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5 . .J" -F ~r7J ~?„Z,} ~~. •' ..Js• •s.t'e!.Ji C' ~,. 4~ w, but I've often wt„n. ~ w•hen you are smoking bstained. and so on. Ii anyone tried to charar- :nt "talk to him, talk ta bf our research involves -ended interviews with as a feeling. They also j xlogous to hunger. But n't know how else to ) I 4, "'t 3 i 9~ rs-o 1' The Case for Medium-Nicotine, Low-Tar, Low-Carbon Monoxide Cigarettes MICHAEL A-H. RUSS€LL Institute of Psychiatry The Maudsley Hospital London SE5 Enqland The Quest for less harmful cigarettes has been dominated by an obsession with machine-smoked yields. The tendency for smokers to regulate their smoke intake (Sebaehta 1978; Russell 1979) has been largely ignored, even by those such as Gori and Lynch (1978j and Wynder and Hoffmann (1979) who should know better. In consequence, emphasis has been placed' on low-tar, low- : nicotine cigarettes, and limits on tar and nicotine yields have been proposed'by Wynder and Hoffmann (1979) that are really quite arbitrary. On the basis of machine-smoked yields the smoking of large cigars should be the most deadly form of tobacco use, but epidemiological studies show them to' be far less harmful dran.cigarettes. One would have hoped that this discrepancy would have made us more cautious about extrapolating too directly from smoking machine to sszioker and that it would have made us place as much emphasis on measuring the smoke intake of smokers as has been placed on the smoke output of cigarettes. In this dscussion, data will be presented suggesting that the tar and nicotine intake of smokers is largely unrelated to the tar and nicotine yields of the cigarettes they smoke. Questions will be raised about the interpretation of epidemiological studies that have shown lower health risks for smokers of filter-tipped and lower-tar cigarettes. These findings could be accounted for by biases in the samples and the changes that have oceurred over the years in the quality and carcinogenicity of tobacco tar, rather than by an assumed reduction in the quantity of tar intake. Finally, a case will be made for a medium- nicotine, bw-tar, low-carbon monoxide (CO) cigarette, or at lcsst for some more systematic research in this direction. This is based on the premise, admittedly a little over-simplified, that people smoke mainly for nicotine but die to a large extent from tar an1 CO. ACCEPTABIUTY AND SE1F-REGULATION At the heart of the matter are two problems: acceptability and sc:f-re_ulation. 297

~ ---~--------..--___------_ cmphasi. on Ihe p• valinn of I'lavor and Ihe uw of Ilavor udditivcx. iluw olLcr I':rclors rcltued to .inc may he involved. Greater use of air-cured tobaccos with nwrc nikalinc .mnkc would improvc Ihe avaiiabilily of nicotino. Also. Ihe widcr u.c of longer cignrclics could be another factor. Longer cigarettes have a lunger slandard bult length 1•or Ihc dctanninatiun of machine-smokcd yiclds. 'fhi. Icaves dle American smoker more opportunity than his counlcrparl iu Uritain to cumperr.satc and extract more than the standard yield by taking one lu two extra pufl'.. COMPENSATORY INCREASE IN INHALATION \Vhelher it is achievcd by increasing the number of cigarettes smoked, the amounl or smoke inhalcd from each cigarelte, or a combination of bolh, compcnsation'1•or smoke dilution depends ultimately on Increasing Ihe overall •rmount of rliluted smoke inhaled over a given period of time. The fact that it requires proportionally more of Ihe diluted smoke to make up for a given loss of atrongcr. less dilute, smoke means that Ihe increase in inhalation necessary ni maintain .mokc intake is reciprocally related to the degree of dilution. This produces a hypcrhoiic curve (Fig. 2) from which it can be Keen how a smokcr must increase inhalation in geometric fashion to compensate completely [or progressive dilution of mainstream smoke. Understanding of this relationship helps to explain why smokers found it acceptable to switch from plain cign- rcttcs with nicotine yields of 2.5 mg or more to fiiter-tipped cigarettes with I 20 40, so 80 loo R thtulionol tmoho (.) Figure 2 1'hcrwrucal relaiion.hip hriwrcn xmr.ke dilulinn nnd Ihe iikrrurc in the v,Awne rd snnrke IhM il u rN•ec><ary la inhale ro mainmin intake and compensWe complclety. ( Reprinted, wilh pcnniasiiar. trran 5•non d al. 197d./ nicMino yields of 1.2-1.5 mg, and why acceptability deci" ">rapidly as nicotine yields fall below about 0.6 mg. RELATION OF NICOTINE YIELD OF CIGARETTES TO BLOOD-NICOTINE LEVEL OF SMOKERS In a recent study of 206 women and 124 men who had been smoking their usual cigarettes in their usual way (Russell el a(. 1980), we analyzed the relation of the blood-nicotine levels of the smokers to the nicoline yields of their ciga- retlcs. The results are shown In Figure 3. The most striking feature is the wide variation In blood-nicotine levels (4-72 ng/ml), which bear very little relation In the nicotine yields of the cigarettes. It Is also apparent that the blood•nicotine levels of the men and women were similar, and that il is possible for smokers to get high blood-nicotine levels from a low-nicotine cigarette delivering only 0.6 mg nicotine. The average levels for smokers of the three main types of cigarette, plain (unlipped), filter (unvenlilated), and ventilated filter, ue sh p in Table 1 /. -7 lkTpt •:, stidiffc~ilces!~iG'11i0anochindt>Ijlt~rl'yTe s; ;(h'~,g, di( crent B ~:of`clpurdllc~ the• bio~_nicotme` Icvcis. oE'tiie slttokc fs„ werc oniy slighli~ I'ri\VFa n tl ose on 16e~(ovlre~'-nTc"Qlinc""branda.,^,~~t he nier;m diffe~e/ices' •were not ~ ~i"allsi ligally,ga~~nff"~t'c'ant,~„Csee~.6~p •1'1: an~l'"tft_~ re~o,(~`' f i,'1o,.~,+n co in_ e t~~~;~ t0 m Ell •• •. . a . 0 .a••. •~ 4... a s0 0 • 10 • a 0 : s • : ° a ,s . i s ~ a s 0 r r r r . . .- ~ 0.5 1.0 1.$ 1.0 2.11 0.5 1.9 1.5 2.0 LS ).o ).S A Nkoline yleb Imq/cigarellel Nicotine yield Imqlcparelter Flgura 3 (lhrwlmicrnine kvr4 rrY.nnrkrrM pwNlrJ a0ainsl /he nicrainc yir Wr nr tlheir ririrrne.. All nn.kcrc haJ Gren >muking their own aelr•selcc_tcd ManA M Ihcir uauol way. t,11 I'lain; 1•t on.enu/ared 1ihcr. to) veMilaled (ilmr. (Reprimed, with permi.rion, from Rr.rcll el al. 19N0.) ' • ~ ' r tfiMtOrreS WVZ

vv A `VS 8 C 4 U V C N C v~ C C a0 t0 ~ ~1 „ 1 0 0 0 - N N N N N N ~ Y .tl 0 3 E ~ - 00 N1O P O I « t 1 P O N o0 000 $ 43 na~o,en t~ - ao .8 ~ 8,g 0 6 C C fi x 0 K = a o ~ a u > 0 oi N N N N I N u J n N a~ c ~ Y t V ~ v.4~ V.v,k. 1. "1 M r'1 `I rl M v,o c ~ r > ~ 03 'x k c o O u o » w, o o .•_ ~ 0 u p o C R y ~ rif~ln°O o• o. eZ w r•! .i a ~ 'w . ° ri- .~° 3 . ~ c go E~ 7 Y D Y N-1[ U C w :e ^ ^, y1 C [ E v J i1 u Y n o u3 L 7 -:h:2 e e ~ ~ ~ G ^ I °° Y V N E ~ •- o, C V ~ A u V ~ 0 o V a y' ~ ~Q'S: > tJmu z Eu i:r . ,.v.. 3 w ./ J+ V a Madlum•Nlcotln.. Low•Tar Clg.• "ss 1301 • , . ~tlcotine•Xield~~~lgar~tte'bl~btllQl~;Igpi(jcsnt:DAl~rw~hcn m01e,'pb~tfill•cc- ~ ;~ ~ M....L • ...+. .. _ . . . ....~ ~. ..+, ~„le~gr~l t~t> aro.usCd~~` r o 0.26 in the women (p <.~1) and r= 8.17 tn t e - men (p < 0i.03)'41'hZr overall correlation (men and women combined) between blood nicotine and nicotine yield of cigarelte, though statistically significant, was low (0.21. p < .001) showing that the nicotine yield of the cigarettes accounted for only 4.4% of the variation Irl,bjpod-nicptinc, )ev,Slx. -rw.+7 ~..r ~ ~Ti&i-iric8tine and catbox~'herrlpglobig;,tCOHb~ levels';~e,prultablytthe .,~ W- M M U• ~r. •.. .~ ~e F tndicca.ift th~ ~mount of amokc lakcn-into~the lungs of smoki:~N:ti:Wuhout ~ nHil dl~atlon' ihere' It : n6gligilile,wqksoiplloq~o,f, li~c~iirip,ritld~~ hz ~ Nongc f~ ~~, 4 ~ h~e of CO~Ib ~2, ~ hout;; R "{411 e/ al • 1973,,Wald et a1.;1975)..makes it ' '"bettcr markey of ovcrall smoke,intt~ke over the cour£e of . dsyr;w`~tereas p~ak.,~ ~~b~ood nicot~e. I[~evel 1is deteined nlore by, Netilnta~l(L froirl-tllZs pretctlmgj Igare(te.'(Russellrind Feyera~ 14~8~, liis di~rcrencs~reAected~inihc rcelationsrwilh cigaiefte consumjifion which, though low, were higher in th, case of COHb than for blood nicotine. Even with COilb, the correlation with ~ cigarette consumption was only 0.3 and Indicates that the number of cigarettes smoked accounted for less than 10% of the variance in the amount of smoke taken Into the lungs. To gain sonic idea of how the nicotine nd CO Intake of the smoking population may have changed over the past 20 years a comparison was made between three main types of cigarette. 1. Plain (nonfilter) cigarettes (tar yield 24 mg or more, nicotine 1.7 mg or more), which were the closest approximation available to the high-tar, high-nicotine plain cigarettes of the 1960s. 2. Typical middle-tar, medium-nicotine cigarettes with unventiiated filters (tar 17-20 mg, nicotine 1.2-1.4 mg), which have been the popular cigarettes of lile 1970s. 3. Typical low-tar, low-nieotine cigarettes with ventilated filters (tar 8-11 mg, nicotine 0.6-0.9 mg), which have been promoted by health authorities ar the safer cigarette of the late 1970s but which have been used regularly by no more than 12% of the smoking population (NOP Market Research Ltd. 1979). Since only four of the 206 women smoked plain cigarettes this comparison was confined to men. The 15 male smokers of cigarettes in the plain category mentioned above were compared with IS other male smokers of cigarettes in each of the unventilated and ventilated filter categories. Cigarette consumption and (he length of the cigarettes (small or standard si:e) were matched in the three groups. None of the plain cigarettes smoked was,kin f!-sizcd. The blood- nicotine nnd COI Ib levels of smokers in these three groups are shown in Figure 4, together with the average daily cigarette consumption of the smokers and the avcr.agc standard tar, nicotine, and CO yields of their cigarettes. • II can bc seen tltot the blood•nicotine levels of smokers of plain, unventi- latcd lilter and ventilated fillcr cigarettes (means 17.4, 33.9, and 32.9 nt;/ml respectively) did not differ signilicanlly despite the large iliffcrcnces in nicotine I i

M.A.H, qussoll x. 'rhe COI Il+s, howcvcr. wcre significantly diffcrent (means 6.2, 8.2, and • rc.pectivcly) wi11t snfukcrs of plain cigarettes tending to have lower levels tlre ulher two groups. In stlmmary then, this study of sntokers who were smoking their own ;elcctcd hrunds in their usual way showed that cigarette consumption, tar licotinc yield of cigurettes, and type of cigarette made very little difference accounlcd for very little of the variance in blood-nicotine and COHb s. This suggests th:d dle suinke intake or smokers is determined largely by indivi duul patterns of puffing and inhalation and that the assumed health ntages of smqking cigoreuesl with lower machine-smokFd tar and nicotine s is largely tjCfscl by the tendency for smokers to modify their smoking rn to rcgulofc their intake to a fairly constant level. Morcover, the very I tendency for smokers of lower-nicotine cigarettes to have lower blood- inc levels could be due mainly to the sample.having selected their own J nf cigarettes. It is possible that Ihe smokers who had chosen lower inc brands may have been those with slightly lower blood-nicotine levels •e muking the swilch and that this factor, ralher than any reduction of e after switching, could have accounted for the low correlations observed cen blood-nicotine level and nicotine yield of cigarette. 1,~ rw Ith,. AVNI, nU.r d~ rl•iw . : ; 2. { JI ."r . . .. , / I 1 1 lw.l« .IrA .•MIINd llbcr MIMI• r.. whh Illr« 11r N•4, •rlry, i • . .. , , r re 4 vri.on of btood•nicoline and COIIb fevels of 13 male smokers of plain ellarerlas with Kd rroupa of smokers ol, mirfdle-ut, medium-nicorine eigarettes with unvenlilaled fillers and :rs of lor-lu. tow••nicmine ciKaet/es with venlitaled Rltcn. The groups were matehed for tic con>umplion and site of cirareue. Avcr.ge eonsumption for the grawps nf low•Lr, e~rar and plain cipartna ~motcrs wa% 21.9. 24.9, and 19.5 respactively for cigarettes smoked : day and 41.2. 41.9. and 43.7 fm usual daily ennsumpuon. AveraEeyields of thc tigarelues cJ hy each Kroup re.pcclivcly were 9.), 11.3, and 26.4 mj alr 0.11. 1.30. and 1.96 me oe: 11.7. 17.11. and 14.11 mg CO. An.ly.is of variance for matchcd groups showed no icaul difference in 16e bh.rd nicmine level. »f snwkers In Ihe Ilueo srnups (F - 0.6, rJf 2/2b, but the COIIb levels were signilicandy dilftrenl (F * 611, r(/2/2N,p <.01). tdsdlum-Nleotln., Low•Tar CIL .as /308 COMPARISON WITH FORCED SWITCHING STUDIES Forced switching refers to the situation In which smokers arc required by thc conditions of a study to switch to high- or low-nicotine cigurcttcs. This contrasts with the conditions of our recent study in whiclh the smokcrs had selected their own brands. I am aware of only three forced switching studies that included measures of blood nicotine and COFIb (Russell et al. 1975h: Sutton et al. 1978; Ashton et al. 1979). All three were short-term studies, 2 weeks or less. Blood-nicotine levels were not significantly increased after switching to higher-nicotinc cigarettes (Russell et ai. 1975b; Ashton et al. 1979). This.agrees with the data on smokers using their self-selected•brands (Fig. 3 and 4;,Table 1). However, when nicotine yields were reduced, blood- nicotine levels were lowered; albeit proportionately less than the reduction in cigarette yield (Russell el al. 1975b; Strtton et al, 1978; Ashton e_t al. 1979). This contrasts with the data on smokers who had self-selected their lower- nicotine brands. The smokers In the forced switching studies were not satisfied by smoking cigarettes with reduced nicotine yields, possibly because they did not compensate completely and thereby allowed their blood-nicotine levels to decrease. It Is unlikely, therefore, that they would have remained on such low-nicotine cigarettes had they tried switching under natural conditions. All this suggests that,. under natural conditions, switching to lower-nicotine ciga- retles tends to occur and be maintained only when compensation is complete and enables the switch to be achieved without reducing nicotine and tar intake. IMPLICATIONS FOR LESS HAZARDOUS CIGARETTES Although the plain cigarettes of the 1950s and earlier had tar and nicotinc yields about twice the levels of the middle-ulr, medium-nicotine cigarettes with unventilated filters that have been the most popular type since the late 1960s. it is very unlikely that the intake of tar and nicotine in those days was propor- tionately higher. Indeed, our data suggest that the intake was probably similar or only slightly higher. But epiderniologisls claim to have shown that lung cancer rates have betn reduced by switching to filter-lipped cigarettes and it has been widely assumed that this is due to a reduction of tar intake (Bross and Gibson 1968; Wynder et al. 1970; HHammond et al. 1976; Dean e1 al. 1977• Auerbach et al, 1979)• Either our data and conclusions are wrong or ttre Interpretation and assumptions based on the epidemiological evidence are wrong. How then can our data be reconciled with the epidemiological data? First, the epidemiological data are based on sclf-selected samples, i.c., those smokers who were the first to switch to ffl/er-lippcd cigarettes were compared with those who for their own reasons had not switched. Bcsidcs the many.. social factors, it is quite possible ahat Ihe first to switch were thosc who inhaled less. I•t_cannol. Iherefore, be assumcd Ihnt switching per se reduced the incidence ef iung cnnccr. Sccond, thc gradual decline ili lung cancer. even among smokers. Is,.not necessarily due to the cnncurrenf switchimr nt'Ihc 91:4tr4Srzoz

4.H. nussell population to fiiler-tippeJ cigarettes with lower tar and nicotine yieids, r the same period, changes In the processing of tobacco have resulted luclinn in its specific carcinogenicity (Gori 1976). The reasons are tatcly unknown. Thus a given amount of tobacco Iar from the cigarettes 970s is lu.s likely to proJucc cnnccr than Ihe some umuunt of tar fronj :s or Ihe 1950s. c epidemiological evidence may nol. Ihcrefore, challenge our eonclu- scems thut the cancer risks from smoking have been reduced although and nicotine intake by smokers have remained largely unchanged. Ihe switch to cigarettes with unventilated itlters may have done more un good. It may have increased the CO intake of smokers and thereby ncd to an increase in smoking-related coronary artery disease. Unventi- Uers do not reduce CO yields (Russell et al. 1975a), but, because the rapping tends to be less porous than the rest of ihe wrapping paper, CO of cigarettes with unventilated filters are a little higher than plain cs (Russcll ci al. 1973a; Wald et al. 1977). Wald (1976) made out a ise for attributing the increase In coronary artery disease in Britain to the ;o cigarettes with unventilated filters and has suggested Usat this Is due to xr CO yield. I would agree but suggest that the increase in CO Intake is .re to self-regulation of tar and nicotine, and hence total smoke, intake han to the slight increase in CO yield. In other words, the main reason ain cigarettes are less harmful in CO terms than unventilated filter cs is because they are inhaled less deeply. hat about low-tar, low-nicotine cigarettes with ventilated filters? Due to ttilation of the filters, the CO yields are lowered to levels that are, on :, even less than those of plain cigarettes (Russell et al. 1975a; Wald et 17). Ilowever, most of this advantage is offset by the tendency for ,s to smoke them more intensively and to inhale more deeply to compen- r the reduction of tar and nicotine. Likewise, for the same reason, tar and c intake is only slightly reduced, anJ the reduction is statistically signifi- Ay when correlational tests are used. conclusivn, the current low-lar, low-nicotine approach to safer ciga- s severely limited not only by the lack of acceptability of such cigarettes o bccause of the tendcncy of smokers to Inodify their smoking pattern to e their smoke intake. The extent to which this (s due to a desire for e is unknown but crucial. I have suggested before (Russell et al. 1973; 1 1976) that a low-tar, low-CO, but medium-, rather than low-, nicotine te might reduce tar and CO intake more than occurs with low-tar, O. low-nicotine cigarettes. It might also be more acceptable to smokers. indings reported here support the view that a new approach in this on would bc worth investigation. OWLEDGMENTS : Ihc Mcdicad Research Council. London, England for financial support, . , ,c.~~,~~szzoz Medlum-Nlaotine, Low-Tar Clps ' /307 Jean Crutch for secretarial assistance, and my colleagues Stephen Su11on, Martin Jarvls, and Martin Raw for their constructive comments. r , REFERENCES Ashton, H.. R. Stepney, and J.W. Thompson. 1979. Self-litration by cigarette snsokers. Brir. Med. J. 2037. ,Auerbach, O., B.C. Hammond, and L. Garflnkel. 1979. Changes In bronchiol epithelium In relation to cigarette smoking,.1933-1960 vs 1970-1977. N. Engl. J. Med. f00:381 ' . ~ Bross, I.D.I. and I(. Gibson. 1968. Risks of lung cancer in smokers who switch to filter cigarettes. Am. J. Public Hndrb 58:1396. Dean, O., P. N. Lee, O. F. Todd, and A.J. Wicken. 1977. Report on n serrmd relroslrer- rJre mortality study In North East England. Part l. Research Paper 14. Tobacco Research Council, London. Oori, O.B. 1976. Low-risk cigarettes: A prescription. Science 19411243. Oorf, O.B. and C.J. Lynch. 1978. Towards less ha:ardous cigarettes.J. Am. Med. Assoc. ' 240:1233. Nammond, B.C., L. Oarflnkel, H. Scidmsn, and E.A. Lew. 1976. Tar and nicotine t content of cigarette smoke in relation to death rates. Enrlron. Rcs. 12:263. Lee, P. N., ed. 1976. SrarJiries of mroklnt In ltie United Kingdom. Research Paper 1, 7th edition and supplements. Tobacco Research Council, London. NOP Market Research Ltd. 1979. Survey on smoking habits carrkd out for Oflice of population Censuses and Surveys. London. Russell, M.A.11. 1976. L.ow-lar, medium-aieotine cigarelles: A new approach to safer smoking. Brit. Med. J. 1 r 1430. . 1979. Tobacco dependence: Is nicotine rewarding or aversive? Nor. Insr. Drus Abuse Rrs. Mwroxr. Ser. 23:100. Ruuell, M.A.IIr and C. Fcyerabend. 1978. Cigarette smoking: A dependence on high. nicotine boli. Drug Mea:h. Re.•. 8:29. Russell, M.A.H.. P. V. Cole, M.S. Idle, and L. Adan:s. 1973a. Carbon monoxide yiclds of cigarettes and their relation to nicotine yield and type of f iUer. Bril. Mrd. J. 3•71. Russell, M. A. H., M. Jarvis, R. lycr, and C. Fcyerabcnd. 119110. Relatiun of nicotine yield of cigarettes to blond nicotine level of smokers. !lrir. Mrd. J. (in press). Russe_ll, M.A.H., C. Wilson, U.A. Patel, P.V. Cole, and C. Feyerabcnd. 1973. Com- parison of the effect on tobacco consumption and carbon monoxide absorption of changing to high and low nicotine cigarettes. Drir. Merl. J. 4:312. . 1973b. Plasma nicotine levels after smoking cigarettes with hiEh, medium and low nicotine yields. Brlr. Med.J. 2t414. ~ Schachter, S. 1978. Pharmacological arid psychological delenninants of smoking. Ann. Inrern. Med. AAt 104. ' Sutton, S.R., C. Feycrabend, P.V. Cole, and M.A.Ii. Russell. 19711. Adjustment of smokers to dilution of tobacco smoke by ventilated cigarette holders. Clin. /Yurr. nnrrol. Thrr, 24:395. Todd, G.F. 1973. Clwnre.s in smokinfi Irmrrrns In rhe UK. Tohaeeo Research Cnuncil, Lnndon. . .