Immunological Reactions Caused by Cigarette Smoking

and฀ display฀ an฀ abnormal฀ cell฀ surface฀ [7] .฀ The฀ alveolar฀ macrophages฀ of฀ smokers฀ exhibit฀ abnormal฀cytokine฀reactions฀in฀response฀to฀a฀variety฀of฀stimuli฀ [8–10] .฀Unlike฀lymphocytes฀ from฀peripheral฀blood,฀lymphocytes฀from฀smokers’฀lungs฀display฀diminished฀proliferative฀ responses฀to฀mitogens฀polynuclear฀hydrocarbons฀and฀concanavalin฀A฀ [11] .฀In฀smokers,฀the฀ total฀ white฀ cell฀ count,฀ including฀ polymorphonuclear฀ cells,฀ eosinophils,฀ monocytes฀ and฀ T-lymphocytes,฀is฀increased฀ [12] :฀killer฀T-lymphocyte฀counts฀in฀smokers฀are฀reduced,฀but฀ revert฀to฀normal฀levels฀within฀1฀month฀after฀smoking฀cessation฀ [13] .฀Serum฀concentrations฀of฀ IgG฀and฀IgE฀are฀elevated฀in฀smokers฀ [14] .฀Some฀of฀the฀reactions฀described฀are฀probably฀pro- moted฀by฀immunological฀processes฀ [15] .฀The฀increased฀permeability฀of฀pulmonary฀capillar- ies฀is฀also฀a฀consequence฀of฀inlammatory฀reactions.

5.2 Cigarette Smoking and Lung Cancer

For฀the฀most฀part฀a฀disease฀with฀a฀fatal฀outcome,฀lung฀cancer฀is฀on฀the฀increase฀and฀is฀ caused฀primarily฀by฀cigarette฀smoking,฀as฀demonstrated฀by฀numerous฀studies฀from฀all฀over฀ the฀world฀Table฀ 5.1 .฀Lung฀cancer฀may฀be฀causally฀related฀to฀cigarette฀smoking฀in฀90฀of฀ cases฀in฀men฀and฀in฀79฀of฀cases฀in฀women฀ [17] .฀Conversely,฀85฀of฀all฀cases฀of฀lung฀ cancer฀would฀be฀preventable฀if฀cigarette฀smoking฀were฀to฀be฀given฀up฀ [18] .฀Likewise,฀there฀ are฀established฀associations฀between฀passive฀smoking฀and฀susceptibility฀to฀lung฀cancer฀ [19,฀20] .฀Female฀smokers฀are฀at฀very฀much฀greater฀risk฀than฀male฀smokers฀for฀developing฀ adenocarcinoma฀AC฀of฀the฀lung฀ [21] .฀Age฀of฀smoking฀initiation฀and฀the฀number฀of฀ciga- rettes฀ smoked฀ daily฀ are฀ crucial฀ determinants฀ of฀ the฀ risk฀ for฀ bronchial฀ carcinoma,฀ with฀ smoking฀initiation฀in฀early฀adolescence฀leading฀primarily฀to฀small฀cell฀bronchial฀carci- noma฀odds฀ratio฀OR฀3.0฀[95฀CI:฀1.1–8.4];฀furthermore,฀this฀risk฀is฀not฀abolished฀by฀ smoking฀cessation฀ [22] .฀An฀association฀has฀been฀demonstrated฀between฀disease฀prevalence฀ Population Number Deaths Cigarette฀smokers British฀doctors 34,000฀M ฀ 441 ฀14.0 6,104฀F ฀ ฀ 27 ฀ 5.0 Swedish฀Study 27,000฀M ฀ ฀ 55 ฀ 7.0 28,000฀F ฀ ฀ ฀ 8 ฀ 4.5 Japanese฀Study 122,000฀M ฀ 940 ฀ 3.76 143,000฀F ฀ 304 ฀ 2.03 ACS฀“25฀State฀Study” 358,000฀M 2,018 ฀ 8.53 483,000฀F ฀ 439 ฀ 3.53 US฀Veterans฀Study 290,000฀M 3,126 ฀11.28 Canadian฀Veterans 78,000฀M ฀ 331 ฀14.20 ACS฀“9฀State฀Study” 188,000฀M ฀ 448 ฀10.73 Californian฀men฀nine฀ ฀occupational฀groups 68,000฀M ฀ 368 ฀ 7.81 Table 5.1 ฀฀฀Smokers’฀ increased฀ risk฀ for฀ developing฀ lung฀ cancer,฀ based฀ on฀ data฀ from฀ prospective฀ studies.฀The฀risk฀for฀non-smokers฀is฀1.00฀ [16] M฀male;฀F฀female and฀ sociological฀ differences฀ among฀ smokers฀ [23] .฀ Smoking฀ cessation฀ can฀ reduce฀ the฀ development฀of฀squamous฀cell฀carcinoma฀SCC฀or฀AC. A฀survey฀of฀smoking฀behaviour฀comparing฀patients฀with฀bronchial฀carcinoma฀and฀con- trols฀revealed฀an฀increased฀risk฀OR฀of฀14.9฀for฀cigarette฀smokers,฀9.0฀for฀cigar฀and฀cigarillo฀ smokers฀and฀7.9฀for฀pipe฀smokers.฀In฀all฀three฀groups,฀the฀duration฀and฀intensity฀of฀smoking฀ were฀co-determinants฀of฀cancer฀development฀ [24] .฀The฀risk฀of฀cancer฀has฀been฀shown฀to฀be฀ increased฀by฀consumption฀of฀dark฀tobacco฀varieties฀ [11,฀25,฀26] .฀Lifetime฀ilter฀cigarette฀ smoking฀in฀men฀and฀women฀reduces฀the฀frequency฀of฀SCC,฀but฀not฀of฀AC฀of฀the฀lung฀ [27] . There฀has฀been฀a฀rapid฀rise฀in฀lung฀cancer฀in฀all฀countries฀of฀the฀world฀where฀cigarette฀ consumption฀has฀increased.฀Lung฀cancer฀incidence฀in฀the฀USA฀has฀increased฀2.5-fold฀since฀ 1950฀ [28] ,฀relecting฀the฀spiralling฀rise฀in฀cigarette฀consumption฀during฀the฀period฀after฀the฀ First฀World฀War฀and฀continuing฀into฀the฀1960s.฀The฀risk฀of฀death฀from฀lung฀cancer฀is฀20฀times฀ higher฀among฀women฀who฀smoke฀two฀or฀more฀packs฀of฀cigarettes฀per฀day฀than฀women฀who฀ do฀not฀smoke.฀Since฀1950,฀there฀has฀been฀a฀600฀increase฀in฀death฀rates฀from฀lung฀cancer฀ among฀women฀Fig.฀ 5.1 ,฀primarily฀caused฀by฀cigarette฀smoking฀ [29] .฀Corresponding฀studies฀ have฀conirmed฀similar฀increases฀for฀many฀countries฀ [30–32] .฀A฀total฀of฀590,000฀smokers฀ died฀of฀lung฀cancer฀in฀the฀developed฀countries฀in฀1995฀alone฀ [31] .฀Rising฀lung฀cancer฀mortal- ity฀should฀be฀viewed฀not฀only฀in฀terms฀of฀the฀increasing฀prevalence฀of฀the฀disease,฀but฀also฀of฀ its฀extremely฀lethal฀nature;฀treatment฀successes฀have฀had฀only฀marginal฀impact฀on฀the฀5-year฀ survival฀rate฀when฀all฀tumour฀types฀are฀taken฀into฀account.฀According฀to฀one฀study฀conducted฀ in฀118,000฀Californians,฀between฀1960฀and฀1997,฀lung฀cancer฀deaths฀increased฀in฀men฀from฀ 1558฀to฀1728฀and฀even฀more฀clearly฀in฀women฀from฀208฀to฀806฀ [29] .฀The฀number฀of฀ciga- rettes฀smoked฀correlates฀very฀closely฀with฀the฀increased฀lung฀cancer฀risk฀ [33,฀34] . The฀question฀as฀to฀whether฀women฀are฀more฀sensitive฀than฀men฀to฀the฀toxic฀products฀of฀ smoke฀has฀been฀answered฀in฀the฀negative฀for฀the฀time฀being฀on฀the฀basis฀of฀the฀data฀from฀ the฀Renfrew฀and฀Paisley฀study฀ [35] .฀According฀to฀these฀results,฀all-cause฀mortality฀in฀men฀ was฀ slightly฀ higher฀ than฀ in฀ women฀ where฀ both฀ men฀ and฀ women฀ were฀ light฀ smokers฀ 35 30 25 Breast cancer Lung cancer Rate100,000 women Year 20 15 10 5 1930 1936 1942 1948 1954 1960 1966 1972 1978 1984 1990 1996 Fig. 5.1 ฀฀฀Age-adjusted฀death฀rates฀for฀lung฀cancer฀and฀breast฀cancer฀among฀women฀in฀the฀United฀ States฀from฀1930฀to฀1996.฀Death฀rates฀were฀age-adjusted฀to฀the฀1970฀population฀ [29]