ChronicObstructivePulmonaryDisease(COPD):Practice

Essentials,Background,Pathophysiology
PracticeEssentials
Chronicobstructivepulmonarydisease(COPD)isestimatedtoaffect32millionpersonsintheUnitedStates
andisthethirdleadingcauseofdeathinthiscountry.[1]Patientstypicallyhavesymptomsofchronicbronchitis
andemphysema,buttheclassictriadalsoincludesasthma(seetheimagebelow).

Venndiagramofchronicobstructivepulmonarydisease(COPD).Chronicobstructivelungdiseaseisadisorder
inwhichsubsetsofpatientsmayhavedominantfeaturesofchronicbronchitis,emphysema,orasthma.The
resultisairflowobstructionthatisnotfullyreversible.
Chronicbronchitisisdefinedclinicallyasthepresenceofachronicproductivecoughfor3monthsduringeach
of2consecutiveyears(othercausesofcoughbeingexcluded).Emphysemaisdefinedpathologicallyasan
abnormal,permanentenlargementoftheairspacesdistaltotheterminalbronchioles,accompaniedby
destructionoftheirwallsandwithoutobviousfibrosis.

Signsandsymptoms
Patientstypicallypresentwithacombinationofsignsandsymptomsofchronicbronchitis,emphysema,and
reactiveairwaydisease.Symptomsincludethefollowing:
Cough,usuallyworseinthemorningsandproductiveofasmallamountofcolorlesssputum
Acutechestillness
Breathlessness:Themostsignificantsymptom,butusuallydoesnotoccuruntilthesixthdecadeoflife
Wheezing:Mayoccurinsomepatients,particularlyduringexertionandexacerbations
ThesensitivityofphysicalexaminationindetectingmildtomoderateCOPDisrelativelypoor,butphysicalsigns
arequitespecificandsensitiveforseveredisease.Findingsinseverediseaseincludethefollowing:

Tachypneaandrespiratorydistresswithsimpleactivities
Useofaccessoryrespiratorymusclesandparadoxicalindrawingoflowerintercostalspaces(Hooversign)
Cyanosis
Elevatedjugularvenouspulse(JVP)
Peripheraledema
Thoracicexaminationrevealsthefollowing:
Hyperinflation(barrelchest)
WheezingFrequentlyheardonforcedandunforcedexpiration
Diffuselydecreasedbreathsounds
Hyperresonanceonpercussion
Prolongedexpiration
Coarsecracklesbeginningwithinspirationinsomecases
Certaincharacteristicsallowdifferentiationbetweendiseasethatispredominantlychronicbronchitisandthat
whichispredominantlyemphysema.Chronicbronchitischaracteristicsincludethefollowing:
Patientsmaybeobese
Frequentcoughandexpectorationaretypical
Useofaccessorymusclesofrespirationiscommon
Coarserhonchiandwheezingmaybeheardonauscultation
Patientsmayhavesignsofrightheartfailure(ie,corpulmonale),suchasedemaandcyanosis
Emphysemacharacteristicsincludethefollowing:
Patientsmaybeverythinwithabarrelchest
Patientstypicallyhavelittleornocoughorexpectoration
Breathingmaybeassistedbypursedlipsanduseofaccessoryrespiratorymusclespatientsmayadoptthe
tripodsittingposition
Thechestmaybehyperresonant,andwheezingmaybeheard
Heartsoundsareverydistant
OverallappearanceismorelikeclassicCOPDexacerbation
SeeClinicalPresentationformoredetail.

Diagnosis
TheformaldiagnosisofCOPDismadewithspirometrywhentheratioofforcedexpiratoryvolumein1second
overforcedvitalcapacity(FEV1/FVC)islessthan70%ofthatpredictedforamatchedcontrol,itisdiagnosticfor
asignificantobstructivedefect.Criteriaforassessingtheseverityofairflowobstruction(basedonthepercent
predictedpostbronchodilatorFEV1)areasfollows:
StageI(mild):FEV180%orgreaterofpredicted
StageII(moderate):FEV15079%ofpredicted

StageIII(severe):FEV13049%ofpredicted
StageIV(verysevere):FEV1lessthan30%ofpredictedorFEV1lessthan50%andchronicrespiratory
failure
Arterialbloodgas(ABG)findingsareasfollows:
ABGsprovidethebestcluesastoacutenessandseverityofdiseaseexacerbation
PatientswithmildCOPDhavemildtomoderatehypoxemiawithouthypercapnia
Asthediseaseprogresses,hypoxemiaworsensandhypercapniamaydevelop,withthelattercommonly
beingobservedastheFEV1fallsbelow1L/sor30%ofthepredictedvalue
pHusuallyisnearnormalapHbelow7.3generallyindicatesacuterespiratorycompromise
Chronicrespiratoryacidosisleadstocompensatorymetabolicalkalosis
Inpatientswithemphysema,frontalandlateralchestradiographsrevealthefollowing:
Flatteningofthediaphragm
Increasedretrosternalairspace
Along,narrowheartshadow
Rapidlytaperingvascularshadowsaccompaniedbyhyperlucencyofthelungs
Radiographsinpatientswithchronicbronchitisshowincreasedbronchovascularmarkingsandcardiomegaly
AdvantagesofhighresolutionCTincludethefollowing:
Greatersensitivitythanstandardchestradiography
Highspecificityfordiagnosingemphysema(outlinedbullaearenotalwaysvisibleonaradiograph)
MayprovideanadjunctivemeansofdiagnosingvariousformsofCOPD(eg,lowerlobediseasemaysuggest
alpha1antitrypsin(AAT)deficiency
Mayhelpthecliniciandeterminewhethersurgicalinterventionwouldbenefitthepatient
Othertestsareasfollows:
HematocritPatientswithpolycythemia(hematocritgreaterthan52%inmenor47%inwomen)shouldbe
evaluatedforhypoxemiaatrest,withexertion,orduringsleep
SerumpotassiumDiuretics,betaadrenergicagonists,andtheophyllineacttolowerpotassiumlevels
MeasureAATinallpatientsyoungerthan40yearsorinthosewithafamilyhistoryofemphysemaatanearly
age
Sputumevaluationwillshowatransformationfrommucoidinstablechronicbronchitistopurulentinacute
exacerbations
Pulseoximetry,combinedwithclinicalobservation,providesinstantfeedbackonapatient'sstatus
Electrocardiographycanhelpestablishthathypoxiaisnotresultingincardiacischemiaandthatthe
underlyingcauseofrespiratorydifficultyisnotcardiacinnature
Thedistancewalkedin6minutes(6MWD)isagoodpredictorofallcauseandrespiratorymortalityin
patientswithmoderateCOPD[2,3]patientswithCOPDwhodesaturateduringthe6MWDhaveahigher
mortalityratethandothosewhodonotdesaturate

Twodimensionalechocardiographycanscreenforpulmonaryhypertension
Rightsidedheartcatheterizationcanconfirmpulmonaryarteryhypertensionandgaugetheresponseto
vasodilators
SeeWorkupformoredetail.

Management
SmokingcessationcontinuestobethemostimportanttherapeuticinterventionforCOPD.Riskfactorreduction
(eg,influenzavaccine)isappropriateforallstagesofCOPD.Approachestomanagementbystageincludethe
following:
StageI(mildobstruction):Shortactingbronchodilatorasneeded
StageII(moderateobstruction):Shortactingbronchodilatorasneededlongactingbronchodilator(s)
cardiopulmonaryrehabilitation
StageIII(severeobstruction):Shortactingbronchodilatorasneededlongactingbronchodilator(s)
cardiopulmonaryrehabilitationinhaledglucocorticoidsifrepeatedexacerbations
StageIV(verysevereobstructionormoderateobstructionwithevidenceofchronicrespiratoryfailure):
Shortactingbronchodilatorasneededlongactingbronchodilator(s)cardiopulmonaryrehabilitationinhaled
glucocorticoidsifrepeatedexacerbationlongtermoxygentherapy(ifcriteriamet)considersurgicaloptions
suchaslungvolumereductionsurgery(LVRS)andlungtransplantation
Agentsusedincludethefollowing:
Shortactingbeta2agonistbronchodilators(eg,albuterol,metaproterenol,levalbuterol,pirbuterol)
Longactingbeta2agonistbronchodilators(eg,salmeterol,formoterol,arformoterol,indacaterol,vilanterol)
Respiratoryanticholinergics(eg,ipratropium,tiotropium,aclidinium)
Xanthinederivatives(ie,theophylline)
Phosphodiesterase4Inhibitors(ie,roflumilast)
Inhaledcorticosteroids(eg,fluticasone,budesonide)
Oralcorticosteroids(eg,prednisone)
Beta2agonistandanticholinergiccombinations(eg,ipratropiumandalbuterol,umeclidinium
bromide/vilanterolinhaled)
Beta2agonistandcorticosteroidcombinations(eg,budesonide/formoterol,fluticasoneandsalmeterol,
vilanterol/fluticasoneinhaled)
Pulmonaryrehabilitationprogramsaretypicallymultidisciplinaryapproachesthatemphasizethefollowing:
Patientandfamilyeducation
Smokingcessation
Medicalmanagement(includingoxygenandimmunization)
Respiratoryandchestphysiotherapy
Physicaltherapywithbronchopulmonaryhygiene,exercise,andvocationalrehabilitation
Psychosocialsupport

Indicationsforadmissionforacuteexacerbationsincludethefollowing:
Failureofoutpatienttreatment
Markedincreaseindyspnea
Alteredmentalstatus
Increaseinhypoxemiaorhypercapnia
Inabilitytotolerateoralmedicationssuchasantibioticsorsteroids
SeeTreatmentandMedicationformoredetail.

Background
Chronicobstructivepulmonarydisease(COPD)isestimatedtoaffect32millionpersonsintheUnitedStates
andisthethirdleadingcauseofdeathinthiscountry.[1]Patientstypicallyhavesymptomsofchronicbronchitis
andemphysema,buttheclassictriadalsoincludesasthma(asseenintheimagebelow).(SeeClinical
Presentation.)

Venndiagramofchronicobstructivepulmonarydisease(COPD).Chronicobstructivelungdiseaseisadisorder
inwhichsubsetsofpatientsmayhavedominantfeaturesofchronicbronchitis,emphysema,orasthma.The
resultisairflowobstructionthatisnotfullyreversible.
InWesternEurope,Badham(1808)andLaennec(1827)madetheclassicdescriptionsofchronicbronchitis
andemphysemaintheearly19thcentury.ABritishmedicaltextbookofthe1860sdescribedthefamiliarclinical
pictureofchronicbronchitisasanadvanceddiseasewithrepeatedbronchialinfectionsthatendedinrightsided
heartfailure.Overall,thismaladycausedmorethan5%ofalldeathsintheMiddleAgesandearlier.The
conditionwasmostcommonamongthepoortherefore,itwasattributedto"bad"living.
Developmentsinthe20thcenturyincludedthewidespreaduseofspirometry(seeWorkup),recognitionof
airflowobstructionasakeyfactorindeterminingdisability,andtheimprovementofpathologicmethodsto
assessemphysema.ParticipantsintheCibasymposiumof1958proposeddefinitionsofchronicbronchitisand
emphysema,incorporatingtheconceptofairflowobstruction.
Chronicbronchitisisdefinedclinicallyasthepresenceofachronicproductivecoughfor3monthsduringeach

of2consecutiveyears(othercausesofcoughbeingexcluded).Emphysema,ontheotherhand,isdefined
pathologicallyasanabnormal,permanentenlargementoftheairspacesdistaltotheterminalbronchioles,
accompaniedbydestructionoftheirwallsandwithoutobviousfibrosis.
Airflowlimitationinemphysemaisduetolossofelasticrecoilanddecreaseinairwaytethering,whereaschronic
bronchitisleadstonarrowingofairwaycaliberandincreaseinairwayresistance.Althoughsomepatients
predominantlydisplaysignsofoneofthesediseasesortheother,mostfallsomewhereinthemiddleofthe
spectrumbetweenthe2conditions.
PastdefinitionsofCOPDhavebeenpessimisticatbest,indicatingthatthediseaseprocessisirreversibleand
thattherapyhaslittletooffer.However,amoreoptimisticviewhascometobewidelyaccepted.TheGlobal
InitiativeforChronicObstructiveLungDisease(GOLD)guidelinesdefineCOPDasadiseasestate
characterizedbyairflowlimitationthatisnotfullyreversible,isusuallyprogressive,andisassociatedwithan
abnormalinflammatoryresponseofthelungstoinhalednoxiousparticlesorgases,[4](SeeClinical
Presentation.)
OralandinhaledmedicationsareusedforpatientswithstableCOPDtoreducedyspnea,improveexercise
tolerance,andpreventcomplications.MostofthemedicationsusedinCOPDtreatmentaredirectedatthe
potentiallyreversiblemechanismsofairflowlimitation.(SeeMedication.)

Pathophysiology
Pathologicchangesinchronicobstructivepulmonarydisease(COPD)occurinthelarge(central)airways,the
small(peripheral)bronchioles,andthelungparenchyma.MostcasesofCOPDaretheresultofexposureto
noxiousstimuli,mostoftencigarettesmoke.Thenormalinflammatoryresponseisamplifiedinpersonsproneto
COPDdevelopment.Thepathogenicmechanismsarenotclearbutaremostlikelydiverse.Increasednumbers
ofactivatedpolymorphonuclearleukocytesandmacrophagesreleaseelastasesinamannerthatcannotbe
counteractedeffectivelybyantiproteases,resultinginlungdestruction.
Theprimaryoffenderhasbeenfoundtobehumanleukocyteelastase,withsynergisticrolessuggestedfor
proteinase3andmacrophagederivedmatrixmetalloproteinases(MMPs),cysteineproteinases,anda
plasminogenactivator.Additionally,increasedoxidativestresscausedbyfreeradicalsincigarettesmoke,the
oxidantsreleasedbyphagocytes,andpolymorphonuclearleukocytesallmayleadtoapoptosisornecrosisof
exposedcells.Acceleratedagingandautoimmunemechanismshavealsobeenproposedashavingrolesinthe
pathogenesisofCOPD.[5,6]
Cigarettesmokecausesneutrophilinflux,whichisrequiredforthesecretionofMMPsthissuggests,therefore,
thatneutrophilsandmacrophagesarerequiredforthedevelopmentofemphysema.
Studieshavealsoshownthatinadditiontomacrophages,Tlymphocytes,particularlyCD8 +,playanimportant
roleinthepathogenesisofsmokinginducedairflowlimitation.
Tosupporttheinflammationhypothesisfurther,astepwiseincreaseinalveolarinflammationhasbeenfoundin
surgicalspecimensfrompatientswithoutCOPDversuspatientswithmildorsevereemphysema.Indeed,

mountingevidencesupportstheconceptthatdysregulationofapoptosisanddefectiveclearanceofapoptotic
cellsbymacrophagesplayaprominentroleinairwayinflammation,particularlyinemphysema.[7]Azithromycin
(Zithromax)hasbeenshowntoimprovethismacrophageclearancefunction,providingapossiblefuture
treatmentmodality.[8]
InpatientswithstableCOPDwithoutknowncardiovasculardisease,thereisahighprevalenceof
microalbuminuria,whichisassociatedwithhypoxemiaindependentofotherriskfactors.[9]

Chronicbronchitis
Mucousglandhyperplasia(asseenintheimagesbelow)isthehistologichallmarkofchronicbronchitis.Airway
structuralchangesincludeatrophy,focalsquamousmetaplasia,ciliaryabnormalities,variableamountsof
airwaysmoothmusclehyperplasia,inflammation,andbronchialwallthickening.

Histopathologyofchronicbronchitisshowinghyperplasiaofmucousglandsandinfiltrationoftheairwaywall
withinflammatorycells.

Histopathologyofchronicbronchitisshowinghyperplasiaofmucousglandsandinfiltrationoftheairwaywall
withinflammatorycells(highpoweredview).

Damagetotheendotheliumimpairsthemucociliaryresponsethatclearsbacteriaandmucus.Inflammationand
secretionsprovidetheobstructivecomponentofchronicbronchitis.Neutrophiliadevelopsintheairwaylumen,
andneutrophilicinfiltratesaccumulateinthesubmucosa.Therespiratorybronchiolesdisplayamononuclear
inflammatoryprocess,lumenocclusionbymucusplugging,gobletcellmetaplasia,smoothmusclehyperplasia,
anddistortionduetofibrosis.Thesechanges,combinedwithlossofsupportingalveolarattachments,cause
airflowlimitationbyallowingairwaywallstodeformandnarrowtheairwaylumen.
Incontrasttoemphysema,chronicbronchitisisassociatedwitharelativelyundamagedpulmonarycapillary
bed.Thebodyrespondsbydecreasingventilationandincreasingcardiacoutput.ThisV/Qmismatchresultsin
rapidcirculationinapoorlyventilatedlung,leadingtohypoxemiaandpolycythemia.Eventually,hypercapnia
andrespiratoryacidosisdevelop,leadingtopulmonaryarteryvasoconstrictionandcorpulmonale.Withthe
ensuinghypoxemia,polycythemia,andincreasedCO2retention,thesepatientshavesignsofrightheartfailure
andareknownas"bluebloaters."

Emphysema
Emphysemaisapathologicdiagnosisdefinedbypermanentenlargementofairspacesdistaltotheterminal
bronchioles.Thisleadstoadramaticdeclineinthealveolarsurfaceareaavailableforgasexchange.
Furthermore,lossofalveolileadstoairflowlimitationby2mechanisms.First,lossofthealveolarwallsresultsin
adecreaseinelasticrecoil,whichleadstoairflowlimitation.Second,lossofthealveolarsupportingstructure
leadstoairwaynarrowing,whichfurtherlimitsairflow.
Emphysemahas3morphologicpatterns:
Centriacinar
Panacinar
Distalacinar,orparaseptal
Centriacinaremphysemaischaracterizedbyfocaldestructionlimitedtotherespiratorybronchiolesandthe
centralportionsoftheacini.Thisformofemphysemaisassociatedwithcigarettesmokingandistypicallymost
severeintheupperlobes.
Panacinaremphysemainvolvestheentirealveolusdistaltotheterminalbronchiole.Thepanacinartypeis
typicallymostsevereinthelowerlungzonesandgenerallydevelopsinpatientswithhomozygousalpha1
antitrypsin(AAT)deficiency.
Distalacinaremphysema,orparaseptalemphysema,istheleastcommonformandinvolvesdistalairway
structures,alveolarducts,andsacs.Thisformofemphysemaislocalizedtofibrousseptaortothepleuraand
leadstoformationofbullae(asseenintheimagesbelow).Theapicalbullaemaycausepneumothorax.
Paraseptalemphysemaisnotassociatedwithairflowobstruction.

Grosspathologyofadvancedemphysema.Largebullaearepresentonthesurfaceofthelung.

Grosspathologyofapatientwithemphysemashowingbullaeonthesurface.
Thegradualdestructionofalveolarseptae(shownintheimagebelow)andofthepulmonarycapillarybedin
emphysemaleadstoadecreasedabilitytooxygenateblood.Thebodycompensateswithloweredcardiac
outputandhyperventilation.ThisV/Qmismatchresultsinrelativelylimitedbloodflowthroughafairlywell
oxygenatedlungwithnormalbloodgasesandpressuresinthelung,incontrasttothesituationinchronic
bronchitis.Becauseoflowcardiacoutput,therestofthebodysuffersfromtissuehypoxiaandpulmonary
cachexia.Eventually,thesepatientsdevelopmusclewastingandweightlossandareidentifiedas"pinkpuffers."

Athighmagnification,lossofalveolarwallsanddilatationofairspacesinemphysemacanbeseen.

Emphysematousdestructionandsmallairwayinflammation
Emphysematousdestructionandsmallairwayinflammationoftenarefoundincombinationinindividual
patients,leadingtothespectrumthatisknownasCOPD.Whenemphysemaismoderateorsevere,lossof
elasticrecoil,ratherthanbronchiolardisease,isthedominantmechanismofairflowlimitation.Bycontrast,
whenemphysemaismild,bronchiolarabnormalitiesaremostresponsibleforthemajorityofthedeficitinlung
function.Althoughairflowobstructioninemphysemaisoftenirreversible,bronchoconstrictiondueto
inflammationaccountsforsomereversibility.Airflowlimitationisnottheonlypathophysiologicmechanismby
whichsymptomsoccur.

Dynamichyperinflation
Lungvolumes,particularlydynamichyperinflation,havealsobeenshowntoplayacrucialroleinthe
developmentofdyspneaperceivedduringexercise.Infact,theimprovementinexercisecapacitybroughtabout
byseveraltreatmentmodalities,includingbronchodilators,oxygentherapy,lungvolumereductionsurgery
(LVRS),andmaneuverslearnedinpulmonaryrehabilitation,ismorelikelyduetodelayingdynamic
hyperinflationratherthanimprovingthedegreeofairflowobstruction.[10,11,12,13,14,15,16,17]Additionally,
hyperinflation(definedastheratioofinspiratorycapacitytototallungcapacity[IC/TLC])hasbeenshownto
predictsurvivalbetterthanforcedexpiratoryvolumein1second(FEV1).[7]

Etiology
Cigarettesmoking
TheprimarycauseofCOPDisexposuretotobaccosmoke.Overall,tobaccosmokingaccountsforasmuchas
90%ofCOPDrisk.
Cigarettesmokinginducesmacrophagestoreleaseneutrophilchemotacticfactorsandelastases,whichleadto
tissuedestruction.ClinicallysignificantCOPDdevelopsin15%ofcigarettesmokers,althoughthisnumberis
believedtobeanunderestimate.Ageofinitiationofsmoking,totalpackyears,andcurrentsmokingstatus
predictCOPDmortality.

PeoplewhosmokehaveanincreasedannualdeclineinFEV1:thephysiologicnormaldeclineinFEV1is
estimatedtobe2030ml/y,buttherateofdeclineinCOPDpatientsisgenerally60ml/yorgreater.
Secondhandsmoke,orenvironmentaltobaccosmoke,increasestheriskofrespiratoryinfections,augments
asthmasymptoms,andcausesameasurablereductioninpulmonaryfunction.
AstudybyNagelmannetalconcludedthatlungfunctiondeviationandlungstructuralchangesarepresentin
peoplewhosmokecigarettesbeforetheclinicalsignsofairwayobstructionrevealthem.[18]Thesechangescan
bedetectedbybodyplethysmographyanddiffusingcapacitymeasurementwithroutinespirometry.

Environmentalfactors
COPDdoesoccurinindividualswhohaveneversmoked.[19]Althoughtheroleofairpollutionintheetiologyof
COPDisunclear,theeffectissmallwhencomparedwiththatofcigarettesmoking.Indevelopingcountries,the
useofbiomassfuelswithindoorcookingandheatingislikelytobeamajorcontributortotheworldwide
prevalenceofCOPD.LongtermexposuretotrafficrelatedairpollutionmaybeafactorinCOPDinpatients
withdiabetesandasthma.[20]

Airwayhyperresponsiveness
Airwayhyperresponsiveness(ie,Dutchhypothesis)stipulatesthatpatientswhohavenonspecificairway
hyperreactivityandwhosmokeareatincreasedriskofdevelopingCOPDwithanaccelerateddeclineinlung
function.NonspecificairwayhyperreactivityisinverselyrelatedtoFEV1andmaypredictadeclineinlung
function.
ThepossibleroleofairwayhyperresponsivenessasariskfactorforthedevelopmentofCOPDinpeoplewho
smokeisunclear.Moreover,bronchialhyperreactivitymayresultfromairwayinflammationobservedwiththe
developmentofsmokingrelatedchronicbronchitis.Thismaycontributetoairwayremodeling,leadingtoamore
fixedobstruction,asisseeninpersonswithCOPD.

Alpha1antitrypsindeficiency
Alpha1antitrypsin(AAT)isaglycoproteinmemberoftheserineproteaseinhibitorfamilythatissynthesizedin
theliverandissecretedintothebloodstream.Themainpurposeofthis394aminoacid,singlechainproteinis
toneutralizeneutrophilelastaseinthelunginterstitiumandtoprotectthelungparenchymafromelastolytic
breakdown.SevereAATdeficiencypredisposestounopposedelastolysiswiththeclinicalsequelaofanearly
onsetofpanacinaremphysema.ToseecompleteinformationonAlpha1AntitrypsinDeficiency,pleasegotothe
mainarticlebyclickinghere.
AATdeficiencyistheonlyknowngeneticriskfactorfordevelopingCOPDandaccountsforlessthan1%ofall
casesintheUnitedStates.SevereAATdeficiencyleadstoprematureemphysemaatanaverageageof53
yearsfornonsmokersand40yearsforsmokers.
Nearly24variantsoftheAATmoleculehavebeenidentified,andallareinheritedascodominantalleles.The
commonMallele(PiM)maybefoundin90%ofpeople,andhomozygous(PiMM)phenotypesproduceserum

levelswithinthereferencerange.ThehomozygousPiZZstateisthemostcommondeficiencystateand
accountsfor95%ofpeopleintheseverelydeficientcategory.

Intravenousdruguse
Emphysemaoccursinapproximately2%ofpersonswhouseintravenous(IV)drugs.Thisisattributedto
pulmonaryvasculardamagethatresultsfromtheinsolublefiller(eg,cornstarch,cottonfibers,cellulose,talc)
containedinmethadoneormethylphenidate.
ThebullouscystsfoundinassociationwithIVuseofcocaineorheroinoccurpredominantlyintheupperlobes.
Incontrast,methadoneandmethylphenidateinjectionsareassociatedwithbasilarandpanacinaremphysema.

Immunodeficiencysyndromes
Humanimmunodeficiencyvirus(HIV)infectionhasbeenfoundtobeanindependentriskfactorforCOPD,even
aftercontrollingforconfoundingvariablessuchassmoking,IVdruguse,race,andage.[21]
Apicalandcorticalbullouslungdamageoccursinpatientswhohaveautoimmunedeficiencysyndromeand
Pneumocystiscariniiinfection.Reversiblepneumatocelesareobservedin1020%ofpatientswiththisinfection.

Vasculitissyndrome
Hypocomplementemicvasculitisurticariasyndrome(HVUS)maybeassociatedwithobstructivelungdisease.
Othermanifestationsincludeangioedema,nondeformingarthritis,sinusitis,conjunctivitis,andpericarditis.

Connectivetissuedisorders
Cutislaxaisadisorderofelastinthatischaracterizedmostprominentlybytheappearanceofprematureaging.
Thediseaseusuallyiscongenital,withvariousformsofinheritance(ie,dominant,recessive).Precocious
emphysemahasbeendescribedinassociationwithcutislaxaasearlyastheneonatalperiodorinfancy.The
pathogenesisofthisdisorderincludesadefectinthesynthesisofelastinortropoelastin.
MarfansyndromeisanautosomaldominantinheriteddiseaseoftypeIcollagencharacterizedbyabnormal
lengthoftheextremities,subluxationofthelenses,andcardiovascularabnormality.Pulmonaryabnormalities,
includingemphysema,havebeendescribedinapproximately10%ofpatients.
EhlersDanlossyndromereferstoagroupofinheritedconnectivetissuedisorderswithmanifestationsthat
includehyperextensibilityoftheskinandjoints,easybruisability,andpseudotumorsithasalsobeenassociated
withahigherprevalenceofCOPD.

Salladisease
SalladiseaseisanautosomalrecessivestoragedisorderdescribedinScandinaviathediseaseischaracterized
byintralysosomalaccumulationofsialicacidinvarioustissues.Themostimportantclinicalmanifestationsare
severementalretardation,ataxia,andnystagmus.Precociousemphysemahasbeendescribedandlikelyis
secondarytoimpairedinhibitoryactivityofserumtrypsin.

Epidemiology
TheNationalHealthInterviewSurveyreportstheprevalenceofemphysemaat18casesper1000personsand
chronicbronchitisat34casesper1000persons.[22]Whiletherateofemphysemahasstayedlargely
unchangedsince2000,therateofchronicbronchitishasdecreased.Anotherstudyestimatesaprevalenceof
10.1%intheUnitedStates.[23]However,theexactprevalenceofCOPDintheUnitedStatesisbelievedtobe
underestimated.Thisislargelyduetothefactthatitisanunderdiagnosed(andundertreated)disease,
becausemostpatientsdonotpresentformedicalcareuntilthediseaseisinalatestage.
TheexactprevalenceofCOPDworldwideislargelyunknown,butestimateshavevariedfrom719%.The
BurdenofObstructiveLungDisease(BOLD)studyfoundaglobalprevalenceof10.1%.[24]Menwerefoundto
haveapooledprevalenceof11.8%andwomen8.5%.Thenumbersvaryindifferentregionsoftheworld.Cape
Town,SouthAfrica,hasthehighestprevalence,affecting22.2%ofmenand16.7%ofwomen.
Hannover,Germany,ontheotherhand,hasthelowestprevalence,of8.6%formenand3.7%forwomen.The
differencescanbeexplainedinpartbysiteandsexdifferencesintheprevalenceofsmoking.Asnotedabove,
thesereportsarewidelybelievedtobeunderestimatesbecauseCOPDisknowntobeunderdiagnosedand
undertreated.Additionally,theprevalenceinwomenisbelievedtobeincreasing.
AlthoughcurrentratesofCOPDinmenarehigherthantheratesinwomen,theratesinwomenhavebeen
increasing.COPDoccurspredominantlyinindividualsolderthanage40years.
Severe,earlyonsetdiseaselikelyrepresentsadistinctgenotypeandismorecommonlyseeninfemales,
AfricanAmericans,andthosewithamaternalfamilyhistoryofCOPD.[25]
AstudybyMintzetalestimatedtheprevalenceofunidentifiedCOPD.[26]UsingtheLungFunction
Questionnaire(LFQ)andspirometryresults,thestudydeterminedthatapproximately1in5patients(21%)
aged30yearsorolderwithahistoryofsmokingfor10yearsorlongerseeninaprimarycarecenterislikelyto
haveCOPD.
InastudybySpitzeretalinGermany,airflowlimitationasmeasuredbyspirometrywassignificantlymore
commoninadultswithposttraumaticstressdisorderthanincontrols.Resultswereadjustedforlifestyle,clinical,
andsociodemographicfactors.[27]

Prognosis
COPDisthethirdleadingcauseofdeathintheUnitedStates.[1]IntermsofCOPDastheunderlyingcauseof
death,absolutemortalityratesforUSpatientsaged25yearsorolder(2005)were77.3deathsper100,000
malesand56.0deathsper100,000females,or64.3personsper100,000overall.Internationally,overall
mortalityratesfromCOPDvarymarkedly,frommorethan400deathsper100,000malesaged6574yearsin
Romaniatofewerthan100deathsper100,000populationinJapan.
TheFEV1wasusedtopredictoutcomeinCOPDuntilotherfactorswereidentifiedtoplayaroleindetermining
theoutcomeofCOPDpatients.ThesediscoveriesresultedinthecreationofthemultidimensionalBODEindex

(bodymassindex,obstruction[FEV1],dyspnea[modifiedMedicalResearchCouncildyspneascale],and
exercisecapacity[6MWD]).[28]Thisindexwasdevelopedtoassessanindividualsriskofdeathor
hospitalization.
Prognosisisbasedonapointsystem,withall4factorsusedtodeterminethescore,asfollows:
Bodymassindex:greaterthan21=0pointslessthan21=1point
FEV1(postbronchodilatorpercentpredicted):greaterthan65%=0points5064%=1point3649%=2
pointslessthan35%=3points
ModifiedMedicalResearchCouncil(MMRC)dyspneascale:MMRC0=dyspneiconstrenuousexercise(0
points)MMRC1=dyspneiconwalkingaslighthill(0points)MMRC2=dyspneiconwalkinglevelground,
muststopoccasionallyduetobreathlessness(1point)MMRC3=dyspneicafterwalking100yardsorafew
minutes(2points)MMRC4=cannotleavehousedyspneicdoingactivitiesofdailyliving(3points)
Sixminutewalkingdistance:greaterthan350meters=0points250349meters=1point150249meters
=2pointslessthan149meters=3points
Theapproximate4yearsurvivalbasedonthepointsystemaboveisasfollows:
02points=80%
34points=67%
56points=57%
710points=18%
TheuseofaclinicalscoringsystemreinforcesthatdeterminantsofprognosisinCOPDremainmultifactorial.
Waschkietalarguedthatobjectiveassessmentsofphysicalactivity,including6minutewalktestresults,are
bestabletopredictmortality.[29]However,additionalsocioeconomicfactorsalsolikelyplayaroleinCOPD
prognosisforexample,aretrospectivecohortstudyhighlightedtheincreasedriskofCOPDrelatedmortalityin
patientswhoresideinisolatedruralareas.[30]
AstudybySundhetaldeterminedthattheClinicalCOPDQuestionnaire(CCQ),whichestimatesqualityoflife
inpatientswithCOPD,iseffective.[31]TheCCQidentifiedthatheartdisease,depression,andunderweight
statusareindependentlyassociatedwithlowerhealthrelatedqualityoflifeinpatientswithCOPD.
Inamulticenter,prospective,observationalstudyof201consecutivepatientswithmoderatetosevereCOPD,
MartinezGarciaetalreportedthatinadditiontosmoking,pulmonaryhypertension,anddeclininglungfunction,
allofwhichareknownriskfactorsformortalityinpatientswithCOPD,[32]bronchiectasis,whichiscommonin
patientswithmoderatetosevereCOPD,isindependentlyassociatedwithincreasedriskofallcausemortality.
[32,33]

Inthisstudy,thosewhohadbronchiectasiswerefoundtobe2.5timesmorelikelytodiethanthosewhodidnot.
[33]Bronchiectasisremainedanindependentfactorafteradjustmentfordyspnea,partialpressureofoxygen,

bodymassindex,presenceofpotentiallypathogenicmicroorganismsinsputum,presenceofdailysputum
production,numberofsevereexacerbationsandperipheralalbumin,andultrasensitiveCreactiveprotein
concentrations.

PatientEducation
ItisimportanttoeducatethepatientwithCOPDaboutthediseaseandtoencouragehisorheractive
participationintherapy.The2mostessentialpointsforthepatienttounderstandareasfollows:
Thedangersofsmokingandtheimprovementinqualityoflifeattainablewithsmokingcessation
Theneedtoseekmedicalcareearlyduringanexacerbationandtonotwaituntiltheyareindistress
Formoreinformation,seeEmphysema.