Chronic Obstructive Pulmonary Disease YRIGHT …...Education is at the heart of patient care. A...
Transcript of Chronic Obstructive Pulmonary Disease YRIGHT …...Education is at the heart of patient care. A...
Education is at the heart of patient care.
A teaching hospital of Harvard Medical School
ChronicObstructivePulmonaryDiseaseGoingBeyondtheWheeze
RichardM.Schwartzstein,MD
Chief,DivisionofPulmonary,CriticalCareandSleepMedicine
EllenandMelvinGordonProfessorofMedicine
HarvardMedicalSchool
Director,ShapiroInstituteforEducationandResearch
COPYRIG
HT
A teaching hospital ofHarvard Medical School
Disclosures
• Ihavenorelationshipswithcommercialentities.• IreceivesupportfromtheNIHformyresearchondyspnea.
COPYRIG
HT
A teaching hospital ofHarvard Medical School
GoalsandObjectives• Todescriberecentinsightsintotheepidemiologyand
pathologyofCOPD• ToincorporateknowledgeaboutCOPDphenotypesinto
decision-makingabouttreatmentoptions• Todelineatethekeyelementsofthephysiologyofairflow
obstructioninemphysemaandtheimplicationsoftheseprinciplesforclinicalpractice
• TodetailtheessentialelementsintheevaluationofpatientswithCOPDandtohighlightcommonpitfallsintheassessmentofthesepatients
• TooutlinetherapeuticadvancesinthetreatmentofCOPD
COPYRIG
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A teaching hospital ofHarvard Medical School
COPD– Definitionincludes:• Chronicairflowobstruction• Rangeofpathologicchangesinthelung(abnormalinflammatoryresponsetonoxiousparticlesorgases)
• Extra-pulmonaryeffects• Theobstructionisprogressive• Mayhaveelementsofairwaysreactivity,i.e.,theobstructionmaybepartiallyreversible
• “Preventableandtreatable.”
COPYRIG
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A teaching hospital ofHarvard Medical School
DiagnosisofCOPD– GOLDUpdate
AJRCCM2017;195:557-582 COP
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A teaching hospital ofHarvard Medical School
COPD- Definition“…aclinicalsyndromecharacterized bychronicrespiratorysymptoms, structural abnormalities(airwaysdisease,emphysema, orboth),lung-function impairment (primarilyairflowlimitationthatispoorlyreversible)oranycombinationofthese.”
CelliB,WedzichaJA.NewEnglJMed2019;381:1257-1266.
COPYRIG
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A teaching hospital ofHarvard Medical School
COPD–oldphenotypes• Chronicbronchitis:productivecoughfor3months ineachof2consecutive years
• Emphysema: abnormalpermanentenlargementoftheairspacesdistaltotheterminalbronchioles, accompaniedbydestructionoftheirwalls,andwithoutevidenceoffibrosis
• Other:bronchiectasis, airwayreactivity
COPYRIG
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A teaching hospital ofHarvard Medical School
COPDPhenotypesareGrowing• Hersh etal.,COPD2007;4:33191patientsearlyonset,severeCOPD(FEV1<40%pred):emphysemapredominant,lowFEV1,lessbronchospasm
• Friedlanderetal.,COPD2007;4:355“Frequentexacerbater,”pulmonarycachectic,rapiddecliner,airwayshyperresponsive,impairedexercisetolerance
• Jankowich andRounds,Chest2012;141:222 (review)Combinedpulmonaryfibrosisandemphysemasyndrome;spiro maybenormal,butCTwithextensiveemphysema
COPYRIG
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A teaching hospital ofHarvard Medical School
FrequentExacerbator
2138 pts-ECLIPSE study (Eval of COPD Longitudinally to Identify Predictive Surrogate End points). Exacerbation freq in 3 yrs. Multivariate analysis. New Engl J Med 363:1128, 2010
COPYRIG
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A teaching hospital ofHarvard Medical School
COPDEPIDEMIOLOGY:StillGrowingNewEnglJMed2019;381:1257-1266
COPYRIG
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A teaching hospital ofHarvard Medical School
GOLDClassificationGlobalInitiativeforChronicObstructiveLung Disease
AmJRespCritCareMed176;532-555,2007
COPYRIG
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A teaching hospital ofHarvard Medical School
ShouldPeoplebeScreened forCOPDwithSpiro?• Linetal.,AnnIntMed2008;148:535
– USPreventativeServicesTaskForce– Metaanalysis- couldyoupreventCOPDexacerbations?Reducemorbidityandmortality?Enhancesmokingcessation?
– Screen833ptstoprevent1COPDexacerbation– NodatatosuggestdecreaseM&M– Nodatatosupportenhancedsmokingcessation
• Note:FEV1/FVCratiodeclineswithnormalaging• Controversyabout“smalllungs”ingrowthanddevelopment
COPYRIG
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A teaching hospital ofHarvard Medical School
LungSizeatBirth:DiagnosisofCOPDNewEnglJMed2019:381;1248-1256
COPYRIG
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A teaching hospital ofHarvard Medical School
RateofHospitalizationforCOPD(comparedtoCAD)PersistsDespite
DecreaseinSmoking
Likely related to aging population.AJRCCM 2017;195:287-291.
COPYRIG
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A teaching hospital ofHarvard Medical School
COPDMortality• “Chroniclowerrespiratorydisease”nowthethirdleadingcauseofdeathintheUS.
• Numberofwomendying>men(studiessuggestwomenmaybemoresusceptibletocigs:Silvermanetal.AJRCCM2000;162:2152)
• Onlydiseaseintop10à mortality increasing.• Evensmokers<1ppdhaveé mortalitycomparedtonon-smokers Inoue-Choietal.JAMAIntMed2017
COPYRIG
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A teaching hospital ofHarvard Medical School
COPD- CausesofDeathpulm>cardiovasc>cancer NEJM356;851854,2007
COPYRIG
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A teaching hospital ofHarvard Medical School
COPD- RiskFactors• Cigarettes- activeandpassivesmoking(30-50%ofcurrent/formersmokershaveairflowobstruction)
• Airwaysreactivity:“DutchHypothesis”– commonlinksbetweenCOPDandasthma
• Geneticsusceptibility– alpha1anti- trypsindeficiency– Othergenesmayexplainvariabilityinriskwithsmoking
• Bacterial,viralinfections;cigsmokereducesimmuneresponse– interferon,IL-1(Chest143:196,2013)
• Airpollutionandoccupationalexposures
COPYRIG
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A teaching hospital ofHarvard Medical School
SmokingasRisk:duration>intensity
Smokingdurationgreaterriskforemphysemathancigarettesperday
Thorax 2018;73:414-421
COPYRIG
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A teaching hospital ofHarvard Medical School
DutchHypothesis• Firstproposedin1961• Threeprinciples
– VariousformsofCOPDhaveoverlappingfeatures– Oneformofobstructivelungdisease(asthma)mayevolveintoanother(COPD)
– Developmentofobstructivelungdiseaseresultofcombinationof:1)inflammationandairwayreactivity2)geneticpredisposition3)environmentalfactors
COPYRIG
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A teaching hospital ofHarvard Medical School
Asthma-COPDOverlapSyndrome(ACOS)
Chest 2019;155:168-177Estimated present in 15-45% of people with obstructive lung disease
COPYRIG
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A teaching hospital ofHarvard Medical School
Emphysema(lungsmorecompliant)inNonsmokingAsthmaPatients
Chest 2018;153;6118-629
COPYRIG
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A teaching hospital ofHarvard Medical School
GeneticRiskFactors• Alpha1anti-trypsin• 30-50%oflungfunctionmaybedeterminedbygenetics;susceptibilitytoCOPDlikelypolygenic.Familystudies:SiblingsofCOPDpatientsincreasedrisk
AmJRespirCritCareMed164:1419, 2001• Genesactivatedbysmokingmayleadtodisease(Chest133:1344, 2008)OR maybeprotective(protectivegenesinpromoterregionMMP12associatedwithhigherFEV1,reducedriskofCOPD-NewEnglJMed361:2599,2009)
COPYRIG
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A teaching hospital ofHarvard Medical School
GeneticsandDiseaseInsights• COPDGeneStudy
– Analysisof2500peopleofAfricanandEuropeanancestry;multivariatelogisticregressionmodeling
– African-Americansmorelikelytohaveearlyonsetdisease
AmJRespirCritCareMed2011;184:414-420• GeneticsandCOPDphenotypes
– 12,031subjects– Fivelociidentifiedwithemphysemarelatedphenotypes,onewithairway,twowithgastrapping
AmJRespirCritCareMed2015;192:559-569
COPYRIG
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A teaching hospital ofHarvard Medical School
Smoking® Inflammation• Inflammation- increasedneutrophilsinmucosa;increasedCD-8cellsinsubepithelium.
MaestrelliP.AmJRespirCritCareMed2001
• LVHmorecommoninCOPDpts(evenwithnormalO2levels)withouthxofhypertensionc/wcontrols
Andersonetal.Chest143:91,2013
• Datafeedscontroversyaboutsteroidsandanti-oxidants
COPYRIG
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A teaching hospital ofHarvard Medical School
PresenceofIL-17AinLungTissueandSeverityofDiseaseAmJRespirCritCareMed2016:193:1092-1100
COPYRIG
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A teaching hospital ofHarvard Medical School
Mepolizumab– AntibodytoInterleukin5• Phase3trial;
randomized,placebo,doubleblinded
• 462patients;eosinophilicphenotype(eos150-300/ml);highdoseICS
• Reducedcumulativeexacerbationsover52weekswhenaddedtosteroids
COPYRIG
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A teaching hospital ofHarvard Medical School
MuscleDysfunctioninCOPDSystemiccatabolicstate?
Am J Respir Crit Care Med 2015;191:616COP
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A teaching hospital ofHarvard Medical School
MuscleDysfunctioninCOPDAm J Resp Crit Care Med2018;198;175-186
COPYRIG
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A teaching hospital ofHarvard Medical School
COPDPhysiology
• Lossofelasticrecoil• Airwaysobstruction- the‘equalpressurepoint’
• Hyperinflation• AutoPEEPCOPYRIG
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A teaching hospital ofHarvard Medical School
LungParenchymasupportsAirwaysSchwartzsteinRM,ParkerMJ,RespiratoryPhysiology2005
COPYRIG
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A teaching hospital ofHarvard Medical School
Hyperinflation
• Shorteningofmusclesleadstoamechanicaldisadvantageintheattempttogeneratenegativeintra-pleuralpressure
• Contributestothedevelopmentofventilatorymusclefatigue
• Maystimulatechestwallreceptorscontributingtodyspnea
COPYRIG
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A teaching hospital ofHarvard Medical School
Auto-PEEP
• Persistenceofpositivepressureintheairwaysattheendofexhalation
• Associatedwithhyperinflation• Resultsinanadditionalburdenduringinspiration- a‘thresholdinspiratoryload’COPYRIG
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A teaching hospital ofHarvard Medical School
AutoPEEP• AutoPEEPaccompaniesexpiratoryflowlimitation
• Heterogeneouslungunitswithvariabletimeconstants(TC=RXC)
• Contributestoworkofbreathing,dyspnea
Marini,AJRCCM2011;184:756
COPYRIG
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A teaching hospital ofHarvard Medical School
Dyspnea:Morethanyouthought…• Basicphysiologyofdyspnea iscomplex- manyfactorscontributetorespiratorydiscomfort
• Thequalitiesofrespiratorydiscomfort vary;mayprovideinsightintotheetiologyofthedyspnea
• Levelofdyspneamore closelycorrelatedwith5-yearsurvival thanFEV1(Chest121:1434, 2002)
• Dailyphysicalactivity isindependentpredictorformortalityandhospitalizationduetoexacerbation (Chest142:338, 2012;andThorax67:117,2012)
COPYRIG
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A teaching hospital ofHarvard Medical School
DescriptorsofDyspnea• Mybreathdoesnotgoinall
theway• Mybreathingrequireseffort• IfeelthatIamsmothering• I feelahungerformoreair• Mybreathingisheavy• Icannottakeadeepbreath• Ifeeloutofbreath• Mychestfeelstight• Mybreathingrequiresmore
work
• IfeelthatIamsuffocating• Ifeelthatmybreathstops• Iamgaspingforbreath• Mychestisconstricted• Mybreathingisrapid• Mybreathingisshallow• IfeelthatIambreathingmore• Icannotgetenoughair• Mybreathdoesnotgooutall
theway
COPYRIG
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A teaching hospital ofHarvard Medical School
PhysiologyofDyspnea• ‘Tightness, constriction’ - bronchospasm• ‘Urgetobreathe,airhunger’- increasedrespiratorydrive:e.g.,CO2,severeasthma, CHF
• ‘Effortofworkofbreathing’ - increasedmechanical impedance
• ‘Unsatisfied inspiratory effort’ - hyperinflation• ‘Heavybreathing, breathingmore’-deconditioning
COPYRIG
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A teaching hospital ofHarvard Medical School
PulmonaryFunctionTests• Spirometry - maybemoreconsistent inCOPDthanarepeakflows
• Lungvolumes- airtrapping, hyperinflation;bewareofimpactofbullousdiseaseonheliumdilutionmeasurements oflungvolumes
• Diffusingcapacity- predictiveofdesaturation• Flowvolume loop- mayhelpdistinguish“pure”emphysemaandasthma
COPYRIG
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A teaching hospital ofHarvard Medical School
PFT’sinCOPD
COPYRIG
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A teaching hospital ofHarvard Medical School
Flow-volumeCurveinCOPD
COPYRIG
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A teaching hospital ofHarvard Medical School
Oximetry• Assessoxygenationatrest• Desaturationonexercise(correlatewithlowdiffusingcapacityPFT’s)
• Considernocturnaloximetryifevidenceofrightheartfailureorpolycythemia
• Increasingdataonroleofpulmonaryhypertensionasfactorindecreasedexercisecapacity
COPYRIG
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A teaching hospital ofHarvard Medical School
It’sNeverTooLateToStopSmokingSchwartzsteinRM
Smokers lose one decade of life expectancy; stop by age 40, reduces risk by 90%NEJM 368:4, 2013
COPYRIG
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A teaching hospital ofHarvard Medical School
SmokingCessation:Multi-prongedApproach• Behavioral(telephoneandgroupcounseling)andpharmacotherapyinterventionscombinedbestresults
• PatnodeCDetal.AnnIntMed,2015-- ReviewofreviewsforUSPreventiveServicesTaskForce– Behavioralinterventions(phone,counseling,etc.)pluspharmacotherapy1.76oddsratioofsuccesscomparedtousualcare
– Nicotinereplacement,buproprionandvareniclinealleffective(vareniclinemosteffective)
• Quitesmokingà reducedriskofdementia(Choietal.AnnClinandTranslationalNeuro2018)
COPYRIG
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A teaching hospital ofHarvard Medical School
ElectronicCigarettesNEJM2016;375:1372-1381
• Batteryoperated,nicotinedeliverydevices;producevaporwithnicotineandpropyleneglycolorglycerol
• 18%quitsmokingwithe-Cigsinrandomizedtrialc/w10%incontrol(standardnicotinereplacement;lowersuccessratethanmoststudies)(NEJM2019;380:629)
• 1/3ofusershaveneversmokedcigarettes;vapormaycontainformaldehydeandothercarcinogensà recentmini-epidemicofacutelungreactionsanddeaths(NEJMSeptember6,2019- epub)
• Nicotinemaybe“gatewaydrug;”associatedwithotherdrugabuse(NEJM2014;371:932);particularproblemforadolescentssusceptibletoaddiction(AnnIntMed2015;163:59-60)
COPYRIG
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A teaching hospital ofHarvard Medical School
E-CigarettesandSmokingCessation• Supplementaryuseofe-cigsforpatientsbeingdischargedfromhospitalwithgoalofsmokingcessationà lessabstinencefromsmokingat6months(Rigottietal.,AnnIntMed2018)
• PopulationstudyinEurope;cross-sectionallogisticalregressionofassociationofe-cigsandbeingformersmokerà e-cigsassociatedwithloweroddsofbeingaformersmoker(Kuliketal.,AmJPrevMed2018;54:603-609)
COPYRIG
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A teaching hospital ofHarvard Medical School
BronchodilatorsinCOPDInspirationorExpiration?
• Taubeetal.AJRCCM162:216,2000
– Betaagonists:∆FIV1(inspiratoryflow!)bestpredictorofdecreaseddyspnea;∆ICalsobetterthanFEV1.
• O’Donnelletal.EurRespirJ.18:914,2002
– Postsalbutamol,83%ofpatientsimprovedlungvolumemeasurements,i.e.,lesshyperinflation,inabsenceof∆FEV1
• Cellietal.Chest124:1743,2003
— TiotropiumincreasedICmorethanFEV1
COPYRIG
HT
A teaching hospital ofHarvard Medical School
GoalsofTherapyinCOPD?• FEV1– severity• ChangeinFEV1–progression
• Exacerbations–activity
• Qualityoflife,symptoms– Impactonpatient
• Future:biomarkers;diseaseactivity Am J Resp Crit Care Med 2016;194:541-549
COPYRIG
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A teaching hospital ofHarvard Medical School
GoalsofTherapyinCOPDEvolving
Am J Resp Crit Care Med 2016;194:541-549COPYRIG
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A teaching hospital ofHarvard Medical School
LABA+LAMAvs.LABA+ICSNEJM2016;374:2222-2234
• Indacterol+GlycopyrroniumvsSalmeterol+Fluticasone
• 11%reductioninannualrateofCOPDexacerbationwithoutsteroids
• Absoluteratereduction:4.03to3.59
Time to First Exacerbation
COPYRIG
HT
A teaching hospital ofHarvard Medical School
WithdrawalofInhaledSteroidsDecreasesPFTsNEJM2014;371:1285
• 2485pts,hxofCOPDexacerbation;tio+salmeterol+ICS
• RandomlyassignedtostopICSover12weeks
• NodiffinexacerbationsbutgreaterdeclineinFEV1withstopinICS
AJRCCM2017;195:1189
• ↑bloodeos→↑riskexacerbationpoststoppingICS
COPYRIG
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A teaching hospital ofHarvard Medical School
De-escalationofTripleTherapyandIncreasedExacerbations:Assoc.WithEosOverall,smalldecreaseinFEV1withnodiff.inexacerbations.HigherexacerbationriskandfallFEV1inpts.with> 300bloodeos/microliter
Am J Resp Crit Care Med 2018;198;329-339
COPYRIG
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A teaching hospital ofHarvard Medical School
GOLDSummaryonBronchodilators
COPYRIG
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A teaching hospital ofHarvard Medical School
Corticosteroids• Approximately1/3ofpatientswillrespondtosteroidswithimprovedlungfunction
• Cannotpredictwhichpatientswillrespondbasedonpreandpostbronchodilatorchallengewithbetaagonist
• SmallchangesinFEV1maymakebigchangesindyspnea
• Increasingevidenceonroleofbloodeosinophilsasmarkerforresponsiveness
COPYRIG
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A teaching hospital ofHarvard Medical School
PneumoniaandMortalityinCOPD• LimitsofstudiesofpneumoniainCOPDandICS
– Riskofbias– Lackofsystematicascertainmentofpneumonia;dependenceonadverseriskreporting
– Retrospective,observationalstudydesigns
• Noevidenceofincreasedmortality• Possible“double-effect”– anadverseeffectplusanunexplainedmitigatingeffect;ICSmayimprovemortality
AmJRespirCritCareMed2015;191:141-148
COPYRIG
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A teaching hospital ofHarvard Medical School
InhaledSteroidsandPneumonia• CochraneDatabaseSystematicReview2014
– Randomizedcontrolledstudies;atleast12weeksduration
– BudesonideorFluticasonevs.placebowith/withoutLABA
– ICSincreasednon-fatalseriousadversepneumoniaevents,i.e.,requirehospitaladmission
– Nodifferenceinoverallmortalityrates
COPYRIG
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A teaching hospital ofHarvard Medical School
ICSAssociatedwithLowerRiskofHospitalizationinOlderPtswithCOPD
Retrospective longitudinal population cohort age > 66 with COPD in Canada.Exposure = new receipt of ICS.Y-axis = proportion free of hospitalization.AnnalsATS 2019;16:1252-1262
ICS
No ICSCOPYRIG
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A teaching hospital ofHarvard Medical School
InhaledSteroidsandRiskofTBandFlu
• Systematicreview;randomized,controlledtrials– 25forTB(showningraph),26forinfluenza
• HigherriskforTB(butfewevents);nodifferenceforflu
Chest 2014;145:1286
COPYRIG
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A teaching hospital ofHarvard Medical School
ProphylacticAntibioticsandCOPDExacerbations
• CochraneReview2013• SevenRCTs;studiesinvolvedmacrolideseithercontinuousorintermittent;duration3to36months
• Results:numberofpatientsexperiencingexacerbationsreducedfrom69to54%;statisticallybutnotclinicallysignificant↑QOL
• Nomajorproblemswithresistantorganisms
COPYRIG
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A teaching hospital ofHarvard Medical School
Azithromycinfor3monthsforHospitalizedCOPDExacerbations
• Randomized,double-blinded,placebocontrolled• PatientshospitalizedforCOPDexacerbation;randomizedwithin48hourstoazithromycinvsplacebofor3months(addedtostandardtreatmentwithsteroidsandin-hospitalantibiotics).
• Followedfor6months;treatmentfailure(increaseinmedsorhospitalization)was49%intreatmentgroup;60%inplacebo
Vermeersch K,etal.AmJRespir Crit CareMed- October2019- epub
COPYRIG
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A teaching hospital ofHarvard Medical School
COPDReadmissions– onlyhalfduetoRespiratoryillness
• 26millionadmits• 3.5%COPD• 20.2%readmitin30days;onlyhalfduetorespillness
• Dualmedicare–medicaidhigherrisk
Chest 2015;147:1219
COPYRIG
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A teaching hospital ofHarvard Medical School
KeyPointsonAnti-Inflammatories
COPYRIG
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A teaching hospital ofHarvard Medical School
OxygenTherapy- IndicationsChest 138:179, 2010
Note: use of O2 for sats 89-93 with mild exercise desat–no mortality benefitNEJM 2016;375:1617.
COPYRIG
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A teaching hospital ofHarvard Medical School
OxygenandMortality• COT– continuousoxygentherapy(24hrs/day)
• MRC– MedicalResearchCouncil(15hrs/day)
• NOT– nocturnaloxygentrial
Chest138:179,2010
COPYRIG
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A teaching hospital ofHarvard Medical School
Roflumilast– Phosphodiesterate4Inhibitor• Anti-inflammatoryagent• 2placebo-controlled,multi-
centertrials;note:inhaledsteroidsstopped
• 3091pts,overage40,FEV1<50%predicted
• Roflumilast500mcg/day• Exacerbationsreduced1.37
to1.14(p<0.003)• FEV1increased48ml
• Calverleyetal.Lancet2009;374:686
Roflumilast reduced frequency of exacerbations in severe COPD patients with freq exacerbator phenotype. Wedzicha et al.Chest 143:1302, 2013; Martinez et al. AJRCCM 2016;194:559-567
Eos > 150 predictor of effect as wellAJRCC 2018;1268
COPYRIG
HT
A teaching hospital ofHarvard Medical School
COPDandPrognosisThe“BODE”Index
• MultidimensionalgradingsystemthatincorporatesrespiratoryandsystemicexpressionsofCOPDüBody-massindex(B)üAirflowobstruction(O)üDyspnea(D)üExercisecapacity(E)
• HigherBODEscore® greaterriskofhospitalizationanddeathCellietal.NEnglJMed350:1105,2004Ongetal.Chest128:3810,2005
COPYRIG
HT
A teaching hospital ofHarvard Medical School
NutritionandCOPD• Bodyweighthasindependenteffectonsurvival• Thresholdvalueof25kg/m2 belowwhichmortalityriskincreased
• Possibleroleofsystemicinflammation;notmalnutritionperse.Increasedmarkersofcatabolism,e.g.,IL-6DebigareRetal.Chest124:83,2003
• Inunderweightpatient,unclearweightgainenhancessurvival
• VitDinptswithlowlevelsmayreduceexacerbationsLehoucketal.AnnIntMed156:105,2012
COPYRIG
HT
A teaching hospital ofHarvard Medical School
Exercise
COPYRIG
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A teaching hospital ofHarvard Medical School
PulmonaryRehabilitation• Importanceofdeconditioningasalimitingfactorinmany
patientswithCOPD;• Mechanismofeffectprobablyvarieswithpatient:
1)reconditioning;2)moreefficientuseofbreathingmuscles;3)strengtheningofbreathingmuscles;4)desensitizationtodyspnea
• Upto14%ofptswithCOPDstopexercisingduetolegdiscomfort(FEV144%pred.)Chest144:491,2013
• Patientsreporting“moderateorvigorousphysicalactivity”eachweek,significantreductioninreadmitrateafterexacerbationAnnAmThorSoc11:695;2014
COPYRIG
HT
A teaching hospital ofHarvard Medical School
PulmonaryRehab• Riesetal.,AnnIntMed1995A)IncreasedtreadmillenduranceB)DecreaseddyspneaC)Decreasedmusclefatigue
-- Effectslastedfor12monthsoffollow-up
A
B
CCOPYRIG
HT
A teaching hospital ofHarvard Medical School
MaintenanceRehabforTwoYears
Afterinitialrehabprogram,groupsrandomizedtorepeatvisitsq2weeksvs.controlworkingontheirown.Maintained6MWDbetterwithsupervision.BaselineFEV1<40%predicted.AJRCCM2017;195:622-629
COPYRIG
HT
A teaching hospital ofHarvard Medical School
PulmonaryRehab- EfficacyCochraneDatabase; systematicreview2015;February 23
• 65RCT’sreviewed;3822participants• MeanFEV139%predicted• Statistically significant improvement inQOLoutcomes
• Significant increase in6MWTdistance
COPYRIG
HT
A teaching hospital ofHarvard Medical School
COPDExacerbations
COPYRIG
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A teaching hospital ofHarvard Medical School
VolumeReductionSurgery• Physiologicprinciples:A)reducethehyperinflationofthechest;B)allowmorenormalportionsofthelungtoexpandandreceivegreaterventilation/perfusion
• Appeartobefewercomplicationswiththoracoscopic vsmediansternotomyapproach
• Improvement inQOLmeasures, eg.,physicalandsocialfunctioning, vitality (Chest115:383, 1999)
COPYRIG
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A teaching hospital ofHarvard Medical School
NETTStudySubgroupAnalysis
• PredominantlyUpperLobeEmphysemaand LowExerciseCapacity– Mortalitylowerinsurgeryvsmedicaltherapy(p=0.005)
• Non-upperLobeEmphysemaand HighExerciseCapacity– Mortalityhigherinsurgerythanmedicalgroup(p=0.02)
COPYRIG
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A teaching hospital ofHarvard Medical School
EndobronchialValvesandCoilsHomogeneousemphysema;nocollateralvent;93patients;randomized
• SignificantbutmarginalabsolutechangeinFEV1
• Improvedqualityoflifeat3months
AmJRespir Crit CareMed194:1073,2016
Endocoilscompressemphysematouslung•315pts;bilateralcoils•↑6MWD(10mvslossof7.6m)•ImprovedQOLmeasures•Complications34.8%vs19.1%incontrolJAMA2016;315;2178
COPYRIG
HT
A teaching hospital ofHarvard Medical School
LungTransplantation
• Singlelungtransplantationissuccessfuldespitetheverycompliantnatureofthelungleftbehind
• Longwaitfordonororgan• Survivalstill50%atfouryearsCOPYRIG
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A teaching hospital ofHarvard Medical School
GOLDSummaryforAdvancedCOPD
COPYRIG
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A teaching hospital ofHarvard Medical School
COPDSummary• COPDassociatedwithvaryingphenotypes;roleofinflammationleadstotherapeuticstrategies
• Elasticrecoilkeytophysiologyofemphysema• SmallchangesinFEV1andlungvolumesmayresultinbigchangesindyspnea;hyperinflationmajorconsequenceofobstruction
• FunctionallimitmaynotbefromCOPD;considerrehab• HypoxicpatientsneedsupplementalO2
• Increasinglylinktreatmenttophenotype,impactonpatient
COPYRIG
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