIES AND PECTORAL
MUSCLE AND THERE'S NEW BIOMARKER
WORK AND SOME WORK ALSO THAT HAD
BEEN COMPLIMENTARY TO THE
CANNABIS USE IN ASSOCIATION NOT
ONLY WITH PHYSIOLOGICAL CHANGE
BUT WITH CT MEASURE.
AND AN AREA OF GREAT INTEREST IS
THE PHYSIOLOGY MEASURE AND THE
CARDIO PULMONARY STRESS AND SOME
PEOPLE HAVE ALLUDED TO THE QUIET
ZONE WHERE THERE'S BEEN PREVIOUS
WORK DONE AND RECENTLY IN THE
LAST DECADE SHOWING THE
NARROWING AND REDUCED NUMBER OF
TERMINAL BRONCHIAL THAT PRECEDES
EMPHYSEMA.
WE'RE LOOKING AT THE VASCULAR
CENTRIC PORTION OF COPD.
TO START TO BE INTERESTED IN
SOME OF THE PHYSIOLOGY FEATURES
OF AND THE PRESENCE OF THE MILD
COPD COHORT AND THE RELATIONSHIP
BETWEEN SOME CLINICAL OUTCOME
SUCH AS DYSAPNEA AND RELATED
ACTIVITY.
WHERE THE MICROVASCULATURE
DYSFUNCTION AND YARD YO
PULMONARY EXERCISE TEST.
WE DO BELIEVE THERE'S INDICATION
THAT COULD PRECEDE THE LEVEL OF
DETECTION BY THE CT SCAN AND
THERE IS ALSO WHEN IT IS
DETECTED EARLY ON THE VASCULAR
DYSFUNCTION IN COPD HAS BEEN
SHOWN TO BE REVERSIBLE USING THE
NITRIC OXIDE EFFECT YOU CAN SEE
ON THE PANEL.
WE HAVE DETERMINED ALSO ON
EXERCISE THE EFFICIENCY MEASURED
BY V CO2 AND REFERENCE
POPULATION THERE'S BEEN A
PUBLICATION ON THAT.
THERE ARE NOW CORRELATION WITH A
TEST THAT WOULD BE EASIER TO
MEASURE AND SOME IMAGING ALSO
AND THAT IS QUITE IMPORTANT
BECAUSE THE CVO2 ASSOCIATED WITH
THE PEAK WORK HAS BEEN PRESENT
IN A QUARTER OF THE COPD
REGARDLESS OF THE GOLD STATE AND
THIS IS WHERE THE LONGITUDINAL
DATA WILL BE IMPORTANT THAT
IMPAIRED EV EFFICIENCY WOULD BE
A POTENTIAL CONTRIBUTOR TO
DYSAPNEA.
WE HAVE INITIATED SOME WORK IN
PRISM.
THIS IS A PUBLICATION IN PRESS
ON THE CARDIOVASCULAR RISK AND
PRESENCE OF THE PRISM.
THE TOP PANEL BEING THE
PREVALENCE AND THE LOWER PANEL
BEING THE INCIDENTS ON
THREE-YEAR WHERE WE ATTEMPT TO
LOOK OVER A LONGER PERIOD OF
TIME AND THIS IS INDEPENDENT OF
THE KNOWN RISK FACTOR, AGE, SEX,
SMOKING AND HYPERTENSION AND
THOSE WHO DIDN'T HAVE
CARDIOVASCULAR DISEASE TO START.
THEN THERE IS MORE GOING ON ALSO
COMPARING PRISM TO COPD AND
CONTROL AND WORK AND PREPARATION
TO SHOW REDUCED LIMIT FOR VOLUME
EXPANSION WITH AN ACCELERATED
ACHIEVEMENT WITH VT ON IC IN
ABOUT 70% OF PATIENTS WITH
PRISM.
AND THIS IS MAINLY A FEATURE
THAT REDUCES OPERATING LIMIT.
WE THINK THAT CANCOLD HAS A
FUTURE IN TERMS OF RESEARCH AND
IMPLEMENTING COHORT AND IN TERMS
OF DETERMINATES OF DISEASE
PROGRESSION FOR USING THE
LONGITUDINAL EVALUATION I THINK
OUR EFFORT SHOULD BE UNDERTAKEN
FROM NOT ONLY THE MAIN AND KNOWN
RISK FACTOR BUT LOOKING AT THE
NEW RISK FACTOR AND
CHARACTERIZING THE POPULATION
BETTER AND HAVE GWAS
CHARACTERIZATION AND OLD
CHEMICAL POPULATION FOR EXAMPLE
AND LOOKING AT THE MODERN
SOCIETY EXPOSURE SUCH AS
POLLUTION, WILDFIRE.
WE HAVE A PROJECT GOING ON RIGHT
NOW ON THIS AND WITH THE 10 TO
12 YEAR MEDIAN FOLLOW-UP AND
THINK THE DATA WILL BRING INTO
OUR UNDERSTANDING OF THE
PATHOGENESIS AND RISK FACTOR.
ALSO A BETTER UNDERSTANDING OF
HETEROGENEITY AND
INTERRELATIONSHIP BETWEEN
MEASURABLE STRUCTURAL FROM THE
CT SCAN WITH THE NEW BIOMARKER
AND FUNCTIONAL ABNORMALITY FROM
THE FUNCTION TEST AND DURING
EXERCISE AND ALSO CLINICAL
OUTCOME IN PATIENTS WITH MILD
DISEASE.
WE THINK MILD DISEASE IS THE KEY
HERE OPPOSED TO WORKING WITH
DISEASE THAT IS ALREADY WELL
WHERE THE DAMAGE IS ALREADY IN
PLACE WHERE WE CAN LOOK AT
DISTINCT PHYSIOLOGICAL DISEASE
MICROVASCULATURE DYSFUNCTION AND
PHYSIOLOGY FROM CT SCAN IMAGING
TO SEE IF IT WILL BETTER HELP US
PREDICT DISEASE PROGRESSION AND
THINK SPECIFIC
PATHOPHYSIOLOGICAL PHENOTYPE MAY
HAVE BIOLOGICAL SIGNATURE
UNDERSTANDING THE HETEROGENEITY.
I THINK THERE'S NICE
COLLABORATION ON THE BIOLOGICAL
DETERMINATES AND GENETIC
SIGNATURE AND ALSO LOOKING AT
THE PROGNOSTIC AND COMORBIDITY
IN PARTICULAR CARDIOVASCULAR
COMORBIDITY AND LOOKING AT THE
STRUCTURAL FINDING AND CLINICAL
OUTCOME BASED ON ESTABLISHING A
NEW RISK FACTOR AND COPD
ENDOTYPE AND OFFER TRANSLATIONAL
RESEARCH AND FINAL
ACKNOWLEDGEMENT AS I SAID
THERE'S A HUGE AMOUNT OF PEOPLE
THAT DOESN'T SHOW ON THE SLIDE
BUT IT'S IMPORTANT TO REALIZE
THERE'S A SITE INVESTIGATOR
ACROSS CANADA FROM WHOM THIS
WOULD NOT HAVE BEEN POSSIBLE.
FINANCIAL PARTNER THAT INCLUDES
CLINIC RESEARCH RESPIRATORY
NETWORK AND SOME OF OUR OWN
INSTITUTIONS FROM THE TWO
CO-P.I. AND UCB AND MYSELF IN
THE McGILL UNIVERSITY AND THE
PRIVATE SECTOR THAT HAS BEEN
VERY GENEROUS GIVING MONEY TO
SUPPORT THIS WITHOUT HAVING ANY
WORD TO SAY IN THE DEVELOPMENT
OF THIS COHORT THAT IS ABOUT
PATHOGENESIS AND PATHOPHYSIOLOGY
OF THE DISEASE.
AND THANK YOU FOR YOUR TIME AND
GIVING ME THE OPPORTUNITY TO BE
HERE THIS MORNING.
>> THANK YOU.
>> THANK YOU SO MUCH.
THAT WAS A GREAT TO HEAR FROM
OUR CANADIAN COLLEAGUES.
NOW WE'RE GOING FURTHER THE
FURTHEST ZOOM IN YOUR PRIZE IS
BEING UP IN THE MIDDLE OF THE
NIGHT.
THANK YOU FOR JOINING US FROM
THE TASMANIAN LONGITUDINAL
CENTER DR. SHYAMALI DHARMAGE AND
DR. BUI FROM THE MELBOURNE
POPULATION AND GLOBAL HEALTH.
TAKE IT AWAY.
>> THANK YOU SO MUCH.
I'M SHYAMALI DHARMAGE.
THE CURRENT P.I. OF THE
TASMANIAN LONGITUDINAL HEALTH
STUDY WITH DR. BUI WHO HAS DUB A
LOT OF WORK WITHIN THE STUDY.
SO THIS IS THE STRUCTURE OF THE
PRESENTATION.
FIRST, I'LL BRIEFLY TALK ABOUT
THE TASK OF THE TASMANIAN
LONGITUDINAL HEALTH STUDY AND
WHAT DATA HAVE BEEN COLLECTED.
THEN WE'LL TALK A LITTLE BIT
MORE ABOUT HOW TAHS HAS
CONTRIBUTED TO THE FIELD OF
COPD.
WE FOCUS MAINLY ON THE UNIQUE
FINDINGS OF THE TAHS RATHER THAN
EVERYTHING WE HAVE DONE.
AND FINALLY I'LL TALK ABOUT WHAT
IS NEXT IN TAHS AND BEYOND.
THOSE WHO HAVEN'T BEEN TO OUR
AUSTRALIA WE HAVE A BEAUTIFUL
UNIVERSITY WITH VERY OLD
BEAUTIFUL BUILDINGS.
ALSO MODERN BUILDINGS SUCH AS
THIS.
IF YOU'D LIKE TO WELCOME US
YOU'RE WELCOME TO VISIT US AS
WELL.
NOW TO TALK ABOUT THE TASMANIAN
HEALTH STUDY.
TAHS WE STARTED BACK IN 1961.
I'M OLD BUT NOT THAT OLD.
I TOOK OVER THE STUDY AS THE
P.I. IN 2000.
SO WHEN TAHS STARTED IN 1968, IT
STARTED IN 1968 BY INVESTIGATING
ALL 7-YEAR-OLD SCHOOL CHILDREN
IN TASMANIA THAT INCLUDED 8,000
OR SO CHILDREN AND PARENTS IN
TOTAL 45,600.
THE 7-YEAR OLD SCHOOL CHILDREN
HAD LUNG FUNCTION DONE.
EVERYONE ELSE INCLUDING THIS HAD
FIELD QUESTIONNAIRES ON THEIR
HEALTH STATUS AND DR. WASHKO
TALKED ABOUT THE LUNG STUDY
FOCUSSED ON RESPIRATIVE HEALTH
AND THAT'S WHAT THEY DID AT THE
TIME.
I'LL ACKNOWLEDGE THOSE WHO STUDY
THE STUDY HEATHER GIBSON AND
PUBLIC HEALTH PHYSICIAN AND
STATISTICIAN.
THREE GREAT PEOPLE STARTED THE
STUDY AND HAD A GREAT MISSION AT
THE TIME AND COLLECTED A HUGE
AMOUNT OF DATA AND WE ARE LUCKY
TO HAVE THIS STUDY.
HOWEVER, WE HAVE THIS HISTORICAL
STUDY STARTED IN 1968.
NOT A LOT OF MODERN MEASUREMENTS
HAD BEEN DONE AT THE TIME AND
THAT'S THE LIMITATION.
TO GO BACK TO THE FOLLOW-UPS
THAT HAVE HAPPENED SINCE IT
STARTED.
THE 7-YEAR-OLD SCHOOL CHILDREN
COHORT HAVE BEEN FOLLOWED UP
EVERY DECADE AND WE HAVE JUST
STARTED TO START THE SEVENTH
DECADE FOLLOW-UP.
THE PARENTS AND THE SIBLINGS
WERE ALSO FOLLOWED UP RECENTLY
AND SIBLINGS TEST AND PARENTS
QUESTIONNAIRES.
SINCE I TOOK OVER AT THE P.I. IN
2000 WE HAVE DONE FIVE MAJOR
FOLLOW-UPS AND ARE DOING THE
CURRENT FOLLOW-UP.
THAT'S WHAT ARE COMPLETING SINCE
2000.
AND THERE'S DOMAINS.
THERE'S LIFESTYLE AND GENETIC
FACTORS AND COMPLEX LUNG
FUNCTION TESTS, ENVIRONMENT
OCCUPATION AND CLINICAL DATA AND
BLOOD SAMPLES AND BIOMARKERS
HAVE BEEN DONE AND WE HAVE
COLLECTED COMORBIDITIES.
THIS TABLE SUMMARIZES THE DATA
COLLECTION.
THE FIRST THREE FOLLOW-UPS FOCUS
ON SERVICE AND LUNG FUNCTION.
BUT SINCE 2000 WE HAVE FOCUSSED
ON A NUMBER OF OUTCOMES AND
COLLECTED BLOOD SPECIMENS AND
JUST DONE THE EXOME SEQUENCING
OF 600 PEOPLE AND HAVE DONE A
NUMBER OF BIOMARKERS.
WE HAVE DONE EPI GENGENOMICS AN
PROTEOMICS ON SMALLER SAM AND
THERE'S AN A STUDY FROM
DR. WASHKO AND HAN AND WE'RE
LUCKY TO HAVE THEM JOIN THE
STUDY.
NEXT TO THE CHANGING LANDSCAPE
OF COPD AND HOW IT'S
CONTRIBUTED, AS WE KNOW, THERE
HAVE BEEN A NUMBER OF CHANGES IN
THE WAY THAT COPD HAS BEEN
VIEWED AND I DON'T HAVE TO
EXPLAIN THESE THINGS TO THIS
AUDIENCE.
WE KNOW IT'S A SINGLE ENTITY
RELATED TO FUNCTION DECLINE AND
SMOKERS DISEASE.
NOW WE KNOW THERE ARE DIFFERENT
LUNG FUNCTION PATHWAYS AND
MULTIPLE RISKS THAT INTERACT
WITH EACH OTHER NOT JUST
SMOKING.
MORE IMPORTANTLY, WE KNOW IT HAS
EARLY ORIGINS.
MORE THAN 80% OF COPD ORIGINATES
IN EARLY LIFE.
AND THEY CAN ACCENTUATE RISK
FACTORS.
IF WE FOCUS ON WHAT WE HAVE DONE
ON COPD AND TESTS LOOK AT OTHER
OUTCOMES.
THESE ARE THE THEMES WITHIN
TAHS.
AS I SAID BEFORE, WE ARE GOING
TO JUST FOCUS ON EARLY LIFE
RISKS AND WITHOUT RISK.
LUNG FUNCTION TRAJECTORIES IS
ONE OF OUR STRENGTHS AND THEN
PREDICTION AND DETECTION
ALGORITHMS WE'RE LOOKING AT AND
I'LL HAND IT OVER TO DINH.
>> WE LOOKED AT KEY FINDINGS FOR
THE AREA.
EARLY LIFE DETERMINATES IS A KEY
AREA WITH RICH DATA WITH EARLY
LIFE AND IT INCREASED THE RISK
OF COPD AND LOW BIRTH WEIGHT IS
ASSOCIATED WITH LUNG FUNCTION
DEFICIT AND NOW THE IMPACT OF
PRETERM AND THE COPD.
IN FACT COPD RELATED TO PRETERM
BIRTH IS CONSIDERED A SUB TYPE
IN THE RESEARCH.
LOOKING AT RATIO AT SEVEN YEARS
WAS ASSOCIATED WITH INCREASED
RISK OF COPD AND 45 YEARS.
AS YOU CAN SEE THE COPD GROUPS
HAVE A LOWER LUNG FUNCTION.
WE ARE PAPERS ON THE IMPACT OF
EARLY LIFE INFECTIONS AND
SMOKING EXPOSOME.
AND SMOKING ASSOCIATED WITH
BRONCHITIS ASSOCIATED WITH
OBSTRUCTIVE LUNG DISEASE.
INTERESTI
INTERESTINGLY LUNG FUNCTION
DEFICIT WAS ASSOCIATED WITH
SMALLER LUNGS IN MIDDLE AGE.
WE THEN INVESTIGATED PROFILES OF
EARLY LIFE RISK FACTS AND IMPACT
OF COPD AND IDENTIFIED SIX
DISTINCT PROFILES OF RISK
FACTORS USING ANALYSIS.
THIS HEAT MAP SHOWS PROBABILITY
ACROSS SIX PROFILES.
OVER ALL THE PROFILES HAVE
DIFFERENT IMPACTS ON COPD AND
THE PROFILE WITH FREQUENT CHILD
ASTHMA HAVE THE HIGHEST RISK OF
COPD IN MIDDLE AGE.
ALSO WE INVESTIGATED THE
INTERACTION BETWEEN LIFE TIME
RISK FACTORS FOR EXAMPLE LOOKING
AT RISK FOR THE RISK OF AIR FLOW
OBSTRUCTION IN MIDDLE AGE AND
ASTHMA WERE INDEPENDENTLY
ASSOCIATED HOWEVER, THE
REDUCTION IN THE RATIO IN PEOPLE
WITH BOTH ASTHMA AND SMOKING
SHOWS EFFECT.
AND LOOKED AT THE IMPACT OF
SMOKING AND OCCUPATIONAL
EXPOSOME IN MIDDLE AGE.
AUTO SMOKING INCREASING LUNG
FUNCTION DECLINE RATES.
AND OBSERVED INTERACTION BETWEEN
PRE TERM BIRTH AND SMOKING ON
MIDDLE AGE AND INCREASED THE
RISK OF COPD AND APPARENT
AMONGST SMOKERS AND LOOKED
ACROSS PRETERM GROUPS AND
STRATIFIED BY SMOKING STATUS AND
YOU SEE THE GROUPS MUCK SMOKERS
AND REPEATED LUNG FUNCTION WHICH
ALLOW US TO INVESTIGATE THE
PATHWAYS OF COPD.
WHILE THE STUDY LOOKED AT WHAT
HAPPENED IN LIFE OR CHILDHOOD WE
LOOKED AT THE GROUPS AND
IDENTIFIED SIX TRAJECTORIES.
AND IT'S IN THIS TRAJECTORY AND
LOOKING AT EARLY LOW AND NORMAL
DECLINE, AVERAGE, EARLY MIDDLE
AVERAGE AND RAPID DECLINE.
WE IDENTIFIED DIFFERENT
TRAJECTORIES OF RISK OF COPD
INCLUDING THE DECLINE AND ADDED
TRAJECTORIES LOW AND THE BELOW
AVERAGE.
ALSO ASSOCIATED WITH COPD THEY
TECHNOLOGY CONTRIBUTED TO 75% OF
COPD AND LOOKED AT OBSTRUCTION
BASED ON THE LIFE TIME ON RATIO
AND WE IDENTIFIED TRAJECTORIES
AND CLASSIFIED PEOPLE WITH LOW
RATIO TRAJECTORIES AND THOSE
WITH THE LOW FEC AND NORMAL FEV1
RATIO TRAJECTORIES HAD
RESTRICTED PATTERN.
AND THOSE WITH LOW RATIO BUT
NORMAL TRAJECTORIES AS
OBSTRUCTIVE PATTERNS AND NORMAL
FOR BOTH TRAJECTORIES.
AND THIS IS THE HIGHEST RISK OF
COPD AND THE STRONGEST
ASSOCIATED WITH RISK FACTOR IT'S
ALSO GOES TO MENTAL HEALTH
DISORDERS.
AND THE PATTERN HAS THE SECOND
HIGHEST RISK OF COPD.
THE RESTRICTIVE PATTERN HAS
EVIDENCE OF LUNG RESTRICTION
WITH LOWER LUNG CAPACITY AND HAS
PREVALENCE AND AT RISK OF
MULTIPLE MORBIDITIES INCLUDING
OBESITY, DIABETES,
CARDIOVASCULAR ISSUES,
HYPERTENSION AND SLEEP APNEA.
AND THE LIFE TIME RISK FACTORS
LEADING TO COPD WE MOVE TO
PREVENTION AND PREDICTION.
ONE KEY QUESTION IS TO IDENTIFY
WHAT IS THE LIFE TIME FUNCTION
TRAJECTORIES IN COPD PATIENT AND
USING BIOMEDIARKERS IS A POTENT
WAY AND THE RATE MAY BE
DIFFERENCE BETWEEN COPD FROM THE
FUNCTION DECLINE TRAJECTORY AND
THE COPD WITH NORMAL LUNG
FUNCTION DECLINE AND WE HAVE
FUNDING AND DOING MORE
BIOMARKERS.
WE HAVE DEVELOPED A MODEL TO
PREDICT AIR FLOW OBSTRUCTION
BASED ON THE CHARACTERISTIC
USING THE STUDY AND WE'RE
LOOKING AT OTHER COHORTS AND WE
ARE DEVELOPING ON ONLINE TOOL.
>> WE HAVE INVESTIGATING FACTORS
THAT CAN AFFECT LUNG FUNCTION
AND COPD AND THESE FACTORS SPAN
FROM PRECONCEPTION TO NEWBORN,
CHILDHOOD AND ADULTHOOD.
HERE'S A SUMMARY OF LIFE TIME
RISK FACTORS THAT CAN INCREASE
THE RISK OF COPD.
WE HAVE INVESTIGATED MOST OF
THESE FACTORS.
AND THIS KNOWLEDGE IS CRITICAL
FOR DEVELOPING PREVENTIVE
STRATEGIES FOR DEVELOPING
CLINICAL RISK OF COPD.
OUR FINDINGS HAVE INFORMED THE
NOVEL COPD CLASSIFICATION
ACCORDING TO MAJOR RISK FACTORS
IN THE LAST CONSORTIUM.
CAN WE HAVE AN OPTIMISTIC
FUNCTION FOR COPD AND CAN WE
CURE PEOPLE?
IF SO, THERE'S NO QUESTION WE
NEED TO FOCUS ON PRE-COPD AND
COLLABORATIONS WITH RESEARCHERS
AND ONE OF THEM WILL BE
PRESENTING HERE TODAY
DR. HANSBRO FROM SYDNEY AND HAVE
A PROBLEM TO PREVENT COPD BY
EARLY DETECTION AND MANAGEMENT.
WE IDENTIFIED SO MANY RISK
FACTORS THAT COULD BE USED TO
INFORM THE PREVENTION BUT IT IS
BEYOND AN INDIVIDUAL'S CONTROL
SOME RISK FACTORS.
IN THAT CASE IN ORDER TO CURE
COPD CAN WE DETECT COPD EARLY
AND MANAGE THEM SO IT IS NOT
SYMPTOMATIC MANAGEMENT.
WE CAN CURE.
IN ORDER TO DO THAT WE LOOKED AT
BASIC MECHANISMS THROUGH
EXPERIMENTAL RESEARCH USING
CELLULAR RESEARCH AS WELL AS
ANIMAL STUDIES.
CELLULAR RESEARCH COULD INCLUDE
THINGS LIKE ORGANOIDS AND HAVE
WORK FOR FUNDING.
WE HAVE ALSO PROPOSED A SERIES
OF CLINICAL TRIALS ON COPD.
>> TWO-MINUTE WARNING.
>> THE DIAGRAM SUMMARIZES THE
PROGRAM WE HAVE PROPOSED.
AND YESTERDAY WE SUBMITTED A
GRANT PROPOSAL TO DO A
RANDOMIZED CONTROL TRIALS ON
FUNCTION TRAJECTORIES.
FIRST HOW TO GET BIOLOGY THROUGH
MULTI-OMICS AND THERAPEUTICS
THROUGH EXPERIMENTAL RESEARCH
AND TESTING INTERVENTIONS.
THESE ARE THE STEPS WE HAVE TO
TAKE IF WE WANT TO FIND A CURE
FOR COPD.
IT'S A BIG TEAM AND BIG STUDY
TO ACHIEVE THAT.
THANK YOU VERY MUCH FOR INVITING
US AND LISTENING TO US.
>> HE'D LIKE TO THANK THE
SPEAKERS FOR A WONDERFUL
OVERVIEW OF THE COHORTS.
AND FOCUS POTENTIAL
COLLABORATIONS BETWEEN THE
COHORTS OR HELPFULLY THOSE OTHER
SCIENTISTS ON HERE.
WE'D LIKE TO ASK QUESTIONS
STEPHANIE'S GOING TO GIVE IN A
SECOND TO EACH OF THE COHORTS
STARTING IN THE ORDER YOU
PRESENTED.
TWO MINUTES PER PERSON AND ONE
RESPONDER PER COHORT.
DR. CHRISTENSON.
>> WE'LL COLLATE OTHER PEOPLE'S
QUESTIONS IN THE CHATS AS THE
P.I.s ANSWER.
WE HAD ONE OVER ARCHING
QUESTION.
THAT IS WE'RE HEARING FROM GREAT
COHORTS AND I WANTED IDEAS FROM
THE P.I.s YOU BRAIN STORM ON
WAYS IN WHICH WE CAN INCREASE
COLLABORATION ACROSS THE COHORT
AND WITH BASIC SCIENTISTS TO
FURTHER OUR UNDERSTANDING OF
COPD PATHOPHYSIOLOGY AND
QUESTION 1A IS HOW DO
RESEARCHERS WHO ARE NOT
CURRENTLY PARTICIPATING IN THOSE
COHORTS HOW DO THEY CONNECT WITH
YOU TO POTENTIALLY START
COLLABORATING.
MAYBE WE'LL START WITH THE COPD
COHORT AND IN TWO MINUTES MAYBE
ONE P.I. PER STUDY.
>> THE ISSUE'S AROUND
COLLABORATION.
WE TRIED TO HAVE
COLLABORATIONTOWN THE COHORTS
AND -- COLLABORATION BETWEEN THE
COHORTS AND THERE'S BEEN
COLLABORATION BETWEEN THE
COHORTS.
MANY ARE GETTING THEIR OMICS
DATA THROUGH TOP MED AND THE TOP
MED LUNG WORKING GROUP AND COPD
WORKING GROUP AND PULMONARY
FUNCTION WORKING GROUP AND IT'S
BEEN A NICE PLATFORM AND THE WAY
IS TO GET THE INVESTIGATORS AND
BASIC SCIENTISTS WORKING
TOGETHER AND THE COLLABORATIONS
HAVE GROWN ORGANICALLY BUT I
THINK THE OPPORTUNITY TO
PARTICIPATE IN WORKING GROUPS IS
AVAILABLE IN COPD.
I KNOW IT IS IN OTHER COHORTS AS
WELL PARTICIPATING IN OTHER
WORKING GROUPS IS AN OPTION.
THE BEST APPROACH WOULD BE TO
THINK ABOUT REACHING OUT TO
INDIVIDUAL INVESTIGATORS.
JAMES AND I WOULD BE HAPPY TAKE
INQUIRIES AND THEY ASK ABOUT A
GENE RELATED TO THE PROTEOMICS
OR TRANSCRIPTOMICS AND WE LOOKED
UP STUDIES IN THE PAST AND
THINKING OF MORE DURABLE AND
DEEPER COLLABORATION TO SAY HOW
CAN WE INVESTIGATE THE IMPACT OF
THE COPD GENETIC RISK PROFILE ON
MY MODEL SYSTEM WOULD BE THINGS
I'M HAPPY TO DISCUSS AS WELL.
DID YOU WANT TO ADD ANYTHING?
>> JUST WE ENCOURAGE
COLLABORATION.
WE HAVE A STUDIES COMMITTEE AND
WELCOME ANYBODY TO INTERACT AND
GATHER DATA OR SHARE IDEAS.
>> MEILAN, SAME QUESTION,
PLEASE.
>> SORRY.
THE SPIROMICS WEBSITE IS A GOOD
SOURCE OF INFORMATION.
WE'VE BEEN TRYING TO HARMONIZE
THE DATA ACCESS AND REQUEST
PROCESS TO BE SIMILAR TO COPD
GENE IT MAKE IT EASIER FOR
EVERYONE.
IF YOU GO TO THIS I THINK TYPE
IN THE WORD SPIROMICS IF YOU GO
TO THE WEBSITE YOU'LL PULL UP
PUBLIC INFORMATION ABOUT WHAT
DATA SETS ARE AVAILABLE AND THEN
YOU CAN SUBMIT A REQUEST FOR
MANUSCRIPT PROJECT AND REQUEST
FOR ANCILLARY STUDIES AND FOR
THE DATA.
THERE'S A DATA USE AGREEMENT AS
WELL.
WE TRIED TO HARMONIZE THE FORMS
TO TAKE EITHER VERSION BUT HAVE
SIMILAR DATA ON IT.
WE TRIED TO TO MAKE IT EASIER
FOR PEOPLE.
>> WE CO-CHAIR THE ANCILLARY
COMMITTEE FOR THE SPIROMICS
FAMILY OF STUDIES AND WE'D BE
HAPPY TO TALK TO PEOPLE WITH
JUST IDEAS FOR PRE-INQUIRPRE-IN.
>> I WANT TO SAY THAT TO THE
BASIC SCIENTISTS THERE'S A LOT
OF PEOPLE WHO DO MORE
TRANSLATIONAL RESEARCH IN A LOT
OF THE COHORTS THAT ARE VERY
WILLING TO WORK WITH PEOPLE WHO
ARE DOING MORE BASIC RESEARCH
WHO KNOW THE COHORTS VERY WELL
AND COULD POTENTIALLY HELP YOU
SO YOU'RE NOT JUST LOADED WITH
CLINICAL DATA YOU DON'T KNOW HOW
TO USE.
WE'RE WILLING TO COLLABORATE AND
TRY TO MAKE THAT DATA EASIER.
IT'S A MUCH MORE COLLABORATIVE
PROCESS THAN BASIC LABS WHICH
ARE LAB FOCUSSED.
SO WE'RE MAKING SURE PEOPLE
UNDERSTAND THAT.
IS GRAHAM ON.
>> YEAH, I CAN'T TURN MY VIDEO
ON.
>> THIS IS DR. BERIMO.
THESE ARE INTERESTING STUDIES
AND THERE ARE OPPORTUNITIES NOW
TO INVESTIGATE WHAT'S GOING ON
AT THE TISSUE LEVEL OF THE LUNG.
DURING THESE VARIOUS TYPES OF
CLINICAL PRESENTATIONS.
THE BIOMARKER HAS PROVEN MORE
AND MORE RELIABLE AND REFLECTING
WHAT'S GOING ON WITH THE
DISEASE.
IT DETECTS ELASTIC TISSUE
BREAKDOWN AND APPEARS WITH TIME
GOING ON WITH THE STUDIES
ELASTIC TISSUE BREAKDOWN IS
STILL A FUNDAMENTAL MECHANISM IN
COPD AND HERE YOU HAVE VARIOUS
PHASES IN THE DISEASE AND EARLY
STAGES AND LATE STAGES AND SO ON
AND BIOMARKER RESULTS
PARTICULARLY WITH REGARD TO
ELASTIC DEGRADATION WOULD BE I
THINK VERY SIGNIFICANT IN TRYING
TO UNDERSTAND WHAT'S GOING ON
WITH THE DISEASE AT THESE
VARIOUS STAGES OF LIFE.
THERE'S MORE RELIABLE BIOMEDICAL
WE HAVE AND URGE YOU TO INCLUDE
IT IN YOUR STUDIES.
>> THANK YOU.
>> ANOTHER GOOD POTENTIAL AREA
OF COLLABORATION.
IF PEOPLE HAVE SPECIFIC IDEAS I
THERE WERE SOME AROUND OR
QUESTIONS AROUND AIRWAY DISEASE,
AROUND OTHER EXPOSURES BUT
GRAHAM WOULD YOU MIND ANSWERING
FOR US YOUR IDEAS ON
COLLABORATION AND HOW PEOPLE CAN
USE YOUR DATA?
>> YEAH, SURE.
I AGREE WITH EARLIER COMMENTS I
THINK GETTING IN TOUCH WITH
NASCENT INVESTIGATORS AND
JOINING THE CLUB, SHALL WE SAY,
IS A GOOD WAY TO GO BECAUSE THE
DEA DATA IS COMPLEX AND HARD TO
DOWNLOAD AND DEAL WITH IT.
MESA STARTED AS A FEW HUNDRED
INVESTIGATORS.
IT'S NOW A FEW THOUSAND
INVESTIGATORS.
ANYBODY CAN JOIN.
THERE'S NO PARTICULAR AND WE
CONTINUE TO DO TO WHEN WE START
ON THE MULTI-OMICS WE NEED TO
UNDERSTAND EVERYTHING.
THE OTHER COMMENT IS THAT
THERE'S INCREASING EFFORTS FOR
HARMONIZATION ACROSS THE STUDIES
WHICH WILL MAKE THINGS A BIT
EASIER AND SOME OF THOSE WERE
ALLUDED TO ALREADY.
AND WE ARE ALSO THERE'S A
COLLABORATION FOR COHORTS ACROSS
RESEARCH THAT IS NOT LUNG
FOCUSSED BUT HAS A FAIR AMOUNT
OF LUNG PHENOTYPING THAT WILL
INCREASINGLY BE HARMONIZED AND
HOPEFULLY AVAILABLE IN A CENTRAL
SOURCE VIA THE NIH.
THAT'S ALSO ONE WAY TO GET
INVOLVED WITH MULTIPLE WORK.
THANK YOU.
>> THANK YOU.
DR. WASHKO CAN YOU TELL US ABOUT
ALA AND CARDIA.
>> I WOULD ECHO WHAT EVERYONE
SAID.
I AGREE THAT IF WE LOOK AT
CARDIA BECAUSE IT'S BEEN SUCH A
TRUE LIFE COURSE STUDIED IT'S
LIKE SECRETS HIDDEN IN PLAIN
SITE.
THE NAVIGATION OF THE DATA OF
TOP MED IS VERY INTIMIDATING.
REACH OUT TO US AND HAPPY TO
GUIDE THINGS.
BEING ON THE INSIDE IS
CONSIDERED A CARDIA PERSON OR A
LUNG HEALTH PERSON EVEN NAVIGATE
THOSE DATA.
ALA JUST GETTING GOING.
WE'RE OPEN TO ALL FORMS OF
COLLABORATION AND BUILDING
BRIDGES WITH OTHER COHORTS AND
WE'VE BEEN INTENTIONAL IN
HARMONIZING A LOT OF THE DATA
WITH THE LONG OBSERVATIONAL
STUDIES TO ACTUALLY ENHANCE
COMMUNICATION.
SO IF PEOPLE FIND SOMETHING THEY
CAN DIRECTLY COME OVER TO
ANOTHER COHORT.
THAT IS BY DESIGN WITH THE GOAL
AND HOPE THAT PEOPLE START
WORKING WITH ALL THE DATA THAT
WE HAVE.
>> PROFESSOR BOURBEAU.
>> I AGREE WITH WHAT'S BEEN SAID
THE EASIEST QUESTION IS ANSWER
IS THE SECOND ONE AND THE NEEDS
AND THE EASIEST WAY TO ACCESS US
IS THROUGH THE WEBSITE.
WE HAVE DONE QUITE A BIT OF WORK
IN THE LAST COUPLE YEARS WHERE
YOU CAN ACCESS WHAT IS
ACCESSIBLE.
WE HAVE NOW A SYSTEM THAT
ALLOWED PEOPLE TO APPLY TO THE
WEBSITE WHERE THERE IS A FORM TO
APPLY AND WE HAVE A COMMITTEE IN
PLACE TO REVIEW THE PROPOSAL AND
THE POSSIBILITY FOR PEOPLE
OUTSIDE CANADA TO DO THE
ANALYSIS WHERE EVERYTHING IS ON
THE CENTRAL PLATFORM AND WORK TO
HAVE THAT APPROVED AND HAVE THAT
IN PLACE.
I WOULD RECOMMEND PEOPLE TO GO
ON THE WEBSITE AND SEE WHAT WE
HAVE ALREADY DONE AND SUMMARY
KEY MESSAGES AND WHAT WOULD BE
ACCESSIBLE NOW AND WHAT IS
COMING WITH THE FOLLOWING
VISUAL.
I WOULD PROBABLY END BY THE
FIRST QUESTION IS AND THERE'S AN
ART AND BEYOND THAT I WOULD SAY
IF WE REALLY WANT TO GO TAKE
HUGE ADVANTAGE OF TAKING ALL THE
COHORT WITH THE SIMILARITY,
DIFFERENCES AND COMPLEMENTARTY
AND THERE'S HARMONIZATION.
THAT'S SOMETHING THE NHLBI, NIH
WOULD LIKE TO THINK ABOUT AT
LEAST TO RECEIVE OR HAVE FUNDING
WE CAN PUT TOGETHER A PROPOSAL
AND WHAT WOULD IT TAKE TO REALLY
GET TOGETHER.
EVERYTHING HAS TO DO WITH
RESEARCH QUESTION AND OTHER
THING IS MAY BE MORE COMPLICATED
BUT AT THE END OF THE DAY IT
NEEDS A PROJECT WHERE THERE
WOULD BE MORE THAN ONLY MUTUAL
INTEREST BUT SOMETHING WE CAN
PLAN OVER THE YEAR THAT WOULD
REALLY -- IT'S BEEN DONE IN THE
CARDIOLOGY COHORT WHERE THERE'S
BEEN HARMON AND A GROUP IN
COLOMBIA HAS DONE WORK WHERE WE
CAN LEARN FROM OTHERS AS WELL IN
THIS.
IT NEEDS TO BE HARMONIZED AND
NOT ONLY LOCAL INITIATIVE.
THE LAST FROM THE HEALTH STUDY
AND WAYS TO COLLABORATE AND
THERE WAS AN INVESTIGATOR COHORT
AND IT WAS A SMALL NUMBER OF
INVESTIGATORS.
SINCE I HAVE TAKEN OVER AND
EXPANDED COLLABORATIONS BECAUSE
I WOULD LOOK FOR COLLABORATION
TO MAKE OUR WORK BETTER.
HOWEVER, UNLIKE THE MESA COHORT
IT'S NOT LIKE HUNDREDS BUT IT IS
A BIT CLOSE TO TASK BUT WE DO
HAVE A WEBSITE.
WE HAVE A WAY OF APPLYING FOR
DATA THERE ARE DATA ON THE
WEBSITE YOU HAVE TO CUT AND
PASTE ON THE DATA REQUEST FORM
AN IT GETS AUTOMATICALLY SENT TO
THE DATABASE MANAGER BUT THE
PROPOSAL HAS TO BE APPROVED BY
THE TEST TABLE COMMITTEE.
SO THERE'S A PROCESS BUT WE ALSO
HAVE POLICIES AROUND HOW WE LOOK
AT PAPERS AND THE POLICY IS ON
THE WEBSITE.
THE FIRST QUESTION ABOUT
COLLABORATIONS I TOTALLY AGREE
WITH THE FACT THAT IT'S NOT JUST
GETTING TOGETHER AND TALKING
ABOUT IT BUT HAS TO BE A
PROJECT.
THE TASK HAS COLLABORATED WITH
EUROPEAN COHORTS AND IT'S CALLED
AGING LUNG COHORT AND WE HAVE A
CONSORTIUM AND THAT EXPIRED IN
2020.
WE BROUGHT SIMILAR COHORTS
TOGETHER AND CROSS SECTIONAL
STUDIES AND THAT WORKED WELL.
WE HAD WORK PACKAGES AND WE
STARTED A COLLABORATION AND
STARTED IT THROUGH DR. WASHKO
AND IT'S CALLED AUSTRALIAN
U.S. COHORT COLLABORATION.
THAT'S ONE COHORT TOGETHER BUT
IF YOU WANT TO HAVE A CONSORTIA
IT HAS TO BE FUNDED BUT THAT'S
THE WAY FORWARD BECAUSE
INDIVIDUALLY THERE'S SO MUCH WE
CAN TWO -- DO AND IF WE THINK
OF MECHANISTIC STUDIES THEY HAVE
TO BE REPLICATED AND WE ALWAYS
ASK FOR REPLICATIONS NOW.
WE SHOULD COME TOGETHER AS A
CONSORTIUM AND I THINK IT NEEDS
TO BE A PROJECT CAN'T BE JUST
INTEREST.
I FULLY AGREE.
>> WOULD YOU ALLOW ME TO ADD
SOMETHING?
>> PLEASE.
TO REINFORCE IT'S NOT ONLY ABOUT
THE EPIDEMIOLOGY STUDY AND
ANSWER QUESTION AND
HARMONIZATION OF THE COHORT BUT
DO LEAD YOUR PROJECT AND THAT'S
THE REASON WHY WE'RE HERE FOR
TWO DAYS AND TO THE FUNDAMENTAL
RESEARCH BECAUSE THIS WOULD BE
EXTREMELY POWERFUL IF WE WERE
WORKING TOGETHER IN THE
HARMONIZATION OF THE COHORT NOT
ONLY DEFINING THE QUESTION YOU
CAN ANSWER BETTER FROM AN
EPIDEMIOLOGY POINT OF VIEW AND
THE MECHANISTIC DIFFERENT WAY OF
LOOKING AT MECHANISTIC FROM
BIOLOGICAL ETCETERA AND FROM
WHERE ALL THE FUNDAMENTAL
QUESTION COULD LEAD STO THE
GROUP OF RESEARCH AND RESEARCHER
TO BE PART OF THAT CONSORTIUM
AND WOULD BE POWERFUL ACROSS THE
SPECTRUM AND BENEFICIAL NOT ONLY
FROM A COHORT POINT OF VIEW BUT
ACCESS TO NEW RESEARCH QUESTION
AND DEVELOPING MORE FUNDAMENTAL
RESEARCH.
>> THANK YOU.
VERY USEFUL.
I THINK YOU'RE TOUCHING ON WHAT
SOME OF THESE OTHER QUESTIONS
THE FOLLOW-UP QUESTION TO THIS
QUESTION AND I WILL SAY STARTING
WITH WE'RE HEARING HOW DO WE
TOUCH BASE WITH SOME OF THESE
COHORTS BUT DOES ANYBODY HAVE
OUT OF THE BOX IDEAS HOW TO
POTENTIALLY IMPROVE CROSS-COHORT
COLLABORATION AND WE TALKED
ABOUT PUB MED AS ONE WAY BUT
DOES ANYBODY HAVE IDEAS HOW TO
PUSH THIS FORWARD BECAUSE THERE
ARE SUBSTANTIAL BARRIERS HERE.
>> I THINK THERE COULD BE A REAL
CATALYST.
BECAUSE WE HAVE TO HAVE OUR DATA
THAT COMES FROM TOP MED INTO THE
CATALYST.
>> WOULD YOU MIND SAYING WHAT IT
IS.
>> NHLBI REPOSITORY OF A
PLATFORM ALL THE OMICS DATA GOES
SUBMITTED ARE COPD AND CT SCANS
THERE AS WELL AS AND OTHER
EFFORTS TO GET ADDITIONAL
IMAGING DATA AND PHENOTYPE DATA
AND MY UNDERSTANDING IS THE TOP
MED THE C4R WILL GO THERE.
RATHER THAN TRYING TO CREATE A
NEW CLOUD ENVIRONMENT I THINK WE
SHOULD REDOUBLE OUR EFFORTS TO
GET DATA IN THE MOST HARMONIZED
FORMAT WE CAN INTO THE CATALYST
SO INVESTIGATORS CAN GET ACCESS
TO IT.
>> CAN I ASK ANYONE WHO MIGHT
KNOW THIS, IS IT POSSIBLE TO PUT
THE NON-AMERICAN COHORTS INTO
THE SITE?
GRAHAM, YOU'RE NODDING.
>> SO THE QUICK ANSWER IS YES.
THERE ARE DIFFERENT AREAS WITHIN
BIO DATA CATALYST.
I WAS GOING TO ADD IN TERMS OF I
PUT IN THE CHAT A COLLABORATIVE
COHORT OF RESEARCH IS IN PROCESS
OF HARMONIZING COHORTS THOSE
MENTIONED TODAY AND THAT'S
INITIALLY FOR COVID RESEARCH BUT
WE'RE WORKING TO EXPAND IT.
ONE OF THE NICE THINGS IS
BETWEEN EPIDEMIOLOGIC ANALYSES
THE COMPUTE POWER IS LESS
BURDENSOME IN THE CLOUD THAN
LARGE SCALE OMIC ANALYSES.
THAT THEN THE DATA IS IN ONE
PLACE AND YOU ANALYZE THERE'S AN
A VARIETY OF WAYS TO WORK THIS
OUT.
THIS IS MOVING WELL.
YOU HAD A COMMENT.
>> THIS COULD BE GOOD IF THE
P.I.s CAN GET TOGETHER AND TALK
ABOUT THIS.
WE ARE ALL BUSY WE DON'T WANT
ANOTHER MEETING.
I THINK SOME DOWNGOING
DISCUSSIONS IS NEEDED BECAUSE IT
CAN'T HAPPEN OVERNIGHT.
>> FERNANDO DO YOU HAVE
SOMETHING ON THE CATSELT.
>> IT'S FUNDED BY THE ERS THAT
HAS BASKETBALL ABLE TO DO THIS
FOR EARLY LUNGS FUNCTION AND
COPD AND THEY ORGANIZED COHORTS
ACROSS EUROPEAN COMPONENTS AND
THAT'S BEEN HIGHLY SUCCESSFUL.
AC
>> WHAT ARE THE RESOURCES THAT
CAME UP IN THE CHAT IS BIO LINK.
ANDESE OF USING THAT AND
HARMONIZING THE DATA SETS.
THERE ARE OBSTACLES AND BETWEEN
COUNTRIES THINGS CAN GET MORE
COMPLICATED.
THAT'S WHY IF YOU WANT TO DO
THAT FROM A USA POINT OF VIEW
THAT MAY BE KIND OF EASIER.
YOU ALREADY HAVE SOME INITIATIVE
GOING ON.
IF YOU WANT TO LOOK AT THE
LARGER PERSPECTIVE, THEN I THINK
THIS GROUP WOULD BE A STARTING
POINT AND THAT COULD EVOLVE OVER
TIME WHERE OTHER COHORTS COULD
BE HARMONIZED.
THERE'S A LEGAL ISSUE ALSO.
AS A RESEARCHER YOU THINK DOING
THAT WITH VERY GOOD INTENTION
BUT WHEN IT COMES TO IMPLEMENT
ANY OF THIS IT IS SO COMPLICATED
FROM A LEGAL POINT OF VIEW
SHARING TISSUE AND DATA AND
THINGS LIKE THAT IS NOT
SOMETHING EASY.
THAT'S WHY IT NEEDS TO BE
ORGANIZED FROM THE POINT OF VIEW
THAT WE CAN SHARE GOOD
EXPERIENCE AND FERNANDO
MENTIONED OTHER COUNTRIES AND WE
CAN WORK ON HARMONIZATION AND WE
HAVE TO COME UP WITH A PLAN AND
THAT NEEDS TO BE DONE TO THE
FUNDING AND HAVING A GOOD PLAN
AND TOGETHER GET AND TRY TO
DISCUSS THAT.
EVERYTHING HAS TO START WITH A
PROJECT AND THINGS THAT ARE
CONCRETE AND ADDRESS A RESEARCH
QUESTION PEOPLE CAN SHARE AND
PUT THIS IN PLACE AND SEE IT IS
FOOE
FEASIBLE AND WORKING.
>> THE CHALLENGES OF
INTERNATIONAL COLLABORATION ARE
REAL AND IMPORTANT AND I THINK
THIS IS WHERE SOME OF THESE
MODELS OF FED RATED DATA
ANALYSIS HAVE BEEN DEVELOPED IN
EUROPE BECAUSE OF THE EFFORTS TO
WORK AROUND THE GDPR ARE WORTH
CONSIDERING AND IT STAYS AT THE
LOCAL INSTITUTION BUT THE
ANALYSIS IS DONE IN A FEDERATED
AND COLLABORATIVE WAY IS
SOMETHING WE COULD THINK ABOUT
TO EXTEND THE REACH OF THE
COHORTS BEYOND THE U.S.
WHAT I'M STRIKE IS THE CAT SAN
MODEL IS WHAT THEY'VE DONE
SUCCESSFULLY.
THEY'RE INTERESTED IN PARTNERING
TO DO SOMETHING SIMILAR IN THE
U.S. AND WOULD BE HIGHLY
FRUITFUL.
I'M ON THE STEERING COMMITTEE
AND I NOW AT THE LAST ERS THERE
WAS SOMETHING SIMILAR AND
BRINGING IN JOB COHORTS.
ERS MAY BE THE NEXT OPPORTUNITY
MANY OF US CAN GET TOGETHER TO
OFFLINE TALK ABOUT THIS.
>> OUTSIDE THE MEETING YOU MAY
NEED MORE MEETINGS.
>> IT WAS FUNDED UNDER CRC.
ARE YOU ELIGIBLE FOR CRC FUNDING
OR ONLY EUROPEANS?
>>
>> THE LAST MEETING THE QUESTION
WAS WHETHER SOMETHING SIMILAR
COULD BE DONE.
IT WAS A MODEST AMOUNT OF
FUNDING PROVIDED VIA THEIR
COLLABORATION MECHANISM.
>> I THINK THEY HAVE INDUSTRY
FUNDING.
>> TO EXPAND ON THE COMMENT THE
COLLABORATION BETWEEN CARDIA AND
TAHS WAS BORN OUT OF I DON'T
KNOW HOW MANY MEETINGS OF
GETTING TOGETHER OVER A SPAN OF
MAYBE TWO YEARS AND GROWING AND
SHAPING AND I THINK TO ECHO
DR. BOURBEAU IT CHRIS --
CRYSTALIZES AND WE HAD TO
REALIGN TRAJECTORIES, REBUILD
ALL THESE AND BUI HAS DONE A LOT
OF THAT WORK.
IT'S ALL POSSIBLE BUT IT IS A
TRMENT AMOUNT OF WORK.
IT'S NOT JUST A COMMON ACCESS
POINT YOU DOWNLOAD DATA FROM.
>> SEEMS THERE'S SEVERAL
QUESTIONS IN THE CHAT ABOUT BIO
SPECIMEN ACCESS PARTICULARLY
THOSE COMING FROM THE LUNG.
HOWEVER, REALLY BIO SPECIMEN
ACCESS IN GENERAL THEY WANT TO
KNOW HOW WE ACCESS SOME OF THE
DATA.
THERE'S AN INCREDIBLE AMOUNT OF
WORK THAT GOES IN THE STAM PALS
BUT HOW DO WE MAKE IT EASY FOR
SO ONE HOW DO WE MAKE IT EASY
FOR BASIC SCIENTIST TO ACCESS
THESE OR CAN YOU TOUCH ON HOW
SCIENTISTS ACCESS THE BIO
SPECIMENS AND CAN WE TOUCH UPON
WHO ACTUALLY HAS SAM SAMPLING
THE LUNG.
IT'S OKAY IT RAISE YOUR HAND OR
SPEAK UP.
>> JEFF, I THINK YOU'RE ME BEST
PERSON TO ANSWER THIS INVOLVED
IN THE CONSORTIUM AND COPD AND
SPIROMICS.
I THINK YOU UNDERSTAND THIS AS
WELL AS ANYBODY DOES.
>> I THINK FOR COPD GENES THEY
BOTH HAVE FAIRLY ROBUST AND NOW
INCREASINGLY HARMONIZED
MECHANISMS TO SOLICIT OR SUBMIT
ANCILLARIES.
KINDS OF CONTACTS ARE WAN DA AND
MYSELF.
I'M ON BOTH SPIROMICS AND COPD
GENE AND KENNY SAY GOOD PERSON
TO TALK TO.
THE QUESTION I SAW IN THE CHAT
WAS WHAT ABOUT SOME OF THE OTHER
COHORTS THAT I THINK GRAHAM SAID
MESA HAS SOME BIO SPECIMENS BUT
CAN YOU ELABORATE.
>> MESA HAS HAD A LOT OF BLOOD
FOR A LONG TIME AND OTHERS ARE
COLLECTING NASAL SAMPLING ON THE
COHORT AND HAIR FOLLICLES.
>> RUSS, DO YOU WANT TO JUMP IN
THERE?
>> THIS IS FROM A FEW MINUTES
AGO.
AND THERE'S A POTENTIAL OPTION
FOR COLLABORATION.
WE USE IT A LOT FOR OMICS DATA.
AND EVEN DATA NOT IN TOP MED.
YOU CAN PUT NON-TOP MED DATA
INTO DATA CATALYST TO MAKE IT
CLEAR TO EVERYBODY.
THERE'S NO SUBSTITUTE FOR
IN-PERSON MEETING AND THE OTHER
MODEL I THINK I WOULD LOVE TO
EMULATE IS THE CHARGE MODEL AN
IN-PERSON MEETINGS THAT ARE
WONDERFUL.
IT'S GROWN FROM MY UNDERSTANDING
IN THE LAST DECADE.
BUT I FEEL WE NEED SOMETHING
LIKE CHARGE THAT HAS IN-PERSON
MEETINGS WITH ONE COHORT SUCH AS
THE ONES ON THE CALL.
>> I'M SEEING IN THE CHAT FROM
DR. NOEL SOMETHING THAT SUGGESTS
WE BRING UP AGAIN ENVIRONMENTAL
EXPOSURES OTHER THAN SMOKING ARE
INCREASINGLY BEING RECOGNIZED TO
BE IMPORTANT AND POSSIBLY
ADDITIVE OR BUT IT'S NOT CLEAR
TO THE PEOPLE IN THE COHORTS
WHAT EPIDEMLOGIC DATA IS
AVAILABLE IN THE COHORTS.
AND STARTING WITH DR. SHYAMALI
DHARMAGE.
>> YES, WE HAVE A LOT OF
ENVIRONMENTAL EXPOSURES AND
GIVEN THE LIMITED TIME WE HAVE
AIR POLLUTION DATA AND
OCCUPATIONAL HISTORY DATA THAT
HAS BEEN QUOTED USING METRIXES
AND WE HAVE ENVIRONMENTAL DATA
THAT HAVE BEEN BEEN EXTRACTED
FROM DIFFERENT DATABASES BECAUSE
WE KNOW WHERE THEY LINK.
AND WE HAVE CAPTURED THE
ENVIRONMENTAL DATA.
WE HAVE GONE BACK AND COLLECTED
THE WORK.
THERE'S MODELS THAT GENERATE AIR
POLLUTION AND THAT WHAT WE HAVE
DONE IS WE HAVE NOT ONLY
COLLECTED ENVIRONMENTAL DATA
SINCE 2000 WE GOT ENVIRONMENTAL
DATA.
WE HAVE COLLECTED DATA THAT WAY.
WE'VE WORKED WITH THE CONSORTIUM
FOR THE DATA FROM THE
PARTICIPANT SIX-DIGIT
RESIDENTIAL POSTAL CODE AT
BASELINE ASSESSMENT.
WE'RE LOOKING IN CANADA THERE'S
NOT AS MUCH AS MOVEMENT IN TERMS
OF THE POPULATION MOVING WITHIN
THE COUNTRY OR OUTSIDE THE
COUNTRY.
THIS IS A FRACTURE AND AGAIN
WE'VE BEEN WORKING FROM AVERAGE
AGE OF FOR EXAMPLE, THE BM2.5
CONCENTRATION ASSESSED ON THE
ONE BY ONE KILOMETER AND ON THE
GRID COVERING THE NORTH AMERICA
SOLUTION IN AGING AND THERE'S A
LOT OF THINGS VERY WELL KNOWN.
THERE'S AN EXPERT IN THE FIELD
BY ITSELF AND WE DEVELOPED
MODELS.
WE'RE VERY MUCH INTERESTED IN
THE ACUTE AFFECT OF THE
POLLUTION.
WE HAVE HAD SOME DUPLICATION.
ONE IS WE'RE INTERESTED
WILDFIRES AND EQUATIONS CAN
PREDICT YOUR EXPOSURE LONG-TERM
AND AT THIS WILDFIRE WE'RE MORE
AND MORE INTERESTED IN THE ACUTE
AFFECT BUT IN THE LONG-TERM
AFFECT.
IT'S A BIT MORE COMPLICATED THAN
THAT IN THE AREA YOU HAVE TO
TAKE INTO ACCOUNT TEMPERATURE,
COLD, WARM AND THE OTHER FACTOR
YOU HAVE TO TAKE INTO
CONSIDERATION.
AND THIS NEEDS TO BE WORK WITH
AN EXPERT GROUP THAT CAN PUT
INTO THIS AND IT'S A REAL
COLLABORATION AND PARTNERSHIP.
I THINK WE'RE GETTING BETTER IN
TERMS OF THE MEASUREMENT OF THIS
ALSO AND BETTER IN TERMS OF
TRYING TO INDIVIDUALIZE THE AND
LONG-TERM EXPOSURE WITH ALL THE
FACTORS THAT HAVE IMPORTANCE IN
GLOBAL WARMING.
>> THERE'S A RICH DATA WITH ARD
YA AND A QUESTIONNAIRE DATA I
THINK IS HARMONIZED WITH OTHER
COHORTS IN THE AND GEOLOCATED
DATA.
WE HAVE BOTH SES AND
NEIGHBORHOOD DEPRIVATION
PROXIMITY TO GREEN SPACE.
AS THE OTHER INHALED EXPOSURES.
IF WE LOOK TO THE LUNG/HEART
COHORT THEY'RE REFLECTING TRUE
LIFE COURSE ADDRESS HISTORY AND
THE GOOD NEWS IS BECAUSE THESE
PEOPLE ARE YOUNG WE HAVE
SATELLITE DATA DATING BACK TO
ESSENTIALLY THEIR BIRTH.
WE'LL KNOW WHERE THEY LIVED AND
HAVE HIGH RESOLUTION ESTIMATES
OF PARTICULATE EXPOSURE IN
ADDITION TO MORE STANDARD
ASSESSMENTS.
AND DR. RICE IS LEADING THOSE
EFFORTS WITHIN THE LUNG HEALTH
COHORT.
I'D ENCOURAGE PEOPLE IF THEY
WANT MORE DETAILS TO REACH OUT
DIRECTLY TO MARRY AND I CAN HELP
CONNECT PEOPLE BUT THERE'S MORE
DATA.
>>
>> JOE COFFMAN LEFT THE LARGEST
STUDY SINCE THE STUDIES THAT WAS
THE BASIS FOR THE CLEAN AIR ACT
AND PRESENTED ON OZONE AND
EMPHYSEMA DATA FROM THAT.
THERE'S A LOT OF CARDIOVASCULAR
PAPERS AND BASICALLY MODELS AND
VALIDATED EXPOSURES FROM
POLLUTANTS FROM 1990 THROUGH THE
END OF THE CURRENT EXAM.
IT'S EXTENSIVE AND BEYOND THAT
BEYOND THAT COLLABORATIONS OVER
THE YEARS AND THERE'S FACTORS
WHICH ARE PRODUCING STATE OF THE
ART MEASURES AS DESCRIBED,
ETCETERA.
>> MEILAN PERHAPS YOU CAN
DESCRIBE SPIROMICS
>> I THINK WE HAVE NARA ON THE
CALL.
>> THAT'S A BETTER PERSON.
ARE YOU ON?
>> I KNOW SPIROMICS ORIGINALLY
WAS LOOKING AT LARGELY AMBIENT
AIR POLLUTION THAT WAS BASED ON
LOCATION INFORMATION.
AND USED SOME BASIC COMPLICATED
MODELLING TO UNDERSTAND THE
HISTORICAL EXPOSURES OVER THE
PAST DECADE OR SO.
THERE'S A LIMITED AMOUNT OF
INDOOR AIR POLLUTION DATA THAT
WAS INCORPORATED AS WELL.
AND IT'S A SPIROMICS 1 VISIT AND
NOT ABLE TO BE WELL EXTRAPOLATED
FOR BEYOND SPIROMICS FINDINGS.
>> WE HAVE LONGITUDINAL
QUESTIONNAIRE DATA ON TOBACCO
AND VAPING AND OCCUPATIONAL DATA
AND SOCIO ECONOMIC STATUS AND
GIS CODING TO LINK TO
RESIDENTIAL ADDRESSES TO AIR
POLLUTION AND QUESTIONNAIRES ON
A SUBSET OF THE COHORT.
ONE THING TO POINT OUT IS THE
METABOLOMICS MASS SPEC DATA TO
BE A VALUABLE TOOL FOR STUDIES
AND IF CHEMICALS COULD BE
IDENTIFIED ARE BEING MEASURED IN
THAT METABOLOMICS DATA.
AND IF YOU HAVE THE RIGHT DATA
TO IDENTIFY THE MASS SPEC
PROFILES AND THERE ARE
INVESTIGATORS WHO SPECIALIZE IN
THIS COULD LEAD TO THE
IDENTIFICATION OF THOUSANDS OF
CHEMICALS.
IT'S SOMETHING WE SHOULD THINK
ABOUT FOR MANY OF THESE COHORTS.
>> THERE'S EXPOSURE
HARMONIZATION TO YOUR MEETING
COULD BE A GOOD AIM OF YOUR
MEETING.
I DON'T KNOW IF YOU HAD
ADDITIONAL QUESTIONS.
ONE OF THE THINGS I WAS SEEING
IN THE CHAT WITH AROUND LOOKING
AT AIRWAY CENTRIC DISEASE VERSUS
EMPHYSEMA AND THOUGHT IT MIGHT
BE A GOOD -- GEORGE WAS TALKING
ABOUT THIS EARLIER WE WEREN'T
FOCUSSING ON RADIO DRAFK
MEASURES IN THIS MEETING BUT IT
MIGHT BE A NICE PLACE TO GIVE A
LITTLE PLACE WHERE PEOPLE CAN
LOOK AT THE RADIO GRAPHIC
MEASURES AND HOW TO HELP EARTH
THE QUESTIONS OR USE IN
CONJUNCTION WITH THE BIO
SPESMANS TO LOOK AT AIRWAY
DISEASE VERSUS LUNG TISSUE
OBSTRUCTION.
>> THE IMAGING WORKING GROUPS
FOR A LOT OF THE COHORTS ARE
INCREDIBLY ACTIVE AND THERE'S
ALREADY A LOT OF CROSS
FERTILIZATION BETWEEN
INDIVIDUALS LIKE DAVID LYNCH AND
ERIC HOFFMAN INVOLVED IN THE CPG
AND SPIROMIC STUDIES.
GEORGE HAS BEEN ACTIVELY WORKING
WITH THEM TO IN RESPECT TO LHC
AND I THINK THE IMAGING GROUP
HAS A LIFE OF THEIR OWN AND IT'S
IMPORTANT FOR HELPING DEFINE
SPECIFIC PHENOTYPES LIKE VEEP
THE INDIVIDUAL ANALYSIS WITH THE
MUCUS PLUGGING IS NOW A VERY HOT
AREA IN COPD AND PEOPLE ARE
TRYING TO DEVELOP WAYS TO
ANALYZE THAT IN A MORE
QUANTITATIVE FASHION.
>> IF THERE'S SOMEONE INTERESTED
I THINK YOU CAN HOP ON TO ANY
ONE OF THE WORKING GROUPS AND
THE CPG MAY BE ONE OF THE MORE
BROAD ONES AND WILL GIVE A NICE
INTRODUCTION TO WHAT'S GOING ON
IN THE SPACE IN PARTICULAR.
>> AS A TRANSLATIONAL RESEARCHER
SOME RADIO GRAPHIC FINDINGS THE
OBJECTIVE MEASURES OF EMPHYSEMA
OR AIRWAY WALL THICKENING,
PULMONARY DISEASE CAN BE HIGHLY
RELATED TO FINDINGS IN BIO
SPECIMENS.
JUST THINKING ABOUT OF THOSE
THINGS BEYOND LUNG FUNCTION
EXPOSURES WE HAVE A LOT OF THESE
OTHER MEASURES IN SOME OF THE
STUDIES AND I'M SURE THE PEOPLE,
GRAHAM AND GEORGE, HAVE BEEN
WORKING ON THIS A LOT AND MAYBE
CAN COMMENT FURTHER.
>> I COMPLETELY AGREE.
THERE ARE TO MY PERSPECTIVE
DIFFERENT DISEASES WE END UP
WITH DIFFERENT CHANGES IN
STRUCTURE.
AS I SHOWED IN THE GENERAL
POPULATION THERE'S DIFFERENT
PEOPLE WITH DIFFERENT THINGS
GOING ON IN THE LUNGS AND DON'T
NECESSARILY COALESCE WITH SPIRO
METRIC COPD AND OFTEN I THINK
EASIER TO GET BIOLOGICAL
SIGNATURES FOR THE EVEN SMALLER
SAMPLES.
ONE OF THE AREAS IS IN THE
ENDOTHELIUM AND WE CAN IMAGINE
IN TERMS OF THE YARD YO
VASCULATURE AND THE SPECIMENS IN
THE COHORTS ARE BLOOD.
THE BLOOD OBVIOUSLY USED
DIRECTLY BUT ASPECTS OF THE
BLOOD AND ENDOTHELIUM AND WE CAN
SUGGEST MORE DIRECTLY
PHENOTYPES.
>> THE CONCEPT OF MANY OF OUR
BASIC SCIENCE INVESTIGATORS MAY
OBTAIN BIO SPECIMENS FROM THEIR
OWN INSTITUTIONS RATHER FROM AN
EXISTING BIO BANK WHICH GIVES
ADVANTAGES TO FRESH SAMPLES BUT
WHEN DO YOU THAT YOU SHOULD GET
THE IMAGING ON THE BIO SAMPLE
AND USE ONE OF OUR IMAGING
GROUPS AND TO TELL YOU HOW TO
INTERPRET THE SMALLER IMAGES AND
WHERE THE SUBTYPES ARE.
YOU CAN GET GOOD QUALITY CT
IMAGING AND SHARE THAT WITH THE
GRUP TO CHARACTERIZE IT.
>> I THINK GEORGE WILL GET THE
LAST WORD DOWN TO TWO MINUTES.
>> FABULOUS COMMENT.
THANK YOU.
>> ONE FINAL PLUG FOR THE
IMAGING IT'S ALMOST A RENEWABLE
RESOURCE.
YOU CAN MAKE DIGITAL COPIES AND
HAND THEM UP UNLIKE BIO
SPECIMENS THAT ARE CONSUMED.
WE ENCOURAGE PEOPLE TO REACH OUT
TO ALL THE TEAMS AND GET COPIES
OF THE DATA AND WE CAN ALL HELP
YOU WORK WITH IT.
>> THANK YOU.
I THINK WE'VE DONE IT.
>> YES.
I THINK WE'RE TWO MINUTES BEFORE
OUR TIME.
SO I THINK IT'S TIME FOR A BREAK
AND I REALLY THANK YOU ALL FOR
ALL THE SPEAKERS AND THERE'S A
LOT OF WORK AHEAD OF US BUT
THERE ARE A LOT OF OPPORTUNITIES
FOR COLLABORATION I HOPE
EVERYBODY ON THE CALL IS
STARTING TO REALIZE THAT MAYBE
IT MAKES IT A LITTLE BIT LESS OF
A BARRIER TO WORKING WITH SOME
OF THE GROUPS SEEING WHAT THEY
HAVE.
ANY LAST WORDS, JEF?
>> NOPE.
EVERYBODY BE BACK AT 1:30.
>> WE'RE BACK AT 1:30 EASTERN.
>> THANK YOU.
THANKS, EVERYBODY.
>> ON BEHALF OF MY ORGANIZERS
AND MY CO-CHAIR I'M HAPPY TO
INVITE TO YOU DAY ONE OF THE
PATHOGENESIS OF COPD.
WE HAVE SIX OUTSTANDING SPEAKERS
FOR THIS SESSION AND I THINK IT
WILL GIVE US A BROAD SWATH OF
THE UNDERSTANDING OF THE UNIQUE
BIOLOGY THAT IS BEING STUDIED IN
THIS DISEASE.
I'LL TURN IT OVER TO DR. HUANG.
>> THANK YOU.
I'M PERSONALLY LOOKING FORWARD
TO THE SESSION AS A
TRANSLATIONAL SCIENTISTS.
IT'S MY PLEASURE TO INTRODUCE
DR. KRISTOPHER GAGGAR TALKING
ABOUT EXOMES AND COPD.
>> CAN YOU SEE MY SLIDES?
>> I THINK IT NEEDS TO BE
ADVANCED.
>> ARE YOU SHARING YOUR OWN
SLIDES?
>> I GOT THEM.
I'M SHARING NOW.
>> YOU'RE CURRENTLY NOT SHARING
NOW.
I'LL STOP SHARING AND YOU CAN
PUT YOUR SLIDES.
>> FIRST OFF I'D LIKE TO SAY I'M
VERY HONORED TO BE A PART OF
THIS EVENT.
I'D LIKE TO THANK EVERYONE FOR
THE OPPORTUNITY TO GIVE A TALK
TODAY.
I'M KRISTOPHER GENSCMER AND THE
AFFECT OF PROTEASES ON COPD.
THEY'RE DERIVED FROM MOST CELL
TYPES AND EXTRA CELLULAR
VESICLES HAVE BEEN DIVIDED INTO
THREE CATEGORIES AND THEY CHANGE
OVER TIME AS MORE
CLASSIFICATIONS OF EVs GET
DISCUSSED.
THEY'RE ALL VERY SMALL.
THIS GRAPHIC ILLUSTRATES SOME OF
THE COMPLEX PROCESSES I WON'T
GET INTO TODAY FOR TIME THAT ARE
REQUIRED FOR EXTRA CELLULAR
VESICLE RELEASE.
THE SMALLER VESICLES ARE
GENERATED THROUGH THIS BODY
PATHWAY RELEASED.
THEY CONTAIN NUCLEIC ACIDS AND
EXPOSED PROTEASES.
VESICLES ARE BUDDING FROM THE
CELL MEMBRANE 3,000 TO 1,000 NAN
YO OMETERS IN SIZE AND THEY
RESULT FROM THE APOPTOSIS OF
CELLS.
I'LL BE REFERRING TO EXOSOMES
SIZE EVs WHEN I REFER TO EXTRA
CELLULAR VESICLES.
SOME HAVE BEEN DISCOVERED IN
EXTRA CELLULAR VESICLES FROM
MATRIX DEGRADATION LIKE
ELASTASES TO THE GENERATION OF
PRO-INFLAMMATORY SIGNALS LIKE
GENERATION OF PGP FOUND IN EVs
AS WELL AS THE LGPT4.
WE'LL FIND RIDGE REGARD TO
ELASTASE THE ASSOCIATION WITH
SOME PROTEASES ON THE EV SURFACE
RENDERS THEM RESISTANCE TO THEIR
PROTEASE INHIBITION FACILITATING
THE DISRUPTION OF THE PROTEASE,
ANTI-PROTEASE BALANCE.
A LOT OF THE PROTEASE WORK SIN
RESISTANCE TO THE ENDOGENOUS
PROTEASE AND SHOW YOU THE EXTRA
VESICLES FROM NEUTROPHILS.
PANEL A RELEASE THE SKOE
CENTIMETERS AND WHEN THE
NEUTROPHILS GET ACTIVATE AND
RELEASE THEIR GRANULES THEY CAN
BIND BACK TO THE SURFACE OF THE
EXTRA CELLULAR VESICLE THUS
KEEPING THE ALPHA 1 ALPHA
TRIPSON INCAPABLE BEING SOCKET
ED -- ASSOCIATED WITH THE
VESICLE AND IF YOU CAN DISRUPT
THIS YOU CAN ALLOW IT TO BE
CAPABLE OF BEING INHIBITED BY
ALPHA 1 ANTI-TRIPSON AGAIN AND
YOU TAKE NEUTROPHILS FROM
PERIPHERAL BLOOD AND YOU
STIMULATE DEGRANULATION YOU'LL
GENERATE TWO COHORTS OF EXTRA
CELLULAR VESICLES.
THE EVs ISOLATED FROM EACH OTHER
SHOW TWO SEPARATE CONDITIONS BUT
NO DIFFERENCE IN SIZE OR SHAPE
WHEN LOOKED AT UNDER THE
MICROGRAPH AND UNDER FLOW
CYTOMETRY YOU'LL SEE MORE
SURFACE ELASTASE ON THE SURFACE
OF THE EXTRA CELLULAR VESICLES
FROM ACTIVATED NEUTROPHILS FROM
THEY
-- THE QUIESCENT AND IS THIS
PROTEOLYTICALLY ACTED VATED.
THESE EVs ASSOCIATE WITH KOL
AGAIN FIBRILS.
WE GOT A MICROGRAPH OF THEM BY
THEMSELVES AND QUIESCENT ALONG
WITH THE FIBRILS AT TIMES ZERO.
IF YOU LOOK AT THE SAME FIBRILS
24 HOURS LATER YOU SEE A MORE
DRASTIC CHANGE IN THE PHENOTYPE
AND QUIESCENT NEUTROPHILS DO NO
DAMAGE AND THOSE INCUBATE FROM
DEGRANULATED NEUTROPHILS SHOW
THE FIBRILS IN THE PROCESS AND
PANEL F SHOWS A BLOWUP OF THE
ACTIVATED EXTRA CELLULAR VESICLE
NEAR POINT OF DEGRADATION.
THEY HAVE PROTEOLYTICALLY
ACTIVATED CELLS.
WHAT WE DO IS YOU
THE EXTRA CELLULAR VESICLES IN
THE MOUSE MODEL INTRATRACHEALLY
TO OBSERVE ENLARGEMENT IN THE
EMPHYSEMA PANEL AND YOU SEE THE
NORMAL LUNG AND THOSE WITH
QUIESCENT NEUTROPHILS SHOW NO
CHANGE SHOWING XENO TROPIC
AFFECT AND THE ACTIVATED
NEUTROPHILS INCREASES THE
ALVEOLAR ENLARGEMENT AND PANEL B
IS A MEASUREMENT OF THE
INTERCEMENT IN THE RED COLUMN
YOU SEE THE INCREASE IN SIZE AND
PANEL C IS PULMONARY FUNCTION
TEST AND SEE IN INCREASE IN
AIRWAY RESISTANCE WHEN GIVEN THE
ACTIVATED EXTRA CELLULAR
VESICLES AND IN B THE HALLMARK
OF THE EMPHYSEMA MODEL.
NEUTROPHIL ELASTASE GOES TO THE
SURFACE VIA IONIC CHARGE AND
INCUBATING THEM FROM AN
ACTIVATED NEUTROPHIL SUCH AS
WITH SULPHATE YOU CAN REMOVE THE
ELASTASE FROM THE SURFACE
ALLOWING IT TO BE INHIBITED BY
THE ALPHA TRIPSAN.
YOU SEE THE EXOSOME POPULATION
AND IN GREEN YOU SEE ALPHA
TRIPSAN WITH THE EXTRA CELLULAR
VESICLES IN THE BLUE WITH NO
TRIPSAN SHO SHOW NO TRIPSAN TO
INHIBIT THE ELASTASE.
IN TEAL AT THE BOUGTTOM IF YOU
ACTIVATE AND USE THE INHIBITOR
YOU SEE THE RECOVERABILITY TO
INHIBIT THE ELASTASE IN THE
MODEL.
THE IN VIVO AFFECTS THE
NEUTROPHIL ELASTASE THROUGHOUT
THE INTERACTION YOU CAN SEE AS
IN THE SAME MODEL PREVIOUSLY.
THE ACTIVATED NEUTROPHILS AND IN
THE MIDDLE SHOW THE ALVEOLAR
ENLARGEMENT AND YOU INDICATE THE
IT'S ABLE TO INHIBIT ALL THE
UNFOUND NEUTROPHIL ELASTASE AND
THIS SHOWS AIRWAY RESISTANCE AND
THAT IS DECREASED WITH THE EXTRA
CELLULAR VESS KICLES STRS TREAT
YOU GET A DECREASE IN ACTIVATE
EXOSOMES BUT NOT THOSE TREATED
WITH THE SULPHATE.
AND BRINGS TO THE MOUSE MODEL.
IN THE LEFT EXTRA CELLULAR
VESICLES RESISTANCE TO THE
ANTITRIPSAN AND THEY CAUSE
DAMAGE TO COLLAGEN.
IF YOU ERROR TO TREAT THEM THE
SULPHATE YOU RELEASE THE
ELASTASE INHIBIT THE DEGREDATION
AND REDUCED AIRWAY DAMAGE.
BRINGS US TO THE POINT OF THE
QUESTION REMAINING ARE THE EVs
GENERATED FROM ACTIVATED
NEUTROPHILS CAN THEY BE FOUND IN
THE COPD PATIENTS GIVEN THE
PHENOTYPE.
IT'S IMPORTANT BECAUSE THE
PRESENCE OF THESE EXTRA CELLULAR
VESICL
VESICLES DEFICIENCY AND YOU SEE
THE EVs THOSE FROM ACTIVATED
NEUTROPHILS AND INCREASE IN
NEUTROPHIL ELASTASE AND FIND A
HIGHER PERCENTAGE OF ELASTASE
POSITIVE EXTRA CELLULAR VESICLES
BETWEEN THE COPD AND NEVER
SMOKING PATIENT.
IS AND THOSE ON THE RIGHT SHOW
NO APPRECIABLE CHANGE IN THE
ALVEOLAR SIZE BUT IF YOU GIVE
THEM RECOVERED FROM COPD
PATIENTS YOU SHOW DRASTIC
DEGRADATION AND DAMAGE IN THE
LUNG ARCHITECTURE AND THE
ALVEOLAR ENLARGEMENT AND SINCE
IT'S EXOSOMES TO ILLUSTRATE THE
CONTRIBUTION THE ACTIVITY YOU'RE
SEEING DUE TO NEUTROPHIL AND
LOOK AT THE ELASTASE INHIBITOR
CAUSED BY THE NEUTROSOME AND
LOOKING AT THE COHORT OF VARIOUS
SMOKING DEGREES AND DISEASE
PATHO
PATHOGENICITY.
YOU CAN SEE COPD PATIENT WHO'S
ARE CURRENT SMOKERS TENDED TO
POSSESS EXTRA CELLULAR VESICLES
MOST PATHOGENIC AND COPD PATIENT
WHO'S DECREASED DECREASED THE
SMOKING EFFECT BUT WERE STILL
HIGHER THAN THE NEVER SMOKERERS.
THEY NEVER RETURNED BACK TO
NORMAL.
INTERESTINGLY, CURRENT SMOKERS
WHO DID NOT HAVE COPD THEY'RE
EXTRA CELLULAR VESICLES WERE
ABLE TO CAUSE ALVEOLAR
ENLARGEMENT SIMILAR TO THOSE WHO
HAD COPD BUT SHOWING THE
PATHOGENICITY OF THE VESICLES.
PEOPLE WHO QUIT SMOKING
DECREASED THE EXTRA CELLULAR
VESICLES BUT DID NOT RETURN BACK
TO THE BASELINE THE MEDIAN OF
THE NEVER SMOKERS.
THERE'S AN THAT NEEDS TO BE
EXAMINED FURTHER.
AND THAT BRINGS ME TO WHERE WE
GO WITH THE VESICLES.
ALL THE PATIENT DATA WE'VE SEEN
SO FAR TO THIS POINT WERE SINGLE
SNAPSHOTS IN TIME.
IT'S VERY IMPORTANT TO
CHARACTERIZE THESE PATIENT EXTRA
CELLULAR VESICLES
LONGITUDINALLY.
DOES THIS CONTINUE WITH DISEASE
OR DURATION.
IF YOU QUICK SMOKING WOULD YOU
RETURN BACK TO A BASELINE OR
BEGIN TO SEE A CHANGE OF THOSE
THAT WILL GO ON TO DEVELOP COPD
AND THOSE WHO WILL SORT OF
DECREASE DOWN THE BASELINE.
IT'S ALSO IMPORTANT TO LOOK AT
PRO VERSUS ANTI-INFLAMMATORY
SOURCES.
NEUTROPHIL THE MACROPHAGES AND
MONOCYTES AND EPITHELIAL CELLS
WHICH PROVIDE ANTI-CELLULAR
VESICLES.
CELLULAR SENESCENCE IS IMPORTANT
TO LOOK AT THE HALLMARK OF COPD
WITH SENESCENCE THEY'RE
PHENOTYPICALLY DIFFERENT AND
UNDERSTANDING HOW THAT
CONTRIBUTES TO COPD PATHOGENESIS
IS IMPORTANT AS WELL AND LOOKING
AT SINGULAR VESICLES UP TO THIS
POINT EVERYTHING IS LARGE
QUANTITIES OF EVs AND TO
IDENTIFY THE CHARACTERIZATIONS
WITH REGARDS TO CARGO AND CELL
SIGNALLING WILL BE MORE USEFUL
DOWN THE ROAD.
I'D LIKE TO THANK OUR GROUP AT
UAB THAT HAS DONE A LOT OF THE
WORK THANK YOU.
>> THANK YOU, KRIS.
TO REMIND OUR SPEAKERS, WE ARE
LOOKING AT 15-MINUTE TALKS.
WE'LL GET A TWO-MINUTE WARNING.
I FORGOT TO MENTION THIS UP
FRONT, MY APOLOGY.
QUESTIONS PUT IN THE CHAT,
PLEASE.
WE WON'T HAVE A QUESTION ANSWER
SESSION BETWEEN TALKS.
OUR NEXT TALK IS FARRAH
KHERADMAND FROM BAYLOR COLLEGE
OF MEDICINE AT YUM CELL
DYSFUNCTION IN COPD.
>>I WANT TO THANK THE ORGANIZERS
FOR THE OPPORTUNITY TO TALK.
I WANT TO THANK KRIS FOR
BRINGING US BACK TO THE LEVEL
I'M PROBABLY GOING TO BE ALSO
TALKING TO YOU NOT THE LEVEL WE
LEARNED EARLIER TODAY AND WE
STARTED LOOKING AT THE ADAPTIVE
RESPONSE TO SMOKING AND THE TWO
STORIES, THE FIRST PART OF WHICH
IS PUBLISHED.
I'M GOING TO USE THAT AS A WHY
WE'RE MOVING IN THE DIRECTION
WE'RE GOING BUT THEY'RE
INTERRELATES.
WHAT I'D LIKE TO DO IS AND THE
IDEA THE NEUTROPHILS IS DRIVING
THE DISEASE AND WE'RE FOCUSSING
ON A PARTICULAR CYTOKINE AND
IL17A KNOWN TO BE CRITICAL IN
DRIVING NEUTROPHILS INTO THE
LUNGS.
LET ME START TELLING YOU PART 1
OF THE STORY WHICH START FROM
WORK IT STARTED FROM A STUDENT
WHO CAME TO MY OFFICE AND IF YOU
EXPOSED MICE TO A PROLONGED
PERIOD OF CIGARETTE SMOKE YOU
SEE A DEFINITIVE CHANGE IN THEIR
IL17 ADAPT IMMUNE CELLS CHANGES
YOU WOULD SEE AND THAT'S MARK BY
INCREASE IN IL17 IN THE T CELLS
AND THAT WAS OBVIOUSLY FOLLOWED
BY SOME QUANTITATIVE DATA WE
SHOWED THAT BOTH VOLUME AND
DENSITY, THESE ARE THINGS THAT
WE LEARNED ABOUT TODAY IN THE
COPD COHORT STUDIES THE VOLUME
GOES UP AND THE DENSITY GOES
DOWN IN MICE THAT ARE EXPRESSING
PROFOUND IL17A PRODUCTION IB
THEIR CD 3.
WE WENT ON TO SHOW IN FACT THE
IL17A THE DEFICIENCY ADVOCATED
IN MICE AND IF YOU EXPOSE MICE
GLOBALLY DEFICIENT IN IL17 FOR A
PROLONGED PERIOD OF TIME FOR
CIGARETTE SMOKE THEY HAVE
ATTENUATED RESPONSE AND SHOWN IN
THE HISTOLOGY WHERE THE IL17
DEFICIENT MICE HAVE ATTENUATED
EMPHYSEMA AND IT WAS ALLUDED TO
DURING THE MORNING SESSION HOW
MUCH OF INFECTION PART OF THE
DISEASE THAT WE KNOW ABOUT AND
AS CLINICIANS TAKE CARE OF IS
ACTUALLY MAYBE DRIVING THE
DISEASE.
SO IN ORDER TO GET TO THE SECOND
PART OF THIS AND AGAIN THIS IS
PUBLISHED WORK I'LL GO OVER
QUICKLY WE TOOK TWO COHORTS OF
MICE EXPOSED THEM TO AIR OR
CIGARETTE SMOKE FOR THREE MONTHS
AND EXPOSED THEM TO INFLUENZA
VIRUS AND THE HUMAN ISOLATES THE
MICE AND EUTHANIZED THEM AND
AFTER EMULATING WHAT HAPPENS IN
CLINICS NOT SURPRISINGLY WE
FOUND MICE EXPOSED TO CIGARETTE
SMOKE AND INFLUENZA IN FACT MOST
OF WHICH SUCCUMB TO THEIR DEATH
AND WE EUTHANIZE THEM AT THE END
OF TWO WEEKS AND MICE EXPOSED TO
THE AIR AND WERE INFECTED WITH
INFLUENZA STARTED RECOVERING TWO
WEEKS.
SOMETHING WE DO SEE IN HUMANS
AND THE NEUTROPHILS WAS
INCREASED SIGNIFICANTLY IN MICE
EXPOSED TO CIGARETTE SMOKE AND
INFLUENZA.
THIS IS SOMETHING THAT I WANTED
TO SHARE WITH YOU WHICH IS VERY
TELLING THAT WE KNOW TERTIARY
LYMPHOID STRUCTURES ARE MADE IN
THE LUNG AFTER INFECTION AFTER
TRYING TO HEAL FROM THE
INFECTION I'LL GET TO IN THE
SECOND PART OF MY TALK AND I'LL
SHARE UNPUBLISHED WORK BUT THAT
INFLAMMATION IS REALLY MORE
DISORGANIZED AND THROUGHOUT THE
LUNG AND DOES NOT FORM THE
STRUCTURES.
AND TO HAVE A FEW CRITICAL DATA
I WANTED TO SHOW THE T CELL HERE
SPECIFIC TYPE OF ADAPTIVE IMMUNE
CELLS TO THE MUCOSAL LINING
THEY'RE NORMALLY EXPRESSING
IL17.
WE DON'T KNOW WHY BUT MAYBE PART
OF WHY THEY'RE THERE AND WHEN
MICE ARE EXPOSED TO INFLUENZA
THE AMOUNT OF THE IL17
SIGNIFICANTLY GOES DOWN IN GAMMA
DELTA T CELLS AND THOSE EXPOSED
TO CIGARETTES WERE INCAPABLE OF
SWITCHING THE PHENOTYPE.
IF YOU LOOK AT THE SAME T CELLS
PRODUCING INTERFERON GAMMA AND
FOR MOST WHO KNOW ABOUT THE
DISEASE OR INFECTION YOU NEED
THIS IN ORDER TO RECOVER FROM A
VIRAL INFECTION, THESE MICE ARE
INCAPABLE TO PRODUCE INTERFERON
GAMMA AT THE MUCOSAL LEVEL AND
SYSTEMIC.
INTERESTINGLY WE DIDN'T FIND A
SIGNAL IN THE CD8 T CELL WHICH
IS IS ANOTHER STORY I'LL SHARE
AT SOME OTHER TIME.
IMPORTANTLY WHILE WE FOUND
THERE'S QUITE A BIT OF
IMMUNOGLOBULIN PRODUCED IN THE
CIGARETTE SMOKE OR FLU INFECTED
COHORT, THE ANTIGEN SPECIFICITY
WHEN THE B CELLS LEARN ABOUT THE
ANTIGEN AND GO ABOUT CHANGING
THEIR PHENOTYPE THERE'S A
HYPERMUTATION HAPPENING TO MAKE
ANTIGEN SPECIFIC NEUTRALIZING
ANTIBODY ARE REDUCED IN THE MICE
IN THE AIRWAY AS WELL AS
SYSTEMICALLY.
INDICATING THAT THERE'S A
SIGNIFICANT REDUCTION IN THE
ANTIVIRAL IMMUNITY AND STILL
TRANSLATES TO TRANS
TRANSCRIPTIONAL FACTOR SOMETHING
TO PAY ATTENTION TO INTERFERON
RESPONSE IN THE IR7 AND IF3.
TWO OF THE IMPORTANT
TRANSCRIPTION FACTORS CRITICAL
FOR INDUCING ANTIVIRAL IMMUNITY
ARE REDUCED.
AGAIN, TO FINISH THIS PART OF
THE STORY, WE AGAIN WENT TO IL17
GLOBAL DEFICIENT MICE AND DID
WILD TYPE MICE AND IL17
DEFICIENT AND EXPOSED THEM TO
AIR OR CIGARETTE SMOKE AND FOUND
WHILE WILD TYPE SMOKE INFECTED
MICE SIGNIFICANTLY SUCCUMB TO
THEIR DISEASE THE LACK OF IL17
FROM THE GET GO PROTECT THE
MICE.
THAT IS SORT OF WHAT WANT TO DO
IS SUMMARIZE THIS PART OF THE
PRECLINICAL DATA THAT MICE WILL
DIE WHEN INFECTED WITH LETHAL
DOSES OF INFLUENZA AND LOWER
TITERS OF NEUTRALIZING
ANTIBODIES PRESENCE IN THE LUNG
AND GLOBAL DEFICIENCY WHICH HAS
SOME CLINICAL IMPORTANCE BUT IN
HUMANS WOULD BE PROTECTIVE IN
INFLUENZA.
IN THE LAST FEW MINUTES I WANT
TO SHARE WITH YOU SOME OF THE
WHY AND HOW AS PART OF THIS
STORY THAT IS NOT PUBLISHED.
TO GAIN INSIGHT INTO HOW THE
CIGARETTE SMOKE ALTERS
NEUTRALIZING ANTIBODY WE MINED
THE B CELL TRANSCRIPTOMIC
SIGNATURES AND FOUND THE B CELL
RECEPTOR SIGNALLING PATHWAYS AND
KINASE ARE ALTERED IN A COHORT
OF ABOUT 40 PATIENTS WHO NEVER
SMOKED COMPARED TO THOSE WHO
SMOKED.
THESE ARE NOT INFECTED PEOPLE.
THESE ARE POPULATION STUDIES AND
SIGNALLING IS ALTERED WHEN THEY
SMOKE.
TO ADDRESS THE QUESTION, HOW
DOES SMOKING REDUCE B CELL
RESPONSE IN INFLUENZA INFECTION.
WE GO BACK TO OUR ANIMAL MODEL
AND EXPOSED MICE TO CIGARETTE
SMOKE AND INFECTED THEM WITH
INFLUENZA AND EUTHANIZED MICE TO
LOOK AT THE LUNG AND DRAINING
LYMPH NODE POPULATION AND INDEED
WE FOUND MEMORY B CELLS WITHIN
THE LUNG ARE SIGNIFICANTLY
REDUCED AS SHOWN HERE AND AS
SUMMARIZED IN THE QUANTITATIVE
THAT IT REDUCES B CELLS IN THE
LUNG AND LOOKED AT WHAT HAPPENED
WITHIN THE B CELLS AND WHAT WE
FOUND IS THAT CIGARETTE SMOKE
REDUCES THE INFLUENZA SPECIFIC B
CELL CENTERS IN THE LUNG AS WELL
AS IDENTIFIED THAT AGAIN THROUGH
SPECIFIC STUDIES.
WE WENT ON IT LOOK AT THE LT CEL
HELPER CELLS TO GO THROUGH
SOMATIC HYPERMUTATION AND
THERE'S A REDUCTION IN THE T
CELLS AND WE AGAIN SHOWED THAT
AND IN THE LAST PART OF THE TALK
WE THEN WANTED TO PUT THE
CIGARETTE SMOKE ASIDE.
LET'S FOCUS ON IL17.
IT'S SOMETHING THAT WE HAVE
ANTIBODIES AGAINST SO CAN WE
RECAPITULATE WHAT HAPPENS WITH
CIGARETTE SMOKE IN A MODEL
LOOKING AT THE POPULATION AND B
CELL FORMATION.
AND SO THIS TIME THERE'S A
COHORT OF MICE WERE NEVER
EXPOSED TO CIGARETTE SMOKE,
HOWEVER, THE DAY BEFORE THEY
WERE INFECTED THEY WERE GIVEN
IL17A IN ONE DOSE FOLLOWED BY
THREE DOSES.
EMULATING WHAT CIGARETTE SMOKE
MAY BE DOING IN THE LUNG AND THE
MICE SIX DAYS AFTER INFECTION
WERE EUTHANIZED AND INDEED WE
FOUND THAT BOTH ALPHA BETA T
CELLS WERE SIGNIFICANTLY REDUCED
WHEN MICE RECEIVED IL17A WITH
INFLUENZA.
INTRANASALLY IL17 ALSO REDUCES
GERMINAL CENTER CELLS AND
FINALLY WE FOUND THAT THE
INTRANASAL IL17 CAN REDUCE
HELPER CELLS USING NUCLEAR
TETRAMERS WE OBTAINED.
I WANTED TO TAKE A MINUTE TO
TELL YOU THAT ACTIVE SMOKING
INCREASES IL17 IN THE LUNGS.
AS KRIS MENTIONED THE
NEUTROPHILS COME IN THE LUNG.
WELL, IL17 IS CRITICAL FOR THE
NEUTROPHILS.
IN ADDITION IL17 REDUCES
NEUTRALIZING ANTIBODIES AGAINST
VIRUSES.
SMOKING REDUCES ACTIVATION IN
THE LUNG DRAINING LYMPH NODE AS
WELL AS ABLE TO RECAPITULATE THE
INFECTIONS WE SEE.
SOME OF THE EFFECTS OF CIGARETTE
SMOKE AND JUST GETTING IL17 WE
SHOWED THE PHENOCOPY OF THE
ALPHA B CELLS.
I WANT TO ADVERTISE FOR A
COMPREHENSIVE REVIEW OF THE
TOPIC WE JUST PUBLISHED IN
PHYSIOLOGICAL REVIEWS AND YOU
WANT TO FOLLOW-UP ON THE
STORIES.
THANK YOU FOR THE TIME AND I'M
HAPPY TO STOP.
>>
>> WONDERFUL.
WE ARE SPOT ON AND DOING GREAT
ON TIME IN SUMMARIZING DATA IN A
SHORT FASHION.
NEXT IS DR. RENAT SHAYKHIEV TO
TALK ABOUT THE SMALL AIRWAY
PROGENITOR CELL DYSFUNCTION.
>> MY FOCUS OF MY LAB IS DISTAL
AIRWAYS BECAUSE OF THEIR
POSITION IN THE AIRWAY BRIDGING
SYSTEM.
THESE ARE THE LAST BRIDGES OF
THE AIRWAY WHERE COPD IS THOUGHT
TO BEGIN.
THEY GO TO RESPIRATORY
BRONCHIOLES AND THIS IS THE AXIS
WHICH THE DISEASE EVOLVES AND WE
FOCUS ON THIS PARTICULAR AREA.
THERE'S A LOT OF EVIDENCE
SUGGESTING THOSE CHANGES
HAPPENING IN DISTAL AIRWAYS
INCLUDING NARROWING OF LUMEN AND
DISAPPEARANCE OF THE NORMAL
STRUCTURE ORGANIZED TERMINAL AND
PRE-TERMAL BRONCHIOLES AND AIR
TRADING CAN BE SEEN IN
INDIVIDUALS NOT ONLY WITH COPD
BUT ALSO IN PEOPLE AT RISK ALL
THE SUBJECTS WITHOUT COPD.
AS DISEASE PROGRESSES YOU CAN
SEE PROGRESSION OF ANATOMICAL
CHANGES GOING MORE DISTALLY LIKE
CHANGES IN THE RESPIRATORY
BRONCHIOLES CONTRIBUTING TO
EMPHYSEMA AND IT'S POORLY
STUDIED AND IT'S HARD TO SAY
WHAT STARTS FIRST.
RESPIRATORY BRONCHIOLES GIVEN
TERMINAL BRONCHIOLES AND HARD TO
DETECT THE EARLIEST CHANGES IN
THIS TRANSITIONAL REGION IS
CHALLENGING.
AT THE MOMENT I'LL SAY IF
CHANGES HAPPEN IN RESPIRATORY
BRONCHIOLES AND EMPHYSEMA
BECOMES MORE DIFFUSED AND
DETECTABLE.
AND TO UNDERSTAND THE BIOLOGY OF
THE REGION WITHOUT DISEASE AND
HOW IT CHANGES TO COPD AT SINGLE
CELL LEVEL AND EQUATION SPECIFIC
LEVEL.
AND HOW TO MODEL THE CHANGES AND
FIND MAPS WE CAN TARGET AND
THERE ARE MAJOR BARRIERS I WANT
TO SHARE WITH YOU WHICH I AM
DEALING WITH EVERY DAY.
THE AIRWAYS TO ACCESS THROUGH
CONVENTIONAL WAYS.
YOU CANNOT REACH THEM THROUGH
REGULAR MICROSCOPY.
THE REGION CANNOT BE
RECAPITULATED IN MOUSE AND
LOOKING AT CELLULAR ELEMENTS ARE
NOT PRESENT IN THE MOUSE LAB AND
ALMOST NEVER GET RO1 TO STUDY
THE REGION YOU NEED TO KNOW THE
QUESTION BEFORE YOU KNOW
ORGANIZATIONAL AND WHAT IS THE
BIGGER PICTURE OF CHANGES IN
COPD.
WE FOUND ANOTHER ROUTE BECAUSE
WE COULDN'T START AND WE FOUND A
WAY OF STARTING.
BY FOCUSSING ON AGING OF DISTAL
AIRWAYS MANY CHANGE IN DISTAL
AIRWAYS ALSO HAPPEN IN OLDER
SUBJECTS WITHOUT DISEASE.
SO WE INSTITUTES NHLBI A
CO-FUNDED PROGRAM IN WHICH WE
WANTED TO ESTABLISH METHODOLOGY
TO DISSECT THE SMALL RANGES AND
SEE HOW BIOLOGY OF THE RANGES
CHANGE IN INDIVIDUALS WITH
DIFFERENT AGE AND ALSO AS LATE
TRANSITION TO COPD AND INCREASE
COLLABORATION TO GET NORMAL LUNG
TISSUE AND TO GET SAMPLES FROM
PEOPLE WITH AGING-RELATED LUNG
DISEASE AND BY COMPARING
DIFFERENT PATHOLOGIES TO SEE
WHAT IS UNIQUE WITH COPD.
THIS IS THE LOBULE AND THE UNIT
WHERE ALL THE CHANGES HAPPEN AND
THE LUNG DISEASE.
THIS IS THE LAST VISIBLE AIRWAYS
YOU CAN SEE.
HOW TO CONNECT THEM IN A PRECISE
WAY AND THE APPROACH BY WHICH
INJECTING AIR TO THE LAST
VISIBLE AIRWAY WE CAN DELINEATE
THE PATHWAY THAT AIR TRAVELS TO
THE LOBULES AND NOW WE CAN
DISSECT THE PATHWAY AND GET TO
THE LAST VISIBLE AIRWAY AND THE
LAST VISIBLE AIRWAY WOULD BE THE
PRETERMINAL BRONCHIOLE AND WE
REACHED THE LEVEL OF WHERE THE
TRANSITION TO THE LOBULE AND THE
PRETERMINAL BRONCHIOLES LEADING
TO THE ENRICHED TISSUE GOING TO
THE RESPIRATORY REGION AND BY
INJECT INK IN THE AIRWAY WE CAN
DISSECT THE UNIT OF THE LAST
PRE-BRONCHIOLE WHERE ALL THE
DISEASE-RELATED BIOLOGY HAPPENS.
AND SO THIS IS ANOTHER EXAMPLE
SHOWING WE CAN VISUALIZE AIR
TRANSPORT THROUGH THE AIRWAYS
AND THIS TRACKING IN THE AREA OF
BIFURCATION WHERE IT'S HARD FOR
AIR BUBBLES TO MOVE AND THIS IS
THE ALVEOLAR REGION AND YOU SEE
THE ALVEOLI AND THE AIR BUBBLES
WHICH END UP IN THE ALVEOLI
AFTER THE INJECTION OF AIR WHICH
I SHOWED.
AND THERE'S DIFFERENT LEVELS OF
AIRWAYS FROM THE SAME PATIENT WE
CAN FOLLOW THE WHOLE SYSTEM UP
TO OPEN THE BRONCHIOLES TO THE
RESPIRATORY REGION WHERE WITH A
MULTI-MARK ING APPROACH AND
IDENTIFY UNIQUE BIOLOGY AND WHAT
WE FOUND IS THERE'S A BRIDGE
CELL POPULATION GOING TO THE
CLINICAL AND BASIC SCIENCE AND
BRIDGES THIS WITH THE ALVEOLAR
EPITHELIUM AND THESE ARE IN THE
CELL POPULATION SECRETORY CELLS
IN THE AREA OF TRANSITION FROM
TERMINAL TO RESPIRATORY
BRONCHIOLES THESE ARE RED CELLS.
WE WERE ABLE TO USE DIFFERENT
MARKERS TO SHOW DIFFERENT FROM
CLASSICAL POETIC --
HEMATOPOIETIC CELLS AND THEY
TRANSITION TO THE DISTAL REGION.
AND WE FOUND IN ADDITION TO THE
TASK LONG THE PROXIMAL DISTAL
AXIS AND WE CALL THEM SECRETORY
CELLS AND THEY WERE LOST AND THE
CELL POPULATION WHICH WE KNOW
LITTLE ABOUT SIMILAR TO
ARROCYTES WHICH MAKE THE
CAPILLARY INTERFACE IN THE AL
ALVEOLI.
AND THESE ARE THE CAPILLARIES OF
THE CELLS OF THE ALVEOLI IN THE
REGION OF TRANSMISSION WHERE THE
BIOLOGY HAPPENS.
IT'S NOT UNIQUE TO CHANGES TO
COPD.
WHEN WE LOOKED AT THE SAME
SINGLE-CELL DATA OF ALL THE
INDIVIDUALS OLDER THAN 60 YEARS
OLD WE SAW THE SAME CHANGES AND
THE CAPILLARY CELL POPULATION
SUGGESTING THAT MAYBE SOME KIND
OF REGION SPECIFIC NEEDS
COMPOSED TO REGION SPECIFIC
CAPILLARIES AND SMOOMAL CELLS A
CELLS WHICH REGENERATE IN THE
PRESENCE OF THIS UNIQUE REGION
SPECIFIC EPITHELIAL CELL
POPULATION AND THE BRONCHIOLES
ABSENT IN MICE AND THE TB-RB
JUNCTION ABSENT IN MICE AND
SUGGESTING THE UNIQUE BIOLOGY IS
HAPPENING IN THE TRANSITIONAL
REGION AND HOW IT CHANGES IS
IMPOSSIBLE TO MIMIC RECAPITULATE
USING MOUSE SO WHAT WE NEED TO
DO IS ESTABLISH A HUMAN-BASED
MODEL AND HOW DO WE IDENTIFY THE
AIRWAYS?
WE SEPARATED BASAL SELLS FROM
THE BRONCHIOLES FROM THE SAME
PATIENTS FROM PROXIMAL AIRWAYS
AND WHEN WE DIFFERENTIATE THE
CELLS WE WERE ABLE TO
RECAPITULATE THE CELLS WITH ALL
THE MARKERS OF TASKS AND FOCUS
ON A2 TRANSCRIPTION FACTOR.
AND AT THE SINGLE CELL LEVEL
THERE ARE TWO SAMPLES ONE WHICH
WAS SUCCESSFUL HAVING THE MEMORY
TO REGENERATE TASKS IN VITRO
DATA AND THE TASKS ARE THE SAME
WE SEE IN EXPRESSING THE CELLS
AND 32 ALSO.
WHAT IS THE MEMORY IN STEM CELLS
WHICH ALLOWS THE STEM CELLS TO
REGENERATE IN THE ABSENCE OF IN
VIVO IN NICHE AND WE SAW THE
BASAL CELLS EXPRESSED MARKERS
AND TRANSCRIPT FACTOR.
WE WENT TO CHROMATIN LEVEL AND
WE FOUND IN DISTAL AIRWAYS THE
RED COLORS ENRICHED
TRANSCRIPTION FACTORS IN DISTAL
AIRWAY BASAL CELLS RELATED TO
THE TRANSCRIPTION FACTORS I
DIDN'T SHOW ALL OF THEM BUT IF
YOU WANT TRANSCRIPTION FACTORS
MOST SPECIFIC TO PROXIMAL
AIRWAYS AND PIONEERED FACTORS
AND ARE IMPORTANT FOR
MAINTAINING DIFFERENT TYPE OF
MEMORY.
AND DIFFERENT MEMORY
TRANSCRIPTION FACTORS TO
PROXIMAL AND DISTAL AIRWAYS AND
ENRICHED IN BASAL AND
INTERMEDIATE CELLS IN THE
PROXIMAL AIRWAYS.
AND ACTUALLY THAT WAS FUNDED BY
NIH THAT'S WHY I SHOWED THE
SLIDE.
MANY THINGS YOU'RE GOING TO DO
BASED ON YOUR ENTHUSIASM IF NOT
SUPPORTED BY THE STUDY SECTION
OPINIONS.
AND THIS IS THE ENRICHMENT OF
THE DISTAL MEMORY IN THE AREA
WHERE BRONCHIOLES TRANSITION AND
WHEN WE LOOKED AT THE INITIAL
DATA OF COPD WE ALSO LOOKED AT
THIS DETECTABLE FEATURE OF
BROTHER -- BRONCHIOLES IN THE
SURROUNDING CELLS.
WHAT HAPPENS WHEN THE BASAL
CELLS PROGRESS?
THAT'S ANOTHER SAMPLE.
THIS COULDN'T MAKE SQUAMOUS CELL
FACTORS FOR THE DISTAL AIRWAYS.
THE CELLS BECOME SQUAMOUS AND
SENESCENT AND HAVE SENESCENT
MARKERS AND EXPRESSION OF GAMMA
RECEPTOR.
AND THAT'S A CONNECTION TO THE
NEW SYSTEM BECAUSE WE FOUND IN
COPD AND ALSO IN ALL THE
SUBJECTS THERE'S INCREASED
FREQUENCY OF INTERFERON GAMMA
HIGHLY EXPRESSING T CELLS.
SUGGESTING A NUMBER OF T CELLS
RECEPTORS MAY INCREASE CELLS
WITH MEMORY OF REGIONAL
DIFFERENTIATION.
AND THAT CD 8 CELLS RIGHT NEXT
TO BASAL CELLS AND THESE ARE THE
TASKS.
EVERYTHING HAPPENS IN THIS
NICHE.
WE SHOWED THE DATA IN REGIONS OF
CD 8 POSITIVE CELLS IN THE COPD
AND I WON'T GO INTO FOCUS BUT
WHAT I WANT TO END WITH IS
BRIDGING THE GAP IN NHLBI
PROPOSES.
BY SEEING INCREASED PATHOLOGY WE
SEE INTERNAL BRONCHIOLES THERE'S
IN WAY TO IMAGE THAT.
IS THERE THE PATHOLOGY IN THE
PROXIMAL AIRWAYS AND THIS
CULMINATES IN THE BRONCHIOLES.
I MET ALL THESE PEOPLE AND
LOOKED AT SPIROMETER DATA AND
BRONCHOSCOPY SAMPLES AND THE
SCORE OF DISTAL ENRICHMENT WAS
REGULATED IN SMOKERS AND FORMER
SMOKERS WHO DON'T HAVE AIRWAY
OBSTRUCTION SUGGESTING NOT ONLY
THE GENES ARE DETECTABLE AND
MEMORY IS BEGINNING TO BE
ACQUIRED.
AND DIFFERENTIATION IS LOST
SMOKERS WITHOUT LUNG DISEASE AND
OTHER MARKERS WHICH ARE MARKERS
OF DISTAL AIRWAY MEMORY.
AND THOSE SMOKERS WHO HAVE
DRAMATIC LOSS OF MEMORY HAVE
HIGHEST LEVEL OF SYMPTOMS WHICH
DEFINES PRE-COPD PEOPLE WHO
DON'T HAVE AIRWAY OBSTRUCTION
BUT HAVE COPD AND BY BIOLOGICAL
OBSTRUCTION WE CAN USE
LONGITUDINAL NATURE OF SPIROMICS
TO SEE IF IT'S TRUE IN PATIENTS
AND THERAPY COULD BE RESTORATION
OF THE DID I DISTAL REGION AND
RESTORING GOOD MEMORIES WHICH IS
STORED IN THE PROGENITOR CELLS
AND BECAUSE OF AGING OR
PROCESSES SPECIFIC TO
DEVELOPMENT OF COPD.
THANK YOU.
>> EXCELLENT TALK AND WORK.
NEXT TALK WILL BE FROM THE ROLE
OF PULMONARY MODELLING IN THE
MECHANISMS OF COPD FROM IRINA
PETRACHE.
>> THANK YOU FOR INVITING ME TO
PRESENT BRIEF OVERVIEW OF HOW TO
THE LING ENDOTHELIUM MAY
CONTRIBUTE TO COPD AND DIFFERENT
PHENOTYPE.
I'LL REMIND YOU OF THE
IMPORTANCE OF THE LOCATION AND
FUNCTION OF VARIOUS ENDOTHELIAL
CELLS THE OTHER LUNG STRUCTURES
AND CELLS AND HOW CAN BE A DOOR
TO SYSTEMIC PATHOGENESIS OF COPD
AND HOW IMPORTANT THE
HETEROGENEITY IS IN DISEASE
DEVELOPMENT AND GO OVER ACUTE
VERSUS ADAPTIVE CHANGES TO
CIGARETTE SMOKE AND HOW THEY MAY
INFLUENCE VARIOUS DISEASE
PHENOTYPES.
SUCH AS CAPILLARY DROP OUTS AND
PRESENT IN EMPHYSEMA IN THE PULL
MONET
MONETARY HYPERTENSION AND REMIND
YOU ENDOTHELIAL CELLS ARE
CRUCIAL FOR THE DEVELOPMENT OF
INFLAMMATION AND AIR SPACE
REMODELLING AND REMODELLING SUCH
AS VASCULAR WALL.
AS THE PREVIOUS SPEAKERS I'LL
FOCUS ON THE DISTAL AIRWAY
FOLLOWING ON THE OBSERVATIONS
THAT IN EARLY OR PRE-COPD OR
EARLY DISEASE, THIS IS A SIGN OF
MAJOR CHANGES.
REMINDING YOU THAT THE DISTAL
LUNG IS ENRICHED IN PULMONARY
CAPITAL CELLS AND FORM A NETWORK
OF SHORT VESSELS LIKE CAPILLARY
POSTS AND CONSTITUTE 32% OF THE
MASS OF THE ALVEOLI.
AND REMIND YOU IT'S DIFFICULT TO
VISUALIZE THE PULMONARY VASCULAR
SYSTEM IN CROSS-SECTIONAL LUNG
TISSUE WE PRIMARILY USE TO
INVESTIGATE THE LUNGS.
WE HOPE TO ADD ANOTHER LAYER OF
SOPHISTICATION AND UNDERSTANDING
TO THE TWO-DIMENSIONAL
VISUALIZATION OF THE VESSELS.
UNLIKE THE AIRWAYS THE VESSELS
DO NOT BRANCH IN A DICHOTOMOUS
FASHION AND THEY CAN FORM FROM
LARGER VESSELS RATHER THAN A
LOGICAL EXTENSION OF THE
MICROVASCULATURE.
AND VARIOUS INVESTIGATORS HAVE
TRIED TO CLASSIFY THE VESSELS
AND YOU'LL SEE IN THE LITERATURE
VARIOUS NOMENCLATURE WE HAVE TO
PAY ATTENTION TO AS WE DESCRIBE
COPD.
I WANTED TO HIGHLIGHT THE WORK
OF OUTSTANDING VISUALIZATION OF
THE HISTOLOGY REMINDS US THE
ENDOTHELIAL CELLS IN VASCULATURE
IS NOT ISOLATED.
IT'S IN CLOSE CONTACT WITH THE
SMOOTH MUSCLE LAYER AS WELL AS
TO ALVEOLI DIRECTLY IN THE
STRUCTURE OF THE LUNG.
AND AGAIN HERE PULMONARY AND
LARGE ARTERY IN ENDOTHELIAL CELL
CAN BE CLOSE TO A LARGE AIRWAY
AS WELL AS CELLS FROM THE DISTAL
LUNG.
THE ENDOTHELIAL CELLS HAVE A
DIFFERENT TRANSCRIPTOME AND
THESE ARE TRANSCRIPTOMIC
ANALYSIS VERSUS SYSTEMIC
ENDOTHELIAL CELLS.
THROUGH WORK DONE BY DR
DR. STEPHANS AND COLLEAGUES THE
LARGE ARTERY ENDOTHELIAL CELLS
HAVE A HIGHER PROGENITOR
CAPACITY.
MORE SO RECENT RNA SEQ SHOWS TWO
TYPES OF EPITHELIAL CELLS OF THE
MICROVASCULATURE WITH THE SUB
TYPE BEING PARTNERS TYPE 1 CELLS
IN GAS EXCHANGE AND WITH THE
MORE AND G CAP OR GENERAL
CAPILLARY ENDOTHELIAL CELLS
PARTICIPATING IN THE CROSS TALK
AND IN THE PROGENITOR CELL
FUNCTION FOR THE AEROCYTE.
THERE'S PLENTY OF WORK I DON'T
HAVE TIME TO GO TO HOW IMPORTANT
THEY ARE IN THE REGENERATION OF
THE LIST TAL LUNG STRUCTURE.
-- DISTAL LUNG STRUCTURE.
HOW DO WE UNDERSTAND THE
IMPORTANCE OF ENDO THELIUM TO
THE THREE MAJOR PHENOTYPES OF
EMPHASIZE WE'VE BEEN TALKING
ABOUT SINCE THE MORNING WHERE IN
THE CHRONIC BRONCHITIS AIRWAY
THICKENING AND INFLAMMATION IS
CONTRIBUTING TO BY LEAKY BRONCHO
THELIAL CELLS AND HAVE TO DEAL
WITH THE PATHOGENESIS AND
THERE'S LITTLE WORK THERE WHERE
WE UNDERSTAND THE SIMILARITY
WITH COPD AND MANY DIFFERENCES.
WE POSE THE LUNG ENDOTHELIAL
CELLS RESPONSE TO CIGARETTE
SMOKE AND OTHER EXPOSOME WE
STILL HAVE TO STUDY MAY
DETERMINE THE DISEASE PHENOTYPE.
I WANT TO REMIND THE AUDIENCE
ESPECIALLY THE CLINICIANS THOUGH
THE AIRWAY AND THE EPITHELIAL
CELLS IS FIRST SEEING THE
CIGARETTE SMOKE 2,000 COMPOUNDS
THE ENDOTHELIUM QUICKLY IS
EXPOSED TO THE SAME THROUGH
ABSORPTION OF THE TOXIC
CHEMICALS.
SO WE HAVE SHOWN WITH EXPOSURE
VIA THE INHALATION THERE'S
LEUKOCYTES AND DECREASED FLOW
AND THIS MAY BE IMPACTED BY
MULTIPLE SUSCEPTIBILITY FACTORS
SUCH AS LOSS OF CFTR SEEN IN THE
MOUSE WHEN THEY GO THROUGH THE
ACUTE CHANGES IN SMOKE
INHALATION.
HERE WE'RE MOSTLY INTERESTED IN
SEEING WHAT HAPPENS AFTER
DECADES OF SMOKING.
THIS WAS A SEMINOLE PAPER THAT
SHOWS ENDOTHELIAL CELL APOPTOSIS
IS DIRECTLY CAUSATIVE OF
EMPHYSEMA IN THE ALVEOLAR CELL
LOSS AND WE HAVE IDENTIFIED THE
IMPORTANCE OF SINGLE LIPID
SIGNALLING IN THE POST
TRANSCRIPTIONAL AFFECT OF
SMOKING AND BLOCKADE IN THE
SPACE AND USING COLLABORATIVE
WORK WITH SAMPLES FROM THE COPD
GENE AND OTHER COHORTS, WE HAVE
IDENTIFY A PERIPHERAL BLOOD
SIGNATURE USING METABOLOMICS AND
EVENTUALLY GENOMICS OF AN
ALTERED SINGLE-LIPID METABOLISM
IN COPD AND SIGNAL FOR A
PHOSPHATE SIGNALLING IN THE
COHORT OF EMPHYSEMA OF COPD
ASKER BASES.
THIS WAS -- EXACERBATION AND
THIS CAME FROM DONOR LUNGS OF
SMOKERS VERSUS NON-SMOKERS WHERE
WE SAW AGAIN SIGNAL FOR A LOW
S1P ENVIRONMENT AND TO REMIND
EVERYONE, S1P AND THE RECEPTOR
S1P1 IS IMPORTANT FOR THE
MAINTENANCE OF VESSELS AND FOR
REPAIR.
AGAIN, THERE'S THE UNBIASSED
SIGNALS CONFIRMED BY OTHER
STUDIES INCLUDING IN MICE, WE
THINK BOTH SINGLE LIPID
METABOLISM MAY BE IMPORTANT IN
THE SIGNAL TOWARDS DISTAL CELL
LOSS AND INJURY.
TO MAKE HUNDREDS OF PAPERS FROM
OTHER LABS AND AS WELL AS OUR
CONTRIBUTIONS TO THE IMPORTANCE
OF THE ENDOTHELIAL CELLS IN
EMPHASIZE PATHOGENESIS I'M
HIGHLIGHTING IN PINK WHERE THE
PATHOGENIC MECHANISMS THAT HAVE
BEEN SHOWN IN OTHER CELL TYPES
TO BE IMPORTANT AND MANY OF YOU
WILL TALK ABOUT THEM TODAY, THEY
HAVE ALSO BEEN SHOWN TO BE
PERTINENT IN THE ENDOTHELIAL
CELLS IN RESPONSE TO CIGARETTE
SMOKE DAMAGE.
AND OUR LAB HAS FOCUSSED ON
THESE POTENTIAL TARGETS AND
SERAMIDE HAS BEEN INVOLVED IN
INFLAMMATORY AND THE REPAIR AND
THEN VERY WELL KNOWN
SUSCEPTIBILITY FACTOR IN
FUNCTION AS WELL AS LOSS OF CFTR
FUNCTION HAVE BEEN SHOWN TO BE
DAMAGING TO THE ENDOTHELIAL
CELLS IN THE LUNG.
AND SHOWS THEY'RE IMPORTANT IN
DEVELOPMENT AND CONTINUE TO
STUDY THE HYPERTENSION PHENOTYPE
BECAUSE IT ACCOUNTS FOR A LOT OF
MORTALITY AS WELL AS INCREASES
THE RISK OF EXACERBATIONS AND TO
POINT TO THERE'S A PHENOTYPE
THAT'S OUT OF PROPORTION.
THE PULMONARY HYPERTENSION IS
OUT OF PROPORTION TO THE LUNG
DYSFUNCTION AND WE KNOW VERY
LITTLE AS TO HOW THAT OCCURS.
THERE'S PROPOSED MECHANISM THAT
HAVE TO DO WITH MECHANICS,
HYPOXIA AND REMODELLING.
I'M GOING TO FOCUS ON SOME OF
THE WORK THAT WE AND OTHERS ARE
DOING TO BETTER UNDERSTAND THE
PATHOGENESIS OF THESE.
I WANTED TO HIGHLIGHT ONE OF THE
FIRST PAPERS THAT POINTED TO THE
CULPRIT FOR BOTH EMPHYSEMA
REMODELLING IN MICE AND TO
MENTION THAT THE MODELLING IS
STILL UNCLEAR AS TO WHERE IT
OCCURS.
WE TOOK THAT ON WITH A
COLLABORATION AND THERE WAS A
COHORT AND HAVE ADVANCED LUNG
DISEASE AND UNDERGOING LUNG
TRANSPLANTATION AND FEW SAMPLES
BUT WE LOOKED AT THE REMODELLING
AND WHERE DOES IT OCCUR IN
ESTABLISHED CONFIRMED COPD PH
AND ALL HONOREES OF THE CLASSES
I DEFINED PREVIOUSLY HAVE
EVIDENCE OF REMODELLING THAT
DON'T CORRELATE WITH THE MEAN
PRESSURE IN THE COPD AND COPD
PH.
WE THEN LOOKED AT ENDOTHELIAL
CELLS WITHIN THE LARGER VESSELS
OR MICROVASCULATURE AREAS AND
SAW A CHANGE AT THE LATE STAGE
OF DISEASE AND HE HEMODYNAMIC
CHANGES OF M -- PH.
IT'S ADAPTATION OF THE
ENDOTHELIUM AFTER THEY SEE
CERAMIDE AND IN RESPONSE TO
CHRONIC SMOKING ENDOTHELIAL
CELLS ADAPT AND LESS APOPTIC
THAN OTHER CELLS AND THINK IT
MAY HAVE TO DO WITH ADAPTATION
IN MICRORNA CONTENT.
AND THEY'RE RICH IN THE NEURON
26 BUT THERE WAS A NET LOSS IN
ENDOTHELIAL CELL CENTRIC RNA AND
THIS IS CONSISTENT WITH THE LUNG
OF MICE EXPOSED TO SMOKE IN COPD
LUNG TISSUE AS WELL AS IN HUMAN
LUNG TISSUE WE EXPLORED.
TO MAKE A LONG STORY SHORT SINCE
WE PUBLISHED THERE'S A DIFFERENT
FUNCTION IN LARGER ENDOTHELIAL
CELLS SUCH AS SYSTEMIC
VASCULATURE COMPARED TO SMALL
ENDOTHELIAL CELLS WHERE WE HAVE
SHOWN MECHANISTICALLY THEY'RE
REFLECT DECREASED PROLIFERATION.
IN THE INTEREST OF TIME I'LL
SKIP TO THE SCHEMATIC TO POINT
TO YOU THE SAME MICRO-RNA HAS A
DIFFERENT FUNCTION IN
ENDOTHELIAL CELLS COMPARED TO
SMALL ENDOTHELIAL CELLS AND MAY
BE RELEVANT TO PULMONARY
HYPERTENSION IN COPD TO SMALL
AND LARGE VESSELS DIFFERENTIALLY
AND ADAM 9 IS A TARGET SHOWING
INCREASE IN SMOKE AND COPD LUNGS
AND FOUND IT INCREASING THE
VESSELS OF THE COPD AND COPD PH
TISSUES AVAILABLE.
I THINK THE BETTER DISEASE
MODELS THAT MAKE US MORE NIMBLE
TO TEST THE HYPOTHESIS COMING
FROM OUR COLLEAGUES WITH HE
CLINICAL RESEARCH AND NEED
BETTER COHORTS AND DO THE
COMPLEXITY AND I THINK WE'RE
RIPE FOR THAT AND THE CLUE FOR
WHO AFTER SMOKING OR OTHER
EXPOSURES DEVELOPS PULMONARY
HYPERTENSION OR CHRONIC
BRONCHITIS AND OTHER INFLUENCES
AND THANK YOU FOR THE
OPPORTUNITY AND FOR THE FUNDING
AGENCIES WHO SUPPORT OUR WORK.
INCLUDE NHLBI.
THANK YOU.
>> WE'RE DOING WELL ON TIME I'M
HOPEFUL WE'LL HAVE A GREAT HOUR
OF DISCUSSION.
NEXT IS PHIL HANSBRO FROM
UNIVERSITY OF SYDNEY.
I'M SURE IT'S EARLY IN THE
MORNING.
HE'LL TALK TO US ABOUT THE
MICROBIOME.
>> THANK YOU TO THE ORGANIZERS.
IT'S ABOUT 3:00 IN THE MORNING
AND HERE'S MY DISCLOSURES.
NOTHING RELEVANT TO TODAY.
I'LL TALK ABOUT MICROBIOME IN
COPD AND COMPONENTS SUCH AS LPS
AND COMPONENTS CAN IMPACT IMMUNE
CELLS AND DRIVE INFLAMMATION
WITH MODIFYING T CELLS AND MACRO
PHAGES AND INCREASING IMMUNE
DISEASE ALL OF WHICH CAN HAVE
BENEFICIAL EFFECTS AND CREATE
FATTY ACIDS THAT CAUSE IMMUNE
SUPPRESSION AND SUPPRESS THE
INFLAMMATORY RESPONSES OF
MACROPHAGES AND NEUTROPHILS AND
HAVE DELETERIOUS AFFECTS IN THE
LUNG BUT CAN BE DERIVED FROM THE
LUNG OR GUT.
SEQUENCE ADVANCES HAVE BEEN ABLE
TO HELP US AND THERE'S VARIOUS
WAYS TO ANALYZE THE MICROBIOME
TELLING US WHAT BACTERIA IS
THERE AN METAGENOMIC TO SKRNS
THE MICROBIAL DNA TO IDENTIFY
THE SPECIES AND FUNCTIONS OF DNA
IN A PARTICULAR SAMPLE.
THIS ENABLES TO US TO IDENTIFY
THE SPECIES THAT ARE PRESENT AND
ASSOCIATE WITH DISEASE FEATURES
AND ALSO HOW THEY MIGHT BE
DRIVING THE DISEASE FEATURES AND
HELPS US WORK OUT WHAT THE ROLES
OF THE BACTERIA ARE IN HEATH AND
DISEASE.
-- HEALTH AND TODAY.
ONE CHALLENGES IN THE MICROBIOME
SPACE IS WORKING OUT CAUSE AND
EFFECT.
THE VAST MAJORITY OF STUDIES ARE
ASSOCIATIONAL STUDIES IN HUMAN
SAMPLES.
THERE'S A PLETHORA AND FOR THE
FIELD TO DEFINE THE CAUSE AND
EFFECT IN MICROBIOME.
A GOOD WAY FORWARD IS TO
CHARACTERIZE THE MICROBIOME, USE
INTEGRATED OMIC TO WORK OUT M
METAGENOMICS TO DEFINE HOW THE
MICROBIOTA ARE IMPACTING THE
BIOLOGICAL PROCESSES AND USE
ANIMAL MODEL TO WORK OUT CAUSE
AND EFFECT AND TRANSLATE THE
FINDINGS TO HUMAN DISEASE IN
COPD.
THERE'S BEEN NUMEROUS STUDIES OF
THE LUNG MICROBIOME IN COPD.
THERE'S LOTS OF STUDIES AND
THERE'S AN INCREASE IN MICROBIAL
INFLUENCES.
AND WHAT STUDYS HAVE SHOWN
DIFFERENT METABOLITES AND AFFECT
ON CELLULAR PROCESSES THAT
IMPACT ON THE COPD PHENOTYPE.
AND THE MOST RECENT STUDIES
PROFILE THE MICROBIOME AND
METABOLITE CHANGES AND NEED TO
MOVE TO CAUSE AND EFFECT HERE.
IN THE GUT, THERE'S BEEN LESS
STUDIES.
ONLY A FEW.
THEY'VE IDENTIFIED DIFFERENCES
IN HEALTHY SMOKERS AS WELL AS IN
COPD AND START TO USE ANIMAL
MODELS ON THE MICROBIOME AND HOW
AFFECT ON COPD TO MODIFY THE
DISEASE COURSE.
YOU CAN MODIFY THE DIET TO
INCREASE SOME FACTORS LIKE
TRYPTOPHAN OR WHATEVER TO
IMPROVE COPD SYMPTOMS IN MICE WE
CAN REDUCE DELETERIOUS BACTERIA
AND HAVE BENEFICIAL AFFECTS ON
PATHOGENESIS AND USE FECAL
TRANSFERS AND HIGH FIBER DIET TO
REDUCE THE COPD FEATURES IN
MICE.
THERE'S WAYS TO MODIFY THE
MICROBIOME.
THIS IS THE CRUCIAL PATHWAY WE
CAN LOOK AT IN TERMS OF
MODIFYING THE MICROBIOME IN
COPD.
WE CAN INTERVENE TO HAVE AN
IMPACT ON THE DISEASE PROCESS.
WE CAN USE DIETS AND MODIFYING
THE DIET TO ALTER THE GOOD
MICROBIOTA AND CHANGE THE
MICROBIOTA AND METABOLITES THEY
PRODUCE TO AFFECT INFLAMMATION
AND IMMUNE RESPONSES AND MAY
IMPACT COPD.
ONCE WE KNOW THE MOLECULAR
MAKEUP WE CAN USE MOLECULARLY
TARGETED DIETS TO REVERSE THE
CHANGES IN THE GUT.
WE CAN ALSO USE MICROBIOME
INTERVENTIONS AND USE BENEFICIAL
BACTERIA TO REVERSE THE DISEASE
FEATURES AS WELL.
WE NEED TO USE MICROBIOLOGY AND
CAUSE AND EFFECT STUDIES TO WORK
OUT CAUSE AND EFFECT OF THE
BACTERIA AND HOW THEY'RE
INFLUENCING DISEASE.
JUST SOME EXAMPLES OF HOW WE
MIGHT DO THIS.
SO THIS IS UNWPUBLISHED DATA
TAKING COHORTS OF COPD PATIENTS
VERSUS HEALTHY CONTROLS AND HAVE
DONE AN ANALYSIS OF THEIR DIET.
WHAT WE CAN SEE IS COPD PATIENTS
HAVE A LOWER FIBER DENSITY IN
THEIR DIET COMPARED TO HEALTHY
PEOPLE AND IF WE STRATIFY COPD
PATIENTS ACCORDING TO HOW MUCH
FIBER THEY TAKE IN, THOSE THAT
TAKE ON MORE FIBER HAVE GOT A
BETTER LUNG FUNCTION.
THEN WE CAN PROFILE THE GUT AND
LUNG MICROBIOME.
THIS IS PUBLISHED WORK WE CAN
PERFORM METAGENE I'MICS --
METAGENOMICS AND SEE DIFFERENCES
AND CORRELATE THE SPECIFIC
BACTERIA WITH THE SPECIFIC
DISEASE FEATURES AS WELL AS AND
PERFORM METABOLOMICS ON THE GUT
SAMPLES AND CORRELATE THE
DIFFERENT BACTERIA, THE GENES
THEY ARE PRODUCING WITH THE
METABOLITES THEY PRODUCE WITH
DISEASE FEATURES IN PEOPLE.
WE CAN GENERATE THE NETWORK
PROCESSES AND LINK THESE
MICROBIOMES THE METABOLITES WITH
DISEASE FEATURES.
THAT'S REALLY CLOSED TO GETTING
THE BEST WE CAN DO TO A CERTAIN
EXTENT IN HUMAN SAMPLES.
WE CAN THEN USE ANIMAL MODELS TO
TRANSLATE THESE FINDINGS INTO
CAUSE AND EFFECT.
THE BENEFIT OF ANIMAL MODELS IS
THAT WE CAN COLLECT ALL THE
SAMPLES AND COPD THAT HAVE BEEN
PRODUCED AND WHOLE BODY
EXPOSURES AND EXACERBATIONS AND
USE GERM-FREE MICE WHICH IS
TOOLS AND DEFINE CAUSE AND
EFFECT AND CAN TEST BACTERIAL
TRANSFERS AS POTENTIAL
INTERFERENCE IN COPD AND THE
BACTERIA IS DIFFERENT BETWEEN
MICE AND HUMANS.
WE CAN SEE HERE DIFFERENTSES IN
MAJOR FAMILIES AND MAJOR
GENERATE BETWEEN MOUSE AND
HUMANS.
OVERALL THE FUNCTION AL BACTERIL
POPULATIONS ARE SIMILAR BETWEEN
MOUSE AND HUMANS AND PRODUCE
SIMILAR LEVELS OF METABOLITES.
IF WE LOOK AT THE FUNCTIONAL
COHORTS OF BACTERIA ARE SIMILAR
BETWEEN HUMANS AND MICE AND
GIVES CONFIDENCE TO GIVE ANIMAL
MODELS TO STUDY COPD AND LOOK AT
THE CHANGES IN THE GUT
MICROBIOMES IN COPD MICE
COMPARED TO HUMANS ALSO TAKE
BACTERIA AND METABOLITES AND POP
THEM IN ANIMAL MODELS TO LOOK AT
THE IMPACT OF DISEASE FEATURES.
WE CAN GO BOTH WAYS.
THESE ARE ANIMAL MODELS
CIGARETTE SMOKE EXPOSURE AND
INFLAMMATION WITH CELLS AND
CYTOKINES AND KENOKINES AND
EMPHYSEMA AND LOOK AT IMPAIRMENT
OF GAS EXCHANGE AS WE SEE IN
PEOPLE EXACERBATE THE INFECTION
WITH STREP PNEUMONIA OR
INFLUENZA.
WE CAN LOOK AT THE GUT
MICROBIOME IN THE COPD MODEL AND
LINK WE FIND TO SPECIFIC DISEASE
FEATURES.
WE FIND THIS LINK TO
INFLAMMATION AND EMPHYSEMA AND
AKKERMANSIA IN RESPONSES IN TLR
AND LACHONSPIRACEA IMPROVES LUNG
FUNCTION AND WE SEE THE CHANGES
THAT OCCURRED IN THE MODELS WE
CAN THEN USE INTERVENTIONS WITH
DIETS OR MICROBIOMES.
THIS IS HIGH FIBER DIETS AS A
POTENTIAL THERAPY.
IF WE LOOK AT SMOKING MICE WE
SEE REDUCTION IN THE SHORT CHAIN
FATTY ACIDS BUT WITH A HIGH
FIBER ACID AS THEY COME BACK TO
BASELINE.
AND THEN WE CAN HAVE A LOOK AT
WHAT HAPPENS TO THE DISEASE
FEATURES AND THE HIGH FIBER DIET
OR SHORT CHAIN FATTY ACIDS
SUPPRESS COLLAGEN AND EMPHASIZE
IN THE MOUSE MODELS AND IMPROVE
LUNG FUNCTION.
THIS IS WHERE WE USED MICROBIOME
TRA
TRANSFERS AS A POTENTIAL
TREATMENT AND PERFORMED
TRANSFERRED TO MODIFY THE GUT
MICROBIOMES IN THE MICE AND CAN
SEE REDUCED AIRWAY INFLAMMATION
MACRO PHAGES, COLLAGEN AND LUNG
EMPHYSEMA AND CHANGES AS WELL
AND PERFORM THE MICROBIOME
ANALYSIS AND SHOW THE DIFFERENCE
BETWEEN COPD AND HEALTH AND
NON-SMOKING AND IF WE DO THE
MICROBIOME TRANSFERS THIS
NORMALIZES THE MICROBIOMES AND
IDENTIFY THE SPECIES ALTERED IN
COPD AND HOW TO REVERSE THEM
USING THE MICROBIOME TRANSFERS.
NOW WE'VE ESTABLISHED A PIPELINE
AND THIS SAY FIVE-YEAR GRANT
WE'RE DOING WHERE WE CAN DEFINE
THE CHANGES IN IMMUNITY AND TEST
THE DIETARY INTERVENTIONS IN
ANIMALS AND PUT THEM STRAIGHT
INTO AN ADAPTIVE CLINICAL TRIAL
IN COPD PATIENTS.
I THINK THIS IS A GOOD
OPPORTUNITY FOR US ALL TO WORK
TOGETHER TO HARNESS THE CHANGES
IN MICROBIOME AND ANALYZE THEM
IN DISEASE AND IDENTIFIED
DIFFERENCES IN DISEASE AND USE
ANIMAL MODELS TO DEFINE HOW HE
MICROBIOME CHANGES OCCUR IN THE
DEVELOPMENT AND PROGRESSION AND
EXACERBATIONS OF COPD AND
IDENTIFY THE SPECIFIC FACTORS
AND PROCESSES THAT REVOLVED AND
COMBINE WITH MULTIOMICS AND DO
INTERVENTION STUDIES TO DEFINE
CAUSE AND AFFECT AND OFFICIALLY
IDENTIFIED THERAPIES AND
TRANSLATE THESE USING HUMAN
CELLS AND TISSUE ANALYSIS LIKE
WE ARE HEARING ABOUT IN THE
WORKSHOP AND THEN TAKE THESE IN
TO CLINICAL TRIALS AS POTENTIAL
TREATMENTS.
I WANT TO HIGHLIGHT SOME OF THE
IMPORTANT RECENT PUBLICATIONS
FOR MANY PEOPLE IN THE
CONSORTIUM AND ENHANCE WHAT
WE'RE TALKING ABOUT IN THE
WORKSHOPS.
I'LL LEAVE IT THERE.
THANKS.
>> THANK YOU, PHIL FOR A GREAT
TALK AND GET SOME COFFEE.
THANK YOU TO THE SPEAKERS FOR
CONSIDERATION OF OUR SCHEDULE.
OUR LAST SPEAKER AND I ALSO
APPRECIATE ALL THE DISCUSSIONS
GOING ON IN THE CHAT AS WELL.
THERE'S GREAT QUESTIONS BEING
ASKED SHOULD LEAD IT A LIVELY
OPEN DISCUSSION.
THE LAST SPEAKER IS AUGUSTINE
CHOI AT FROM CORNELL AND TALK
ABOUT SENESCENCE AND CELL DEATH
AND MITOCHONDRIAL DYSFUNCTION.
GREAT TO SEE YOU AND THE FLOOR
IS YOURS.
>> THANK YOU VERY MUCH.
CAN YOU HEAR ME OKAY?
>> ABSOLUTELY.
>> THANK YOU AND ED WIN FOR THE
INVITATION AND ORGANIZING
COMMITTEE AND THE LUNG DIVISION
AT NHLBI AND I THANK ALL THE
SPEAKERS AND ATTENDEES FOR THEIR
COMMITMENT TO COMBAT COPD.
SO BEFORE I GET INTO ROLE OF
COPD, LET ME ANIMATE THE REST OF
THE ANIMATION HERE.
IN TERMS OF PATHOGENESIS OF COPD
IN THE LAST DECADES, SO THIS IS
NOT INCLUSIVE LIST BUT I THINK
ALL OF US AGREE INFLAMMATION
CELL DEATH AND ANTIOXIDANT AND
PROTEASE AND ARE PROCESSES
REPORTED TO PLAY AN IMPORTANT
ROLE IN PATHOGENESIS OF COPD.
I WANT TO SHARE A COUPLE SLIDES
HOW WE STUMBLED INTO THE ROLE OF
MITOCHONDRIA.
WE WERE NOT A MITOCHONDRIAL LAB.
WE WITNESSED AUTOPHAGY AND IN A
SERIES OF REPORTS REPORTED SMOKE
INDUCED AN OXIDATIVE STRESS
CAUSING AN IMBALANCE OF ROS
ACTIVATING H STACK MOLECULES AND
TURNED OUT THE H STACK IS
REGULATED AND ACTIVATES
AUTOPHAGY PROCESSES THE LCB
PROTEIN AND INSTEAD OF THE USUAL
PROSURVIVAL EFFECT OF AUTOPHAGY
TOO MUCH AUTOPHAGY WAS
DELETERIOUS IN SMOKE INDUCED
EMPHYSEMA.
IT'S NOT A SURPRISE AND TOO MUCH
AUTOPHAGY CAN BE A BAD PLAYER
FOR YOU.
THIS IS HOW WE GOT STARTED IN
THE ROLE OF AUTOPHAGY AND
EMPHYSEMA.
AND BEYOND THE STUDIES WE WENT
INTO STUDYING SELECTIVE
AUTOPHAGY AND THIS IS STUDIES
DONE BY A GRADUATE STUDENT AT
THE TIME AT PITTSBURGH AND
BRIGHAM AND SUSAN CLUNIN WHO
JOINTLY DID A STUDY SHOWING THE
ROLE OF SELECTIVE AUTOPHAGY HOW
CIGARETTE SMOKE DYSFUNCTION IS
REGULATED BY CILIA PHAGY AND
SELECTIVE AUTOPHAGY WE GOT
INTERESTED IN MITOPHAGY IN THE
EXPERIMENTAL MODEL OF EMPHYSEMA
AND LINKED THE PROCESS TO A MOTE
OF NECROP TOSIS AND THEY WERE
LOOKING AT MODELS OF SEPSIS.
AND STUMBLED INTO AN INTERESTING
FINDING WITH MITOCHONDRIAL
HOMEOSTASIS AND DEFICIENT MICE
IN MACROPHAGES.
THEY DERIVED FROM THE LC
B KNOCKOUT MICE AND THERE WERE
ENLARGED MITOCHONDRIA.
ONE OF THE EFFECTS OF
MITOCHONDRIAL DYSFUNCTION
MORPHOLOGICALLY.
WITH THAT THERE WAS A PAPER
LINKING THE IMMUNE RESPONSES
AUTOPHAGY BY INHIBITING
MITOCHONDRIAL DNA RELEASE
MEDIATED BY THE INFLAMMASOME.
SO THIS IS ABOUT 10 YEARS AGO
AND HOW WE GOT INTERESTED IN
MITOCHONDRIA.
ICONIC AND PIONEER IN THIS FIELD
DR. SHARP WHO TRAGICALLY PASSED
AWAY FOUND MITOCHONDRIA WAS
IMPORTANT IN THE INFLAMMASOME.
IT'S A SECOND MESSENGER
ORGANELLE AND WITH SECOND
IMPORTANT MESSENGERS AND MORE TO
COME IN THE FUTURE.
AROUND THAT TIME WE WERE JOINED
AS A POST-DOCTORAL FELLOW AND
THERE'S A PROFESSOR AT TRINITY
COLLEGE IN DUBLIN WHO WAS IN OUR
PROGRAM PROJECT WITH THE BOSTON
GROUP WITH ED SILVERMAN AND
OTHERS AND OUR JOB WAS TO
DELINEATE THE MECHANISM OF ONE
OF THE GWAS -- CAN YOU ANIMATE
IT, PLEASE.
THE TOP GWAS AND OUR JOB
DELINEATE THE MECHANISM HOW IT
COULD MEDIATE PATHOGENESIS OF
SMOKING AND EMPHYSEMA.
AS A SUMMARY USING IN VITRO
MODELS AND TARGETED MICE AND
SOME HUMAN SAMPLES, SUSAN WAS
ABLE TO SHOW THIS INDEED WAS
VERY IMPORTANT IN THE
PATHOGENESIS OF EMPHYSEMA AND
IRON METABOLISM INCLUDING
MITOCHONDRIAL RN WAS IMPORTANT
IN THE PATH AGAIN --
PATHOGENESIS.
MITOCHONDRIA CAN RELEASE SIGNALS
FROM DAMAGED MITOCHONDRIA AND
WE'LL FOCUS ON MITOCHONDRIAL DNA
FOR THE TALK.
AND WE THANK THE COHORT AND
FERNANDO FOR HIS SAMPLES OF
PLASMA AND LOOKING AT PROOF OF
CONCEPT, CAN WE DETECT CELL-FREE
MITOCHONDRIAL DNA IN THE PLASMA
OF PATIENTS WHO ARE SMOKERS AND
CLASSIFY THEM TO DIFFERENT
SEVERITY OF COPD.
WE WERE INTRIGUED BY THE
OBSERVATION HERE YOU SEE THE
COPY NUMBER AS YOU PROGRESS FROM
MILD TO MODERATE TO SEVERE COPD.
WE W
WE WERE A BIT DISAPPOINT WHEN WE
DOESN'T SEE ASSOCIATION BETWEEN
THE PLASMA COPD AND OUTCOME AND
WE LOOKED AT A VARIETY OF
EXTENSIVE LIST OF CLINICAL COPD
OUTCOMES.
INTERESTINGLY, THEY WERE
INTERESTED IN THE ROLE OF KIDNEY
DYSFUNCTION AND MITOCHONDRIAL
DYSFUNCTION AND KIDNEYS IN
SMOKING EMPHYSEMA AND WE WERE
ABLE TO OBTAIN AGAIN FROM
SPIROMICS COHORT THE SAME PAL --
SAMPLES FROM THE DATA AND THE
MITOCHONDRIAL DNA WITH EXERCISE
TOLERANCE AND SYMPTOM BURDEN OF
SMOKERS WITHOUT AIRWAY
OBSTRUCTION IN THIS STUDY.
SO IN PURSUING THIS WE FOCUSSED
ON THE MITOCHONDRIAL DYNAMICS
AND PLAYING A ROLE IN
PATHOGENESIS OF COPD.
WE'LL ALLOW DETAILS AND
MITOCHONDRIAL HOMEOSTASIS
DEPENDENT ON FUSION, VISION OR
BIO GENESIS.
WE'LL FOCUS ON THE TALK THE ROLE
OF DIFFUSION AND THE OUTER
MEMBRANE FUSION MITOFUSION 1 AND
2 AND LOOKED AT THE MICE FROM
MITOFUSIN 1 AND 2 AND DOUBLE
KNOCKOUTS AND HAVE DONE
EXPERIMENTS IN THE PULMONARY
FIBROSIS MODEL AND COPD AND WE
REPOR
REPORTED THAT IT MEDIATE THE
LUNG FIBROSIS IN A MODEL AND
THERE'S ANOTHER REPORT HOW
CRITICAL MITO FUSIN 2 SUPPRESSES
ENDOTHELIAL CELL VIA MODULATION
OF THE BETA 10 SIGNAL.
WITH STARTED TO DO STUDIES IN
THE MODEL OF SMOKE-INDUCED
EMPHYSEMA.
THIS IS PART OF THE PROGRAM
PROJECT WITH THE CORNELL AND
BOSTON COLLEAGUES AND MITOFUSIN
1 BUT NOT 2 IS PROTECTIVE FOR
SMOKE INDUCED LUNG INJURY.
SO I DO WANT TO FINISH THE NEXT
TWO OR THREE MINUTES ON AN ANGLE
WITH A BIOLOGIST AND THIS IS A
PAPER FROM A RESEARCH SCHOLAR
FROM JAPAN AND OTHERS AND
REVERSING THE MODEL BY
PROGENITOR CELLS ISOLATED FROM
THE LUNG.
THIS PAPER SHOWED THAT AND ONE
PAPER I WANT TO SHARE WITH YOU
AND WE DON'T HAVE COMPELLING
EVIDENCE YET THAT MITOCHONDRIAL
DYSFUNCTION PLAYS A ROLE BUT
THIS IS USING ELASTIS MODEL
SHOWING DELIVERY OF SPECIALIZED
LUNG ENDOTHELIAL CELLS
PROGENITOR CELLS MITIGATED THE
DEVELOPMENT OF EMPHYSEMA
FOLLOWING ELASTASE BY MLI AND
HISTOLOGICAL SLIDES.
THE MECHANISM OF THAT COULD BE
FURTHER LOSS OF ENDOTHELIAL CELL
PROTECT FROM THE EMPHYSEMA
PHENOTYPE AND SHOWING AGAIN THAT
YOU HAVE AFFECTS.
THAT IS THE SLIDES AND THIS IS
MY LAST SLIDE SHOWING YOU WHAT
THE FUTURE STUDIES HERE ARE
LOOKING AT SMOKING INDUCED
EMPHYSEMA AND FIBROSIS AND LOOK
AT THE ROLE OF AUTOPHAGY AND
DYSFUNCTION AND GETTING IN THE
MITOCHONDRIAL DNA MUTATIONS IN
THE CELL-FREE PLASMA AND URINE
FROM PATIENTS WITH SPIROMICS
COHORT.
THANK YOU FOR YOUR ATTENTION.
>> WONDERFUL SUMMARY.
WE FINISHED RIGHT ON TOP OF THE
HOUR.
I'M IMPRESSED.
WE WERE THINKING HOW TO KICK OFF
THE DISCUSSION, IN CASE
INDIVIDUAL NOT PRESENT THIS
MORNING FOR DISCUSSION SO WHERE
WE LEFT OFF BEFORE THE LUNCH
HOUR WAS TALKING ABOUT SORT OF
THE AMAZING RESOURCES OF DATA
AND POTENTIAL SAMPLES AVAILABLE
FOR KLIN CALICO HORTS AND
DOVETAILED INTO DISCUSSION OF
ACCESS AND LIMITATIONS OF THAT.
WE THOUGHT FOR EACH OF THE
SPEAKERS WE'D START BY ASKING
YOU NOT REALLY A SIMPLE QUESTION
BUT I THINK WE SAW EXAMPLES FROM
VARIOUS SPEAKERS OF POTENTIAL
SUCCESSES IN LEVERAGING COHORTS
AND SAMPLES AND THE QUESTION IF
HAVE ONE SPECIFIC DESIRE OR NEED
FOR YOUR LINE OF INVESTIGATION
YOU'D LIKE TO HAVE FULFILLED
FROM ACCESS TO CLINICAL COHORTS
FROM DATA OR BIO MATERIAL WHAT
WOULD THAT BE OR MAYBE
HIGHLIGHTING FOR THE AUDIENCE
AND DISCUSSANTS AND STAKEHOLDERS
BARRIERS YOU'D LIKE TO SEE
ADDRESSED AND OVERCOME TO MOVE
TOWARDS TRANSLATION.
I THINK WHY DON'T WE START WITH
OUR FIRST SPEAKER DR. GENSCHMER
AND IF YOU HAVE ONE COHORT IN
TERMS OF BIO SPECIMENS WHAT
WORLD IT BE?
>> AND I'M VERY EXCITED TO LOOK
INTO THAT.
AND ANY COHORT OVERTIME WITH THE
SAME PATIENT MULTIPLE TIME
POINTS IS IDEAL FOR MY STUDIES.
>> CAN WE SPECIFY PEOPLE WHAT
THEY NEED IF IT'S BLOOD IT'S
SIMPLE FOR US AND OTHERS MAY
REQUIRE ADDITIONAL WORK BECAUSE
THEY MAY NOT HAVE BEEN
COLLECTED.
>> I'LL GO BACK TO ONE.
I'M CURRENTLY LOOKING MOSTLY AT
THE FLUIDS OF PATIENTS.
I'VE BEGUN LOOKING AT SPUTUM AND
IF I WAS ABLE TO FIND A SIMILAR
BIOMARKER OR PHENOTYPE WITHIN
THOSE SAMPLES THEN THAT WOULD
DEFINITELY BE SOMETHING I'D WANT
TO LOOK INTO.
>> YOU BRING UP A GREAT POINT OF
WHAT'S AVAILABLE AND MAY NOT BE
SURMOUNTABLE FOR THE
LONGER-STANDING COHORTS.
DR. FARRAH KHERADMAND.
>> SO I THINK WHAT YOU'RE
GETTING AT IS HOW DO WE
INTEGRATE WHAT WE DO IN THE LAB
WITH THE COHORT STUDIES.
I THINK MANY PEOPLE OBVIOUSLY
NOTED AND IT'S BEEN PUBLISHED
MANY TIMES OVER THAT YOU HAVE A
HETEROGENOUS POPULATION AND THEY
HAVE INVARIABLY COME ACROSS A
LOT OF INFECTION WHICH IS SORT
OF MISSING IN THE ANIMAL MODELS
WHERE WE ACTUALLY JUST EXPOSE
MICE TO A VERY STERILE
ENVIRONMENT.
WHAT I WANT TO POINT OUT IS THAT
EVEN THOUGH IT SEEMS
ARTIFACTUALLY UNREAL FROM WHAT
HAPPENS IN A HUMAN POPULATION
AND WE DON'T SIT IN A CAGE IN A
STERILE ENVIRONMENT UNTIL WE
DIE, WE RUN AROUND AND GET
INFECTIONS.
IT ADDS A LEVEL OF COMPLEXITY TO
THE DISEASE IN ITSELF.
IT IS IMPORTANT FOR COHORT
STUDIES TO TAKE INTO ACCOUNT NOT
JUST COPD EXACERBATION BUT TO
THE BIOMARKERS AND TRY TO
COLLECT TO UNDERSTAND IS IT FOR
INSTANCE THAT WHEN WE IMMUNIZE
PEOPLE, ARE THE RESPONSE TO THE
IMMUNOGEN, THAT BEING THE FLU OR
COVID VACCINE, GOD FORBID, IS
THEIR IMMUNE RESPONSE THE SAME
AS IF YOU WERE NOT AN ACTIVE
SMOKER.
I CAN TELL YOU THAT I THINK SOME
OF THE FUNDAMENTAL QUESTIONS CAN
BE ADDRESSED IN A COHORT STUDY
PEOPLE WERE TALKING ABOUT THIS
MORNING, 7,000, 10,000, 4,000, I
THINK THAT'S COLLECTIVE
INFORMATION THAT NEEDS TO BE PUT
TOGETHER TO TRY TO DECIPHER WHAT
IS IT ABOUT CIGARETTE SMOKING
AND IMMUNE RESPONSE.
DOES THAT ANSWER YOUR QUESTION?
>> I THINK IT DOES.
I THINK THERE'S MESSAGES IN THE
CHAT SPRING BOARDING OFF THAT
AND CLARIFYING WHAT WE CAN DO
WITH EXISTING DATA FROM THE
COHORTS GIVEN THEIR LARGE SAMPLE
SIZE DOVETAILING THAT WITH WHAT
YOU'RE SEEING IN THE MECHANISTIC
STUDIES AND STILL ROOM TO GROW
AND EXPAND THAT SPACE.
>> YOU DOVETAILED IT NICELY WITH
THE LUNG SPACE.
ANY THOUGHTS OR ORTHOGONAL IDEAS
YOU'D LIKE TO SHARE AND BRING UP
FOR DISCUSSION?
>> I THINK THE OVER ALL
CONCEPTUAL DEPTH IS NOT JUST
PEOPLE WHO STUDY BIOLOGICAL
CREATIONS BUT PROPORTIONAL TO
THE ANATOMICAL DISTANCE BETWEEN
THINGS THAT HAPPEN AND WHICH WE
STUDY.
I THINK THE CLOSER WE GET TO THE
APPROACH IN WHICH WE FIND SOME
BIOLOGICAL MARKERS OR SOME
BIOLOGICAL FEATURES WHICH SIGNAL
ABOUT WHAT'S HAPPENING IN THE
PARTICULAR AREA OF DISEASE
DEVELOPMENT YOU CAN DEFINE WHAT
INJURY IS.
WHAT IS INJURY AND WHAT IS THE
INITIAL EVENT AND HOW IT
CORRESPONDS TO SYSTEMIC MARKERS
AND PHYSIOLOGICAL FEATURES WHICH
WE CAN MEASURE IN PATIENTS.
I THINK THAT IS MOST INFORMATIVE
IN TERMS OF GUIDING CLINICAL
STUDIES AND FUTURE INTERVENTIONS
BECAUSE THEY'LL INFORM US ABOUT
CHANGES HAPPENING IN TERMS OF
DISEASE DRIVING PROCESS INTO
DISEASE AND MY EXAMPLE WAS ONE
OF THEM IN WHICH WITH YOU CAB
TRY TO SWITCH FROM TERMINAL
BRONCHIOLES TO THE AIRWAYS AND
SPIROMICS CAN DO BRONCHIAL
AIRWAYS AND PROXIMAL AIRWAY AND
SURE SIGNATURES CAN BE FOUND BY
ANALYZING THE LONGITUDINAL DATA
SETS.
>> THANK YOU.
I'LL HIGHLIGHT WONDERFUL
EXAMPLES FROM DEEP STUDIES AND
TO GO BACK TO THE INITIAL
COMMENT OF THE SECTION THAT MAY
NOT BE POSSIBLE FOR OTHER
COHORTS.
COLLECTIVELY IT WOULD BE NICE TO
DOVETAIL IT AS WE MOVE FORWARD
TO WHAT OPPORTUNITIES ARE THERE
TO EITHER ADD THAT OR LEVERAGE
OTHER TECHNIQUES TO ASSAY THE
INACCESSIBLE OR SPACES BECAUSE
WE DON'T WANT TO LIMIT TO ONE
COHORT GIVEN THE HETEROGENEITY
OF COHORTS WE HAVE ACCESS TO.
IRINA PETRACHE.
>> I LIKE THE ANSWERS GIVEN.
INSTEAD OF LISTING THE
APPRECIATION RESOURCE HAVE NOT
BEEN COLLECTED YET IN THE CROSS
SECTIONAL STUDIES WE HAD, I
WANTED TO POSE A POTENTIAL
APPROACH OR OPPORTUNITY WE HAVE
ON THE BASIC SCIENCE THERE'S
BEEN QUITE A RICH AMOUNT OF DATA
THAT IS COMING THROUGH WITH
POTENTIAL TARGETS.
AND PERHAPS THE LACK OF
ENTHUSIASM OF MOVING THEM TO
BEDSIDE IS RELATED TO THE FACT
THAT TESTING FOR THE RELEVANCE
FROM THE MOUSE OR CELL CULTURE
OR INTO COHORTS AND LOOKING FOR
A SIGNAL LIKE NEEDLE IN A
HAYSTACK IS NOT ONLYING BUT OF
THE -- ONLY DAUNTING BUT
RESULTS IN NEGATIVE DATA AND MAY
DIMINISH THE ENTHUSIASM OF
FUNDING AGENCIES OR BIG PHARMA
TO REALLY LEAVE OR MOVE IT
FORWARD SUCH AS COPD.
AND I THINK THE OPPORTUNITY FOR
THE SUBPHENOTYPING LIKE
IDENTIFYING AND COUPLE
INDEPENDENTLY VALIDATED TARGETS
CAN WE LEVERAGE THE WEALTH OF
THE CLINICAL DATA AND BIOMARKER
DATA TO UNDERSTAND IN WHICH
INDIVIDUAL AND WHICH EXPOSURE
AND MICROBIOME AND DIET IS THAT
TARGET RELEVANT.
AND PUTTING THOSE TOGETHER I
THINK WITH THE ADVENT OF LARGE
INFORMATIC CAPABILITIES WE CAN
GET THERE.
>> I AGREE WITH WHAT THEY'RE
CHATTING ABOUT MAKING WHAT WE
KNOW FROM THE BASIC SCIENCE AND
COULD WE POTENTIALLY RECLASSIFY
PHENOTYPES.
IT'S SOMETHING WE HAD IN THE
LAST QUESTION AND MAYBE WE'LL
GET THERE.
PHIL, THOUGHTS?
>> YOU'RE GOING TO HATE ME FOR
THIS ABOUT WHAT WE NEED FROM
MICROBIOMES TO THIS BECAUSE IF
YOU COULD GO TO THE SUPER MARKET
AND GET SAMPLES YOU WANTED OFF
THE SHELF WE'D GET STABLE
DISEASE AND EXACERBATIONS AND
WANT GUT, LUNG AND BLOOD SAMPLES
THAT MATCH FROM THE SAME
PATIENTS AND GUT BIOPSIES TO DO
THE FULL METABOLOMICS AND LOOK
AT THE FACTORS OF PATHOGENESIS.
WHERE WE NEED TO COME TO AS A
FIELD IS THIS IS WHAT WE NEED
THIS IS WHAT'S POSSIBLE AND WHAT
WE CAN GET TO BETTER UNDERSTAND
THE DISEASE.
>> THERE WAS A COMMENT ABOUT THE
ONE MECHANISM APPROACH WE ALL
ASPIRE TO BECAUSE THAT CHALLENGE
I THINK WAS OUTLINED AND THERE'S
NHLBI HERE HOW TO SUPPORT THE
COMMUNITY IN NOVEL COLLABOR
COLLABORATIONS AND LOOKING AT
LINES RELATED TO SAY THE DISEASE
PHENOTYPE ASSOCIATED WITH COPD
PROGRESSION AND VASCULATURE
RELATED TO EMPHYSEMA AND
CORRELATIONS.
I THINK THAT WOULD BE NICE ALSO
TOE TALK ABOUT STRATEGIES TO
MOVE FORWARD IN TERMS OF
FUNDING.
IN THE U.S. SIDE THERE'S
CHALLENGES IN BRINGING FORWARD
THE BIGGER, BROADER IDEAS AND
FRANKLY FUNDAMENTAL TO ADDRESS
THE NEWER LINES OF INVESTIGATION
WHERE WE'D LIKE TO KNOW
TECHNOLOGIES AND IDEAS.
ORE TO AMIT.
>> THANK YOU AND THERE'S
THOUGHTFUL ANSWERS THERE.
I WANT TO JUMP BACK TO WHAT
IRENA SAID AND I THINK IT'S
SHOWING UP IN THE CHAT.
IT'S GOING TO BE HIGHLY RELEVANT
TO EVERYBODY I THINK ON THE
CALL.
THE IDEA OF THE DISEASE OF COPD
AND IT'S POSSIBLY SO MANY
LITTLER DISEASES AND ENDOTYPING
AND USING CF AS AN EXAMPLE
BECAUSE IT'S A SPACE I KNOW.
AS A MONOGENIC DISEASE IT WAS
FOCUSSED ON THE DEVELOPING
THERAPIES AGAIN THE GENE THERAPY
AND WHAT IT LOOKED LIKE IS
THAT'S HARDER WHILE THE PATHWAY
WORKS THE THERO TYPING IS MORE
DIFFICULT AND NOT JUST ONE DRUG
OR GENE.
IT'S A BIT MORE COMPLICATED THAN
THAT.
KNOW TAKING A COMPLICATED
DISEASE LIKE COPD HOW DO YOU GO
TO THE MECHANISTIC QUESTIONS.
ARE THE MECHANISMS WE'RE SEEING
ARE THEY PREVALENT IN ALL TYPES
OF COPD OR WILL THEY NEED TO BE
REALLY -- WILL THE MECHANISTIC
ENDOTYPING PUT US IN DIFFERENT
CLASSES OF COPD OR OTHER
FEATURES THAT WILL DRIVE US INTO
ENDOTYPING PROPERLY AND HOW DO
YOU TAKE THAT TO A THEROTYPE?
IT'S A LOADED QUESTION.
I DON'T KNOW WHO WANTS TO TAKE
THE FIRST SHOT ON IT BUT IF
ANYBODY IN THE PARTICIPANTS
WOULD LIKE TO ADD TO THE CHAT,
PLEASE DO.
IT'S WHAT WE'RE ALL GETTING AT
IS THAT.
I'LL BE QUIET AND LET YOU GUYS
WHOEVER WANTS TO TAKE A SHOT
FIRST.
PHIL, YOU'RE UNMUTED SO YOU'RE
GOING FIRST.
>> IT'S A GREAT QUESTION AND
RAISES IMPORTANT POINTS.
AS TRANSLATIONAL PEOPLE WE NEED
TO KNOW WHAT WE'RE TRYING TO
TREAT.
WITH ASTHMA IT'S A BIT MORE
DEFINED.
YOU HAVE NEUTROPHILIC ASTHMA AND
PUT IT INTO DIFFERENT COHORTS OF
PEOPLE AND TRY TO BREAK IT DOWN
AS YOU SAID INTO DIFFERENT
POPULATIONS THAT MIGHT BENEFIT
FROM SPECIFIC TARGETED
THERAPIES.
HOW DO WE DO THAT IN COPD?
WE ALL LEARNED THAT -- WE ALL
HEARD ABOUT THAT WHEN WE HEARD
OF TYPES OF COPD.
HOW ELSE CAN WE BREAK DOWN COPD
POPULATIONS AND TRY TO MODEL
THOSE TYPE TO IDENTIFY SPECIFIC
THERAPIES FOR SPECIFIC GROUPS OF
PEOPLE.
THAT'S A GREAT QUESTION.
HOW DO WE DO THAT AND HOW CAN WE
MODEL IT TO COME UP WITH BETTER
SOLUTIONS?
>> ANYBODY ELSE WANT TO TAKE A
SHOT ON GOAL?
>> WHAT PHIL BRINGS UP IS
CRITICAL BORROWING FROM OTHER
DISEASES AND TALKING TO
CARDIOLOGISTS THEY WANT TO KNOW
IF IT'S HALF GRAPH OR WHATEVER
THEY'RE DISCUSSING WHEREAS WE
CALL EVERYONE COPD AND AND
THERE'S THE TRAJECTORY OF THE
DISEASE.
WE KNOW THERE'S EXTRA ONES
IDENTIFIED AND WE DON'T ALL HAVE
THE SNIPS AND THEY DON'T ALL
HAVE IT.
A LITTLE BIT BITS ALONG WITH
LIVING IN THE CITY WHERE IT'S
POLLUTED AND SMOKING.
UNLESS WE START LOOKING AT THE
DISEASE IN A DETAIL, ORIENTED
MANNER I THINK MOST CLINICAL
TRIALS WILL FAIL AS THEY HAVE IN
THE PAST.
>> WOULD A TRIALIST LIKE TO
SPEAK UP ABOUT THAT QUICKLY?
>> THERE WAS A BIG DOCUMENT IN
LANCET WITH THE COPD COMMISSION
AND LOOKED AT THE TAXONOMY OF
COPD AND SHOULD WE FIRST APPLY
THIS IDEA OF ETIOTYPES AS ONE
WAY OF BETTER CHARACTERIZING THE
HETEROGENEITY OF DISEASE AND
DISCUSSION AROUND PRO-COPD AND
HOW WE CHARACTERIZE THAT AND A
SEPARATE DISCUSSION ABOUT
ENDOTYPES AND PHENOTYPES WITH
RESPECT TO DRUG DEVELOPMENT
THERE'S NEWER DRUGS TARGETING
SPECIFIC PATHWAYS LIKE L33, TYPE
2 INFLAMMATION.
THE CHALLENGE WE HAVE IS THAT WE
DON'T HAVE GOOD WAYS OF
PHENOTYPING THEM IN CLINIC.
WE DON'T GET LUNG FUNCTION WE
DON'T EVEN KNOW THE RAPID P
PROGRESSERS AND HAVE DRUGS TO
MATCH IT UP.
THERE'S NOT HUGE I MPETUS TO DO
THAT AND AS WE GET NEWER DRUGS
FOR INSTANCE THE DATA LOOKING
POTENTIALLY PROMISING.
WE MAY HAVE MORE DRUGS FOR TYPE
2 INFLAMMATION AND I THINK
HOPEFULLY THE CLINIC WILL CATCH
UP BUT HOW DO WE IDENTIFY THE
UNIQUE SUBTYPES OF PATIENTS IN
REAL LIFE.
>> YOU MADE GREAT POINTS AND
YOUR THOUGHTS ABOUT THE DEVE
DEVE -- DEFILLA MAB AND THEN YOU
HAD A DRUG THAT CAN TARGET THE
ORIGINAL MECHANISM.
YOU HAVE TO PROVE IT AND YOU
HAVE TO PROVE THE MECHANISM
YOU'RE TARGETING IS REAL AND NOT
A CONSEQUENCE OF YOU LOOKING FOR
THE MECHANISM INSIDE THE STUDY
AND HOW DO YOU FIND THE
BIOMARKER AND CONSISTENTLY SHOW
OVER AND OVER AGAIN IN MULTIPLE
COHORT IT'S A READ OUT OF A
PROCESS THAT CAN BE TARGETED
SUCCESSFULLY?
>> EXCELLENT.
ANY OTHER TAKES ON THE GENERAL
QUESTION?
I THINK TOMORROW THERE WILL BE A
LONG SESSION TO COVER THIS TOPIC
SO I DON'T BELABOR IT THAT MUCH
LONGER BUT I'D LIKE TO PIVOT TO
ONE MORE QUESTION.
FOR THE SPEAKERS AND ANYBODY
ELSE WHO MIGHT BE INTERESTED,
WHAT'S EXCITING TO YOU AND WHAT
ARE YOU SEEING IN THE WORLD OF
LUNG DISEASE OR CANCER?
MAYBE IN YOUR OWN RESEARCH YOU
THINK IS UNIQUE IN UNDERSTANDING
THE BIOLOGY OF COPD EVEN BETTER?
I'VE BEEN EXCITED ABOUT THE
DEVELOPMENT OF SPATIAL
TRANSCRIPTOMICS AS AN AREA OF
LEARNING A BIT MORE ABOUT WHAT
MIGHT BE GOING ON IN SPECIFIC
MISSIONS VERSUS THE WHOLE
DIGESTIONS.
IS THERE ANYTHING ELSE RIGHT NOW
YOU GUYS ARE SEEING IN COPD OR
UNRELATED DISEASE THAT'S
EXCITING AND SHOULD BE INVESTED
OR CONSIDERED AS WE MOVE FORWARD
IN COPD.
ANYBODY?
PHIL, YOU'RE UNMUTED SO YOU GO
FIRST AGAIN.
>> NOW I KNOW HOW TO GET MY
RESPONSES IN.
SO I THINK THE NEW OMIC
TECHNOLOGY IS EXCITING.
YOU MENTIONED SPATIAL
TRANSCRIPTOMICS AND SPATIAL
PROTEOMICS AND WE START TO LOOK
AT AND I THINK WE HAVE TO DO IT
THIS WAY, WE START TO LOOK AT
EACH ONE OF THESE OMICS
INDIVIDUALLY.
WE HAVE TO BECAUSE THEY'RE
COMPLICATED AND NEED TO MAXIMIZE
WHAT WE GET FROM EACH ONE AND
OVER TIME WE NEED TO WORK OUT WE
NEED TO WORK OUT HOW WE
INTEGRATE A LOT OF THESE
FINDINGS TO MORE HOLISTICALLY
UNDERSTAND DISEASE.
ONCE WE DO THAT WE CAN FIND
POTENTIALLY NEW TARGETS THAT
CONTROL ENTIRE DISEASE PATHWAYS
WE'VE NOT DISCOVERED YET.
THAT BE ONE WAY.
MAYBE THAT'S PIE IN THE SKY.
NEVERTHELESS I THINK MAXIMIZING
THE USE OF THE GENOMIC AND
SPATIAL TRANSCRIPTOMIC AND NOW
PROTEOMICS WILL ALLOW TO US
PROGRESS.
YOU MENTIONED ALL THE FAILS BUT
ONE PRESENTATION AT ATS ABOUT
BRONCHIECSTASIS THAT PREDICTED
DISEASE PROGRESSION.
THAT'S HOW TO USE THE
TECHNOLOGIES AND BETTER
UNDERSTAND DISEASE AND COME UP
WITH BETTER DIAGNOSTICS AND
TREATMENTS.
>> I WANT TO BE AS AWAKE AS PHIL
IS.
I WANT TO KNOW HIS MICROBIOME.
I HAVE BEEN INVOLVED IN ADVANCES
IN THREE DISEASES AND WE TALKED
ABOUT CF.
THE SUCCESS IN CF IS AMAZING AND
I THINK WE HAVE SO MUCH TO LEARN
FROM THAT AND I'M NOT GOING TO
REPEAT WHAT WAS SAID.
THE SECOND IS LUNG CANCER.
YOU ARE TAKE THE MOST FATAL
CANCER OF ALL AND WE'RE MAKE
SUCH GREAT IMPACT BECAUSE OF
PERSONALIZATION AND EARLY
DETECTION.
MOVING THE EARLY DETECTION AND
IMPROVING THE DEFECTION OF COPD,
IMPROVING OUR METHODOLOGIES
BEFORE FEB1 MAY BE A CLUE.
AND FINALLY IN CARDIOVASCULAR
DISEASE THEIR IMPROVING ON THE
CHOLESTEROL AND ON TRAPONIN.
IF YOU LOOK AT BAD VERSUS GOOD
CERAMIDE RATIO AND MAJOR ADVERSE
CARDIOVASCULAR EVENTS IT'S A
HUGE REFINEMENT BROUGHT TO YOU
CURTSY OF TARGETED METABOLOMICS
AND NEVER GIVING UP ON THE
METHODS YOU HAVE AND I'M HAPPY
TO BE PART OF THIS.
>> ANYBODY ELSE?
>> I LOVE THE QUESTION.
ANOTHER IRISH IN COPD AND MAYBE
ANY OTHER LUNG DISEASE PEOPLE
WHO STUDY ONE INDIVIDUAL LUNG
DISEASE LIKE THE IDEA OF BIOLOGY
MANY DON'T STUDY THE SAME
ANATOMICAL STRUCTURE AND SAME
ALVEOLI AND CELLS IN COPD AND
SAME IN LUNG CANCER NOT ONLY IN
TERMS OF CLINICAL STUDIES BUT
BIOLOGY.
AND LOOKING HOW THEY'RE SIMILAR
IN COPD, OR WHAT I BELIEVE AND
DIFFERENT PATHWAYS AND BIOLOGY.
IN FACT IT'S LIKE COMPETITION
FOR THE SAME CELL TYPE AND
DIVIDING THEM NOT COMPARING OR
UNDERSTANDING THE PRINCIPLES BUT
WHAT ARE THE UNIVERSAL KINDS OF
MECHANISMS OR PATHWAYS WHICH ARE
OF INTEREST FOR ALL THE
PATHOLOGISTS.
THAT MAY HOLD IMPORTANT VALUE
FOR UNDERSTANDING THE MECHANISM
LEADING TO DIFFERENT CLINICAL
FEATURES.
I THINK HAVING THE INTEGRATED
APPROACH NOT BY DIVIDING INTO
DIFFERENT PATHOLOGIES BUT TRYING
TO INTEGRATE THE KNOWLEDGE IN
DIFFERENT LUNG DISEASES.
THAT WOULD BE ONE OF THE
DIRECTIONS TO FIND AN ANSWER.
>> AND CAN I SAY SOMETHING,
WE'RE AN INTIMATE GROUP OF 200
PEOPLE OR SO, WHAT I'VE SEEN
OVER THE LAST 20 YEARS IN THE
FIELD IS THAT THERE'S LESS AND
LESS INTEREST IN IMMUNOLOGY IN
PARTICULAR AND THE MOST ADVANCES
MADE IN TREATMENT OF LUNG CANCER
IS IMMUNE CHECKPOINT INHIBITORS
AS A RESULT OF UNDERSTANDING HOW
IMMUNE CELLS CAN BE HARNESSED IN
ORDER TO TREAT CANCER.
SO CAN WE DO REVERSE ENGINEERING
UNDERSTANDING HOW IMMUNE CELLS
ARE TRYING TO DO REVERSE
ENGINEERING.
WE KNOW CELLS DIE AND THERE IS
AUTOPHAGY AND ALL KINDS OF
THINGS AND WHAT I'M NOT HEARING
IS THAT WE KNOW THERE IS A
DESTRUCTION OF THE LUNG.
WE KNOW IT IS SYSTEMIC AND
CARDIOVASCULAR'S INVOLVED AND
MULTIPLE ORGANS ARE INVOLVED AND
WE KNOW THERE'S A SYSTEMIC
RESPONSE TO CIGARETTE SMOKING
BUT NOT LOOKING AT THE 800 POUND
GORILLA IN THE ROOM BECAUSE LESS
PEOPLE ARE INTERESTED IN
UNDERSTANDING IMMUNOLOGY OF COPD
AND MORE INTERESTED IN FINDING
BIOMARKERS.
NOT THAT THERE'S ANYTHING LONG
WITH UNDERSTANDING BIOMARKERS
NEED TO FUNDAMENTALLY GET TO
WHAT IS IT THAT AFFECTS OTHER
SYSTEMIC ORGANS.
>> I THOUGHT ABOUT WHETHER OR
NOT SOMETHING LIKE WHAT MARK
DAVIS HAS BEEN TALKING ABOUT
ABOUT A SYSTEMS IMMUNOLOGY AND
SPATIAL IMMUNOLOGY APPROACH
MIGHT OFFER US MORE TO BE SAID
THEN JUST SAYING WE MEASURED T
CELLS.
THIS GIVES A NICHE -- THE
SPATIAL NICHE AND AN IDEA OF THE
SPATIAL OMICS.
I DON'T KNOW HOW CLOSE THAT IS
TO REALITY BUT I KNOW THEY'VE
DONE IT IN OTHER DISEASES.
>> TO FOLLOW-UP ON THAT I THINK
WE CAN HAVE MORE DATA TO WHAT
I'M SAYING.
EVEN WITHIN THE CD 8 AND 4
POPULATION THERE'S SO MANY
SUBSETS OF T CELLS WITHIN THAT
POPULATION.
THE SINGLE CELL OMIC STUDIES CAN
INFORM US AND TELL US WHY
SOMEONE WHO SMOKES HAVE THEIR
MUCOSAL IMMUNITY ACT SO
DIFFERENT FROM THEIR SYSTEMIC
AND VICE VERSA.
THEY'RE ALL IMPORTANT QUESTIONS.
WE CAN'T LOOK AT A CD4
POPULATION AND SAY THEY'RE ALL
CD4.
SAME WITH MACROPHAGES.
THERE'S SO MANY TYPES THAT REACT
DIFFERENTLY IN THE LUNG IN
RESPONSE TO ENVIRONMENTAL
ANTIGENS AND CALL THEM
MACROPHAGES.
UNTIL WE GET INTO SUBSET OF
CELLS AND UNDERSTAND THE
INDIVIDUAL CONTRIBUTION I DON'T
THINK WE'LL UNDERSTAND MUCH
ABOUT THIS DISEASE PAT
PATHOPHYSI
PATHOPHYSIOLOGY.
>> TO BROADEN ON WHAT YOU SAID,
WHAT DR. CRAPO SAID THIS MORNING
I TEND TO AGREE WITH THE
IMPORTANCE OF FLVRMENT --
INFLAMMATION A LOT OF THIS AND
THE ROOT OF INFLAMMATION IS
GENERALLY CELLS OF IMMUNE
SYSTEM.
I'D ECHO THE SENTIMENT HE HAD.
>> AND INVOLVING THE TECHNOLOGY
POSED ABOUT SYSTEMS IMMUNOLOGY
AND SPATIAL TRANSCRIPTOMICS.
AS A TRANSLATIONAL PERSON I'M
THINKING HOW DO YOU SCALE THAT
UP AND DEPLOY THAT INTO A
CLINICAL COHORT AND THERE'S A
RECURRENT THEME ON THE CONVERSE
AND HOW YOU POTENTIALLY
INTRODUCE THE TECHNIQUES TO
BETTER CHARACTERIZE THE PATIENTS
AND COHORTS AND THE PHENOTYPES
BASED ON LARGER BIOMARKERS AND
TRANSLATE THAT TO BETTER MODELS
CAN BE MADE FOR THE PHENOTYPES
DEFINED FOR OUTCOME TRAJECTORIES
AND THERE'S DISCUSSION WITH
FERNANDO AND OTHERS ABOUT HOW TO
TAKE THAT INFORMATION.
DO WE NEED TO DEFINE IMMUNOLOGIC
DATA OR GENE EXPRESSION DATA TO
BETTER HONE IN ON POSSIBLE
MECHANISMS THAT SMARTER THAN ME
CAN DEVELOP.
HOW DO WE ACTUATE THE
IMPROVEME
IMPROVEMENTS AND TAKE CLINICAL
FINDINGS AND MARRY IT.
>> I'LL SAY I THINK WE'RE IN THE
WALKING STAGE OF THIS RIGHT NOW.
WE'RE NOT QUITE AT THE RUNNING
STAGE.
BUT I DO LIKE THAT WE'RE
STARTING TO WALK.
THAT'S AT LEAST SOMETHING TO BE
SAID FOR THAT.
I WANT TO HEAR FROM YOU AS WELL.
>> IN RESPONSE TO FARRAH ANOTHER
LEVEL OF COMPARTMENTIZATION AND
PEOPLE IN RESPONSES OF
INFLAMMATION BARELY ATTACH THEIR
LEVEL OF WHAT A PARTICULAR CELL
TYPES WITHIN THE DISEASE
PATHOLOGICAL REGION WITH THE
IMMUNE SIGNALS.
THOSE STUDIES ARE NEEDED FOR
HUGE AMOUNT OF INFORMATION WE
KNOW ABOUT INFLAMMATORY AND
IMMUNITY AND LINK IT TO THOSE
SPECIFIC PATHOLOGICAL CHANGES
AND STRUCTURAL AND EPITHELIAL
CELLS AND STROMAL CELLS AND
FIBROBLASTS AND SO ON AND SEE
HOW THE DIFFERENT CELL TYPES
XHBLTH
>> I MISSED PART OF THE
DISCUSSION.
THE ADVANTAGE OF BEING REMOTE
AND I GOT A CALL FOR A PATIENT.
WHAT I'M HEARING I LIKE VERY
MUCH WHAT I'M HEARING.
BUT I THINK WHAT YVONNE IS
SAYING IS QUITE IMPORTANT.
WE HAVE TO TRY TO TAKE ADVANTAGE
OF THE LARGE COHORT AND AGAIN
NOT TO SAY EVERYTHING HAS TO BE
DONE WAS WORK HAS TO BE DONE IN
VITRO, IN VIVO, I DON'T THINK
WE'RE TAKING FULL ADVANTAGE OF
THE POTENTIAL WE HAVE HERE.
AND SOME OF THESE THERE'S MANY
FROM WHAT WE HEARD THIS MORNING
THAT ARE TO A CERTAIN LEVEL
MAT
MATURE AND THERE'S BEEN
CHARACTERIZED QUITE A BIT.
THAT MAY STILL REQUIRE THE FIRST
QUESTION WE HAVE TO ASK
OURSELVES IS WHAT CAN WE DO WITH
WHAT WE HAVE BECAUSE WITH YOU
MAY NOT HAVE THE RIGHT BIO
SPECIMEN AND OFTEN THE TISSUE IS
MISSING EXCEPT FOR BLOOD AND
SOMETIMES BRONCHOSCOPY WITH
LAVAGE BUT WE CANNOT ADD THROUGH
ANCILLARY STUDY BECAUSE IN MANY
COHORT WE WOULD HAVE THE
POSSIBILITY OF DOING ADDITIONAL
MESH URASUREMENT AND THE MORE
COMPLICATED BUT I'D START WITH
ASKING MYSELF WITH WHAT CAN WE
DO WITH WHAT WE HAVE BETTER AND
WITH YOUR EXPERTISE AND ANYONE
WHO DOES OUTCOME RESEARCH LIKE
MYSELF AND IF THERE IS ANY
ADDITIONAL NEED AND HOW CAN WE
WORK THAT TOGETHER THAT THERE IS
PLACE FOR ANCILLARY STUDY WHERE
IN THE SAMPLE OF OUR COHORT WE
CAN BUILD A SUBPROJECT THAT
WOULD ALLOW US TO MOVE AHEAD?
I THINK THE PROBLEM IN COPD AS
LUNG WE CAN'T DEVELOP THE
UNDERSTANDING OF THE MECHANISTIC
POINT OF VIEW.
IT'S GOING TO BE VERY DIFFICULT
TO HAVE NEW TARGETS FOR NEW
TREATMENT AND WE'RE TALKING
TREATABLE BUT IT'S VERY MUCH
CLINICAL AND/OR A BASE TO
LIMITED UNDERSTANDING WE HAVE
SOME TIME BY ACCIDENT AND THE T2
INFLAMMATORY PROCESS BEEN
DISCOVERED MORE LATELY AND THE
BIOLOGICAL ITL5 ARE NOT COMING
FROM A GOOD UNDERSTANDING OF
MECHANISM IN THE FIRST PLACE.
NOW WE'RE KIND OF GOING
BACKWARDS AND SAME IMMUNOLOGY
AND WHAT FARRAH WAS PROPOSING
THAT SEEMS TO ME VERY APPEALING.
HOW CAN WE THAT BETTER WITH WHAT
WE HAVE RIGHT NOW.
>> ANY ADDITIONAL COMMENTS?
I THINK THAT WAS A THOUGHTFUL
STATEMENT BY DR. BOURBEAU.
ONE THING THAT'S IMPORTANT AND
GOES BACK TO OUR DISCUSSIONS
FROM EARLIER TODAY, I THINK
THERE'S GREAT INTEREST FROM
INVESTIGATORS TO USE THE SAMPLE
GIVEN AND THE KEY IS TO TAKE THE
SAMPLES AND UTILIZE THEM TO NEW
TECHNOLOGIES OR AS AN EXAMPLE,
LUNG BIOPSIES THAT MAY BE STORED
FOR A CERTAINLY COHORT FOR
SPATIAL.
IT'S IMPORTANT AND THE MORE
BASIC SCIENTISTS MAY NOT KNOW
IT'S FROM A TERTIARY OR DISTAL
AIRWAY OR AREA WITH HIGH
EMPHYSEMA.
IT'S VERY IMPORTANT THAT
COMMUNICATION IS MADE, THE
HANDOFF IS MADE.
THE CLINICAL IMPLICATIONS ARE
MORE CLEAR.
TO SAY AGAIN IT'S A
COMMUNICATION THING.
I DON'T THINK WE ALL ANTICIPATE
WE'LL GET A WHOLE BANK OF
SAMPLES.
MAYBE THAT.
THAT'S WHAT A THOUGHT COULD BE
AS WELL.
>> I'M NOT SURE AND IT'S WHAT I
WAS TRYING TO SAY.
HOW CAN WE LINK THIS BETTER
BECAUSE THERE'S A GROUP DOING
QUITE WELL IN CHARACTERIZING IT
AND AT THE SAME TIME THREES
ANOTHER GROUP THAT HAS THE
EXPERTISE IS AND SOME TECHNOLOGY
THAT COULD BE USED HOW DO WE PUT
THAT TOGETHER.
I WAS LISTENING EARLIER ON.
WE HAVE AN OUR QUESTIONNAIRE AND
THE FORMATION HAD NOT BEENIZED
AT ALL.
IT WAS GOOD THERE WAS GOOD
INTENTION AND HYPOTHESIS WHEN WE
STARTED THE COHORT BUT HOW CAN
WE PUT THAT TO BETTER USE IN
LIGHT OF YOUR PRESENTATION AND
SOME OTHER MEASUREMENT AND CAN
WE SEE AND BE ABLE TO TEST AND
WE'LL BE ABLE TO SEE OVER 12
YEARS AND A CHANGE IN COPD.
THIS IS THE KIND OF THING THAT
JOINING THOSE TOGETHER WOULD
ALLOW US TO VALIDATE SOME OF
THESE HYPOTHESIS.
>> CAN I RESPOND TO THAT?
WE WAN GUT, LUNG, BLOOD SAMPLES
BUT IF IT'S NOT POSSIBLE YOU
WILL STILL BE ABLE TO DO
METABOLOMICS ON BLOOD SAMPLES
COLLECTED AND LINK THE
QUESTIONNAIRES AND BE ABLE TO
IDENTIFY FOR EXAMPLE HOW MUCH
FIBER PEOPLE WERE EATING AND
THEN MATCH THAT TO METABOLOMICS
AND DISEASE FEATURES.
IF YOU HAVE SAMPLES FOR
MICROBIOMES THERE'S MORE POWER
TO THE SAMPLES YOU'VE ALREADY
GOT.
YOU'RE RIGHT THERE'S A LOT OF
THINGS WE CAN DO WITH SAMPLES
ALREADY COLLECTED AND DATA
ALREADY COLLECTED.
THAT'S BEEN A MASSIVE EFFORT BY
PEOPLE.
>>
>> WE'VE BEEN TALKING AND HAVE
GOT SAMPLE AND BLOOD SAMPLES.
ANOTHER WAY TO ADD ON TO THAT IS
LEVERAGING OTHER COHORTS FOR
VALIDATION.
IF JEAN HAS METABOLOMICS AND
VALIDATE AND THERE WAS A
QUESTION A WHILE BACK I WANTED
TO BRING FORWARD AND IT HAS TO
DO INCREASING SAMPLE SIZE OF
HUNDREDS TO THOUSANDS OF
OBSERVATIONS AND WE HEAR ABOUT
THE LIMITATIONS OF SINGLE-CELL
DATA AT THE MOMENT AND NF3 OR 10
AND I WANT TO BRING THAT
QUESTION FORWARD AND HEAR THE
THOUGHTS FROM THE PANEL HERE.
IS IT POSSIBLE DO SINGLE CELL
OVER A POPULATION AND WOULD THAT
BE USEFUL WOULD WE UNCOVER OTHER
HETEROGENEITY AND MECHANISMS
BEYOND WHAT WE SEE FROM THE
HANDFULS OF LUNG TISSUE AND FEEL
FREE TO CHIME IN.
I KNOW YOU'VE DONE WORK IN THE
SPACE AS WELL.
>> IT'S POSSIBLE, HE SAYS.
NOT SURE IF IT'S USEFUL YET.
>> ADDS WE MOVE FORWARD THAT'S
GOING TO BE VALUABLE.
AND THE MORE WE GET THE MORE
POWERFUL THE DATA BECOMES.
>> IT'S IMPORTANT FOR PEOPLE TO
REALIZE THAT SAMPLING OF A WELL
PHENOTYPED COHORT DOESN'T HAVE
TO BE THE ENTIRE SAMPLE.
LIKE WITH FLOW CYTOMETRY WITHIN
MINUTES WE CAN TELL WHAT'S GOING
ON.
WE SAY FOR AN EXTRA MINUTE TO DO
100,000 BUT YOU DON'T NEED
100,000 OR 10,000 YOU CAN DO
WHAT IS COMMONLY DONE IS EXTREME
PHENOTYPING.
YOU TAKE A COHORT WITH AN
EXTREME PHENOTYPE AND TRY TO
LEVERAGE ONE AGAINST THE OTHER
AND DECIPHER WHAT IS ABOUT ONE
PHENOTYPE STARTING AT AGE 40 AND
START GOING DOWN THE SLIPPERY
PATH OF DEVELOPING LATE-STAGE
EMPHYSEMA VERSUS SOMEONE WHO
BARELY GETS EMPHYSEMA AND LIVES
FOR 100 YEARS AND THERE'S THINGS
THAT CAN BE DONE AND DOESN'T
HAVE TO BE DIDN'T ON EVERY
SINGLE ONE.
IF YOU HAVE A GENEROUS COHORT
YOU CAN IDENTIFY THE EXTREME AND
STUDY THOSE.
>> I'D LIKE TO ADVOCATE FOR THE
NUMBER OF SINGLE-CELL STUDIES
AND YOU CAN LOOK AT THE OMIC
DETERMINATES OF SING OF SINGLE
CELL PARAMETERS YOU CONDITAN'T
FROM CELLS IF A FEW PEOPLE.
IF YOU CAN DO A CELL-BASED MOUSE
STUDY IN THE LAB WOULD HAVE
HUNDREDS OF OBSERVATIONS CHANGE
YOUR APPROACH?
THEY WERE LOOKING AT
REPRODUCIBILITY OF STUDIES AND
HOW MUCH IT IMPROVED OF THE
SAMPLE SIZE AND YOU HAD A LOT OF
FALSE POSITIVES AND YOU HAD A
POINT WHERE YOU PROBABLY AREN'T
GETTING MORE.
IS THERE SOMETHING FROM THE
HETEROGENEITY OF THE STUDIES YOU
CAN LEARN FROM?
>> AN ISSUE IS THE MICE ARE
INBRED MICE AND SUM LAR AND ONE
OF THE ISSUES HAS ALWAYS BEEN
HOW REPRESENTATIVE ARE THE
ANIMAL MODELS BUT MICE
THEMSELVES AND THERE'S BEEN
INTEREST IN MODELS OF OUT BRED
MICE AND SEE IF YOU GET A MORE
REPRESENTATIVE PHENOTYPE FOR THE
MODEL WITH AN OUTBRED MICE THAN
VARIATION YOU SEE IN HUMANS.
I'M NOT IN EXPERT IN THAT SPACE.
I JUST KNOW THE MODELS
THEMSELVES AND REPEATING A
THOUSAND MEASUREMENTS ON A MODEL
THAT DOESN'T REALLY CAPITULATE
THE DISEASE YOU THINK IS
IMPORTANT MAY NOT BE SUPER
HELPFUL BUT IF IT'S CAPITULATING
A PART OF A DISEASE YOU THINK IS
VERY IMPORTANT THEN IT MAY BE
HELPFUL TO HAVE MORE
OBSERVATION.
I'LL LEAVE IT AT THAT AS A BROAD
STATEMENT BUT WOULD LOVE OTHER
PEOPLE TO COMMENT.
>> I THINK ON FOCUSSING
HETEROGENEITY IS IMPORTANT FOR
COPD AND ANY KIND OF DISEASE.
AND WHAT IS COMMON FOR ALL
PATIENTS IN COPD AND BY
COMPARING FEWER SAMPLES FROM
PATIENTS TO THOSE WHO DON'T HAVE
DISEASE, WHAT ARE THOSE
UNIVERSAL FEATURES WE CAN
CAPTURE?
I THINK YOU GUIDE THE PRINCIPLE
FEATURES WHICH CAN BE DETECTED
AND THEN MAYBE USED AS A BASIS
FOR NEXT-LEVEL STUDIES FOCUSSING
ON HETEROGENEITY.
DO YOU HEAR ME?
>> YES.
>> AND CREATING DIFFERENT TYPES
OF SAMPLES FROM TRE SAME PATIENT
IN WHICH WE DON'T NEED TOO MANY
DIFFERENT SAMPLES BUT AND WHAT
WE SEE IN TERMS OF PHYSIOLOGY OR
BLOOD OR BLOOD FUNCTION OR OTHER
PARAMETERS.
IT MAY BE IMPORTANT IN DEALING
WITH HETEROGENEITY AND THERE'S
ONE OR TWO SAMPLES WHICH CAN
GIVE INTERESTING DATA BUT DON'T
GO TO THE GROUP WHICH CAN GIVE
STATISTICS AND PHENOTYPES YOU
MAY NOT ABLE TO CAPTURE
STATISTICALLY.
>> I AGREE.
I CONCUR AND AGREE WITH ED'S
COMMENT AND WHEN IS A CONFIDENCE
LEVEL GOOD ENOUGH TO PURSUE A
CERTAIN TARGET OR CERTAIN
MECHANISM.
THAT GOES FOR ANY SAMPLES, IN
MICE, IN PRIMARY CELLS FROM
DIFFERENT DONORS, ETCETERA.
AND I THINK I'VE BEEN EXCITED TO
LEARN ABOUT NEW METHODOLOGY TO
SCALE UP REDUCE COST AND SOME
EXPERIMENTS WE DO AND TAG EACH
CELL AND SAMPLE.
USING THE TECHNOLOGY FOR SINGLE
CELL RNA SEQ FOR SCALING UP
HOMOGENOUS POPULATIONS AN
REPRODUCIBILITY AND WHAT'S
ADAPTIVE AND WHAT MAY NOT BE
ADAPTIVE.
I WILL LOOK AT THE REFERENCE I'M
TALKING ABOUT AND PUT IT IN THE
CHAT SHORTLY.
>> WE'RE COMING UP TO THE END OF
THE HOUR.
ANY FINAL QUESTIONS OR POINTS
ANY OF THE SPEAKERS WOULD LIKE
TO MAKE IN TERM OF ANYTHING YOU
WANT TO ADD ON TO TO FROM THIS
VERY ROBUST DISCUSSION.
IT'S BEEN WONDERFUL.
AND I THINK MORE CREATIVELY ON
MORE THOUGHTFUL STUDY SECTIONS
WHICH INCLUDE PEOPLE INTERESTED
IN HUMANS AND INTERESTED IN
DISEASE NOT ONLY MOUSE BUT
BIOLOGISTS INTERESTED IN
UNDERSTANDING DISEASE IN HUMAN
MODELS WHICH MAY NOT BE ONE
HYPOTHESIS BUT A BIGGER SCOPE
APPROACH AND PRODUCING HIGH BOTH
SIS FOR THE FIELD.
-- HYPOTHESIS FOR THE FIELD.
>> SOMETHING THAT COULD CAPTURE
A LOT OF WHAT WE'VE BEEN TALKING
ABOUT IS INTEGRATING PEOPLE WITH
ANIMAL MODELS.
WE KNOW WHAT THE DISEASE
FEATURES ARE IN ANIMAL MODELS
AND MATCH THE OMICS DATA FROM
THE ANIMAL MODELS TO HUMAN
DISEASE THAT WILL SHOWS THE
DISEASE FEATURES AND THE
PATHWAYS THE MOUSE MODELS
REPRESENT IN HUMAN DISEASE AND
UNDERSTAND MECHANISMS OF
INDIVIDUAL DISEASE FEATURES AND
IDENTIFY TARGETS FOR THE DISEASE
FEATURE CONTRIBUTING TO THE
ENDOTYPING DISCUSSION WE HAD AS
WELL.
>> I WANT TO ECHO SOMETHING ON
THE TALK WHICH IS ONLY WHETHER
WE TALKED ABOUT AND THE ABILITY
TO GET ACCESS TO THE INDIVIDUAL
MODELS IN MANY CASES EXPOSURE
SYSTEMS AND TISSUES FROM THE
ANIMALS OR MODELS WOULD BE
IMPORTANT THROUGH INVESTIGATORS
OR COHORTS OR NIH, THROUGH I
DON'T KNOW HOW INVESTIGATORS MAY
GET ACCESS TO UNIQUE MODELS AND
TISSUES.
AND I WANT TO CAPTURE THE
ESSENCE OF WHAT YOUR SAYING.
>> ABSOLUTELY A STREAMLINE WAY
TO COLLABORATE WITH THESE
TISSUES AND PHIL YOU'RE VERY
GENEROUS BUT THERE'S DIFFERENT
EXPOSURE SYSTEMS, DIFFERENT
MODELS AND THAT COULD BE ONE WAY
TO INCREASE AS MENTIONED BEFORE
WITHOUT EACH INDIVIDUAL PERSON
SITTING THERE AND TRYING TO
EXPOSE 350 MICE.
>> YVONNE, DO YOU HAVE ANYTHING
ELSE YOU'D LIKE TO ADD?
>> I DON'T.
I THINK IT'S BEEN A GREAT 57
MINUTES OF DISCUSSION.
MEILAN, ANY OTHER THOUGHTS?
>> A MASTERFUL JOB OF TRYING TO
MANAGE OVER 100 VERY ACTIVE
PARTICIPANTS ON ZOOM AND CHAT.
I'VE BEEN TRYING TO KEEP UP WITH
BOTH.
QUITE IMPRESSIVE YOU'RE DOING A
BETTER JOB THAN I AM.
I WANT TO THANK EVERYONE.
I HAVEN'T HAD AN OPPORTUNITY TO
PARTICIPATE IN A WORKSHOP THIS
LARGE OR IN SCOPE BEFORE.
IT'S KIND OF FUN FOR ME AND I
HAVE A CHANCE TO INTERACT WITH
PEOPLE FROM ACROSS THE WORLD IS
ALSO A REAL TREAT.
ED, DID YOU WANT TO SAY ANYTHING
OR NIH COLLEAGUES?
>> I WOULD ECHO WHAT YOU SAY AND
SAY I'M PLEASED WITH THE WAY THE
FIRST DAY'S GONE AND PUCTUALITY
OF THE SPEAKERS AND LEAVING
SUFFICIENT TIME TO HAVE GREAT
DISCUSSIONS FOR BOTH SESSIONS.
HOPEFULLY WE'LL REPEAT THIS
TOMORROW.
>> I THINK TODAY'S A GREAT DAY.
THANK EVERYONE FOR THE
PARTICIPATION.
WE LOOK FORWARD TO ANOTHER
EXCELLENT DAY.
EVERYBODY HAVE A GREAT EVENING.
>> WE'LL LET PHIL GO TO GET SOME
SLEEP.
>> THANK YOU.
>> SEE YOU TOMORROW.