ChronicObstructivePulmonaryDisease

andAsthmaUpdate

JohnL.Faul,MDFCCPAssistantProfessor,DivisionofPulmonary/CriticalCareMedicineStanfordUniversity.ChronicObstructivePulmonaryCOPD:OutlineEpidemiologyDefinitionsMedicalmanagementHypoxiaInfectionsVaccination

.COPD:OutlineEpidemiology.UniversalProblem

.UniversalProblem

.COPD:epidemiology14millionintheUSwithCOPD12.5millionwithchronicbronchitis1.65millionwithemphysema4thleadingcauseofdeathinUS3rdmostfrequentdiagnosisofpatientsreceivinghomecare.COPD:epidemiology14millioniPrevalenceofCOPDintheUS*Age-adjustedto2000USpopulation.?Representsastatisticallysignificantdifferencefromrateamongmales.Manninoetal.MMWR.2002;51(SS-6):1-16.Rate/1,000Population*020304050607080901980198219841986YearMaleFemaleTotal101988199019921994199619982000Since1987,theprevalenceofCOPDamongwomenhasbeensignificantlyhigherthanthatamongmen???????????????.PrevalenceofCOPDintheUS*ACOPD:

TheUsualSuspects.COPD:

TheUsualSuspects.COPD:riskfactorstobaccosmokingaccountsfor80-90%oftheriskofdevelopingCOPDageofstarting,totalpack-yearsandcurrentsmokingstatusarepredictiveofmortalityonly15%ofsmokersdevelopclinicallysignificantCOPDalpha1-antitrypsindeficiency(accountsforlessthan1%ofallCOPDcases)occupationalexposurestodustsandfumes.COPD:riskfactorstobaccosmokLungfunctiondeclineswithage.LungfunctiondeclineswithagElastictissueislostinemphysema.ElastictissueislostinemphCOPD:definitionsChronicbronchitis---aclinicaldefinition:“thepresenceofchronicproductivecoughfor3monthsineachof2successiveyearsinapatientinwhomothercausesofchroniccoughhavebeenexcluded”Emphysema---apathologicdefinition:“abnormalpermanentenlargementoftheairspacesdistaltotheterminalbronchiolesaccompaniedbydestructionoftheirwalls”.COPD:definitionsChronicbronc

Pinkpuffers

&

Bluebloaters

.

Pinkpuffers

&

BlueCOPD:HyperinflationIncreasedretrosternalairspaceFlatdiaphragmsIncreasedAPdiameter.COPD:HyperinflationIncreasedCOPD.COPD.COPD:OxygentherapyOxygentherapyinCOPD:extendslifeinhypoxemicpatientsNOTTtrial,AnnIntMed1980;93:391-398MRCtrial,Lancet1981;1:681-685strengthenscardiacfunction,improvesexerciseperformanceandADLswhenFEV1<1.0L(or<50%predicted)an ABGshouldbedoneHomeO2costsintheUS/yr:$2,400,000,000.COPD:OxygentherapyOxygentheOxygenDissociationCurve1008060BelowPaO2=60mmHg,Hemoglobinrapidlylosesoxygencarryingcapacity (West:TextbookofPhysiology)

HemoglobinSaturation%406080__________40__200iiiAt80mmHg,95%satAt60mmHg,90%satAt40mmHg,70%satPaO2(mmHg).OxygenDissociationCurve10080HypoxicPulmonaryVasoconstrictionThelungregulatesbloodflowaccordingtoitsoxygencontentAlowvenousoxygencontent(lowoxygencontentinthepulmonaryartery)preventsbloodflowtothelungBloodFlow%Airsack(Alveolar)OxygenWest:TextbookofPhysiologyOxygen-sensitivechemoreceptorslocatedinthepulmonaryarteriolearethedominantcontrollersofpulmonaryvasculartone FishmanAP:Hypoxiaonthepulmonarycirculation.Howandwhereitacts. CircRes1976;38:221–231.HypoxicPulmonaryVasoconstricCOPD:acaseinpointCC:Mrs.H.isa67y.ofemalewith worseningdyspneaxseveralyearswhopresentsfor2ndopinionregardingdiagnoses,andmanagement,ofher“breathingproblem”herpastdiagnoseshaveincludedasthma,bronchitis,andemphysemashewantstoknowexactlywhatshehas....COPD:acaseinpointCC:MrsCOPD:acaseinpointHerdyspneaismuchworseinthelastyear,tothepointthatshecannolongerbatheorcookwithouthelp...Shehasanoccasionalcough,productiveofscantsputum...Shesmoked2ppdx40yearsbutquit6yearsago....COPD:acaseinpointHerdyspnCOPD:acaseinpointShetakesthefollowingmedications:albuterolMDI2-4puffsQIDandprnthisisher“favorite”medicineatroventMDI2puffsQIDshe’snotsurethisonehelps,butmaybetheophylline200mgBIDsomedoctorgaveherthis“yearsago”prednisone10mgQDcontinuouslyfor3yearswithoccasionalincreasesshe’snevertakenanyestrogenreplacement.COPD:acaseinpointShetakesCOPD:acaseinpointShe’stakesantibiotics6-7times/yearwhenherbreathing“getsreallybad”She’sbeenon

oxygen

butdoesn’tlikeitShe’stooshortofbreathtodoanyexerciseShehasbeeninthehospital4timesinthelastyearandwasintubatedonce,6monthsagoHPI:.COPD:acaseinpointShe’stakExacerbationofCOPD

Anthonisenetal,AnnIntMed1987;106:196Saintetal,JAMA1995;273(12):957If2of3followingcriteriaaremet:increasingdyspneaincreasedsputumvolumeincreasedsputumpurulence.ExacerbationofCOPD

If2of3ExacerbationofCOPD

NoninfectiousandinfectiousInfectionsincludeviralControversialifallsputumculturesarecausativeForpatientswith2orespecially3cardinalfeatures,antibioticsareusefulShortcoursesofantibioticsareuseful AmsdenGWetal.,Chest2003:123:772-777.ExacerbationofCOPD

NoninfecAntimicrobialTherapyOralagentsusedearlierintherapyMonotherapyusedwheneverpossiblePatientcompliance(once-dailydosing)Comprehensivediseasemanagement.AntimicrobialTherapyOralagenVaccinationsandCOPD

Annualinfluenzavaccine:Reductionsinexacerbationratesparticularlywithin3weeks.Noevidenceofaneffectofintranasalliveattenuatedviruswhenthiswasaddedtoinactivatedintramuscularvaccination.

Pneumococcalvaccineevery5yearsNoevidencethatpneumococcalvaccinereducestheseverityofCOPDPoolePJ.CochraneDatabaseSystRev.2000;(4):CD002733.LeechJA.CMAJ.1987:136(4):361-5.

.VaccinationsandCOPD

AnnualiCOPD:oralsteroidsforERdischargesAaronSD.NEnglJMed.2003;348(26):2618-25.

%relapsefreeDayn=147,Pred40/dayfor10days***.COPD:oralsteroidsforERdisVladtheInhaler.VladtheInhaler.COPD:inhaledsteroidsandLABACalverleyP.Lancet.2003Feb8;361(9356):449-56ChangeInFEV1(ml)

n=1465******.COPD:inhaledsteroidsandLABPeakFlowRates

Tiotropium

versus

Salmeterol

DonohueJFChest2002.122:47-55.

.PeakFlowRates

Tiotropium

vCOPD:smokingcessationTobaccosmokingisthemostimportantfactorinCOPD,andstoppingsmokingistheonlyinterventionknowntomodifythenaturalhistoryofairwaysobstruction..COPD:smokingcessationTobaccoCOPD:smokingcessation%abstinence**TonstadS.EurHeartJ.2003May;24(10):946-55..COPD:smokingcessation%absti

COPD:advancedtherapiesBullectomyLungvolumereductionsurgery(LVRS)TransplantationSurgeryforemphysema:.

COPD:advancedtherapiesBulleGOLD’03ClassificationofCOPD*respiratoryfailure:PaO2<60mmHgwithorw/oPaCO2>50mmHg.GOLD’03ClassificationofCOTherapyatEachStageofCOPDGoldUpdate2003*FEV1/FVC<70%.TherapyatEachStageofCOPDG

COPD:managementStopsmokingLong-termoxygenInhaledsteroidsandlong-actingbetaagonistsDietandexerciseTreatacuteexacerbationsMonitorlungfunctionVaccinate.

COPD:managementStopsmoking.AsthmaFactsintheUnitedStatesAnnualnumberofhospitalizations:478,000Annualnumberofdeathsfromasthma:4,657Annualnumberofworkdayslost:14.5millionAnnualnumberofschooldayslost:14millionEstimateddirectandindirectmedicalcosts:$16billion(needsvalidation)MorbMortalWklyRep.2002March29;51:1-13..AsthmaFactsintheUnitedStaSmoothMuscleDysfunctionAirway

InflammationInflammatoryCellActivationMucosalEdemaProliferationEpithelialDamageB.MembraneThickeningBronchoconstrictionBronchialHyperreactivityHypertrophyHyperplasiaSymptoms/ExacerbationsAsthmaPathophysiology.SmoothMuscleAirway

InflammatFlow(l/s)Vol(l)-20-41324521345-6Pre-albuterolPost-albuterolPredictedSpirometry.Flow(l/s)Vol(l)-20-413245213EosinophilsinHumanBronchi.EosinophilsinHumanBronchi.ChangesinEG2duringFPtherapy

FaulJL,Thorax1998.53,753-61.ChangesinEG2duringFPtheraChangeinMeanPeakFlowwiththerapyHaahtelaT.NEnglJMed1994,331:700.ChangeinMeanPeakFlowwithChangeinMeanPeakFlowwiththerapyGreeningAP.Lancet1994,344:219-24.ChangeinMeanPeakFlowwithStudyDayProbability

ofRemainingintheStudy1.00.80.60.40.2Sal/FP100/50

FP100

Salmeterol50

Placebo*3%0 7 14 21 28 35 42 49 56 63 70 77 11%35%49%ComparisonofAsthmaTherapiesKavuruMetal.JAllergyClinImmunol.2000;105:1108-1116..StudyDayProbability

ofRemaiTimetoFirstExacerbation*10095908580750 2 4 6 8 10 12 14 16 18 20 22 24TimetoFirstExacerbation(weeks)Exacerbation-Free

Patients(%)FP88mcgb.i.d.+Salmeterol

FP220mcgb.i.d.MatzJetal.JAllergyClinImmunol.2000;105:162S..TimetoFirstExacerbation*100Kavuruetal.JAllergyClinImmunol.2000;105:1108-1116.

Dataonfile,GlaxoWellcomeInc.WeekMeanChange

fromBaseline

inFEV1(%)3025201510500 2 4 6 8 10 12 Endpoint15%

[0.28L]5%

[0.11L]2%

[0.01L]Sal/FP100/50FP100Salmeterol50Placebo25%

[0.51L]**P0.008vsFP100,salmeterol50,andplaceboatendpoint.Dosesinmcgb.i.d.PatientsTreatedWithADVAIR?Diskus?100/50hadaSignificantlyGreaterImprovementinFEV1.Kavuruetal.JAllergyClinINoonanetal.AmJRespirCritCareMed.1999;159(3):640.Reissetal.ArchInternMed.1998;158:1213-1220.FEV1(%

ChangefromBaseline;Mean

±SE)StudyWeeks(Postrandomization)302520151050-5036912151923313947526068768492100108116124132140CumulativeExtensionPlaceboMontelukastBeclomethasonePrimaryStudyPatients(15Years)NotControlledonPRNBeta-Agonists

ImprovedFEV1(Study1andExtension).Noonanetal.AmJRespirCritProportion

ofPatients

WithoutAsthmaAttackDaysSinceRandomizationBeclomethasone(n=248)Montelukast(n=379)Placebo(n=253)P=0.006MontelukastvsplaceboP=0.001BeclomethasonevsplaceboP=0.129Montelukastvsbeclomethasone10.950.900.850.800.750.700102030405060708090Patients(15Years)NotControlledonPRNBeta-Agonists

Malmstrometal.AnnInternMed.1999;130:487-495.Inthisstudy,allpatientsbenefitedfrommandatoryuseofspacers,enforcedcompliance,andrigorousmonitoringofpatients.Proportion

ofPatients

WithoutAnti-IgEAsthmaTherapiesruhMAbE-25****NS*MilgromH.NEnglJMed.199923;341(26):1966-73.Sx.Anti-IgEAsthmaTherapiesruhMASTHMA:acaseinpointCC:Ms.B.isa22

y.ofemalewith episodicdyspneax2yearswhopresentsfor2ndopinionregardingdiagnoses,andmanagement,ofher“breathingproblem”herpastdiagnoseshaveincludedasthma,bronchitis,andallergiesshewantstoknowexactlywhatshehas....ASTHMA:acaseinpointCC:MASTHMA:acaseinpointHerdyspneaismuchworseinthelastyear,tothepointthatsheoccasionallyhastoskipclassandonceshehashadtogototheED...Shehasanoccasionalcough,productiveofgreensputum...Sheneversmokedsheisallergictopollenandcats...She’saStanfordstudentwhoeatsa“healthydietandtakeslotsofvitamins”.ASTHMA:acaseinpointHerdysAcaseinpointShetakesthefollowingmedications:albuterolMDI2-4puffsQIDandprnthisisher“favorite”medicineprednisone10mgQDsheisjustfinishingasteroidtaperthatwasprescribedafterhermostrecentEmergencyRoomvisitshe’snevertakenanysteroidinhaler,becausetheydon’tworkandshe’sfearfuloftheiradverseeffects.AcaseinpointShetakesthefCOPD:acaseinpointShe’stakesantibiotics5times/yearwhenherbreathing“getsreallybad”ShesometimeswheezesafterexerciseShehasbeenintheED4timesinherlifetime,wasadmittedonce,buthasnotbeenintubatedHPI:.COPD:acaseinpointShe’stakConsiderationsinAsthmaTherapyEfficacyConvenienceControlAdverseeffects.ConsiderationsinAsthmaTheraAdverseeffectsofAsthmaTherapyBetaagonists:tremor,tachycardiaInhaledsteroids:Voice,Bones,?MetabolicLKRAs:HeadachePrednisone:Cushing’ssyndrome.AdverseeffectsofAsthmaTher012340130135140145140145150012346.56.05.55.04.50.0Time(yrs)Time(yrs)StandingHeight(cm)Standing-heightVelocity(cm/yr)NEnglJMed2000;343:1054-63.BudesonideNedocromilPlaceboBudesonideNedocromilPlaceboLong-TermEffectsofBudesonideorNedocromilinChildrenwithAsthma.012340130135140145140145150012TheRuleofTwos

(WhoNeedsControllerTherapy)Twobeta-agonistcanisters/yearTwodosesofbeta-agonist/weekTwonocturnal