Bronchial Carcinoma Respiratory Tract

of฀ lung฀ cancer฀ [164–170] .฀ No฀ differences฀ in฀ GST฀ polymorphism฀ have฀ been฀ discovered฀ between฀active฀smokers฀and฀passive฀smokers฀ [171] .฀NAT2฀slow฀acetylators฀evidently฀dis- play฀reduced฀metabolism฀of฀carcinogenic฀arylamines.฀In฀addition,฀a฀signiicant฀association฀ has฀been฀demonstrated฀between฀GST฀M1฀allele฀0:฀GSTM1-0฀and฀lung฀cancer฀OR,฀1.41;฀ CI,฀1.23–1.61฀ [172] .฀Smokers฀with฀the฀GSTM1null฀genotype฀have฀considerably฀higher฀ PAH–DNA฀adduct฀levels฀than฀smokers฀with฀the฀GSTM1+฀genotype฀ [170] .฀Combination฀of฀ GSTM1-0฀together฀with฀two฀allelic฀variants฀of฀cytochrome฀P4501A1฀m2m2฀and฀ValVal฀ further฀increases฀the฀risk฀of฀lung฀cancer฀see฀Table฀ 5.3 ฀in฀ Chap.฀5 .฀Combination฀of฀GSTM1-0฀ and฀NAT2฀slow฀acetylation฀is฀associated฀with฀a฀7.8-fold฀increase฀CI:฀1.4–78.7฀in฀the฀risk฀ of฀bronchial฀carcinoma฀ [172] .฀The฀non-smoker฀is฀at฀greater฀risk฀as฀a฀slow฀acetylator,฀whereas฀ the฀smoker฀is฀at฀a฀greater฀risk฀as฀a฀rapid฀acetylator,฀as฀a฀function฀of฀pack-years฀of฀smoking฀ [168,฀173] .฀Other฀authors฀have฀disputed฀this฀association.฀NAT1฀polymorphism฀is฀reported฀to฀ be฀important฀for฀the฀development฀of฀lung฀cancer฀ [174] .฀p53฀mutations฀are฀clearly฀increased฀ in฀ smokers฀ compared฀ with฀ ex-smokers฀ and฀ non-smokers฀ OR,฀ 9.08;฀ CI,฀ 2.06–39.98,฀ whereas฀K-ras฀mutations฀displayed฀no฀differences฀between฀the฀various฀groups฀deined฀in฀ terms฀of฀smoker฀status฀ [175] . Early฀studies฀on฀ETS฀exposure฀in฀women฀focused฀on฀countries฀in฀Asia฀and฀the฀Far฀East:฀ increased฀cancer฀risks฀were฀reported฀for฀ETS-exposed฀women฀who฀also฀inhaled฀carcino- gens฀from฀cooking฀oils฀at฀high฀temperatures฀ [176–178] .฀As฀an฀additional฀factor,฀these฀ETS- exposed฀ women฀ may฀ also฀ themselves฀ have฀ been฀ smokers฀ in฀ the฀ past.฀ Epidemiological฀ studies฀from฀the฀USA฀and฀other฀industrialised฀countries฀have฀shown฀a฀slight฀but฀detectable฀ risk฀increase฀for฀bronchial฀carcinoma฀in฀passive฀smokers:฀in฀New฀Zealand,฀for฀example,฀ relative฀risks฀of฀1.3฀CI:฀1.1–1.5฀have฀been฀reported฀for฀both฀men฀and฀women฀exposed฀to฀ passive฀smoking฀at฀home,฀and฀of฀2.2฀CI:฀1.4–3.0฀for฀both฀men฀and฀women฀exposed฀to฀ passive฀smoking฀in฀the฀workplace฀ [179,฀180] .฀In฀a฀further฀study,฀the฀risk฀of฀lung฀cancer฀ more฀than฀doubled฀for฀women฀who฀reported฀40฀or฀more฀smoke-years฀of฀household฀expo- sure฀during฀adulthood฀OR,฀2.4;฀CI,฀1.1–5.3,฀or฀22฀or฀more-smoke-years฀of฀exposure฀dur- ing฀childhood฀or฀adolescence฀OR,฀2.4;฀CI,฀1.1–5.4฀ [181] .฀Recent฀research฀has฀conirmed฀ that฀never-smoking฀women฀exposed฀to฀ETS฀from฀spouses฀are฀at฀increased฀risk฀of฀lung฀ cancer฀compared฀with฀unexposed฀never-smoking฀women฀OR,฀1.29;฀CI,฀1.17–1.43฀ [161] . The฀possible฀association฀between฀ETS฀exposure฀during฀childhood฀and฀the฀development฀ of฀bronchial฀carcinoma฀in฀later฀years฀has฀been฀investigated฀in฀a฀multicentre฀case-control฀ study฀Fig.฀ 9.8 .฀While฀the฀association฀was฀rejected฀on฀the฀basis฀of฀the฀results฀ [182] ,฀weak฀ evidence฀emerged฀for฀a฀positive฀correlation฀emerged฀between฀the฀risk฀of฀lung฀cancer฀and฀ exposure฀to฀workplace฀and฀spousal฀ETS฀ [182] . Other฀studies฀have฀reported฀lower฀lung฀cancer฀risk฀levels฀for฀passive฀smokers฀OR,฀1.3;฀ CI,฀ 0.8–1.8฀ [183–185] .฀ The฀ risk฀ of฀ lung฀ cancer฀ was฀ increased฀ where฀ ETS฀ exposure฀ occurred฀at฀a฀young฀age:฀the฀risk฀was฀highest฀for฀children฀exposed฀below฀the฀age฀of฀7฀years฀ OR,฀3.46;฀CI,฀1.80–6.65,฀but฀was฀also฀signiicant฀for฀children฀aged฀between฀7฀and฀14฀ years฀ OR,฀ 3.08;฀ CI,฀ 1.62–5.57฀ and฀ for฀ adolescents฀ aged฀ between฀ 15฀ and฀ 22฀ years฀ OR,฀3.10;฀CI,฀1.52–6.31฀ [186] .฀Similarly,฀high฀risk฀rates฀have฀been฀recorded฀in฀women฀ whose฀husbands฀smoked฀particularly฀strong฀Russian฀cigarettes฀known฀as฀“papirosy”฀OR,฀ 2.12;฀ CI,฀ 1.32–3.40฀ [187] .฀ The฀ data฀ recorded฀ in฀ ETS-exposed฀ children฀ were฀ not฀ con- irmed฀in฀another฀study฀ [182] ฀or฀the฀lung฀cancer฀risk฀was฀increased฀only฀for฀women฀exposed฀ to฀ETS฀in฀the฀workplace฀OR,฀1.5;฀CI,฀0.8–3.0฀ [188] .฀In฀a฀comparison฀of฀3,138฀ETS- exposed฀non-smoking฀women฀with฀1,747฀smoking฀women,฀death฀from฀bronchial฀carci- noma฀was฀recorded฀in฀0.2฀of฀non-exposed฀non-smoking฀women,฀0.9฀of฀the฀ETS-exposed฀ non-smoking฀women฀and฀8.0฀of฀the฀women฀who฀smoked,฀indicating฀that฀ETS-exposed฀ women฀had฀a฀4.5-fold฀higher฀risk฀of฀lung฀cancer฀than฀non-exposed฀non-smokers฀ [189] . Not฀all฀studies฀ever฀conducted฀to฀assess฀the฀risk฀of฀lung฀cancer฀with฀ETS฀exposure฀can฀ be฀accepted฀ [190] .฀While฀an฀evaluation฀of฀numerous฀studies฀indicates฀that฀the฀excess฀risk฀ of฀lung฀cancer฀is฀24฀ [190] ,฀it฀is฀recommended฀that฀all฀the฀data฀should฀be฀re-analysed฀with฀ Odds Ratio 95 CI 0.1 1 S D1 D2 D3 GB F P2 P1 ES I1 I2 I3 10 0.60 0.55 0.45 0.95 0.62 0.60 0.33–1.08 0.19–1.59 0.25–0.82 0.38–2.35 0.27–1.40 0.17–2.12 0.94 0.82 1.08 0.77 1.09 2.09 0.78 0.51–1.75 0.51–1.33 0.42–2.81 0.31–1.92 0.53–2.26 0.71–6.11 0.64–0.96 Odds Ratio 95 CI S D1 D2 D3 GB F P2 P1 ES I1 I2 I3 0.1 1 2.29 2.01 1.35 2.04 2.03 0.73 1.39 1.14 1.12 1.10 0.72 1.22 0.88 0.65–8.07 0.71–5.67 0.43–4.28 0.71–5.80 0.76–5.38 0.32–1.66 0.30–6.48 0.35–3.56 0.46–2.66 0.38–1.36 0.66–2.23 0.40–1.95 0.88–1.47 10 Fig. 9.8 ฀฀฀Risk฀of฀bronchial฀carcinoma฀odds฀ratio฀OR฀associated฀with฀passive฀smoking,฀based฀on฀ studies฀in฀various฀countries฀ [170] .฀Upper฀panel:฀ETS฀exposure฀during฀childhood;฀heterogeneity฀ test฀between฀centres:฀c 2 ฀=฀10.45,฀df฀=฀11,฀p฀=฀0.49.฀Lower฀panel:฀Exposure฀to฀workplace฀or฀spousal฀ ETS;฀heterogeneity:฀c 2 ฀=฀6.76,฀df฀=฀11,฀p฀=฀0.82.฀Ov฀overall caution.฀Similar฀risk฀increases฀have฀been฀reported฀for฀ETS-exposed฀women฀24฀and฀ men฀34฀ [191] .฀According฀to฀another฀meta-analysis฀of฀ETS฀exposure฀and฀lung฀cancer฀ based฀on฀14฀published฀studies,฀the฀increase฀in฀lung฀cancer฀risk฀is฀39฀for฀non-smoking฀ women฀whose฀husbands฀smoke฀25฀cigarettesday,฀and฀91฀where฀ETS฀exposure฀occurs฀ predominantly฀in฀the฀workplace฀ [192] . In฀ETS-exposed฀non-smokers,฀additional฀radon฀exposure฀is฀reported฀to฀be฀particularly฀ dangerous฀in฀terms฀of฀the฀development฀of฀lung฀cancer฀maximal฀OR฀increase฀from฀1.08฀ [0.8–1.5]฀to฀1.44฀[1.0–2.1]฀ [193] .

9.6 Complications of Anaesthesia

In฀younger฀children,฀in฀particular,฀ETS฀exposure฀is฀associated฀with฀delayed฀growth฀of฀the฀ lungs,฀with฀reduced฀FEV 1 ฀and฀diminished฀respiratory฀capacity฀ [194–196] .฀ETS฀exposure฀ causes฀an฀increase฀in฀children’s฀plasma฀cotinine฀levels฀ [197–202] .฀Since฀cotinine฀has฀an฀ elimination฀half-life฀of฀19–40฀h,฀the฀plasma฀cotinine฀level฀relects฀smoke฀exposure฀over฀the฀ preceding฀3–4฀days฀ [199] .฀N 2 OO 2 -halothane฀anaesthesia฀was฀implemented฀as฀indicated฀in฀ 575฀children฀aged฀between฀1฀month฀and฀12฀years฀who฀were฀free฀from฀respiratory฀tract฀and฀ cardiovascular฀disease.฀The฀children’s฀urine฀was฀collected฀for฀the฀determination฀of฀coti- nine฀levels.฀At฀the฀end฀of฀anaesthesia,฀the฀recovery฀room฀nurse฀documented฀any฀airway฀ complications฀that฀may฀have฀occurred.฀Urinary฀cotinine฀levels฀40฀ng฀cotinineml฀urine฀ correlated฀with฀the฀number฀of฀unwanted฀complications฀of฀anaesthesia฀OR,฀2.3;฀CI,฀1.2– 4.5;฀Fig.฀ 9.9 .฀Children฀whose฀parents฀smoked฀30฀cigarettesday฀had฀a฀44฀airway฀com- plication฀rate,฀compared฀with฀only฀25.5฀in฀children฀whose฀parents฀were฀non-smokers฀ [203] .฀The฀urinary฀cotinine฀levels฀measured฀in฀the฀children฀were฀too฀low฀for฀them฀to฀have฀ been฀active฀smokers฀themselves.฀Ultimately,฀the฀incidence฀of฀airway฀complications฀fol- lowing฀anaesthesia฀is฀doubled฀when฀the฀parents฀are฀smokers฀ [203] A฀study฀by฀Reisli฀et฀al.฀evaluated฀the฀effects฀of฀ETS฀on฀onset฀and฀recovery฀time฀after฀ single฀dose฀of฀rocuronium฀in฀children.฀Forty฀children฀between฀4฀and฀10฀years฀were฀enrolled฀ 10 10–39,9 40 Continine [ng per ml urine] 10 20 30 40 50 60 70 80 Unwanted respiratory complications [] Fig. 9.9 ฀฀฀Unwanted฀ respiratory฀complications฀in฀ 88฀out฀of฀365฀children฀with฀ a฀urinary฀cotinine฀level฀ 10฀ngml,฀in฀30฀out฀of฀91฀ children฀with฀an฀intermediate฀ urinary฀cotinine฀level,฀and฀in฀ 18฀out฀of฀43฀children฀42฀ with฀a฀urinary฀cotinine฀ level฀40฀ngml฀signiicant฀ differences฀between฀the฀ groups;฀p฀=฀0.01฀ [203] into฀the฀study฀ [204] .฀Children฀who฀have฀no฀familial฀smoking฀history฀were฀included฀in฀the฀ irst฀group฀whereas฀passive฀smokers฀included฀in฀the฀second฀group.฀Sevolurane฀in฀50฀O 2 ฀ and฀50฀N 2 O฀was฀used฀for฀induction฀of฀anaesthesia.฀Evoked฀adductor฀pollicis฀electromyo- graphy฀was฀used฀to฀monitor฀neuromuscular฀block.฀The฀T95฀and฀T25฀values฀were฀recorded.฀It฀ was฀shown฀that฀the฀T95฀values฀±SD฀for฀rocuronium฀were฀110.1฀±฀39.3฀s฀and฀79.3฀±฀35.6฀s฀for฀ group฀1฀and฀group฀2,฀respectively฀฀p฀฀0.05.฀The฀T25฀value฀of฀group฀2฀was฀40.1฀±฀10.6฀min;฀ compared฀with฀group฀1฀values฀30.85฀±฀7.02฀min,฀it฀was฀signiicantly฀longer฀฀p฀฀0.01.฀ Therefore,฀it฀can฀be฀concluded฀that฀passive฀smoking฀children฀consume฀less฀rocuronium฀ than฀non-smokers฀during฀similar฀anaesthesia.฀A฀history฀of฀passive฀smoking฀must฀also฀be฀ taken฀into฀consideration฀during฀preoperative฀evaluation฀of฀paediatric฀patients฀ [204] . Overall,฀it฀should฀be฀noted฀that: • ฀ Girls฀are฀more฀susceptible฀than฀boys฀to฀such฀complications฀ [205,฀206] ฀because฀of฀the฀ more฀favourable฀ratio฀of฀respiratory฀tract฀to฀lung฀size฀in฀boys฀ [206,฀207] . • ฀ Girls฀respond฀more฀sensitively฀than฀boys฀to฀cholinergic฀stimuli฀ [208] . • ฀ Low฀maternal฀socioeconomic฀status฀is฀associated฀with฀persistent฀lower฀respiratory฀tract฀ infections฀and฀inluences฀the฀complication฀rate฀ [209] . • ฀ According฀to฀one฀retrospective฀study,฀laryngospasm฀is฀ten฀times฀more฀common฀in฀chil- dren฀exposed฀to฀ETS฀compared฀with฀non-exposed฀children฀ [210] . • ฀ Oxygen฀desaturation฀following฀anaesthesia฀was฀observed฀more฀frequently฀in฀the฀recov- ery฀room฀in฀ETS-exposed฀children฀than฀in฀non-exposed฀children฀ [211] . • ฀ By฀using฀a฀pre-anaesthesia฀questionnaire฀or฀by฀determining฀urinary฀cotinine-levels,฀the฀ paediatric฀anaesthetist฀should฀take฀steps฀to฀prevent฀those฀complications฀of฀anaesthesia฀ that฀are฀more฀likely฀to฀occur฀in฀ETS-exposed฀children.

9.7 Otitis Media

Otitis฀media฀affects฀up฀to฀46฀of฀young฀children฀up฀to฀the฀age฀of฀3฀years฀and฀is฀the฀condi- tion฀ most฀ commonly฀ prompting฀ medical฀ consultations฀ in฀ this฀ age฀ group฀ Table฀ 9.8 ฀ [213–217] . Variable Odds฀ratio฀95฀CI฀ p฀ Number฀of฀cigarettes฀smoked฀10฀vs.฀³10 1.89฀1.22–2.91 ฀ 0.004 Child’s฀place฀of฀residence฀during฀the฀irst฀year฀of฀life฀ household฀vs.฀day฀care฀vs.฀private฀creche 2.94฀1.55–5.54 ฀ 0.001 Maternal฀educational฀level฀12฀vs.฀³13฀years 1.55฀1.05–2.30 ฀ 0.03 Doctor฀visits฀number฀during฀the฀past฀12฀months ฀ £3 1.00 ฀ 4–10 2.50฀1.70–3.67 ฀0.001 ฀ ³11 2.01฀0.96–4.18 ฀ 0.06 Table 9.8 ฀฀฀Inluence฀of฀maternal฀smoking฀on฀the฀risk฀of฀otitis฀media฀in฀young฀children.฀Calculations฀ based฀on฀a฀multivariate฀logistic฀regression฀model฀ [212]