Smokers display inter-individual differences in terms of lung changes and functional lesions
[131] .Changesintheterminalregionsofthebronchialtree,thelossofbronchiolar
consistency due to inlammatory processes and alveolar destruction lead to increasing functionalimpairment
[128,129,131,132] .Inlammatoryprocessessustaintheprogres-
sion of COPD [133]
. Smoking-induced pulmonary emphysema is centrilobular and is principallyrestrictedtotheupperlungsegments,wheretheattachmentofthealveolito
thebronchiolesbecomeslostseeTable 5.4
foranoverviewofthesechanges [128]
.Itis postulatedthatinCOPD,aprotease-antiproteaseimbalanceleadstoaccelerateddestruc-
tionoflungtissue,withproteolyticactivitybeingenhancedbycigarettesmoke [134]
. Neutrophilsareencounteredinlargernumbersinthelowerrespiratorytractofsmokers,
especiallyinthosewithCOPD.Theconcentrationofinlammatorycellsandtheirprod- uctsinthelowerrespiratorytractcorrelatesnegativelywithFEV
1
[135]
.Moreover,smok- ershavehigherelastaselevelsinBALluidthannon-smokers
[136] ,aswellasa50
reduction in a
1
-antiprotease activity [76]
, probably as a result of oxidation processes causedbycigarettesmoke.BiopsystudiesindicatethatinsmokerswithexistingCOPD,
there is increased expression of the adhesion molecules E-selectin on vessels and ICAM-1onbasalepithelialcells
[137] .Theadhesionmoleculesareimportantinprepar-
ing cells for the inlammatory processes and hence, for the pathogenesis of airways obstructioninsmokers.
Until a few years ago, emphysema was considered to be the decisive criterion for COPD;now,however,greaterimportanceisassignedtotheinlammatoryandstructural
changesinthesmallerairways [131]
.CTscansofthelungsofpatientswithadvanced COPDhaverevealedthatdetectableemphysemawasalsopresentinfewerthanonethird
ofpatientswithrespiratorylimitation [138]
.Eveninyoungsmokersandthechildrenof womenwhosmoke,respiratorybronchiolitisistheirstpathologicalsignofdisturbedlung
functionandthisoccurswithoutobstructionFig. 5.4
[139]
.Inoldersmokers,theinlam- matorychangesareaccompaniedbyconnectivetissuedeposition
[132] .Followingthora-
cotomy,thickeningofthebronchiolarmembrane0.4mminternaldiameterby50and ofthebronchiolesby100wasdetectedonlyinsmokers.Theseindingsalsocorrelated
withtheresultsofpreoperativepulmonaryfunctiontests [132]
.Areductioninwallthick- nessbronchialatrophyandthinningofthebronchialwallhasalsobeendetectedinsmok-
ers, a possible indicator of airways collapse [51]
. Hypertrophy of the bronchiolar musculaturehasbeenobservedinsmokers,possiblycontributingtobronchialobstruction
inCOPDpatients. Thickeningofthepulmonarymusculararterywall,particularlyoftheintimallayer,is
seeninsmokerswithmildCOPD [140]
.Thesevascularchangesareassociatedwithdis- turbancesofventilationandperfusionandwithareducedvascularreactionintermsof
pO
2
changes [140]
.Todate,itisuncleartowhatextenttheseindingscontributetothe development of COPD. However, pulmonary vessel resistance at least is increased in
patientswithemphysema.Thesehaemodynamicfunctionaldisturbancescorrelatewith reduceddiffusioncapacity,butnotwithbronchialobstruction.Theclinicalcorrelateof
thesechangesisincreasedcoughandmucussecretion,reducedelasticrecoil,increased expiratoryobstruction,increasedrespiratorywork,dyspnoea,wheezingandreducedgas
exchange.Theserespiratoryproblemshavebeeninvestigatedinlong-termstudies [32]
. Wheezingwasthemostcommonindingamongsmokers,beingencounteredin11of
menand9ofwomen.
5.3.2 Important Risk Factors for COPD
For more than 60 years now, COPD has been recognised as a consequence of cigarette smoking,especiallysincemorethan80ofallCOPDpatientsaresmokersandalsodieasa
resultofthiscondition [17]
.Mortality,morbidityandpulmonaryfunctionhavebeenassessed invariousretrospectiveandprospectivestudiesintensofthousandsofpatients
[141,142] .
FEV
1
isalreadyreducedin25-year-oldsmokersandthiseffectincreasesovertime.Aclose associationexistsbetweencumulativecigaretteconsumptionanddecliningpulmonaryfunc-
tion [116,143]
.Inthiscontext,thetarandnicotineyieldsofthecigarettessmoked,theuse ofiltertipsandthemethodofsmokingareimportant,butnotcrucialfactors
[144] .Initially,
smokershaveanormalforcedexpiratoryvolume;diminishedFEV
1
withclinicalsignsof dyspnoeadevelopsinonly15–30ofcaseswithinafewyears
[128,145] .
Thesmoking-relatedchangesco-existalongsideallergicprocesses,someofwhichare alsogeneticallydeterminedinthesenseofan“asthmaticconstitution”
[146] .Methacholine
asabronchoconstrictororb
1
-mimeticsasbronchodilatorsareimportantpredictorsforthe smoking-relateddeteriorationofpulmonary-function
[147–149] .Bronchialhyperrespon-
sivenessisanimportantriskfactorforthedevelopmentofCOPD.Inadditiontodecreases inpulmonaryfunctionindices,IgElevelsandeosinophilandleucocytecountshavebeen
showntobeincreasedinsmokers;thesevariablesreturnedtonormalonsmokingcessation [148]
.Incaseswheresmokerswereawarethattheyhadanallergicconstitution,theywere moreoftenpreparedtostopsmokingthannon-allergicindividuals
[150] .Overall,how-
ever,itisnotclearwhethereosinophiliaorincreasedIgElevelsinsmokersareriskfactors ormarkersforpulmonaryobstruction
[150,151] .
5.3.2.1 Genetic Factors
COPDisknowntoshowfamilialclusteringandgeneticfactorshavebeenobserved.This doesnotincludea
1
-antitrypsindeiciency,whichleadstoaclearlyaccelerateddeclinein pulmonaryfunctionmoreinsmokersthaninnon-smokers
[145] .Irrespectiveofsmoking
status,smokerswithanantiproteasedeiciencydisplayconsiderableheterogeneityinterms ofseverityofbronchialobstruction
[128,152] .
5.3.2.2 Occupational and Environmental Factors
Awiderangeofvapours,dustsandgaseshaveaharmfuleffectonpulmonaryfunction, leadingtotheincreasedoccurrenceofchronicbronchitiscoughandsputum.Broncho-
obstructivereactionswithareductioninFEV
1
arealsoknowntooccurinresponsetoexog- enousfactors.TheseverityofCOPDisclearlyintensiiedincigarettesmokersindeveloped
countries [126]
.Evensevereairpollutionorexposuretocement [153]
mayhaveanadditive effectonthecondition,irrespectiveoftheharmfuleffectsofcigarettesmoke
[147] .
5.4 Cigarette Smoking and Bronchial Asthma
Cigarettesmokinghasadeleteriouseffectonphysicalperformanceinpeoplewithasthma [154]
.Passiveexposuretocigarettesmokesee Chap.9
isalsodangerousforchildrenand leadstoincreasedasthmamorbidity
[4] .Asthmasufferersshould,therefore,bestrongly
advisednottostartsmokingortostopsmokingasquicklyaspossible.
5.4.1 Caveats Concerning the Informative Value of Studies
Prospective,randomised,double-blindandplacebo-controlledstudiestoinvestigateapos- sibleassociationbetweencigarettesmokingandbronchialasthmaarenotacceptableon
ethicalgrounds;consequently,onlycohortandcase-controlstudiesareavailable.Forthe mostpart,suchstudiesuseextentofcigarettesmokingasaparameter,buttheinformation
providedbypatientsfrequentlyfailstorelectthetrueextentofconsumption.Urinaryand serumconcentrations-ofcotinine,exhaledCOandnicotinelevelshavealsobeenusedas
aidstoassessment [155]
.Onefurthersourceofbiasisthatasthmaticpatientswithsevere symptomspossiblysmokelessthanthosewithnoappreciablesenseofbeingunwell.This
alreadyresultsinsmokerselectioninthisdiseasegroup [156,157]
. Eventheclinicaldiagnosisofbronchialasthmaisproblematicbecauserhonchiand
wheezingmayanticipatethediagnosisbyseveralyears [158]
andfurthermore,thereis symptomoverlapwithCOPDe.g.wheezing,dyspnoea,emphysema.Reversibleorirre-
versiblebronchialobstructionmayalsooccurinbothconditions.b
1
-adrenoceptorstimu- lantsareneithersensitivenorspeciicenoughtopermitdiscriminationofthetwodiseases
[159] .Likewise,theadministrationofhistamineormethacholinetoprovokeabronchial
spasmisnotspeciicforbronchialasthmabecausetheresponsemayalsooccurinchronic bronchitis,sarcoidosis,bronchiectasisorrhinitis
[160,161] .
Whileanallergicdispositioncanbeidentiiedinasthmatics,theparametersusedskin testing,IgElevelsandeosinophilcountarenotreliableassessmentcriteria.Immediate-
typeskinreactionsarelinkedwithIgEantibodies [162]
andarefrequentlypositivein asthmatics
[163] .However,IgElevelsareneithersensitivenorspeciicforthediagnosis
ofasthma [160]
,evenifassociationswithreducedpulmonaryfunctionhavebeendetected speciicallyinasthmatics
[164] .Eosinophilspossiblyplayanimportantroleintheinlam-
matorychangesseeninasthmatics [165]
.
5.4.2 Cigarette Smoking and Bronchial Asthma in Adults
Despitevariousstudiestoinvestigatethepossibleassociationbetweenbronchialasthma andcigarettesmoking,suchanassociationhasnotbeendemonstrated
[158,166,167] .
The NHANESI Study included patients from 100 different communities in 38 US