Smoking and Parkinson’s Disease

to฀never-smokers฀was฀0.4฀0.2–0.7฀for฀current฀female฀smokers฀and฀0.3฀0.1–0.8฀for฀cur- rent฀male฀smokers.฀For฀both฀sexes,฀the฀strength฀of฀the฀association฀decreased฀with฀time฀ since฀quitting,฀but฀increased฀with฀the฀number฀of฀cigarettes฀per฀day฀and฀pack-years฀of฀smok- ing฀ [131] .฀An฀inverse฀association฀between฀smoking฀and฀the฀incidence฀of฀Parkinson’s฀dis- ease฀ therefore฀ exists฀ in฀ both฀ men฀ and฀ women฀ [137] .฀ These฀ data฀ were฀ conirmed฀ in฀ a฀ meta-analysis฀ [136] .฀According฀to฀the฀EUROPARKINSON฀Study฀Group,฀a฀family฀history฀ and฀smoking,฀especially฀in฀the฀elderly฀75฀years฀old,฀interact฀synergistically฀to฀increase฀ the฀risk฀for฀the฀development฀of฀Parkinson’s฀disease฀OR฀=฀17.6;฀CI:฀1.9–160.5฀ [137] .฀At฀ the฀same฀time,฀on฀the฀basis฀of฀the฀dopaminergic฀action฀of฀nicotine,฀experimental฀animal฀ work฀tends฀to฀support฀the฀theory฀that฀cigarette฀smoking฀confers฀a฀protective฀effect฀in฀terms฀ of฀Parkinson’s฀disease.฀Recent฀experiments฀in฀mice฀and฀rats฀indicate฀that฀the฀ l -form฀of฀ nicotine฀exerts฀a฀neuroprotective฀effect฀in฀animal฀models฀of฀parkinsonism฀induced฀by฀ diethyldithiocarbamate฀or฀methamphetamine฀ [138] .฀Initial฀studies฀in฀humans฀also฀conirm฀ that฀nicotine฀administration฀slow฀intravenous฀infusion฀followed฀by฀transdermal฀nicotine฀ patch฀application฀leads฀to฀improvements฀in฀extrapyramidal฀functioning฀and฀reaction฀time,฀ and฀to฀decreased฀tracking฀errors฀ [139] . Neuroleptic-induced฀ parkinsonism฀ in฀ smokers฀ is฀ associated฀ with฀ higher฀ neuroleptic฀ doses฀ [140] .฀Evidently,฀by฀increasing฀the฀induction฀of฀drug-metabolising฀enzymes฀in฀the฀ liver,฀the฀smoker฀attempts฀to฀reduce฀the฀unwanted฀effects฀of฀neuroleptics.

7.2 Ocular Diseases

Unlike฀the฀ears,฀eyes฀are฀very฀much฀more฀at฀risk฀from฀the฀effects฀smoking฀than฀was฀previ- ously฀assumed.฀When฀the฀increased฀level฀of฀risk฀associated฀with฀smoking฀is฀present฀in฀con- junction฀with฀other฀risk฀factors,฀numerous฀ocular฀diseases฀may฀occur฀in฀intensiied฀form.฀ Pupil฀ diameter฀ in฀ smokers,฀ immediately฀ after฀ smoking฀ one฀ tobacco฀ cigarette,฀ is฀ slightly฀ smaller฀than฀that฀of฀non-smokers฀after฀sham-smoking฀ [141] . This฀is฀another฀ield฀in฀which฀hardly฀any฀publication฀differentiates฀the฀effects฀of฀nico- tine฀from฀those฀of฀inhaled฀smoke.฀Chronic฀hypoxaemia฀over฀a฀period฀of฀decades฀clearly฀ also฀plays฀a฀pivotal฀role฀in฀the฀context฀of฀eye฀disease.฀It฀is฀therefore฀unsurprising฀that฀the฀ number฀ of฀ ocular฀ diseases฀ in฀ cigarette฀ smokers฀ has฀ not฀ only฀ undergone฀ a฀ quantitative฀ increase,฀but฀also฀that฀more฀ocular฀diseases฀are฀thought฀to฀be฀associated฀with฀smoking฀ [142] .฀Aside฀from฀diabetic฀retinopathy฀and฀open-angle฀glaucoma,฀macular฀degeneration฀ often฀leading฀to฀blindness,฀Graves’฀ophthalmopathy,฀and฀lens฀opacity฀cataract฀develop- ment฀have฀recently฀been฀linked฀with฀smoking.

7.2.1 Diabetic Retinopathy

As฀with฀other฀complications฀of฀type฀I฀or฀II฀diabetes฀mellitus,฀a฀special฀role฀in฀the฀pathogen- esis฀is฀played฀by฀glycated฀proteins,฀including฀haemoglobin,฀which฀are฀deposited฀in฀various฀ organs,฀including฀the฀vascular฀wall,฀kidneys฀and฀retina฀ [143] .฀Recent฀research฀indicates฀ that฀smoking฀inluences฀these฀glycation฀processes฀ [143] . An฀older฀study฀in฀a฀sample฀of฀181฀diabetic฀patients฀with฀diabetic฀retinopathy฀already฀ showed฀that฀the฀progression฀of฀the฀disease฀in฀smokers฀increases฀as฀a฀function฀of฀pack-years฀ of฀smoking฀and฀the฀duration฀of฀diabetes฀ [144,฀145] ,฀with฀prevalence฀among฀men฀reportedly฀ being฀higher฀than฀among฀women฀ [145,฀146] .฀This฀association฀has฀not฀been฀conirmed฀in฀ studies฀involving฀larger฀number฀of฀patients฀ [147–149] .฀Instead,฀it฀is฀believed฀that฀the฀for- mation฀of฀glycohaemoglobin฀as฀a฀result฀of฀smoking฀tends฀to฀encourage฀nephropathy฀rather฀ than฀retinopathy฀ [148,฀150] .฀Elsewhere,฀an฀association฀was฀suspected฀only฀in฀men฀with฀a฀ younger฀onset฀of฀disease฀ [151] ,฀or฀the฀relations฀between฀cigarette฀smoking฀and฀retinopathy฀ or฀nephropathy฀were฀variable฀depending฀on฀the฀statistical฀models฀used฀ [152] .฀The฀recently฀ published฀EURODIAB฀IDDM฀Complications฀Study฀also฀found฀an฀increased฀risk฀for฀the฀ development฀of฀diabetic฀retinopathy฀in฀smokers฀only฀where฀there฀was฀an฀early฀onset฀of฀ IDDM฀together฀with฀a฀genetic฀component฀for฀hypertension฀ [153] .

7.2.2 Cataract and Lens Opacity

The฀ 86 rubidium฀eflux฀technique฀rubidium฀is฀a฀mimic฀of฀potassium฀has฀been฀used฀in฀ani- mal฀experiments฀to฀study฀the฀inluence฀of฀tobacco฀smoke฀on฀cultured฀rat฀lenses,฀which฀are฀ metabolically฀active฀and฀have฀functional฀defence฀systems.฀It฀was฀found฀that฀the฀smoke฀ particles฀are฀actively฀transported฀into฀the฀lens฀and฀are฀not฀absorbed฀as฀a฀result฀of฀increased฀ permeability;฀ histologically,฀ the฀ lenses฀ also฀ exhibited฀ morphological฀ changes฀ such฀ as฀ hyperplasia,฀hypertrophy฀and฀multi-layering฀of฀epithelial฀cells฀ [154] .฀In฀addition,฀the฀heavy฀ metals฀copper,฀lead฀and฀cadmium฀inhaled฀from฀cigarette฀smoke฀accumulate฀in฀the฀lens฀and฀ are฀possibly฀involved฀in฀cataract฀development฀ [155] .฀Moreover,฀the฀inhaled฀nitrous฀gases฀ and฀NO,฀which฀accumulate฀in฀the฀anterior฀chamber฀during฀ocular฀inlammation,฀lead฀to฀ changes฀in฀a-crystallin฀indicative฀of฀oxidative฀damage฀which฀show฀up฀as฀increased฀luo- rescence฀ l -kynurenine฀may฀be฀an฀intermediate฀causative฀agent฀ [156] . A฀clinical฀study฀in฀838฀watermen฀investigated฀the฀occurrence฀of฀nuclear฀or฀cortical฀lens฀ opacities,฀and฀a฀dose-dependent฀association฀was฀found฀in฀smokers฀between฀nuclear฀opacity฀ and฀pack-years฀of฀smoking฀ [157] ,฀a฀inding฀that฀has฀been฀conirmed฀in฀other฀studies฀ [149,฀ 158–160] .฀These฀lens฀opacities฀regressed฀partially฀on฀smoking฀cessation฀ [157] .฀A฀10-year฀ prospective฀study฀in฀17,824฀physicians,฀in฀whom฀557฀incident฀cataracts฀were฀conirmed฀ during฀5฀years฀of฀follow-up,฀demonstrated฀that฀the฀risk฀of฀cataract฀in฀heavy฀smokers฀20฀ cigarettesday฀was฀doubled฀compared฀with฀never-smokers฀RR฀=฀2.16;฀CI:฀1.46–3.20,฀ with฀nuclear฀sclerotic฀changes฀being฀observed฀in฀particular฀RR฀=฀2.24;฀CI:฀1.47–3.41฀ [161] .฀Past฀smokers฀had฀an฀elevated฀risk฀of฀posterior฀subcapsular฀cataract฀RR฀=฀1.44,฀ whereas฀ current฀ smokers฀ of฀ 20฀ cigarettesday฀ did฀ not฀ have฀ an฀ increased฀ cataract฀ risk฀ [161] .฀The฀association฀between฀pipe฀smoking฀and฀nuclear฀cataract฀OR฀=฀3.1;฀CI:฀1.5–8.2฀ was฀stronger฀than฀the฀association฀with฀cigarette฀฀smoking ฀[162] . Additional฀ moderate฀ alcohol฀ intake฀ £4฀ drinksday฀ lowered฀ cataract฀ prevalence,฀ whereas฀heavy฀alcohol฀consumption฀potentiated฀the฀effects฀of฀cigarette฀smoking฀OR฀com- pared฀with฀non-drinkers฀=฀3.9;฀CI:฀0.9–16.6฀ [162,฀163] .฀The฀incidence฀of฀cataracts฀in฀