Bronchial Asthma in Children

airways฀disease;฀for฀the฀speciic฀medical฀diagnosis฀of฀“asthma,”฀this฀association฀is฀less฀ clear฀ [183] .฀The฀younger฀the฀children฀affected,฀the฀more฀deinite฀the฀association฀of฀passive฀ smoking฀with฀the฀bronchitic฀and฀asthmatic฀symptoms,฀as฀also฀relected฀in฀hospital฀admis- sions฀ [183–187] .฀In฀contrast฀to฀maternal฀smoking,฀paternal฀smoking฀was฀not฀found฀to฀exert฀ any฀signiicant฀effect.฀A฀tendency฀for฀colds฀to฀go฀to฀the฀chest฀and฀for฀reduced฀FEV 75 ฀and฀ FEV 85 ฀has฀been฀shown฀to฀correlate฀directly฀with฀salivary฀cotinine฀levels฀ [185] . One฀ sociomedical฀ study฀ showed฀ an฀ association฀ between฀ maternal฀ smoking฀ and฀ a฀ ฀medical฀diagnosis฀of฀asthma฀in฀the฀child฀only฀where฀the฀mothers฀had฀12฀or฀fewer฀years฀of฀ education฀ [188] . The฀use฀of฀pulmonary฀function฀measurements,฀bronchial฀hyperresponsiveness฀measure- ments฀and฀skin฀prick฀tests฀as฀atopy฀markers฀to฀permit฀an฀objective฀diagnosis฀of฀asthma฀has฀ yielded฀differing฀conclusions฀concerning฀the฀association฀between฀childhood฀asthma฀and฀ passive฀smoking฀ [155,฀178,฀179,฀182,฀185,฀189,฀190] .฀The฀majority฀of฀studies฀in฀which฀ pulmonary฀function฀has฀been฀measured฀reveal฀a฀decrease฀in฀functional฀indices฀in฀passive฀ smoking฀children.฀Two฀studies฀showed฀no฀association฀ [178,฀190] .฀The฀inluence฀of฀passive฀ smoking฀on฀skin฀prick฀test฀results฀is฀controversial฀ [188,฀191,฀192] . 5 27 55 Weeks after birth 50 100 Vmax FCR [mls] 150 200 250 Fig. 5.5 ฀฀฀Maximum฀ expiratory฀low฀at฀functional฀ residual฀capacity฀during฀the฀ irst฀year฀of฀life.฀♦฀Healthy฀ control฀group;฀■฀children฀of฀ women฀who฀smoked;฀ ▲ ฀total฀ cohort฀ [180] Asthma severity Lung function FEV1 PC20; histamine [mgml] Mother Nonsmoker Smoker Nonsmoker Smoker Bronchial responsiveness Score Mother 10 100 80 60 40 20 .03 .06 125 .25 .5 1 2 4 8 16 5 Fig. 5.6 ฀฀฀Passive฀smoking฀and฀childhood฀bronchial฀asthma.฀The฀igure฀illustrates฀asthma฀severity,฀ the฀extent฀of฀reduced฀pulmonary฀function฀and฀the฀increased฀bronchial฀responsiveness฀to฀histamine.฀ Study฀conducted฀in฀94฀children฀aged฀between฀7฀and฀17฀years฀with฀a฀history฀of฀asthma.฀In฀each฀case,฀ the฀pairs฀of฀columns฀represent฀non-smoking฀and฀smoking฀mothers฀from฀ [181] Serum฀IgE฀levels฀and฀prevalence฀of฀eosinophilia฀were฀reported฀to฀be฀increased฀in฀one฀ study฀in฀9-year-old฀children฀of฀smoking฀parents฀ [193] ;฀likewise,฀elevated฀IgE฀levels฀have฀ been฀detected฀in฀the฀cord฀serum฀in฀children฀of฀smoking฀mothers฀ [77,฀194] .฀Children฀whose฀ parents฀smoked฀during฀pregnancy฀displayed฀more฀intense฀reactions฀following฀histamine฀ challenge฀ [195] .฀ Bronchial฀ responsiveness฀ as฀ tested฀ by฀ challenge฀ methods฀ was฀ consis- tently฀increased฀in฀asthmatic,฀passively฀smoking฀children฀ [188,฀189,฀196,฀197] . Passive฀smoking฀also฀relects฀the฀asthma฀of฀affected฀children฀increased฀occurrence฀of฀ exacerbations,฀but฀not฀the฀frequency฀of฀hospital฀admissions฀ [198–200] .฀The฀association฀was฀ clear฀between฀maternal฀smoking฀number฀of฀cigarettes฀and฀the฀deterioration฀of฀pulmonary฀ function฀together฀with฀increased฀histamine฀responsiveness,฀with฀the฀effect฀on฀lung฀function฀ occurring฀principally฀during฀cold฀wet฀weather฀ [197] .฀When฀parental฀maternal฀cigarette฀ consumption฀was฀restricted,฀childhood฀asthma฀status฀and฀lung฀function฀improved฀ [181] . To฀summarise,฀it฀may฀be฀concluded฀that฀there฀is฀a฀clear฀association฀between฀passive฀smok- ing฀and฀childhood฀obstructive฀and฀non-obstructive฀airways฀disease,฀with฀smoke฀exposure฀ apparently฀exacerbating฀pulmonary฀function฀and฀the฀course฀of฀asthma.฀However,฀there฀is฀as฀ yet฀no฀convincing฀evidence฀that฀asthmatic฀diseases฀are฀directly฀caused฀by฀passive฀smoking.

5.5 Bronchitis and Pneumonia

Active฀smoking฀provokes฀acute฀respiratory฀tract฀diseases.฀While฀respiratory฀tract฀diseases฀ are฀not฀found฀more฀commonly฀in฀smokers฀than฀in฀non-smokers,฀when฀they฀do฀occur,฀the฀ lower฀respiratory฀tract฀is฀more฀often฀involved,฀leading฀to฀a฀more฀protracted฀duration฀of฀ cough฀and฀more฀frequent฀pathological฀indings฀on฀auscultation฀ [201,฀202] .฀In฀one฀cohort฀ study฀in฀male฀college฀students,฀smokers฀were฀found฀to฀have฀a฀signiicantly฀higher฀number฀ of฀doctor฀visits฀and฀an฀even฀higher฀number฀of฀medical฀consultations฀for฀respiratory฀tract฀ symptoms฀ [203] .฀A฀clear฀dose–response฀relationship฀was฀found฀between฀smoking฀dura- tionconsumption฀and฀the฀number฀of฀doctor฀visits฀for฀respiratory฀problems.฀In฀the฀smoker฀ group,฀colds฀were฀more฀commonly฀associated฀with฀cough,฀mucus฀production,฀shortness฀of฀ breath฀and฀rhonchi฀ [204] . For฀children,฀passive฀smoking฀has฀long฀been฀regarded฀as฀a฀risk฀factor฀for฀the฀develop- ment฀of฀lower฀respiratory฀tract฀diseases.฀In฀the฀USA,฀each฀year,฀150,000–300,000฀children฀ below฀the฀age฀of฀18฀months฀are฀reported฀to฀suffer฀from฀respiratory฀tract฀infections฀bron- chitis฀or฀pneumonia฀as฀a฀result฀of฀passive฀smoking฀at฀home฀ [4] . Active฀cigarette฀smoking฀is฀associated฀with฀a฀higher฀complication฀risk฀for฀pneumonia,฀ especially฀inluenza฀pneumonia:฀in฀one฀group฀of฀250,000฀veterans,฀mortality฀from฀inlu- enza฀pneumonia฀was฀1.78฀times฀higher฀among฀smokers฀than฀among฀non-smokers฀ [142] .฀ The฀incidence฀and฀severity฀of฀inluenza฀A฀H1-N1฀are฀also฀increased฀in฀smokers฀50฀vs.฀ 30฀for฀non-smokers฀ [46] .฀During฀a฀severe฀inluenza฀epidemic,฀the฀incidence฀of฀clinical฀ as฀well฀as฀subclinical฀infections฀based฀on฀antibody฀titres฀was฀increased฀among฀smokers฀ [205] ;฀while฀smoking฀exerted฀no฀effect฀on฀disease฀severity,฀the฀persistence฀of฀antibody฀ titres฀in฀smokers฀was฀reduced.฀This฀may฀be฀one฀reason฀for฀increased฀susceptibility฀to฀inlu- enza฀infections฀ [206] .

5.6 Other Lung Diseases Influenced by Cigarette Smoking

This฀category฀principally฀includes฀a฀respiratory฀bronchiolitis-associated฀interstitial฀lung฀dis- ease฀ [207] ฀and฀pulmonary฀Langerhans฀cell฀granulomatosis฀ [208,฀209] .฀Pulmonary฀haemor- rhage฀ associated฀ with฀ Goodpasture’s฀ syndrome฀ type฀ is฀ also฀ signiicantly฀ associated฀ with฀ cigarette฀smoking฀ [50] .฀Women฀with฀breast฀cancer฀who฀smoke฀tend฀to฀develop฀lung฀metas- tases฀more฀frequently฀than฀non-smokers฀ [210] .฀In฀contrast,฀sarcoidosis฀ [211] ฀and฀allergic฀ pneumonitis฀occur฀more฀rarely฀in฀smokers฀than฀in฀non-smokers.฀Idiopathic฀pulmonary฀ibro- sis฀is฀common฀among฀heavy฀smokers฀than฀former฀smokers฀OR฀=฀−2.3;฀CI:฀1.3–3.8฀vs.฀1.9฀ CI:฀1.3–2.9,฀and฀the฀disease฀may฀even฀have฀its฀onset฀after฀sudden฀smoking฀cessation฀ [73] .฀ Obviously,฀explanations฀for฀the฀various฀diseases฀are฀to฀be฀sought฀in฀the฀effects฀of฀smoking฀on฀ the฀inlammatory฀processes฀in฀the฀lung,฀on฀immune฀function฀and฀on฀vascular฀permeability. Smokers฀are฀presumed฀to฀have฀a฀higher฀risk฀than฀non-smokers฀for฀developing-varicella฀ pneumonia฀ [110,฀212] .฀Radiologically,฀pneumonia฀can฀be฀detected฀on฀the฀basis฀of฀diffuse฀ interstitial฀or฀patchy฀iniltrates฀in฀up฀to฀20฀of฀adult฀cases฀ [213] ,฀though฀often฀without฀ clinical฀symptoms.฀The฀pulmonary฀symptoms฀usually฀set฀in฀during฀the฀irst฀days฀after฀the฀ onset฀of฀rash,฀and฀consist฀of฀cough,฀dyspnoea฀and฀varying฀degrees฀of฀hypoxaemia฀caused฀ by฀inlammation฀and฀swelling฀of฀the฀bronchial฀epithelium฀ [206,฀214] .฀In฀untreated฀adults,฀ the฀mortality฀rate฀from฀varicella฀pneumonia฀is฀approximately฀10,฀but฀may฀be฀as฀high฀as฀ 50฀where฀there฀is฀severe฀pulmonary฀involvement฀leading฀to฀pulmonary฀failure฀ [206] .

5.7 Concluding Remarks

• ฀ Current฀knowledge฀indicates฀that฀there฀is฀an฀established฀association฀between฀smoking฀and฀ various฀forms฀of฀lung฀cancer.฀Exposure฀over฀months฀and฀years฀to฀the฀various฀inhalational฀ products฀of฀tobacco,฀such฀as฀benzo[a]pyrene,฀nitrosamines฀NNK,฀NNN,฀solvents฀ben- zene,฀crotonaldehyde,฀formaldehyde฀and฀ 210 polonium,฀is฀an฀important฀aetiological฀factor.฀ The฀organic฀compounds฀are฀metabolised฀activated฀by฀various฀enzymes฀in฀the฀CYP฀sys- tem฀and฀then฀form฀adducts฀with฀DNA฀in฀lung฀tissue฀and฀with฀leucocytes.฀In฀addition,฀the฀ activity฀of฀the฀GST฀system฀plays฀an฀important฀role฀in฀the฀detoxiication฀elimination฀of฀ carcinogens. • ฀ A฀signiicant฀risk฀for฀the฀development฀of฀lung฀cancer฀has฀been฀identiied฀in฀individuals฀ with฀ high฀ inducibility฀ of฀ CYP1A1฀ and฀ reduced฀ activity฀ of฀ glutathione฀ S-reductase฀ GSTM1฀00.฀The฀risk฀for฀bronchial฀carcinoma฀is฀particularly฀increased฀in฀carriers฀of฀the฀ GSTM1฀00฀system.฀Bronchial฀carcinoma฀is฀commonly฀encountered฀and฀some฀90฀of฀ cases฀are฀smoking-related;฀worldwide,฀its฀prevalence฀is฀increasing฀more฀among฀women฀ than฀men. • ฀ As฀the฀practice฀of฀smoking฀light฀cigarettes฀has฀become฀more฀widespread,฀there฀has฀been฀ an฀increase฀in฀the฀prevalence฀of฀AC,฀a฀form฀of฀lung฀cancer฀that฀is฀less฀amenable฀to฀treat- ment฀than฀SCC.