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I I I I I I I I I ~ I I I I I I Journal of Epidemiology and Community Heulth, 1986. 40, 80-55 Reduction of tar, nicotine and carbon monoxide intak in low tar smokers .14 A H RUSSELL.` M J JARVIS.` C FEYERABEND,' AND Y SALOOJEE= From the Addiction Research Unit. ` Institute of Psychiatry, 101 Denmark Hill, London SES BAF; Poitp Unit,=:yew Cross Hospitai, London SE14; and Anaesthetic Research Laboratory.' St Bartholomew's Hasp(a London ECI SUMMARY Blood nicotine, cotinine, and carboxyhaemoglobin (COHb) concentrations we measured in 392 smokers (255 women and 137 men) of "middle tar" (17-22mg), "low to middk (1 1-16mg), and "low tar" (< 1 1 mg) cigarettes. Since tar intake cannot yet be measured direcil we devised an index to estimate it based on the use of measured levels of an intake marker (e blood nicotine) and the ratio of the tar to marker yields of the cigarettes. This approach wt validated by its,ability to enhance the prediction of levels of one marker by use of another. F~ practical test, using COHb and the CO/nicotine yield ratio of the cigarettes, the mean nicotine concentration of the low tar smokers was predicted to be 31•9ng/ml compared wi measured mean of 31•8ng/ml. Our main findings were that despite substantial compe increases in inhalation, the low tar smokers took in about 25% less tar, about 15% less nicotine,s>D about 10% less carbon monoxide than smokers of middle and low to middle tar cigarettes. T3q results indicate that low tar cigarettes of the type available in Britain since the late 1970s are li7t6 to prove less harmful than other brands. Monitoring of smoke intakes could suppleme epidemiological approaches and provide earlier evidence of whether changing cigarette desigt lead to any significant dosage reduction that could affect the risk of disease. For more than a decade many countries have had policies for reducing the tar and nicotine yields of cigarettes. Such policies are based on the assumption that the amounts taken in by smokers will also be reduced. so lowering tlieir risk of developing smoking related diseases. It has become apparent. however. that much of the potential health benefit is undermined by the tendency of smokers who smoke lower yielding cigarettes to smoke them more intensively. Several studies have shown that despite large reductions in the machine smoked yields of their cigarettes (up to 40%) smokers who have chosen to smoke a lower yielding brand have blood nicotine,l' cotinine3 and COHb" concentrations similar to or only slightly lower than those of other smokers. In this paper we compare blood nicotine, cotinine. and COHb levels in smokers of "low tar" (LT) cigarettes (<10•5mg tar per cigarette) with those of "low to middle" and "middle tar" smokers to see the extent to which lower yields are associated with lower intakes. Although tar intake is of particular concern. no direct measures are yet available. We have devised and validated an index of tar intake based on 80 the blood levels of a marker such as nicotine or C and the tar/nicotine or tar/CO yield ratios of tt cigarettes. We use this index to estimate the t intake of LT smokers compared with smokea i other brands. Subjects and methods The study population consisted of cigarette smoim who attended the Maudsley Hospital smokers' eiiti during 1978-81. We excluded those who staob cigars or hand rolled cigarettes and six subjectsvi smoked cigarettes in the "middle to high";.'t category (23-28mg/cig). The number of subja after these exclusions was 255 women and 137 am All subjects attended in the afternoon. having ba instructed to smoke their usual brand in their usa way. On arrival they were asked to smoke one of the cigarettes, and a venous blood sample was taken te minutes after they had finished it. Plasma nicoti: and cotinine concentrations were measured by g: chromatography" and CO intake was meastae using an IL 182 CO-oximeter or an Ecolyzer.' 12 tar. nicotine, and CO yields of the cigare"We ~ ~ d '

I I I I I I I I I I I I ~ ~ I I I I Reduction of tar. nicotine and carbon monoxide intake in low tar smokers 81 obtained from the tables published bv the Health Departments of the United Kingdom. An index of tar intake was derived from the measured intake of a marker and the ratio of the tar to marker yields of the cigarette. For example, the index of tar intake using plasma nicotine concentration as a marker was derived as follows: TI (Nic) = Plasma nicotine xTar yield of cigarette Nicotine yield of cigarette = Plasma nicotine x T/N yield ratio Such an index assumes that the intake of different smoke components relative to one another is in proportion to their concentrations in the smoke. Since we measured more than one marker it was possible to test the validity of this approach by its ability to predict the levels of one marker from another better than the simple correlation between the two. Rrsalts Table 1 gives the details of the cigarette consumption and intake measures of men and women according to the tar group of their cigarettes. On average, the women were two years younger than the men, and more of them were LT smokers (43 v 31%, X1=5•0, p<0•05). Although daily cigarette consumption was sliahtly lower in the women, the number of cigarettes Smoked before the blood test on the day they were seen was similar in men and women. There were no statistically significant sex differences in any of the three intake measures (table 1). There was no relation between tar group and dsuette consumption. In particular, there was no tendenc} for LT smokers to smoke more cigarettes. However, in both men and women• the blood levels of all three intake measures were significantly lower in the LT smokers. The average levels in the men and women combined for middle• low to middle. and LT smokers respectively were: 38•8, 37•0, and 31•8ng/mi nicotine; 367. 416, and 333ng/ml cotinine; and 7-8, 8•0, and 7• 1%, COHb. In no case did the low to middle tar group differ significantly from the middle tar group, whereas in each case the levels in the LT smokers were significantly lower than in the other two groups. RELATION OF CIGARETTE YIELDS TO CONCENTRATIONS IN BLOOD In the figure the individual values for each marker are plotted against the corresponding standard machine smoked yields of the cigarettes smoked. The data for men and women were combined because their patterns were similar and the regression lines for men and women did not differ significantly. The pattern was also similar for the three intake measures, showing wide variation between subjects but little relation to cigarette yields. The correlations between cigarette yields and blood concentrations were statistically significant but low. The cigarette nicotine yield accounted for only 6•8% of the variance in blood nicotine and 1• 7% of the variance in blood cotinine. Likewise, CO yield accounted for only 6-396 of the variation in COHb. NICOTINE, CO, AND TAR INTAKE Table 2 compares the intakes of LT and non-LT smokers. The average blood nicotine and cotinine Table I Cigarette consumpdort and intake measures of men and wonten smokers of different types of cigarette Mex Wawe. ror/r Smamc.i ntnrJk.an o(diff- L.w r Lav r Midd7e ra (e- 70) wi/trr r (o-25) Le. r (s.t2) Midlille r (*-I09) WrAd/e r (n.37) Low r (e-I09) Ma. (x-f37) Wawa (n-2SS) Eet,.eew r 2roupt ae+.een"aa 1 3b-t 40-7 42•8 37•0 39 5 39-t 40•4 38J F-3•S. p<0•0S F-3•9. p<0•05 YWt cosom"M (Mi). Tr 17•9 15-3 9.1 lt! 15•1 9•2 14•i 13•9 Wk+Ofyt 1•4t 123 0•{4 1•47 128 0•i7 1•24 1•li F>100•p<0•001 F-0•9, NS C4rla. Abotqxide 17.1 15.0 10.9 17•4 14•4 11.0 14•{ 142 F>l00, p<0•00I F-0•3. NS ~iltaoe an.~.mpoo~; o.abepa day ~ 32 6 29•1 31•9 2a•9 32•4 2910 31•{ 29•0 F-0-6. NS F-4•9. p<0-05 r 14•6 14•0 1S•S 13•7 16•3 13•0 14•t 13•i F-0•9. NS F-1•3. NS rlr.~ rom.r (ni/.i) 3t 3 37•9 34•t 39-1 36•4 30 7 37-2 33•1 F-10•7, p<0,0o1 F-0•i. NS p~t .efitrat ( tW d) 357 43$ 392 370 403 327 382 354 F-3-0. p-0•031 F-0•3. NS cow (1!) 7•6 !-4 7•4 7•9 7 i 6•9 7•7 7•4 F-3-7. r<0a0S F-0•2. NS ~ AB.w,.e tbe .as (« ue ~otw,...er tar awp. Tre tar Qe~pc d a.r ,~pnees.ete au~o..eK.mo~aR eb Ae wblalea tsble..aN ey IYe +~~ D1}rtreaa d the Uwad Kiugido..d t+ee r(oYows: Middie tar (17-22.WaB)• Low to etddle tv (11-l6nt/dS)• a.d Low tu (0-10m{taS). The "40d lorrboaa d the dMteretws bstreeta tat awps aed aesec are bred oa twway ANOV As. Tltste wert so upufiant taterocoom. The pium mwrac "IOr Ys 1od a fwlkr ea,.bees. The tmsl iautpk .nt,.vW.b/e pluam cdtn.e data wnbas 241. but they d1d aot differ ttas tie romn.du 0( tYe+rb>em t. "`afiow ewtaa .ad v.rne/a. I

82 N A H Russell• J•! J Jarvis, C Feverabend. and Y Salooj, 90-7 80-W IA 400 0 . . a. 300 . w ~ • 200 : 100 - . ! ~ ~ 1 r ~ ~ ~ ~ 0•4 0.6 0.8 1 0 1.2 1.4 1 6 1 8 Nicotine yield ( mg lcigorette ) 22 20 18 16 14~ 2 2 0 , . ..i • 1100 10001 ~ 900 E 800 " 700 4 C 600 V0 500 0.4 0.6 0 8 1.0 1.2 1 4 1•6 1•t Nicotine yield (mg/cigarette) 6 10 14 18 22 26 30 Corbon monoxide yield (mg/cigerette) Blood nicodne. codnine, and COHb cortcentradons ojindividual smokers plotted against the euoane or carbon niowartis yiddr of dtdr eigaretus. The linear regression lines are also shown. The regression data were as follows: Blood nieoit 21 •8+11 •7 nicodwe yield, r=0•16, p<0•001; Blood eotunine=274 +71 •S nicoane ytelQ r=0•13. p<0•OISr COHb=4•7 0•10 carbon monoxide yield. r=0•15, p<0•001. concentrations of LT smokers were respectively 1714, and 12% lower than in non-LT smokers. The reductions in these two measures of nicotine intake were therefore substantiallv less than the 3914. reduction in the average nicotine yield of the LT cigarettes, indicating the extent to which the LT smokers were compensating for lower yields by increased inhalation. Similarlv, the reduction in CO intake was only 1U•6'% compared with the 341% reduction in CO yield. Tar intake indices were calculated based on the use uf blood nicotine. cotinine, and COHb as markers. I can be seen in table 2 that there is good agreemen between the three estimates. On average tbt estimated tar intake of the LT smokers was aboal 25% less than that of the non-LT smokers.

I I I Raducliost of tar, nicotine and carbon monoxide intake in low tar smokers 83 Tabk 2 Average percentage reductions In tar. nicottne. ~ tn/ earbon monoxide intake of !oK• tar smokers in ;otwp.rtson with smokers of higher yield brands. I ~ I NOn low Wr Low aCr tnto4es an,okm tn=:4L le-1J1) +.Reducnon cors. ru: Tar rrY (y/eW 17 z 9.2 46 R Msut Veid (ei/at) 1 a: 0.96 39 3 CO OY (.ra9) 16 6 11 0 34 I 1INeeYe 123 (008) 108 (010) 1.1"' TR0 IN" 106(001) 0.85 (001) 198••• Ir9 fit 1411111111111 dff#Aw (ytiaq 38 3(0•91) 31.8 (0 99) 17 0•'• ll111111111sWr(rytlal) 379 (137) 333 (162) 121' COWAM 781(0.18) 706(0a20) 106" ir1o .l.r i.akc TI tt.q 469 (11 2) 341 ( t0 4) 27 3 'n (ty0 4601 (166) 3543 (164 1 13 0"' 11 (OD) 8 13 (0119) 5 93 (0 16) 27 1"' %oV-' The pluma axmtne data are naxd on smaller sample. oi t in non la. u roieraaaW 951ov tar unoken. but these wbsampks did not ditter trom the nardor d tYe eb/cas tn aay of the oaBer eeawra used. The peranta8e 0111111111101110 ill C10Ftb nas -la+lated after tubcsabn 0.7 to cortea (or the WdWand Ind h'ao.-smoken. standard eras arc +ho" n pareaclwes. nietdF~ 7M e>~boa aad adacea of tar f wkewvre eompxted (or tndmdual -#m 4ise aresapn8 them to obnte -the poup meaw. Stattwal "11111111kaboe ot dtderenoes are basad on i tests between non br tar and tow tar 'Eotaa: '~p<OaOOt. "p<0 01. 'p<O OS. I YAL{DATION OF THE 1tNDEX OF TAR INTAKE It it not possible at present to validate the index of tar taAate against a direct measure. However, if a similar tndex of intake of one marker (eg, COHb) based on the bvels of another marker (eg, blood nicotine) can bt shown to enhance the prediction bf actual mewtred levels of the first marker, some validity for the ratio based index of tar intake can reasonably be it~sed. ta predicting COHb from blood nicotine we found that the index of CO intake (based on the blood ~ nicotine concentration and the CO/nicotine yield ratio) predicted COHb substantially and significantly better than blood nicotine concentration on its own (ie, without taking account of the CO/nicotine yield I ratio of the cigarettes). The correlation of the index with COHb was 0•72 compared with 0•60 between blood nicotine alone and COHb. The index therefore aaounted for 52% of the variation in COHb Icompared with 36% in the case of blood nicotine alone. Likewise, in predicting blood nicotine from COHb, the correlation with the index of nicotine tntake (based on COHb and the nicotine/CO yield ratio) was 0•69 compared with 0-60 between blood aiootiae and COHb alone, a highly significant fapt+ovement. f.orrelat;onal data of the type described above are oooettaed with predicting intakes of individual sipkers. When comparing large groups or POPtdations, however, much of the variation due to individual differences in intake and differences in half-lives of the markers. etc. will be balanced out. The abilitn of the index to predict the average levels of smoke components in the LT smokers as a group from the average levels found in the non-LT smokers is illustrated in table 3. The predictions are close to the measured means. suggesting that the estimated reduction in the tar intake of LT smokers, shown in table 2. is also likely to be fairly accurate. Discussion Smokers of LT cigarettes had a lower intake of tar, nicotine, and CO than the smokers of higher yielding brands. On average, their estimated intake of tar was about 25%t lower. their intake of nicotine was about 15% lower (1714, and 12% as measured by blood nicotine and cotinine respectively). and their intake of CO was about 10OA, lowec. These differences are substantially less than the reductions in the standard machine smoked yields of their cigarettes (47%. 39%. and 340(r for tar. nicotine. and CO yields respectively). and this indicates the extent to which the LT smokers were smoking and inhaling more intensively, presumably to compensate for the lower yields. However, it is clear that despite such compensatory changes in smoking behaviour their intake of the three major smoke components was still lower to a statistically and clinically significant degree. The results were essentially the same in men and women. There were no significant differences between the sexes in the blood levels of any of the intake measures or in the degree of reduction found in LT smokers. Table 3 Comparison of the average levels of smoke components measured in low tar smokers with those predicted from the levels in non low tar smokers using the intake index based on a different ietake marker tn"ke WArk. tue/ Jo. Irtined Me.re/ Mwewr orediesef o.1detrdw /evN tevd COHb (+~) Blood auonnc 7 0 7.1 COHb (~.) Blood mudne 7 3 6 9 Blood rucottne (n8/ml) COHb 31 9 31 8 Bktod cataae (uB/nN) COHb 316 333 wAeee blood cat mne ooooeetntwns were uud u the aaarter or the aeeawre to be Pradaaed the values aro based on fewer sub)eua. TAe tonwla tue4 for the pedKtm o( COHb trow biood ntooune a tbo.n bdo.r. srM(ar (onnrLe .we used to pred6a the levels of other oomOoeeata us+wg approqnate maetun. Fredbot" COHb ut COHb in Blood nrcoune x CORvioatne yield ratw d LT s.oten LT -non LT % smohen ataa/eers Blood rucoanexCOtHt6oune yrcld ratio of roa LT saeoten A

I I I I I I I I I I I I I I I 84 M A H Russell, M J Jarvis, C Feyerabend, and Y Salooj The reductions in nicotine and CO intake are based on observed levels measured by methods of established reliability. Our findings are consistent with our earlier study' and the more recent report of Ebert et al' in showing wide individual variation in blood nicotine concentrations with only a small proportion of the variance accounted for by the nicotine yield of the cigarettes. In our present report. however. we have focussed not on how low the correlation is between nicotine yield of cigarettes and blood nicotine concentrations in smokers but rather on the clinical significance of the slope of the regression lines. In other words, we are less concerned here with how much compensation occurs and more concerned with the extent to which it is incomplete. In this respect we disagree with Benowiu et al,' who conclude that "smokers of low yield cigarettes do not consume less nicotine". Using blood cotinine as their measure of intake, the correlation with yield of cigarette was 0• 15, which is similar to our value of 0• 13. However, the sample of Benowitz a a! was, at 137, too small to detect a 12-179t, reduction in nicotine intake as was found in our LT smokers. Our findings also differ slightly from those of Wald et al, who measured COHb levels only and concluded that CO intake was not reduced in smokers of cigarettes with ventilated filters (mainly LT) compared with smokers of cigarettes with unventilated filters (mainly non-LT).' Their results were based not on the measured COHb levels but on an index which corrected for the previous day's smoking and the reported number of cigarettes smoked on the day and would have relied to some extent on the accuracy of such sdf-reports. Our estimate of the reduction in tar intake should be viewed with some caution. The index on which it is based is not a direct measure. Due to lack of reliable evidence we have had to assume that the tar to marker ratios under human smoking conditions are similar to those derived from the standard machine smoked yields or that, if altered, they are altered similarly in LT and non-LT smokers. While it is well known that the yields of all components vary according to the intensity of puffing, it is not clear what happens to the ratios between yields of one component and another. It has been shown that the T/N ratio is reduced by increasing the rate of puffing but increased by taking larger puffs.' Fortuitously, this might mean that when both puff rate and puff volume are increased the' T/N ratio remains fairly constant. The effect on T/N ratios of various attempts to replicate human smoking conditions have so far had conflicting results."" When more reliable data become available it will be possible to refine our index for estimating tar intake. Meanwhile, the fact that the index, in its present form, has been shown to predict intake better than simple correlation with *~ marker and the fact that by its use the levels of on4~ marker, predicted from another, were close to themeasured levels suggest that our estimate of t$ft reduced tar intake of LT smokers may be fairly accurate. It is noteworthy that part of the estimated reduction in tar intake reflected the lower ratios of tar to marker yields of LT cigarettes. In other words, tat yields were reduced proportionally more than nicotine and CO yields. Had the reduction in tar yields been proportionally the same, the reduction in tar intake would have been similar to the 10-15% reduction in CO and nicotine intake instead of the 25% reduction estimated. This points to the importance of considering the ratios of the yields of various smoke components to one another as well as their simple reductions. Two things should be borne in mind wiit considering our results. Firstly, our sample consisQ of heavy smokers whose average daily consumptioj of 30 cigarettes per day was almost double that at smokers in the general population. It is possible that the results would be different in lighter smoker3. Secondly, the LT smokers were self selected in the sense that they themselves had chosen to smoke a LT brand. It is possible that if they smoked a higher yidd brand their smoke intake would still be lower than that of non-LT smokers so that their lower intake cannot be attributed to the lower yields of their cigarettes. No prospective study has been published which examines whether natural switching to LT cigarettes is accompanied by a reduction in smoke intake. Self-selection problems have also bedevilled most of the epidemiological studies of the relative risks of lower yield cigarettes." The mo.re robust studies based on age-specific secular trends have shown that the lung cancer risk from smoking filter tipped cigarettes of the type now rated as middle tar appeas to be lower than that of smoking plain cigarettes af the mid-I950s and before. But they cannot tell utyet about the risk of present-day LT cigarettes and Me may have to wait until the year 2000 for this. Indeet, cigarettes and people's smoking habits and choice of cigarettes are now changing so fast that it is difficdt to see how epidemiology alone. besides the probtetas of long delays, could in future come up with any definitive answers. On the other hand, repeated monitoring of smoke intake using several measures could provide us with ready commonsense answers as the years go by and smoking habits and the design of cigarettes change. This could be done as regularly as the Government Chemist now monitors the yields of cigarettes. All the main intake measures can be done by non-invasive methods.

I I I I I Reduction of tar, ntcotine and carbon monoxide intake in low tar smokers 85 In conclusion, heavy smokers of present-da} LT cigarettes with ventilated filtets, despite substantial compensatory increases in inhalation. take in about 25% less tar, about 15'%, less nicotine, and about 1 Uth, less CO than heavy smokers of higher yielding brands. Part of the reduction in tar intake is due to differences in the ratio of the yields as opposed to simple reductions in yields. We cannot say from the present data whether smokers who have not yet switched to a LT brand would show similar re.ductions if they did. ' We thank the Medical Research Council for financial ` support and our colleagues Dr Stephen Sutton and - Dr Robert West for valuable advice. ~ References ' Rusaell M I I I I I I I I AH, Jarvis M, lyer R. Feyerabend C. Relation of tsiootine yield of cigarettes to blood nicotine coocentradons in smokers. Br Med J 1980; 230: 972-6. 'Ebert RV, McNabb ME, McCusker KT. Snow SL.JAMA 1983; 250: 2840-2. 'Beno.vitz NL, Hall SM. Herning PJ, Jacob P, Jones RT. Osman AL. Smokers of 'low-yield cigarettes do not cansume kss nicotine. N Eng1 J Med 1983; 304: 139-42. ' Wald NJ. Boreham J. Bailey A. Relative intakes of tar. nicottne, and carbon monoxide from cigarettes of different yields. Thorax 1984; 39: 361-4. 'Feyerabend C. Russell MAH. Assay of nicotine in biological materials: sources of contamination and their elimination, J Pharm Pharmacol 1980; 32: 178-81. 'Feyerabend C. Russell MAH. A rapid gas-liquid chromatographic determination of cotinine in biological fluids. Analyst 1980; 105: 998-1001. 'Jarvis MJ, Russell MAH. Saloojee Y. Expired air carbon monoxide: a simple breath test of tobacco smoke intake. Br Med J 1980; 281: 484-5. 'Creighton DE. Lewis PH. The effect of smoking pattern on smoke deliveries. In: Thornton RE. ed. Smoking behaviour: physiological and psychological influences. London: Churchill Livingstone, 1978; 301-14. 'Stepney R. Would a medium-nicotine, low-tar cigarette be less hazardous to health? Br Med 1 1981; 293: 1292-6. 10Koziowski LT. Rickert WS. Pope MA. Robinson 1C. Frecker RC. Estimatintt the vield to smokers of tar. ntcnttne. and carbon monoxide from the "lowest % teld". ventilated filter-ctltarettes._Br J Addtn 198=: 77: 159-65. "Hoffmann D, Adams J>), Haley NJ. Reported cigarette smoke values: a closer look. Am J Public Health 1983; 73: 1050-3. "Rawbone RG. Switching to low tar cigarettes: are the tat league tables relevant? Thorax 1984; 39: 657-62, 76 Russell MAH. Are cigarettes getting safer? Br J Addict 1984; 79: 241-3. I