>> TO THOSE JOINING BY VIDEOCAST
SEND YOUR QUESTIONS USING THE
SEND LIVE FEEDBACK AND STATE THE
SPEAKER AND/OR TOPIC TO WHOM
YOU'RE DIRECTING YOUR QUESTIONS.
SPEAKERS, KEEP YOUR QUESTIONS TO
THE ALLOTTED TIME FRAME LEAVING
TIME FOR QUESTIONS AFTER YOUR
TALK.
YOU'LL RECEIVE AN AUDIBLE
TWO-MINUTE WARNING WHERE YOU
SHOULD WORK TO WRAP THINGS UP.
THERE WILL BE A PANELLED Q&A
DISCUSSION AT THE END OF EACH
SESSION.
ANYONE CAN SUBMIT QUESTIONS AT
ANY TIME AND THE MODERATOR WILL
ASK ON YOUR BEHALF DURING THE
DISCUSSION.
IF YOU REQUIRE CLOSED
CAPTIONING, PLEASE CLICK ON THE
CAPTIONS BUTTON FOUND ON THE
BOTTOM OF YOUR SCREEN.
IF YOU EXPERIENCE TECHNICAL
DIFFICULTIES DURING THE WORKSHOP
PLEASE CONTACT MYSELF OR
BRITTANY BELAFONA.
THE WORKSHOP IS OPEN TO THE
PUBLIC AND AVAILABLE FOR VIEWING
IN THE COMING WEEKS AND OPEN TO
THE PUBLIC.
I'D LIKE TO INTRODUCE
DR. MARISHKA BROWN FOR THE
OPENING REMARKS.
DR. BROWN IS THE DIRECTOR OF
NATIONAL CENTER OF SLEEP
DISORDERS RESEARCH TO DISCOVER
IN HEALTH AND HER PARTNERSHIP
BUILDING HAS HELPED SUSTAIN A
ROBUST RESEARCH NETWORK BRINGING
THE BENEFITS OF NIHs RESEARCH
AND THE MEDICINE OF PUBLIC
HEALTH.
NOW, DR. BROWN, THE FLOOR IS
YOURS.
>> THANK YOU, ALFONSO.
CERTAINLY ANYTHING ON MY
BACKGROUND IS AVAILABLE ONLINE.
WE WELCOME EVERYONE TO THE
WORKSHOP.
WE'RE EXCITED.
THIS IS THE NHLBI SPONSORED
WORKSHOP ENTITLED THE
HETEROGENEITY AND SEX AND GENDER
DIFFERENT DIFFERENCES IN SLEEP
APNEA AND IMPLEMENTATION AND IN
THE AFTERNOON AND THANK YOU FOR
JOINING US THIS MORNING, THIS
WORKSHOP IS GOING TO EXAMINE THE
VARIABILITY IN SLEEP APNEA
ETIOLOGY AND LOOK AT SEX, GENDER
AND SLEEP DISPARITIES.
FOR INDIVIDUAL DIFFERENCES AND
PATHOBIOLOGY AND RESPONSE TO
TREATMENT IT'S OUR STATED
PRIORITY IN THE NIH SLEEP
RESEARCH PLAN THE NHLBI
STRATEGIC VISION AS WELL AS THE
NHLBI WIDE RESEARCH PLANS.
THE HETEROGENEITY OF OSA AND
IMPACT OF CHRONIC CONDITION
SUGGEST THE PERSONALIZED
APPROACHES ARE NEEDED FOR
SUCCESSFUL DIAGNOSIS AND
IMPLEMENTATION AND TREATMENT.
TO THAT END THE GOALS ARE TO
DELINEATE DIAGNOSIS, TREATMENT,
IMPLEMENTATION AND HIGHLIGHTING
RESEARCH FOCUSSED ON SEX AND
GENDER DIFFERENCES TO DISCUSS
PERSONALIZED CARE AND PRECISION
MEDICINE BASED APPROACHES IN OSA
AND TO ZBUS HOW THE
IDENTIFICATION OF CURRENT
RESEARCH METRICS CAN BE
TRANSLATED TO CLINICAL PRACTICE
ACROSS THE LIFE SPAN AND AMONG
POPULATIONS DISPROPORTIONATELY
IMPACTED.
NEXT I'D LIKE TO INTRODUCE OUR
CO-CHAIRS.
FIRST STARTING WITH THE DIRECTOR
OF THE U CHICAGO SLEEP PROGRAM.
HER WORK HIGHLIGHT THE CRITICAL
ROLE OF SLEEP AND ENERGY
METABOLISM AND THE IMPACT OF
SLEEP AND SLEEP APNEA AND OUR
CURRENT CARE OF THE NIH SLEEP
RESEARCH ADVISORY BOARD AND OUR
NEXT MEETING IS GOING TO BE ON
THURSDAY DECEMBER 5 STARTING AT
11:00 A.M. AND PLACE ON OUR
SLEEP RFA LIST SERVE FOR THOSE
WHO ARE NOT SUB SCRIBED, PLEASE
DO BECAUSE WE POST OUR
ACTIVITIES AND EVENTS AS WELL AS
FUNDING OPPORTUNITIES ON THE
LIST SERVE.
NEXT UP IS BOB OWENS PROFESSOR
OF MEDICINE AT THE UNIVERSITY OF
SAN DIEGO AND BOARD CERTIFIED
CRITICAL CARE AND SLEEP MEDICINE
PHYSICIAN.
HIS RESEARCH HAS FOCUSSED ON OSA
PATHOGENESIS INCLUDING THE
PHYSIOLOGY OF THE UPPER AIRWAY
AND LUNG VOLUMES AND EXPRESSION
OF OSA.
HE SERVES AS THE CHAIR OF SLEEP
AND RESPIRATORY ASSEMBLY OF THE
AMERICAN THORACIC SOCIETY.
OUR LAST CO-CHAIR AND HE IS AN
ASSISTANT PREVENTION WITH THE
DEPARTMENT OF MEDICINE AND A.I.
AND HUMAN HEALTH AND SERVES AS
DIRECTOR OF THE SLEEP AND
CIRCADIAN ANALYSIS GROUP AT
MOUNT SINAI AND MATHEMATICIAN
AND HIS RESEARCH INTERESTS ARE
IN THE DEVELOPMENT OF MARKERS
RELATED TO SLEEP DISORDERS AND
SHORT AND LONG-TERM
CONSEQUENCES.
MORE RECENTLY, HIS WORK IS AIMED
AT DEVELOPING METRICS OF SLEEP
APNEA SEVERITY BEYOND THE INDEX
USING PHYSIOLOGY GUIDED
ARTIFICIAL INTELLIGENCE AND
MACHINE LEARNING METHODS.
WITH THAT I'M GOING TO TURN IT
BACK OVER TO ALFONSO TO OPEN UP
OUR FIRST SESSION.
>> ALL RIGHT.
THANK YOU DR. BROWN FOR THE
OPENING REMARKS.
TO KICK THINGS OFF WE'LL START
WITH THE KEY NOTE SESSION
INCLUDING THREE SPEAKERS.
OUR FIRST SPEAKER IS DR. MONICA
MALLAMPALLI AND HER PRESENTATION
IS EXCITED EVERY BREATH COUNTS
ADVOCATING FOR PERSONALIZED
APPROACHES TO SLEEP APNEA CARE.
WHEN YOU'RE READY THE MIKE IS
YOURS.
>> THANK YOU, ALFONSO.
THANK YOU, I WAS DIAGNOSED 10
YEARS AGO AND ALSO A TRAINED
BASIC RESEARCHER.
LEFT RESEARCH TO GO INTO POLICY
ADVOCACY AND IN THE AREA OF
WOMEN'S HEALTH ABOUT 15 YEARS
NOW.
I'M THRILLED TO BE HERE AND TALK
ABOUT MY PERSPECTIVES COMING IN
AS A PATIENT AND SCIENTIST AS
WELL AS SOMEBODY WHO AS BEEN IN
THE POLICY WORLD.
I HAVE NO CONFLICTS OF INTEREST.
AS FOR THE DISCLOSURE, I WANT TO
MENTION WE HAVE A MECHANISM TO
WORK WITH OUR INDUSTRY PARTNERS
AND APPOINTED AS A PUBLIC MEMBER
TO THE HHS PAIN COORDINATING
COMMITTEE.
AND WE'RE A NONPROFIT 501C3
ORGANIZATION AND WE ALWAYS KEEP
THE PATIENT IN MIND AND IT'S
100% VOLUNTEER DRIVEN.
FOR MORE ON OUR PROGRAMS AND
EVERYTHING WE DO VISIT OUR
WEBSITE AT APNEA PARTNERS.org.
WE PROMOTE FOR SCREENING,
MANAGEMENT AND OPTIMAL HEALTH
FOR THOSE WHO SUFFER FROM SLEEP
APNEA.
WE BELIEVE THERE'S GAPS WITH
SCREENING, DIAGNOSIS, TREATMENT
AND MANAGEMENT AND TAKE THE
EQUITY LENS TO EVERYTHING WE DO
AND THE SEX AND GENDER LENS AND
SPEAK TO A BROADER AUDIENCE
BECAUSE THERE'S STILL PEOPLE YET
TO BE DIAGNOSED AND PEOPLE
DIAGNOSED ARE YET TO GET TREAT
ED -- TREATED AND SOME HAVE
DIFFICULTY GETTING TREATMENT.
ONE SIZE DOES NOT FIT ALL.
WE CANNOT TAKE THAT APPROACH AND
THIS IS WHAT WE NEED TO THINK
FOR A WHILE AND THERE'S A
DIFFERENCE BETWEEN EQUALITY
VERSUS EQUITY.
ON THE TOP OF THE DIAGRAM YOU
CAN SEE WHEN YOU HAVE TREATMENT
YOU ASSUME WORKS FOR EVERYBODY,
THAT'S WHAT LEADS TO
DISPARITIES.
AND THERE'S VARIABLES THAT ARE
IMPORTANT TO KEEP IN MIND, SEX,
GENDER, ABLE AND RACE.
UNLIKE OTHER VARIABLES, SEX IS
BINARY AND THIS IS IMPORTANT
WHEN YOU THINK OF PERSONIZED OR
INDIVIDUALIZED APPROACH TO
TREATMENT.
AGAIN, I WANT TO REITERATE WHAT
SOME KNOW AND SOME DON'T BUT SEX
AND GENDER ARE NOT THE SAME.
SEX IS A BIOLOGICAL VARIABLE AT
THE CHROMOSOMAL COMPLEMENT AND
ACCORDING TO SEXUAL ORGANS AND
WHEN WE TALK ABOUT THE SEX
DIFFERENCES THE BIOLOGICAL AND
GENDER IS SOCIAL AND CULTURAL
INFLUENCES IN BIOLOGICAL FACTORS
AND YOU'LL SEE WHEN IT COMES TO
METABOLISM AND RENAL FUNCTION
AND PHARMACO DYNAMICS AND
EFFICACY AND SAFETY.
ESSENTIALLY FROM HEAD TO TOE AS
DEPICTED ON THE RIGHT BY OFFICE
OF RESEARCH ON WOMEN'S HEALTH.
30 YEARS AGO WOMEN WERE NOT
INCLUDED IN BIOMEDICAL RESEARCH.
ESSENTIALLY SPECIFIC BIOLOGY AND
ANATOMY AND PHYSIOLOGY WAS
IGNORED.
THEREFORE TREATMENTS AROUND DID
NOT WORK WELL FOR WOMEN AND THIS
CARTOON DEPICTS IT WELL.
WE HAVE STUDIES ON FRUIT FLIES,
MICE, HAMSTERS, FROGS, MONKEYS
MEN WITH THIS CONDITION AND
WOMEN AS MEDICAL SUBJECTS NEVER
OCCURRED TO ANYBODY AND WE STILL
HAVE A LONG WAY TO GO IN
ENSURING WE HAVE EQUITABLE
DIAGNOSIS AND TREATMENT.
THIS IS THE NATIONAL ACADEMY OF
MEDICINE.
EVERY CELL AS A SEX.
MEDICAL PRODUCTS VARY FROM MEN
TO WOMEN THE FIRST STEP TO
INDIVIDUALIZED TREATMENT.
UNDERSTANDING THE SEX
DIFFERENCES IN DISEASE
PREVENTION, DIAGNOSIS AND
TREATMENT WILL TRANSFORM DISEASE
RESEARCH TO IMPROVE CARE FOR
BOTH.
AGAIN, I SAY BOTH WOMEN AND MEN
SO WE'RE NOT EXCLUDING EITHER OF
THOSE SEXES.
SO WHAT HAPPENS WHEN YOU IGNORE
SEX AND GENDER DIFFERENCES?
IT LEADS TO HEALTH DISPARITIES.
THERE'S AN OVERUSE OF MALE
ANIMAL MODELS AND CAN IGNORE
SPECIFIC RESEARCH.
IT'S HARD TO DEFINE MECHANISMS
IN HEALTH AND DISEASE.
IT'S DIFFICULT TO REPORT
EFFECTIVENESS OF AN INTERVENTION
FOR WOMEN AND WOMEN HAVE MORE
ADVERSE EVENTS TO MEDICATIONS
BUT UNREPORTED AND WOMEN HAVE
TROUBLE ACCESSING HEALTH CARE
AND FACE GENDER BIAS.
THIS IS A WORKSHOP FROM 2012 ON
SCIENTIFIC REPORTING OF
RESEARCH.
I'M NOT GOING TO GET IN THE
PRECLINICAL SIDE EXCEPT BY
SAYING IT'S ESSENTIAL TO INCLUDE
THE SEX OF ANIMALS OR CELLS YOUR
STUDYING AND REPORTING THAT IN
THE LITERATURE IS IMPORTANT.
I DO WANT TO POINT OUT A COUPLE
THINGS WHEN IT COMES TO CLINICAL
STUDY DESIGN.
THE STUDY SHOULD BE DESIGN FOR
STRATIFIED RANDOMIZATION BY SEX
AND ALSO IT TELL US THAT STUDIES
SHOULD BE DESIGN WITH ADEQUATE
STATISTICAL POWER WITH SUBGROUP
DESIGN AND BEFORE YOU START YOUR
STUDY AND ONE REASON FOR
REPORTING SEX SPECIFIC RESULTS
SHOULD INCLUDE A REASONABLE
LIKELIHOOD SEX-BASED
ASSOCIATIONS MUST EXIST.
IT'S CRITICAL AND IMPORTANT WHEN
RESEARCHERS START TO DESIGN
THEIR EXPERIMENTS OR STUDIES.
IT'S EQUALLY IMPORTANT HOW YOU
REPORT YOUR RESULTS INCLUDING IN
THE TITLE ABSTRACT AND IN THE
RESEARCH PAPER.
I'M NOT GOING TO GO INTO MORE
DETAILS BUT I'LL ENCOURAGE
EVERYONE TO LOOK AT THIS REPORT.
YOU KNOW 2014 THERE WAS A SEX AS
VARIABLE POLICY AND NOW MAKE A
CASE WHY YOU USE ONE SEX AND NOT
BOTH.
AND THERE'S REAL WORLD POLICY
IMPLICATIONS FOR NOT STUDYING
SEX DIFFERENCES.
THE SLEEP COMMUNITY IS AWARE OF
THE OPEN-END STORY WHERE FDA
RECOMMENDED LOWER DOSE OF AMBIEN
FOR WOMEN AND SAW WOMEN WERE
METABOLIZING THE SAME DOSE
SLOWER THAN WOMEN AND FDA 2014
CAME UP WITH THE FIRST SEX
SPECIFIC GUIDELINES.
IT'S IMPORTANT TO NOTE THERE
WERE A LOT OF PUBLICATIONS BY
DR. TOMORR ROWE AND IT'S IMPORT
TO KNOW WHERE THE LITERATURE IS
AND WHAT INFORMATION WE HAVE
WHILE DESIGNING TREATMENTS.
ALL THIS IS HAPPENING DURING THE
OPEN ENDED STORY.
I WAS AT THE SOCIETY FOR WOMEN'S
HEALTH RESEARCH AND LAUNCH THE
SLEEP AND SEX DIFFERENCES
PROGRAM BECAUSE WE REALIZED
THERE WAS A NEED TO HAVE THE
CONVERSATIONS AROUND SEX
DIFFERENCES AND SLEEP.
WE DID A ROUNDTABLE DISCUSSION
IN 2013 AND RELEASED A REPORT
EXPLORING SEX AND DIFFERENCES OF
SLEEP HEALTH.
THIS REPORT WILL RECEIVE
NATIONAL ATTENTION AND ANOTHER
REPORT ON WOMEN AND SLEEP AND
FIND ALL THIS AT SWHR.org.
SO COMING TO SLEEP APNEA,
THERE'S A SEX GAP THAT CURRENTLY
EXISTS AND DISPARITIES WHEN IT
COMES TO DIAGNOSIS AND
TREATMENT.
PRACTICE GAPS AND SLEEP APNEA
CARE TO TREATMENT EXIST AND ARE
IMPACTING WOMEN.
IT PRESENTS DIFFERENT IN FEMALES
COMPARED TO THEIR UNIQUE BIOLOGY
COMPARED TO MALES.
WOMEN REPORT SYMPTOMS
DIFFERENTLY SUBJECTING THE NEED
FOR SEX SPECIFIC SCREENING
TOOLS.
SEX DIFFERENCES AND ANATOMY
CONTRIBUTE TO HIGHER ASSOCIATED
SLEEP APNEA IN FEMALES AND
CHALLENGES IN QUALITY AND
EQUITABLE CARE IN WOMEN.
NOT ENOUGH CARE IS FOCUSSED ON
FEMALE PATIENTS DUE TO THE
EXISTING MYTHS AND THESE ARE THE
MYTHS WE NEED TO OVERCOME.
THIS GIVES YOU A REAL WORLD
EVIDENCE OF WHAT WE'RE HEARING
DIRECTLY FROM PEOPLE WHO WITH
LIVED EXPERIENCES AND STRUGGLING
WITH OR LIVING WITH OSA.
SOME INDICATE GENDER
DIFFERENCES.
WOMEN REPORT HIGHER RATES OF OSA
SYMPTOMS THAN MEN AND WOMEN WERE
EXPERIENCING FATIGUE COMPARED TO
70% OF WOMEN.
THE WORK IN PRODUCTIVITY WAS
HINDERED AND MORE IMPACTFUL IN
WOMEN WITH 92% OF WOMEN SAID IT
IMPACTED THEIR ACTIVITIES AND
ALSO THERE WAS AN IMPACT ON THE
RELATIONSHIPS WHERE WOMEN
EXPRESSING THEY WERE MORE
EFFECTED BY SOME OF THESE OR NOT
BEING ABLE TO FULLY PRESENT AND
REPORTED MORE EXHAUSTION
INTERFERING WITH THEIR
RELATIONSHIPS.
I ALSO WANT TO HIGHLIGHT A
COUPLE OF THESE ABSTRACTS
PRESENTED IN 2022 AND THERE ARE
A FEW OTHERS THAT I DIDN'T SHARE
HERE TODAY BUT WANTED TO AGAIN
EMPHASIZE THERE'S DATA COMING
OUT OF SOME OF THESE COMPANIES
ALSO STUDIES AND SHOWING THERE
ARE GENDER DIFFERENCES.
FOR EXAMPLE, WOMEN WITH OSA HAVE
A HIGHER PREVALENCE OF THE
CONDITIONS, MOOD DISORDERS AND
INSOMNIA DIFFERENT THAN MEN AND
IN THE OTHER ABSTRACT THERE WERE
GENDER DIFFERENCES WITH COMORBID
CONDITIONS.
HOW DO WE THEN GO ABOUT CLOSING
THE GAP IN SLEEP APNEA?
WE WANTED TO USE THE HEALTH
EQUITY LENS IN CLINICAL PRACTICE
AND DISMANTLED THE CURRENT
SYSTEMS THAT CONTINUE TO
PERPETUATE THE EXISTING
INEQUITIES.
HIGHLIGHT THE CONSEQUENCES OF
FAILING TO ADDRESS SOCIAL ISSUES
AND MAKE SURE THE BASELINE OF
NEEDS ARE MET AND TRAIN
CLINICIANS ON WOMEN-SPECIFIC
HEALTH ISSUES SO WE CAN
ELIMINATE THE BIAS.
CONTINUE TO EDUCATE AND EMPOWER
POPULATIONS TO ENABLE THEM TO
TAKE AN ACTIVE ROLE IN THEIR
HEALTH.
TO SOME EXTENT ALSO FALLS ON
ADVOCACY ORGANIZATIONS SUCH AS
OURS.
WE'LL CONTINUE TO DO ADVOCACY
AND ENSURE WE CONTINUE TO
EDUCATE PATIENTS ON THESE
ISSUES.
WE'RE DOING OUR PART ALREADY AS
YOU KNOW.
WE HAVE BEEN CREATING
WOMEN-SPECIFIC RESOURCES AND
WE'LL CONTINUE TO DO THAT.
ALSO ADD SOME PERHAPS MEN
SPECIFIC RESOURCES AS WELL SINCE
WE KNOW THERE'S GENDER
DIFFERENCES THAT EXIST.
I WANT TO LEAVE YOU WITH A
COUPLE SLIDES.
I HOPE YOU DO YOUR PART AS WE DO
OUR PART BUT I WANTED TO SORT OF
SHARE THIS FROM A PAPER FROM
2016 AND ONLY 76% OF THE CELLS
ARE UNSPECIFIED.
WE DON'T KNOW THE SELF.
WE KNOW 80% OF ANIMAL STUDIES
USE MALE MICE.
67% OF HUMAN TRIALS INCLUDE ONLY
MALES.
ALL THE NUMBERS ARE CHANGING.
I THINK WE'RE EDGING CLOSER TO
50%.
51% OF THE GLOBAL FEEL
POPULATION IS FEMALES AND 80% OF
HEALTH CARE CONSUMERS ARE WOMEN
WHEN IT COMES TO CLINICAL CARE.
SO I ENCOURAGE EVERYONE TO
CONSIDER THE BIOLOGICAL
POSSIBILITY WHICH AGAIN I
MENTIONED BEFORE TO ENSURE THERE
IS AN ASSOCIATION THAT COULD BE
BIOLOGICALLY BELIEVABLE IF
YOU'RE A BASIC RESEARCHER DOING
CELL BASED STUDY OR HUMAN
RESEARCH BUT TO KEEP THAT IN
MIND.
I WANT TO ALSO EMPHASIZE THE
FOUR Cs THE OFFICE OF RESEARCH
ON WOMEN'S HEALTH.
DESIGN YOUR STUDIES TAKING SEX
INTO ACCOUNT AND TABULATE THE
DATA BY SEX AND ANALYZE BY SEX
AND FINALLY REPORT AND PUBLISH
SEX-BASED DATA.
I LEAVE YOU WITH THE ONE EXAMPLE
BY FROM THE PAIN RESEARCH WHICH
CLEARLY SHOWS THE PAPER AND
REPORTING PAIN DIFFERENCES AND
SHOWS THE SEX DIFFERENCES IN THE
TITLE, THE ABSTRACT IS CLEAR
INDICATING WHAT'S BEING STUDIED.
THE METHODS ALSO INDICATES WHAT
IS STUDIED AND THE RESULTS WERE
REPORTED DIFFERENTLY FOR FEMALES
AND MALES AND AGAIN IF YOU HAVE
NOT DONE THAT, YOU WOULD NOT
HAVE SEEN ANY DIFFERENCE HERE
AND THANK YOU OPEN TO SOCIAL
MEDIA SO ALSO VISIT OUR WEBSITE.
HAPPY IT TAKE ANY QUESTIONS.
>> THANK YOU, NEXT IS
DR. PUNJABI IN HETEROGENEITY IN
PERSONAL I'VEED CARE IN OSA.
>> I'VE BEEN GIVEN CHARGE TO
FOLLOW IN DR. MALLAMPALLI'S
STEPS AND LOOK AT THE RESEARCH
GAPS AND HOW TO ADVANCE THE
FIELD AND MOST HAVE BEEN
INVOLVED IN GENERATING THE DATA
I'LL PRESENT AND I'LL ADDRESS
CHALLENGES AND THEY'RE FAR ALONG
WITH THE ISSUE OF CARE AND
HYPERTENSION.
WITH EVERY POINT WE'LL DRAW HOW
HYPERTENSION IS INVOLVED IN THE
CHALLENGES WE HAVE IN THE FIELD
OF SLEEP APNEA.
THERE'S VARIABILITY IN SYMPTOMS
AND TREATMENT RESPONSE WITH
SLEEP APNEA AND THERE'S FACTORS,
DEMOGRAPHIC, PHYSIOLOGIC AND
ENVIRONMENTAL AND I'LL LET OTHER
SPEAKERS GET INTO SPECIFIC
DIFFERENCES OR SEX DIFFERENCES
AND WHY ARE SOME FACTORS ISSUES
HERE AND WE'RE IN CONSIDERATION
OF BIOLOGICAL AGE AND AGE IS
IMPORTANT FOR HETEROGENEITY, THE
RACIAL AND ETHNIC DIFFERENCES
AND UNDERLYING GENETIC
DISPOSITION AND DATA ON
GEOGRAPHIC LOCATIONS AND OSA CAN
INFLUENCE THE RISK AND
EXPRESSION OF DISEASE ITSELF.
I THINK UNDERSTANDING ALL OF
THIS AND THE MOTIVATION FOR THIS
IS OF COURSE TO DETERMINE HOW WE
ADDRESS DISPARITIES AND OPTIMIZE
TREATMENT WITH THE GOAL OF
INDIVIDUALIZING CARE.
MY DISCLOSURES ARE NONE.
THIS FIGURE FROM A PAPER IN THE
LANCET SORT OF 10 YEARS OKAY
SUMMARIZED THINGS I WANT TO
EMPHASIZE IN THE BRIEF TIME
HERE.
IT ALL THE KEY FEATURES.
IF YOU THINK OF THE PATHOGENIC
MECHANISMS THERE'S A LOT KNOWN
ABOUT MUSCLE FUNCTION AND
AROUGHING -- AROUSAL FUNCTIONS
AND THERE'S UPSTREAM EVENTS THAT
LEAD TO THESE MECHANISMS FROM
THE STANDPOINT OF THE
MANIFESTATION AND THEN THERE'S
WHAT TO DO ABOUT THEM.
I THINK WHAT I WANT TO FOCUS ON
IS THE FIRST TWO PANELS IS HOW
SOME RISK FACTORS CONTRIBUTE TO
THE HETEROGENEITY
MECHANISTICALLY AND TALK ABOUT
PHYSIOLOGY AND WHAT WE KNOW
ABOUT HOW HETEROGENEITY AND WHAT
ABOUT OBESITY AND SEX AND AGE IS
CONTRIBUTING TO THIS THAT WE'RE
OBSERVING.
SO SEX DIFFERENCES IS A NATURAL
TRANSITION.
MEN ARE MORE LIKELY TO HAVE
SLEEP APNEA BUT WOMEN GOING
THROUGH MENOPAUSE THE RISK IS
HIGHER.
THERE'S DISTRIBUTION AND AFLAT
-- ANATOMY AND HORMONAL AFFECTS
AND IT CONTRIBUTES TO THE
DISPARITY AND CASE
IDENTIFICATION OF THE DISORDER.
AND THIS IS A NICE GRAPHIC THAT
SUMMARIZES WHAT I SAID.
THERE'S AN UNDERDIAGNOSED WELL
ESTABLISHED WOMEN ARE LIKELY
UNDER OR MISS DIAGNO
THERE'S DIFFERENCES IN
PREVALENCE AND IN PRESENTATIONS,
INSOMNIA, A LITTLE MORE
DEPRESSION, FATIGUE, HEADACHES
ONE IS MORE BIOLOGICAL THAN THE
OTHER.
WHEN YOU LOOK AT THE PHYSIOLOGIC
EXPRESSION OF THE DISEASE
THERE'S DIFFERENCES.
STATE DEPENDENT DIFFERENCES WHEN
IT COMES TO REM ANDNON-REM AND
COMORBIDITIES LOOK DIFFERENT IN
MEN AND WOMEN.
QUALITY OF LIFE, FEMALE PATIENTS
REPORT WORSE QUALITY OF LIFE
WITH SYMPTOMS OF SLEEPINESS
INSOMNIA THEN MEN DO AND THINK
OF TREATMENT RESPONSES.
IF SOME OF THESE BIOLOGICAL SEX
ISSUES HOW IT PRESENTS,
TREATMENT MAY NEED TO BE OCCUR
TRAILED WHERE FOCUSSING ON
ISSUES THAT MATTER IN THE
INDIVIDUAL ITSELF.
SO LET'S START WITH WHAT
POSSIBLY ARE SOME SEX
DIFFERENCES.
THESE ARE DATA FROM A STUDY
PUBLISHED LOOKING AT HOW
DIFFERENCES IN THE X AXIS AND
SEVERITY BASED ON THE ACTUATIONS
AND HOW THEY DIFFER BETWEEN MEN
AND WOMEN AND FROM THE
STANDPOINT OF NREM.
LOOKING AT WOMEN THE DARK LINE,
WOMEN TEND TO HAVE LESS DISEASE
SEVERITY AND THIS IS BREATHING
RATES IN WOMEN RIGHT HERE AND
MEN.
SO MEN AND WOMEN OVERLAP BUT
WHEN YOU LOOK ATNON-REM INDEXES
THEY MEN HAVE A HIGHER NON-REM
INDEX THAN WOMEN AND THERE'S SEX
INTERACTIONS IN THE SLEEP
BREATHING.
WHAT'S THE PATHOPHYSIOLOGY OF
THAT?
I'LL REPORT TO THE STUDY WHICH
LOOKED AT A NUMBER OF FACTORS
NOT JUST BIOLOGICAL SEX BUT
OTHER FACTORS AND I'LL PRESENT
MORE KEY FIGURES HIGHLIGHTING
THESE ISSUES AND I'LL PICK ON
THE FIRST TOPIC OF SEX CLEARLY
MALES VERSUS FEMALES HIGHER ROOM
INDEX AND WHEN YOU LOOK AT
TRAITS FROM VENTILATION AND
NASAL PRESSURE YOU CAN LOOK AT
COLLAPSIBILITY, COLLAPSIBILITY
IS HIGHER IN MEN THAN WOMEN.
YOU CAN LOOK AMOUNT COMPENSATION
FROM THE STANDPOINT ON WHAT
HAPPENS WHEN IT GOES UP.
IT'S DIFFERENT IN MEN THAN
WOMEN.
FEMALES HAVE A HIGHER
COMPENSATORY DRIVE.
FINALLY, THE BOUNDARY RESPONSE
TO REDUCED VENTILATION, NOT MUCH
DIFFERENCE BUT STILL MAY BE SOME
BORDERLINE DIFFERENCES IN MEN
VERSUS WOMEN.
KEEP THIS IN MIND BECAUSE I'LL
KEEP COMING BACK TO THIS AND AGE
DIFFERENCES AND OBESITY RELATED
DIFFERENCES AND RACE-BASED FFER.
THIS COULD BE PARTLY FROM THE
GEOGRAPHY OF HOW FAT IS
DISTRIBUTED AND NOT JUST
ANATOMICAL.
THERE'S A LOT GOING ON IN FAT
DISTRIBUTION VARIES AND IT'S
DOWN STREAM SIGNAL PATHWAYS TO
CONTROL VENTILATION AND UPPER
AIRWAY.
LET ME SWITCH TO HYPERTENSION.
THIS IS A SLIDE FROM
HYPERTENSION IN THE UNITED
STATES COMPARING MEN VERSUS
WOMEN.
WOMEN HAVE A HIGHER PREVALENCE
OF HYPERTENSION PARTICULARLY
18-39 THERE'S A DIFFERENCE OF
ALMOST TWOFOLD AND WHE YOU LOOK
AT MEN VERSE US WOMEN THERE'S
SOME EQUALIZATION BUT MEN ARE
LEAD FROM THE STANDPOINT OF
OF HYPERTENSION AND 60 OR
MORE, THERE'S SOME EQUALIZATION
AT THAT POINT.
GENDER DIFFERENCES BUT NOT JUST
GENDER BUT AGE DIFFERENCES.
SO WHAT ABOUT AGE-RELATED
VARIABILITY.
WE ALL KNOW IT INCREASES WITH
AGE AND THERE MAY BE DIFFERENCES
IN PRESENTATION AND CHANGES IN
UPPER AIRWAY ANATOMY AND MUSCLE
FUNCTION AND ADULTS MAY HAVE
APNEA PROLONGED AND WE HAVE DATA
FROM THE HEALTH STUDY TWO
DECADES AGO SHOWING WITH
INCREASED AGE THERE'S HIGHER
DISPOSITION OF INCREASED SLEEP
APNEA WITH A PLATEAU AROUND 65
AND LOOKING AT THE UPPER AIRWAY
MECHANICS AND THIS IS A SMALL
SAMPLE BUT AS AGE INCREASES
THERE'S AN INCREASE IN THE
STRUCTURE SUGGESTING AGE-RELATED
VULNERABILITY IS A PHYSIOLOGIC
PHENOMENON AND CAN BE EXPLAINED
AND WHAT THE DETERMINATES ARE
REMAIN UNKNOWN.
I'LL GO BACK TO ANOTHER STUDY
WHICH ISH A CANADIAN STUDY
SHOWING IT'S
'S NOT JUST IN THE
U.S. BUT ALSO WORLDWIDE, THAT
THE PREVALENCE OF SLEEP APNEA AS
A PROMINENCE OF AGE IS DIFFERENT
AND EVERY AGE WOMEN HAVE A LOWER
PREVALENCE.
IT INCREASED OVER TIME AS YOU
GET TO THE HIGHER DECILES AND
CONVERGES OR STARTS TO CONVERGE
IN THE 70s AND 80s.
BUT AGAIN, GENDER BY AGE
DIFFERENCES.
AND HYPERTENSION, SAME THING.
WE SEE THE SAME THING IN MEN
THERE'S SOMEWHAT OF A CE AND
CONVERGENCE GOING TO 70 PLUS BUT
AGE RELATED PREDISPOSITION IS
SIMILAR TO AGE-RELATED
PREDISPOSITION TO SLEEP APNEA.
WHAT ABOUT RACE AND ETHNICITY.
AFRICAN AMERICANS AND ASIANS
HAVE A HIGHER RISK COMPARED TO
CAUCASIANS DESPITE SIMILAR BMI
AND THERE'S GENETIC
PREDISPOSITION.
AND THESE FACTORS LOOKKT TO THE
RISK AND THE COMORBIDITIES
ASSOCIATED.
GOING BACK TO THE SLIDE LOOKING
AT THINGS SUCH AS RACE.
NO MATTER YOU LOOK AT IT WHETHER
SEVERE APNEA INDEX OR
COLLAPSIBILITY MEASURE THERE'S
RELATE-RELATED DIFFERENCES IN
WHAT HAPPENS WITH REGARDS TO THE
UNDERLYING PATHOPHYSIOLOGY WIN
SLEEP APNEA AND IT'S IMPORTANT
WITH HYPERTENSION.
.
LOOKING IRRESPECTIVE OF WHEN
WERE DIAGNOSED HAVE HIGHER
HYPERTENSION THAN CAUCASIAN.
AND THERE'S VARIANCES AND SLEEP
APNEA COULD BE DUE TO LIFESTYLE,
OBESITY RATES AND ACCESS TO
HEALTH CARE AND SLOWER SOCIO
ECONOMIC STATUS IS ASSOCIATED
WITH HIGHER PROPENSITY OF SLEEP
APNEA AND DIAGNOSIS AND
TREATMENT.
THAT WOULD BE PART BECAUSE
THERE'S DISPARITIES IN ACCESS TO
DIAGNOSTIC TESTING AND THERAPY.
THERE'S A SUBSTANTIAL GEOGRAPHIC
AND SOCIO ECONOMIC VARIABILITY.
HERE'S HEAT MAPS PUBLISHED FROM
A VARIETY OF AUTHORS LOOKING AT
HOW SLEEP APNEA VARIES AS A
FUNCTION OF WHERE WE ARE YOU'VE
SEEN ESTIMATES THAT RANGE FROM
5-15% AND SIMILAR ESTIMATES HAVE
BEEN FROM SPAIN AND THAT WAS IN
THE U.S. AND THERE'S A HIGHER
PROPENSITY IN BRAZIL.
MALES 25% ARE AFFECTED BY AGE OF
15 OR MORE.
THERE'S OCCURRENCES THAT OCCUR
ACROSS TRE GLOBE ANDNDS IS A
SLIDE OF A HEAT MAP
DEMONSTRATING DIFFERENCES THAT
OCCUR GEOGRAPHICALLY.
AGAIN IT'S NOT A HOMOGENEOUS
DISEASE WHETHER YOU LOOK AT
DEMOGRAPHICS OR GLOBAL FACTORS.
TURNS OUT, HYPERTENSION HAS THE
SAME EFFECT.
IF YOU LOOK AT DETERMINATES OF
HIGH BLOOD PRESSURE IN THE
UNITED STATES THERE'S
RACE-RELATED DIFFERENCES IN THIS
ASSESSMENT OF THE REGARD STUDIO,
HYPERTENSIONS IS MORE PROMINENT
IN CERTAIN GROUPS AND I LOOKED
AT HYPERTENSION IN LOW AND
MIDDLE INCOME COUNTRIES.
THIS PREDICTS HYPERTENSION WITH
THE WEALTHIEST HAVE MORE
HYPERTENSION AND THAT HELD
THROUGH THE CONTINENTS ASSESSED
IN THIS STUDY.
WE HAVE MONITORS OUT THERE AND
THE STUDY LOOKED AT THAT AND
NUMEROUS STUDIES LOOK AT THE
DIFFERENT CLASSIFICATION.
VARIANCE WILL VARY ON WHAT TESTS
YOU USE AND SO FORM.
THIS PROBLEM OF VARIABILITY
DATES BACK ALMOST 20 YEARS WHEN
AN ARTICLE BY A GROUP LOOKED AT
HOW AHI VARIOUS WHEN YOU KEEP
CHANGING DEFINITIONS.
IT'S NOT A KNEW PHENOMENA.
IT'S AN ONGOING DEBATE FOR WELL
OVER TWO DECADES.
THIS SHOWS WHAT MATTERS.
IF YOU THINK ABOUT WHETHER YOU
USE SOMNOGRAPHY YOU'LL SEE THE
PREVALENCE CHANGES WHERE THE
TECHNOLOGY IS USED AND I'LL COME
BACK TO LOTS OF PATHOGENIC
MECHANISMS.
THERE'S UPSTREAM RISK FACTORS
AND HAVE TO UNDERSTAND THEM TO
UNDERSTAND THE BEST WAY TO
PERSONALIZE IT AND THERE'S
DIFFERENT HYPERTENSION AND ALL
UT THINGS.
WHAT THEY'VE DONE IS EMBRACED
THE HETEROGENEITY AND SHOW THE
SPECIFIC
TARGETS AND DRUGS FOR
AMERICAN PATIENTS SHOULD FOCUS
ON CALCIUM BLOCKERS AND THERAPY
AND OLDER ADULTS FOCUS ON
CALCIUM CHANNEL TO REDUCE STROKE
YOUNG ADULTS, DIFFERENT
APPROACH.
HYPERTENSION HAS COME AND THIS
SAYS IT THE BEST.
WE HAVE TO BE REALLY CAREFUL.
WE CANNOT GO TO A STATE OF
INFORMATION OVERLOAD.
THIS GRAPHIC SHOWS THAT WHEN YOU
THINK ABOUT HOW YOU'LL PRESCRIBE
SOMETHING YOU CAN DO IT BY
DIAGNOSIS OR INCORPORATE AGE,
SEX, OTHER DETERMINATES AND
FIGURE OUT WHAT THE RIGHT THING
IS BUT WE DON'T WANT TO GET INTO
A HIGH INFORMATI STATE BECAUSE
WE'LL GET TO A FIELD OF DIMMISH
-- DIMINISHING RETURNS AND YOU
HAVE TO BE CAREFUL WITH THE
DIAGRAM AND HAVE TO FIND THE
PERFECT SWEET SPOT WITH THE
BENEFIT TO COST RATIO IS
OR THETREATMENT.
HYPERTENSION HAS SO MANY NO
NOMENCLA
NOMENCLATURES.
THERE'S DIFFERENT TYPES AND
PATTERNS AND SYSTOLIC,
SECONDARY, RESISTANT, WHITE
COAT, THE LIST GOES ON AND ON
BUT SO DOES OUR LIST.
I COULD GO ON AN ON.
WE HAVE TO MINIMIZE SOME OF THIS
STUFF.
YES, WE MACHINE LEARNING IS
COMING AND HERE AND CAN MAKE E
PREDICT BUT WE HAVE TO BE
CAREFUL.
WE CAN'T MAKE IT SO COMPLEX
BECAUSE MACHINE LEARNING SHOULD
BE TRAINED ON HIGH QUALITY DATA
INTERPRETABLE AND WITH RELIABLE
DATA.
DATA QUALITY WITH E.H.R. IS A
CONCERN.
WE HAVE TO THINK ABOUT THESE
MELD -- MODELS TO UNDERSTAND
CLINICAL VARIANTS.
THEY COULD BE MISSINGTHATA IN
SOME OF THESE THINGS.
AS WE MOVE FROM THE POINT OF
VALIDATING SOME HETEROGENEITY
METRIC WE HAVE TO BE CAREFUL
IT'S DONE WITH CAUTION
UNDERSTANDING THE LIMITATION OF
DATA ITSELF.
I'LL END THERE AND THANK YOU FOR
YOUR TIME.
>> THANK YOU, DR. PUNJABI.
NEX
NEXT I DR. OWENS WITH HOW DO WE
GET PERSONALIZED MEDICINE WITH
OSA.
>> THANK YOU FOR ORGANIZING
THIS.
THANK YOU TO MONICA AND NARESH
FOR THEIR TALKS AS WELL.
YOU CAN SEE I WAS HOPING TO
CREATE A FRAMING TALK FOR THE
NEXT 10 MINUTES OR SO.
I THINK WE'VE HEARD QUITE A BIT
ABOUT THE PERSPECTIVES FROM
PATIENTS.
I THINK WE HEARD A LITTLE BIT
ABOUT THE RESEARCH.
I WANT TO TALK ABOUT HOW THIS
PLAYS OUT IN THE CLINIC AND HOW
WE HAVE SLEEP APNEA NOW AND WE
HAVE THIS ONE SIZE FITS ALL
APPROACH.
WE HAVE PATIENTS LIKE A
40-YEAR-OLD MAN, SNORING, APNEA
AND A -- OBESITY AND ORDER A
TEST AND YOU ORDER PEP AND HE
FEELS GREAT BUT WE HAVE OTHER
PATIENTS WHO COME IN WHO ARE
KIND OF SIMILAR.
THIS TIME IT'S A 41-YEAR-OLD
WOMEN WITH SOME OF THE SAME
SYMPTOMS BUT NOW MORE OF
INSOMNIA AND HER CHIEF COMPLAINT
IS I WAKE UP A LOT AT NIGHT.
YOU ORDER A SLEEP STUDY,
DIAGNOSIS SLEEP APNEA AND TRY C
PAP AND THE PATIENT SAYS I FEEL
WORSE THAN BEFORE AND CAN'T USE
ITS SO WE'RE LEFT THINKING.
SOME COME IN WITH NO REAL
SYMPTOMS BUT SENT IN BY THEIR
CARDIOLOGIST AND THEIR CHIEF
COMPLAINT IS MY DOCTOR SENT ME
AND YOU DO A TEST AND ORDER THE
C PAP AND PATIENT SAYS DO I NEED
THIS.
WHAT WOULD BE A BETTER FUTURE
FOR SLEEP APNEA MANAGEMENT?
WE'RE TALKING ABOUT PERSONALIZED
MEDICINE.
YOU SAW AMY JORDAN AND OTHERS
THOUGHT ABOUT THIS AND ALLAN
PACK THOUGHT ABOUT THIS AND
HE'LL BE SPEAKING AND WE HAVE
BEEN TALKING ABOUT EACH
INDIVIDUAL HAS GENETICS AND
ENVIRONMENT AND END UP WITH
THESE PERSONALIZED PHENOTYPES.
YOU TAKE VARIABLES FROM THE PSG
AND MAYBE TAKE BLOOD WORK AND
LOOK AT BLOOD PRESSURE AND HAVE
THE PATIENT FILL OUT
QUESTIONNAIRES TO GET AN IDEA
HOW AN INDIVIDUAL PATIENT IS
IMPACTS.
THE EUROPEAN SLEEP RESEARCH
SOCIETY SAID LET'S TAKE SOME
CLINICAL TRAITS, MAYBE TRY TO
COMBINE THEM WITH THE UNDERLYING
CAUSES AND LINK UP WITH THERAPY.
STO GET TO PERSONALIZED MEDICINE
YOU HAVE TO RECOGNIZE NOT ALL
PATIENTS WITH A CONDITION LOOK
THE SAME.
I'M GOING TO CALL THAT A
PHENOTYPE.
YOU HAVE TO HAVE AN
UNDERSTANDING OF THE DIFFERENT
MECHANISTIC PATHWAYS OR ENDOTYPE
AND DIFFERENTIATE THE PATHWAYS
AND HOPEFULLY HAVE A THERAPY TO
MANIPULATE THE PATHWAY AND
CHOOSE THE RIGHT OUTCOME TO SHOW
AN EFFECT.
FOR EXAMPLE I'LL LOOK AT ASTHMA
AND SHOW HOW IT HAS MOVED TO A
PERSONALIZED MEDICINE APPROACH.
IT'S NO LONGER EVERYBODY GETS
THE SAME IN HALERS AND THE
RECOGNITION WAS SOME DEVELOPED
ASTHMA AS CHILDREN ASSOCIATED
WITH ATP AND A LOT OF ALLERGIC
SYMPTOMS AND OTHERS DEVELOPED IT
AS OLDER ADULTS, OFTEN WOMEN,
OFTEN ASSOCIATED WITH OBESITY.
AND THIS ANTIBIOTIC -- ANTIBODY
IF YOU GIVE IT AND LOOK AT THE
OUTCOME OF FEB1 THE DRUG DOESN'T
SEEM TO DO ANYTHING.
IT'S ONLY WHEN YOU GIVE IT TO
SELECTED ASTHMA PATIENTS AND
LOOK AT ASTHMA EXACERBATIONS IT
HAS A BIG EFFECT.
I THINK WE NEED TO DO THE SAME
IN O SLEEP APNEA NOT
ALL PATIENTS WITH OSA LOOK THE
SAME AND NEED TO UNDERSTAND THE
DIFFERENT MECHANISTIC PATHWAYS.
I BORROWED THE SLIDE AND WHAT
WARE TALKING ABOUT HERE TODAY
ARE PHENOTYPES SLEEP APNEA CAN
PRESENT DIFFERENTLY AND WOMEN
TEND TO REPORT SYMPTOMS
DIFFERENTLY THAN MEN AND ALSO
THE DEF
ENDOTYPES AND PHYSIOLOGY ARE
DIFFERENT BETWEEN MEN AND WOMEN.
IF YOU HAVE A PATIENT WHO HAS A
LOT OF SYMPTOMS WE'LL TREAT AND
AND IF THERE'SERY SYMPTOMATIC
EVEN IF ADHERENCE IS LOW YOU'LL
PERSIST WITH THERAPY.
A BIG CHANGE IN THE LAST 10-15
YEARS IS PATIENTS WHO DON'T HAVE
A LOT OF SYMPTOMS YOU PROBABLY
DON'T NEED TO BE AGGRESSIVE
ABOUT DIAGNOSING SLEEP APNEA AND
MAY NOT NEED TO TREAT.
WE'RE USING ENDOTYPES IN A CRUDE
WAY WITH AND YOU'LL THINK OF C
PAP AND WEIGHT MANAGEMENT AND
NOT SEND THEM FOR NERVE
STIMULATOR THERAPY AND IF YOU
HAVE A PATIENT WITH A LOW BMI
AND THIS ANATOMICAL AIRWAY
YOU'LL THINK OF SURGICAL
MANAGEMENT.
IT'S EASY TO INCORPORATE THE
ENDOTYPES BUT HARD TO KNOW WHAT
TO DO WITH PATIENTS IN THE
MIDDLE AND THOUGHT TO LOOK AT
OTHER FIELDS.
IS MOST DON'T MEASURE HORMONE
LEVELS BECAUSE WE HAVE A LOT OF
OUTCOME DATA AND COMPARATIVE
EFFECTIVENESS STUDIES IN
DIFFERENT GROUPS.
WE KNOW IF YOU HAVE DIABETES,
YOU SHOULD USE ACE-ARB.
AND I THINK CANCER IS THE BEST
EXAMPLE OF PERSONALIZED
MEDICINE.
YOU WOULD LOOK AT CELLS UNDER A
MICROSCOPE AND DESCRIBE WHAT YOU
SEE.
NOW THE MEASUREMENT OF CANCER IS
GETTING TO INDIVIDUAL ANTIGENS
AND GENETICS.
NOW YOU HAVE CAR T THERAPY FOR A
SOLUTION FOR THAT INDIVIDUAL AND
WITH PROSTATE AND BREAST CANCER
LARGE STUDIES FOCUS ON
PATIENT-CENTRIC OUTCOMES.
SHOULD WE DO SURGERY, RADIATION?
AND THERE'S A RECOGNITION SOME
OUTCOMES ARE IMPORTANT FOR
RESEARCHERS LIKE
PROGRESSION-FREE SURVIVAL IS NOT
NECESSARILY IMPORTANT FOR
PATIENTS.
SO WHAT'S THAT MANE FOR
OBSTRUCTIVE SLEEP APNEA.
THIS IS WHERE THIS CATHEDRAL
WHERE MY WIFE'S FAMILY IS FROM.
THESE ARE STANDARDIZED
MEASUREMENTS EVERYONE AGREED TO
THIS IS HOW BIG A LOAF OF BREAD
SHOULD BE AND WHAT IS OUR
MEASUREMENT IN SLEEP APNEA?
WHAT ABOUT THE ALL THESE THINGS
AND LIMITATION AND HYPOXIC
BURDEN.
HOW MUCH DO WE NEED TO THINK
ABOUT?
AND OUTCOMES OF COURSE WE HAVE A
VARIETY OF OUTCOMES, WHICH ARE
THE MOST PATIENT CENTRIC AND
SHOULD WE BE CONCERNED ABOUT?
AND THE OTHER THING THINKING OF
SLEEP APNEA IS HOW DETAILED DO
WE NEED TO BE IN OUR
UNDERSTANDING.
IF YOU WHEN
WE THINK OF ENDOTYPES AND
PHENOTYPES HOW MANY CLUSTSERS
AND FOR ENDOTYPES DO WE NEED A
CERTAIN PHENOTYPE AND THIS
HETEROGENEITY MAY NOT BE AS
IMPORTANT AND IF CPAPs WORK DO
WE NEED THIS LEVEL OF DETAIL?
AS WE HEAR THE TALKS TODAY AND
TOMORROW I WANT TO FRAME THE
DISCUSSION BY SAYING WHAT KIND
OF MORE -- MEASUREMENTS ARE
NEEDED FOR PERSONALIZED OSA
THERAPY AND CLINICAL OUTCOMES
AND SESSION 3 WE'LL DIVE IN THE
HETEROGENEITY.
IF WE AGREE ON SOME OF THESE
METRICS, HOW WILL WE GET THESE
INTO THE CLINIC AND MOVE THEM
FORWARD?
WE HAVE AN EXECUTIVE SUMMARY
COMING FROM THE WORKSHOP TODAY
AND TOMORROW BUT WANT TO
ENCOURAGE DISCUSSION AND
COLLABORATIONS.
SO I'LL END WITH A PICTURE OF
BIOLUMINESCENCE HERE WHERE WE
LIVE AND WORK AND THANK YOU VERY
MUCH.
>> NEW FOR THE FANTASTIC
OVERVIEW AND FRAMEWORK AND TO
THE FIRST TWO PRESENTERS.
IF YOU HAVE QUESTIONS RELATED TO
THE INITIAL TALKS HOLD THEM TO
THE PANEL DISCUSSION OR
TOMORROW'S ROUNDTABLE DISCUSSION
AND WE'LL SWITCH TO AN EMOJI FOR
THE AND WE'LL EXPERIMENT A
LITTLE BIT.
WHEN YOU SEE THAT, PLEASE WORK
TO WRAP UP.
WITH THIS, DR. OWENS, I'LL
CONVENIENTLY PASS THE MIKE TO
YOU AS THE NEXT MODERATOR.
>> THANK YOU, ALFONSO.
SO, TODAY WE'LL START WITH
SESSION 1, OUTCOMES ACROSS THE
LIFE SPAN, CLINICAL RELEVANCE.
WE'VE ENCOURAGED TIME FOR
QUESTIONS AND WILL HAVE SPEAKERS
WITH 15 MINUTES AND I'D LIKE TO
DIVE IN TO STAY ON TIME.
OUR FIRST SPEAKER IS DR. AMAL
ISAIAH PROFESSOR OF PEDIATRICS,
DIAGNOSTIC AND RADIOLOGY AND
NUCLEAR MEDICINE AND DIRECTOR OF
OAT YO LARYNGOLOGY AT THE
MARYLAND SCHOOL OF MEDICINE AND
HIS PRESENTATION IS PREDICTIVE
MODELS FOR OSA TREATMENT
OUTCOMES.
DR. ISAIAH, THANK YOU VERY MUCH
FOR PRESENTING TODAY.
>> I'M AN ONCOLOGIST AT THE
UNIVERSITY OF MARYLAND
INTERESTED IN PEDIATRIC SLEEP
MEDICINE RELATING TO OUTCOMES OF
PEDIATRIC OBSTRUCTIVE SLEEP
APNEA AND THE ROLE THE PEDIATRIC
UPPER AIRWAY PLAYS A ROLE IN IT.
TODAY I'M GOING TO SPEAK ABOUT
PREDICTIVE MODELLING FOR
OBSTRUCTIVE SLEEP APNEA
TREATMENT OUTCOMES.
I REALLY THOUGHT PEDIATRICS AT
THE CORE OF HETEROGENEITY
BECAUSE WE STILL FOLLOW VERY
MUCH A ONE SIZE FITS ALL
APPROACH AND THIS TOPIC IS RIPE
FOR DISCUSSION.
IN TERMS OF DISCLOSURES I DO
ROYALTIES FROM THE SCHOOL AT THE
UNIVERSITY OF MARYLAND AND OUR
WORK IS FUNDED BY THE NHLBI.
THE FIRST OBJECTIVE IS TO
UNDERSTAND THE SCOPE OF THE
PROBLEM ESPECIALLY THE
HETEROGENEITY RELATED TO SOCIAL
ECONOMIC STARTS AND SOME OF THE
SOLUTIONS THAT WE CAN PROPO HES
TO NOT JUST UNDERSTAND BUT TREAT
PEDIATRIC OSA BETTER.
AND IT'S ACRONYMS MAKE IT HARD
FOR ME TO COMMUNICATE THESE TO
OUR PATIENTS AND SOMETIMES MY
COLLEAGUES WHO MAY NOT BE IN THE
FIELD.
SLEEP DISORDER TREATMENT HAVE
SOME WHO CANNOT GET DIAGNOSIS OF
OBSTRUCTIVE SLEEP APNEA.
OBSTRUCTIVE SLEEP DISORDER
BREATHING IS ATTRIBUTABLE TO THE
BURDEN ARRIVING FROM THE UPPER
AIRWAY SPECIFICALLY.
WHEN I SAY OBSTRUCTIVE SLEEP
APNEA IT'S FIRMLY GROUNDED IN
THE PROBLEMS IN THE POPULATION
AND NOT TOUCH ON THE PHENOTYPES
TEE FIND IN LITERATURE SUCH AS
THE UPPER AIRWAY SYNDROME AND
SNORING BECAUSE IT COULD BE
BEYOND THE SCOPE OF OUR
DISCUSSION HERE.
WHAT HAVE WE DONE SO FAR?
THIS ONE SLIDE SUMMARIZES WHAT
WE FIND IN DISRUPTIVE SLEEP
APNEA.
ABOUT 5% PEOPLE PRESENTED
SNORING AS A PRIMARY SYMPTOM AND
UNDER GO DIAGNOSIS BY THE
SOMNOGRAPHY AND TO THE RIGHT IS
A BUNCH OF MIXED ANALYSIS
REPRESENTATION OF STUDIES FROM
ACROSS THE WORLD SHOWS THE
INCREASING PREVALENCE OF OBESITY
AND THE MOST IMPORTANT THING IS
WE ONLY HAVE ONE TREATMENT FOR
MOST OF THEM PRESENTING TO MY
CLINIC.
WE OFFERED TO REMOVE THE TONSILS
AND ADENOIDS AND MOST THE TIME
THEY HAVE RESEARCHED THE TOPIC
OR SPOKE TO SOMEBODY ELSE WHO
SAID LOOK IT'S TIME TO GET YOUR
CHILD'S TONSILS AND ADENOIDS
AND 10% HAVE BLEEDING AS A
COMPLICATION AND MANY OF THEM
DID NOT GET BETTER AFTER SURGERY
AND TO MAKE MATTERS WORSE, SOME
DO DIETS AS A COMPLICATION OF
THE SURGERY.
I WANTED TO EXEMPLAIFY THE
PROBLEM IT'S PROBLEMATIC BECAUSE
OVER THE YEARS WE'VE CHOSE
GENERATING SYSTEMS AND WE WE
HEARD A HINT ABOUT IT EARLIER.
WE SWITCHED FROM THE RESPIRATORY
DISTURBANCE INDEX TO THE APNEA
METRIC AND THERE'S A BUNCH OF
METRICS PEOPLE CONSTANTLY PUT
OUT.
NONE OF THEM REALLY MAKE A
DIFFERENCE TO OUR POPULATION
BECAUSE MANY OF THEM ARE UNABLE
TO GET SLEEP STUDY.
YESTERDAY IN MY CLINIC I ORDERED
IT FOR SOME OF THEM AND I WAS
TOLD LOOK, IT'S OKAY THAT WE
WAIT FOR SIX MONTHS TO GET ONE.
THIS IS FUNDAMENTALLY
PROBLEMATIC BECAUSE THESE ARE
KIDS AT RISK FOR SLEEP APNEA AND
I COULD GET THEM IN THE
TREATMENT PIPELINE EARLIER BUT
BECAUSE WE HAVE TO RELY ON POLY
SONOGRAPHY AND MANY ARE MINORITY
POPULATIONS THAT DO NOT GET
ACCESS TO TREATMENT RIGHT AWAY.
DESPITE US DESCRIBING THE SCOPE
OF THE PROBLEM NONE OF US CAN
SEEM TO AGREE ON TREATMENT
GUIDELINE.
WE HAVE THE AMERICAN ACADEMY ON
SLEEP GUIDELINES ON THE
SOMNOGRAPHY AND THE AMERICAN
ACADEMY OF OTOLARYNGOLOGY AND
HEAD AND NECK SOCIETY AND
EVERYBODY SEEMS TO HAVE I
DIFFERENT SET OF CRITERIA BUT
THERE'S NO CONVERGENCE AND HAVE
TECHNOLOGY THAT UNFORTUNATELY
DOESN'T APPEAL IN MODERN SENSE
BECAUSE IT COSTS A LOT OF MONEY
AND FUNDAMENTALLY KNACK --
INACCESSIBLE FOR A LARGE NUMBER
AND DOES IT PREDICT MORBIDITY?
AND IS THERE A BETTER WAY TO
COLLECTION THIS AND COVER THE
POPULATION BETTER WITH IT?
SO WHEN I LOOK FOR SEX
DIFFERENCES, I WAS UNABLE TO
FIND MUCH ON IT WHICH HOPEFULLY
SUPPORTS THE COST OF THIS
WORKSHOP.
FIRST -- THE CAUSE OF THE
WORKSHOP.
FIRST IN THE SCHOOL AGE GROUP
THESE ARE X-RAYS FROM CHILDREN
FROM SCHOOL AGE KIDS AS WELL AS
ADOLESCENT KIDS THE FUNDAMENTAL
DIFFERENCE WE SEE FROM THE
LATERAL VIEW OF THE HEAD AND
NECK THERE'S ANGULATION AND IT
INCREASES THE COLLAPSIBILITY IN
BOYS COMPARED TO GIRLS.
I'M USING SEX ASSIGNED AT BIRTH
AS THE THE SURROGATE MEASURE FOR
THE DIFFERENCES AND TRANSITION
TO ADULTS GENDER STARTS PLAYING
A SIGNIFICANT ROLE AS WELL.
WE KNOW THERE'S QUITE A BIT OF
CONFOUNDING FROM SOCIO ECONOMIC
STATS AND AT THE SAME TIME IT
CONTRIBUTES BRAIN DEVELOPMENT
SOCIO ECONOMICS CAN PLAY A ROLE
AND CONTRIBUTE TO BRAIN OUTCOMES
AS WELL.
A LOT OF STUDIES IN THE PAST
HAVE SHOWN THERE'S QUITE A BIT
OF HETEROGENEITY THAT RESULTS
FROM RISK PROFILES THAT RESULT
FROM WHERE KIDS LIVE OR SOCIO
ECONOMIC STARTS.
I ENCOUNTERED THIS ON A DAY TO
DAY BASIS.
THERE'S SLEEP MED SIS PHYSICIANS
THAT CALL THE PRESENCE OF SLEEP
APNEA SOMETIMES USING 1.5 AND
FOR SEVERITY I'M NOT SURE THEY
CONTRIBUTE TO OUR TREAT OUTCOMES
AND WHEN WE PROPOSE THE OHI FOR
5 AND FOR 10 SOMETIMES WE DON'T
PROP
PROPOSE AND SOME PATIENTS COME
FROM SOCIO ECONOMIC ADVANTAGE
COMPARED TO DISADVANTAGE AND
LIKELY NOT HAVE AN OUTCOMES
BASED ISSUE COMPARED TO CHILDREN
FROM THE LOWER SES AND THESE
THRESHOLDS OCCASIONALLY LEAD TO
PROBLEMS.
SURGERY IT NOT WITHOUT RISK.
MANY COME BACK FROM BLEEDING AND
END UP NEEDING A LONG HOSPITAL
STAY TO GET OUT.
HERE'S KEY QUESTIONS.
CAN WE PREDICT MORBIDITY BETTER
RELATED TO SLEEP APNEA AND
SCREEN BETTER AND IS THERE A
ROLE FOR A.I.
AND THE FIRST DIFFERENCES IN
OUTCOMES IS THE COMPLICATION OF
OBESITY.
IT MAKES IT WORSE IN REMOVAL OF
ADENOIDS AND WE KNOW THE
PRESENCE OF OBESITY DOES LEAD TO
INFERIOR TREATMENT OUTCOME USING
THE MEASURE.
AND THIS THIS CONTRIBUTE TO REAL
WORLD ENVIRONMENTS AND 90% OF
WOMEN PRESENTING WITH SLEEP
DISORDER TREATMENT UNDER GO
TREATMENT WITH TONSILLECTOMY AND
ADENECTOMY A STUDY AND THERE'S
QUESTIONS THAT COULD ARISE IN
DIFFERENT DIRECTIONS.
SO HERE WE SHOW THE BURDEN OF
SYMPTOMS.
ON THE Y IS THE EHI.
--SORRY, PARENT REPORTED
BEHAVIOR.
THIS SHOWS WHAT THE PARENTS ARE
REPORTING APPEARS TO SUGGEST
WHAT THE CHILDREN ARE
EXPERIENCING IN TERMS OF ADVERSE
BEHAVIORAL OUTCOMES.
BUT WHEN WE SUBSTITUTE THE
SYMPTOM PROFILE WITH AHI THERE'S
WEAK RELATIONSHIP BETWEEN THE
TWO.
AND THEN THIS SPILLS OVER TO
TREATMENT OUTCOMES ASKING
PARENTS THEY APPEAR TO BELIEVE
HIGHER SYMPTOM BURDEN PRIOR TO
THE TREATMENT OFFERED AND IT
APPEARS AS IF THAT CARRIES OVER
TREATMENT OUTCOMES OPPOSED TO
FOLLOWING AHI AND THIS
CONTRIBUTE TO WHAT WE HAVE AAS A
CONUNDRUM FOR PEDIATRIC OSA AND
WE MAY REFER THEM BUT PART IS
WHAT WE SEE AS THE CONTRIBUTIONS
TO THE SYSTEM PRESENTATION AND
AHI FROM RACE AND PATIENT WHICH
ARE NOT ACCOUNTED FOR IN OUR
RISK STRATIFICATION METRICS.
AND I WANT TO PUT IN A PLUG FOR
TECHNOLOGY BECAUSE ARTIFICIAL
INTELLIGENCE MADE ITS WAY TO
MAINSTREAM RISK STRATIFICATION.
THIS IS A PAPER FROM LAST YEAR
WHICH TALKED ABOUT WHAT'S CALLED
OXYNET.
IT'S A DEEP LEARNING BASED
ALGORITHM.
WHAT THAT MEANS IS THERE'S
FUNDAMENTALLY A NEURAL NET-BASED
ALGORITHM THAT COULD CLASSIFY
PATIENTS OR PREDICT THE PRESENCE
OF SLEEP APNEA SEVERITY BASED ON
OX METRIC
FEATURES.
THE REASON I FEEL IT'S
SIGNIFICANT FOR REAL WORLD
PRACTICE IS MANY CANNOT AFFORD
TO GET IN THE CLINIC TO GET A
SOMNOGRAPHY DONE.
IN FACT THEY COULD BENEFIT
SIGNIFICANTLY FROM EARLY
DIAGNOSIS EVEN FROM A MISSED
DIAGNOSIS.
THE COUNTER ARGUMENT WE HAVE IS
THAT IN RETURN FOR THE INCREASED
RELIABILITY OF THE DIAGNOSIS
WE'RE SACRIFICING THE OUTCOMES
BECAUSE MANY OF MY PATIENTS IN
BALTIMORE CAN IN THE GET INTO A
TREATMENT FOR MONTHS.
THE QUALITY OF LIFE REFLECTS ON
THEIR PERFORMANCE AS WELL.
AND THIS IS THE ARCHITECTURE AS
WE START WITH THE PREDICTIVE
MODELS AND IT'S IMPORTANT TO
LOOK AT THE FEATURES WE HAVE,
PATIENT DEMOGRAPHICS AND SOCIO
ECONOMIC CHARACTERISTICS AND
THEIR INDIVIDUAL HABITS GO TO AN
ALGORITHM RANKING THEM TO
IMPORTANCE AND TRAIN THEM USING
THE DATA WE HAVE AND USE THE
STANDARDIZED DATA SETS WE HAVE.
WE SPENT A LOT OF TIME AND
EFFORT IN COLLECTING THE DATA
SUCH AS THE CHAT DATA SET WHICH
HAS BEEN INCREDIBLY USEFUL AS A
GROUP TO COME UP WITH BETTER
WAYS TO PREDICT OSA AS WELL AS
TO PREDICT OUTCOMES RELATED TO
IT.
IN CONCLUSION, WE FEEL THAT
PEDIATRIC OSA IS ASSOCIATED WITH
SIGNIFICANT HETEROGENEITY AND
CONTINUE TO FOLLOW THE ONE SIZE
FITS ALL APPROACH.
WE FEEL THERE'S A SIGNIFICANT
ROLE FOR MACHINE LEARNING AND
UNTAPPED ESPECIALLY IN CHILDREN
AND HOPING IF INCORPORATED
CORRECTLY CAN BRING DOWN THE
COST OF HEALTH CARE FOR CERTAIN
COMMUNITIES.
>> THANK YOU FOR THE GREAT TALK.
I LOOK FORWARD TO SOME QUESTIONS
AT THE END OF THIS SESSION.
WE'RE GOING TO MOVE TO OUR NEXT
SPEAKER.
THE NEXT SPEAKER IS DR. SUINGSAN
RED INFORMATION LINE.
THE PROFESSOR OF SLEEP MEDICINE
AT HARVARD MEDICAL SCHOOL,
PROFESSOR OF EPIDEMIOLOGY AT THE
KHAN SCHOOL OF PUBLIC HEALTH AND
AT BRIGHAM AND WOMEN'S HOSPITAL
AND HER PRESENTATION IS
SEX-GENDER DIFFERENCES IN OSA
PRESENTATION POLY SOMNOGRAPHY
AND MECHANISMS IN HEALTH
DISPARITIESES AND LIFE COURSE
PERSPECTIVE.
>> THANK YOU ALL FOR A FANTASTIC
AND CRITICALLY IMPORTANT
SYMPOSIUM AND THE OPPORTUNITY TO
SPEAK.
I'LL KICK OFF A NUMBER OF THE
THEMES THE PRIOR SPEAKERS
MENTIONED AND PARTICULARLY
EMPHASIZING SOME OF THE
HETEROGENEITY IN HOW SLEEP APNEA
PRESENTS AND LOOK AT THIS FROM
THE HEALTH DISPARITIES AND LIFE
COURSE PERSPECTIVE.
HERE'S MY DISCLOSURES.
THE MOST IMPORTANT GOES TO
DR. MALLAMPALLI'S STATEMENT OF
DIFFERENTIATING SEX AND GENDER
AND THE LITERATURE MAKES IT
DIFFICULT TO MAKE THE
DISTINCTION.
I'LL GOING TO GENERALLY REFER TO
SEX NOTING ONE RESEARCH NEED IS
THE ABILITY TO GENERATE DATA TO
DISTINGUISH BETWEEN THE
CONCEPTS.
WE HEARD EARLIER THERE ARE SEX
DIFFERENCES IN HOW SLEEP APNEA
PRESENTS IN MEN AND WOMEN.
AND I WANT POINT OUT WE KNEW
THIS FROM RESEARCH MORE THAN 20
YEARS AGO THAT MEN TEND TO MORE
LIKELY WITH ANY GIVEN L OFIV
SLEEP APNEA REPORTNE SNE AND
SNORTING, GASPING AND SLEEPINESS
AND WOMEN REPORT UNRESTED SLEEP,
FATIGUE, INSOMNIA AND DEPRESSION
SYMPTOMS.
IN FACT A FEW YEARS AGO, A LARGE
REPORT FROM A SLEEP CLINIC
REEM IN CLINICAL LI
PRACTICE NDS ARE SIMILAR.
WHAT YOU SEE ON THE RIGHT-HAND
SIDE IS IN FACT WOMEN RELATIVE
TO MEN PRESENTING WITH SLEEP
APNEA ARE MORE LIKELY TO HAVE
INSOMNIA, MEMORY PROBLEMS,
FATIGUE AND LESS LIKELY TO
WITNESS APNEAS.
WHAT THAT IMPLIES IS THAT OUR
CURRENT FOCUS ON SLEEPINESS AS A
SYMPTOM RATHER THAN INSOMNIA AND
THE USE OF REPORTED APNEAS MAY
CONTRIBUTE TO UNDER DIAGNOSIS IN
WOMEN.
THERE'S BEEN AN INCREASING
INTEREST IN THE OVERLAP OF
INSOMNIA OR SLEEP APNEA AND WE
MAY BE MISSING THAT ESPECIALLY
IN WOMEN.
THERE'S DIFFERENCES IN POLY
SOMNOGRAPHIES SHOW MALES ARE
DEEPER INSATURATION AND IN
PARTICULAR BLACK FEMALES HAVE
SHORTER EVENTS WITH LESS
DESATURATION AND WOMEN TEND TO
HAVE LESS COLLAPSIBILITY SO THE
SLEEP APNEA IS MORE SUBTLE AND
NOT AS A FLAGRANT APNEA BY HY
HYPONEA AND AGAIN WHAT I WANT TO
POINT OUT HERE IS THE CAUSE OF
THIS REM DOMINANCE.
WE MAY UNDERSTAND ESTIMATE SLEEP
APNEA IF WE DON'T HAVE ADEQUATE
ASSESSMENT OF REM OR USE A HOME
SLEEP APNEA TEST THAT DIDN'T
REPORT OUT THE REM VERSUS
NON-REM APNEA AND WHEN WE YOU
THE 4% DE SATURATION CRITERIA,
WE WILL HAVE WIDER DISPARITIES
BETWEEN MEN AND WOMEN AND THE
BIGGEST DISPARITY IS WHEN WE
LOOK THE THE ENTIRE PERIOD OF
THE NIGHT AND USED A 4% DESAT
WHERE THE RATIO OF THE HI IN MEN
AND WOMEN WAS CLOSE TO 2.AND IT
NARROWS USING THE 3% BUT STILL
SIGNIFICANT UNLESS WE LOOK AT
REM OR THE RATIO WILLIAMS CLOSE
TO 1.
MEASURING THE SUBTLE DIFFERENCES
MAY UNDERESTIMATE DIFFERENCES IN
WOMEN AND HERE'S A LARGE COHORT
OF MEN AND WOMEN WITH STUDIES IN
THE NEW MOM TO BE STUDY.
IT DID REPORT A MODEST
ASSOCIATION BETWEEN SLEEP APNEA
AS MEASURED BY THE AHI AND RISK
OF DEVELOPING PREECLAMPSIA.
HOWEVER, WHEN YOU GO BEYOND THE
HYPONEAS AND TAKE THE FLOW
SYSTEM UNOBSTRUCTED AND ABLE TO
QUANTIFY THE SCOOPING OR AIR
FLOW OBSTRUCTION AND USE THAT AS
A QUANTITATIVE VARIABLE, WE HAVE
A MUCH STRONGER OF PREECLAMPSIA
A
AND THE ASSOCIATION PERSISTS.
MANY ON THE CALL HAVE BEEN
INVOLVED DEVELOPING TOOLS TO
REALLY CHARACTERIZE THE
ENDOTYPES OR MECHANISTIC TRAITS.
YOU HEARD A LITTLE BIT OF THAT
INCLUDING LOW AROUSAL THRESHOLD,
UNSTABLE CONTROL AND LOOP GAIN
AND AIRWAY MUSCLE COMPENSATION
AND THE ROLE OF ANATOMY.
HIGH AND THERE'S BEEN LITTLE
VARIATION HOW THE FACTORS VARY
BY SEX BUT KNOW THERE'S ANATOMIC
DIFFERENCES AND MEN HAVE MORE
FAT IN THEIR AIRWAY AND A LONGER
MORE COLLAPSABLE AIRWAY.
DR. PUNJABI REFERRED TO THIS
STUDY WHERE WE USED THE
TECHNIQUES DEVELOPED TO APPLY E
THE COHORTS THAT DID POLY
SOMNOGRAPHY AT HOME AND THEY
HAVE INCREASED COLLAPSIBILITY
AND LOOP GAIN AND DEFICITS IN
DIFFERENTIAL COMPENSATION THAT
ACCOUNT FOR THEIR ELEVATED AHI.
IN CONTRAST, WOMEN HAVE
DECREASES IN THEIR AROUSAL
THRESHOLD MORE LIKELY TO WAKE UP
WITH A RESPIRATORY DISTURBANCE.
THEY HAVE INCREASE IN UTILITY L
AND LESS COLLAPSIBILITY.
IF YOU ACCOUNT FOR THE ENDOTYPES
ONE-THIRD OF THE DIFFERENCES IN
REM.
IN ADDITION THERE'S INTEREST IN
THE SLEEP APNEA RESPONSE
METRICS.
ONE AND THERE'S A DELTA LATER
RATE WITH APNEA AND HYPOPNEA AND
NOW I ADDED THE HEART RATE
RESPONSE.
THOUGH MEN HAVE DEEPER
DESATURATIONS THEY TEND TO HAVE
LESS OF A HEART RATE RESPONSE AS
YOU COULD SEE IN THIS PARTICULAR
FIGURE.
IN CONTRAST, IN THIS BLACK
FEMALE DESPITE SMALL DESACH AND
SHORTER VENT DURATIONS YOU HAVE
THIS MARK LEERT RATE RESPONSE.
THE EXTREMES ARE DIFFERENCES
SEEN BETWEEN BLACK FEMALES AND
WHITE MEN.
OTHER DATA PREDICTS
CARDIOVASCULAR MORBIDITY AND
MORTALITY.
THE IMPLICATIONS ARE THAT WOMEN
MAY HAVE LESS HYPOXIC BURDEN BUT
A GREATER CARDIOVASCULAR
AUTONOMIC SYSTEM RESPONSE AND
THE DELTA HEART RATE MAY BE A
PHENOTYPE THAT'S PARTICULARLY
APPROPRIATE TO GET AT SEX AND
GENDER AND RACE-RELATED
PHENOTYPES THAT PREDICT DISEASE.
MOREOVER THIS AROUSAL PHENOTYPE
OR LOW AROUSAL THRESHOLD, HIGH
AROUSABILITY MAY BE A MARKER OF
INSOMNIA AND PREDICT POOR CPAP
RESPONSES AND THOUGH THE
ENDOTYPES CAN BE CONSIDERED AS
WELL AS THE SEVERITY MARKERS,
THESE ARE ACTUALLY RELATED.
ON THE TOP ROWS ARE THE REND
TYPES AND BOTTOM ARE OUR
SEVERITY MARKERS PEOPLE WITH A
HIGHER LOOP GAIN HAVE A HIGHER
RESPONSE AND THOSE WITH A HIGHER
COLLAPSIBILITY HAVE A HIGHER
HYPOXIC BURDEN AND THOSE WITH A
LOWER AROUSAL THRESHOLD WILL
HAVE A HEART RESPONSE TO ANY
GIVEN DESATURATION.
YOU CAN TRY TO CREATE A CAUSAL L
CHAIN OF RELATING THE
MECHTRAITS OR ENDOTYPES
WITH CARDIOVASCULAR AND
DIABETES.
AND IN THIS SCHEMA WE SUGGEST
THESE ENDOTYPES LIKE LOOP GAIN
AND NEURAL MUSCULAR COMPENSATION
WILL INFLUENCE AIRWAY PATENSY
BUT IN SPECIFIC MANNERS IN
PRESENTING APNEA OR SHORT OR
LONG EVENT WITH OR WITHOUT
AROUSAL AND WITH OR WITHOUT
DESATURATION WILL INFLUENCE THE
SEVERITY MARKERS OF HYPOXIC
BURDEN, UTILITORY BURDEN AND
NEED TO BE CONTRIBUTED IN THE
CAUSAL LINK TO END OCCURAN
DAMAGE.
BE THERE'S AN AVERAGE HYPOPNEA
DURATION AND AVAILABLE IN MOST
HOPE SLEEP TESTS AND IS A POOR
MAN'S MARKER OF YOUR AROUSAL
THRESHOLD AND ALSO TRAIT LINE.
IT HAS A HIGH HERITABILITY OF
60% AND SEVERAL POSITIVE GWAS
FINDINGS FOR IT.
EVENTS ARE SHORTER IN WOMEN AND
SHORTEST UP AFRICAN AMERICAN
WOMEN AND AS YOU CAN SEE ON THE
RIGHT-HAND SIDE PEOPLE WITH THE
SHORTEST EVENTS IN THE QUARTILE
ARE MORE LIKELY TO HAVE AN
11-YEAR INCREASED MORTALITY AND
DISASSOCIATION BETWEEN THE AHI
AND MORTALITY MISTAKE -- MOSTLY
IN MEN AND CAN PREDICT MORTALITY
IN MEN AND WOMEN.
AND IN HISPANIC COMMUNITY HEALTH
STUDY WE CAN IDENTIFY COMPOSITES
THAT AND ENDOTYPES AND CREATE
METABOLOMIC RISK SCORE AND
THERE'S A RISK SCORE THAT MAPS
TO THE SHORT EVENT PHENOTYPE.
AND IN THE END TYPES IN THE I
AR PREDICTS DIABETES IN THE
POPULATION.
HERE YOU CAN SEE CLEARLY AGES HO
40-49 MEN HAVE A FOURFOLD HIGHER
OF SLEEP APNEA AT AHI GREATER
THAN FIVE AND NARROWS AFTER
MENOPAUSE IN WOMEN IT GOES UP
FROM 4% TO 7% PREVALENCE AND THE
DIFFERENCES ARE MUCH MUCH
NARROWER.
AND MOST STUDIES EXAMINE SLEEP
APNEA AT ONE POINT.
MOST COHORT STUDIES SLEEP APNEA
ARE ABOUT AGE 60BO THEN LOOK
FOR THE DEVELOPMENT OF
CARDIOVASCULAR DISEASE AFTER
THAT INITIAL SLEEP STUDY.
USUALLY YOU HAVE FIVE OR EIGHT
YEARS OF FOLLOW UP.
IN FACT IN THE SLEEP STUDY WE
INITIALLY REPORTED NO FINDINGS
BETWEEN THE BASELINE SLEEP STUDY
AND OUTCOMES LIKEIK MORTALITY A
HEART DISEASE.
WOMEN ARE AT INCREASED RISK AS
THEY AGE WITH DEVELOPING
CARDIOVASCULAR IF YOU FOLLOW
THEM LONG ENOUGH.
AND AFTER 13 YEARS OF FOLLOW
UPWOMEN WERE 26% HIGHER THAN
THOSE WITHOUT SLEEP APNEA AND WE
DID NOT SEE IN THE MEN.
THEY HAD MARKERS OF SUB ELEVATED
CARDIOVASCULAR DISEASE AND
PROBABLY WERE EXPERIENCING
ADVERSE EXPOSURES CONTRIBUTING
TO HEART DISEASE THAT NEEDED TO
BE MEASURED OVER LONGER PERIOD
OF TIME AND THAT CONCEPTUAL
MODEL IS SHOWNE WHERE SLEEP EP
APNEA INCRTER IN LIFE
COURSE IN WOMEN THAN MEN AND
ONLY STUDY THEM FOR A FEW YEARS
TO LOOK AT RISK OF CLINICAL
OUTCOMES WE MAY UNDERESTIMATE
THEIR EFFECTS WITHOUT GATHERING
DATA COMPARED TO MEN WITH A
LONGER PERIOD OF TIME WHEN
STUDIED THEM.
I WANTED TO BRIEFLY MENTION WE
HAVE TO ASK OURSELVES WHY ARE
MEN AND WOMEN DIFFERENT?
OTHERS TALKED ABOUT HORMONAL
DIFFERENCES AND THERE'S CLEARLY
A LOT OF BIOLOGICAL DIFFERENCES
AND CAN'T UNDERESTIMATE OUR
SOCIAL ENVIRONMENT AN THERE'S A
COMBINED MODEL THAT EMPHASIZES
THE INFLUENCES OF INSTITUTIONS,
NEIGHBORHOODS, HOUSING,
INDIVIDUAL AND INTERPERSONAL
FACTORS THAT MAY ACUTE LIFE TIME
PHYSIOLOGICAL STRESSES AND
THOUGH THE MODEL HAS BEEN USED
FOR SLEEP APNEA WE HAVE NOT
ATTRIBUTED IS TO THIS AND
CORRELATING TO INFLAMMATION AND
LEADING TO ADVERSE OUTCOMES.
TO CONCLUDE THE AREAS I'D LIKE
TO EMPHASIZE IS THAT I THINK
THERE'S THIS OPPORTUNITY TO
INVESTIGATE THE SHORT EVENT, LOW
AROUSAL PHENOTYPE AND ITS IMPACT
ON DOWN STREAM PATHWAYS THAT MAY
ALLOW US TO ALSO INTERROGATE
MECHANISTIC PATHWAYS AND
LEVERAGE THESE SIMPLIFIED
ENDOTYPES AND SEVERITY METRICS
POTENTIALLY COMBINING THOSE WITH
OTHER DATA FOR EXAMPLE FROM
OMICS.
SECONDLY, VERY UNDER STUDIED IS
UP STREAM RISK FACTORS THAT MAY
INFLUENCE STRESS AND
INFLAMMATION AND CONTRIBUTE TO
HETEROGENEITY BY SEX AND RACE
AND GENDER.
AND FINALLY THE NEED TO APPLY
IMPROVED PHENOTYPE AND USING A
GENDER SPECIFIC LENS AND THAT'S
SHOWN WITH THE GOAL WHEN A
PATIENT COMES INTO CLINIC WE'LL
BE ABLE TO IDENTIFY THE FEMALE
SPECIFIC PS REM
DOMINANT, HYPOPNEA CENTRIC AND
THE LIFE COURSE EFFECT FOCUS AND
WITH CONSIDERATION OF GENDER
SPECIFIC SOCIAL SUPPORTED
BEHAVIORS VERSUS AN AIRWAY
THANK YOU VERY MUCH..
.NK YOU, SUSAN.
FASCINATING TO THINK NOT ALL
APNEA AND HYPOPNEAS ARE THE
SAME.
WE'LL AGAIN HAVE OUR QUESTIONS
AT THE END OF THE SESSION.
I'D LIKE TO INTRODUCE OUR NEXT
SPEAKER, DR. NICHA AURORA.
SHE'S THE ASSOCIATE PROFESSOR OF
MEDICINE AT THE RUTGERS ROBERT
WOOD JOHNSON MEDICAL SCHOOL.
HER PREPARATION IS TITLED OSA
AND MID LIFE NOT JUST FOR MEN
ANYMORE.
DR. NISHA AURORA, THANK YOU.
>> TO CLARIFY I'M ACTUALLY AT
NYU.
I MOVED ACROSS THE RIVER.
I'M IN THE MORE EXPENSIVE AREA
BUT I'M EXCITED TO BE HERE AND
BE A PART OF THE WORKSHOP AND
SIMILAR TO WHAT YOU'LL HEAR MY
BE A REPEAT BUT IT'S GOOD TO
REPEAT THINGS AND DRIVE THEM
HOME AND GET TO TALK ABOUT MY
FAVORITE GROUP OF PEOPLE WHICH
IS MIDDLE AGE WOMEN AND MEN.
I'LL GET STARTED.
I HAVE NO CONFLICTS OF INTEREST.
AND AGAIN THE OBJECTIVES FROM
WHAT I UNDERSTAND IS TO HELP US
IDENTIFY GAPS IN OPPORTUNITIES
THAT WILL ALLOW US TO ADVANCE
OUR UNDERSTANDING OF THE SEX
DIFFERENCE SCIENCE IN OSA AND
ALSO TO TARGET OUTCOME
IMPROVEMENT IN PATIENT
EXPERIENCE.
SO WE'LL KEEP THAT IN MIND AS WE
MOVE FORWARD.
SO, YOU'RE ALL FAMILIAR WITH THE
STATISTICS THAT CAME OUT IN 1993
INITIALLY THE INITIAL OSA
PREVALENCE ESTIMATES BEING 24%
IN MEN, 9% IN WOMEN.
THIS IS STRAIGHT FROM THE SLEEP
STUDY ITSELF.
WHEN YOU LOOKED AT THE GAP IT
SEEMED LARGE, THREE TO FIVE
VERSUS ONE IN THE GENERAL
POPULATION AND EIGHT TO TEN TO
ONE IN THE CLINICS.
SINCE THEN THERE'S BEEN A NUMBER
OF COHORT STUDIES SHOWING THE
PREVALENCE OF OSA IS HIGHER IN
WOMEN THAN WE PREVIOUSLY
THOUGHT.
AND THE GAP IS ACTUALLY NARROWER
THAN WE PREVIOUSLY THOUGHT.
AND YOU CAN SEE THE VARIOUS
PREVALENCE ESTIMATES ACROSS
DIFFERENT TYPES OF COHORTS AND
SOME OF THE VARIATION IN THIS IS
BECAUSE AGAIN THE WAY AHI
DEFINED AND DIRECT OBSERVATION
VERSUS STATISTICAL MODELLING.
AND OF COURSE AS HAS BEEN
DISCUSSED AND MENTIONED AND
WORTH REPEATING, WE'VE COME A
LONG WAY HOWEVER, THE FACT OF
THE MATTER IS THAT OSA CONTINUES
TO BE UNDERESTIMATED IN GENERAL
AND PARTICULARLY IN WOMEN.
AND SOME OF THAT HAS TO DO WITH
OUR CASE IDENTIFICATION.
YOU JUST SAW THESE SLIDES.
THIS LIST OF SYMPTOMS ON
DR. REDLINE'S SLIDE ABOUT HOW
MEN PRESENT AND IT'S DIFFERENT
FOR WOMEN AND THE ISSUE HAS BEEN
BECAUSE MEN WERE PRIMARILY THE
GENDER OR SEX THAT WERE STUDIED,
OUR SCREENING TOOLS HAVE
FOCUSSED ON THE SYMPTOMS OF MEN
AND THE SLEEPINESS SCALE HAS
WIDESPREAD USE FOR DETERMINING
PROPENSITY OF SLEEPINESS AND
ALSO HAS BEEN BY DEFAULTBYLT US
FOR OSA SCREENING IN PRIMARY
CARE CLINIC.
THE BOTTOM LINE IS WOMEN ARE
LESS LIKELY TO PRESENT WITH
SLEEPINESS AND HAVE OTHER
ATYPICAL SYMPTOMS.
THE EFFORT IS MORE LIKELY TO
DETECT SLEEPINESS IN MEN THAN
WOMEN AND STRONGLY CORRELATES
WITH ALL LEVELS OF OSA SEVERITY
IN MEN VERSUS WOMEN WHERE IT
ONLY CORRELATES WITH MODERATE TO
SEVERE OSA.
WHAT I THOUGHT WAS FASCINATING
IS THE STUDY THAT CAME OUT IN
2008 DEMONSTRATED ON MSLT, WOMEN
WERE SLEEPY OBJECTIVE BUT IT
JUST WAS NOT CAPTURED ON THE
SLEEPINESS SCALE.
THIS WAS PARTICULARLY TRUE IN
POST MENOPAUSAL WOMEN.
SO THERE ARE SEVEN SCREEN TOOLS
WE SHOULD CONSIDER.
THERE'S STOP BACK AND BERLIN
THAT ARE SPECIFIC FOR SLEEP
APNEA AND THE OTHERS WERE
CONSIDERED IN PREDICTING SLEEP
APNEA DID WELL IN PREDICTING
SLEEP APNEA WITH HIGHER
SENSITIVITY IN WOMEN AND IT WAS
AN INSOMNIA SCALE AND IN OUR
CURRENT SLEEP APNEA TRIALS
LOOKING AT MEN VERSUS WOMEN WE
ARE USING THE INSOMNIA SCALE AND
FATIGUE SEVERITY SCALE TO
UNDERSTAND THE SYMPTOMS IN
WOMEN.
WE SHOULD CONSIDER SCREENING
TOOLS MAYBE MODIFYING OUR TOOLS
A BIT AND NOT USING UNIFIED CUT
OFF THRESHOLDS THAT MAY HELP
IMPROVE ACCURACY IN GENERAL.
WE NEED TO PAY ATTENTION TO THE
SYMPTOM IN SLEEPINESS IN WOMEN
MORE AND MORE.
THIS PHENOTYPE HAS LONG BEEN
ASSOCIATED WITH MALE SEX AND
RELATED TO HEALTH RELATED
QUALITY OF LIFE, CARDIOVASCULAR
OUTCOMES, INFLAMMATION BUT IN
FACT THERE'S EMERGING DATA THAT
SHOWS EXCESSIVE DAYTIME
SLEEPINESS MAY BE ASSOCIATED
WITH WORSE MORBIDITY AND
MORTALITY IN WOMEN.
AND THIS WAS A STUDY THAT CAME
OUT LAST YEAR FROM THE MAYO
CLINIC, SOME OF MY GREAT
COLLEAGUES THAT BASICALLY SHOWED
IN ALMOST 15,000 PEOPLE WITH
OSA, THE HAZARDS RATIO, SIX
YEARS OUT FOR-TYPE II DIABETES
WAS EQUAL IN MEN AND WOMEN AND
ALL CAUSE MORTALITY WAS ONLY
ELEVATED IN WOMEN ON THE
SLEEPINESS SCALE AND S
THOUGHT PROTHO THINK ABOUT
AND HOW TO CAPTUREAP SLEEPINESS
PERT AND THIS CAN HAVE A BIGGER
IMPACT IN WOMEN.
WE'VE TALKED ABOUT PSG FINDINGS
AT THE LOW AHI AND OXYGEN AND
LESS NEUROMUSCULAR AND SEE MORE
POSITIONAL OSA.
THIS IS WHERE I THINK THE
OPPORTUNITY IS.
THAT IS TO REALLY SIT BACK AND
THINK AND WHAT ARE WE MISSING IN
THE HST?
I THINK THE ISSUE IS WE'RE NOT
CHARACTERIZING OBSTRUCTIVE
EVENTS WITH SLEEP ARCHITECTURE
AND THAT'S A PROBLEM IN WOMEN
WHERE WE SEE DIFFERENT
PRESENTATIONS.
WE HAVE TO THINK ABOUT DO WE
NEED TO GET GENDER SPECIFIC
ABOUT THE DIAGNOSIS FROM ONSET
OR DO MODIFIED PSG IN WOMEN THAT
INCLUDES AN EEG AND OTHER
PARAMETERS THAT MIGHT CAPTURE
SLEEP APNEA IN THEM BETTER.
MEN AND WOMEN ARE VERY DIFFERENT
AND WANT TO TURN OUR ATTENTION
TO A LITTLE BIT OF WHAT'S GOING
ON.
I KNOW YOU ALL KNOW THIS BUT
IT'S GOOD TO SIT BACK AND REVIEW
IT.
SO THERE'S BASIC ANATOMICAL
DIFFERENCES BETWEEN MEN AND
WOMEN.
WOMEN TEND TO HAVE A MORE STABLE
AIRWAY DURING SLEEP WHEREAS MEN
HAVE LONGER MORE COLLAPSABLE
AIRWAYS AND HAVE VERY DIFFERENT
FAT DISTRIBUTION.
WE ALSO KNOW MEN AND WOMEN ARE
VERY DIFFERENT IN TERMS OF THEIR
HORMONES.
IT'S NOT JUST ABOUT THE SPECIFIC
HORMONES, ESTROGEN AND
PROGESTERONE AND TESTOSTERONE
BUT THE VARIABILITY IN THE LIFE
SPAN.
I LIFE THIS COMPARISON BECAUSE
IT DRIVES IT HOME.
AT THE TOP YOU SEE WOMEN HAVE
VARIABILITY MONTH TO MONTH
PRE-MENOPAUSAL AND VARY DURING
PREGNANCY AND UP AND DOWN DURING
PERIMENOPAUSE AND SETTLE OUT IN
MENOPAUSE.
MEN ON THE OTHER HAND GO UP AT
AGE 16 AND STAY THERE.
IT'S VERY SIMPLE AND
STRAIGHTFORWARD.
WHAT'S BECAUSE OF THE VARIATION
AND THE UP AND DOWN IN WOMEN'S
HORMONES THAT'S IN SOME WAYS LED
TO US BEING LEFT OUT OF STUDIES.
IT'S TOO HARD TO STUDY TOO MUCH
OF A CHALLENGE BUT IN FACT I
THINK IT'S EXTREMELY INTERESTING
AND EXACTLY WHAT WE SHOULD BE
STUDYING.
WE SHOULD BE LOOKING AT THE
HORMONAL VARIATION AND
HETEROGENEITY OF HORMONES ACROSS
THE LIFE SPAN.
I THINK THAT WILL ADD A LOT TO
OUR UNDERSTANDING OF NOT JUST
SLEEP APNEA BUT THE OUTCOMES
ETCETERA.
THERE'S ESSENTIALLY THREE TO
FOUR STATES WITH HORMONAL
VARIATION ACROSS THE LIFE SPAN.
BEING MENOPAUSAL IS THE STATE
WITH THE LEAST RISK FOR SLEEP
APNEA AND POST MENOPAUSE IS THE
STATE OF MOST RISK FOR SLEEP
APNEA.
THIS IS RELATED TO THE FACT THAT
ESTROGEN AND PROGESTERONES ABATE
DURING MENOPAUSE.
THEY'RE IMPORTANT IN OTHER
EFFECT AGAINST OSA FROM THEIR
EFFECTS ON UPPER AIRWAY DILATOR
MUSCLES AND ANOTHER THING TO
THINK ABOUT IS ESTROGEN IS A
MAJOR ANTI-OXIDANT DEFENSE
SYSTEM AND OBSTRUCTIVE SLEEP
APNEA PRODUCES AN OXIDATIVE
STRESS ENVIRONMENT.
THE MEETING OF THESE TWO
CONDITIONS AND YOU HAVE MORE
HEIGHTENED OXIDATIVE STRESS IS
IMPORTANT AND NEEDS TO BE
THOUGHT ABOUT.
SO JUST TO SUMMARIZE THAT PART
WE KNOW MENOPAUSE IMPOSES A
SIGNIFICANT RISK FOR OBSTRUCTIVE
SLEEP APNEA.
THERE'S ALSO A REDUCTION IN WHAT
IS KNOWN AS LONG-TERM
FACILITATION OF UPPER AIRWAYS
AFTER MENOPAUSE.
WE CAN'T SEEM TO RECRUIT AS WELL
AND THE MUSCLES DON'T FUNCTION
AS WELL WHEN THERE'S A STRESS
AND THE UPPER AIRWAYS ARE
COLLAPSING.
IT DOESN'T HAVE THE SAME ABILITY
AS BEFORE.
I THINK ANOTHER AREA WE REALLY
NEED TO THINK ABOUT IS HOW TO
DISTINGUISH AGING AND BMI
EFFECTS AND WILL HELP UNDERSTAND
THE SEX DIFFERENCES THAT COME TO
BE.
LET'S MOVE ON TO WHAT WE SEE IN
TERMS OF CARDIO METABOLIC
OUTCOMES AND OSA AND GENDER AND
SEX ISSUES.
I WANT YOU ALL TO SEE THERE'S A
LOT OF WORK ONGOING AND
INCREASING OVER THE LAST TWO
DECADES THAT SHOWS THERE ARE
IMPORTANT SEX DIFFERENCES IN
TERMS OF OSA AND OUTCOMES
WHETHER IT'S ENDOTHELIAL
DYSFUNCTION, SUBCLINICAL
ATHEROSCLEROSIS OR DISEASE
SPECIFIC DIFFERENCES, CORONARY,
ARTERY, CALCIUM SCORES, THERE'S
A LOT OF DIFFERENCES AND WE
REALLY NEED TO FOCUS ON THESE.
THESE ARE SECONDARY EVENTS AS
WAS LAST YEAR.
HEART FAILURE ESPECIALLY
PRESERVES, EJECTION FRACTION
LATER FAILURE ARE IMPORTANT
DIFFERENCES ASSOCIATED WITH OSA
AND WE NEED TO THINK ABOUT AND
STRATIFY BY SEX.
IT TURNS OUT WOMEN PROBABLY HAVE
WORSE ENDOTHELIAL FUNCTION, ON
SUBCLINICAL ATHEROSCLEROSIS
TOWARDS CARDIOVASCULAR OR
METABOLIC DISEASE WITH OSA.
THERE WAS A NICE STUDY THAT
LOOKED AT DIFFERENT DISORDERS
AND OSA AND FOUND A LOT OF SEX
AND GENDER SPECIFIC DIFFERENCES
BETWEEN MEN AND WOMEN WITH OSA
WITH WOMEN HAVING MORE
HYPERTENSION, ISCHEMIC HEART
DISEASE AND DEPRESSION AND SEEMS
TO BE A HIGHER HEALTH CARE
UTILIZATION IN WOMEN WITH OSA.
I THINK A LOT OF IS ATTRIBUTED
TO THE FACT THEY HAVE ATYPICAL
SYMPTOMS.
IN MY OWN CLINIC THEY GO TO
SEVERAL DIFFERENT DOCTORS BEFORE
THEY END UP GETTING DIAGNOSED.
THESE ARE IMPORTANT THINGS TO
THINK ABOUT.
WHERE WE ARE REALLY LACKING IS
THERAPY.
THIS IS AN AREA I THINK A BIG
OPPORTUNITY FOR US TO REALLY
PROGRESS THE FIELD.
WHAT WE DO KNOW IS THAT
TREATMENT IS DELAYED IN WOMEN
COMPARED TO MEN AND MAY HAVE TO
DO WITH THE FACT THE DIAGNOSIS
IS DELAYED.
THERE'S PRESSURE REQUIREMENTS
THAT ARE LOWER.
AND ORAL APPLIANCES TEND TO BE
MORE EFFECTIVE IN WOMEN BUT
THESE ARE SMALL STUDIES, S
POPULATIONS, MODEST SAMPLE
SIZES.
AND THE THINGS I THINK WE NEED
TO CONSIDER GOING FORWARD, ONE
IS DOES THE DURATION NEED TO BE
LONGER AND NOT JUST USE THE
MEDICARE CUT-OFF CRITERIA TO SEE
THE REM WE'RE SEEING MORE IN
WOMEN AND WHAT ABOUT HRT?
IT'S BECOMING MORE AND MORE
COMMONLY USED THESE DAYS.
IT SEEMS TO BE A TREND AND I'M
SEEING A LOT OF THAT IN MY
CLINICS AS WELL.
AND COMISA AND THINK OF
CO-TREATMENT OF THE INSOMNIA
TREATMENT IN WOMEN WITH COMISA
AND WITH WEIGHT MANAGEMENT
THERE'S SEX DIFFERENCES.
GLP1 AND WE SAW THE STUDY WITH
HOW SLEEP APNEA IMPROVES AND
THERE'S SEX DIFFERENCES EVEN
WITH GLP1 RECEPTOR AGONIST WITH
WOMEN TYPICALLY LOSING MORE THAN
THE MEN.
WHAT WAS NEW TO ME WAS THE FACT
THAT THAT WEIGHT LOSS ACTUALLY
DROPS OFF IN WOMEN IN THEIR
LATER MOST MENOPAUSAL YEARS
AFTER THE AGE OF ABOUT 65 THE
WEIGHT LOSS REALLY SLOWS DOWN.
YOU MAY NOT SEE THE SAME EFFECT
IN WOMEN AGE 65 AND BEYOND.
>> WE HAVE PROBABLY ONE TO TWO
MINUTES, PLEASE.
>> GOT IT.
I'LL RUN THROUGH THIS QUICKLY.
OUTCOMES WITH PAP THERAPY OR
TREATMENT, THIS IS A VERY NICE
STUDY FROM 2012 OVER 1,000
WOMEN.
CPAP HELPS FOR BOTH GROUPS.
THIS IS OUR OWN STUDY
DR. DRPUNJABI AND I WAB FORTUNAE
ENOUGH TO DO TO LOOK AT GLYCEMIC
VARIABILITY IN MEN AND WOMEN
WITH SLEEP APNEA AND TYPE II
DIABETES AND THERE WAS ALMOST AN
EQUAL SPLIT OF MEN AND WOMEN AND
WE SAW WOMEN SEEMED TO RESPOND
TO THREE MONTHS OF PAP THERAPY
IN TERMS OF STANDARD DEVIATION
AND THE MEN DIDN'T.
AND GLUCOSE LEVELS IS
INTERESTING AND SPURRED MY
INTEREST IN SEX-SPECIFIC
DIFFERENCES IN OSA AND OUTCOMES.
THESE ARE THE BIG C PAP RCT
TRIALS THAT HAVE COME OUT IN THE
LAST TWO DECADE.
YOU CAN SEE THE PERCENTAGE OF
WOMEN IN THIS IS KIND OF
EMBARRASSING ALMOST.
THE MOST IS MAYBE A THIRD.
I SHARED THIS WITH WOMEN FROM MY
STUDY AND THEY'RE ALWAYS AMAZED.
THEY GET SO EXCITED ABOUT
PARTICIPATING IN TRIALS AND
CHANGING THESE NUMBERS.
I THINK THAT IS WHERE WE CAN
TRULY, TRULY MAKE A DIFFERENCE
AND MOVE THE FIELD FORWARD IS
GETTING MORE WOMEN EXCITED ABOUT
PARTICIPATING IN OUR STUDIES.
SO WITH THAT I'M GOING TO STOP.
I'LL GIVE IT BACK TO YOU.
>> YOUR LAST SLIDE IS INCREDIBLY
IMPACTFUL.
I LIKE THE NO DATA COLUMN IN
WOMEN.
MY APOLOGIES AGAIN FOR YOUR
AFFILIATION OBVIOUSLY RUTGER'S
LOSS AND NYU'S GAIN, THANK YOU.
FOR THOSE ON THE CALL OR IN THE
WEBCAST IN PREPARATION FOR THE
QUESTION AND ANSWER SESSION
WHICH WE WILL HAVE AFTER OUR
NEXT SPEAKER, IF YOU HAVE A
QUESTION, YOU CAN PLACE IT INTO
THE Q&A BOX.
PLEASE DON'T USE THE CHAT.
PLEASE PUT THEM IN THE Q&A BOX
YOU'LL ALSO SEE.
SO IF YOU'RE STARTING TO THINK
OF QUESTIONS FOR THE NEXT
SESSION, YOU CAN START PUTTING
THOSE IN.
LET ME INTRODUCE OUR SESSION'S
LAST SPEAKER DR. PAUL MACEY.
PROFESSOR AND DIRECTOR THE THE
UCLA SCHOOL OF NURSING.
HIS PRESENTATION IS TITLED SEX
GENDER DIFFERENCES IN COGNITION
IN MIDDLE AGE AND OLDER ADULTS
WITH OSAs.
WE'RE MOVING RIGHT DOWN THE AGE
SPECTRUM.
IF YOU'RE ABLE TO SHARE YOUR
SLIDES, PLEASE.
ING
>> IT'S BEEN GREAT HEARING THE
TALKS TODAY.
SO, THIS IS A FEW MINUTES TO
THINK ABOUT COGNITION AND HOW
THAT VARIES AND REALLY WHAT DO
WE THINK OF IN COGNITION?
WE CAN SAY MEMORY, ATTENTION,
EXECUTIVE FUNCTION, PROCESSING
FIELD.
THE FIELD OF COGNITION IS E
ENORM
ENORMOUS.
I FIND IT INTERESTING TALKING TO
PATIENTS WHO COME AND JOIN OUR
STUDIES AND THE THINGS THEY TALK
ABOUT A LOT IS RELATED TO
COGNITION.
92% OF WOMEN TALK ABOUT
DIFFICULTIES AT WORK.
IT INCLUDES THINKING AND BEING
ON TOP OF THINGS SO COGNITION IS
AN IMPORTANT OUTCOME TO MANY
PATIENTS.
I'LL GO INTO SOME DETAILS BUT
THERE'S MANY STUDIES THAT LOOK
AT COGNITION.
THERE'S NOT A LOT OF CONSISTENT
MEASURES.
AND THERE'S IMIN MEN THERE'S
MORE DECLINE IN EXECUTIVE
FUNCTION AND VERBAL MEMORY AND
WOMEN MAY EXPERIENCE MORE BLOW
NOUNCED EFFECTS ATTENTION AND
VERBAL MEMORY AND CERTAINLY WITH
AGE THIS IS COMPOUND WITH SLEEP
APNEA AND SEX BUT WE HAVE
STUDIES SHOWING HIGHER SEVERITY
IN SLEEP APNEA ASSOCIATED WITH
WORSE PERFORMANCE EVEN WITH THE
AHI WHICH IS NOT AN AGREE
MEASURE AS WE'VE HEARD.
IN TERMS OF INTERACTIONS, OVER
TIME MEN MAY SHOW GREATER AGE
RELATED AFFECTS WITH THE SLEEP
APNEA AND WOMEN SHOWING MORE
GENERAL PATTERNS.
THERE'S A LOT OF VARIABILITY
HERE.
IS THIS IS AN EXAMPLE.
THERE'S HUNDREDS OF STUDIES
WHERE SOMEONE GOES AND DOES A
TEST.
THIS IS SOMETHING WE DO A SHORT
MEMORY TEST.
IT'S NOT REALLY DESIGN FOR
GENERAL COGNITIVE PERFORMANCE
BUT IT IS USED BECAUSE IT ONLY
TAKES A FEW MINUTES OPPOSED TO
SEVERAL HOURS AS A COGNITIVE
TEST.
THERE'S A COUPLE OF AREAS THAT
SHOW UP AS DELAYED RECALL AND
ATTENTION AS IMPACTED AND THEN
WE SEE WHEN WE SEPARATE OUT WE
SHOULD BE SEPARATING OUT WOMEN
FROM MEN AND WOMEN HAVE A LOWER
DELAYED RECALL.
AND IT'S LIKE LOWER.
IT'S NOT HUGE AND THERE'S MANY
STUDIES THAT WILL SHOW SOME
EFFECTS AND -- I DID PULL OUT
THIS RECENT ONE THAT LOOKED AT A
LARGE NUMBER AND TO LOOK AT
WELL, WHEN WE LOOK AT THE LIVE
SCAN WHAT CAN WE SEE?
THIS IS LOOKING AT 250,000
PEOPLE AND WHAT THEY FIND IN
FEMALES ARE SAYING THERE'S HIGH
RISK OF PRELIMIDEALING WITH NOV
SITUATIONS, SHORT MEMORY AND IF
YOU LOOK AT THE EFFECT SIZES AND
THE SIGNIFICANCE YOU SEE THOUGH
THERE'S SIGNIFICANCE
STATISTICALLY IT'S ONLY THIS ONE
THAT STAND OUT CONTROLLING FOR
FACTORS AND WITH MALES NOT A
STRONG ASSOCIATION BETWEEN SLEEP
APNEA AND IMPAIRMENT.
IT'S A LITTLE BIT SURPRISING BUT
IT MAY BE BECAUSE OF THE BIG
HETEROGENEITY AND THE COGNITION.
WHY MIGHT BE THE SEX DIFFERENCES
WE SEE?
THE AUTOMATIC THING I HEAR ARE
HORMONAL DIFFERENCES AND WE
HEARD ABOUT THE PATHOPHYSIOLOGY
AND I LOOK AT THE BRAIN AND THE
DIFFERENT DISEASE
CHARACTERISTICS BETWEEN MEN AND
WOMEN WOULD IT RELATE TO
COGNITION.
THIS IS MY AREA AND WE REPRESENT
IN GRAY AREAS THAT SHOW A
DIFFERENCE.
WHAT I'VE PUT IS TWO PANELS.
SO THIS IS THREE ANGLES AND THE
GRAY AREAS ARE A SIGN WHERE THE
BRAIN IS REDUCING LIKE GETTING
SLIGHT THINNER AND SMALLER AND
ON SHOWING THE ABLE AND THE
AFFECT OF SLEEP APNEA.
BASICALLY I THINK AN IMPORTANT
MESSAGE IS ONE, WE CAN SEE THE
BRAIN IS AFFECTED IN SLEEP APNEA
AND THE SLIDE IT WAS EARLY ON
BUT MAYBE THE EFFECT IS SIMILAR
IT AGE.
THE IDEA THAT AGE MIGHT -- WE'RE
NOT SEEING A MASSIVE IMPACT IN
THE BRAIN SOME CHANGE AND SOME
PEOPLE TALK ABOUT OSA
EXACERBATING AGING EFFECTS.
WHEN WE THINK OF COGNITION WE
THINK OF THE HIPPOCAMPUS AND WE
DID A HYPOTHESIS GENERATING
STUDY THAT DID SHOW IN A SMALL
NUMBER OF PEOPLE THERE WERE
CHANGES IN THE HIPPOCAMPUS AND
THIS IS HOW ITS REPRESENTED THE
COLOR ON THE BACKGROUND
REPRESENTING AREAS WHERE THERE'S
A SMALLER HIPPOCAMPUS THAN OTHER
AREAS.
AND A COUPLE MORE STUDIES.
THERE WAS A COLLABORATION
BETWEEN EUROPEAN AND AUSTRALIAN
GROUP WHERE THEY LOOKED AT
POSTMORTEM PEOPLE AND THE
OUTLINES ARE OF THE HIPPOCAMPUS
AND THIS UPSIDE-DOWN HOOK SHAPE
SHOWED PEOPLE WITH SLEEP APNEA
HAD A SMALLER HIPPOCAMPUS AND A
FOUND A RECENT STUDY USING A
EUROPEAN DATA BANK LOOKING AT A
LARGER NUMBER OF SLEEP APNEA
PATIENTS OVER 20,000.
AND WHAT'S INTERESTING IS THEY
FOUND THIS EFFECT ON THE
HIPPOCAMPUS AND IT'S A
STATISTICAL NUMBER BUT IT'S 34
WHEREAS ALL THE OTHER AREAS WERE
13, 9, 8, 7.
IN THE LARGE STUDY IT SHOWED A
DIFFERENCE IN THE HIPPOCAMPUS.
IF I COULD DO A FACE SLAP EMOJI
I WOULD BECAUSE THERE'S NO
DIFFERENCE HERE IN THESE STUDIES
AND WE LOOKED AT A LARGER COHORT
AND LOOKED AT JUST THE
HIPPOCAMPUS.
IT WAS UNDER 100 SLEEP APNEA
SUBJECTS AND COMPARED IT TO 900
CONTROLS.
THIS IS THE SHAPE OF THE
HIPPOCAMPUS AND THE COLORED
AREAS SHOWED WHERE THERE'S A
CHANGE IN THE HIPPOCAMPUS.
WHEN WE FIRST LOOK AT IT
COMBINED WE SEE THESE
COROLLARIES ON THE LEFT IS A
FEW.
WHEN WE SEPARATE IT OUT AND SAID
WELL, LET'S JUST LOOK AT THE
HEALTHY NON ASSIGNED FEMALES
THAT HAVE THE CONDITION.
WHAT STANDS OUT IS MORE COLORED
AREAS.
THAT MEANS WE SEE -- WE ARE
SENSITIVE TO THE EFFECT OF SLEEP
APNEA HAPPENING SPECIFICALLY IN
THE FEMALES.
SO THIS WAS VERY STRIKING TO US.
IT'S LIKE IF YOU LOOK AT THE
BRAIN YOU DON'T SEE THE FULL
EFFECT BUT IF YOU ASK THE
QUESTION WHAT HAPPENS IN WOMEN
AND MEN YOU DETECT MORE GOING ON
AND SIMILAR WITH MALES.
SO, WE FOUND THERE WAS NO
SIGNIFICANT EFFECT BRAIN
STRUCTURE AND COGNITIVE
PERFORMANCE AND THEY'RE SAYING
MAYBE THERE'S NOT MUCH
DIFFERENCE.
ONE THING WE CAN TAKE FROM THIS
IS WHILE IT'S NICE TO SEE THE
HIPPOCAMPAL DIFFERENCE IT'S NOT
THE CAUSE OF COGNITIVE SYMPTOMS.
SO WHAT ABOUT TREATMENT?
THIS IS ONE STUDY HIGHLIGHTED IN
GREEN THE VALUES THAT SHOW A
SIGNIFICANT IMPACT FOR SIX
MONTHS OF C PAP TREATMENT IN
DIFFERENT COGNITIVE AREAS.
AND WHAT ABOUT OTHER TREATMENTS?
WELL, WHAT ABOUT HORMONES?
AGAIN, THIS IS SORT OF THE
AUTOMATIC RESPONSE, WHAT HAPPENS
WITH TESTOSTERONE AND IS THERE
LINK OUTSIDE OF OSA.
MAYBE IT CAN HELP MEN WITH LOW
TESTOSTERONE.
COGNITION IS NOT IMPACTED.
HRT, THERE MAY BE A DIRECTION
TOWARDS IMPROVEMENT BUT NOT AN
IMPACT AND WHAT'S INTERESTING
AND A THOUGHT EXPERIMENT IS WHAT
HAPPENS WHEN YOU GIVE HORMONES
AND TESTOSTERONE FOR FEMALES AT
BIRTH META-ANALYSIS SHOWS IT
LEANS TO THE RIGHT AND VISUAL
SPATIAL IMPROVES SLIGHTLY TO
MAYBE TESTOSTERONE IS RELATED TO
THIS SEX SPECIFIC DIFFERENCE BUT
THEN IF WE LOOK AT ESTROGEN AND
FEMALE HORMONES GIVEN TO MALE
ASSIGNED AT BIRTH WE SEE AN
IMPROVEMENT.
IT'S NOT LIKE A CORRELATED
EFFECT.
SO THE TAKE HOME IS THEY HAVE AN
IMPACT ON SLEEP APNEA AND IT'S
NOT ONE DIRECTION SO IT'S NOT A
SIMPLE ANSWER.
AGAIN WE LOOK AMOUNT WHAT DO
PEOPLE TALK ABOUT?
THERE'S THE COGNITIVE ISSUES AND
SLEEPINESS AND FOGGINESS AND
DIFFICULTY AND DISTRESS.
MANY SHOW COGNITION IS IMPAIRED
BY STRESS.
WE ALSO KNOW SLEEP CAN CAUSE
AFFECT AND IF THAT WAS TRUE THEN
WHAT WE SEE IN THE SAME
AUSTRALIAN STUDY WE SEE BIG
DROPS IN STRESS AND WHEN WE LOOK
AT THE EFFECT SIZES OF COGNITION
THEY'RE NOT VERY BIG.
IN OTHER WORDS, YES, WE IMPROVED
FROM REDUCED STRESS BUT DON'T
GET A LOT OF DIFFERENCE IN
COGNITION SO PROBABLY NOT A
LARGE IMPACT THERE.
SO THEN THE LAST PLACE I WANT TO
GO WITH THIS IS WHAT MIGHT HELP
AND THIS IS REALLY THINKING
AHEAD.
CPAP IS NOT CONSISTENT BY PERSON
THE IDEA OF STRESS REDUCTION
AGAIN MIGHT VARY BY PERSON BUT
NOT A CAUSAL RANK AND HORMONES
PROBABLY NOT AND IF WE CONSIDER
THE IDEA OF AN INDIVIDUAL WITHIN
THEIR ENVIRONMENT AND WE LOOK AT
WHAT HELPS OUTSIDE OF SLEEP
APNEA THERE'S A WHOLE LIST.
AND PHYSICAL ACTIVITY, COGNITIVE
DECLINE IS TWICE AS MUCH IN
ACTIVE VERSUS ACTIVE ADULTS AND
AND TIME OUTDOORS INCREASES
COGNITION SIMILAR TO EXERCISE.
GETTING US TO THINK OUST BEYOND
THE SLEEP COGNITION.
AND IS IT GOING TO HELP IN OSA.
FOOD FOR THOUGHT I HOPE.
>> THANK YOU, DR. MACEY.
A COUPLE HOUSEKEEPING, AS NOT
COMMON IN THESE THINGS WE'RE
RUNNING A LITTLE BIT BEHIND AND
HAVE QUESTIONS FOR THE PANEL FOR
THE NEXT EIGHT MINUTES AND HAVE
A TEN INSTEAD OF 15 MINUTE
BREAK.
SOME SPEAKERS HAVE HAD TO LEAVE
AND SO I THINK I'LL SPEAK FOR
ALL OF THEM WHEN SAYING IF ANY
OF OF YOU HAVE QUESTIONS, YOU
COULD DIRECT THEM TO THE
SPEAKERS' E-MAIL FOR A QUESTION
OFFLINE.
I ALSO WANT TO INTRODUCE FIVE
DISCUSSANTS WE'VE INVITED FOR
FIVE DAYS OF THE WORKSHOP I WANT
TO THANK PATRICK, MIJI, HAMIDI
AND DIEGO AND OTHERS FOR THEIR
CONTRIBUTIONS AS WELL.
THERE'S QUESTIONS IN THE
QUESTION AND ANSWER.
I WOULD LIKE TO ASK THE FIRST
QUESTION WHICH COMES FROM DIEGO
BUT I THINK FROM A COUPLE PEOPLE
AND I'LL ASK DR. MACEY AND MAYBE
DR. ISAIAH BUT I THINK ONE THING
THAT'S BEEN BROUGHT UP IS THE
DISRUPTION OF SLEEP APNEA.
IF YOU'VE HAD IT FROM CHILDHOOD
WHAT'S THE IMPACT ON COGNITION.
DR. MACEY CAN YOU CONTROL FOR
HOW LONG SOMEONE'S HAD SLEEP
APNEA.
AS WE THINK OF WOMEN WHO MAYBE
HAVE LESS SLEEP APNEA UNTIL
MENOPAUSE IS THAT TIME VARIABLE
DIFFERENT BETWEEN MEN AND WOMEN
AND THE LONGER TERM IMPACTS.
MAYBE DR. MACEY FIRST AND THEN
DR. ISAIAH, THOUGHTS FROM
CHILDHOOD AS WELL.
GOOD MY THOUGHT THAT COMES TO
MIND IS FIRST ON THE COGNITION
SIDE THERE'S SO MANY WAYS TO
MEASURE AND MOOSHGERS AND
MEASURES THAT WE HEARD IN THE
FIRST TALKS.
-- MARKERS AND MEASURES WE HEARD
IN THE FIRST TALKS.
IF YOU DON'T SLEEP WELL THERE'S
AN IMMEDIATE IMPACT, THAT'S
GOING TO AFFECT YOUR PERFORMANCE
THE NEXT DAY.
NOW, THEN THERE'S THE QUESTION
OF SOMETHING DETERIORATING AND I
SHOWED PICTURES OF CHANGES IN
THE BRAIN AND OTHER PEOPLE HAVE
SHOWN THAT TOO.
SO THE CONCERN THERE WOULD BE
MAYBE THERE'S SOMETHING THAT'S
CAUSING A LOT OF DAMAGE AND
AFFECTS FUNCTION OVER TIME.
I WISH I WOULD MORE DEFINITE BUT
AND EXERCISING OUTDOORS WILL IT
HAVE A THREE OR FOURFOLD
IMPROVEMENT IN YOUR COGNITION?
WHAT WOULD IT DO IF WE MEASURED
COGNITION AND SLEEP APNEA AND
WOULD IT MATTER HOW LONG YOU HAD
SLEEP APNEA.
TO WHAT DEGREE CAN YOU RECOVER
BACK AND CERTAINLY ANECDOTALLY
AND I LOVE THE TALK ABOUT THE
NFA YOU GAVE WITH THE MALE WHO
COMES IN AT AGE 60 AND STARTS
USING C PAP AND FEELS 20 YEARS
YOUNGER AND SUDDENLY THEY
REALIZE IT WAS JUST SLEEP APNEA
AND WOULD NEVER HAVE A NIGHT
WITHOUT C PAP.
THAT PERSON SO MUCH HAS BEEN
RECOVERED IT MAKES US THINK EVEN
IF THEY HAD 20 YEARS OF SLEEP
APNEA A LOT COULD COME BACK.
>> LET ME JUMPING IN THERE.
IT'S INTERESTING AND IN THE CHAT
WHAT'S REVERSIBLE OR NOT?
MANY WERE DISAPPOINTED BY THE
SAVE TRIALS RESULT BUT IF YOU'RE
TRYING TO AFFECT PATHWAYS THERE
FOR 10 YEARS AND HAVE CORONARY
ARTERY DISEASE CAN YOU REVERSE
THAT OR NOT?
AND TWO QUESTIONS LINKED,
DR. ISAIAH, YOU MENTION THE
BOTTLENECKS OF TESTING.
IS THERE AN URGENCY LIKE I NEED
TO FIX THIS NOW BECAUSE OF BRAIN
DEVELOPMENT OR FUNCTION AT
SCHOOL AND BEHAVIORAL THINGS AND
ALSO THERE'S BEEN A COUPLE
QUESTIONS ABOUT WHAT'S YOUR TAKE
ON NON-TRADITIONAL FORMS OF
TESTING FOR CHILDREN I THINK
THAT WOULD BE A THEME FOR ALL OF
US HERE AS WELL.
>> THANK YOU FOR THOSE
QUESTIONS.
THEY'RE VERY INTERESTING ONES
AND ONES I GRAPPLE WITH EVERY
DAY.
I'D LIKE TO CITE DR. REDLINE'S
WORK AND UNDERSTANDING AS FAR AS
COGNITION'S CONCERNED BASED ON
THE RESULT FROM CHAT AND PATS
WHAT WE KNOW SO FAR IS
SUPPORTIVE CARE IS A BIG BUCKET
FROM THE REAL WORLD ENVIRONMENT
AND KIDS WHO MAY BE PUT ON
INTRANASAL CORTICOIDS AND THE
CAVEAT IS OVER SEVEN MONTHS IN
THE CHAT STUDY THOR -- OR THE
PAT STUDY, DR. REDLIN CAN TALK
ABOUT IT MORE BUT WE'VE SEEN
CHILDREN AND THOSE WHO SNORE HAD
PERSISTENT PROBLEM BEHAVIORS BUT
THE COGNITION DOESN'T APPEAR TO
WORSEN OVER TIME.
WHILE IT'S REASSURING IN SOME
WAYS, THERE'S ALSO THE QUESTIONS
REGARDING OKAY WE'RE DOING THAT
DURING A PERIOD OF BRAIN
PLASTICITY.
KIDS BELOW THE AGE OF 4 THE
BRAIN IS STILL DEVELOPING AND
CAN SURVIVE HYPOXIC INSULTS AND
SAME WITH KIDS IN ADOLESCENCE
AND IT SETS THE TONE FOR
NATURALISTIC STUDIES BECAUSE
PREVIOUSLY THERE WAS A POINT OF
TIME I REMEMBER IN TRAINING WE'D
RUSH THESE KIDS TO SURGERY
SOMETIMES EVEN DO TRACHEOSTOMIES
WITH KIDS AND NOW WE KNOW IT
DOESN'T APPEAR TO AT LEAST FROM
OUR DATA SETS QUALITY OF LIFE IS
IMPAIRED AND COGNITION IS
SOMEWHAT WELL PROTECTED.
MAYBE THERE'S VULNERABLE GROUPS
THAT NEED TO ACCESS THOSE
PROTECTIVE FACTORS.
OVER ALL I THINK WE HAVE
ADDITIONAL INFORMATION IN RECENT
TIMES FROM THESE RANDOMIZED
CONTROL TRIALS AS WELL AS
OBSERVATIONAL STUDIES TO SAY IT
MAY NOT BE COGNITION BUT
DEFINITELY BEHAVIOR AND QUALITY
OF LIFE AND OTHER SUBJECTIVE
FACTORS MAY BE THE MOST
IMPACTED.
>> THANK YOU.
I THINK WE HAVE JUST TIME FOR
ONE MORE QUESTION.
NAJIM YOU HAVE YOUR HAND UP.
>> THANK YOU FOR NARESH'S
COMMENT AS WELL AND IN THINKING
ABOUT HETEROGENEITY ARE SOME
OUTCOMES NOT REVERSIBLE WHERE
YOU GET TO THE INADVERTENT
HYPOXIA THE OBJECTIVE FUNCTION
MAY NOT GET MUCH BETTER AND PART
OF THE HETEROGENEITY TRYING TO
FIGURE OUT WHICH PATIENTS YOU
WOULD BE MORE LIKELY TO RESPOND
FROM AN OUTCOME STANDPOINT BY
TREATING IT BECAUSE IT'S
POSSIBLE IT'S TOO LATE AND WITH
ILB THERE'S CT AND FIBROSIS AND
IN GIVING THE PERSON STEROIDS
BUT THEY'LL PROBABLY DO BETTER
AND WONDERING WHETHER THERE'S
SOMETHING SIMILAR WITH THESE
PATIENTS AS WELL.
I WANTED TO MAKE A POINT WITH A
QUESTION, IS GUESS.
>> HOPEFULLY THAT WILL BE PART
OF IT AS WELL.
WELL, THANK YOU ALL.
I DID CONFIRM THE CHAT WILL LIVE
ON IN ETERNITY.
I THINK THERE'S ROBUST
DISCUSSION IT'S OVERWHELMING TO
HAVE THE CHAT AND Q&A AND TALK
TO EVERYBODY BUT IF YOU WOULD
LIKE TO PUT SOME THOUGHTS IN THE
CHAT IT WILL BE THERE AND AGAIN
AS WE GO FORWARD TODAY I HOPE
WE'RE ABLE TO PRESERVE TIME FOR
GREAT CHAT.
BUT THANK YOU TO ALL OF OUR
SPEAKERS IN SESSION ONE AND TAKE
A SHORT BREAK AND BE BACK IN
ABOUT EIGHT MINUTES OR SO IF
WE'RE STICKING SO THE ORIGINAL
TIME SCHEDULE.
I'LL LEAVE THAT TO ALFONSO AND
MARISHKA.
>> WE'RE STICKING TO THE
ORIGINAL SCHEDULE SO EIGHT
MINUTES.
>> RECONVENE AT 1:50 EAST COAST TIME. THANK YOU.
I'LL BE MO MODERATING
SESSION 2 MANIFESTATIONS OF OSA
IN PREGNANCY AND MENOPAUSE AND
HAVE THREE SPEAKERS AND EACH
SPEAKER WILL HAVE UP TO 15
MINUTES TO PRESENT.
I'LL PROBABLY INTERJECT WHEN YOU
HAVE TWO MINUTES LEFT.
OUR FIRST SPEAKER IS FRANCESCO
FACCO AT THE UNIVERSITY OF
PITTSBURGH.
PER PRESENTATION IS TITLED SLEEP
APNEA IN PREGNANCY A BRIEF
REVIEW OF CURRENT KNOWLEDGE AND
INTRODUCTIONS TO THE NICHD
MATERNAL FETAL MEDICINE UNIT
NETWORKS SLEEP TRIAL.
DR. FACCO OVER TO YOU NOW.
>> I'M HAPPY TO PRESENT THE
REGARDING SLEEP APNEA IN
PREGNANCY AND INTRODUCE THE
SLEEP TRIAL I'M INVOLVED WITH.
I HAVE NO CONFLICTS OR
DISCLOSURES
IT'S NICE TO REVIEW A CAUSAL
DIAGRAM WHERE A STUDY IN SLEEP
APNEA IN PREGNANCY IS IMPORTANT.
WE KNOW WOMEN CAN COME INTO
PREGNANCY ALREADY WITH
PREEXISTING SLEEP ISSUES LIKE
SLEEP APNEA.
BUT WE ALSO KNOW THE
PATHOPHYSIOLOGIC CHANGES OF
PREGNANCY CAN EXACERBATE THE
SEASON OR CAUSE A NEW ONSET OF
SLEEP CONDITIONS ESPECIALLY
WEIGHT GAIN AS IT PERTAINS TO
SLEEP APNEA.
WE'RE ALL FAMILIAR WITH THE
IMPACT SLEEP APNEA HAS ON REST
FRAGMENTATION AND RESPIRATORY
PATTERNS AND THE CHANGES HAVE
BEEN WELL STUDIED OUTSIDE OF
PREGNANCY AND SHOWN TO BE
ASSOCIATED WITH DYSREGULATION OF
APPETITE AND DERANGEMENTED IN
THE HPA ACCESS AND INCREASE TO
SHIFT TO SYMPATHETIC ACTIVITY AT
NIGHT AND STRESS AND SYSTEMIC
INFLAMMATION.
IN PREGNANCY WE KNOW THESE
PATHWAYS THAT HAVE BEEN
ASSOCIATED WITH SLEEP APNEA HAVE
ALSO BEEN LINKED TO ADVERSE
PREGNANCY OUTCOMES.
NOTABLY TO GLUCOSE DYSFUNCTION
AND METABOLIC DYSFUNCTION AND
GESTATIONAL DIABETES AND
ABNORMALITIES THAT INCREASE THE
RISK OF PREECLAMPSIA.
SOME OF THE MOST COMPLETE DATA
COMES FROM THE NEW MOM TO BE
COHORT.
IT WAS WOMEN FOLLOWED
PROSPECTIVELY ACROSS PREGNANCY
AND HAD VISITED IN THE FIRST
TRIMESTER IN THE EARLY SECOND
TRIMESTER AND THEN THE LATE
SECOND AND EARLY THIRD
TRIMESTER.
AS PART OF THIS COHORT SLEEP
DATA WAS COLLECTED.
A VARIETY OF SLEEP MEASURES WERE
USED BUT IN PARTICULAR AT VISIT
ONE AND THREE THERE WAS HOME
SLEEP TESTING IN WHAT WAS CALLED
THE SLEEP DISORDER BREATHING
STUDY OF THIS NEW MOM TO BE
COHORT.
IN THIS COHORT WE RECRUITED OVER
3700 WOMEN AND HAD COMPLETE
SLEEP TESTING RESULTS IN EITHER
EARLY OR OR MID PREGNANCY FOR
ABOUT 3500 WOMEN ADEQUATE DATA
FOR ONE OR BOTH STUDIES IN ABOUT
3300 WOMEN WHO PARTICIPATED IN
THIS SUB STUDY.
WHAT WE FOUND THE PREVALENCE IN
SLEEP APNEA AND AHI GREATER TO 5
IN THE STUDY WAS ABOUT 3% IN
EARLY PREGNANCY 3.5% AND ABOUT
8% IN MID PREGNANCY.
AND THE VAST MAJORITY OF THE
CASES OF SLEEP APNEA BOTH IN
EARLY AND IN MID PREGNANCY WERE
NOTED TO BE MILD.
WHEN WE LOOKED PARTICULARLY AT
THE PREVALENCE IN OTHER HIGHER
RISK SUB GROUPS IN THIS COHORT,
WE DID FIND SNORERS WITH OBESITY
HAD A 20% AND THE MAJORITY HAD
MILD SLEEP APNEA.
IN THIS STUDY THE PARTICIPANTS
AND PROVIDERS WERE ALL BLINDED
TO THE SLEEP APNEA RESULTS
UNLESS SEVERE SLEEP APNEA OR
HYPOXEMIA WERE ALERTED AND THERE
WERE PROTOCOLS IN PLACE FOR
THOSE SETTINGS.
THIS ALLOWED US TO LOOK
CAREFULLY AT HOW SLEEP APNEA IN
PREGNANCY MAY IMPACT ADVERSE
PREGNANCY OUTCOMES IN THIS
COHORT THAT WE HAD GOOD
OBJECTIVE SLEEP APNEA DATA
BLINDED TO PARTICIPANTS AN
PROVIDERS AND IN THIS SLIDE WE
LOOK AT THE RATE OF PREECLAMPSIA
IN BLUE AND THOSE WITH OSA IN
YELLOW.
YOU CAN SEE THE RATE OF
PREECLAMPSIA WAS HIGHER IN
PARTICIPANTS WITH OSA AND WE DID
ADJUSTED ODDS RATIOS LOOKING AT
ADJUSTMENTS FOR AGE, BMI,
PRESENCE OF CHRONIC HYPERTENSION
AND WEIGHT GAIN BETWEEN VISITS
AND FOUND ADJUSTED ODDS RATIOS
FOR EARLY AND MID PREGNANCY OF
1.94 FOR PREECLAMPSIA AND OSA.
THE GESTATIONAL DIABETES DATA
WAS EQUALLY OR MORE COMPELLING
IF YOU SEE H S THE RATES WERE
MUCH HIGHER FOR GESTATIONAL G
DIABETES IN PARTICIPANTS WITH
OSA IN BOTH EARLY OSA OR MID
PREGNANCY OSA WITH ADJUSTED ODDS
RATIO FROM 3. 7 TO 3.4 AND
WE'RE SEEING ROBUST ASSOCIATIONS
THAT SEEM TO BE INDEPENDENT OF
KNOWN IMPORTANT CONFOUNDERS
DESPITE THE FACT THE MAJORITY OF
PARTICIPANTS THE PHENOTYPE IS
MILD.
VERY FEW PARTICIPANTS HAD
MODERATE SLEEP APNEA IN THE
COHORT AND SEEING THE
ASSOCIATION IN WHAT WOULD
GENERALLY BE THOUGHT OF AS MILD
PHENOTYPE OF OSA.
SO WHAT DO WE KNOW ABOUT
TREATING OSA WITH THE MOST
COMMONLY PROSCRIBED TREATMENT
CPAP IN PREGNANCY.
THE DATA REMAINS LIMITED.
THERE'S CASE REPORTS AND CASE
SERIES THAT HAVE BEEN PUBLISHED
RETROSPECTIVE AND PROSPECTIVE
CASE SERIES AND RECENTLY SMALL
TRIALS HAVE ALSO BEEN PUBLISHED.
I THINK THIS IS AN EXCITING AREA
OF RESEARCH I THINK PREGNANCY IS
AN IDEAL SCENARIO TO BETTER
UNDERSTAND THE ROLE OF PAP AS
A PREVENTIVE STRATEGY BECAUSE
THE PHYSIOLOGY OF A PREGNANT
PERSON CAN BE INTENSIVE IN EARLY
PREGNANCY TO DEVELOPING
HYPERTENSION IN THENHE SPAN 30
TO 40 WEEKS.
AND AGAIN CAN BE NORMAL GLYCEMIC
IN EARLY PREGNANCY AND GET TO
THE POINT OF REQUIRING INSULIN
BY THE THIRD TRIMESTER AND HELPS
UNDERSTAND CPAP AS PRIMARY
PREVENTION OF CERTAIN CARDIO
METABOLIC MORBIDITIES.
ONE OF THE TRIALS RECENTLY
PUBLISHED I THINK IS IMPORTANT
TO HIGHLIGHT, THIS IS THE
LARGEST TRIAL TO DATE THAT IS
RANDOMIZED OF SLEEP APNEA
TREATMENT IN PREGNANCY.
IT COMES OUT OF A RESEARCH GROUP
IN THAILAND AND CARE FOR OSA IN
PREGNANCY LESS THAN 16 WEEKS AND
THE PRIMARY OUTCOME WAS PRENATAL
BLOOD PRESSURE TREND OF SYSTOLIC
AND DIASTOLIC MEASUREMENTS
ACROSS PREGNANCY.
THEY HAD 153 IN THE CPAP AND 157
IN THE USUAL CARE GROUP.
C PAP ADHERENCE HAD AN AVERAGE
USE AT 2.5 HOURS PER5 NIGHT AND
THE OVER ALL FINDINGS WHICH I'LL
SHOW IN MORE DETAIL IN THE NEXT
SLIDE IS IT REDUCED BLOOD
PRESSURE WITH LARGE EFFECTS ON
DIASTOLIC AND MEAN ARTERIAL
PRESSURE COMPARED TO SYSTEMIC
BLOOD PRESSURE.
THEY'RE LOOKING AT PATIENTS
WITHOUT CPAP THERAPY IN BLUE AND
THE WITH CPAP AND THE RED DOTS.
YOU CAN SEE IT APPEARS THE CPAP
GROUP HAD STATISTICALLY
SIGNIFICANT REDUCTIONS IN THE
BLOOD PRESSURE ACROSS PREGNANCY.
THEIR SAMPLE SIDE WAS LIMITED IN
TERMS OF LOOKING AT ADVERSE
PREGNANCY OUTCOMES BUT DID CHART
ABSTRACTION TO LOOKED AT HIGHER
TENSIVE DISORDERS AND FOUND
STATISTICALLY SIGNIFICANT
DIFFERENCES AND 13.7% RATE IN
THE CPAP GROUP AND THIS IS AN
EXCITING FINDING WITH THEIR
BLOOD PRESSURE TRENDS.
THERE'S LIMITATIONS TO THIS
TRIAL.
AND ENROLLMENT CRITERIA BUT
THERE WAS COMPELLING DATA TO
KEEP US MOTIVATED TO CONTINUE
WITH OUR TRIAL WHEN THIS TRIAL
WAS PUBLISHED.
NOW THE INTRODUCTION TO THE MFMU
MATERNAL FETAL MEDICINE UNIT
SLEEP TRIAL.
THE FMFU IS A CONSORTIUM OF 14
CENTERS THAT PARTICIPATE IN
JOINT PROTOCOLS IN OBSTETRICS
AND CONDUCT RANDOMIZED CONTROL
TRIAL.
IT'S RAN THROUGH THE NICHD AND
ONE OF THE TRIALS THAT'S ONGOING
IS OUR SLEEP TRIAL.
IT'S A MULTI CENTER RCT OF SLEEP
APNEA IN PREGNANCY AND WE SCREEN
INDIVIDUALS WITH BMI GREATER OR
EQUAL THAN 30 AND ASK THEM TO
PERFORM AT HOME SLEEP TESTS AND
WE'RE DEFINING AS AN AHI GREATER
THAN 5.
OSA POSITIVE SUBJECTS ARE
OFFERED RANDOMIZATION INTO OUR
TRIAL AND RECEIVE AUTO TRITATING
CPAP OR CONTROL.
THE PRIMARY HYPOTHESIS OF THE
TRIAL IS TREATMENT OF OSA WITH
CPAP IN PREGNANCY WILL RESULT IN
REDUCTION OF DISORDERS IN
PREGNANCY.
WHEN WE LOOK TO SEE OUR INTENDED
RATES OF PREECLAMPSIA UP OUR
TREATMENT GROUP AND
NON-COMPLIANT AND WE'RE OVER 66%
COMPLETED IN THIS TRIAL AND HOPE
TO HAVE A COMPLETION OF
ENROLLMENT BY EITHER THE FALL OF
2025 OR EARLY SPRING OF 2026.
SO THE SCREEN PORTION OF THE
TRIAL IS BASED ON SCREENING
PARTICIPANTS WITH A BMI GREATER
OR EQUAL TO 30.
THE REASON WE FOCUSSED ON THIS
GROUP OF PREGNANT INDIVIDUALS IS
FROM THE NEW MOM-TO-BE DATA
THESE INDIVIDUALS HAD THE
HIGHEST RATE BY ASSESSMENT, 20%
OF THE COHORT HAD MILD OR
MODERATE SLEEP APNEA BY MID
PREGNANCY IF THEIR BMI WAS
GREATER OR EQUAL TO 30.
THIS WAS THOUGHT TO BE THE
POPULATION MOST AT RISK AND
HENCE THAT'S HOW WE DECIDED HOW
TO TARGET THE SCREEN IN THIS
PARTICULAR STUDY.
REGARDING OF THE TIMING OFHEF
PREGNANCY.
IT'S AN INTERESTING BALANCE
QUESTION BECAUSE OBVIOUSLY THE
RATE OF SLEEP APNEA WILL GO TO
THE GAIN AND AFFECTSFF PROGRESSE
INTO THE THIRD TRIMESTER.
IN TERMS OF THE SAMPLE AND
FINDING SLEEP APNEA SUBJECTS
LATER IN PREGNANCY IS OPTIMAL
BUT WE ALSO NEED TO UNDERSTAND
WE HAVE TIME TO ENGAGE IN HAVE E
NEED TIME WITH THE PARTICIPANT
TO GET THINGS ENGAGED IN ORDER
TO SEE A TREATMENT EFFECT.
EARLIER IN PREGNANCY OPTIMIZES
THAT TIMING QUESTION AND TIME OF
THE PARTICIPANTS.
WE HAVE TO BALANCE THOSE TWO
ISSUES WHEN WE THINK ABOUT
SCREENING AND TREATMENT OF
PATIENTS IN PREGNANCY AND WE
CAME TO A CONCLUSION THAT OUR
INITIATION WINDOW WITH 16 WEEKS
TO 20 WEEKS AND SIX DAYS
GESTATION.
WE DIAGNOSE WITH A HOME SLEEP
APNEA TEST AND USE THE RESMED
APNEA LINK IN THE STUDY.
THEY'RE ALL CENTRALLY REVIEWED
SLEEP APNEA TESTS AND AFTER
CENTRAL REVIEW DETERMINE YOUR
INCLUDED IF YOUR SCORE GREATER
THAN 5 BUT LESS THAN 30 AND HAVE
A SEVERE HYPOXIA EXCLUSION AND
URGENT ALERT PROTOCOL.
SO WE EXCLUDE PARTICIPANTS FROM
RANDOMIZATION IF THEY MEET
CRITERIA OR SEVERE SLEEP APNEA.
AS WE SAW IN NEW MOMS TO BE
WE'RE SIMILAR SEEING IT'S A RARE
SITUATION IN PREGNANCY.
WE ANTICIPATED IT TO BE LESS
THAN 1% OF OUR SCREENS AND IN
FACT IT HAS BEEN.
>> YOU HAVE ABOUT A MINUTELEFT.
>> OUR TWO ARMS ARE CPAP VERSUS
SLEEP HYGIENE CONTROL AND USE
AUTO TRITATING ACPAP IN THE
STUDY AND CPAP EDUCATION AND
FOLLOW-UP IN THE CPAP ARM
THERE'S COMPLIANCE MONITORING
AND THE PARTICIPANTS ARE
ENCOURAGED AND INSTRUCTED HOW TO
GET THEIR OWN COMPLIANCE DATA
VISIBLE TO THEM ON THEIR SMART
DEVICE AND HAVE A COMPLIANCE
INCENTIVE AS WELL AS WEEKLY
FOLLOW-UPS WITH THE
PATS.
THE PRIMARY OUTCOME ARE
DISORDERS OF PREGNANCY,
GESTATIONAL PREECLAMPSIA AND WE
HAVE OTHER PRE-SPECIFIED
SECONDARY OUTCOMES VERY
IMPORTANTLY, VERY WELL
INTERESTED IN THE GESTATIONAL
DIABETES DATA AND PRETERM BIRTH
DATA AND BIRTH WEIGHT.
THE TRIAL IS REGISTERED FOR
ANYONE WHO WANTS MORE
INFORMATION OR WANTS TO FIGURE
OUT IF THERE'S A SITE NEAR THEM.
AND THIS IS THE CLINICAL
TRIALS.gov IDENTIFIER.
AND I'LL END ON THIS SLIDE.
IT'S THE HIGH PRIORITY
QUESTIONS.
I HOPE THIS TRIAL WILL ANSWER.
OUR PRIMARY OUTCOME IS AIMED TO
DETERMINE IF SLEEP APNEA IN
PREGNANCY IS A PREVENTIV
STRATEGY FOR ADVERSE PREGNANCY
OUTCOMES IN OUR HIGHER RISK
COHORT AND HOPE THE TRIAL CAN
GATHER DATA TO UNDERSTAND
BARRIERS TO AND OPTIMAL CARE IN
ORDER TO OPTIMIZE CPAP
COMPLIANCE IN PREGNANCY.
I'LL STOP THERE.
THANK YOU, AARON.
>> THANK YOU VERY MUCH.
>> THIS MFMU TRIAL VERY
IMPORTANT.
THE RESULTS ARE POTENTIALLY
TRANSFORMATIVE FOR SLEEP
RESEARCH AND ALSO HAS
IMPLICATIONS FOR SLEEP APNEA
SCIENCE THAT GO BEYOND
PREGNANCY.
WE'LL BE VERY INTERESTED IN
SEEING HOW THE RESULTS OF THIS
TURN OUT.
THANK YOU FOR THE OVERVIEW.
>> WE'LL GO TO THE NEXT SPEAKER,
DR. GHADA BOURJEILY A HEALTH
MEDICINE POLICY AND PRACTICE AND
DIRECTOR OF WOMEN'S RESEARCH AT
BROWN UNIVERSITY HEALTH IN THE
DIVISIONS OF PULMONARY CRITICAL
CARE AND SLEEP AND EXTRACTIVE
MEDICINE AT THE WARREN ALFRED
MEDICAL SCHOOL AND BROWN
UNIVERSITY.
HER PRESENTATION IS TITLED
PREGNA
PREGNANCY, A UNIQUE PHENOTYPE
FOR OSA.
>> CAN YOU SEE MY SLIDES?
>> YES.
>> GREAT.
THANKS FOR THE INTRODUCTION.
THESE ARE MY DISCLOSURES.
THEY HAVE NOTHING TO DO WITH
WHAT I'M GOING TO TALK ABOUT
TODAY.
SO WHY IS SLEEP DISORDER
BREATHING AND OSA IN PREGNANCY
UNIQUE.
I'D LIKE TO START BY DATA MOST
KNOW ABOUT THE PLA TERM
MORTALITY RATE IN THE U.S. HAS
GONE UP OVER THE LAST COUPLE OF
DECADES OR SO AND AS YOU CAN SEE
AND HEAR IT'S SIGNIFICANTLY
HIGHER THAN MANY OTHER DEVELOPED
COUNTRIES IN NORTH AMERICA,
AUSTRALIA AND EUROPE.
AND THERE ARE ALSO SOME RACIAL
AND ETHNIC DISPARITIES IN
PREGNANCY RELATED DEATHS IN THAT
BLACK WOMEN AND AMERICAN
CANADIAN AND ALASKAN NATIVE
WOMEN ARE AT HIGHER RISK
COMPARED TO WHITE WOMEN.
WHEN WE LOOK AT CAUSES FOR
PREGNANCY RELATED DEATHS, YOU
CAN SEE THE ONES LABELLED IN RED
ARE THE ONES THAT HAVE BEEN
DESCRIBED AS BEING ASSOCIATED
WITH SLEEP DISORDER BREATHING
AND OSA.
SO THE REASON IT'S IMPORTANT IS
BECAUSE WE NEED TO THINK
CREATIVELY ABOUT WAYS TO IMPROVE
MATERNAL HEALTH AND REDUCE
MATERNAL MORBIDITY AND SLEEP AND
SLEEP DISORDER BREATHING ARE
IMPORTANT WAYS TO DO THAT.
IN THE NEXT 12 MONTHS, BEAR WITH
ME, WE'LL TRY TO COVER WHERE
PREGNANCY IS A UNIQUE STANDPOINT
FROM BIOLOGY, DIAGNOSIS AND
TREATMENT.
FROM AN OUTCOME STANDPOINT
THERE'S UNIQUE FEATURES
ASSOCIATED WITH OSA IN
PREGNANCY.
THE SHORT DURATION AS MENTIONED
BETWEEN EXPOSURE AND OUTCOME CAN
ADD TO THE CHALLENGES OF TIMELY
DIAGNOSIS AND INITIATION OF
THERAPY BUT IT'S THE PERFECT
EXAMPLE OF WHY WE SHOULD STUDY
THAT POPULATION.
WE HEARD ABOUT CARDIOVASCULAR
AND METABOLIC OUTCOMES FROM THE
PREVIOUS TALK AND THE
OPPORTUNITY TO PREVENT THESE
OUTCOMES.
BUT THERE'S ALSO DATA OSA IS
ASSOCIATED WITH WORSE OUTCOMES
IN WOMEN THAT HAVE DEVELOPED
PREECLAMPSIA WITHOUT OSA AND
FURTHER INTERVENTION TO TREAT
OSA AND SLEEP DISORDER BREATHING
AND THIS WAS LED BY A SAMPLE OF
75,000 WOMEN WITH PREECLAMPSIA
AND WE DEMONSTRATED THERE WAS A
HIGHER ASSOCIATION WITH SEVERE
MATERNAL MORBIDITY, SEVERE
CARDIOVASCULAR MORBIDITY AND
HEALTH CARE UTILIZATION IN WOMEN
THAT HAD PREECLAMPSIA AND OSA
COMPARED TO THOSE THAT HAD
PREECLAMPSIA BUT DID NOT HAVE
OSA.
AND STIMULI MY IMPACT NEONATAL
HEALTH OUTCOMES AND GROWTH
OUTCOMES VARY BY THE DEFINITION
WHETHER IT'S SUBJECTIVE,
OBJECTIVE OR DEFINEDED BY ICD
CODES.
UNFORTUNATELY WE FOUND THAT
ROUGH OUTCOMES WERE DEFINED IN
20 WAYS.
THAT SUGGESTS THERE'S DEFINITELY
ROOM FOR IMPROVEMENT AND WE NEED
TO BETTER UNDERSTAND THIS BUT
YOU CAN TELL THERE'S
ASSOCIATIONS WITH SMALL FOR
GESTATIONAL AGE AS WELL AS LARGE
FOR GESTATIONAL AGE AND THAT
DEPENDS ON POPULATIONS STUDIED
AS WELL AS THE METHODOLOGY USED
TO DEFINE THE OUTCOMES AS WELL.
AND A FEW YEARS AGO WE
DEMONSTRATED AN ASSOCIATION
BETWEEN SLEEP DISORDER BREATHING
AND CONGENITAL ABNORMALITIES.
IN A DATA SET OF ABOUT 1.5
MILLION LINKED MOM AND BABY
DATA, WE EXAMINE THE RATES OF
CONGENITAL ABNORMALITIES AND
SINCE THEN THE ASSOCIATION HAS
BEEN DEMONSTRATED IN OTHER
COHORTS.
WHEN WE THINK OF OSA IN GENERAL
WE THINK OF THIS TYPE OF
PHENOTYPE AND MALE OBESITY BEING
A RISK FACTOR.
PREGNANCY KIND OF LOOKS LIKE
THIS BUT MECHANICALLY PLAY
POSSIBLY BE DIFFERENT AND THE
DEVELOPMENT OF THE INCREASE IN
ABDOMINAL CONTENTS IS DIFFERENT
AND THE CONCEPTION PRODUCT AND
VISCERAL FAT FOR INSTANCE ARE
COMPLETELY DIFFERENT
CONTRIBUTORS.
IN ADDITION TO THAT, THREE
MONTHS LATER, THAT PERSON STILL
LOOKS THE SAME AND THE PREGNANT
PERSON LOOKS LIKE THIS.
THERE'S MULTIPLE FACTORS THAT
WILL BE INFLUENCED BY THE SHORT
TIMING OF THIS EXPOSURE.
SO IN PREGNANCY THESE MECHANICAL
PROPERTIES AND ANTHROPOMORPHIC
DECREASES IN THE SUPINE POSITION
AND PRESSURE IN THE COURSE OF
PREGNANCY AND LOWER IN THE
POSTPARTUM PERIOD.
THERE'S OTHER FACTORS LIKE
ESOPHAGEAL REFLUX AND WE'LL TALK
ABOUT HOW BIOLOGY IS DIFFERENT
IN THE PREGNANT POPULATION AS
WELL.
WE HEARD ABOUT SEX HORMONES
EARLIER WE HEARD ABOUT ESTROGEN
AND PROGESTERONE IN THE COURSE
OF PREGNANCY AND LEVELS INCREASE
UP PREGNANCY AND HAVE RECEPTORS
IN THE UPPER AIRWAY AND
IMPLICATED WITH FLUID REGULATION
AND HAVE I A DIRECT EFFECT LIKE
SMOOTH MUSCLE DILATION AND
LEADING TO NASAL CONGESTION AND
SYSTEMIC EFFECTS AND INCREASED
IN THE VASCULAR VOLUME THAT MAY
IMPACT THOSE AND HEARD
PROGESTERONE IS A STIMULANT AND
HEARD OF THE PRE-MENOPAUSAL BE
PROTECTIVE AND POST-MENOPAUSAL
PERIOD IS ELEVATED RISK THIS IS
THE NORMAL HORMONAL LEVELS AND
IS THE AFFECT DIFFERENT AND DO
THEY NOW HAVE A MORE
PREDISPOSING OF SLEEP DISORDER
BREATHING IN ADDITION TO THE
PROTECTION AGAINST THE
DISORDERED BREATHING.
WE DEMONSTRATED PROGESTERONE
LEVELS ARE LOWER WITH OSA
COMPARED TO THOSE WITHOUT OSA
AND HEARD ABOUT THE EFFECTIVE OF
ESTRADIOL ON OXIDATIVE STRESS.
THIS IS AN EXAMPLE.
ESTRADIOL SEEMS TO PROTECT
AGAINST CARDIORESPIRATORY
DYSFUNCTION AND THOSE THAT HAVE
REPLACEMENT HAD LOWER DIASTOLIC
AND SYSTOLIC NUMBERS AND
SIMILARLY OXIDATIVE STRESS
APPEARS TO IMPROVE UP A RESPONSE
TO ESTRADIOL REPLACEMENT AFTER
MULTIPLE ORGAN SYSTEMS.
AND THERE'S OTHER STUDIES SHOW
IT EXPRESSES INFLAMMATORY
MARKERS SUBJECTING UNIQUE
MECHANISTIC PATHWAYS IN THE
POPULATION.
IN ADDITION THERE'S FLOUINFLUEN
THE HEALTH OF THE MOTHER AND
CHILD AND PLACENTA.
A DECADE AGO WE HAD SHOWN THAT
PLACENTA SECRETED IN MARKERS IN
WITH OSA WERE ALTERED IN A
SIMILAR FASHION TO AND LOOKED AT
TISSUE AND DEMONSTRATED HYPOXIA
IN WOMEN WITH OBSTRUCTIVE SLEEP
APNEA COMPARED TO THOSE WITHOUT
AND INCREASED MARKER OF A TYPE
OF HYPOXIA IN WOMEN COMPARED TO
CONTROLS.
A COUPLE YEARS AGO THIS STUDY
AND WHEN THEY LOOKED AT SPECIFIC
PATHWAY GENES STOOD OUT FOR
REOXYGENATION AND NOW WHAT ABOUT
DIAGNOSIS AND HOW WE CALL
PATHOLOGY IN THE PREGNANT
POPULATION?
WE LOOKED AT FLOW IN PREGNANT
WOMEN AND MATCHED FOR BMI AND
AHI AND NOT PREGNANT AND
DEMONSTRATED AND YOU CAN SEE
PREGNANT WOMEN ARE IN THE TOP
SCREAM IN RED.
WE DEMONSTRATED AIR FLOW
LIMITATION WAS SIGNIFICANTLY
MORE COMMON IN PREGNANT COMPARED
TO NON-PREGNANT WOMEN.
AND WHEN COMPARED WE WERE ABLE
TO SEE TO THE ONES THAT LATER
DEVELOPED GESTATIONAL
HYPERTENSION HAD HIGHER AMOUNTS
THAN THOSE THAT DIDN'T DEVELOP
IT AND WE LOOKED AT PULSE
TRANSIT TIME AND THAT'S A
MEASURE OF HOW LONG IT TAKES FOR
BLOOD TO TRAVEL FROM THE
CONTRACTION OF THE LEFT
VENTRICLE.
THE CONSTANT WE DEFINED AND THIS
WAS THE MEASURE FOR PULSE
TRANSIT TIME AND THIS MEASURE
HAD BEEN USED IN THE PEDIATRIC
POPULATION AND THIS IS A NICE
REPRESENTATION OF HOW WHEN
ESOPHAGEAL PRESSURE GOES DOWN
THERE'S A DROP IN PULSE TRANSIT
TIME THAT HAPPENS REPEATEDLY.
SO WE DECIDED TO LOOK AT THAT IN
THE PREGNANT POPULATION AND SEE
HOW IT COMPARES TO LOOKING AT
APNEA, HYPOPNEA MEASURES.
WE DEMONSTRATED PULSE TRANSIT
TIME DROPS WERE MORE COMMON IN
WOMEN WHO SNORE AND HAD A
HYPOPNEA LESS THAN 5 AND WOMEN
THAT SNORED WITH A SCORE HIRE
-- HIGHER THAN 5.
WHEN WE CATEGORIZED IN THE PULSE
TRANSIT TIME EVEN IN THE HIGHEST
CATEGORY WHERE MORE THAN 30
EVENTS DROPS WERE OCCURRING, THE
VAST MAJORITY HAD AN H OF AHI
LESS THAN 5 AND NOT DETECTED BY
OUR CONVENTION AND EXTRAPOLATING
FOR THE NON-PREGNANT DEFINITION
POPULATION.
WE TOOK THIS FURTHER AND LOOKED
AT AHI BELOW THE CUT OFF AND HOW
IT HEIGHT BE ASSOCIATED WITH
SOME MENTAL HEALTH SYSTEMS.
WE DEMONSTRATED THAT INCREASING
LEVELS OF AHI BELOW THE 5 SCORE
WAS ASSOCIATED WITH HIGHER
DEPRESSION SCORES IN LATER
PREGNANCY.
AND THIS JUST GOT ACCEPTED DAYS
AGO AND DEMONSTRATED IN WOMEN
NEGATIVE 4 OSA IN EARLY AND LATE
PREGNANCY, IF THEY HAD OBESITY
AND SNORED MORE THAN 60% HAD A
NOCTURNAL DIPPING A PHYSIOLOGIC
MEASURE WHEN LACKING CAN BE
ASSOCIATED WITH BOTH ADVERSE
PREGNANCY OUTCOMES AND HERE
IRRESPECTIVE OF WHAT THE AHI CUT
OFF WAS THE LACK OF NOCTURNAL
DIPPING WAS PREVALENT IN THIS
POPULATION THAT HAD REGULAR
SCORING AND BY DEFINING
PATHOLOGY THE SAME WAY WE DEFINE
IT IN THE NON-PREGNANT
POPULATION, IT MEANS THAT WE'RE
ONLY IDENTIFYING THE TIP OF THE
ICEBERG IN TERMS OF PATHOLOGY
AND MAY BE LEAVING MANY WOMEN
UNTREATED.
>> ONE MINUTE LEFT.
>> SO SPEAKING OF TREATMENT, WE
KNOW THAT YOUNG WOMEN HAVE THE
LOWEST ADHERENCE OF CPAP AMONG
OTHER AGE GROUPS AND GENDERS.
AND CPAP ADHERENCE IS PRETTY BAD
IN THE STUDIES THAT HAVE BEEN
PUBLISHED TO DATE AND THEY GO
FROM LESS THAN 30 MINUTES TO
ABOUT THREE AND A HALF HOURS PER
NIGHT AND THERE ARE RACIAL
DISPARITIES THAT EXIST.
SO WE HAVE RECENTLY COMPLETED A
QUALITATIVE ASSESSMENT OF
PREGNANT AND NON PREGNANT WOMEN
INITIATED ON CPAP WITHIN A SHORT
PERIOD OF TIME AND WERE ABLE TO
IDENTIFY FACTORS THAT WERE NOT
SPECIFIC TO PREGNANCY.
SOME THAT WERE PREGNANCY
SPECIFIC AND SOME EXACERBATED BY
PREGNANCY.
IN SUMMARY, SEX AND GENDER HAVE
SPECIFIC IMPLICATIONS FOR SLEEP
DISORDER BREATHING IN PREGNANCY
AND IT IMPACTS BREATHING IN
UNIQUE WAYS AND VICE VERSA AND
WE NEED TO THINK OF SLEEP
DISORDER BREATHING AS A UNIQUE
OPPORTUNITY TO PREVENT AND
IMPROVE MATERNAL HEALTH OUTCOME
AND FOCUS ON MATERNAL AND
NEONATAL HEALTH AND CONSIDER
IMPLEMENTATION STRATEGY FOR
TREATMENTS THAT CONSIDER BOTH
THE PHYSIOLOGY OF PREGNANCY AND
ALSO THE UNIQUE NEEDS OF THIS
PERINATAL POPULATION AND AT SOME
POINT WE DO NEED TO ADVOCATE FOR
SLEEP DISORDER BREATHING FOR
WOMEN NOT AIMING AT IMPROVING
PREGNANCY OUTCOMES THERE'S WOMEN
DENIED COVERAGE FOR TREATMENT AT
SLEEP APNEA IN PREGNANCY AND
THOUGH MATERNAL MORTALITY IS
IMPROVING WE NEED TO DO BETTER
AT IDENTIFYING RISK FACTORS.
>> THANK YOU FOR THE
PRESENTATION A LOT OF IMPORTANT
DATA RELATED TO RISK FACTORS AND
UNIQUE PHENOTYPES AND SEVERAL
MECHANISMS THAT ARE LINKING
SLEEP APNEA WITH CARDIOVASCULAR
OUTC
OUTCOME THANK YOU.
WE'LL MOVE ON TO THE FINAL
SPEAKER.
SORRY, I FORGOT TO PUT ON MY
VIDEO IF IT'S WORKING.
WE8 WELL, THE LAST SPEAKER IS
DR. HADINE JOFFE IN THE FIELD OF
WOMEN'S HEALTH AND EXECUTIVE
DIRECTOR OF THE MARY OREGON
CONNOR CENTER AND FOUNDER OF THE
WOMEN'S HORMONES AT AGING
PROGRAM IN THE DEPARTMENT OF
PSYCHIATRY AT BRIGHAM AND
WOMEN'S HOSPITAL AT HARVARD
MEDICAL SCHOOL.
AND TODAY SHE'LL BE TELLING US
ABOUT SLEEP AND PARTICULAR
PHENOTYPES LIKE SLEEP
FRAGMENTATION REFLECTING
IMPORTANCE IN MENOPAUSE.
>> HERE'S MY DISCLOSURES.
YOU'VE HEARD A LITTLE BIT ABOUT
MENOPAUSE.
AND THAT PERSON HAS 12 MONTHS OF
AMENORRHEA AND THE AVERAGE AGE
IS 51, 52, LEADING UP TO THAT IS
THE PERIMENOPAUSE LASTING UP TO
FOUR YEARS AND YOU SEE IN THE
TOP RIGHT IN MENOPAUSE THERE'S A
TREMENDOUS RANGE IN CHAOTIC
VARIABILITY IN ESTRADIOL AND
DECLINE I PROGESTERONE RELATED
TO OVULATION AND THE TIME OF
SIGNIFICANT HOT FLASHES BRIDGES
THIS FINAL MENSTRUAL PERIOD.
SO WHEN WE THINK ABOUT SLEEP IN
MID LIFE AND MENOPAUSE THERE'S
MANY CAUSES IDENTIFIED AT
LENGTH.
AND I'LL BE TALKING MOSTLY ABOUT
HOT FLASHES BECAUSE THAT'S THE
MOST COMMON AND A A BIT
ABOUT OSA AND THEY CAN MULTI
PRESENT.
AND A STUDY SHOWED SLEEP
MAINTENANCE IS THE MOST COMMON
SYMPTOM.
WAKED UP REPEATEDLY OCCURS IN
42% OF THE POPULATION SO NOT
ONLY ARE SLEEP PROBLEMS COMMON
IN THIS MID LIFE POPULATION BUT
ALSO IT'S PRIMARILY
CHARACTERIZED BY SLEEP
INTERRUPTION AND SLEEP
MAINTENANCE CONCERNS AND THEY
PRESENT WITH SLEEP INTERRUPTION
ABOUT 20% AND A LOT IS RELATED
TO HOT FLASHES AND WE DO KNOW
SLEEP APNEA AND OTHER FACTORS
CONTRIBUTE.
SO YOU HAVE HEARD ABOUT OSA
RELATED TO MENOPAUSE.
I'M BRIEFLY GOING TO MENTION IT
TO SAY WE DO SEE AHI RISES
FLAUNL ANNUALLY BY 4% PER YEAR
AND WHETHER THE AHI THRESHOLD
WAS 5 OR 15 THERE WAS A DOUBLING
AND TRIPLING OF RISK AS WOMEN
BECOME POST MENOPAUSAL AND WE DO
PRESENTATIONS DIFFERENT AS YOU
HEARD EARLIER AND KNOW AGE AND
BMI AND NECK CIRCUMFERENCE DON'T
EXPLAINING THIS EMERGENCE AND
THERE'S DATA SHOWING
PROGESTERONE AND ESTRADIOL
EFFECTS MAY BE CONTRIBUTING.
AT AN IMPORTANT TIME WHEN WOMEN
ARE UNDER DIAGNOSED AND
UNRECOGNIZED FOR HAVING SLEEP
APNEA.
I'LL NOW SHIFT TO NIGHT SWEATS,
NIGHTTIME NOT FLASHES WHICH
COMMONLY OCCUR AS THE CAUSE OF
SLEEP DISRUPTION AND KNOW SO
LITTLE ABOUT SLEEP APNEA AND
MENOPAUSE AND THE CO-OCCURRENCE.
WHAT ARE HOT FLOORS?
THERE'S PERCEPTIONS YOU SEE IN
THE FIGURE ON THE TOP RIGHT
PERCEPTION OF HEAT, SWEATING
SENSATION IN THE THORAX, UPPER
CHEST AND HEAD.
YOU SEE INCREASE IN CORE BODY
TEMPERATURE THAT DISSIPATES AND
UNDERSTAND THE NEUROPEPTIDE
BIOLOGY THAT UNDER LIES IT IN
THE BRAIN.
THEY'RE EXTREMELY COMMON ABOUT
80% AND THE DURATION IS SEVEN,
EIGHT, NINE YEARS.
AT THE AGE OF 60 WHEN WE START
LOOKING AT SLEEP APNEA OFTEN A
THIRD OF WOMEN WILL STILL HAVE
VASO MOTOR SYMPTOMS WHICH IS THE
MEDICAL TERM FOR HOT FLASHES AND
NIGHTTIME HOT FLASHES OR NIGHT
SWEATS.
WE KNOW THEY PERSIST DAY AND
NIGHT AND WHETHER PEOPLE ARE
AWAKE OR ASLEEP.
AND WE ALSO KNOW THEY'RE THE
SECOND MOST COMMON CONCERN
AFTER -- SORRY, THE SLEEP
PROBLEM IS THE SECOND MOST
COMMON CONCERN THAT LEADS WOMEN
TO SEEK TREATMENT AFTER HOT
FLASHES AT THE STAGE OF LIFE.
WHEN YOU LOOK FOR A HOT FLASH
POPULATION ABOUT TWO-THIRDS WILL
HAVE SIGNIFICANT SLEEP PROBLEMS.
SOME STUDIES WE'VE DONE USING
EXPERIMENTAL PARADIGM
DEMONSTRATED THE IMPACT OF HOT
FLASHES ON SLEEP DISTURBANCE.
THIS FROM A STUDY WHERE WE
INDUCE THIS IN HEALTHY
VOLUNTEERS AND WE KNOW WHETHER
DONE IN WOMEN OR WOMEN OR FOR
FIBROIDS OR ENDOMETRIOSIS OR
PROSTATE CANCER TWO-THIRDS
PEOPLE FLASH AND ONE-THIRD DON'T
AND ABLE TO TAKE ADVANTAGE OF
THE FLASH FREQUENCY AND IDENTIFY
NIGHTTIME AND DAYTIME HOT
FLASHES AND OBJECTIVE WITH SKIN
CONDUCTANT MEASUREMENT.
WE LOOK AT NORMAL HEALTHY
VOLUNTEERS AND LOOK AT CHANGES
BEFORE AND AFTER THE EMERGENCE
OF HOT FLASHES BEFORE IN THE
STUDY OF CONSTANT ESTRADIOL
SUPPRESSION.
THIS IS TO CHARACTERIZE WHAT
WE'RE TALKING ABOUT.
AND THE FINDINGS FROM THE STUDY
SHOWED THE FREQUENT HOT FLASHERS
IN THE DEEP PINK HAD AN
EMERGENCE OF NUMBER AWAKINGS IN
POLY SOMNOGRAPHY AND SEE THE
TRAJECTORY TOWARDS MORE
WAKEFULNESS AND EVENTS AND
GREATER ACCUMULATION OF WASO
WITH NOCTURNAL FREQUENCY.
WE ALSO SAW A SHIFT TO MORE
LIGHT SLEEP AND MORE TIME IN
WAK
WAKE.
VASO MOTOR PROBLEMS AFFECT
SLEEP.
WE SEE THE LIGHTER SLEEP AND
ALSO MORE SLEEP-STAGE
TRANSITION.
MORE FRAGMENTED SLEEP PATTERN.
THEY'RE MOSTLY ASSOCIATED WITH
WAKE EPISODES IN EEX BUT NOT
EXCLUSIVELY SO PEOPLE DO FLASH
WHEN THEY DON'T WAKE.
THEY DON'T WAKE FOR ALL OF THEM
AND IF YOU ASK THEM THEY DON'T
REMEMBER ALL THE HOT FLASH
EPISODES THEY HAD.
BUT IMPORTANTLY AND
INTERESTINGLY IN INDIVIDUALS
HAVING NOCTURNAL HOT FLASHES
WASSOO ACCUMULATION ONLYNL
ACCOUNTS FOR 20% OF THE NUA
SO YOU SEE A LOT IN THE ABSENCE
OF THE HOT FLASH EVENT.
THERE'S A GREAT DEAL OF SLEEP
FRAGMENTATION BETWEEN THE MOTOR
SYSTEM EVENTS THAT'S QUITE
DISRUPTIVE OF SLEEP QUALITY AND
SEE LENGTHENING OF TOTAL SLEEP
TIME.
THE CONCEPT IS IT'S NOT JUST
SMOOTH SAILING WITH SLEEP IN
BETWEEN THE SLEEP EVENTS.
I'VE LOOKED AT SLEEP CONTINUITY
AND I'M TALKING IN THE ABSENCE
OF APNEA AND SHIFTING OUR MENTAL
HEALTH MESSAGE TO FOCUS ON SLEEP
INTERRUPTION AS HAVING
POTENTIALLY IMPORTANT ADVERSE
HEALTH OUTCOMES AND I'M GOING TO
SHOW YOU SOME OF THOSE DATA.
WE KNOW OF COURSE FROM A WEALTH
OF ROBUST DATA THAT SHORT TOTAL
SLEEP TIME IS ASSOCIATED WITH
MULTIPLE ADVERSE NEUROCOGNITIVE
AND METABOLIC OUTCOMES BUT
THAT'S NOT THE PATTERN OF SLEEP
DISTURBANCE RELATED TO HOT
FLASHES.
SO WE'VE ASKED THE QUESTION IN
THE SETTING OF A PRESERVED TOTAL
SLEEP TIME, WHAT DO WE SEE IN
THE AFFECTS OF SLEEP
FRAGMENTATION.
A STUDY I'VE CONDUCT AND WANT TO
CITE MY TREMENDOUS COLLABORATORS
ON THIS AMONGST MANY OTHERS, WE
HAVE LOOKED AT THIS
EXPERIMENTALLY AND THE DESIGN IS
AN IN PATIENT EXPERIMENTAL
DESIGN IN THE HIGHEST AND LOWEST
ESTRADIOL STATE USING MENOPAUSE
UNDER STRICT REGULATION AND ABLE
TO HAVE BLOCKS TO LOOK AT HIGH
ESTRADIOL, UNINTERRUPTED SLEEP
CONTEXT AND THEN FRAGMENT THEIR
SLEEP AND I'LL DESCRIBE AND DO
THAT EXPERIMENTALLY AND REPEAT
THE SAME SLEEP BLOCK TWO AND
THREE NIGHTS OF UNINTERRUPTED
AND FRAGMENTED SLEEP IN THE LOW
ESTRADIOL SLEEP IN CONTROLLED
NEW PATIENT CONDITIONS.
TO CAPTURE THE WAY WE DO THIS IS
WE PUT THE ACOUSTIC STIMULUS
DISPLAYED TO THE PARTICIPANT
THROUGH A SPEAKER IN THEIR HEAD
AND THE ALARM WAKES THEM EVERY
15 MINUTES AND HAVE TO STAY
AWAKE TWO MINUTES AND THEY HAVE
TO PUNCH THE MARKER INDICATING
THEY'RE AWAKE.
WE GIVE THEM AN HOUR OF
ADDITIONAL WAKEFULNESS MIMICKING
THE EXTREMES OF SLEEP
FRAGMENTATION RELATED TO HOT
FLASHES.
WE GET THEM TO GET TO A FULL
EIGHT HOURS BY GIVING THEM AN
EXTRA HOUR IN BED.
WE'RE ABLE TO VALIDATE AND
DOCUMENT THAT WE INDUCED THE
WAKEFULNESS AND THAT'S THE
PARADIGM.
WE USED IT IN A VARIETY OF WAYS
TO LOOK AT THE OUTCOME HERE.
I'M GOING TO SHOW YOU PERCEIVED
SS AND OBJECTIVE
ALERTNESS.
THIS ON A SELF-REPORTED SLEEP
MEASURE WE WERE ABLE TO SHOW THE
EMERGENCE OF SLEEP FRAGMENTATION
DID LEAD TO A WORSE PERCEIVED
SLEEPINESS AND ESTRADIOL
SUPPRESSION DID NOT HAVE EFFECT.
AND WHEN WE LOOKED AT RATE OF
RESPONSIVITY AND ALERTNESS WE
FOUND BOTH LET TO DIMINISHED
ALERTNESS AND ABLE TO IDENTIFY
WHILE ESTRADIOL TRANSITIONS
OCCUR ACROSS THE MENOPAUSE
TRANSITION WE CAN SEE THE
MODIFIABLE EFFECT DOES HAVE
THESE ADVERSE EFFECTS ON HEALTH
AND ACUTE CHANGES IN WELL BEING.
SIMILARLY WE'VE BEEN ABLE TO
SHOW ADVERSE EFFECTS ON
EFFECTIVE STATE, UNDERLYING
MOOD.
THESE ARE NON-DEPRESSED
INDIVIDUALS S IN NEGATIVE AND
POSITIVE AFFECT AND THE SLEEP
FRAGMENTATION HAD AN AFFECT AND
RETURN TO BASELINE AFTER
REPEATED FRAGMENTATION AND SLEEP
DISRUPTION IS A MODIFIABLE
TARGET TO SHIFT AFFECT.
SLEEPING TO CARDIO METABOLIC
DISEASE, WE KNOW WEIGHT GAIN AND
PARTICULARLY BODY FAT GAIN IS
COMMON ACROSS THE MENOPAUSE
TRANSITION IN 50% OF INDIVIDUALS
AND ESTRADIOL SUPPRESSION AND AS
NOTED YEARS AGO IN A STUDY
LOOKING AT VISCERAL ADIPOSITY
ACCUMULATION AND BEFORE THE
FINAL PERIOD WHEN LOOKING AT THE
BOTTOM FIGURE YOU STILL SEE A
LOT OF ESTRADIOL BEING PRODUCED.
THAT'S WHEN YOU SEE THE
EMERGENCE OF VISCERAL FAT
ADIPOSITY.
RAISING THE QUESTION MAYBE IT'S
NOT ALL ABOUT THE ESTRADIOL
WITHDRAWAL MAYBE IT'S RELATED TO
OTHER FACTORS IN MENOPAUSE.
HERE WE EXTRAPOLATED FROM THE
QUESTION FROM TOTAL SLEEP TIME
IF THAT IS RELATED TO BODY FAT
GAIN AND MIGHT THE SLEEP
FRAGMENTATION COMMON IN THIS MID
LIFE STAGE CONTRIBUTE TO BODY
FAT GAIN.
>> YOU HAVE ABOUT ONE MINUTE
LEFT.
>> THANK YOU.
SO FIRST I'LL SHOW YOU AND WE
DID SEE THE CHANGES THAT SLEEP
FRAGMENTATION CONTRIBUTED TO
RESPIRATORY QUOTIENT IN THE
DIRECTION OF BODY FAT GAIN.
WE ALSO LOOKED AT MULTIPLE
CARDIO METABOLIC HEALTH OUTCOME
AND WHEN WE LOOK AT THE 16
OUTCOMES, SLEEP FRAGMENTATION
CONTRIBUTED TO ADVERSE CHANGES
OF 46% OF THOSE 16.
ESTRADIOL SUPPRESSION TO 66 AND
IF YOU COMBINE THEM COMBINED
WITH MENOPAUSE 100% OF THE
CARDIO METABOLIC INDICATORS WERE
ADVERSELY AFFECTED.
I WON'T HAVE TIME TO GET IN THE
NATURE OF THE ABNORMALITIES BUT
TO GIVE YOU SOME EXAMPLES WE SEE
LESS SATIATY AND MY MESSAGE IS
FIX YOUR WASO IS WHAT I TELL MY
PATIENTS WHO DON'T TAKE THEIR
SLEEP FRAGMENTATION SERIOUSLY
AND HYPOXIA ITSELF HAS
TREMENDOUS RISK.
THE WASO ITSELF APPEARED TO HAVE
IMPORTANT HEALTH RISK.
I'LL END BY SAYING THERE'S SO IN
QUESTIONS AND THE TWO MOST SIG
QUANTITY ARE FLASHES AND OSA AND
WE KNOW SO LITTLE ABOUT
COMORBIDITY AND DOWN STREAM
EFFECTS ON HEALTH, WELLNESS AND
FUNCTION AND THE INFLEXION POINT
FOR HEALTH OUTCOMES AS WITH AGE
WE KNOW SO LITTLE ABOUT THE
SUSTAIN AFFECTS ON HEALTH.
WE ALSO NEED LOTS MORE
STRATEGIES FOR INTERVENTIONS FOR
TARGETING THE CORE CONDITIONS IN
MID LIFE AND MENOPAUSE AND
PHARMACOLOGIC AND DEVICE IN THE
POPULATIONS HAVE NOT BEEN
STUDIED.
AND WE SHOULD THINK SPECIFICALLY
ABOUT WHAT PEOPLE THINK ABOUT
WHICH IS PRECIPITATING THE
WEIGHT GAIN AND THE WASO AND
PEOPLE CANNOT FALL BACK SLEEP
AND THIS IS A CONCERN FOR
DISPROPORTIONATE POPULATIONS AND
THANK YOU VERY MUCH AND I'LL
TURN IT BACK TO YOU.
>> THANK YOU.
I'D LIKE TO THANK EACH OF YOU
FOR YOUR PRESENTATIONS.
THESE ARE EXCELLENT AND COVERED
A LOT OF INFORMATION ABOUT THE
LIFE STAGES AND TRANSITIONS
WOMEN EXPERIENCE THROUGHOUT
THEIR LIFE TIME.
DR. FACCO TOLD US ABOUT A STUDY
ESTABLISHING SLEEP APNEA AS A
RISK FOR MATERNAL CARDIOVASCULAR
DISEASE AND HOW THE FINDINGS
THEN LED TO WHAT'S A NOW A PHASE
III CLINICAL TRIAL TO FIND OUT
IF REDUCING SLEEP APNEA CAN
IMPROVE OUTCOMES.
DR. GHADA BOURJEILY TOLD US
ABOUT UNIQUE PHENOTYPES THAT
OCCUR DURING GESTATION LIKE AIR
FLOW LIMITATION AND IMPORTANT
RISK FACTORS AND ALSO TALKED
ABOUT SOME MECHANISMS THAT COULD
BE MEDIATING THE AFFECTS OF
APNEA ON PREGNANCY HEALTH AND
ALSO HOW SLEEP MAY BE IMPORTANT
FOR THE PLA TERM FETAL INTERFACE
AND HOW WOMEN SLEEP DURING
PREGNANCY COULD BE AFFECTING
FETAL HEALTH AND DEVELOPMENT AND
DR. JOFFE TALKED ABOUT THE
IMPORTANT INTERFACE BETWEEN
SLEEP AND MENOPAUSE AND HOW SOME
OF THESE INTERACTIONS MAY BE
SIGNIFICANTLY CONTRIBUTING TO
INCREASED CARDIOVASCULAR RISK IN
WOMEN DURING MENOPAUSE.
SO, AT THIS POINT WE CAN TAKE
MAYBE FIVE OR SO MINUTES AND RUN
INTO THE BREAK A LITTLE BIT TO
GO OVER QUESTIONS THAT WERE
OPPOSED.
I'LL TRY TO JUMP BETWEEN THE
CLASS AND Q&A.
A QUESTION SAYS DR. JOFFE,
EXCELLENT TALK.
I THINK WE ALL AGREE ON THAT.
WHICH INTERVENTION DID YOU
RECOMMEND TO REDUCE WAKE ONSET
AND ARE THERE STUDY IN THE AREA?
>> I'LL FOCUS ON THE HOT
FLASH/WASO PROBLEM.
WE HAVE DONE AN NIH SUPPORTED
MULTIPLE CENTER TRIAL CALLED MS
FLASH AND TOOK INDIVIDUALS WITH
HOT FLASHES AND RANDOMIZED THEM
WITH NINE TREATMENTS OVER
MULTIPLE TRIALS.
TWO-THIRDS HAVE MOSTLY A WASO
AFFECT AND LOOKING AT THE
INTERVENTIONS THAT WORKED, THE
INTERVENTIONS THAT WORKED FOR
WASO WERE CBTI OF COURSE HELPED
REDUCE THE WASO, EXERCISE WHICH
DIDN'T HELP THE HOT FLASHES BUT
HELP THE SLEEP DISRUPTION AND
WASO ACCUMULATION, ESTROGEN DID
HELP IN THAT POPULATION, WE ALSO
STUDIED THE SEROTONIN-BASED
ANTIDEPRESSANTS USED TO TREAT
HOT FLASHES AND LAD BENEFIT.
WE SAW BEHAVIORAL LIFESTYLE AND
PHARMACOLOGIC INTERVENTION AND
AMONG THOSE CBTI HAD THE MOST
IMPACT AND SEROTONIN AND
EXERCISE AS WELL.
>> IN THE NEW MOMS TO BE STUDY
AND THE AHI WAS -- IF I'M GOING
TO SAY THIS CORRECTLY THE AHI
WAS ASSOCIATED WITH INCREASED
CARDIOVASCULAR AND GESTATIONAL
DIABETES LIST BUT THE AIR FLOW
LIMITATION WAS ONLY ASSOCIATED
WITH PREECLAMPSIA OR THE
HYPERTENSION RISK BUT NOT THE
DIABETES INDICATING PERHAPS
THESE DIFFERENT PHENOTYPES POSE
DIFFERENT RISKS FOR OUTCOMES OR
MIGHT BE OCCURRING THROUGH MAYBE
DIFFERENT MECHANISMS.
DO YOU HAVE A COMMENT WHY THAT'S
IMPORTANT TO BETTER UNDERSTAND?
>> I THINK REFERRING TO A PAPER
FROM THE NEW MOM TO BE COHORT
LOOKING AT AIR FLOW LIMITATIONS
AND FOUND AS YOU SAID IT DID NOT
CONFIRM THE ASSOCIATION WITH
GESTATIONAL DIABETES BUT DID
FIND THE ASSOCIATION WITH HYPER
TENSIVE DISORDER.
THERE'S NO ASSOCIATION WITH
GESTATIONAL DIABETES SEEMED TO
NOT BE ASSOCIATED WITH THAT.
AND FOR EXAMPLE THE REGULATING
HORMONE AND ITS ROLE IN
GESTATIONAL DIABETES PERHAPS
MORE SO THAN ENDOTHELIAL
DYSFUNCTION AND PREECLAMPSIA AND
THERE WAS THOUGHT PROVOKING DATA
FROM THE NEW MOM TO BE COHORT
AND I'M GLAD YOU POINTED IT OUT.
>> AS A RELATED QUESTION IT
SOUND LIKE SOME OF THE SLEEP
APNEA PHENOTYPES AND ANYONE CAN
ADDRESS THIS, IT SEEMS THE SLEEP
APNEA PHENOTYPES DON'T MEET THE
TYPICAL SEVERITY LEVEL WE
NORMALLY SEE IN THE NON
PREGNANT PEOPLE OR THE SUBTLE
AIR FLOW EVENTS SEEM TO POSE A
CARDIOVASCULAR RISK.
WHY DO YOU THINK IN PREGNANCY
EVEN SMALL -- I'M NOT SURE THIS
IS THE RIGHT WAY TO SAY IT BUT
LOW LEVELS HAVE HIGH IMPACT?
DO PREGNANT WOMEN HAVE INCREASED
SUSCEPTIBILITY TO THESE
EXPOSURES?
OR DO WE NOT HAVE THE
INFORMATION ON THAT YET?
>> I DON'T KNOW OF SOME OF THE
THINGS THAT MAKE PREGNANCY
UNIQUE LIKE WITH BIOLOGY AND THE
HORMONES IF THIS IS ACCELERATING
SOME OF THE MECHANISMS.
YOU'RE RIGHT.
WE SEE SIX MONTHS AFTER AN
EXPOSURE VERSUS WHEN YOU HAVE
SLEEP APNEA OUTSIDE THE PREGNANT
POPULATION THE EXPOSURE IS YEARS
AND YEARS BEFORE YOU SEE THE
OUTCOMES.
SO THERE IS SOMETHING ABOUT
PREGNANCY AND I DON'T KNOW IS IT
HORMONAL OR HOW IT IMPACTS
INFLAMMATORY PATHWAYS THAT MAKES
THEM HAPPEN QUICKER OR MAYBE THE
PLACENTA IS MODULATING SOME
EFFECTS AND MAKING THEM HAPPEN.
I DON'T FLOW.
-- I DON'T KNOW.
>> YOU'RE RIGHT.
WE DON'T KNOW AND COULD THERE BE
PLACENTAL LEVEL EFFECTS THAT
CONTRIBUTE TO SIGNALS FOR
ENDOTHELIAL DYSFUNCTION WE DON'T
SEE IN A NON PREGNANT POPULATION
AND INTERESTING AND FURTHER
RESEARCH IN COHORTS IN NEW MOM
OR OTHER COHORTS THAT HAVE BEEN
SPOKEN ABOUT COULD HELP ANSWER
THAT.
>> THANK YOU.
>> LET'S GO TO OUR PANELISTS
WITH QUESTIONS.
>> CAN I ASK A QUESTION?
>> GO AHEAD.
>> EXCELLENT TALKS.
I COMMEND YOUR WORK.
WE ALL KNOW HOW DIFFICULT IT IS
TO RECRUIT AND GET THEM AND
KEEPING THEM ON TREATMENT.
EXCELLENT WORK.
MY QUESTION/COMMENT IS ABOUT THE
BALANCE WHEN I WE SCREEN AND
TREAT THESE WOMEN AND ALL
UNDERSTAND THE PRAGMATIC
IMPLICATIONS OF THE LONGEST
DURATION AND BENEFIT.
I DON'T THINK REALLY KNOW IF THE
TREATMENT CORRELATES WITH
OUTCOMES.
CLINICALLY WE SEE PROBLEMS IN
THE THIRD TRIMESTER WHEN WOMEN
PRESENT WITH THE GREATEST AMOUNT
OF SYMPTOMS AND THEN COME TO US
AND ARE RUSHING TO GET THEM
TESTED AND STARTED ON TREATMENT.
OF COURSE THERE'S A WHOLE
IMPLEMENTATION PIECE BUT I'M
ALSO WONDERING WHAT YOU THINK
ABOUT THE GAP OR THE FURTHER
NEED TO STUDY THE TIMING OF
DIAGNOSIS OR THE DOSE OR
DURATION AS YOU WERE TALKING
EARLIER TODAY IN RELATION TO NOT
ONLY THE MATERNAL OUTCOMES OF
BLOOD PRESSURE, GLUCOSE AND
CHILD HEALTH OUTCOMES AT THE
PLACENTAL LEVEL AND SOME MAY
HAVE HAD SLEEP APNEA
PRE-PREGNANCY AND DON'T KNOW THE
SLEEP COURSE WAS IT DE NOVO IN
PREGNANCY AND WAS THAT A
PHENOTYPE AND TALK ABOUT
POSTPARTUM AND MENOPAUSE.
TO SAY THAT TEASING OUT OF
TIMING OF DIAGNOSIS AND THE
DURINGATION -- DURATION OF
OUTCOMES.
>> YES TO EVERYTHING YOU SAID.
WHEN YOU PICK A TRIAL AND THE
THIRD TRIMESTER EVALUATION
TREATMENT COULD HAVE BENEFIT IN
TERMS OF PATIENTS ALREADY WITH
PREECLAMPSIA AND ARE THERE
BENEFITS TO BLOOD PRESSURE
CONTROL AND LATENCY AND HAVING
LONGER LATENCY AND NOT HAVING TO
DELIVER EARLIER.
THERE'S SOME DATA THAT'S BEEN
PRESENTED AND PUBLISHED IN THE
PAST.
I THINK IT'S AN EXCELLENT
QUESTION.
LOGISTICALLY IT'S A CHALLENGE
BECAUSE BETWEEN SCREENING,
GETTING TREATMENT AND WE HAVE AN
IDEALIZED SETTING IN A RESEARCH
TRIAL WHERE WE HAVE LIKE NURSES
AND RESEARCH STAFF LIKE ON THE
READY IMMEDIATELY TO GET
SOMEBODY ON THE CPAP MACHINE.
IN THE REAL WORLD IT'S A MORE
COMPLICATED THING.
IT WOULD BE AMPLIFIED MORE IN
REAL WORLD TO GET PEOPLE TREATED
AND COMPLIANT.
BUT YOU'RE RIGHT I DON'T THINK
WE KNOW THERE'S THERE COULDN'T
BE BENEFIT EVEN IN SHORTER
DURATIONS OF THERAPY IF YOU CAN
GET PATIENTS COMBLIENT.
-- COMPLIANT.
>> I WANT TO ADD SOMETHING TO
THIS.
THE BEST TIME TO INTERVENE IS
BEFORE PREGNANCY HAPPENS AND A
LOT OF WORK NEEDS TO BE DONE IN
PRIMARY CARE LEVEL AND SCREENING
YOUNG WOMEN AND IDENTIFYING
DISEASE AND TREATING THEM
BECAUSE IF WE THINK WHEN THE
PREGNANCY OUTCOMESS ARE BEING
DEVELOPED AND BIOLOGY HAPPENS
THAT IMPACTS HOW OUTCOMES ARE
GOING TO HAPPEN.
A COUPLE YEARS AGO WE LOOKED AT
INSULIN RESISTANCE WITH WOMEN
DIAGNOSED WITH OSA AT 11 WEEKS
OF GESTATION.
THE ASSUMPTION IS AT 11 WEEKS IT
PROBABLY PREDATED PREGNANCY
PROBABLY NOT DIAGNOSED AND
LOOKED AT INSULIN RESISTANCE AND
IT WAS HIGHER SO THEIR
PREDISPOSITION TO DEVELOPING
THESE ADVERSE METABOLIC OUTCOMES
ARE PROBABLY ALREADY THERE EARLY
ON.
IN TERMS IS IT EVER TOO LATE TO
DIAGNOSIS SOMEONE WITH
PREGNANCY, THE BULK OF PEOPLE I
SEE ARE IN LATER PREGNANCY BUT I
STILL MAKE AN EFFORT TO MAKE A
DIAGNOSIS BECAUSE OF THE
IMPLICATIONS TO LABOR AND
DELIVERY AND MEDICATION TO USE
AND THE TYPE OF ANESTHESIA AND
MONITORING.
THERE'S A REASON TO MAKE THE
DIAGNOSIS EVEN IF YOU CAN'T
START CPAP TREATMENT OR GET THEM
ACCLIMATED TO TREATMENT,
ETCETERA, DURING THE COURSE OF
PREGNANCY.
>> THANK YOU.
>> THANKS.
WE'LL TAKE TIME FOR ONE MORE
COMMENT JUST TO MAKE SURE
EVERYBODY HAS A BREAK BUT THERE
WERE A COUPLE QUESTIONS RELATED
TO SLEEP AND HOT FLASHES OR
CARDIOVASCULAR INSTABILITY AND
THIS IS ONE OF THEM.
CAN YOU COMMENT ON WHAT WE
CURRENTLY KNOW ABOUT THE
INTERACTION BETWEEN HOT FLASHES
AND SLEEP DISORDER BREATHING
EVENTS SUCH AS THEIR
BI-DIRECTIONALITY?
>> THIS IS AN AREA WE NEED
TREMENDOUS INVESTMENT IN BECAUSE
THEY'RE BOTH VERY COMMON KWNZ
CONDITIONS.
WE DON'T KNOW.
WE DON'T HAVE THE DATA.
WE TYPICALLY EXCLUDED PEOPLE
WITH SLEEP DISORDER BREATHING
FROM HOT FLASHES AND THEY'RE NOT
ALL CAPTURED AND QUANTIFIED
MEANINGFULLY AND THEY BOTH HAVE
CARDIO METABOLIC CONSEQUENCES
AND IT'S AN AREA OF REAL
PRIORITY FOR FURTHER KNOWLEDGE.
AND WE ALSO KNOW THAT HORMONE
THERAPY DOESN'T REALLY TREAT THE
OSA.
IT CAN TREAT THE HOT FLASHES AND
NOT OSA.
WE DON'T HAVE STRATEGIES ALWAYS
TO TREAT THEM IN A COMBINED WAY.
SO WE NEED TO INVEST MORE IN
THAT.
>> THANK YOU.
WE'LL BREAK RIGHT NOW TO MAKE
SURE EVERYONE HAS TIME TO TAKE A
BREAK THESE TALKS REALLY REVEAL
IMPORTANT ASPECTS ABOUT SLEEP
AND PREGNANCY AND IN MENOPAUSE
AND ADDRESS A PUBLIC HEALTH VIEW
THAT SLEEP PROBLEMS THAT OCCUR
DURING THESE TIMES OF LIFE
DURING PREGNANCY AND MENOPAUSE
ARE NOT JUST NORMAL
MANIFESTATIONS IT'S NOT JUST OF
COURSE SOMEONE PREGNANT DOESN'T
SLEEP WELL BECAUSE OF CHANGES.
THEY'RE CONSEQUENTIAL.
HAVING POOR SLEEP DURING
PREGNANCY OR MENOPAUSE IS NOT
OKAY.
THERE NEEDS TO BE MORE
RECOGNITION THEY SHOULD BE
ADDRESSED AND ABOUT THE
IMPORTANCE OF IMPROVING SLEEP
AND MITIGATING THE SLEEP
DEFICIENCY DURING THESE STAGES.
I THINK THAT'S IMPORTANT FOR
PUBLIC HEALTH MESSAGING.
WITH THAT WE'LL TAKE A BREAK
CONVENE AT 3:10 FOR SESSION 3. THANK YOU TO SPEAKERS. WE APPRECIATE IT.
>> I'LL BE MODERATE BEING THE
NEXT SESSION ON VIZIO
PHYSIOLOGIC AND USING MACHINE
LEARNING AND ARTIFICIAL
INTELLIGENCE APPROACHES TO
PROVIDE A COMPREHENSIVE PICTURE
OF THE UNDERSTANDING OF THE
HETEROGENEITY AND WHAT IT MEANS
FOR LONG-TERM HEALTH
CONSEQUENCES.
WE HAVE FOUR TALKS.
THE FIRST THREE ARE SCHEDULED
FOR 13 TO 15 MINUTES AND I'LL BE
PROVIDING PEOPLE WITH A HEADS UP
TO KEEP US ADHERING TO THE
SCHEDULE AND THE FOURTH TALK
WILL BE 30 MINUTES AND FOLLOWING
THE LAST TALK AT 4:30 BE 30
MINUTES FOR GENERAL QUESTION AND
ANSWER.
AND FOR SPEAKERS STILL ON HAVE
QUESTIONS AND FOR COMMENTS
ARRIVING FROM THE TALKS WHICH
SHOULD BE PROVOCATIVE BECAUSE
THEY'RE COVERING AN AREA QUITE
CURRENT, ARTIFICIAL INTELLIGENCE
ANALYSIS OF OSA.
LET ME START TO INTRODUCE IT THE
SPEAKERS.
THE FIRST SPEAKER IS
DR. ALLANPACK PROBABLY KNOWN TO
EVERYBODY ON THE CALL.
THE ASSISTANT DEAN MUCH THE
PROGRAM AND VRCH OF TREATMENT
TRAINING IN THE DEPARTMENT OF
MEDICINE AT THE UNIVERSITY OF
PENNSYLVANIA MEDICAL SCHOOL IN
PHILADELPHIA.
HIS PRESENTATION IS ENTITLED
DIFFERENT DIMENSIONS OF
HETEROGENEITY OF OSA.
THANKS FOR JOINING US ALLAN.
LOOKING FORWARD TO HEARING YOUR
TALK.
SAID HE WANTS TO RUN THE SLIDES.
OKAY.
>> MAYBE WE CAN GIVE HIM A
COUPLE MINUTES.
>> OKAY.
>> THE NEXT SPEAKER IS ANDREW
WELLMAN AND HIS TALK IS RACIAL
DIFFERENCES IN OXYGEN-BASED
ENDOTYPES IN OSA.
TAKE IT AWAY, PLEASE.
>> SOME OF YOU MAY HYPOXIC
BURDEN IS THE MEASUREMENT UNDER
THE CURB WHEN THE SATURATION
DROPS DURING A SLEEP APNEA
EVENT.
I'M NOT GOING TO TALK TOO MUCH
ABOUT THIS OTHER THAN TO SAY
SOME STUDIES ONE FROM OUR LAB
AND ANOTHER ONE INDEPENDENT OF
US SUGGESTED IF YOU HAD A HIGH
HYPOXIC BURDEN YOU HAD LESS
CHANCE OF SURVIVAL.
AND SHOW YOU A PAPER THAT SHOWED
DIFFERENCES IN OXYGEN
MEASUREMENTS.
HOW WILL THAT AFFECT -- HOW IS
DIFFERENT SKIN TONES GOING TO
AFFECT THE HYPOXIC BURDEN
MEASUREMENT WE THINK IS AN
IMPORTANT PREDICTOR OF
CARDIOVASCULAR OUTCOMES IN SLEEP
APNEA.
REAL QUICK, I WANTED TO TALK
ABOUT THE PHYSICS OF PULSE OX
OXIMETRY.
YOU SEEN RED LIGHT THROUGH THE
PULSIFIED TISSUE AND EACH TIME
THERE'S A HEARTBEAT THAT YOU
MEASURE THE RED LIGHT THAT AND
THE AMPLITUDE OF THE INFRARED
LIGHT AND LOOK AT THE RATIO AND
BASED ON THE RATIO YOU GET THE
READING.
THE REASON THE RED LIGHTS -- THE
INFRARED AND RED LIGHT
TRANSMISSION THROUGH THE FINGER
CHANGE IS BECAUSE WHENEVER
HEMOGLOBIN IS OXYGENATED IT
CHAN
CHANGES TRANSMISSION.
WATCH THE ANIMATION AND YOU'LL
SEE THREE DIFFERENT OXYGEN
SATURATION LEVELS.
AGAIN BY GIVING THE RATIO OF THE
RED TO THE INFRARED LIGHT.
IF THE RED LIGHT IS LOW YOU GET
A HIGH READING AND IF THE
AMPLITUDE IS HIGH COMPARED TO
THE BLUE SFLAL YOU GET
READING.
WE WORK WITH PAUL AND HAS
EXPERIENCE IN THE TRIALS AND HIS
PAPER WAS NEVER PUBLISHED.
HE SHINED THE RED LIGHT AND THE
WAVE LENGTH AND YOU GET THE
COUNTS AND THAT'S HOW INTENSE
AND THROUGH AN EAR LOBE IT
REDUCES THE TRANSMISSION BUT
LOOK WHAT HAPPENS WHEN YOU SHINE
IT THROUGH PEOPLE WITH DARK
EARS.
NOT THE RED LIGHT DOES NOT PASS
THROUGH THE BLACK EARS NEARLY AS
WELL AS THE RED EARS.
IF YOU LOOK AT THE INFRARED
LIGHT WITH WHITE EAR AND BLACK
EAR AND NOT MUCH ATTENUATION IN
INFRARED.
NOTICE IF THE RED LIGHT IS SMALL
COMPARED TO THE BLUE LIGHT YOU'D
GET A LARGE SPO2 VALUE.
I'VE NEVER HEARD ANYONE EXPLAIN
WHY.
TO ME SOME SOMEBODY CLAIMS THEY
SOLVED THE RACIAL BIAS IN
OXIMETRY THEY NEED TO EXPLAIN
HOW THEY FIX THIS WE'D LIKE TO
GET FUNDING.
I DON'T KNOW IF YOU JUST TURN UP
THE RED LIGHT INTENSITY WILL IT
FIX THIS, FIX THE SENSOR?
I DON'T KNOW OUT IT SEEMS IT'S A
PROBLEM THAT SHOULD BE DISCUSSED
THE INABILITY OF THE RED LIGHT
TO PASS THROUGH DARK TISSUES.
THIS IS THE NEW ENGLAND JOURNAL
OF MEDICINE PAPER AND I'LL SAY
BRIEFLY, IN WHITE PATIENTS THE
OXYGEN SATURATION WAS
CONSISTENTLY HIGHER BUT THREE TO
FOUR PERCENTAGE POINTS THAN
SELF-IDENTIFIED BLACK PATIENTS.
SO HERE YOU'D GET A MEASUREMENT
OF 91% IN THE WHITE PATIENTS AND
87 OR SO PERCENT IN THE BLACK
PATIENTS.
THERE WERE MANY ETHNIC GROUPS
AND ASIAN AND BLACK AND WHITE
AND HISPANIC PATIENT AND
COMPARED PEOPLE WITH THE SAME
AHI, BLACK AND WHITE PATIENT.
LOOK AT THIS DIFFERENCE THE TOP
IS AIR FLOW AND SATURATION AND
THE DELTA HEART RATE NOTICE THIS
PERSON WITH LOTS OF APNEAS
THERE'S NO DESATURATION AND
HYPOPNEA.
THIS IS CRAZY TO ME.
ALL THESE EVENTS WILL GET
SCORED.
SURELY THERE'S BETTER LUNG
RESERVE AND MAYBE THAT'S THE
ISSUE.
THESE EVENTS AND THIS PERSON IS
REAL.
LOOK AT HOW MUCH HEART RATE
SURGE YOU GET IN RESPONSE TO THE
APNEAS.
THEY'RE NOT AS MUCH AS THE
PATIENT OVER HERE.
THIS PERSON ON THE LEFT I THINK
IS DESATURATING AND YOU'RE JUST
NOT PICKING UP ON IT.
MAYBE THAT'S WHY AND I CAN'T SEE
ANYONE BUT WHEN I SAW THIS IT
KNOCKED ME OUT OF MY SEAT.
FOR 20 YEARS I'VE WITHIN LOOKING
AT READING SLEEP STUDIES AND
TRIED TO GO BACK AND THINK ABOUT
HOW MANY OF MY PATIENTS WITH
DARK SKIN TONE MAYBE HAD LOTS OF
SNORING AND AHI WASN'T VERY
HIGH.
MAYBE THEY ARE WERE TIRED AND WE
JUST WROTE IT OFF.
I DON'T KNOW WHAT TO DO ABOUT
THIS.
I CAN KEEP
P GOING.
WE JUST WENT THROUGH ALL THESE
STUDIES.
PEOPLE WITH -- THIS IS
CONTINUOUS CYCLING HYPOPNEA ON
THE LEFT.
IT'S NOT LIKE IT'S A LITTLE
HYPOPNEA HERE AND THERE THAT
GETS MISSED.
AND BIG HEART RATE SURGES.
TO ME THAT ALONE -- WE HAVE TO
LOOK AT THIS HOW MANY OF
THESE PATIENTS ARE BEING MISSED
OR SYMPTOMS ARE BEING CHOPPED UP
TO LAZINESS OR SOME OTHER REASOA
ON 3% TO 4% DESATURATION.
HOW MANY ARE BEING MISSED?
WE SCORED ON A 50% REDUCTION IN
AIR FLOW AND SAW HOW MANY OF
THOSE -- LET'S CALL THOSE FLOW
EVENTS.
HOW MANY OF THOSE SLOW EVENTS,
HOW MANY NEVER PRODUCED THE
REQUIRED 3%?
15% IN BLACK MEN AND LOOK, 30%
IN PLAQUE WOMEN.
-- BLAWOMEN.
SO 30% OF HYPOPNEAS ARE BEING
MISSED IN OUR BLACK FEMALE
PATIENTS.
AND OF THE MISSED HYPOPNEAS I
THINK ARE REAL PAUSE WHEN WE
MEASURE THE AHI BASED ONLY ON
AIR FLOW IN BLACK INDIVIDUALS,
IT PRODUCED AN INCREASED HAZARD
RATIO FOR CARDIOVASCULAR EVENTS
BUT IF YOU REQUIRED THE AIR FLOW
EVENTS ALSO HAVE DSAP YOU LOSE
THE PREDICTABILITY.
SO THE FLOW EVENTS ARE REAL IN
MY MIND.
SO BASED ON THIS NDING, THERE
WAS AN EXPERIMENT WHERE WEEN HA
PATIENTS DO A 20 SECOND BREATH
HOLD AT FRC AND I JUST WANTED TO
SEE HOW MANY OF THESE 20-SECOND
BREATH HOLDS DURING WAKEFULNESS
WE COULD COACH PEOPLE TO DO THIS
AND SEE HOW MANY TIMES THEY ARE
DESATURATED TO 3%.
AND SO THE DARK SKIN INDIVIDUALS
ON THE RIGHT AND INDIVIDUALS
WITH LIGHT INDIVIDUALS ON THE
LEFT --
>> SORRY TO INTERRUPT THERE'S
ABOUT TWO
UTES LEFT.
THANKS.
THANK YOU.
>> THE WHITE PATIENTS
DESATURATED LIKE 3.5% BUT THE
BLACK PATIENTS DESATURATED ONLY
ABOUT 2%.
THESE ARE MATCHED FOR SEX AND
BMI.
AND BY THE WAY, THERE WAS ONLY A
.2% DIFFERENCE IN THE BASELINE
OXYGEN SATURATION BETWEEN THE
GROUPS.
MEANING THE RACIAL BIAS IS WORSE
FOR DETECTING THESE TRANSIENT
OXYGEN DROPS.
THERE'S REALLYEA NOT MUCH RACIA
BIAS IN THE VALUES LIKE THE
PAPER.
SOMETHING NEEDS TO BE
INVESTIGATED.
BY THE WAY, THE BLACK
INDIVIDUALS IN THE COHORT WERE
NOT DESATURATING BECAUSE SOMEHOW
THEY HAD BETTER LUNGS.
IN FACT WE MEASURED THE EXPIRED
WE HAD THEM EXHALE TO RESIDUAL
VOLUME AND THE OXYGEN DROPPED
MORE THAN THE WHITE PATIENTS BUT
WASN'T EVEN PICKED UP THAT MEANS
FOR THE SAME AIRWAY OBSTRUCTION
THEY HAVE A LARGER DROP AND AND
SMALLER DETECTED DROP AT THE
FINGER TRIP.
-- FINGERTIP.
IS WE WERE MISSING SLEEP APNEA
IN THE PATIENTS.
I'LL STOP THERE BECAUSE I RAN
OUT OF TIME.
>> WE DON'T HAVE DR. PACK YET
AND WE'LL MOVE ON TO
DR. GAYNANOVA AN ASSOCIATE
PROFESSOR OF BIO STATISTICS AT
THE UNIVERSITY OF MICHIGAN ANN
ARBOR AND HER PRESENTATION IS
MACHINE LEARNING FOR GLYCEMIC
MEASURES AND APPLICATIONS FOR
OSA.
ARE YOU READY?
>> YES.
>> THANK YOU FOR STEPPING IN
SHORT NOTICE.
>> THANK YOU.
THERE WAS TALKS TODAY DURING
PARALLELS WITH HYPERTENSION AND
PREVALENCE WITH RSA AND
GESTATIONAL DIABETES.
WHAT I WOULD LIKE TO POINT OUT
IS WE KEEP DOING THIS RANDOMIZED
CLINICAL TRIALS WHERE WE
PRESCRIBE THERAPY TO PATIENTS
WITH DIABETES AND WE KEEP
REACHING INCONCLUSIVE EFFECTS
REGARDING THE EFFECTS OF THE
TREATMENT ON GLUCOSE METABOLISM.
I THINK WITHIN HYPERTENSION THE
CONCLUSION IS MUCH BETTER.
AND SOMETIMES WE MEASURE THESE
THINGS SO WE MEASURED GLUCOSE
USING A1C WHICH IS A CRUDE
SUMMARY BECAUSE IT'S CAPTURING
THE AVERAGE GLUCOSE OVER THE
PRECEDING TWO TO THREE MONTHS.
WHEN WE MEASURE BLOOD PRESSURE
WE USUALLY DO ONE TIME BLOOD
PRESSURE READING.
WHEN WE DO THE USUAL ASSESSMENT
WE DON'T REALLY CAPTURE THE
TEMPORAL VARIABILITY IN THE
MEASUREMENTS AND WE MAY BE
REACHING A LIMITED UNDERSTANDING
OF THE IMPACT OF THE SLEEP APNEA
IN THE MEASURES.
IN THE TALK I'LL FOCUS PRIMARILY
ON GLUCOSE AND I'LL GIVE YOU A
HINT ON HOW THE BLOOD PRESSURE
CONDITION CAN CONNECT THESE DAYS
WE HAVE VARIABLE DEVICES ONE
WILL THE PROMISE OF RICH
TEMPORAL DATA.
THERE'S ADVANCEMENTS IN GLUCOSE
MONITORING AND ADVANCEMENT IN
BLB AND IF WE USE ADVANTAGE OF
THE TEMPORAL CHARACTERISTICS OF
THE DATA WE CAN LOOK AT THE
HETEROGENEITY IN FEATURES ACROSS
PATIENT AND THE RESPONSE TO
TREATMENT.
SPECIFICALLY I'LL FOCUS ON
CONTINUOUS GLUCOSE MONITORS THE
AREA OF MY EXPERTISE.
SMALL WEARABLE DEVICES.
THEY HAVE A LITTLE NEEDLE ON
THEM AND MEASURE INTERSTITIAL
GLUCOSE EVERY FIVE MINUTES.
ONE MONITOR TYPICALLY LASTS 10
DAYS OR 14 DAYS FOR THE FREE
STYLE LIBRE AND THE STANDARD OF
CARE FOR PEOPLE WITH TYPE I
DIABETES AND RECOMMENDED FOR
THOSE ON INSULIN CONTROL AND
INCREASINGLY USED IN CLINICAL
PRACTICE AND RESEARCH STUDIES.
IF WE TAKE A MEAN OF THE PROFILE
HERE'S AN EXAMPLE OF DATA FROM
TWO DIFFERENT SUBJECTS, 24
HOURS.
AND WHAT WE SEE IS THE QUESTION
IS CAN WE DO BETTER AND GO
BEYOND THE MEAN?
THIS IS WHERE THE LITERATURE
WITHIN DIABETES COMMUNITY IN
PARTICULAR HAS SEEN AN EXPLOSION
ON DIFFERENT METRICS OF GLYCEMIC
CONTROL PROPOSED.
ONE OF THE EARLIER PAPER THAT
SUMMARIZES A LOT OF THE METRICS
BUT THERE'S DIFFERENT PAPERS OUT
THERE AND DEVELOP A PACKAGE THAT
CAN CALCULATE OVER 60 METRICS OF
GLYCEMIC CONTROL AND THIS
CREATES A LOT OF CONFUSION FOR
RESEARCHERS AND CLINICIANS ALIKE
TO WHICH METRICS WE SHOULD USE.
THERE'S BEEN A CONSENSUS THAT'S
BEEN REACHED IN TERMS OF THE
MEASURES USED FOR CLINICAL
TRIALS TO MEASURE GLYCEMIC
CONTROL AND I WILL ARGUE IT'S
BEEN REACHED BASED ON
CONSIDERATIONS FOR PATIENTS WITH
TYPE 1 DIABETES.
A LOT OF TIMES WHEN WE SEE
COMORBIDITIES AND SLEEP APNEA
IT'S IN TYPE 2 DIABETES PATIENTS
SO IT'S NOT CLEAR THE METRICS
ARE THE SAME AND THERE WAS
INTERPRETABILITY AND SIMPLICITY
WHERE MAY NOT ALLOW US TO
CAPTURE SIGNALS.
TO SUMMARIZE HERE'S AN EXAMPLE
OF WHERE A PERSON WITH DIABETES
AND TYPICALLY THE TAR GUEST IS
TO BE WITHIN THE RANGE TYPICALLY
WE TAKE THE TEMPORAL PROFILE AND
CREATE SUMMARIES.
SUCH AS THE MEAN, PERCENTAGE OF
TIME AND STANDARD DEVIATIONS AND
SO FORTH.
IF WE TRIED TO USE THEM ALL WE
CAN'T FIND ANY ASSOCIATIONS ALSO
WHEN WE USE MEASURES BASED ON
THRESHOLDS, TIME AND RANGE, THEN
WE HAVE A DEPENDENCE ON THE
THRESHOLD CHOICE.
AGAIN THE THRESHOLDS WERE
DESIGNED FOR PEOPLE WITH TYPE 1
DIABETES IN MIND.
IT'S NOT CLEAR THE SAME
THRESHOLD SHOULD BE USED IF
WE'RE INTERESTED IN SETTING
GLUCOSE WITHIN THE OSA CONTEXT.
AND DR. NISHA RAW--AURORA
MENTION THE TRIAL AND THESE WERE
MEASURED RAT THE
AT THE BASELINE AND THREE MONTHS
LATER AND NO DIFFERENCE WAS
FOUND WHEN LOOKING AT THE
STANDARD DEVIATION.
WITH LOOK AT HOW THE POP THERAPY
IS GOING TO AFFECT TGLUCOSE AND
WE KEEP FINDING NOTHING.
IT COULD BE THERE'S NO SIGNAL OR
NEED TO ADJUST FOR THE
HETEROGENEITY OF SIGNAL BUT
COULD BE WE NEED MORE
INFORMATION FROM THE DATA.
THE IDEA I WANT TO ADVERTISE IS
USING THE DATA.
THE BASIC IDEA IS HERE'S AN
EXAMPLE OF THE PROFILE FOR ONE
PERSON.
THIS IS ROUGHLY SEVEN DAYS OF
MEASUREMENT AND RATHER THAN
CREATING THE SUMMARY SUCH AS THE
MEAN OR STANDARD DEVIATION OR
TIME SPENT WITHIN THE THRESHOLD
WE'RE GOING TO REPRESENT ALL
THIS GLUCOSE MEASUREMENT AS A
MEASUREMENT OVER HERE.
THE IDEA IS KNOWN AS
GLUCODENSITY AND FIRST PROPOSED
AND THE ADVANTAGE OF THE
APPROACH IT IT GOES TO THE
SPECIFIC CHOICES OF THE
THRESHOLD.
I'M SHOWINGOL170 AND 180 SO IT
CAPTURES THE THRESHOLD.
AND CAPTURES A COEFFICIENT OF
VARIATION.
THE IDEA IS TO USE THE DENSITY
AS A PRESENTATION AS AN OUTCOME
OF CHOICE AND THAT WOULD PROVIDE
US MORE POWER TO DETECT
ASSOCIATIONS WHILE ADJUSTING FOR
THE COVARIATES THAT COULD BE
IMPORTANT.
SO SPECIFICALLY WE APPLIED THIS
TO THE BASELINE DATA FROM
STUDIES.
I WANT TO EMPHASIZE IT'S NOT AN
EFFECTIVE POP THERAPY AND
GLUCOSE DISTRIBUTION AND LOOKING
AT A RAY OF 30 PLUS BASELINE
COMMUNITIES SUCH AS SEX, AGE,
RACE, MEDICATIONS, ETCETERA
INCLUDING THE MEASURES OF
SEVERITY.
IT'S A COMBINATION OF THINGS
LIKE AVERAGE AND STANDARD
DEVIATION AND SO FORTH.
AND USE THE MACHINE LEARNING
METHODS TO TRY TO SEE OUT OF ALL
OF THE COVARIATES CAN WE FIGURE
OUT WHICH ONES MAY HAVE A
BASELINE EFFECT AT THE GLUCOSE
VALUES WITH THE IDEA IF WE SEE
THE BASELINE DIFFERENCES
DEPENDING ON SAY SEVERITY OF OUR
RSA WE HAVE SOME HOPE IT WILL
MAKE AN IMPROVEMENT.
THIS IS THE FINDING WE HAVE.
SO BASICALLY WHAT I'M SHOWING
YOU IN THE THREE PANELS OF
COVARIATES WE FOUND TO BE
IMPORTANT WHEN WE DID THIS
BASELINE ANALYSIS.
THE FIRST IS THE BASELINE A1C
MEASUREMENTS A SELF-FULFILLING
PROPHECY AND LOOKED AT THE
MEASUREMENTS OF HEMOGLOBIN A1C
AND LOOKED AT THE BASELINE AND
HOPE THE TWO WILL BE RELATED.
WHAT WE SAW IS THE DISTRIBUTION
THE GLUCOSE GOING FROM THE
LOWER RANGE IN BLUE TO THE HIGH
RANGE OF A1C IN PU
THE TWO DENSITIES HAVE PEAKS
AROUND THE SAME AREA WHICH MEANS
THE DIFFERENCE WAS NOT IN THE
AVERAGE GLUCOSE LUT THE B
DIFFERENCE WAS IN TERMSEN OF
VARIABILITY.
THE SUBJECTS TAKING IT AT
BASELINE WERE PRESENT WITH
HIGHER VARIETY IN GLUCOSE
VOLUMES THAT THOSE THAT DIDN'T.
IT WAS SHOWING THE DIFFERENCES
AT BASELINE.
AND LOOK BEING AT OXYGEN
SATURATION CAN LEAD TO THE
HIGHER GLUCOSEUES AT
BASELINE COMPARED TO
VARIABILITY.
WE'RE CURRENTLY DOING
METHODOLOGICAL WORK TO ADJUST
THE FRAMEWORK WHERE REPEATED
MEASUREMENTS TO LOOK AT THE
AFFECT OF THERAPY AND REEXAMINE
THE DATA USING THE FRAMEWORK.
I WANT IT MENTION WHEN WE GO TO
THE BLOOD PRESSURE WE HAVE
BASICALLY THE SAME ISSUES AND WE
CAN CAPTURE THE DIPPING BUT A
LOT OF TIMES WE USE THE SUMMARY
OVERNIGHT.
AGAIN, WE HAVE A GREAT
OPPORTUNITY TO USE MORE ADVANCED
METHODS HERE SO WE CAN HAVE
BETTER DIFFERENTIATION ACROSS
SUBJECTS AND HAVE PROGRESS BUT
I'LL SKIP IT BECAUSE OF TIME.
THE KEY TAKEAWAYS AND
OPPORTUNITIES I SEE HERE IS WE
HAVE AND WE HAVE MEASURES FOR
GLYCEMIC MEASURES BUT IF WE USE
ADVANCED MACHINE LEARNING METHOD
AND THE FRAMEWORK CAN OFFER US
ADDITIONAL INSIGHTS BEYOND
CONVENTIONAL SUMMARIES.
I THINK BY BETTER ACCOUNTING FOR
THE DATA CHARACTERISTICS WE CAN
DEVELOP MORE PERSONALIZED
PHENOTYPES FOR BLOOD GLUCOSE
METABOLISM AND BLOOD PRESSURE
AND FINALLY GET DATA ON
COMORBIDITIES OF HYPERTENSION
AND WE CAN ADDRESS THE QUESTIONS
AND I'M THANKFUL FOR MY
COLLABORATORS WHO INTRODUCED ME
TO THE QUESTIONS AND STUDY AND I
WANT TO ACKNOWLEDGE NIH SUPPORT.
I KNOW I FINISHED EARLY I THINK
WE HAVE TIME FOR QUESTIONS.
>> RIGHT ON TIME, ACTUALLY.
THANKS SO MUCH.
THANK YOU SO MUCH FOR THE
PRESENTATION.
I'M SURE THERE'LL BE QUESTIONS
ABOUT IT AT THE END.
ALFONSO WE DO NOT HAVE DR. PACK
YET WITH US FROM WHAT WE CAN
SEE.
>> I SEE DR. CK ONLINE.
I DON'T KNOW IF YOU'RE READY?
>> I'M READY TO GO.
>> THANK YOU.
HE'LL TELL US ABOUT DIFFERENT
DIMENSIONS IN HETEROGENEITY.
>> I'LL TALK ABOUT DIFFERENT
DIMENSIONS IN HETEROGENEITY.
THE WAY TO THINK OF PERSONALIZED
SLEEP APNEA IS MRULT --
MULTIPLE SOURCES TO THE RISK
VARIANTS AND DIFFERENT SYMPTOM
SUB TYPES AND DIFFERENT
PHYSIOLOGICAL CHARACTERISTICS D
SATURATION AND DIFFERENT
MOLECULAR RESPONSES SO WE'RE
DEALING WITH A SITUATION WITH
DIFFERENT DIMENSIONS.
AND THIS IS A SLIDE WE SHOWED
EARLIER AND THE REASONS FOR
THESE PATIENTS WITH APPARENTLY
THE SAME DISORDER ACT
DIFFERENTLY BECAUSE OF A
DIFFERENT ENVIRONMENT AND THE
ENVIRONMENT EFFECTS EPIGENETIC
MARKS AND DIFFERENT GENETICS AND
DIFFERENT MICROBIOME AND LEADS
PEOPLE TO BE VERY DIFFERENT
THOUGH THEY'RE THE SAME
DISORDER.
AS A RESULT OF THE BIOLOGICAL
DIFFERENCES YOU GET DIFFERENT
PHENOTYPES AND CHARACTERISTICS.
SOME ARE SLEEPY, SOME ARE NOT,
COMORBIDITIES, DIFFERENT PLEK
PROFILES AND TRANSCRIPTOMICS AND
DIFFERENCES IN PHENOTYPING BOTH
PHYSIOLOGY AND ALSO IMAGING.
THIS IS TRUE IN OSA AND VARIES
BROADLY IN ALL DISORDERS.
ALL PATIENTS ARE NOT IDENTICAL.
AND THE QUESTION IS HOW ARE WE
GOING TO APPROACH THAT?
THE IDEA IS WE'RE TALKING ABOUT
DIFFERENCES AND DIFFERENT
DOMAINS YOU'LL USE MULTIPLE
APPROACHES TO EVALUATE THE
DIFFERENCES.
YOU'LL LOOK FOR PHYSIOLOGICAL
AND CLINICAL DIFFERENCES AN
BIOMARKERS AND OMIC DIFFERENCES
AND GENETIC, EPIGENETIC
DIFFERENCES AND USED UNBIASED
DISCOVERY APPROACHES AND LET THE
DATA SPEAK FOR ITSELF.
THERE'S A HUGE AMOUNT OF
INFRASTRUCTURE TO SUPPORT THE
APPROACH.
PROGRAMS LIKE TOP MED AND NHLBI
AND THE U.K. BIO BANK AND SO ON.
THERE'S A LOT OF PROGRAMS OUT
THERE AND A LOT OF DATA
AVAILABLE FOR US TO APPROACH
THIS.
SO THESE RESOURCES HAVE BEEN
BUILT NOT JUST FOR SLEEP APNEA
BUT MORE BROADLY FOR HOW YOU
APPROACH PERSONALIZED MEDICINE.
THERE'S A VERSION OF
PERSONALIZED MEDICINE I LIKE
CALLED THE FOUR P MEDICINE.
IT WAS A CONCEPT PROPOSED AND
THE FOUR Ps ARE PREDICTIVE.
WE'RE GOING TO USE DATA TO
PREDICT WHO WILL GET DISEASE AND
IF WE CAN DO THAT WE CAN MOVE
MEDICINE FROM TREATING PEOPLE TO
PREVENTION.
IF THEY GET DISORDERS WE'LL
PERSONALIZED AND THE FOURTH P IS
PARTICIPATE.
THAT'S GETTING PATIENTS ENGAGED
IN THEIR OWN CARE.
THERE'S VERSIONS OF PERSONALIZED
MEDICINE AND THIS IS ONE I THINK
IS RELEVANT.
WE HAVE WRITTEN ABOUT THAT FOR A
WHILE ON THE FOUR P APPROACH.
PREVENTION AND PERSONALIZED AND
PARTICIPATING.
WE HAVE DIFFERENT PHYSIOLOGICAL
RISK FACTORS AND THE OBESITY
PATHWAY AND THE NON OBESITY
PATHWAY AND DIFFERENCES IN
NEURAL.
SO PEOPLE ARE GOING TO GET THE
DISORDER FOR DIFFERENT REASONS.
WE HEARD ABOUT ENDOTYPES AND
PROBABLY HEAR MORE AND AIRWAY
AND LOOP GAIN AND AROUSAL AND
UPPER AIRWAY MUSCLE
RESPONSIVENESS AND THE QUESTION
IS CAN THEY ARE BE DETERMINED BY
THE SIMPLE MODEL OF CONTROL?
I THY OF O BELIEVE
THERE'S A REAL NEED FOR
VALIDATION STUDIES BECAUSE TO
BUILD A MODEL YOU HAVE TO MAKE A
LOT OF ASSUMPTIONS AND THE
QUESTION DO THEY DEGRADE WHAT
YOU CAN DO AND WE'RE LOOKING FOR
VALIDATION STUDIES.
AS I'VE INDICATED THERE'S
MULTIPLE PATHWAYS.
THE FACT IS MANY OF THESE
PATHWAYS ARE GOING TO BE
GENETICALLY DETERMINED.
THERE'S DETERMINATES LIKE
OBESITY AND A NUMBER OF GRANTS
TO DETERMINE CRANIOFACIAL
STRUCTURE AND A NUMBER FOR
NEURAL CONTROL AND SOFT TISSUE
PLAYS A ROLE.
SO THERE'LL BE GENEITY AND HERT
GEN EIGHT AND THERE WAS A GWAS
STUDY AND THE SO-CALLED
MANHATTAN PLOT.
THE PEAKS REPRESENT WHERE
THERE'S AN ASSOCIATION BASICALLY
OF VARIANT IN THE REGION AND
THIS IS A LARGE STUDY DONE WHERE
THEY ACCUMULATED VETS AND GAVE
BLOOD AND 90% WERE MALE AND THEN
YOU RUN THESE ANALYSES BASED ON
DIAGNOSES COMING FROM THE E.H.R.
THIS IS FTO AND WE LOOK AT THE
UPSIDE-DOWN AT THE BOTTOM AND
ADJUSTED FOR BMI.
WHAT YOU CAN SEE IS THE O PLOT
COMPLETELY DISAPPEARS YOU HAVE
POLYMORPHISMS ASSOCIATED WITH
OSA AND SOME ARE OBESITY PATHWAY
AND THERE'S A NUMBER IN THE
NON-OBESITY PATHWAY.
AND WE LOOKED AT CASES TO
ANALYZE DATA AND WOMEN AND MEN
AND FOUND THE GENETIC RISK
FACTORS WERE DIFFERENT IN WOMEN
THAN THEY WERE IN MEN.
YOU HAVE TO TAKE THAT CAREFULLY
BECAUSE THE SAMPLE SIZE ARE VERY
DIFFERENT BUT IT'S CONCEIVABLE
THE GENETIC INFRASTRUCTURE THAT
DRIVES THIS IS DIFFERENT FOR MEN
AND WOMEN.
THIS WILL ALLOW US TO DEVELOP A
POLY GENIC RISK SCORES AND IF
YOU CALCULATE THESE THINGS YOU
CAN CALCULATE AND LOOK AT ALL
THE STEPS AND SO ON.
AND ALSO YOU NEED TO BRING IN
RARE VARIANTS IN THE POLY GENIC
RISK STORES AND I CAN PREDICT
WHO WILL DEVELOP OSA AND THAT
WILL CHANGE THE WAY I APPROACH
THE WHOLE THINK AND THINK OF A
PREVENTION.
THE OTHER QUESTION IS IN THE
ASSESSMENT OF VARIANTS WITH
INFORMATION OF THE PATHWAYS TO
THE DISORDER SOME WILL BE DUE TO
OBESITY AND SOME CRANIOFACIAL
AND IF I CAN SHOW THE INDIVIDUAL
HAS ASSOCIATION WITH THE
CRANIOFACIAL VARIANCE IT'S
TELLING ME SOMETHING ON THE
PATHWAYS TO DISEASE.
THE NEXT IS SYMPTOMS AND WE
HEARD OF INSOMNIA SYMPTOMS IN
FEMALES AND WHEN WE TOOK THE
QUESTIONNAIRES AND USED AND SAYS
THERE'S DIFFERENT GROUPS AND
WERE ABLE TO IDENTIFY THE GROUP
AND SOME WERE SYMPTOMATIC AND
SNORED AND SO ON BUT DIDN'T HAVE
COMPLAINTS RELATED TO SLEEP AND
WOKE UP REFRESHED AND A GROUP
THAT WAS VERY SLEEPY AND FELL
ASLEEP DRIVING AND SO ON.
YOU CAN SEE THE DIFFERENT SUB
TYPES AND THE FACT IT IMPROVES
TREATMENT IS REALLY RELATED TO
CLUSTER 3 YOU SEE AND YOU SEE
MINIMAL AFFECTS.
WE REPLICATED THIS IN STUDIES IN
AUSTRALIA AND ALL OVER THE WORLD
AND IN THE U.S. AND WHAT WAS
INTERESTING IS AND PROMINENT
GROUPS COME IN AND TRY TO BUILD
ON THAT.
WHAT'S INTERESTING IS THE
SYMPTOMS NOT ONLY WERE RELEVANT
BUT THE MAJORITY OF EVIDENCE
WOULD INDICATE THEY'RE
PREDICTIVE OF OTHER OUTCOME AND
CARDIOVASCULAR TERMS AND THERE
WAS A PAPER THAT SHOWED AN
INCREASED RISK OF CV EVENTS.
THERE WAS NO INCREASED RISK IN
THE MODERATE SLEEPY OR MINIMALLY
SYMPTOMATIC OR INSOMNIA.
THAT WAS REPLICATED IN OUR STUDY
AND YOU GOT AN INCREASED RISK OF
CV DISEASE AND THE FOUR GAVE A
BETTER DIFFERENTIATION AND A
NUMBER OF STUDIES HAVE SHOWN
THAT AND GREATER BENEFIT WITH
CPAP UNTIL FRENCH COHORT AND
HIGHER INCIDENTS IN CV EVENTS
AND SYMPTOMATIC IN THE OTHER
COHORT.
IN THE STUDIES HAVE SHOWN THE
NEW IDEA.
THERE'S A STRUCTURE TO REALLY
ASSIGN PEOPLE AND IF YOU LOOKED
AT PEOPLE WITH OSA AND AN
ASSOCIATION WITH PEOPLE WITH
HYPERTENSION AND IF YOU FOLLOWED
THEM OVER TIME MOST WERE
UNTREATED YOU FIND HIGHER RATE
OF INFARCTION IN PEOPLE WITH
EXCESSIVE SLEEPINESS.
THERE'S TWO NEGATIVE STUDIES.
ONE FROM THE FRENCH COHORT WHICH
SAID THERE WAS NO THE CV RISK
AND ANOTHER STUDY SHOWING NO
DIFFERENCE IN CV CASES WITH OR
WITHOUT EDS.
AND ONE DIFFERENCE BETWEEN THE
NEGATIVE AND STUDIED RECORDED
WAS THERE WAS MORE CPAP USE.
WHETHER THAT'S THE EXPLANATION
STATISTICALLY IT'S NOT
SUFFICIENT BUT NOTE WORTHY IN
THE STUDIES THAT HAVE POSITIVE
THERE WAS ACCEPT OR MINIMAL CPAP
USE.
WHERE DO WITH GO FROM HERE?
WITH HAVE TO KNOW AS MENTIONED
EARLIER AND ARE YOU STILL GOING
TO BE IN EXCESS AND AND THERE
ARE QUESTIONS WHETHER SOME ARE
ASYMPTOMATIC OR NEED TO BE
TREATED.
AGAIN, WE HEARD EARLIER AND YOU
STILL FIND THE SAME BASIC GROUPS
COME UP.
THERE'S STILL WOMEN EXCESSIVELY
SLEEPY AND THE PROPORTIONS VARY
BETWEEN MEN AND WOMEN BUT THE
BASIC CONSTRUCT DOESN'T CHANGE
AND IMPORTANT TO THINK ABOUT
MOVING FORWARD.
THERE AND WE LOOK AT PULSE RATE
AND AMPLITUDE THAT DROPS.
>> WE HAVE ABOUT A MINUTE LEFT.
>> THERE'S IMPROVED PROTECTION
OF CARDIOVASCULAR RISK.
AND WHAT WE NEED TO DO IS TAKING
INFORMATION ASSESSING DIFFERENT
DIM EDGES AND CAN WE INTEGRATE
THE DIFFERENT TO PROVIDE ONE
COMPREHENSIVE MEASURE.
AND DEVELOP AND VALIDATE POLY
GENETIC RISK SCORES FOR MEN AND
WOMEN.
WE SHOULD THINK ABOUT DEVELOPING
RANDOMIZED TRIALS WITHIN THE
FRAMEWORK OF THE SUBTYPES.
LET'S THINK ABOUT INSOMNIA
BENEFIT AND WE NEED TO MOVE
WHETHER SYMPTOMS OR PHYSIOLOGY
ARE THE BEST AND INTEGRATE
INFORMATION AND FINALLY THIS
ENTIRE EFFORT IN PERSONALIZED
SLEEP APNEA IS FACILITATED BY
RESEARCH CONSORTIUM.
I THINK THAT'S A VERY IMPORTANT
THING TO THINK ABOUT.
SO THANK YOU VERY MUCH.
>> IT SEGUES TO THE LAST TALK BY
DR. PAREKH WHO IS AN ASSISTANT
PROFESSOR IN THE DIVISION OF
PULMONARY CRITICAL CARE AND
SLEEP MEDICINE IN THE DEPARTMENT
OF MEDICINE AT THE ICAHN SCHOOL
OF MEDICINE AT MOUNT SINAI AND
HIS A.I. IN SLEEP APNEA AND
INTEGRATING SKWOERZ AND
BIOMARKERS AND FINDS AND
ENDTIEPT -- ENDOTYPES AND
ELUCIDATE DISEASE HETEROGENEITY
AND HIS TALK THERE BE TO ABOUT
4:30 AND THEN WE'LL HAVE MORE
TIME FOR TALK THAN WE'VE HAD.
>> THIS SEGUES ABOUT THE CARE
AND I'LL BE MORE PROVOCATIVE AND
POINT TO NOT TO WHAT HAS BEEN
DONE BUT THE WANL -- PATHWAY
FORWARD AND THINK OF INTEGRATING
THE DIFFERENT DOMAINS MENTIONED.
I THINK BY NOW ACROSS ALL THE
DIFFERENT TALKS I HOPE YOU'RE
CONVINCED AND IF YOU DIDN'T
ALREADY KNOW OSA IS A
HETEROGENEITY OF OUTCOME AND
THERE'S WE MYRIAD OF PATHWAYS
AND MECHANISMS TO THE EVENTS ARE
DIFFERENT AMONG INDIVIDUALS AND
OUTCOMES AMONG INDIVIDUALS AND
HOW TO WE CHARACTERIZE OSA AND
ITS HETEROGENEITY.
I'LL GIVE A QUICK REVIEW ON THE
DIFFERENT DOMAINS AND SOME OF
THE POINTS.
AND FIRST AND FOREMOST WE HAVE
BEEN DOING THIS SO MANY YEARS
USING CONVENTIONAL PO
POLYSOMNOGRAPHY AND CONTAIN
VARIABLES PATIENTS ARE USED TO
STARTING WITH RESPIRATORY
INDEXES AND VARIATIONS AND
PALPITATIONS AND MACRO AND MICRO
ARCHITECTURES AND MANY OTHERS
AND INFLAMMATION AND LEG
MOVEMENTS AND SO ON.
THERE'S ONE WAY TO CHARACTERIZE
THE HETEROGENEITY WE SEE.
SOME OF THE NEWER MEASURES AND
UNDER THE UMBRELLA TERM OF
PHYSIOLOGICAL BURDENS.
THESE MEASURES TRY TO USE THE
POLYSOMNOGRAPHY AND TRY TO
CHARACTERIZE MORE THAN OTHER
MEASURES.
AND ATTEMPTS IN MANY DIFFERENT
WAYS TO QUANTIFY THE AIR FLOW
AND VENTILATION CHANGES LOOK
BEING AT THE HYPOXIC DOMAIN
LOOKING AT THE OXYGEN SATURATION
CHANGES OVERNIGHT.
THE AROUSAL DOMAIN AND THE
ECONOMIC DOMAIN AND SUPPORTED BY
THE PULSE RATE CHANGES AND THESE
ARE SOME THAT HAVE RECENTLY COME
OUT BUT THERE'S A LOT MORE THAT
CAN COME UP.
AND A POINT OF NOTE THOUGH THE
BURDENS THE TRUE BURDEN IN SLEEP
APNEA IS ONE SO THERE'S ONE TRUE
REGULATORY BURDEN BUT ONE KEY
QUESTION WE SHOULD THINK ABOUT
IS ARE THESE ALL CORRELATED AND
DO THEY ARE GIVE THE SAME
INFORMATION?
THEN THERE'S ENDOTYPES USED TO
CHARACTERIZE OSA OR TYPE OF
OSAs.
I'LL TRY TO SUMMARIZE THIS
BRIEFLY BUT AND LOOKING AT THE
SYSTEM AND AROUSAL THRESHOLD AND
EASE OF SLEEP DISRUPTION BY
RESPIRATORY EVENTS AND
COLLAPSIBILITY BY THE STRUCTURE
OF THE UPPER AIRWAY.
AND THESE HAVE BEEN USED TO
CHARACTERIZE THE HETEROGENEITY.
AND THERE'S SYMPTOM SUBTYPES
BETWEEN COHORTS BASED ON SOME OF
THE QUESTIONNAIRE DATA AND SO
ON.
AND CLINICAL TYPES OF OSA AND
CLASSIFICATION THAT TRIES TO
INTEGRATE THE END ORGAN IMPACT
AND E.H.R. BASED.
THE RESEARCH HAS LOOKED AT
STATS, LAB, SYMPTOM SUPPORTS AND
COMORBIDITIES TO CHARACTERIZE
OSA OR CLUSTERS OR SUBTYPES THAT
CAN COME OUT FROM THE CLINICAL
REPORTS.
THERE'S PLASMA MARKERS AND
THERE'S BEEN STUDIES WITH
SEVERAL MARKERS.
VERY FEW HAVE BEEN REPLICATED
ACROSS THE DIFFERENT DATA SETS
BUT NONETHELESS THEY DO EXIST.
ABAC AND SO ON.
MARKERS OF SYSTEMIC INFLAMMATION
HAVE BEEN LOOKED AT AND TRIED TO
CAPTURE AS OSA AND ITS
HETEROGENEITY.
THE POLY GENETIC RISK SCORE.
IT'S A SPECIFIC SCORE WITH
SUSCEPTIBILITY TO ONE OF THE
PAPERS CORONARY ARTERY DISEASE.
ME TABL ICES -- METABOLOMICS
AND MOVING TO CHARACTERIZING
HETEROGENEITY WITH BIOMARKERS.
THE NEXT WAVE OF TECHNICAL
ADVANCES IN TERMS OF THE
WEARABLES THERE'S SMART WATCHES
AND SOME THAT HAVE RECENTLY HAD
FDA APPROVAL TO USE SOME
MODALITY TO DETECT SLEEP APNEA
OR MEASURES AND PATCHES PEOPLE
HAVE BEEN USING.
SOME ARE AND LOOKING SOME
SURROGATE OF MOVEMENT TO
DETERMINE SLEEP DISRUPTION AND
SLEEP APNEA IN GENERAL AND SOME
ARE TRYING TO USE SOME OF THE
OPTICAL TECHNIQUES TO PRODUCE
THE DIFFERENT CHARACTER ICS OF
OSA.
THERE'S SENSORS PLACED ON THE
BED AND MONITORED AND THE
TECHNOLOGICAL NOVATIONS AND
KNOWING HOW THEY PRODUCE THESE
THINGS AND PRESUMABLY THEY USE
SOME METER OR MOVEMENT-BASED
METRICS.
THERE'S CONTACTLESS MONITORS AND
SIT ON THE NIGHTSTAND AND TRY TO
RECORD THE CHEST MOVEMENTS AND
TRY TO DEDUCE SLEEP APNEA
SEVERITY OR EVENTS AND SO ON.
WE ALSO LOOK AT THE RESEARCH
THAT COULD BE USED TO LOOK AT
THE DYNAMIC MRI.
AND THERE'S BEEN A TECHNIQUE
TRYING TO LOOK AT DIFFERENT
KINDS OF CHARACTERISTICS THAT
COULD DIFFERENTIATE SOME OF THE
SUB TYPES AND A FEW IMAGING IS A
DOMAIN PRESENT.
WE HAVE BEEN CHARACTERIZING OR
STUDY THAT CHARACTERIZE OSA AND
WOULD BE RELATIVELY EASY BUT
IMPORTANT TO INTRODUCE
HETEROGENEITY IN THE DOMAINS IN
OSA.
IF YOU'RE LOOKING AT THE
DIFFERENT DOMAINS AND METRICS
PRESUMABLY WE STACK BLOCKS
WITHOUT THINKING HOW WE SHOULD
BE LOOKING AT ALL THESE THINGS
THEY BENEFIT THE CLINIC AND
PATIENT.
HOPEFULLY BY THE END OF THE TALK
I CAN GIVE YOU SOME SENSE OF
FRAMEWORK THAT COULD BE USED AND
GET YOU THINKING ON HOW WE CAN
THINK IN THE MORE GLOBAL WAY
ABOUT THIS.
THE OTHER THING IS CURRENTLY OUR
REPORTS CONTAIN SO MANY
DIFFERENT METRICS AND SO MANY
MEASURES FORME PATIENTS IT'S HA
TO KNOW WHAT AM I LOOKING AT AND
WHAT I SHOULD BE LOOKING AT AND
IS THERE SOMETHING NORMAL OR
ABNORMAL AND THAT'S PROMPTED
MANUFACTURERS TO COME UP WITH
NEW INFO GRAPHICS IT HIGHLIGHT
TO THE PATIENT WHAT IS IMPORTANT
AND NOT AND SOME SUBTLETIES.
THESE ARE LOOKING AT THE
MEASURES.
IF YOU THINK OF ADDING NEW
MEASURES AND DOMAINS THE REPORT
CAN FURTHER CONFUSE THE PATIENT
MORE.
AND WE ALL WANT TO MOVE TOWARDS
DIGITAL FUTURE WHERE THE FUTURE
CLINIC LOOKS NORMAL AND THE
REPORTS THAT GETS GENERATED ARE
INTERACTIVE FOR THE PATIENTS AND
A CLEAR PATHWAY HOW TO MOVE TO
THAT AND WHILE PRESERVING ALL
THE INFORMING WE WANT TO
PRESERVE.
WE HAVE WAYS OF CHARACTERIZING
OSA AND HAVE HETEROGENEITY AND
CAN WORK ON THAT MORE AND WE
HAVE THE DIMENSIONALITY.
AS WE START ADDING MORE AND MORE
METRICS AND MORE AND MORE DATA
COMES OUT, THE DIMENSION STARTS
TO GROW.
WE DON'T HAVE COMPLETE DATA IN
ALL THE CASES.
FOR EXAMPLE, IF YOU'RE LOOKING
AT STUDIES DONE IN THE PAST
PERHAPS THERE'S SOME NOTHING
PHOTOGRAPHY BUT DON'T HAVE THE
DATA FOR METABOLOMICS AND OTHER
THINGS AND SO ON OR IF THEY
COLLECTED SLEEP INFORMATION VIA
QUESTIONNAIRE BUT NOT
SOMNOGRAPHY SO IT'S NOT COMPLETE
DATA IN ALL CASES.
WE DON'T HAVE AN INTEGRATIVE
SCORE AT THE END OF THE DAY IT
MATTERS IF THERE'S AN INTEGRATED
SCORE ACROSS DOMAINS OR EVEN IF
DOMAIN SPECIFIC YOU HAVE A SCORE
TO TELL THEM WHAT EXACTLY IS THE
ISSUE AND WHAT SHOULD BE THE
LIKELY NEXT STEP IN TERMS OF
SLEEP APNEA MANAGEMENT.
AND NO MATTER THE METHOD OR
TECHNIQUE WE USE IT HAS TO BE
THE RESOURCES WE HAVE IN TERMS
OF INFRASTRUCTURE AND COMPUTING
AND SO ON.
HOW HAVE WE BEEN INTEGRATING
APPROACH TO OSA?
TYPICAL APPROACHES ARE YOU FIND
THE COFOUNDERS AND COVARIATES ON
THE LITERATURE OR DOMAIN
KNOWLEDGE OR USE A LINEAR OR
NON-LINEAR MODEL AND THESE
LINEAR OR NON-LINEAR MODELS HAVE
PREDEFINED EQUATIONS AND WE USE
THAT AND SEE IF THE OUTCOME IS
DETERMINED BY THE DOMAINS OR IF
TREATMENT RESPONSE CAN BE
DETERMINED THAT WAY AND
CHARACTERISTICS ARE MODEL DRIVEN
SO NEED TO KNOW THE ASSUMPTIONS
THAT GOVERN THE MODEL IMPLICIT
DATA AND WHAT CONFOUNDERS AND
WHAT MEASURES OR METRICS AND SO
ON.
IT HAS REQUIREMENTS.
YOU HAVE TO HAVE STATISTICAL
ASSUMPTIONS THAT HAVE TO BE MET
AT EVERY STEP OF THE WAY.
IN ADDITION, DIMENSION REDUCTION
IS ONE OF THE KEY THINGS.
YOU CANNOT HAVE 10 DIFFERENT
MEASURES FOR LOOKING AT OXYGEN
DESATURATION IF THEY'RE ALL
CORRELATED AND LINEAR AND SO ON
YOU HAVE TO REDUCE THE DIMENSION
AND DON'T HAVE STATISTICAL POWER
TO DO THAT SO YOU HAVE TO REDUCE
DIMENSION.
I THINK MULTIMODAL A.I. BEEN THE
HO HOLY GRAIL AND IT'S HAPPENING
IN OTHER FIELDS OF MEDICINE.
AND A LOT OF RESEARCH LOOKED AT
MULTIMODAL A.I. TO PREDICT SOME
DISEASE AS WELL AS LOOK AT
HETEROGENEITY.
ON THE LEFT WE HAVE THIS COULD
BE TRUE FOR ANY DISEASE AND IN
THE CASE OF SLEEP APNEA IT'S
TRUE YOU HAVE DIFFERENT DATA
MODALITIES.
IN SLEEP APNEA WE HAVE MORE DATA
MODALITIES THAN OTHER DISEASES
AND BRINGS WITH IT DIFFERENT
OPPORTUNITIES.
FOR PRECISION HEALTH WE'RE
LOOKING AT CLINICAL TRIALS AND
SURVEILLANCE, DIGITAL TWINS AND
TOUCH ON COPIES.
A.I. IS THE UMBRELLA TERM AND
MACHINE LEARNING FOR DATA IN
SOME CASES FOR IMAGE BASED DATA
AND DEEP LEARNING FAVORED FOR
IMAGE BASED DATA.
THERE ARE TRANSFORMERS THE NEW
MACHINE LEARNING MODELS THAT TRY
IT PAY ATTENTION TO THE CONTEXT
SURROUNDING THE INPUTS AND USED
FOR TIME AND IMAGE BASED DATA
AND ADVANCEMENTS ON NEWER
NETWORKS AND THE GENERATIVE A.I.
HAS MORE CAPACITY TO DIGEST THE
DATA MODALITIES.
AND I'LL TALK ABOUT THIS AS
WELL, ONE OF THE EXCITING THINGS
IS WE DON'T NEED TO HAVE LABEL
DATA OF THE STEPS OF YOUR MODEL.
YOU CAN WORK WITH UNLABELLED
DATA AS WELL.
AND WE'RE LIVING IN DECADES IN
THE MAKING BUT RECENT ADVANCES
USED THE A.I.
THIS IS A GRAPH LOOKING AT THE
NUMBER OF PAPERS.
ESTABLISHED SINCE THE GENERATIVE
A.I. AND SO ON ANDOU CAN SEE
THE SHARP INCREASE AND SIMILARLY
IN TERMS OF THE A.I. MEDICAL
DEVICES THERE'S BEEN UPSWING IN
APPROVALS WITH GENERATIVE A.I.
AROUND THE TIME OF THE PANDEMIC
EXPONENTIAL USE AND SOME HAD
A.I. AND SOME HAD HUMAN
INVOLVEMENT.
AND THE DIFFERENT DATA
MODALITIES WERE PHYSIOLOGICAL
BURDENS AND HR AND BIOMARKERS
AND VARIABLES, IMAGING AND SO
ON.
HOW DO WE COMBINE THESE
DIFFERENT DOMAINS AT THAT LEAD
TO THEN USE SOME OF THE
OPPORTUNITIES DATA PRESENTS US
WITH?
THIS IS WHERE THE TOPIC OF THE
IDEA OF FUSION.
THERE'S SEVERAL TYPE OF FUSION.
IT'S IMPORTANT TO DECIDE WHEN TO
USE THE MODALMODALI
AND YOU FUSE THEM BY DOING SOME
TRANSFORMATION AND CREATE ONE
FINAL MODEL.
IN THIS CASE YOU HAVE
PATHOLOGICAL SCANS TO THEN BE
USED AND HAVE INTERMEDIATE
FUSION TO USE SEPARATE MODELS
FOR SEPARATE DATA MODALITIES AND
FUSE THE OUTPUTS OF THE MODELS
AND CLEARS ANOTHER LAYER OR IRDE
FUSE DATA TO LEARN
CHARACTERISTICS OF THE DATA TO
THEN PREDICT THE INFORMATION YOU
WANT.
FINALLY A LATE FUSION WHERE ATR
EACH LEVEL YOU CREATE THE MODELS
AND GET THE OUTPUT AND GET
PREDICTIVE SCORES AND SO ON AND
USE THE PREDICTIVE SCORES TO
FUSE IN ANOTHER A.I. MODEL AND
THEN YOU GET A FINAL SCO OR A
DIFFERENT TYPE OF SCORE THAT CAN
BE USED.
SO IT'S VERY IMPORTANT AT LEAST
IN THE KWON TEXT OF FUSION TO
KNOW WHICH ONE TO USE AND WHEN
TO USE THE DIFFERENT TYPES OF
EXECUTION.
AND YOU LEARN THE UNDERLYING
PRESENTATION SO IN GENERAL SENSE
WHEN YOU HEAR THE WORD DOG OR
SHOWN THE IMAGE OF A DOG IN YOUR
MIND THE REPRESENTATION IS THE
SAME.
SIMILARLY WE NEED TO COME TO A
POINT WHERE FOR OSA OUR INTERNAL
REPRESENTATION OR DATA
REPRESENTATION IS THE SAME WHERE
THEN HAVING HYPOXIC BURDEN VALUE
OF SO AND SO DESATURATION
PROFILE WITH A GIVE SHAPE AND
THEM HAVING MAYBE SOME OTHER
POLYSO SOME SOMNOGRAPHY OR MARK
THE SAME REPRESENTATION OF THE
DISEASE FOR THE INDIVIDUAL.
AND AHI HAS DIFFERENT DOMAINS
AND HYPOXIC AROUSAL AND THERE'S
AUTONOMIC DEMAIN NOT IN THE AHI
BUT CORRELATED TO AHI.
SO OUR FUSION WAS YOU HAVE
THREES DIFFERENT MODALITIES AND
HOW CAN YOU COMBINE THEM FOR
FUSE THEM WITHOUT USING
CONVENTION STATISTICS AND WE
DERIVED FEATURES AND TRAINED
MACHINE LEARNING FOR DIFFERENT
OUTCOMES.
NOT ONE MACHINE LEARNING FOR AL
DIFFERENT OUTCOMES.
THE IDEA WAS THEN IF AN
INDIVIDUAL HAS HIGH RISK IN
SEVERAL LEVELS YOU CAN USE
SOMETHING ANALOGOUS TO CANCER
AND IF SOMEONE HAS LIKELIHOOD OF
OUTCOMES AND COMPARED TO A.I.
THE MODELS AND YOU CAN SEE THE
FEATURES THAT COME ABOUT IN
PREDICTING SOME OF THESE
OUTCOMES.
FOR EXAMPLE FOR SLEEPINESS WE
SAW APNEAS AND HYPOXIC BURDEN
AND IMPORTANT FEATURES IN
CHARACTERIZING THE
CLASSIFICATION.
AND THIS IS HEALTH STUDY DATA WE
SAW AN EXPONENTIAL INCREASE MEN
WE USED THE FUSION MODEL AND
EXTENDED A.I. CAN ALLOW YOU TO
SEE WHAT FEATURES ARE IMPORTANT
AND LEARN THE DIFFERENT ASPECTS
OF IT.
YOU CAN MOVE BEYOND THAT AS
WELL.
YOU CAN LOOK AT SURVIVAL
TRAJECTORY AND PROFILES AND
USING SLEEP DATA YOU WERE ABLE
TO DERIVE SURVIVAL TRAJECTORY
AND HERE'S AN EXAMPLE OF A
PERSON WHO DIED AND THE
COMBINATION OF DIFFERENT
DOMAINS.
ACCURATELY PREDICTED THEY ARE
WERE AT LOWER TRAJECTORY
COMPARED TO THE AVERAGE GROUP
AND THE RA HI WAS HIGHER SO
ACCORDING TO AHI THEY ARE WERE
NOT A HIGHER RISK AND THIS CAN
PROMPT IF THEY'RE USING THIS TO
INTERVENE.
DR. REKH TALKED ABOUT SYMPTOM
SUB TYPES.
WHAT WE DID LOOKED AT
CLINICAL NOTES AND ASKED THE
QUESTION CAN WE DERIVE TYPES AND
THIS IS IN COLLABORATION AND
USING PROMPT ENGINEERING AND
LARGE LANGUAGE MODELS THAT EXIST
FROM THE OPEN SOURCE
AVAILABILITY MODELS YOU CAN ASK
THE QUESTION CAN YOU EXTRACT THE
RELEVANT SYMPTOMS TO HELP ME
CLASSIFY THE INDIVIDUAL INTO ONE
OF THE OSA CLUSTERS AND GIVING A
PROMPT TO GIVE A REASONING DOES
EYE GOOD JOB AT EXTRACTING ALL
THOSE AND GIVING US THE
REASONING WHY THE SYMPTOM IS
PRESENT.
ONCE YOU GET THE RESPONSES YOU
CAN FUSE THEM AND GET TO THE
SYMPTOMS EFFECTS AND CLUSTERS.
THAT'S ONE FUSION OR EARLY
FUSION. IS AN EXAMPLE OF
INTERMEDIATE FOR LATE FUSION.
I SHOWED THE EVENTS AND THE
SYMPTOM SUBTYPES AND USING
CLINICAL NODE.
IF YOU FUSE THEM TO ANOTHER
MULTIMODEL MODEL TO PREDICT
OUTCOMES YOU HAVE LATE FUSION.
THAT'S WHERE ONE OF THE
POSSIBILITIES IS TO COMBINE
THIS.
WORK IS ONGOING ON THAT AND
WE'RE IN INTERESTING TIME AND IF
GEN A.I. FOR DISEASE CATERS WELL
TO THE DATA SLEEP APNEA
GENERATES.
I'LL QUICKLY TALK ABOUT THE IDEA
OF THE DIGITAL TWIN.
GIVEN RANDOMIZED CONTROL TRIALS
AND THIS IS SOME OF THE WORK AND
LOOK AT HOW INTERVENTION WOULD
HAVE PLAYED OUT AND CREATE A
DIGITAL TWIN ON THE DATA AND
SIMULATE IF THEY WERE IN THE
OTHER ARM NOT WE ONE THEY WERE
RANDOMIZED TO.
YOU CAN USE THE SIMULATION
WHETHER THE INTERVENTION WOULD
BE HELPFUL OR NOT.
WITH THE ADVENT OF GEN A.I. A
VIRTUAL COACH WILL HELP TO NOT
ONLY UNDERSTAND THE
HETEROGENEITY BUT USE IT TO ITS
ADVANTAGE.
A.I. POWERED HEALTH COACHING IS
SOMETHING MOST E.H.R. COMPANIES
ARE PUSHING FOR.
SO FROM THEIR OWN DATA THEY'RE
WORK INTEGRATING AT ALL
POSSIBLE LEVELS AND IT'S
CRITICAL FOR US TO HIGHLIGHT
HETEROGENEITY IN THE DISORDER
WHEN ALL THINGS ARE BEING
DECIDED ABOUT.
THERE'S SMARTPHONE APPLICATIONS
THAT COULD BE USED THIS BE
INTEGRATED INTO THE CLINIC AND
COULD BE HELPFUL FOR THE
PATIENTS TO BE USED.
THERE ARE CHAT BOTS I THINK WE
USE IT FOR DIFFERENT THINGS BUT
IT IS BEING PLANNED TO BE
BROUGHT IN THE E.H.R. CLINIC AND
USE THAT AND HETEROGENEITY
EXISTS NOT ONLY IN THE DISEASE
BUT HOW A PATIENT SORT OF
SELF-PERCEIVES SOME SYMPTOMS AND
SO ON SO IT'S IMPORTANT TO
HUMIDITY IT SHOULD BE EMBEDDED
INTO THE -- HIGHLIGHT IT SHOULD
BE EMBEDDED AND THE CHAT BOTS
ARE NOT REALLY HETEROGENEOUS SO
IT'S IMPORTANT TO CONSIDER THAT.
IT COULD BE USED TO PREPARE
PATIENTS AHEAD OF CLINIC VISITS
AND CAN PROVIDE THEM WITH
CLINICAL TRIAL INFORMATION TO
ALLOW THEM TO RECRUIT INTO THE
OTHERS THEY MAY BE ELIGIBLE FOR.
THE CHALLENGES ARE RELIABILITY
AND SAFETY.
THERE NEEDS TO BE WORKFORCE
TRAINING AND DATA PRIVACY AND
SECURITY AND AS I SAID THE DATA
IT'S TRAINED ON IS NOT ALWAYS
FREE OF BIAS AND IT'S IMPORTANT
TO KEEP THAT IN MIND.
FINALLY I'LL GO THROUGH THE
SOURCES OF BIG DATA AVAILABLE.
ONE HAS SEVERAL OTHER KINDS OF
DATA THAT IS AVAILABLE TO THE
RESEARCHERS.
IF YOU LOOK AT THE GRID IN TERMS
OF THE COHORT METRICS OF THE
DIFFERENT DATA SETS AVAILABLE
THERE'S A LOT OF OUTCOMES AND
DOMAINS FOR RESEARCHERS TO USE
OVER 10 TERABYTE OF DATA AND
THERE'S A STUDY THAT HAS SLEEP
AN RESPIRATORY AND
OTHER CLINICAL DATA SETS ARE
GOING TO BE INCLUDED.
THERE'S TOP MED.
HAS ABOUT 50K PLUS GENOME DATA
AND RNA SEQ AND AN A.I. TO USE
THE DATA TOGETHER.
THERE'S DATA SETS AND THIS IS
THE TIP OF THE ICEBERG AND
SEVERAL HAVE DATA SETS
AVAILABLE.
THERE'S 20,000 SLEEP STUDIES AND
E.H.R. DATA THROUGH THE
UNIVERSITY MEDICAL CENTER WHICH
HAS E.H.R., MEDICARE AND CLAIMS
AND SLEEP STUDIES AND AND
THERE'S SCREEN AND CLINIC DATA
WITH 180 SLEEP STUDIES THAT
COULD BE USED AND A LOT OF DATA
HOUSED IN INSTITUTIONAL SILOS
THAT CAN BE USED FOR THE
ONS ITIED TODAY.
THAT'S WHERE THE GEN A.I. SIGNS.
THE KEY STRATEGY FOR THE
TRANSFORMERS IS ALLOWING THE
NEURAL NETWORKS AND YOU CAN
REMODEL IT AND USE IT FOR ANY
TYPE OF DATA.
IT COULD LEARN REPRESENTATIONS
OF POLYSOMNOGRAPHY DATA AND YOU
HAVE AIR FLOW SIGNAL YOU CAN USE
THAT TO GENERATE A SATURATION
SIGNAL PROVIDED THE DATA YOU
TRAINED ON WAS HETEROGENEOUS AND
HAD VARIANTS WE WERE LOOKING FOR
OR GIVE DATA IT CAN PREDICT WHAT
CAN HAPPEN IF CPAP WAS INITIATED
AND STUDIES DONE IN THE SLEEP
LABS BUT NOT USED AT ALL.
AND NON-COMPLIANCE WITH THERAPY.
TO GIVE YOU A QUICK EXAMPLE YOU
CAN GENERATE FLOW FROM THE
VARIABLES AND YOU COULD USE
ARCHITECTURE TO DIVIDE FLOW
BASED ON USING ALL THE DATA
AVAILABLE TO TRAIN AND LEARN THE
DEPEND
DEPENDENCIES.
THERE'S DIFFERENT BIASES.
HISTORICAL BIASES AND AND THIS
IS REPRESENTED BY HETEROGENEOUS
POPULATIONS AND ARE WE CHOOSING
METRICS OR OUTCOMES THAT MATTER
TO EVERYONE OR ONLY LOOKING AT
THOSE AVAILABLE AND ARRHYTHMIC
BIAS AND BIAS WS MODALITY.
MODEL EXPLAINABILITY ARE
PARAMOUNT TO OVERCOME THE BIAS.
AND BEFORE I GIVE YOU THE FINAL
KEY POINTS, I REALLY WANT TO
STRESS FOR A.I., HETEROGENEITY
ADDS EFFICIENCY AND ACCURACY.
IT'S NOT THE CASE IF YOU HAVE
HETEROGENEOUS DATA A.I. WELL
FAIL.
IT WOULD PERFORM IF YOU'RE
SOPHISTICATED UP USING IT.
WHAT ARE THE PRIORITY QUESTIONS
IN MY OPINION?
USING THE TRANSFORMERS TO USE
THE GAPS BETWEEN HOME SLEEP
STUDY AND VARIABLES COULD BE A
KEY FACTOR.
WE NEED TO UTILIZE SIMULATION TO
LOOK THIS AND WITH THAT I'LL
STOP HERE.
>> THANK YOU.
THAT'S A SUMMARY OF ALL THE
ARTIFICIAL INTELLIGENCE USED IN
SLEEP AND A TASTE OF WHAT HES
GOING TO BE AVAILABLE IN THE
FUTURE AND AN EXCITING PICTURE.
LET ME SUMMARIZE THE TALKS FROM
THE SESSION A LITTLE BIT BRIEFLY
BECAUSE I KNOW WE'RE RUNNING ON.
DR. WELLMAN SHOWED US EXAMPLES
OF WHITE/BLACK DIFFERENCES IN
HYPOXIC BURDEN AS DETECTED AND
CARDIOVASCULAR RESPONSES IN OSA
AND COULD HAVE SIGNIFICANT
LONG-TERM HEALTH CONSEQUENCES
BECAUSE SUSCEPTIBILITY TO OSA
AND THE LONG-TERM HEALTH
CONSEQUENCES FROM OSA DIFFERS
SIGNIFICANTLY BETWEEN BLACK AND
WHITE POPULATIONS.
AND GLUCOSE MONITORING AND SLEEP
STUDIES INCORPORATING THE DATA
WITH THE DATA STREAMS FROM
VARIABLE DEVICES USING THE
APPROACHES TALKED ABOUT IN
MACHINE LEARNING AND ARTIFICIAL
INTELLIGENCE TO INTEGRATE THE
DATA STREAMS TO A COMPREHENSIVE
PICTURE OF SLEEP AND ITS
DISTURBANCES.
DR. PAREKH DESCRIBED THE
PHENOTYPIC DIFFERENCES
CONTRIBUTING TO THE
HETEROGENEITY OF OBSTRUCTIVE
SLEEP APNEA AND MULTIPLE
APPROACHES ARE USED TO DESCRIBE
THE HETEROGENEITY AND THEY PLAY
RESULT IN DIFFERENT OUTCOMES AND
RESPONSE TO TREATMENTS AND EVEN
METHODS FOR PREVENTION OF SLEEP
APNEA IN THE DIFFERENT
POPULATIONS AND FINALLY
APPROACHES FOR THE SUB TYPES OF
SLEEP APNEA AND SHOWED
INCREASINGLY SOPHISTICATED
MACHINE LEARNING AND BIG DATA
APPROACHES CAN HAVE
CHARACTERIZATION AND
CLASSIFICATION MUCH THE CELL
TYPES PERHAPS ULTIMATELY
RESULTING IN MORE EFFECTIVE
TREATMENTS FOR THESE DIVERSE SUB
TYPES OF SLEEP APNEA SO A NICE
WAY OF WRAPPING UP THE DAY'S
TALKS.
WE HAVE SOMETHING LIKE 20
MINUTES OR SO FOR Q&A.
MAYBE IT'S GOOD TO HAVE FURTHER
DISCUSSION ON THINGS POSSIBLE
FOR THE BRIEF MESSAGES IN THE
CHAT.
ONE ONE INTERESTING COMMENTS OR
QUESTIONS WAS TALKING ABOUT
RACIAL BIAS AND DETECTION OF
DESATURATION AND THERE WAS
RACIAL BIAS IN THE FILTRATION
RATE FOR A LONG TIME.
THAT'S PRETTY MUCH BEEN SOLVED
BY INCORPORATING A CORRECTION
FACTOR.
ONE QUESTION IS IF THAT BE
APPROACH OF LOOKING AT
DESATURATION AND TRANSLATING THE
DATA IN AFRICAN AMERICAN PEOPLE
SO THE DESATURATIONS ARE
DEFECTED AND FOR A LONG TIME
OPTICAL ENGINEERS PEOPLE
DESIGNING THESE PULSE OX DEVICES
WHY CAN'T THEY CHANGE THE DESIGN
TO BE MORE SENSITIVE IN PEOPLE
WITH DARK SKIN AND WE DIDN'T
HEAR ANYTHING ABOUT THAT.
PERHAPS YOU CAN COULD COMMENT ON
THOSE TWO ISSUES.
>> DOES
>> I REMEMBER WHEN I FIRST
LEARNED ABOUT PULSE OXIMETRY IN
MEDICAL SCHOOL AND ASKED ABOUT
DARK SKIN AND NAIL POLISH, THEY
TOLD ME IT WAS ALREADY SOLVED
AND DON'T WORRY ABOUT IT.
I CAN'T BELIEVE IT SEEMS --
SUSAN BROUGHT UP THAT PEOPLE CAN
CHANGE LIKE THE WAY THEY'RE
TRYING TO FIX IT NOW IS CHANGE
THE CALIBRATION CURB SO YOU HAVE
A CALIBRATION CURB FOR DARK SKIN
AND DIFFERENT FOR WHITE.
I HAD NOT HEARD OF THAT AND TO
ME IT SEEMS LIKE IT WOULD WORK
AND WOULD LIKE TO KNOW PEOPLE
DOING THAT AND HOW THEY'RE DOING
THAT AND THAT'S JUST A DIFFERENT
CAL OPERATION CURB.
UNTIL I HEARD ABOUT THAT I
WASN'T SURE HOW OPTICAL
ENGINEERS WOULD FIX IT BECAUSE
THE WAY THE DEVICES CORRECT FOR
ERRORS AND NOISE IS THEY SMOOTH
THE SIGNAL.
THEY SMOOTH IT SO MUCH IF WE
WERE TO REMOVE SOME OF THE
SMOOTHING THEY WOULD TURN INTO
STATS BECAUSE THE SIGNAL IS SO
OVER FILTERED.
AND THEY ARE WERE TO DETECT
STEADY STATE OFFSETS FOR PEOPLE
ONE PNEUMONIA AND IN THE ICU AND
IT WAS NOT TO DETECT TRANSIENT
DROPS.
WHENEVER THE ERROR IS THE 3% TO
4% THAT EXISTS BETWEEN WHITES
AND BLACKS ON OXIMETRY -- WHAT'S
THAT DO TO THE 3%, 4% HYPOPNEA
DEFINITION WE HAVE FOR SLEEP AP?
IF SOMEONE CAN FIX THAT I'D LOVE
TO GET HOLD OF THAT DEVICE AND
TEST THAT.
>> THERE'S RACIAL BIAS IN LUNG
FUNCTION SO THE EXCESSIVELY
SLEEPY PHENOTYPES AND THE
CONCERN IN THE HETEROGENEOUS
SLEEP PHENOTYPES WE LOOKED AT
BECAUSE IT'S GOT THE MOST
SIGNIFICANT LONG-TERM HEALTH
CONSEQUENCES AND THE QUESTION IS
WHY?
WHY IS IT EXCESSIVELY SLEEPY
REFLECTS SOMETHING ADVERSE IN
THE CONSEQUENCES?
ANY THOUGHTS ON THAT?
>> I DON'T THINK IT'S SLEEPINESS
PER SE.
IF YOU LOOK AT PEOPLE WITH SLEEP
APNEA, WE DON'T HAVE SLEEP APNEA
THEY'RE EXCESSIVELY SLEEPY AND
THERE'S NO INCREASED RISK OF
OUTCOMES.
I THINK THE WAY TO LOOK AT IT
THE WAY WE LOOK AT IT IS
EXCESSIVE SLEEPINESS IS LIKE A
SYMPTOMATIC BIOMARKER OF WHO'S
AT INCREASED RISK.
THERE'S A MOLECULAR RESPONSE AND
THERE'S A DIFFERENT INFLAMMATORY
RESPONSE AND WE KNOW THAT FROM
OTHER DATA THE CLUSTERS AND SOME
PEOPLE HAVE HIGH INFLAMMATORY
RESPONSES AND IT'S A HIGH
INFLAMMATORY RESPONSE TO
CARDIOVASCULAR RISK AND ALSO
DRIVES SLEEPINESS THAT'S WHY
THEY'RE RELATED.
SO THAT'S THE WAY WE TEND TO
THINK ABOUT IT.
IT'S A SYMPTOMATIC BIOMARKER AND
GETTING TO THE FUNDAMENTAL
QUESTION WHY IS IT?
WHY DO SOME WITH THE SAME
DISEASE HAVE MARGINAL SLEEPINESS
AND SOME DON'T.
>> DIEGO, DO YOU WANT TO COMMENT
ON THAT?
YOU LOOKED AT THIS EXTENSIVELY
TOO.
>> MY HYPOTHESIS IS IN LINE WITH
WHAT ALLAN SAID AND ANOTHER
QUESTION I HAVE IN MY MIND IS
CAN SLEEPINESS OR SYMPTOM
PRESENTATIONS BE A MARKER OF HOW
LONG SOMEONE'S HAD THE DISEASE.
WE HAD DISCUSSION HOW WE CAN
LEVERAGE THE INFORMATION TO PUT
THEM INTO THE PATH OF LIKE
DISEASE PROGRESSION.
SO WHEN A PATIENT COMES IN TO
GET THE DIAGNOSIS WE DON'T KNOW
HOW LONG THEY'VE HAD THE
DISEASE.
AND AND WE LOOKED AT HOW THE
SYMPTOMS TRANSITIONED OVER TIME
BETWEEN THE BASELINE AND
FIVE-YEAR VISIT FROM THE HEALTH
STUDY AND SEE IT TENDS TO BE AN
ATTENUATION OF THE SYMPTOMS.
THOSE EXCESSIVELY SLEEPY OR LESS
SLEEPY BUT IN A SEPARATE
ANALYSIS WE HAVE PUBLISHED AT
THIS POINT THOSE THAT MAINTAIN
SLEEPY OVER TIME THOSE ARE AT
THE HIGHEST RISK.
IT SEEMS TO ME IT IS JUST
TRACKING ALONG WITH SOMETHING
ELSE AND I THINK -- A LOT OF THE
WORK ALLAN IS GOING ON TRYING TO
DESCRIBE THE METABOLIC AND
MOLECULAR MARKERS OF THE
SUBTYPES COULD SHED LIGHT ON
THAT.
>> I AGREE WITH THAT.
>> AND DID YOU HEAR THE
QUESTION, ALLAN?
>> A COUPLE POINTS IF I COULD.
CLEARLY THERE WAS AGREEMENT IN
THIS SESSION ABOUT WHERE WE'RE
AT AND THE MULTIPLE DIMENSIONS
AND MULTIPLE TOOLS ARE THERE AND
I THINK THIS IS APPROACH TO
PERSONALIZED SLEEP APNEA GETS TO
THE MAINSTREAM OF PERSONALIZED
MEDICINE AND WE HAD AN EXCELLENT
TALK OF TOOLS APPLIED IN THE
CANCER WORLD AND SO ON.
IN THE MAINSTREAM OF
PERSONALIZED MEDICINE I THINK
THERE'S A LOT TO GET DONE.
I THINK THE IDEA OF INTEGRATING
ACROSS THE SYMPTOMS AND
PHYSIOLOGY AND BIOMARKERS IS
WHERE WE NEED TO BE.
HOW DO WE PULL THE INFORMATION
TOGETHER AND I THINK WHAT YOU
TALKED ABOUT WAS YOU HAVE
ANALYTICAL APPROACHES THAT ALLOW
YOU TO DO THAT.
THE OTHER THING IS WITHIN THE
SESSION THERE'S BEEN A THEME OF
AGENDA DIFFERENCES AND
PERSONALIZED SLEEP APNEA AND
THEY CAN COME TOGETHER BECAUSE
IF WE'RE GOING TO TACKLE THE
GENDER DIFFERENCES THEY SHOULD
BE WITHIN THE FRAMEWORK AND
BIOMARKER AND SYMPTOM AND
PHYSIOLOGY AND SO ON.
IT'S THE SAME FRAMEWORK THAT
WOULD ALLOW US TO COMPLETELY
CHARACTERIZE THE GENDER
DIFFERENCES AND UNDERSTAND THAT.
S THE SAME HEART DATA HAS BEEN
PRODUCTIVE AND THERE WERE NO
BIOMARKERS IN THERE AND SO ON
AND ONE OF THE CHALLENGES IS
BECAUSE THEY GO UP AND THE
AVERAGE AGE IS 65.
HAVING THE RESOURCES WOULD BE
ENORMOUS TO THE FIELD.
AND IT WOULDN'T BE COMPREHENSIVE
BECAUSE LOTS OF PEOPLE ARE
GETTING STUDIED THE QUESTION IS
HOW DO YOU CAPTURE THE DATA AND
DO IT.
THAT'S ONE OF THE BARRIERS WE
HAVE I THINK.
THE STUDY WAS THE GOLD STANDARD
AND I HAVE CONCERNS ABOUT THAT.
>> WHAT DO PEOPLE THINK ABOUT
THAT?
>> IT'S A VALID CONCERN.
AND TWO STRATEGIES ONE IS
COHORTS THAT IS MORE
HETEROGENEOUS AND SO ON LOOKING
AT CLINICAL POPULATIONS AND
PROSPECTIVE VALIDATION AND NOT
USING ALREADY EXISTING DATA AND
RUNNING THE ALGORITHM IN THE
BACKGROUND AND SLEEP DATA WAS
ONE OF THE FIRST DATA SETS.
>> THE OTHER THING IS IF WE
ORGANIZED AND THESE PROGRAMS
LIKE TOP MED IF YOU DON'T HAVE
COHORTS, THERE'S NOT AS MUCH AS
WITH COHORTS AND GIVE YOU
RESOURCES TO DO THE METABOLOMICS
AND WHOLE GENOME SEQUENCING AND
THAT'S THE WHOLE IDEA.
IF YOU'RE NOT ORGANIZED WITH A
COHORT COLLECTING SAMPLES YOU
CAN'T REALLY ACCESS THE TOP MED
RESOURCE S.
>> A QUESTION, POST PANDEMIC
WORLD THERE'S MORE CONTINUOUS
MONITORING.
THERE'S BEEN A PROLIFERATION OF
DEVICES THAT MEASURE
PHYSIOLOGICAL PARAMETERS.
ACTIGRAPHY COMES TO MIND AND NOW
CONTINUOUS GLUCOSE MONITORING.
IT'S AN UNREGULATED FIELD AND
WHETHER THEY'RE BELIEVABLE IN
THE VALIDATIONS AND I KNOW IT'S
IN THE TRUE FOR ACTIGRAPHY
BECAUSE PEOPLE HAVE COMPARED IT
TO STANDARD POLYSOMNOGRAPHY AND
SOME ARE GOOD AND SO THE NOT SO
GOOD.
DO YOU SEE VARIABILITY WITH
CONTINUOUS GLUCOSE MONITORS.
>> THE WAY THEY ARE WERE DESIGN
IS FOR PEOPLE WITH TYPE 1
DIABETES TO TAKE INSULIN BASED
ON MEASUREMENT.
BECAUSE OF THAT THE ACCURACY FOR
FDA APPROVED DEVICES IS
REGULATED.
THAT SAID THEY'RE NOT PERFECT
AND HAVE A MEASUREMENT ERROR TO
MY KNOWLEDGE IS NOTE ACCOUNTED
UP MOST METHODS.
THEY'RE ALSO ISSUES SUCH AS THE
MISSING DATA.
OVER ALL THE MODELS THAT DON'T
REQUIRE CALIBRATION ARE PRETTY
ACCURATE.
THE PROBLEM IS WE'RE SEEING
INTEREST FROM CONSUMERS WHO
DON'T HAVE DIABETES HAVING
INTEREST AND THEY'RE PRODUCING
CONSUMER-GRADE DEVICES AND I
HAVE A QUESTION IS IT A
DIFFERENCE ON THE ACCURACY THEN
AND IF THERE'S A DIFFERENT IN
THE ACCURACY HOW DOES IT
TRANSLATE TO THE PHENOTYPES WE
MEASURE?
THE SHORT ORDINANCE IS THE
GLUCOSE MEASUREMENTS ARE MORE
COMPARABLE AND ABSOLUTE BUT
STILL HAVE ERRORS.
>>
>> THERE'S RESEARCH GRADE
DEVICES WHICH ARE EXPENSIVE AND
CONSUMER GRADE DEVICES LESS
ACCURATE BUT MORE AMENABLE TO
PURCHASING BY CONSUMERS.
>> IT'S BEEN A GREAT DISCUSSION
AND DEFINING DISEASE WE'RE CLETH
CLOSER IN BEING -- WE'RE
GETTING CLOSER TO DEFINING SLEEP
APNEA AND PROBLEMS IN RACIAL
BIAS AND OTHER ISSUES WILL COME
UP TOMORROW ABOUT TREATMENT AND
COMPLETENESS OF TREATMENT AND
ALLAN ALLUDED TO THIS IN THE
FRENCH STUDY MANY PEOPLE WERE ON
CPAP.
THERE'S SOME PLASTICITY IN
REGARD TO TREATMENT.
THERE WAS WORK LOOKING AT
IMPROVEMENT IN NEUROCOGNITIVE
FUNCTION AND IMPROVEMENTS IN MRI
WITH CPAP ADHERENCE AND IT PLAY
NOT BE THE ONLY TREATMENT AND
MAY BE DIFFICULT TO EMPLOY IN
SELECTED PHENOTYPES AND E
ENDOTYPES AND WE'LL SEE WHERE IT
GOES.
THE ONLY QUESTION IS IN THE
PRELIMINARY DATA WERE YOU USING
HIGH RESOLUTION OXIMETRY OR WAS
IT JUST ONE TYPE?
>> THIS WAS JUST PRELIMINARY
WORK WITH THE OXIMETER.
>> THERE'S PROBABLY A NEED TO
LOOK AT OTHER OXIMETRY
STRATEGIES.
THE WORK NEEDS TO BE REPEATED
AND THE COMMON OXIMETER AND THIS
CHANGING OR NEW CALIBRATION
CURVE THAT SUSAN HAS
MENTIONED -- I WONDERED WHO IS
DOING THAT.
I'D LIKE TO SEE THE RESULTS.
ALL THESE OXIMETERS WILL HAVE TO
GO THROUGH A NEW FDA APPROVAL
PROCESS WHERE YOU HAVE CAREFULLY
MEASURED SKIN TONE.
I WANT TO SEE THE RESULT OF THE
STUDIES THE DIFFERENCE IN THE
STUDIES OFFSET AND TRANSIENT HOW
DOES THAT TRANSLATE TO SLEEP
APNEA AND HOW MANY ARE WE
MISSING AND WHEN WE DO THE
STUDIES, MAYBE WE SHOULD NOT
JUST TEST STEADY STATE BUT TEST
THE ABILITY TO DETECT TRANSIENT
DROPS?
I THINK A LOT OF THE ERROR
CORRECTION IS THEY JUST SMOOTH
IT A LOT.
HUGE TIME CONSTANTS.
THAT'S WHAT WE DO WITH
SPIROMETRY.
YOU OF
>> TIME FOR ONE MORE QUESTION
AND FACTORS THAT LEAD TO THE
HETEROGENEITY OF THE
PRESENTATION OF OSA.
WHAT ABOUT COMORBIDITIES.
WHAT ABOUT PULMONARY DYSFUNCTION
LIKE COPD AND ASTHMA AND FACTORS
THEM INTO THE CLINICAL
MANIFESTATIONS AND THE OUTCOME
AND CONSEQUENCES OF OSA?
MAYBE IT'S ANOTHER CHALLENGE FOR
MACHINE LEARNING AND ARTIFICIAL
INTELLIGENCE.
COMMENTS?
>> WITH COMORBIDITIES AND E.H.R.
YOU FIND THE SAME THING.
YOU FIND GROUPS OF THIS AND
GROUPS OF THAT.
AS YOU INDICATED IF YOU HAVE A
COMBINATION OF COPD AND SLEEP
APNEA AND OVERLAP SYNDROME.
>> OKAY.
>> THERE'S A COUPLE VIDEOCAST
QUESTIONS IN THE Q&A.
>> I FOUND THAT.
I SEE ONE ON COPD.
COMORBIDITIES WAS ONE OF THOSE.
I DON'T SEE ANYTHING ELSE THERE.
THANKS ANOTHER ENGINEERING
QUESTION FOR ANDREW.
PULSE OXIMETERS BEING INFLUENCED
BY SKIN COLOR.
SOME APPARENTLY USE A THIRD
GREEN COLOR OF LIGHT AND THE
ALGORITHMS MAY BEHAVE
DIFFERENTLY WITH RESPECT TO SKIN
COLOR.
DO YOU KNOW HOW GREEN LIGHT --
>> YEAH.
I KNOW GREEN LIGHT DOESN'T
CONSUME THE BATTERY AS MUCH.
THEY ARE USE IT FOR ACTIGRAPHY.
THERE'S CERTAIN CHARACTERISTICS.
I DON'T THINK ADDING A THIRD
WAVE LENGTH WITH SOLVE THE
RACIAL BIAS.
IF SOMEBODY THINKS IT WILL I'D
LOVE TO HEAR HOW BUT THE GREEN
LIGHT WON'T WORK.
PEOPLE HAVE TRIED THAT.
ANY WAY, I'M NOT AN OPTICAL
ENGINEER BUT IT'S A THIRD LIGHT
THEORY WORKS IT DOESN'T MAKE
SENSE TO ME HOW IT WOULD.
>> ONE FINAL COMMENT BECAUSE WE
ARE COMING TO THE TOP OF THE
HOUR.
SLEEPINESS THE PHENOTYPE OF OSA
AND MORE COMPLICATED THAN THAT
SLEEPINESS HAS SEVERAL SUB TYPE
WITH DIFFERENT GENETIC
ASSOCIATIONS.
FURTHER INCREASING THE
COMPLEXITY OF THE MANIFESTATION
OF OSA AND DIFFERENT SUBTYPES OF
SLEEPINESS AND CONSEQUENCES OF
THE TYPES OF SLEEPINESS AS WELL.
>> AND IT MAY BE POSSIBLE BUT
THE GROUP HAS EXCESSIVE
SLEEPINESS AND IF IT'S DRIVEN
GENETICALLY YOU SHOULD BE ABLE
TO DEVELOP A RISK SCORE.
THAT SEEMS POSSIBLE.
>> I AGREE THERE'S MANY CAUSES
FOR SLEEPINESS.
ONE I THINK SHORT SLEEP DURATION
AND CIRCADIAN DISRUPTION AND
OTHER FACTORS NOT BEING CAPTURED
AND UNDERSTANDING GENETIC
MECHANISMS MAY HELP.
WE LOOK AT THE PHYSIOLOGY.
WE LOOK AT DIFFERENCES IN EEG
BIOMARKERS AND THAT'S WORK LED
WITH ALLAN'S GROUP AND NOT AS
MUCH AS EXCESSIVELY SLEEPY.
PERHAPS THERE'S OTHER SIGNALS
AND THAT WERE BEYOND EXPERT
DEFINITIONS OF THE DISEASE.
THERE'S A POTENTIAL OPPORTUNITY
OF PERHAPS REFINING HOW WE'RE
DEFINING THESE AND TAKING
ADVANTAGE OF ALL THE WAYS WE'RE
MEASURING THE DISEASE AND AFREE
WHERE WE HAVE APPROACHES TO HAVE
A MORE REFINED WAY OF WHAT ARE
YOUR CALLING SLEEP APNEA AND THE
DISEASE AND THAT CAN HAVE
SEVERAL IMPLICATIONS HOW WE
IDENTIFY PATIENTS AND HOW WE'RE
DEFINING HOW WE'RE RESPONDING TO
THERAPY.
WHAT DOES IT NEED TO TREAT TO BE
TREATED AND TOMORROW HOPEFULLY
THE DISCUSSION WILL SHED LIGHT
ON THAT AS WELL.
>> THANKS SO MUCH TO THE SESSION
3 SPEAKERS FOR PROVOCATIVE AND
COMPREHENSIVE TALK AND ALL THE
SPEAKERS THAT CAME BEFORE YOU AS
WELL.
WE'RE AT TIME AT 5:00 A LITTLE
AFTER ACTUALLY.
ALFONSO DO YOU WANT TO TAKE CARE
OF THE LOGISTICS.
THANKS.
>> THANK YOU.
BEFORE EVERYBODY SIGNS OFF THANK
YOU TO THE PRESENTERS AND FOR
THE EXCITING DAY ONE OF THE
WORKSHOP AND SPURRED QUESTIONS
AND GREAT DISCUSSION BUT THERE'S
DISCUSSION AND CRITICAL POINTS
THAT WERE PROBABLY NOT ADDRESSED
SO PLEASE BRING THOSE TOMORROW
FOR THE ROUNDTABLE DISCUSSION AT
THE END OF THE DAY WE'LL HAVE.
TOMORROW WORKSHOP'S WILL START
AT 12:00 P.M., HALF AN HOUR
LATER THAN TODAY AND WE'LL BE IN
TOUCH TONIGHT MOST LIKELY AND
HOPE EVERYONE HAS A WONDERFUL
EVENING AND GOOD NIGHT'S SLEEP.
>> THANKS.