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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
HT
A teaching hospital ofHarvard Medical School
COPD– Definitionincludes:• Chronicairflowobstruction• Rangeofpathologicchangesinthelung(abnormalinflammatoryresponsetonoxiousparticlesorgases)
• Extra-pulmonaryeffects• Theobstructionisprogressive• Mayhaveelementsofairwaysreactivity,i.e.,theobstructionmaybepartiallyreversible
• “Preventableandtreatable.”
COPYRIG
HT
A teaching hospital ofHarvard Medical School
DiagnosisofCOPD– GOLDUpdate
AJRCCM2017;195:557-582 COP
YRIGHT
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
HT
A teaching hospital ofHarvard Medical School
COPD–oldphenotypes• Chronicbronchitis:productivecoughfor3months ineachof2consecutive years
• Emphysema: abnormalpermanentenlargementoftheairspacesdistaltotheterminalbronchioles, accompaniedbydestructionoftheirwalls,andwithoutevidenceoffibrosis
• Other:bronchiectasis, airwayreactivity
COPYRIG
HT
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
HT
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
HT
A teaching hospital ofHarvard Medical School
COPDEPIDEMIOLOGY:StillGrowingNewEnglJMed2019;381:1257-1266
COPYRIG
HT
A teaching hospital ofHarvard Medical School
GOLDClassificationGlobalInitiativeforChronicObstructiveLung Disease
AmJRespCritCareMed176;532-555,2007
COPYRIG
HT
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
HT
A teaching hospital ofHarvard Medical School
LungSizeatBirth:DiagnosisofCOPDNewEnglJMed2019:381;1248-1256
COPYRIG
HT
A teaching hospital ofHarvard Medical School
RateofHospitalizationforCOPD(comparedtoCAD)PersistsDespite
DecreaseinSmoking
Likely related to aging population.AJRCCM 2017;195:287-291.
COPYRIG
HT
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
HT
A teaching hospital ofHarvard Medical School
COPD- CausesofDeathpulm>cardiovasc>cancer NEJM356;851854,2007
COPYRIG
HT
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
HT
A teaching hospital ofHarvard Medical School
SmokingasRisk:duration>intensity
Smokingdurationgreaterriskforemphysemathancigarettesperday
Thorax 2018;73:414-421
COPYRIG
HT
A teaching hospital ofHarvard Medical School
DutchHypothesis• Firstproposedin1961• Threeprinciples
– VariousformsofCOPDhaveoverlappingfeatures– Oneformofobstructivelungdisease(asthma)mayevolveintoanother(COPD)
– Developmentofobstructivelungdiseaseresultofcombinationof:1)inflammationandairwayreactivity2)geneticpredisposition3)environmentalfactors
COPYRIG
HT
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
HT
A teaching hospital ofHarvard Medical School
Emphysema(lungsmorecompliant)inNonsmokingAsthmaPatients
Chest 2018;153;6118-629
COPYRIG
HT
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
HT
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
HT
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
HT
A teaching hospital ofHarvard Medical School
PresenceofIL-17AinLungTissueandSeverityofDiseaseAmJRespirCritCareMed2016:193:1092-1100
COPYRIG
HT
A teaching hospital ofHarvard Medical School
Mepolizumab– AntibodytoInterleukin5• Phase3trial;
randomized,placebo,doubleblinded
• 462patients;eosinophilicphenotype(eos150-300/ml);highdoseICS
• Reducedcumulativeexacerbationsover52weekswhenaddedtosteroids
COPYRIG
HT
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
HT
A teaching hospital ofHarvard Medical School
COPDPhysiology
• Lossofelasticrecoil• Airwaysobstruction- the‘equalpressurepoint’
• Hyperinflation• AutoPEEPCOPYRIG
HT
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
HT
A teaching hospital ofHarvard Medical School
Auto-PEEP
• Persistenceofpositivepressureintheairwaysattheendofexhalation
• Associatedwithhyperinflation• Resultsinanadditionalburdenduringinspiration- a‘thresholdinspiratoryload’COPYRIG
HT
A teaching hospital ofHarvard Medical School
AutoPEEP• AutoPEEPaccompaniesexpiratoryflowlimitation
• Heterogeneouslungunitswithvariabletimeconstants(TC=RXC)
• Contributestoworkofbreathing,dyspnea
Marini,AJRCCM2011;184:756
COPYRIG
HT
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
HT
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
HT
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
HT
A teaching hospital ofHarvard Medical School
PulmonaryFunctionTests• Spirometry - maybemoreconsistent inCOPDthanarepeakflows
• Lungvolumes- airtrapping, hyperinflation;bewareofimpactofbullousdiseaseonheliumdilutionmeasurements oflungvolumes
• Diffusingcapacity- predictiveofdesaturation• Flowvolume loop- mayhelpdistinguish“pure”emphysemaandasthma
COPYRIG
HT
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
HT
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
HT
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
HT
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
HT
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
HT
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
HT
A teaching hospital ofHarvard Medical School
GoalsofTherapyinCOPDEvolving
Am J Resp Crit Care Med 2016;194:541-549COPYRIG
HT
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
HT
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
HT
A teaching hospital ofHarvard Medical School
GOLDSummaryonBronchodilators
COPYRIG
HT
A teaching hospital ofHarvard Medical School
Corticosteroids• Approximately1/3ofpatientswillrespondtosteroidswithimprovedlungfunction
• Cannotpredictwhichpatientswillrespondbasedonpreandpostbronchodilatorchallengewithbetaagonist
• SmallchangesinFEV1maymakebigchangesindyspnea
• Increasingevidenceonroleofbloodeosinophilsasmarkerforresponsiveness
COPYRIG
HT
A teaching hospital ofHarvard Medical School
PneumoniaandMortalityinCOPD• LimitsofstudiesofpneumoniainCOPDandICS
– Riskofbias– Lackofsystematicascertainmentofpneumonia;dependenceonadverseriskreporting
– Retrospective,observationalstudydesigns
• Noevidenceofincreasedmortality• Possible“double-effect”– anadverseeffectplusanunexplainedmitigatingeffect;ICSmayimprovemortality
AmJRespirCritCareMed2015;191:141-148
COPYRIG
HT
A teaching hospital ofHarvard Medical School
InhaledSteroidsandPneumonia• CochraneDatabaseSystematicReview2014
– Randomizedcontrolledstudies;atleast12weeksduration
– BudesonideorFluticasonevs.placebowith/withoutLABA
– ICSincreasednon-fatalseriousadversepneumoniaevents,i.e.,requirehospitaladmission
– Nodifferenceinoverallmortalityrates
COPYRIG
HT
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
HT
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
HT
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
HT
A teaching hospital ofHarvard Medical School
COPDReadmissions– onlyhalfduetoRespiratoryillness
• 26millionadmits• 3.5%COPD• 20.2%readmitin30days;onlyhalfduetorespillness
• Dualmedicare–medicaidhigherrisk
Chest 2015;147:1219
COPYRIG
HT
A teaching hospital ofHarvard Medical School
KeyPointsonAnti-Inflammatories
COPYRIG
HT
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
HT
A teaching hospital ofHarvard Medical School
OxygenandMortality• COT– continuousoxygentherapy(24hrs/day)
• MRC– MedicalResearchCouncil(15hrs/day)
• NOT– nocturnaloxygentrial
Chest138:179,2010
COPYRIG
HT
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
HT
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
HT
A teaching hospital ofHarvard Medical School
VolumeReductionSurgery• Physiologicprinciples:A)reducethehyperinflationofthechest;B)allowmorenormalportionsofthelungtoexpandandreceivegreaterventilation/perfusion
• Appeartobefewercomplicationswiththoracoscopic vsmediansternotomyapproach
• Improvement inQOLmeasures, eg.,physicalandsocialfunctioning, vitality (Chest115:383, 1999)
COPYRIG
HT
A teaching hospital ofHarvard Medical School
NETTStudySubgroupAnalysis
• PredominantlyUpperLobeEmphysemaand LowExerciseCapacity– Mortalitylowerinsurgeryvsmedicaltherapy(p=0.005)
• Non-upperLobeEmphysemaand HighExerciseCapacity– Mortalityhigherinsurgerythanmedicalgroup(p=0.02)
COPYRIG
HT
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
HT
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
HT