Tobacco Documents Online

PASSIVE SMOKING MORTALITY A REVIEW AND PRELIMINARY RISK ASSESSmeNT A. Judson Wells 102 Kildonan Glen Wilmington, Delaware 19807 For Prozontation at the 79th Annual Meeting of the Air Pollution Control Association Mlnneaaolle. Minnesota ,hln~ Pg.PT. lflt~R OG-O0.~ IHTROOUCTIO~ In 1901 when IIlreysmaI end Trlchopoulas, at el.~. rlrst publlslsed their studies associating passive smoking vl~h lung cancer, and In tho years Immediately following, there w•s coneldsreble controVefly and skep~lcllm that such an effect could Indeed be real. However. el more papers appeared and neny of the earlier Issues were resolved, there now appears to be a urn-lag conoenlus ¢sncer, or at least that there Is I strong association. G•rrlnk•l, who was one of the most quoted early skeptics, and isis coworkere have recently published • paper] In ~hlch they find • stetlltlcallyIIgnlflclnt doubling of lung center rllkl for married to smokers of 40 or ~rs cigarettes per day compared to women married to nonsmokers. A doll response relationship was of U.5. deati, e from lung cancer associated with passive smoking probably Ills within the $00 to 500g range suggested by Repace and Lowery's risk assessment4. In 198) pipers started to appear mssoClatlng passive smoking with deaths from other cancerS, chronic bronchitis, emphysema end heart disease. ~hese pepers~ like the earlier lung papers~ have attracted debate, but more recent popers support rather then refute the earlier ones, Indicating thor a consensus eventually may be reached In this broader area as veil. It Is the pw~pose of this paper to present a summery of the epideml~loglcal literature on passive s~nkln~ for four major disease categories, namely, lung cancer, other canCers emphysema, observed hetueln direct and passive I~oklng and the probable felon(s: therefor, e~d tO assess it loess in • preliminary way the slonlFIcanca o~ these findings on expected deaths from plosive smoking If the underlying apldewlologlcal results turn out to be correct. Because of the many specialties Involved In such • celculmtlon, namaly~ epldemlology, statistics, population estimates Of passive smokars~ aerosol deposition theory~ lung structure, chemll~ry and carclnogsnesls~ It Is not possible In a paper of this scope to give • detailed end sophlltlceted explanation of aech step, Nonetheless. the estimates ~ade ere believed to be the wost probable numbers considering the data now avellable mlthough it must be raollzed that the confldlnce limits are still broad blelule Of the uncertalntlss that exist at ~vary step. The objective here II to determine the probable future e:tent of the public health risk from passive smoking If the trend In the epIdemlologlcel results continues along the lines It has taken since !~51. The aolds~lologlcmi Iltlreture vii searched Prlmerll~ through the

publications of the U.S. Ggvernment'a Office of Smoking HealthS,i which also provided m printout of all of Its document-s on passive smoking .from 19?g through 196Z. In addition references wera received directly from workars In the field. scape of the Inquiry Included all pipers that contained original data on adult, nonsmoker mortality or cancer morbidity from passive smoking. All of these papers are listed In subsequent tobies or text. From these papers those pertaining lung cancer, other cancer, emphysema and heart disease ve~e sclected for analysis end calculation of death rates. ~eceuse some of tha papers have rather glaring weaknesses, four criteria were used to admit data to tha death rate calculotlonsl I. Retrospective studies should have controls. Observations should be based on exposure beyond fiva years. ), A study should not have serious Internal Ineonalstcoclea. 4. Sufficient date should be presented to allow tha cotculatlc. O( a vorleace. for the eleven studies that met these criteria a relative rib- far each disease and'sex ups estimated (to the extent dote available) by averaging over ill exposures Including exposure exosmokecs, light• medium and heavy smokers. Combined relatl~ risks f6r .each disease category vere calculated by a mold.- analysis technique which weights?the Individual relative risks the Inverse of the variances . Ha other weighting of the accepted studies was attemoted. Some o~ the cancer peper,s reported morbidity relative risks rather than mortality relative risks. ~ouever, an estimate based on published data° Indicates that flv~ year survival rates for both exposed and unexposed cases ere similar. Therefore, the Incidence ratios were used 9god spproxlmatlons to the mortality ratios. The method used to calculate possible deaths from tha COmbined relative risks In the preliminary risk assassmen~ Is described under that heading. There are eighteen studlel nov ivmlllbll that bier on odu~ mortlllt~ or Cancer morbidity From PllllYe tuna Cancer - Female Table | lists the papers on ~eaale Cancer, Shown Is the lead author on the pmper~ the locale of study, the number of calms, the relmtlve risk for the hlgh~" . exposure lie most cases 20 or more cigarettes per dly smoked b~ spouse) and tha lye-tail p-value for that exposure, a relat~.* risk for all exposures combined, Including mxposurm to If those data ore available, end a two-emil p-value for , exposure. A one-tall p-velul for m ~antel extension test trend Is sho~n If available. Zg ZZ O0

There are eight studies thee pass the aforementioned ¢riterleo Trlchopoulos. et el. 10~ have a numerical error In the calculation or relative risks. The values for I-ZO end Zl, cigarettes per day should be 1.95 and 2.55 Instead of Z.4 and 3.4. respectively. Ihe value In Table I of Z.OO Is a weighted average of exposure to ex-smokers as veil as to the tug categories OF smokers. KOO, et alt I~, report on exposures both at home and at york. The work It home and at home plus work are combined here to give the relative risk of 1.25 Ihoun In Table I. The Sandlere et al,|$ , two lung cancer cases among non|~okers. These ~ere determined to be re-ale per privets communication Cram Or. Sandier. rout of the eight lung cancer studies (Trlchopoulos. at el.|0 . Coffee. eL el. I~. Keg. et el. I~ and Sandier. et al.|S ) are el. *~. era mortality studies. GerfJnkeJ. et el.|. Is ~lxed. Since there Is no reason to believe that the very lay Survival rate from lung cancer Is significantly different for nonexposed and exposed cases, the Incidence relative risks were used el mortality relative risks. There are :four studies that do not pest the criteria, namely. n • • . . hlch Is • case study with no ¢on~rol$. Chin. et only, end ~u, et el. 19, which does not report the number of cases and hence does not mllow the calculation OF m variance. The relative risks end significance dote for Knoth. Chap and Kabet and ~ynder were calculated from data I~ the ~apera end from data In a private communication from Or. Kabat. ~.~na Cancer - ~ale. As shown In Table I there are three acceptable passive smoking studies of nonsmoklng moils with lung cancer. The total of exposed cases Is smell but the data are consistent. Co.blned relative risk Is 2.4 end p-0.00~. Inclusion of the three rejected female studies for which variances can be calculated and the one rejected male study would raise the combined ~ale relative risk for lung cancer to about 2.7 end would loser the female relative risk to about 1.42. These changes would change the overall death dote for lung cancer from passive smoking only slightly end in en upward direction. ~her Cancer - Female. There are now four studies ralmtlng passive smoking to cancer other than lung or to total Cancer In ffnales (see Table I1|. This relatively neu area Is more Important In terms of potential number of deaths from passive snaking then Is lung cancer because the relative risks are In the )ape range while the underlying death rates for non-smokers are many times higher. The relative risk shoun for H|reyame In

~J a fable il of l.o0 II obtelned by ~q•blning hls v•lues for hioher and Ioxsr exposures. The ~lllsr ~ relUlt le for totoI Our Inter/it here Ii In m relative risk for cancer other thin lung, not total cancer. However, •ccording to the CllcuJltion described liter, list then 3t of HIIler's total c•ncer shuuld be lung cancer, and the relative risks for lung and totol cancer •re similar. Therefore, his tot•l cancer rilotlve risk Is I good mpproxl•otlon to the relative rllk for c•ncer other then lung. The piper by Sandier, et al.|$, Is •leo directed •t tot•l Therefore, •gain the tot•l cancer relitlvo risk Is • gOOd approximation to other cancer relotlvo risk. Other Cancer , Nile. The detl for c•ncer other thin lun~ for • lies (See Tibia II| ire much scircer ~r~ for females. The results from the two •reliable petersI ore conflicting, neither result Is statistically |lgnlfl¢ont nor It the relative risk. Therefore. • vmlue of 1.0. I~dlcetlno no association, Is assumed for the death rite ¢el¢ol•tlons until • ore date become Ivillible. ~r~r~ Olleete - Female: There ere nov three papers associating passive smoking with he•rt disease omong el•lies lice Table II). IIIrlyl•l'e piper f ¢Ontllnl dltl for IIchlmlc hlirt disease In uo•fn by/ smoking hobit of the husbands for two levcll of exposure. The relative risk for ill exposures of 1.16 Is a welohted overage of the t~o exposure levels. Gillie, et el. I$. report data for myocardial Infarction (HI-/IO) end for other ischemlc heart dime•me (1~D-411-414|. These hove been comblnea to yield the Ischemlc he•re dillies relative risk of 3.6 shown In Table II. Garland, it •1. It, report ~eto for none•eking who were ••rried either to nonsmokers, ix-smokers, or currsn~ s•okerl. The overall relltlvi risk of 3o5 In Toble II calculated fro• I weighted •vet•me of their age idJUlttO mortality fatal ~or exposure to ix-smokers and smokers. ~eirt Oleeisl - Hell. There ire tug papers •ssocloting passive smoking with hle~ disease In •llel. One, ihown In Tibia II. Is GIIIII, eL el. a Their rolltlve rllk of 1.3, ilthough not iLstlstlcllly Ilgnlflcont, Is reinforced by Svendlen. it ~ho ~ound a rilltlve rllk of 2.12 (p-O.lf) for the FlRFIT cohort of relatively high rllk Indlvldu•ls. Since the Lye papers concur end there are no negotlve or neutrol resultb, the GIllie, eL el. result, 1.3. Is used IS the passive lloklng relative rllk for • oil Ischemlc helPS +11t111 In the general population ~ntll '[mnhvlenl lad Chronic BronchUS|!~ Hlroy••o 9 nil thl only diem on these dlseosel, •nd they ere ~or Females ~nly0 As lho~n in Table II • relatlv• risk of 1.4 Is obtained by Combining his .results for high end low lapoturos. 6 L7 900c_i $~eclflc Cancer Sites Other thin Lun~l~ T~ble ill ihous results on passive smoking risks for specific cancer sites other thin lung. It Ii Interesting that the lists other than lung that are norIolly lllOClltld ~lth direct leaking Irl mbSlnt, with the pomslblo axceptlon of cervlw. The dote on braast csncer ore vlr¥ prellmlnlry. HIrm¥i~g ~ reportld this rlsk ilsvstlon for sol esncer sltol becomas non-slgnlfic•nt ~hen lung~ nasal sinus, brmln end breost ere aw©luded. Thl SindIlr. et IS. i$. rslatlvs rllk Is or bordlrlln•l~titlstlcal slgnlflcln~a, it Intlrlltlng this Hlrlylml found ttomoch cencer~ with ~$ ellis, to be Iplclflcllly not •lloclotld Ilth pllllVi smoking, $oeclflc cancer sites othlr than lU~JL~ NIsol Sinus 8film Orsoet¢ Endocrine Stomach (Some stltlstlcml significance clilmed by luthors. Hlrlylml 10 Jlpln Z3 Z,I~ Hlrlyl•l fllri¥lll tO Japan )1.0 Sandier. It Sindlars It II. Buckll¥, it Browne it iI. Sondler, It ol.l~ H, Caroline 55 Z,l~ All Cw~le: of Oeeth. There •re five studies that contain on passive smoking and oil causes of death. The relative rlsk: era diluted by I I•rga number of deaths th•t •re not related to plsllve siokln~ It Ill sO the ferules are scit~ered and fixer. .The Nlller study II In I$~ Is thl pleaser Itudy on mortallty fro• p•sllvi smoking, lli oblervsd i lovlrlng of llfe expectancy from T8.8 years to 7~.7 ye•rl for 601 non-lnoklng wives whose husbsnd| smokld complrld vlth thole vhOll hUlblnds dl~ not a•oke. GIIIII~ et el. IS, oblervad • rolmtlvo risk of females lad 1.0 (ZB CllflI for molel. Garland, oblerved • rll•tlvl rlsk of lo0S (~ CSlll| for fenelel. Svsndsen, at el. ~ observed • rglltlVl rllk of Z.0 (II clses, po0.07) for moles In the ~RflT cohort. T~e only fllgltlve relative rltk co~es from ¥indenboucki~ it el. !~ In Kollond (0.B for flmolell ~07 Clses~ p-0.1Z)o Hovlvsr~ thla study Is flowed In thee non-exposed non-smokers hid i deoth rite IS$ hloher thin dlreCt nook•re so It would not piss crlterlon number three thee • study should not hove • llrlous Inconllstincy. Hiving reviewed the fertility llterlturl on patslyi Inoklng, vhst dosl It ill m~n~ Flrlte there Is quite • bit of It. Second, taken it •uhole there II growing evidence of on association

0 8~-80.~ betxeen passive smoking and fatal dis*ale, the lung caricer data are Particularly persuasive, arid there are prelimlriary data that Indicate en associatiori with total cancer, IschemJc heart disease and emphysema and chronic bronchitis. Third, the cancer patterns In direct seeking and passlvs smoklrig appear to be different. Cancer Site! Table IV shays a comparison of ©ameer sites for direct snaking (from reference 28), and passive smoking (from Table Ill). It Is evident that the entry sites are different, there Is a qualitative difference in the location of the long cancer sites It,30 , end the sites eleevhere In the body (except for cervix) are different. Possible reasons for these differences are discussed later, One concloslon that can be drexn, hovcvarp le that pcsslve smokers are not • mixture of true non-smokers end • small percentage of mlsclesslf|ed direct smokers. Such a mixture vould exhibit the same pattern of excess disease rates as direct smokers except that the IncreaSeS In relative risks voutd be Table IV, Cancer slte patterns In direct arid passive eriokin~ Direct S~oklno Passive Smokln~ Nisei Sinus Pharynx - Larynx Lung - largely Lung - largely bronchial peripheral Esophagus - Stomach Urinary Oladder - Kidney - 8feast - Endocrine glands Cervix Cervix PsrtlcleSize Probably the riost Important difference bat•ann mainstream and sldeetr'~am smoke Is the dlfferanca in effective particle size arid its effect on vhsre the smoke particles ere deposited. A careful study of the smoke end aerosol deposition Ill;erature discloses c number of differ,mesa ~hlch are :u~erlzed In Table V. Direct ~mokers retain about OZ~ ~1 of the tnheled particulate of ~hlch ab~u~ )7~ le retained In the buccal cavity end 4SS In the lover respiratory tract. Aithouoh particle size measurements Z8£00 aerodynamic dlcmetsr Of about O.S~y, the particles, In the lllgh concentration conditions of direct •making. apparently feble Y. Deposition pat~frns in direct l/l~LP.12~JJLi_Jlg~no~ (ntry Site PlrtJculete Inhaled per day. Effective particle size Inhaled, Percent retained In mouth Percent retelned In noes Percerit retalnwd Iri bronchus Percent retained In near alveolar region Percent ratained In or near elvaoll Percent retained, total Percent exhaled Particle Sloe exhaled, ~m Nouth Nose Z40 ~ 0.5 to 3.5 b S 0.4 2O 0 21 0 OZ 19 I0 81 0.7 0.4 abased on IS me. per cloeratte and ZO cigarettes par day. bBaeed ors 100-700 Fg/v~3t and I0 liters/rile. Inhaled for 8 hrs. agglomerate to a muEh larger effective pmrtlcla else. To axhlblt deposition behavior each IS that cited above the effective particle Size vould have to be Iri the S%u rangeJJ. This Increase could be brought about either by direct agglomeration34, by electrical charges generated on the particles J$~ by a dense icy•ring effect~, ar by some ¢oriblnatlon of the~e. Partlcle~ of this effective size ~ouId deposit heavily In the larger bronchial alr~aysJT~ particularly at the bifurcations, and In the larger alr~eye of the alveolar region. The exhaled smoke has a particle size of about O,;ri~ 31. Only about one-fifth of this size uould be deposited, being ~$~ of the let exhaled or about ~ of the ~otal Inhaled. end this vould come dove deep In the alveolar region, In or nrar the ely,oil themselves In contract sldestream smoke Is very dilute. It his • Ill| medllri aerodynlmlc dllqltlr of about O,Im~3| Irid duel not lgglOalrltl. This Is a vary difficult Ilzl to trip In the re,pit•tory tract beclUSC It Is too large to depnllt by dlffusiori and too Imlll tO dlpuslt by Implctlori, Some OF the Imrglr plr~l¢lCl In the sldeetrclm sink• (ebo~t el of the amount InheledJ vouid be dlpollted Ire tha hole 33. The othlr lit that viii deposit 31 ipplrsri~ly gull iii the vly through thl bronchial ind Ilrglr ilvlollr llrva~l i~d dlnUlltl In or nllr elY•oil ;he pirtlcllltl fro~ direct sl~kln9 Ig either deposited In mouth directly, or In the bronchlll rcDIon or near fly•olaf region ~hera It mill ba clelred Into tha mouth, It le ellen i~lJJuued end Jl litblr alJllnltl~ or iblOr~ad Into thl blood Itrlla vii thl gut. This Is believed to rllult In the concerl ehoun In Tabll IY except poeslbly For carvlx, ,1hi plrtlculate, IO

a from passive smoking deposits elthe~ in the nose, resulting In Dalai sinai cancer, or deep In the alveoll From whence It le very difficult to clear Into the mouth, it Is speculated that most of thle particulate II solublllzld or metabolized directly Into the blood or lymph system. It than circulates In these systems and result0 In the cancers obsorved. In p•sslve smoking tho- dlg0stlve related cancers are absent. Another difference betueen melnltree• end sldestream smoke Is the chemistry. Side stream smoke Is Formed at a lower temperature then melnstreem smoke0 and, therefore~ a larger fraction of the • ore complex molecules Is preserved. The amounts of tumorigenic agents In sldestreem end molnstreem s•oke have been measured 39. The I|destrenm/malnstreaa ratios For such •mounts very from for cetechol to $~ for Z-nephthylemlne. The mean value la Therefore, It uould be expected that sldeltreem smoke particulate, per nllllgrem deposited, vouid he~o higher carcinogenic potential than mainstream particulate. Another difference betueen direct smoking and passive smoking the difference In disease susceptibility between the direct end passive smgkerl. Deaths attributed to direct smoking constitute about 18~'o~ total deaths. Thus-• direct smoker dying of • smoking relmted disease, uhlle perhaps more sensitive than the averageof the tot•l population, would not be substantially more the other hand. constitute only • very small percentage of total deaths, In the renan of O.OZ$ to Z.$S. This Is • much emeller proportion tha4 in the case of direct saokingl only the very most ssnlltlve Individuals uould be dying from such in effect, and the expected dose to •thieve such • retpgnse vould be Imsa than that for a direct smoker. One approach to predicting the he•It• effects of passive smoking hal been to factor doun the hee|th effectl of direct smoking by the ratio of Inhaled or deposited emoka doge. As con be seen from ~he date In Table V the dose ratio Is quite high, being about ?0 t~" S00 for Inhaled dose end •bout ~00 to ZlO0 for deposited dose. However, taking Into account the differencee In particle size Iffectl, chemistry end Individual Iusceptlbl|lty, it I| lien thee such i Ilupllstlc dose/responee •pproach unlikely to yield rosalie that are accurate even vlth|n •n order of megnltudo. Just hog dengeroue might pmlslve smoking be7 Table Vl provides • sumary of the combined relative risks for each sex and Probably,the most reliable number In the table Is the 1.40 relative risk For female lung cancer, based, as It let on eight studies Including those by some of the most Prominent Investigators In the field. Ths least reliable nuabers ere those for male other Cancer, vhere an arbitrary relative risk of 1.0, denoting no association, ~as adopted, and for male Ischemlc heart disease. Clearly more uork II needed In these areas, The relative risk for emphysema and chronic bronchitis also has poor statistical significance..but the underlyinu death rates for non- smokers from these diseases Is so IDa thee only • very fe~ deaths would be Involved. T_able Vl, Combined Risk Ratios fro~ [pldemloloa!cel Studies Lung cancer 45) 1.48 (0.001 1.21 - 1.01 Other center Z091 1.5~ (0.001 I.Z6 - 1.94 Ischealc heart dis. ZT~ 1.27 0'.04 1.01 - 1.59 [aphysema t chr. hr. 10Z 1.4 0.|~ 0.9 Lung cancer 13 Z,4S 0.009 1.27 - 4.7Z Other cancer 7 1,0 Ische~l¢ heart dis. 14 1.3 0.46 To calculate numbers of deaths per year from the relative risks In Table Vl It Is necessary to know the total non-smoking population, the percent exposed to sldestream smoke and the death rates for non-sookerl by dls¢lle category• The non-smoker population was estimated From the national health statistics, The percent of non-eiokers exposed to sPOUSe's Imoke u~S estimated from the controls In the U.$. studies In Tables i and !|. Other exposure was estimated using date developed by frlednsn, et el.~0 Non-smoker doeth races For each sex end disease were obtained fro~ Ilammond 41. 8y combining these Inputs it was POSsible to calculate excess death rates due to passive smoking, again by sex and disease, Applying these death rmtes to the non-smoking population passively exposed, the desired number of deaths par year in the U.S. was obtained. Details of this calculation ore In • manuscript thee has been 1ubmltted For publication elseuhare. By this procedure'deathl from passive smoking for lung cancer For males plus Females came to log0 per year, wile centered In the range of 500 to $O00 obtained In m previous study . For other cancer end heart disease the relative risks are In the ss~e range as lung cancer (Table VI)~ but the underlying non-smoker death rates ere much higher. Therefore, the estimated death| are much higher. The total deaths came to 4i,g0g par year OF vhlch Z2,000 uere from cancer (Including the 1800 lung cancer deaths| and from male cancer other then lung but does Include deaths From mils lit•emit heart dllllle It • relative risk of I,|. Thl| IP

UJ a value, as noted earlier. Is supported by Svendscn, et alf|, end Is very ¢luse to till re--ale relative risk Of I.ZT. Even IF these male delths ire excluded, the total passive smoking deaths voold still calculate out to $1.OO0 per year. The epldcmloloolcal literature on ~ortallty from passive smoking Is orowlng. An essoclmtlon betvaen paselve smoking and long cancer Is becoming Increallngly evident, and there are beginnings, it least, of evidence that other cancers and heir[ disease ere also Involved. If these trends continue, lung cancer all| become only the tip of the Iceberg with deaths from these latter diseases amounting to ten to twenty times thole from lung cancer. Tobacco smoke Is knoun to be carcinogenic end to produce heart disease, millions of non-smokers, estimated In this study it ]Z million, arc exposed. ~het me have, In other vords, ere the slovly emerging shapes end dimensions of I major public health problem, furthermore It Is an Indoor problem. That means that It Is a home-oriented and vorkplace problem because that is ~here the average passive pmker spends most of his or her time. There may not be much that con be done about the home letting, but officials end managers eho ere responsible for uorksltes need to become ovate of this Increasingly acknowledged thre|t to the safety of Indoor air and the uorkers who ere exposed to It, Also this Is not i traditional vorkplace air pollutant that from some facet of the mork Itself end on the factory fl0br. Rather It occurs In offices, smoke break rooms, weehrooms and other pieces that hive alveys been considered safel and the pollutant arises not from the ~ork Itselr but from the other vorkers. The first action required Is to protect the non-smokers from ~hl emokerSo The next thing to ~onslder Is • smoke-free uorkplece. ACKHOVL[0GEMEHTS fhs author wishes to ocknouladoe major assistance from Coldltz~ m.D., uho did the statistical meta-analysfs~ end very helpful tuggestlonl from ~llllcm J. Blot~ Ph.D.~ Kenneth P. Cantor~ PhoO.~ Norman II. (delman, ~.0.~ Edwin B. Fisher, Ph.O.~ f. Charles Hiller, H.O.~ James Lo gapmce, Ph.D., Jonathan Samett H,D., Dale P, Sandier. Ph,O,, end frank (. Spelzer, This u0rk was supported In pert by the American Lung Association. The opinions expressed are those of the author. endorsement by the American Lung Association should be Inferred. I) I, T. IIIrayams, "Non-smoking WIVES Of heavy smokers have a higher risk of lung cancers a study from Jooon', J, Z.~IO3 11981). 2. O. Trichopoulos, A. Kalandldl, L. Sparros, O. "Lung cnncer and pODIIvl smoking', ]~[~._~1.~..[~;;£ ~l (1901}. L. Gerflnkelt O. Auerbach, L. Joubert, "Involuntary s~oklng lad lung cencer~ m case control study', ~, HOt. Cancer 75~463 (1995i. 4. J* L, Repace~ A, It, quantitative Environ. |at. lie3 O!blloarophY On smoking O~. Public Health Service 81bllogrlphy Series No. 45~ Public Ilealth Service, gockvllle, ~0, 1919~ 1980~ 1~81, 1~aZ, 190], 19a4. S~oklng end health bulletin, Public Ilcelth 5ervlce~ Rockvllle~ ~0~ 198S Is~ue~. 7, K.T. Hslvorsen, Estimating Populotlon ~rs Ihformltlon ~rom several Independent ~ources, Ooctorol dllsert¢~lo,. IIBrvird School of Public II¢olth, Boston, 1984, p. 46. ~0rk, 1984, p. 7. 9. T. IIIrlylml~ "Passive smoking and I~ng cancer', presented the ~lfth ~orld Conference on Smoking and Ilellth, O. Trlchopoulos, A. Klllndl~l. L. Sporros, "Lung cancer and passive smoklng~ conclusion of Greek study', ~ (1983), II. L. Garflnkel, "Time trends In lung c~ncer mortality among IS, P. Corral, L. ~, Pickle, (. Fonth~m. ~. LIn, ~. 13. C. R. GIIIIs, D. J. IIole~ Y. n, Ifa~thorne~ P. ~o~le, effect of environmental tobocco tmoke In tug ufbon co~unltles In the uelt of Scotland', ~r. J. Reap, ~!~, (supplement No. I)])tlZl (1904). 14. L. C. Koo~ J, H-¢. IIo, D, Si~ "11 passive smoking ~n risk Factor For lung cancer In Chinese vo~en~" J,_Exp, file. Cqnfer R~IZT7 (1904). 15. D, P. 5ondler, R. O. [versos, A. J. ~llcox, "Passive smoking In adulthood end cancer risk', ~m. J. [pld¢~ I;, A. Knoth~ H. Bonn, F, Schmldt, "Pastlvreuchen Lungenkreb~-Ursach~ bel Nlchtreuch/rlnnen",

I1. 10. 23. )2. W. C. Chant H, J, Colbourne, S, C, Fung, H, "aronch|el cancer In Hang Kono 1576-1911~. Dr. J. Cenco~ ]911Be (1975). See also ~. C. than. S. C. Fume. "Lung cancer in non-smokers In Hang Kong'. In Cance, campaign. Yal..~._¢pncer [nldemlaloov. (. Grundmonn. Fischer Yerlaoo Stuttgart. Nan York. ISBZ. pp. 159-202. vhlch appears to be based on the s,me data. Go C. Kabat. E. L. Wynder. "Lung cancer in nonsmokersa, ~i[!r~S3~lZl4 (1984). A. II. ~u. 0. (. Henderson. H. C. Pike. ~o C. Yu. "Snaking end other risk factors For lung cancer In yemen'. J. He*. Cancer Inst. 74t747 (Imam). To .Irayema, "Cancer mortality In nonamoklng yemen vlth snaking husbands based on a large-scale cohort study in G. H. Hiller. "¢ancer~ passive snaking and non-employed end C. Garland. E. Barrett-Conner. L. Sumrae. L. Vlngerd. "EFfects of passive smoking on lechemlc heart dis,,so mortality of nonsmoker|e. Am. J. [pld~m|ol.~ IZ11645 K. H. Svendsen. L." H. Kull~r. J. O. H,stoat passive smoking In the multiple r~sk Factor Intervention .,eating. Hashing*on. O.C.. November. I~OS. J. O. Ouckley. R. H. C. flerrls. R. Doll. ft. P. Vttfey. P. T. UIIIlams. "Case-control study of the hu~bnnds o~ yemen vlth dysplasle or cerclnon~ of the cervix uterl't (Ifall. O. C. 0faun. L..Perelra. J. 8. Gsrner~ ~Cancer or the cervix O. H. fillS,r. "The Pennsylvania study on passive smoklng'~ J. Ores*nine. Illinois ~una Assoc. ~(S);S J. P. Vendenbroucke. J. H. ft. Yerhe~sen. ~eurltz. C. Yam Oar Helde-Ullsel. R. H. Van Oar Held,. VActlve and passive smoking In married ~ouplmll results of ZS year follov~p~ ~. ~d. J. ~1801 luraeon general. I~OZ. Public Health Service, gockvllle, I$0Z. pp. 145-~. L. II. Garland. R. L. B.i.re B. Coulson. J. Stein. "The apparent ~ltel of origin of carclnomo~ o~ the lung'. Radiology ~1 R. G. Vincent. J. ~. Plckren~ ~. ~. Lane. I. Broil. H. Teklt4. L. ~outen~ A. ¢. Gutlerrez. T. Rzepkn. "The changing hlstopathology of lung cancer. • r~vfe~ Of 1682 Cos~sv0 R. J. Nltchell. "Controlled measurement o~ ~moko-p~rtlclo re,enSign In ~h~ respiratory ~BCt'e ~~p~r. J. L. R,pace. A. H. Lovreyt "indoor air pollution, tobacco ~aoke, and public health', ~ ~u4S4 J. Heyder. "Studies O~ particle d,poll*Ion and clearance In humans'~ In Problems of Inhaletory toxicity stud!eL, P. GrosdenoFF, et ml., ads., hHV-Hedlzln-Verlag, ~unlch, 1905, pp. ISS-I60. K. NcCuskar, C. Hiller, N. Nazumder, R. Bone, "Dynamic growth of cigarette smoke particles ", (Abstract), ¢. ~clandrl~ G, Tortoni, ¥. Prodl~ T. Oa Zalacomo, I1o Formlgnanl, C, C. Lombardl, "Depolltlnn of charoed particles In the human a|rvays', J. Aerosol. ~G,|~ H. A. Fuchs, The ~echonlc| or aerosols. Hacmlllan, Hey York, 19~4. pp. 46-45. T. R. Gerrlty, P. S. Leh F. J. Hall. A. Nerlnalll. P. Warner. R. Y. Laurence. "Calculated deposition or Inhaled particle, In ~he olrvay g,nora*lone of normal subjects'. J. ~GPJ.. Physlols Rupirat. £nvlron, Exercise Phvslo_~. F. C. Hiller. K. T. flCCUlker, h. K. ffazumder. J. D. Vlllon. ft. ¢. Bone, *Deposition of sldestream ¢lgerett~ smoke In the human respiratory tract', ~m. Rev. The_he~l~ consequences of smoklna~sn~er. ~Q~~~, Public Ilealth 5ervlce, pp. ed.. Public Ilealth Service, Be~hesde. ~D. 1966. pp. 127-Z04, (Ha*lanai C~nc~r Institute ~onogrlph FlOTE TO EDITORS I~nder thg now federll publlc~|lon r]|h|g to thk ~ ~r~