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•~,,,... .. .. : __ , . ~ . 4 11 ar 1: C.nrrr 11996). 54 97,105 Relationship of passive smoking to risk of lung cancer and other smoking-associated diseases P.N. Let,' J'. Chamberlain & M.R. Aldersont lattrta<tr of Cancer RrscorrA. Cli[ton Road. Balmoru, S.rrrty: UK. Srraae7 In the tanen pan of a large hosptut osc<ontrol study of the estauonship of typc of auprettc smoled to rssk of v.rsous s+nok~n~•aswcratod d~sosa. patrcnts snswerod questwns on the smoking haMes uf; their first spouse and on the extent of pawvc smoke exposure at hornc, at work. during tr-ivcl and dunng leisure. In an eatens+on,or this study an attempt was madc to obuin smoking hat„t dau diroctly from thc apouse of all lifelonj non•smokmg lung on¢r easa and of! two hfelong non-smoking matched controls for och ax. The attempt wst made regardless of whether the pauents had ansivered twssive smoking quartons in hospui'or not. Amongst lifelong non-amokers, passive smoking was aot associated with any sttnofiont incrnse in rnk of luna onxr, ehronic bronchttu, isclwemrc heart disease or stroke tn any analYs.s. Limiutwro of p.st studies on passive smoking ars discussed and the naed for further resnrch undeHincd. From all the availabk evidence. it appean that any eReet of paatve smoke on~ risk of any of thc tnayor, dueasa that have boen atsoctated with active smoking is at most tr+nalL and may not eais+ at all. Srudy of hofpital ii-patirntt In 1977 a large hospital case-control was initiate& to study the relationship or the type of cigarette smoked to risk of lung ancer, chronic bronchitis. ischaemic heart disuse and stroke. This study was nrried out in 10 hospital regions in England; interviewing ended in J'anuarv 1982. The onginal questionnaire did not include questions on passive smoking as it was not considered an important issue in 1977. However„ in 1979 it was decided to extend the questionruire to cover passive smoking for mamed patients for the last four regtons to begin interviewing. Subsequently, in 1991. following publication of the papers by Hirayama (1981) and by Trichopoulos er ol. (1981) elaiming, that non- smoking wives of smokers had a stgnirteantly greater nsk of lung nnctr than non-smoking wives of non.smokers, it was decided to increase the number of interviews of married lung aneer tsses and' controls. The extended questionnaire was then administered to these patients in all hospitals where interviewtng was still continuing. follow-rp stadi• o,/tporrxs of wnn-srnol:ing baspuaf it-potientt In 1982. after interviewing of hospital in-patients had been completed. it was decmded to carry out a follow-up study. In tbis swudy, an attetnpt was Corrsspondencs: P.N. tsc. 'Pteent addtess: 25 Cadar Road Swton Srney. SM2 SDG. tPresent nddrns OQocit of Popylauon C.ensura and Sut+eys. St. Catbenne's Ho.ee. 10 Kinp+ray. L+ondat wCZe uP. made to interview the spouses of all of the marricd~ hospital ip-paticnts with lung cunccr who rcportcd' never having smoked, as well as of two marricd~ norrsmoking controls for cach of thcsc indcx lung cancer nses. The follow-up study was intendcd partly to compare information on spouscs' smoking habits obtainod first-hand with that obtained; second-hand during the in-paticnt intervicws. and partly to obtain some data on spousts' t:mokinL habits for those p.ticnts who had not answered passive smoking quesuons in hospital. This papcr eonecntrates sokly on the issuc of passive smoking in lifelong non-smokcrs. Rcsults relating to type of cigarette smoked arc discribcd efsewhere (Aldsrson et ol.. 19g5). while a dctailsd ieport, availablc on rtquesn from PNL. considers the overall findings from this asccontrol study. Metliods and res'otee St1dy of hoJpt70F M-pQlKntd For oeh of the 4 index diagnoses (lung onc-r ehronic broncliitis, ischaemic heart diseasc ar.,: atrole), the intention was to interview 200 cases and 200 matched' controls in each of the eight sex/age alls (i.e. mak or femak, and aged lS-4a. a3-34, 33-44 or 65-74). This gavc a target of 1~2go0 patients, though for some otegorics (c.g. young femak chronic bronchitics) this would be tsnattainabk. Patients were selected from medical (iaduding elsest medicine). thorac;c surgery„ and tadiot#tcrapy wards. Conuols werc paticnts without one of lti,c four index diagnoses. individually matched to tasa on .ex, age, hospital region and. tn The Maanillan Precs t.W:. I9ZS6

M [.N LEF.rs! when possibk, hospital ward and umc of interview. Subsequcntly, when final~ discharge diagnoses became available. thcy were used to reallocate cases and controls as naessary. Patients without a final diagnosis kept their ysrovisionali diagnosis. Where changes in easecontrol status occurrrd; patients were regroupcd into new case-control pairs as appropriatc. With the assistance or Sir Richard Doll and Mr Rkhar& Pcto„ nori-indcz diagnoses were elassified as follows: class IA 'definitely not smoking assoeiated' class IB 'probably not smoking associated' class 2A 'probably smoking associated' elass 2B 'definitely srnoking associated' Controls with no final diagnosis were considered class IB Overall, thcrc were 12,693 interviews carried out which resulted in 4.950 pairs with class I controls and 7?0 pairs with class 2 controls. There were 3.932 interviews of married cases and controls where the passive smoking questionnaire was completed In order to avoid substantial loss of data, duc to one member of a pair not being married or not completing the passive smoking questionnaire, i1 was dbcided to ignore matching when analysing the passive smoking data and to compare each indcx group with the combined controls. Plumbcrs by sex and ase<ontrol status am givcn in Table k. Table I Numbcrs cf m3rried hospital in-pstii:nts completing passive senoking questionn.ires M.le Feoalc Total' Lung unar 547 245 792 Chronic bronchitis 182 tft 266 kscharmic liean, disease 286 221 507 Stroke 161 137 296 Controh Cbs. IA and lB' 839 713 1,352 Clsu 2A and 2B` 26S 149 417 Total' 2.2E3 1Sl9 3.832 'Othcr diseaxs were eiascified by defrts of .moking asaocistun+ - class IA. dirfiniiely wotl eius 1!. probably aot; class 2A probably. ciasa 2B definitdy. _ In the passive seno.rn$ p.rt of the questionnaire, patients were asked when the marriage started; if and when it had tnded; the number of manufactured cigarettes per day tt+noked by the spouse both during the last 12 months of enarrisge and also at the period of maximum smoking during thc marriase: and whethcr the spouse ever regularly, srnoked hand-rolled aagan:ttes, cigars or a pipe during the marriapc. For smnd or subsequent onarrisges„ questions rttsted to the frrst surriage to give the longcst latcnt interval between exposure and discase onset. The patients were also asked to quantify, according to a four-point tcak (a lot, average, a bttle, not at all), the extent to which they were regularly exposed to tobacco smoke from other people prior to coming into hospital in 4 situations: at home: at work; during daily travel; during leisure time. In the main, questionruire, detailed questions were aakcd~ on smoking habits and on a whok range of possible confounding vatiabks.. Follo»-up srydj oJspot<sea oJnon-smoking liospilol Y!-PorKAJf From the hospital study there were 56 lung cancer cases who reported being lifelong non-smokers, who were married at the time of intervicw and who were not known to have been married previously. In a follow-up to the main study, an attempt was made to interview the spouses of these 56 cases and also the spouses of two life-long non.smoking controls for each ase, 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 wcrc available, thosc interviewed nearest in time to the case were seleeted'. Where suitablc controls in the same hospital were not available, those in the nearest hospital were chosen. Because names and addresses of the patients were not recorded in the hospital study, it was necessaryy to go back to the hospital both to obtain this information and also to get permission to interview their spouses. Following some refusals both by the hospital and by the spouses, successful interviews were obtained from spouses of 34 cases (10 wives and 24 husbands) and 80 controls (26 wives and 54 husbands) whose condition was definitely or probably not related to smoking.. Interviewing was earried out between July 1982 and August 11993. The spouses were asked about their consumption of manufactured eigart:ttcs, cigars and piprs (a) no+.•adays, (b) during the year of admission or the patient or (c) maximum during the whole or the marnagc. The spouses were not asked about the smoking habits of the index patient. Thc spouses wcrc also asked questions onn agc. occup:rtron; social class and' a range of othcr potential confounding factots. Slorfsricol rwrtllods The statistical methods am based on classical proaedures for analysis of grouped data dcnved from casccontrol'i studies (Breslow & Day. 11980). In gencralj the mstenst has becn examined as a 2./t r S ubk, with /l" representing the levels of the

... .. .,.. ... . . . -, . ~„~. .,.M. ,>...,. PASSIVE SMOKING AND Sr.tOK1NCS•tllf.GATLI) f)ISFASFS ~9 , I risk factor of intcrest and S the number or strata used to takc account of potential confoundcrs Results presented arc for thc combined strata and show the rcbtue nsk (Ivtantcl-Hlacnszrl estimate) together with the significancr of its diffcrcnee from a base kvcl,(nsk 1.0). and/or the dnsc-rclated trend. In analyses fof the data collected in hospital. comparisons arc made hetwcen o%cs with a particular indoru discasr and all the controls with diseaxs dsf,nttcly or probably not relatcd to smoking. Stx simple indices of pastive smoke exposure were considered in these latter analyses,. (i)-(tv)eaf+osurc at homc, at work. during Iravel, during leisure. (v) spouse smoking manufactured eigarettes in the Liu 12 monrhs, and (vi) spouse smoking manufacturcd c3garcttes in the whole of the marriage. Bases for (n) arc rtoduxd as not all patients worked In addition, a combined index of .passive smoke exposure was akulated' by the unwrighted sum of the four individual exposure indices (iHiv)!, counting 'noo at all' as 0, 'htrk' as 1, 'average' as 2 and 'a lot" as 3. Rewlts (Anra ton"r The follow-up study concerned 56 lung cancer asa and 112 matched controls who reported never having smoked in their hosrmtal intcrview: Of thrsc„ there were 47 cases (I',S male and 32 (cmalc),and 966 controls (30 male and 66 (cmale) for whom some information on smoking habits of their s(ouscs wass available. Of these 143 patients, informatiam, on spouse smoking was available both from the spouse and from the patient for 59 (4 l'/.), from the spoucc only for SS (3RS:) and from the patient onl) for 29 (20'/.). Table 1f shows the estimated aFe-ad)usted relative risk of lung cancer in relation to spouse smoking during the whole or the marriage. b) scx, sournc of data, and period of smoking. None of the 9 relative risks shown in the table arc statistically significant. When data for both sexes and hoth sourea arc eonsidered, the estimated relativc riskss in relation to spouse smoking arc close to I().11). For individual' sexes or sources, wherc numbers of ases and' controls are smaller, relative risks varyy more from unity, but no consistent pattern iss evident. Similar conclusions were reached; whenn analyses were based on smoking during the year of hospital interview. Herc, the overall relative risk was again close to 1(0.93 with limits 0.11-2.09): Table II1 summariscs concordance between stsoust's manufactured eigarctte smoking habits as reponed' directly and indirectly for the 59 patients with data from both sources Discrepancies were seen for 9 spouses (1 Y/.) in rrs f+ect of smok mE a t some time during marriage and in the c:usc of 2 Talik 11 Relauonshrp bet+reen spouse M manuf.ctured cigarette srnotinf dunng the whole of the esarruEc and risk of IunE nncer amon= lifelong non-smokers Ittandardised for aEel, S/+iasr did anr awrnLr Spnwr awso)<ed Src of Rr)otrnr risl, pnrnr Casn Cownol! Cavs Cnwrrd! (9s:, fururs) aosrl on mrrrrrra af tAr s/msr a JalMr.-ry arly (1!l pwwry Male S 13 S 13 II.0110.23J 111 Female S 16 19 39 1.60046-S.7M) Combined 10 29 24 31 , Ii.33t0.S0-3abt 8osrd on iRtrrnes of tM iwtfrs prit•w u bsrieaf (Jbf prinos) Mtale 7 IS 5 7 1.33(0:37-6:34) Female 9 17 a 20 0 73(0 7a• 240) Combined tb 32 13 27 1.001041-2a+t) aosrd on fwNA swarn af rforwmmierr (IIJ' Rritats)" btak 7 16 8 14 1.30(0:38-4.391 Female 10 21 22 45 t.0M0:37-2.71) Combined 17 37 - 30 S9 1.t1t0.S4-2.)9) 'tlnlr oontrols mduded' in totbw-rp study aons+deoed; a/a this aualyvs t!c spouse was c+ountcd as a s:rtwEn if reponed to be so either dinsttt„ by the spouse durin= follow-up interview, a, indiraetly, by the patient, ie 6ospitaP Note that she 59 patients for .hom informatoon oa spouse smoking was avaitaWc horn both sources are rnduded in all 3 analysa

ton: r N t.rr R,.,r T.Wf IlI Cnncnrdance het.ren spnusr'i manufactured ciprettc smntinE haMts as rttTx+ned s . directfy and mdirertty Sex Of ROfiInr/tC.V ronlroj.IIarYS Mdr Fc+wnlr Carrr Cavroit Ca.rs Caurols Total Sl+ousc a smokct snmetimc in rnarri.IC acrnrdrnR Ib Subject and spouse 2 6 S 113 26 Only suh)ert 1 0 0 3 4 Only spoure I 1 3 0 5 Neither 3 11 1 9 24 % sub7ect;spousc sEracmcni 71% *r/. 67% :a'i =s% Spouse a smoker durinE ycsr of hospital intcrrier accordint to: Suhject and spouse I 6 2 4 13 Only , sublect 0 0 0 1 1 Only spnuse I 0 0 0 I Neither S 12 7 20 44 % suhlen/spouse agresmcnt 86% 96% 1OOy 100;; %% 9T„ spouses (3%) in nes(+cct or smoking during the year of hos;+ital intcrvicw. There was no consistent pattern in the direction of di.crcpancy. Table IV summanscs the results of analyses carried out rehating 7 indices or passive smoke exposure recorded in the hospital interviews to risk or lung canccr among Iifcleng non-smokers. Hcrr the controls used for comparison arc all never smoking patirnts with diseases classified as definitely or probabSy not associated with smoking who completed the passive smoking questionnairc. Overall the results showed no evidence of an effect of passive smoking on lung cancer incidcnce among lifelong non-smokers. In mak yratients, relative risks were increased for some of the indices but numbers of eases were small and none of the differences a(+l•roached statistical significance. in femaks, where numbers of cases were larger, such trends as esisted tended to be ncFativc and indeed were marginally, significsntly negativc (P<0.05) for passive smoking during travei' and during k;isure. For the combined seses no dilTerencxs'or trends wert statistically significant at the 95% eonfidcnee kvcl; such trencfa as existed tending to be slightly ecg.ativt. The relative risk in rclation to the spouse smoking during the whole or the marriage was estimated to be 0.80 for the sexes combined, with 95% oonfidcnoc iimits of 0.43 to 1.50. Stindardisation for working in a dusty job, the variablc al+an from smoking found to have the strongrst association with lung cancer risk in the analyses described in Alderson cr aL. (1985), did not affect the conclusion that passive smoking was not associated with risk of lung cancer among never smokers in our study. Chronic bronchir'u, isdwe.nio Aro.r disease and srrolcr Analyses similar to that shown in Table IV for lung cancer were also carried' out for chronic bronchitis, ischaemic heart disease and stroke. Illustrative results for two of the indices ars presented in Table V. No significant relationship of any index of passive smoking to risk of the 3 diseases was seen.. For the scsa combined, the relative risk in relation to the spouse smoking during the whole of the tturtiage was 0.83 for chronic bronchitis (9Y/% confidenee limits 0.31-2.20), 1.03 for ischacmic heart disease (limits 0.65-1.62) and 0.90 for stroke (limits 0.53-1.52). For stroke there was, in both scses„ an approximate 2-fold incrcasc in risk for patients with a combined passive smoke indci that was high (score of S to 12) compared with those whers it was low (score of 0 or 1). However. •usnbrrs of cases with a high score were low (14 saaks and 7 femaUes) and evrn for the scaes oombined, thc relative risk estimate of 2.18 was not statistically aignificant (limits 0.86-5.48):, In interpreting this tnding, it should be aoted' that aetive smoking was not found' to be ekarly related to strokc in the main study (Aldcrson irr oJ.. 1965), rendering a two-fold irtcirsisc in relation to passive smoking a priori unlikely. - ~ T

PASSIVE SMOKING ANi2 SMUKtNG-Rf.IATF.D DISG/ASES 10t' • TaY1r 1N ' RclatMnshir txt.ern vanous indran of Isassive t+mr+kc calwxurc and nsk of lunp cancrr amonR hktonP non- tmOkrra titandardisn! G.r aFc and; lot spouse smokini .hcthcr thc tnarnaFr .a+ onBiwnE or cndeJl Pauur s"r Alofr ravets ftw.alr prwnrs Srtn rrnwArr.rl tx/rnrrr ndr r/Itrr1 Cav. • Cnw,rnlr R rav~ lr'nnrrmJ.i R fi'avn Ctwtrofs R At home Not at all 9 1'01 1 21 192 I V 29) 1 Lrt tle 2 21 132 6 65 092 8 36 09% AveraEc/a lot I IIt, 1.11 5 61 0.81 6 72 0.8A At «ork Not at all 3 40 Ii 12 113 1 IS 133 1'1 s . Ltttk 6 29 3.24 3 26 1.19 9 55 1.82 AvcraEo'a bt 1 29 046 0 19 00 1 t8 0.19 DunnB travel Not at all a 10t I 28 239 1 36 339 1 Little 3 16 2.06 2 51, 0.33 5 67 064 AveraEc/a lot 0 13 00 0 0 13 3 000 0 26 0.00 . . Trend (IKgalireJ Pc0.05 i DurinB kisurc Not at all 3 45 1 1'S 116 1 18 161 1 Little 4 48 1.12 14 107, 1.05 18 155 1.06 AveraRe,'11ot 5 39 3.18 2 95 018 7 134 0.59 t _ Trend (negative) Pc005 Combined tndcx' Score 0-1 1 27 1I 10 - 75 1 11 102 1 . Score 2-4 7 55 4.34 ' 5 61 063 12 116 1.06' I Score 5-12 2 15 3.20: 0 21 0.00 2 36 0.50 Spousc smoked man nFs in last 12' months No ~ 110 105 1 20 19z 1 30 298 1 Yes 2 29 096 I I 122 0.76 13 151 0 79 Spouse smoked man op in whok of martiage No 7 93 I I3 119 1 20 182 1 Yes S 40 2A7 1:9 229 0 55 24 269 0.80 'Based on sum of 0- not at all. I - bnk. 2- averaEe. 3-a lot (or at home. aa wnrk, during travell dunnE krsure. . 0 Disctassion Over the past 4 years there has been eonsiderabic tr scarch intcrest in the relationship between passive smoking and risk or lung eancer in nonsmokers. \A'hilc some studies have claimed a positi.e e(iect (Htrayama. 1981; iTrichopcwlos rt al.. 198C; Corrca rr af., 196zr Garfinkel rr al.. 1985. Gi!'hs rt al:. 1984. Knoth rr al., 1983). others (Buflkr et al.. 1984. Chan, 1982; GarfrnkeT, 1981; Ksbit and Wyndcr, 191t4 Koo at al.. 1984) have found no sirnifi,:;.n: : rs5:;.. Pr!_:i,r risks of lung nrKxr for non-smoking womcn married to sawkers compared to non-smoking women married to non- smokers range from somewhat over 2 in the Tnchopoulos and Correa wudies to around 0.75 in the Bufficr and Chan studtes. The weighted nel.livc risk from these studies has been estimated by us as approaimately 1.3. M'hik there is. therefore, a tendency for a small positive assrrriarinn between passive smoking and lung anecr, trooent reviews or thcsc data (Lcc, 19u4. Lch.ncn rt al.. 19841 havc eonctuded that overall there is no reliablc aeientific eridena of a causal relationship between passive smoking and lung eanoer. In thesc reviews a numbcr of general points have been madc. First. dosimctric studies have shown that, in eigarcttctquivaknt terms, passive smoking only results in a relatively small eiposure to the non- ttnwker. Hugod er ai. (N978). for e:ampk, showed that even undcr quite es;trcrnc conditions the time taken for a non-smoker to inhale the equivaknt of

102 P.N LF.FF rrof Tabk W Itclahrmshrp hrtrrecn t.o indreo of ras.sive smoke csposurrr and nsl of chromc brnncMtts, i.chacmic bcan drscasc and strokc amonf liklbnf non•smokcrs (standardrsed for aRc and, for spouse t.mokmR rrhethcr the rnarrwge rras onjioinE or ended) Iacamr arw.Ar - Mofr ptfrruS Frrwa/r purnu Srarn cowLMOW/ t:rw.arr wlra/krr/ Caws Cowtrrda R Caus Conrrols R Casn Coaroh R Chronic hrnwrArt..% . Combined rndcs' Score 0-1 1 27 1 7 75 11 9 102 1 Score 2-4 2 55 0.83 4 61 11.03 6 116 1'.00 , Score 5-12 1 13 1.90 1 21 11.03 2 36 1a0 I Spouse smokal msn eiEs in whok of marciaEe No 8 93 1 4 19 1' 12 112 1 Yes 1 40 0.)4 1) 229 1.22 11 269 0.93 hrhonwir Ararr /iarav ComlMned mck.' Score 0-1 15 27 1: 23 75 1 38 102 1 Score 2-4 12 SS 043 9 61 0.59 21 116 0.52 Score %- 12 3 13 0.13 4 21 0.81 7 36 0.61 Spouse smoked man cip in rrhole of marriage - No 26 93 1 22 E9 1 49 182 1 Yes IS 40 114 55 229 0.93 70 269 1.03 Sirolr Coa+bined indca' Score 0- 1 3 27 1 19 75 1 24 102 1 Score 2-4 10 55 I:1 10 61 096 20 116 0 97 Score 5-12 4 15 1.77 7 21 2 W 111 36 2:1',1 Spouse smoked' man t.ip. in whok of marriaEe No 111 93 1 19 89 1 37 192 1 Yes 6 40 0:ga 19 229 0.92 55 269 090 v "8ased on sum of 0= not at alt: I- httk, 2- averajc, 3~ a tot for at home, at Wor1, dunnE rravel;,dunnE kisurs. one eiprettr would be II hours as regards particulate mancr and 50 hours as regards nicotine. Similarly. Jarvis ei aG (1985) have shown that the incrcasc in sativary coaininc in relation to passive smoke exposure is Icss than 1'".6 of that in relation to active smoke exposure. Extrapolating linearly from the 10-fold rrlauvc risk of lung cancer in ttlalion to aclivc smoking would therefore predict a relative risk in relation to passive smoking less than (.1, while a quadratic extrapolation, as suagested by Doll and Peto (1978) would prodict a bwcr risk still. The conflict brtwtrn the dose and the claimed tssponsc is psnicularly dear for the results of Hiraysms .(1981) who found a similar effect on lung cancer for passive smoking as for active smoking of 5 cigarettes a day. Second', al/ the studies suffer from weak exposurc dsta, most studies only obtaining information on the spouse's smoking habits and none obtaining objortive data by, measurement of ambient levels of smoke eonstiiuents in tlsc air of the bortse or workplace and/or of concentrations of oonstilttrnts in body fluids. Third, no studies adequately take into account the possibility that miselassifiution or active smokers as non-smokers may have consistently biased relative risk estimates upward. Active smokcrt have a high relative risk of lung cancer and spouses' smoking habits are positively oorrelated. Because of tAis, it can be shown that if a relatively small proportion of smokers deny smoking, this results in an opporrnt elevation in risk of lung cancer in 'non-smokers' married to smokers compared to 'tson-smokers' aaarried to non-smokers, even when no trw ttifect of passive smoking exists. A demonstration that this source of bias is of real importance can be found in the study of Garfinkel rr aJ. (1483) Based' on unvalidated smoking data taken from~ hospital nota, a relative risk of lung anccr in relation to husband's smoking at home of 1.66 was okulated, with relative risks of at kast 1.3 seen in relstion to each 11 . .q ..-s..T.:'-Ir _...........r.w.o .....

PASSIVE SMOKING AND SMOKING•RLtJ1TCD DISGSfS tIt i . kvet of husband's cigarette smoking and imrebtion to huchand7s aEar and pipe smoking When additional sourocs of information on smoking habits were used, the overall rclativc risk was reduced to a marpnally significant 1.31 with an elevated risk onl) ttatl) discernible in relation to heavy eigarcitc smoking b) the husband. Even hen:, it is notabk that the elevation in risk was not evid'cnt when smoking data were obtained from the subject or her spouse directly, but was only evident when the data wcre obtained from the daughter or son or another informant, i.e. from those people who were less likely to have known the full smoking history. The lower rclauive risk may still havc ariscn wholly or partly as a bias resulting from misclassification of smoking habits. Fourth, many of the studies are open to speeiftc criticisms. For example, thc conclusion of Gillis ee al: (1994) tthat male lung cancer deaths in tson, smokers r sc from 4 per 10,000 in those not exposed to passive smoke to 13 per 110,000 in those who were exposed was based on a total of only 6(t) deaths and was not sutistically signifiant. Also the claim by Knoth •r at (1983) of a relationship between passive smoking and lung cancer in non- smoking womcn was bascd simply on the observation that the proportion of fernak non- smoking lung cancer patients living together with a smoker exceeded the proportion of male smokers as m-,+oned in the previous microansus. ignoring inrer alio the fact that in manv families women live with more than just their husbands. In the present study no significant relationship of passive smoking to lung cancer incidence in lifelong tton-smoken was seen, either in the analyses based on the information collected in hospital or in .ubsequent inquiry of the spouses or both. It: must be pointed out, howevcr, that the number of lung cancer patients who had never smoked was rather small so that', though our findings arc consistent with passive smoking having no elTcct on lung cancer risk at all, they do not escludc the pouibility of a smalli increase in risk, though the upper 9S°/% confidence limit of 1.50 for the estimate of 0.E0 (Table IV) in relation to the spouse smoking during the whole of the marriage is not consistent with some of the larger increases daimed by Hirayama (1981, 1981). Trichopoulos er .f. (1991. 1983) and Correa er o1. (1983)• Though the number of lung cancer patients who had never smoked is smalti varying around 34-50 depending on the analysis, this number is s,ot very difTerent from that rrported in a number oC other studies, e.g the findrnee of Corru ar .i: (1983) xre based on only 30. whik those of Ttiehopoulos er al: (1981)„ even when updated (Ttichopoulos tt ai1:, 1981) were hascd on only 77. The difGrcvlty of obtaining an adequate sample sitt is taesdi:rlinod when onc considers that in our study the 44 never smoking lung cancer patients who compkted passive smoking quationnaires in hospital were estraclod from a total of 792 lung cancer patrcnts.. It would nood a very IarEc eescarch elTort to increase prtrision substantially, and even then one would havc to take care that the magnitude of any biases did not exceed the magnitude of the efioct one was looking for. The two major prospective studics which have so far reportod findings on passive smoking (Hirayarna, 1981; Garfinkcl, 1981)' wcrc not actually designed to investigate this issue and, as a rasult; could only use sl+ousc's smoking as sn index of exposure. Our study, on the othcr hand, though not able to monitor exposure objectively, as would have been preferable, was abk to look at passive smoking in a wider context, by asking about the extent of exposure at home, at work, during travel and at kisurc. Although the answers to thest questions were subjoctivc„ andeould have exhibited some bias, their inclusion perhaps allows greater oonfidenex in the conclusions. tt was interesting that, of the 59 patients for whom spouse's cigarctte smoking habits were obtained from both. the spousr nd the patients, there were 9(IS'.:) patients for whom there was disagtamcnt as to whethcr the spouse had beerr a smoker at some time during the marriage. It seems reasonable to suppose that somc of these were in fact smokers and may have been erroneously classified as non-smokers had only , one source of information bcen used. It was also noteworthy that there was quite a strong correlation in our study between active and pasaivc smoking As illustrated in Table Vl, current smokcrs were considerably more likely to be exposed to passive smokc exposure at home (from sources other than thnr own eiFarettes) than were never or as-smokers. As noted'above, this eorrclation,' coupled with some misclassifieation of smokers as non-smokers. may spuriously inflate the estimate of risk related' to passive smoking. tt is important to carry out further studies to obtain more accurate information on reliability of statements about smoking habits baause of this possibility of bias. Little other evidence is available concerning the relationship bnween, passive smoking and risk of the other smoking-associated diseases in (adult) eon-smokcrs and much of this is opcn to criticism. In his original papcr, H''irayam•a (1981), presented ntlative risks of death for various diseases for non- smoking women according to the husband's smoking habits. Based on a total of 66 deaths, a slight positivc trend for emphysema and asthma wns not sijnificanr while, based on a total of 406 deaths, no indication of a trend al all was tKen for isehacmic heart discasc. In a later paprr, based on

1M P.N LET. rr u/' Table V) Relativc ndd& of having I+awve smole nt+osurc n home Ksordrnj to paircmb own manufacrurcd crprcuc smnlinF hahin (slandardi.ed k+r aEc basc - • - wmhined clas I and 2 cunmrola Rrlainr odd.l9!", rnnfidtwrt lirnrts) O.r .wwri,rwX Jiohrt. Molr Ftwo/t Never 1 1 Ea Current 1.2510>tib I./tll: •.00t2 67-y.9s1: 126(OWI.RS) 2 S 1(1.74-).621 flrrwuared for ttrcnd 124 57.11 25.34 r <0001 <O:00t only a further 98 ischacmic hc.rt dis;casc dcaths, Hirayama (1984) rrportcd a shFht positive trend in r'rsk, but this was not statistiully siFnificant. Garlcrnd rr aL (1985). in a small prospcrtuvc study, reported a 15-fold' higher risk of ischaemic heart disease in non-smukrng C.Irfurnian womcn whosc husbands were eurrent or former smokers eomparcd with those whose hushands were never smnkers, but this enormous and implausihk rcl.tivc risk was only significant at the 90°.* confidence kvcl and' had vcry wide confidcnce hmits, bnng based on only 2 deaths in womcn, whose husbands were eurrcnu smokers. Sandler rr u!: (1985), in a easaeontrol stud) carried out in North Caroltna, reported a strong rrlationship bct..rcn risk of cancer of all sites and' passive smoking This study has been criticised by Lec (1985) who notes that it is basically implausibk that passive smoking should increase risk of cancers not associated with active smoking Lcc also criiiciscd the method of analysis. showing that no association with cancer risk would be found ir a more standard method of analysis was used. Vandcrbrotukc rr o!. (1'984), bascd on a 25 year follow-up of 1.070 Amsterdam married eoupla, recently rcportcd that passive smoking was associated with some decrease in total mortality. There is evidence indicating that young children whosc parents smoke have an eacess incid'cncc of respiratory symptoms and some reduction in pulmonary function. Reviewing this evidence. Lee (1984) noted' that the interpretation or the association is fr!aught with difficulties and that other possibk eaplanations, including social t:lass related factors, parental ncEelct, nutrition, cross- infection and L.ri:.e p::Fn•rncy, had not been taken into aocount ad'equately, so that a causal effect of passive smoking aould atot be inferted. The relevance or these findings to chronic bronchitis or other diseases in adults is in any case not clear. Our analyses showed tso significant efTect of passive smoking on lifelong non-smokers as regards risk of chronic bronchitis, ischaemtc hean disease or stroke. In all the analyses relating the various indices of passive smoke exposure to these discases, no significant differences were seen and slight decreases in nsk were as eommom as slight incrwscs. Wh4 more data would be desirable for thcsc disca~ses, lung cancer continues to be the tna)or smoking associated disease for which passive smoking comes under suspicion, Since all the dtfficultles of carrying out good research have clearly still not yct been overcome, further rescarch is certainly nerdcd Our findings appear eonsistcnt with the general view, based on all the available evidcnce, that any effect of passive smoking on nsk of lung cancer or other smoking-associated diseases is at most quitc small, if it exists at all! The marked increases in risk noted in some studies are more likely to be a rxsuft or bias in the study design than of a true effect of passive smoking. Any views apressed in this p.prr art thou or the authors and not of any other person or, eornpany.. This study was funded by the Tobacco Research Council (now Tobacco Advisory Council), to whom we arr most Eraacful Dr Alderton was thc holdcr of she Cancer Resc.rch Campaign endowed Chair of EprdemioloEr at she Institute of Cancer Research during the period of the study desrpr and field work. Mr. I M.rks from Recarrh Suwrys of Grnt drrtsin Orov6ded advice in the ptYnninj phase and was test+onsibk for nce arterviewen' vital eontnbution to the studY_ Wc tAqnk the many Nminans at the 46 participatmE bosMtals who permitted w to tontsct their patients and all the patients and spouses who answered the questions. Dr R. W.ng, who held a lritnli Council award for the period 19i0-19lS, as well as a eumbor, oor othereoltrasues povided uscful advia at various staRes of the Nudy. Mn DA Forty provided invaluable aatstans in oarrxint out the ttatisuol analyses.

PASSIVE SMOKING AND SMOI:INCr•RF.LATF.f) DISfASfS MOS Refrre.res ALDIF.RSOr:: M R. LLI_ P N t MANC;. R. (I9A5) Rrsks of Hl)CAD; C. HAM'KINS. LH • ASTR1rP. /' O97K) lung c.nccr, dirumc Dronchrtn. nch.emrc hcart dissc Eap.»urc of pasaivc smolcns 1o rohacrn smnlc and strokc in rtlYtton to lyTK of OgarLlle Mnoked J. E.Tdnn Corwn Nl/h . y/, 2M6 conslitucnks Inr Arrh OcnW Fsrrrrri IfltA. !2, 21. 1ARVIS. MJ. RUS.Sf1.L. MAH. FCYERARfND. C & 4 , i , t •RESLOW• N.L i DAY. N L(1911Q), Snmiuk.! Afrtlm[i w C,wkF, Rritorrh t'q/ A- 7hr dnolivu of Cav-rantrol S+rdwr Intcrnatronal AFency for Research on Canctr;. Lyon SUFFLER. P A• PICKLE. L W.. MASOK, TJ ! CONTANT, C (19lN) The ouses of lung onxr in,Tesas In LcnR C4W.rrr Courrs ond P,r.rntM+n. Mvtll! M l Conra• P. (rds) VertaF Chemte Internationrl lnc CHAN: W C(1982) 2ahkn aus HonFlonE. AlrrcG. Med: MbrA.,12a, 16 CORRCA. P.. PICKLC. LW.. FOwT/AM. E. LfN, Y. a HAENS7.EL, M" (1983). Passwc senokinE and kyng Pneet. Ldnrrrc 11. 595. DOLL. R A PETO., R(1976) Gprette smoking and M+ronchial orranoma dotc and time lelationahips among rcEular smokers and 4fclong non-smolers. J. f./idnn Cow.n. !llrh. 32, 303. GARFINKEL L(19B1') Tunc trends in Irn= OrKSr mortalitE artwnE non-smokers and a nole on patsive smoking J. Narl Conrrr, lrru.. ti6, 1061. GA1tFlNKEL, L, AUERlACH. O. i IOURERT• L(1965) Involunury tanokinE and lung oncsr. A otranteol study: J. h'at! Conrrr ltcrt:-7S, 463 GARLAND. C.. SARRCTT-CONNOR., E. SUAREZ. L. CRIQUI. M H A WINOARD- D.L (1985) Effocts of passive xnokine on itrhemtc lrc.n drttase mortality of Ron,smolers A prosT+ectivc stud). Arnrr. J. Eprdrrn.- 121, 645. GILLIS. C R• HOLE. DJ . HAMTHORNE. V.M t WYLE• P. (1I91G1) The effxt of environrncnul toDseso amokc in two urban eommunitrcs in the .est of Seolland. Grrop. J. IRrsp Drr.. iS, (Suprli 133). 121. HIRAYAMA. T(1'91I1) Non-smolrnE .nves of keavy smokers have a higher risk oflunS on¢r. a study from lapan: !r. Alyd J.. ?lua 1!3 HIRAYAMA, T(19&t) LunE cancer in Japan effau of nutrition and passive smoking In (ynR Cowrrr. Caurr.i .nd Irr.rntan Mtxl1• M & Corre.. P. 1e+ls) Verlag Chemte Internattonal Inc othen (1985) Passivic e><pasurc lo tobaoco tunole ohva totinine conantraoons in a ecpre.entatrVc pc+f+ubtUon sampk of aon-srnokrnE ochool<hrldrrn: er Mrd J.. 291. 927,. KARAT• CC a M7NDLR. EL (19N1). Lunp rarnsxr in sw+n-emokers Cowrrr. S3. 1214 KNOTbti A. MHN. H' l SCHMIDT.. F. (1'9R3) Pas.aivc smoking as cause of, lung cunar in fernalc non- smokers. Mrd IC1N . 71, 54 KOO• LC:, HO. tH-C [ SAW. D(19%4) Is fsa-mve pnokrnF an addod risk f.ctor for lung cancer in Chtncsc wMomen? J E=r Cfrn Cenrrr Rrs . 1277. LEE. P.N (19Fa) Paurvc Smoking In SmrsR'inR o+d Nw- L.rrK Cumming. G k BonsiFnort:• G. (ods) Pknum Publishing Cor1+vratton LEE• P N (191f5) Lifetnnc passive smoking and cancer risl Lancet. L 144 LENNERT, G.. GARFINKEL. L. HURAYAMA. T. • 4 others (1981). Round ta6k drscussion. lrer. Afrd.. 13, 730. SANDLER. D P.. WILCOX. A ) t[VEIISON; R_! (19K5). Cumul.tive effects of lifetime smoking on cancer risk Lnrrr. 4 312 TRICIIOPOULOS. D.• KALANDIDI. A.. SPARROS. L t • M.cMAHON• 0 ('1981) Lung cancer and passrvc onokinS !nt J: Crrrrr. 27. I. TRICHOPOULOS., O. KALANDIDI., A t SPARROS. L (1'A83) Lung cancer •nd passive amoking Conclusion of Greek study Lemn: ii, 677. VANDCRSROUCKE. 7 P.. VERHEESLN. 1lH H., DE BRUIN.. A.. MAURITZ, 111 VAN DER Hf.IDr•WESSLL C l VAN DCR HI:IDL. R M (191(1), Active and prsavc smoking in mamed couples tssults of 25 year follo. Irp Ar. Ifrd J.27p1, 1i01t1