Tobacco Documents Online

Br. J. Corrccr (1986); 5419T-105 .., 'I TH1537 Relationship of passive smoking, to risk of lung, cancer and other sm,oking-associated diseases P.N,. Lee,* J. Chamberlain &. M.R. Al'dersont Institutr of Cancer Research, Clifton Rood. BeGnont. Surrey. UX.. Summary In the latter part of a large hospitallcasecontrol study of'the relationship of type of cigarette smokedito risk of various smoking-associated diseases, paticnts answered qucstions on the smoking, habits of their first spouse and on the extent of passive smoke exposure at home, au work,, during travcll and during', Ie'tsure.. In an extcnsion of! this study an attempt was made to obtain smoking, habit data directly from, thee spouses otall l lifctong non,smoking lung cancer cases and of two lifclong non-smoking matched controls for each case. The attempt was made regardless of whether the patients had answered passive smoking questions in hospital or not. /Amongst lifelong non•smokers, passive smoking was not associated aith any significant increase in risk of lung caneer, chronic bronchitis. ischacmic heart disease or stroke in any analysis. Limitatior,s of', pasl studies on passive smoking are discussed and' the, need for furthen rescarch underlined. From, all the available evidenee, it appears that any, effect of passive smoke on risk of any' of thc major diseases that have been associated with active smoking is at most, small, and may not exist at'.alll Sttrrln' of hospital in-patients In 19'77' a large hospital casc-control was initiated to study the relationship of the type of cigarette smoked to risk of lung cancer, chronic bronchitis, ischaemit: heart disease and stroke. This study was carried out in 110 hospital regions in England; interviewing ended in January 1982. The original questionnaire did not include questions on pas'sivc smoking as it' was not considered an important issue in: 1977. Howcvcr; in 1979 it was decided to extend tihe questionnaire to cover passive smokingg for married, patients for the last four rcgions to begin intervicwing: Sitbscqucntlly; in 1981,,, following publication of'the papers, by Hiray.rma (1981) and by Trichopoulos cr al. (1981) clftiniing, tliat, non- smoking wives of smokcrs iiaul ,. ^if__ntty greater risk of lung',canccr than mmn-smoking wives of non-smokers, it was decided to increase the number of interviews of married llmg cancer cases and' controls. The extcnded' questionnaire was then administered to these patients in all hospitals where intcrvicwing;was still continuing. FolJbw-up srudi• of spouses of non-srrrokhn,c hospital in-paricnts In 1982, after interviewing of' hospital in-patients had been completed, it was decided to carry out a fbllow-up study. In this study,, an attempt was Correspondencc: P.Tt: Lee. 'Presettt addr, 25' Cedar Road„ Sutton, Surrey, SM2 SDG: tPracnt address: Office of Population Censuses and SurNeya,, St. Catherine's Ilouse, 10 hingsxvay:, London WC2B 6JP: made to interview the spouses of all of the marricd hospital ip-paticnts with lung cancer who reported never having smoked, as well as of two marr'tcd non-smoking controls for each of these index lung cancer cases. The follow-up study was intended partly to compart: information on spouses' smoking habits obtaincd! Grst-hand' with that obtainad second-hand during the in-patii:nt! interviews, and partly to obtain some data on spouses' srntokingg habits for those patients who had not answered passive smoking questions in hospital. This paper concentrates solcly on the issue of pttssin•e smoking in lirclong non-smokcrs: R'csults: rclating to type of cigarottc smoked arc dcscribcd elsewhere (Aldcrson et, rrl:, 1'985);, while a dctailc& rcport, available on requcst', from, P'NL, considcrs the.oA'erall (iiuuiirigsfr:v:Mthas: !s^--cm,ntirmi studv.. Methods and response StudY of liospitnl inrparients For each o:f the 4 index diagnoses (lung, cancer,, chronic bronchitis, ischaemie heart disease and' stroke),, the intention was to interview 200, cases and 200 matched controls in each, of the eight sex/ngc cells (i.e. malc or female, and aged 35-44; 45-54, 55-64 or 65-74). This gave a target of 12;8001 patients, though for some categorics (c.g'~ young female chronic bronchitics) this wouldl be unattainable. Patients were: selected' from medical (inclttding, chest medicine), thoracic surgery, and radiotherapy wards. Controls wcre patients' without one of' the four index diagnoses; individttally matched! to cases on sex, asc, hospital region and, 0 The Macmillan Press Ltd., 1986 IV

r 98' P.M LEE'er al: when possible, hospital ward and timr of intcrview. Sirbscqucntly, when final discharec diacnoscs became available, they .%,cre uscdl to reallocate cases and controls as ncccssary, Patients .+•i'tihout a final diagnosis kcpt' their provisional diagnosis. Wherce changes in! ca5e.control status occurred. raitients t+•crc rcgrouped into: new case-control pairs as appropriate. Wit'h, the assistance of Sir Richard Doll and Mr Richard' Pcto, non-indcx diagnoses were classi6ed as follows: class IA 'definitely, not smoking associated' class 1B 'probably not smoking,associated' class 2A 'probably smoking associated" class 2a'definitely'smokingassociated? Controlk with no final diagnos~iswere considered class 1B. Overall; there were t2;693 interviews carried out which resultcdl in 4,950 pairs with class 1' controls and1730 pairs with ciass1 controls. There were 3;832' intervicws of married cases and controls where the passive smoking questionnaire was completed! In order to avoidlsubstantial loss of data, due to one member of a pair not being married or noi eompleting the passive smoking' questibnnaire.itU was decided to ignore matching when analysing the passive smoking data and to compare each index group with the combined controls. Numbers by sex and, case-control status arc given in Tablh I'. Table 11 Numbers of married hospitat in,paticnts completing passive smoking questionnairrc ;ttatr Frmafe' Totnl flung,eancer >-t7 245 79, Chronic bronchitis I32' Ca .'.6(, tschacmic heart diseasc 286 221 W Stroke 161 137 '9S' Controls Class I A and 1 B' 839 713 t.~>2 ('Iagc 7h' and 7:R' 2KR' I.tn , Total 2!253, l.ts9 ~.~:,2 'Other, diseases were classified bi• degree ofi smoking association - class IA: definitely raat; class IB: probably not! class 2A: probably: class 2B: definitely: in the passive smoking part of the questionnaire, patients were asked when the marriage started: if and when it hadl ended; the num'ben of manufactured cigarettes per day smokrd' by the spouse both during the last 12' m>anths,ofmarniigrand also at the period of maximum smoking dhring the marriage; and whether the spouse ever regularly smoked', hand-rollcd cigarettes, cigars or a pipe during the marriage. For sccond' or subscqpcnt marriages, questions relatcd'to the Grstmarriage to give the longest latent interval bet.accn exposure and disease onset. The patients were also asked to quantify, according to a four-point scale (a lot. average, a litltle, naU at all), the extent', to which they were regularly exposed to tobacco smoke from othen people prior to coming into hospital in 4 situationsr at homc; at' work; during daily travel: during, leisure time. In the main! questionnaire. detailed questions were asked on smoking habits andl on a whole range of possible confounding variables. lirillotv-ttp study of spouses of non-sntolting ho'spitol, irJ-patients From the hospital study there were 56' lung cancer cases who reported being lifelong non-smokers. who were married at the time of interview and who were not known to have been marrie& previously. In a follow-up to the maini study. an~ attempt was made to intervic+s• the spouses rnf'these 56 cascs and also the spouses of two life-long non-smoking controls for each case, individually matched for sex. marital status and'. 10-ycar agc group and, as far as possible, hospital. Where multiple potential controls in the same hospital were available, those intcrvicrti+ed nearest' in time tt7 the case were selected. Where suitable controls in the samc' hospital wcre not available, those ini the nearest hospit'aL.vcrc chosen. Because names an&addresses of the pat~icnts were not recorded in the hospital study., it was necessary to go back to the hospital both to obtain this information and also to get permission to inlervictiv their spouses. Following, some refusalt both by the hospital and by the spouses. succcssfKtl interviews were obtained from spouses of 34' cases (101 wis•es and 24 husbamds) and S'0 coninols (?6 tt•ivcs and ;4 httsbands) whose condition wa_c d'c(onitcly or probably not related to smoking. lntcrvicwing was carried out bet«•ecn July 1'9S2 ali'id rnu'bu5t i~,io_i.. i iie S;trt.~u~c> wCr~:e asKCd a!DOWt, their consumption of manufactured ciga!retites, cigars and pipes ('a) nowadays, (b) during the year of admission of the pntienr or (c) maximum durin¢ the whole of the marriage. The spouses were not asked about the smoking haktiac of the index patient; The spouses wcrc alto a:sked questions on age, occupataott, sociall class' and a range of other potential confnund!ing, factors. Stnt ixticnl ' i+tctJiorl.r The statistical' methods are based on classical procedures for analysis of groupcd data dcrin•cdl from casc-eontrol studies (Breslow & Day, 1980). Iin, general, the material has been cxaminedl as a 2'x Kx S'table. wibh,K'representing the levels of the

I PASSIVE SMOICING' AND SMOKING-RELATED DISEASES risk factor of intetzsu and S the number of strata used to take account of potential confounders:. Results presented arc for the combined strata and show the relative risk ('Mantcl-Hacnszeli estimate) together with the signi ucance of its difference from a base It:•vel (risk 1.0), and/or the dose-related trend. fin, analyses of the data collected in hospitali comparisons arc madc betwcen cases with a particular index disease and' all the controls wit'h. diseases definitely or probably nou rclated'to smoking. Six simple indices of passive: smoke exposure were: considered in, these latter analyses, (i){iv) exposure at home, at work, during travel, during leisure,, (v) spouse smoking manufactured cigarettes in the last' 12 months, andl (vi)' spouse smoking manufactured cigarettes in the whole of the marriage: Bases for (ii) are reduced as not' a111 patients worked: In addition, a, combined indcx of passive smoke exposure was calculated by thc: unweighted sumi of the four individuali exposure ;ndices (ii){iv), counting 'not at all' as 0, 'littlc' as .'aMerage'as 2 and 'a lbt' as 3. Results l:ung' cancer The follow-up study concerned' 56 lung canccr cases and 112 matched controls who reported never having smoked in their hospital' interview. Of these,, there wcre 4Tcases (15 malc and 32 female) and'96: controls (30 male and' 66 fcmale)i for whom some information ong smoking, habits of their spouses was available. Of these 143 patients, information on spouse smoking,was available botih; from the spouse and from thc patient for 59 (41 %), from the spousc only for 55 (3g'%) and from the patient only for 29 (20%), Table 11 shows the cstimatedl agc-adjusted' relative risk of lung cancer in relation to spouse sntoking, during the whole of the marriage, by sex, sourcc:of data, and period of smoking; None of the 9' relative risks shown in the table are statistically significant. NVhen data for both sexes and, both sources are considered, the estimated relative risks in rclation to spouse smoking are: close to 1('I.11'). For individual sexes or sources, where numbers of cases andi controls are sma'ller, relative risks vary more from unity,, but no consistent pattern is cvidentL Similar conclusions were reached, when analyses were based on smoking during the year of hospital interview. Here, the overall relative risk was again close to 11 (0.93 with limits 0:41-2:09). Table III summarises concordance between spouse's manufactured cigarette smoking habits as rcported directly and indirectily for the 59 paticnts with data from bot'h, sources. Discrepancies were seen for 9 spouses (15%) in: respect of smoking at some time during marriage and ini the case of 2' Table 11 Relationship between spouse?s manufactured cigarette smoking during the whole of the marriage and risk of lung cancer among )ifelong non+smokcrs (standardised for age) Spouse did' not smoke Spouse smokrd Sex of' Rtlative riskk patient' Cases Controla' Cases Controis' (9S'/;,limits) Based on intern•icWa of1hr spouse in fhrtow.up study (114 patients) Male 5 13 5 13 1.01(0.23-4.411) Female , 5 16 19 38 1.60(0.4*-5:78) . Combinedl 10 29 24 51 1.33(0.50-3!48) Based on interviews of the index fratirnt, in hospital ($8 patitnts) Male 7 IL5 5 7 1,53(0:37-6:34) Female 9 17 8 20 0.75(0.24-2.40) Combined 16 32 13 27 1.00(0.41-2.44) Based on both sources of information(Ihf3: paritnts)b' ' Mele 7 16 8' 14', 1.30(0.38-039) Fernale 10 21 22 45' 1.00(P.37-2:71)i Combined' 17' 37 30 59' 1.111(0:51-2:39) , 'Only controls included in follow-up study considered; "In this analysis the spouse was countedias a smokecif reported to be so eithrrdirectly„by the spouse during follow-up interview, or, indireclly, by the patient in hospitalJ Note that the. 59 patients for whom information on spouse smoking was available from bothi sourees are included in all 3 analyses. I I I

100. P.N: LEE et ol. Table IIl Concordance between spouse s manufactured cigarette smoking habits as reported directly andlindirectly S.ex oj'potienti+case control status Ilate Female Cases Controls Cases Controls Total Spouse a smoker sometime in marriage according to: Subject and'spouse 2 6 5 13 26 Only, subjact' I! 0 01 3 4 Only spouse 1 1 3 0 5 Neither 3 11 1 9 24 % subject/spouse agreement 71/ 94%. 671% 88y, 85% Spouse a smoker during year of hospital interview according to: Subject and spouse I 6' 2' 4 13 Only subject 0 0 0 1'. 1` Only spouse I 0 0 0 I Neither 5 12 7 20 44 % subject/spouse agreement 86% 86% 1W/. 1tb./. 96% 97% spouses (3°!e),in respect of'smoking during thc year of hospital interview. There was no consistent pattern in the direction of discrepancy,. Table IV summarises the results of analyses carricdi out rclating, 7 indices of passive smo'kc: exposure recorded'in the hospital interviews to, risk of lung caricer, among lifelong non-smokers. Here the controls uscdi for comparison arc all never smoking patients with diseases clttssified as definitely' or probably not' associated with smoking who completed the passive.smok;ing questionnaire. Overall the results showcd' no evidence of an effect of passive smoking on lung cancer incidence among lifelong, non-smokcrs: In malc paticnts; relative risks were increased fot sonic of the indiccs: but numbers of cases were small and none of the di11I'anerives approached statistical' sigraificanec: In females, wheae numbers of cases ::•c mc .:.r;gcr, suutu trends as existed tcnded'to br negative and indeed were marginally significantly negative (P<0.05)' for passive smoking during travcli and during lcisurc:. For the combined sexes no diftl:rences or trends were statistically significant at the 95°/'a confidence level;, such trends as existed tcnding to be slightly negativc. The relative risk in relartion, to the spouse smoking during the whole of the marriage was estimated to be 0.80 for the sexes combined, with,. 95°/% confidtnce limits of 0.43 to 1.50. Standardisation for working in a dusty job, the variable apart from smoking found to have the strongest association with lung cancer risk in the analyses descnibed'in Alderson et af.' (F985').,,did not affccG the conclusion that passive smoking, was not associated with risk of lung cancer among nevcrr smokers in our study. Cltronic bronctritds, ischaernk hettrt'disease and,stroke Analyses similar to that shown in Table IV for lung canccr wcrc also carried out for chronic bronchitis, ischaemic heart disease and stroke. Illustrati'vee results for two of the indices are presented in Table V. No significant relationship of' any index o!' passive smoking to risk of the 3 diseases was seen. Forr the scxcs combined, the relative risk in rclation to the spouse smoking during the whole of the marriage was 0.83' for chronic bronchitis ('95°l'0 confidence limits 0.31-2.20). 1'.03' for ischaemic heart disease (limits 0.65-1.62) and 090 for st'rokc. (limits 0:53-1.52). For stroke there was, in both sexes, an approximate 2-fold' increase in risk for patients with a combined passive smoke index that was high (score of' 5 to 12) compared with those wherc it was low (score of 0 or 1). However, numbers of cases w3nh a high, score were loM ('14 malt;s and 7' femaJes) and evcn for the sexes combined, the relative risk estimate of 2.18 was not'. statistically significant (limits 0.8fi--5.48). In interpreting this finding, it should be noted that active smoking was not found to bc~clcarly rclated' to stroke inm the main study (Aldcrson er al.. 1985), rcnderin&atwo:fold'increase~in relationitopassiivc smoking a priori: unlikely. . , . . . . : . •:~~:

I P!AiSS1VE SMOKING AND SMOKIiNG-RELATED DISEr'1SES 101 Passiae smoke Slnle patients Female parienrs Sexes tnmAined exposure, indexjlerel' Cases Cnnrrol3 R' Cases Controls R Cases Controls R A't'home Not at all 9 101 1 21 192 I 30 293 I, L'ittlt 2I 21 1.22 6 65 0.92 8 86 0.98 A Nerage; a lot I I I 1.11 5 61 0.81 6 72' 0.86 At work Not at all! 3 40 I 12 113 I 15' 153 I Little 6 29 3.24I 3 26 ' 1.18 9 55 1.82 A'veragya lot 1 29 0.46' 0 19 0.0 1 48 0.19 During travel', Not ~ at all 8 101 I 28 238 I 3& 339 1. Little 1 16 2.'06 2 51 0.33' 5 67 0.64I Average/a lot, 0 13 0.00 0 13 0.00 0 26' 0.00 Trend (negative) P <0.05' During leisure Not at all 3' 45 I 15' 116' 1 18' 161 1 Little 4' 48 1.12 14! 107 1.05 18 155 1 L 06 Average/a lot 5' 39 3.18 2' 95 0.18' 7 134 0.59 Trend (inega t i ve) P<0.05 Combined index' Seorr 0-1! I 27 I 10 75 1 I l 102 1 Score,2-4 7 55 4.34 5 61 0.63 12 ' 116 1.08 Score 5'-12' 2I 15 3:20. 0 21 0.00 2' 36 0.50 Spouse smoked man. cigs:,in last 12'month's No 101 105 ' 1 20 193 1' 30 298 1 Yes 2 29 0.96 11 122 0.76 13 151 0.79 Spouse smoked man: cigs_ in whole of marriage. hlb 7 93' 1' 13 89 1 20 182 I Yes 5 40 2:47 19 229 0.55 ?4~ 269 0.80 Table W " Relationship between various indices of passive smoke exposure, and', risk of lung cancer among lifelong non- smokers (standardiscd for age and, for spouse smoking, whether the marriage was ongoing or endedl' 'Based on sum of 0=not at all. I=little.2=average,3!=a lot forat home, at work, during, trawel; during leisure: Discussion Over the pasv 4 years therc has been considerable research intt:resu in the relationship betwccn passive smoking and risk of lung canccrr in nonsmokers. Whilt some studies have claimed a positive eflfcct' (Hirayartta; 1981; Trichopoulos er al., 1981: Correa er' aL, 1983;' GarJinkel er aL.. 1'985; Gillis er al:. 1984; Knoth er' al:, 1983), others (EiuMcr r•r al:, 1984, Chani 1982; Garfinkcl, 1931; Kabat and Wyndcr, 1984; Koo er al.'. 1984) have found no significant relationship. Relative risks of lung cancer for non-smoking women married to smokers compared to non-smoking womcni married to non- smokers range from somewhat over 2 in the Trichopoulbs and, Correa. studies to around' 0.75 in thc: [ivf(ler and Chan studies Thc:«scightcdl relative risk from, thcsc studics has been estimated by us as approximately 1.3. While thcre is: thcrcfiorc, a tandoncy fior a small positivc assoriarion between passive smoking and lung cancer, recent reviews of these data (,Lee. 19'84;, Lchnert el al:. 1!984) have concluded that overall there is no reliable scicntiCic evidence of' al causal relationship between passive smoking, and lung canccc In thcsc reviews a number of gcncral points havc becn made. First~ d'osimctrie studies havc shown that, in cigarcttc-equivalcnt terms, passive smoking only results in a relatively small cxposurc to the non- smoker. Hugod el al: (1978), for cxample, showed that even under quite extreme conditions the time taken for a non+smokcr to inhale the equivalcnt of o 1m 1 1 M

102 P:Rii LEE et'al. Table V Relationship between two indices of passive smoke exposure and risk of chronic bronchitis, ischaemic heart disease and stroke among lifelong nonysmokcrs (standardised for age and; for spouse smoking. whether the marriage, was ongoing or ended) ~ Passive smoke Ufafe patients Female patients Sexes combined' exposure ind'ex/lerrf fiases Controls R Cases Conrrofs R Cases Controls R Chronic bronchitis Combined index' Score 0-1~ 1 27 11 7, 75 1 8 102 L Score 2-4' 2' 55 0:81 4 61 1 M ' 6 116' 1.00' Score 5-12' 1 I'S 1.90, 1 21 1.03' 2' 36 1.30 Spouse smoked man. cigs. in whole of marriage. No 8' 93 1 4 89 ., 1 12 Ib2 1'. Yes 1 40 0.34 13' 229 1!22' 14 269' U3 f3chaemie heart disease Combined index' Score 0-1 15' 27 1 23 75 11 38, 102 1 Score 2-4 l2 55 0.43 9 61 0.59 21 116 0.52 Score 5-12 3 I5 0.43 4 21 0181 7 36 0.6'1 I Spouse smoked'mand cigs. in whole of marriage No 26 93 I 22 89 1' 48 182: 1 Yes 15 40 1.24 55 229 0_93 70 269 IA3 Stroke Combined index' SQore0- 1, 5 27 1 19 75 1 24 102 1 Score 2-4 Score 5-12' 10 4' 55 15 I'.24, 1.77' 10 7 6',11 21 0J96 26" 20 U11 1!16 36 0.97 2.18 Spouse smoked man: cigs. in µfio'Irof marriage No 18 93' li 119 89 1 37 182 1 Yes 6' 40 ~ 0.84 49 229 0.92 55 269 0.90. 'Bhsed on sum of 0=not at all. 1=dittJe. 2=avcrage. 3 = a lot for at' home, at.work: during travela during leisure. one cigarcttc would be Ili hours as regards particulate matter and 50 homs as regards nicotine. Similarly, Jarvis er at: (11985) havc shown that the increase in salivary cotininc in relation to passive smokc cxposurc is less than 1%o of that' in relation tv o.iivc smoke exposure. ExtrapolatinglincarJyfrom the 104bld relative risk of lung cancer in. relation to active smoking would1 thcrcforc prcdict a relative risk in,rclation to passivc smoking less than 1.14 while a quadratic extrapolation, as suggestedl by Doll and Pcto (1978) would predict a lower risk still. The conflict bctwecn the dose and the claitned rt;sponse is particularly clear for the results of Hirayama ('1981) who found a similar effect on lung cancer for passive smoking as for active smoking of 5 cigarettes a day. Second; all the studies sufferfrom wcak cxposuro data, most studies only obtaining information on the spouse's smoking habits and none obtaining objective data by measuremenu of ambiont' ld vcls of smoke constituents in, the ain ot the home or workplacc and/or of concentrations of'constituents in body fluids. Third, no studies adequately take into account the possiibility thau misclassilecation of active crnnkrts as nCn-sr.tokcm may haYU consistentlyy biased relative risk estimates upward. Active smokers havc a high relative risk of lung cancer and spouses' smoking habits arc positively correlated. Because of this, it cambc shown that if a, relatively smaJll proportion of smokers deny smoking; this results in an apparenP' elevation in risk of lung cancer in 'non-smokers' married to smokers compared to 'non-smokers' married to nontsmokcrs, even when no true cfficct of passive smoking exists. A demonstration that this source of bias is of real importance cani be fbund in i the study of GarGnt.cl et aL ('1985), Based on, unvalidated smoking data taken from hospital notcs, a relative risk of lung cancer in relation to husbandis, smoking at home of 1.66 was calculsttcd; with relative risks oP at least 1..3 seen, in relation to each J. .

PASSIVE SMOKING AND SM JK'J1G-i2ELATED DISEASES 103 0 level of husband's cigarette smoking and in rclhtion to husband?s, cigar and pipc smoking: When additionali sources of information on smoking habits wcrr used; the overall relative risk wass reducedi to a marginally significant 1.31i with an elevated risk only really discernible in relation to heavy cigarette smoking, by the husband. Even hcre, it is notable that the elevation in risk was not cvidtnt when smoking data werc obtained from thce svbject' or her spouse direct0y, but was only evident when the data were obtained from the daughter or son or another informant, i.e. from, those people who were Icss• likely to have known the full', smoking history. The lower relative risk may still have arisen wholly or partly as a bias resulting from misclassi(ication of smokine habits. Fourth, many of the studies arc open to specificc criticisms: For examplc; the conclusion of Gillis rt aG (1'984) that male lung cancer deaths in nonr smokcrs rose from. 4 per 110:000 in those not exposed to passive smoke to 13 per 10.000 in tihosee who were exposed was based on a total of only 6(!) deaths and was not statistically sienilitcant. A9'so the claim by Krpoth eraL ('1983), of ai rclationshiR between passive smoking andl lungcancer ini non- smoking women was based simply on the observation that the proportion of female non- smoking lung cancer patients living together with a: smokcr exceeded the proportion of male smokers as reported in the previous microcer,sus, ignoring inter atio the fact that in many families women live with more than just their husbands. In the present study no significant'rclatirnnship of passive smoking to lung,canccr incidrnce in lifelong non-smokers was seen, either in the analyscs based on the information collcctcd' in hospital', or, in subsequcnt inquiry of thc spouses or ho1h. lt; must be pointed out, however, that the number of lunc cancer, patientswhar had never smoked «•tiurather small so that, thougK our findings arc consistent with passive smoking, having no effect on lung cancer risk at all, they do not cxcludc the possibility of a smallY increase ini risk, though the upper 95% confndence limit of1.5b for theestimatcof 018C0 (Table IW) in relation to the spouse smoking, dutin'g the whole of the marriage is not, consistent with some of'thc larger increases claimcd: by Hirayama (198;1, 1'98A) TrRchopoulos er ral: (1981, 1983) an&Corrca et al. (1983). Though the number of lung cancer patients who had', never smoked is small, varying around 30-50 depending, on, the analysis, this number is not very dilTercnt from that reported in a number of other studies, e.g. the findings of Corrca, et al, ('1983) wcrc based' on only 30, while those of TriehoPoulos en a!: (l981II); even whcw updated (Trichopoulos et, aQ, l!983')laxrc hascdi oni 77. The difficulty of obtaining an adequate sample size is underJined tnccni one consid'crs that, in our study the 44 nc%-cr smoking lung cancer patients who completed passive smoking questionnaires in hospitaL were extracted from, a~ total of 792 lung cancer patients. It would need a very large research cfTfort to increase precision substantially, andi cven then one would have to take care that the magnitude of anyy biases did' not exceed thc magnitude of the cfPc-t one was looking for. The two majon prospective studies whichi have so far reported findings on passive smoking (Hlirayama, 1981; Garfinkel, 1'98'1) were not, actually designed to investigate this issue and, as a~ result, could'.only use spousc's smoking as an index of exposure. Our study, on the other hand, though not' abic to monit~or cxposurc objcctivcly, as would have becn prcft rablc, was able to look at passive smoking in a wider context, by asking about the extent of exposure at home, at' work, during travel and at leisure. Although the answers to these questions were subjective, and could' havc exhibited some bias, th¢ir inclusioni perhaps allows greater confidence in the conclusions. It was interesting that, of the 59 patients for whom spouse's cigarette smoking habits werc obtaincd' from both the spouse and the paticnts, there wcrc 9(15°Jb): patients for whom there was disagreement as to whether the spouse had been ar smokcr at some time during the marriage. It seems~ rcasonablc to suppose that somc of these were in fact smokers and may have been crroneouslv classifucdasnbn-smo4:crs had otelyone source of information been uscd. It was also noteworthy that there was quite a~ strong correlauionm in our study bet%%•cen activcandInas;civti smoking. A~sillustratcd in Table V7, current smokers were considerably more likely to be exposed to p:rssivc, smoke exnosilreat home (~from sources mthcr nh;tn thcir, own cigarettes),than were never or ex-smokers. As noted albovc, thiscorrclhrtion, coup9edl withsomernisclassilication of smokers as nonrsmokcrs, may spuriously in(lalc, the estimate of risk rcladcd to passive smoking. It is important to carry ouP further studies~to obtain more accurate information on rcliability of statements aibout smoking, habits because of this possibility of'bias. Little other evidence isawlilable concerning the relationship between passive smoking and risk of the other smoking-associatod diseases in (adult), non.smokcrs andl much of this is open to criticism. ln his original papt:r, Hiir:lyama(4'98'd)1 presented relative risks of death for various diseases for non- sm>aking, women accbrdin& to thehusbamd'ssmoking habits. Based on al total of 66 deaths, a slight positive trendl for, emphysema and' asthma was not signifcant; while, based on a total of 406 deaths, no indication of a trend ao all was seen for ischacmic heart disease. )ni a later paper, bascd' on

104 P:N. LEE ri nl. Table VI Relative odds af having passive smoke exposure at home according to paticni owni manufacturcd' cicarette smof:ing habits (standardised for ace: base - «omhincd class I' and 2lcontrols) Rc/ntii•c ntld.s (9s",. ennTdrnce linritsl Onn .vnnkinR hcthits. ,11nlc Frnialc Never Ii 11 Ex 1125(0.86-1.81) 1.26(0:815-1.85). Current 4:00(2:67-5.98) 2.51 i(1.7!U-1621. Chi-squared for trend'(i2 df) 57 ' '81 _'5:3 t P <0.00 t i <'0.001 only a fiurthcr 88 ischacmic heart disease deaths. Hiiravama (1984) reported a slight positivc trend in risk. but this was not statistically significant. Garland cr al: (,1985). in a srnall prospective study, reported a lb-foldl higher risk of ischacmic hcart disease in non-smoking CaVifornian women %%-hose husbands were current or former smokors compared with those whose husbands wcrc never smokers, but this enormous and implausibl'c relative, risk was only signircant' at the 90%confidence level and had very wide confidence limits, being based on only 2 deaths in womcn whose husbands were current smokers. Sand)cr er al. (11955). in a casc-control study carried out' in North Carolina; reported a strong relationship btaw,ocn risk of cancer of all sites and' passive smoking. This study has been criticised' by Lee (1985) who notcs thcu, it is basically implausible thart passivc smoking should increase risk' of cancers not associutc& with active smoking. Lee also criaiciscd the method of anaVysis; showing that no association with cancer risk would be found if a more standttrd mcthod of analysis was used. Vandcrbro,tckc cr el: (1984). batsed on a 2S ycar follow=up of I.0'70, Amstertl;unti m;tr~ricd crnuplbs, rccentVy reported that, passive smoking wass associated with some decrcase in total mortalitv. There is evidence indicating that' young childbcn, whose parents smoke have an excess tncldcncC' ol respiratiory,' symptoms and some rcdhctirnn in pulmonary function. Reviewing this evidencc, Lee (1984) noted that the interpretation of the association is fraught with difft:ultics and that other possible explanations, including sociall class related factors, parental negelCt. nutrition. cross- infection and smoking, during pregnancy. had not been taken into account adequately, so than a causal effect of passive smoking could not b¢ inferred. The rclbvancc of these fondir.gs to chronic bronchitis or other diseases in adults is in any case not clear. Our ana9yscs showed no sigrrnificant effect of passive smoking on lifelong non-smokers as rogard5 risk of chronic bronchitis. isehaemic heart disease or strokc: In all the analyses rclating the various indices of passive smoke exposure to thcse diseases; no significant' differences were seen and slighi dbcreases in risk were as common as slie'ht' increases. While more data would be desirable for these diseases, lung cancer continues to be the major smoking associated disease for which passive smoking comes under suspicion. Since all the diffieulties~ of carrying out, good research have clearly still not yct' been osercome. furthcr rescarch is certainly needed. Our findings appear co'nsistentt with the general view. based' on all the available evidence. that any effect of passive smoking on risk of lung cancer or other, smok,ing-associatcd diseases is at most'quite small, if it exists at aIl! The marked increases in risk noted in some studies are moree likely to be a result of bias in the study design thar, of a true cfficct of passive smmking: Any viiws ecprc.csed'in this papcrarc those of the authors and not of any other persnn or companv,:. This study was funded by the Tobacco Research Council /inmv TnNrtccn ^dvisncy , rC*•'^cil).. ... ':!- ..... .._ ..._ ..,.,.... gratcful. Dr Alderson was the holder of thc C:ancer Rcsoaroh, Campaign endowed Chair of Epidemiology at the Institute of Camcer Research during the periodi of thc study dbsignand field work. N1t: I:, Marks from Rcscarch Surveys of Great' Britain provided!advicc in the planning phasc and was responsiblc for the intervic+vcrs"%ital contribution to t'hc study. Wc thank the many clinicians at the 46' participating hospitals who pcrmittctll us to contact their patients andi all the patients andispouscs'w'ho answered the questions. Dr R. Wang. who held:a British Council award for the pcriixl 1980-1983. as well as a numbcr of otbcr colleagues pron•idodiuscful'advice auv-arious stages of th'c study. Mrs B.A. Forcy pro.ddLdl invaluablo` assistance in carrying out the statistical analyses. a

t tr Rekrences PASSIVE SMOKING AND: SMOIEINK3•RELATED DISEASES 105 ALDERSO\, M.R.. LEE: P.N. & WANG. R. (198'5). Risks of lung cancer, chronic bronchitis. ischacmic heart disease and stroke in relation to type of cigarette smoked. J. Epid.:n. Comm. Hldr., 39„286. BR&-,LOW: N.E. A DAY. N:E. (1'980): Statisrical.lftthods in Cancer Research Vol 1- The .lurall:cis of Case-control' Stndies. International Agcncy for Rcsearch on Cancer; Lyon.. BUFF1iER. P.A., PICKI:E. LW.. MA'SON; TJ; & CONTANT. C. (1984). The causes of lung cancer in Texas. In Lung Cancer. Causes and' Pres•ention, Mizell, M. & Cornea; P. (eds). Verlag Chcmia;lnternationallnc: CHAN; W.C. (1982). Zahlen aus Hongkong. Munch, ,Sled. Woch., 124;,16'. CORREA. P.; PICKLE, L.W., FONT}tAM. E:., LIN. Y. & HAENSZEL, W, (1A83). Passive smoking and lung cancer. L:ancet, ii, 595. DOLL„ R: R' PETO. R. (1!978)j Cigarette smoking, andd bronchial carcinoma: dose and time relationships among regular smokers and lifelong non-smokers: J. Epidem. Comm. HJth, 32, 303. GARFINREL, L. (1981). Time trends in~ lung cancer mortality, among, non•smokers and a note on passive smoking. J. Narl Cancer. Insr:, 66, 106:1. GARFINKEL„ L. A~USRBACH. O:, & JOUBERT, L. (I1985): Involuntary smoking and lung cancer: A case-control study: J. Natl Cancer lnsr.. 75, 463. GARLAND, C., BARRETT-CONNOR, E:,, SUAREZ, U., CRIQUI, Nt1H. & WINGAR'D, D.L ('1985). Effects of passive smoking on ischemic heart disease mortality of non-smokers. A prospective study. Amer. J:, Epidem., 121, 645. GILLIS. C.R., HOLE; Da., HAWTHORN$: V. `t. & BIONSLE, P: (1984); The effect oi environmental tobacco smoke in two urban communities in the ..rost of Scotland. Europ. J. Rcsp: Dts:. 65, (Suppl. 133);,121. HiIRAYAMA, T. (1981). Non.smoking wi+-cs of lcavy smokers have a higher risk of lung canccr: a study from Japan. Br. Alyd, J:, 282, 183. HIRAYAMA, T. ('J9ivi). Lung ",,... in Japnn! effects of nutrition and!passive smoking. In Lun,g C'ancrr, Caucrs and Prevention. Mizell, M. & Correa. P: (cds). Vcrlag Chemie International Inc. HUGOD. C.,, HAWKINS. L.H. &' ASTRtJP. P. (1978). Exposure of passive smokers to tobacco, smoke constitucnta.,lnl: Arch. Occup. Enriron, Hlah. 42, 21. 1FARVIS: M.J:, RUSSELI.., MLA.H:. FEYERABEND: C. & 4 others (11985). Passive e:iposure to tobacco smoke: saliva cotinine concentrations in a representative population sample,of non-smoking school-children. Br., b'led.' J:, 291, 927: KABAT. G;C. & WYNDER, E1L. (1!984):, Lung r.tncen in non•smokers. Cancer.,53. 1214. KI:OTH;, A., BOHN;, Hi g: SCHMIDT. F: (1983). Passive smoking; as cause of lung cancer in fcmalb non- smokers. Med 1Clin., 78, 54, K'OO, L.C.. HO, JH-C. & SAW;,D: ('1984). Irpassivrsmokings an, added risk factor for lung cancer in Chinese; women? J: Exp. Clin. Cancer Rcs., 3„277., LEE. P.N. (1984). Passive Smoking. In Smoking and the Lung. Cumming;, G&[ionsignore, G. (cds): Plenum Publishing Corporation., LEE. P.N. (1985). Lifetime passive smoking and cancer risk. Lancer. i. 1~4t4. LEHNERT. G.. GARFINK'EL. L.. }I9RAYANtA, T. & 4 others. (1984). Round table discussion. Prrr. AGcd. 13. 730: S.aNDLER; D:P., WILCOX; A.J. & EVERSONI R'.B. (1'935). Cumulative effects of lifetime smoking on cancer risk. l:arrcrt, li 312. TR9C}IOPOULOS, D:, KALANDIDI, A., SP7ARROS, L. & MhcMAHON, B. (1981). Lung, Canccr and passive smoking. Int. J:,Cancer, 27, I., TRICHOPOULOS;, D.. KALAND'IDII A. & SPARROS, L.. (I1983). Lung cancer and passive smoking: Conelusion of Greek study: Lancet; ii, 677. VANDERBROUCKE, J.P.. VER1}EESEN;J:H.H., DE,BRUIN, A.,, MJ4tJRI'iZ„ B.1:, VAN DER IIEIIDE-WESSE9., C. & VAN DER F3EID'E„ R.M. (1984). Active and passive smoking in married couples: results of 2'5' year follow up. Br. Mtd: J:. 288, 1i081..