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INFNiALATIONiAND ABSORPTION 0'F TOBACCO SMOKE 181 Non-smokers fell within ai relatively narrow range (mean PACO 0.004 mmHg; S.D. 0.002 mmHg) whilst the rangF for smokers was mueh greater(mean,PACO 0:016 mmHg; S.D. Qi008' mmHg). The two populations are significantly different (unpaired t test, p<0.001'). In order to evaluate the suitability of the technique for more detailed studies of' smoking;behaviour the changes in PACO with smoking,were followed over a 12-hour peniod'intwo volunteer, regular smokers of ten to twenty middle tar cigarettes per day. Neither subject had smoked for at least 12 hours prior to the commencement of t'he study period during which they were allowed, tb smoke without restriction: Both smoked the same brand of cigarette whichlyielded 25mg,carbon, monoxide/ cigarette under standard (TRC) machine smoking cond'itions: Before smoking each cigarette and exactly 15 minutes after, measurements of PACO were obtained and the results, from both subjects areshown in, Fig: 14.9. It can be seen that t'hePACO increases with each cigarette smoked (mean increase 0:0036 mrnHg, subject A; mean increase 0.0027 mmHg, subject B) and fell between~smoking, The overaff pattern in both subjects is a rise iim PACO~during the early part of the day with a tendency for the level to plateau after 14.00 hours. In subject B, who.was~asked to chain-smoke four cigarettes at the end of the study period, there was a further increase in the level of PACO. Cigarette butt nicotine analysis The characteristics of a filter cigarette can, by machine smoking the product using standard!(TRC) smoking parameters, be definediin terms of the measured!mainstream smoke nicotine and'a derived filter retention efficiency. The filter retientioniefficiency is calt:ulated from measurements of the mainstream smoke nicotine and the filter, nicotine: NR Filt~er~r~etention effaciency~~(F), = ---- -(4)~~ Ns+NR where NR is the filter nicotine and Ns is the mainstream smoke nicotine. If it is assumed that the filter retention efficiency is a constant for any given product specificatiorrthen, knowing,tihe amount of nicotine retained in the filter after human smoking„it' is possible to estintate the amount of nicotine presented to the smoker (mainstream smoke nicotine). ' N,R(I-F). Na = F .(5) Once the amount of nicotine presented to the smoker has been determined, an index of the way in which the cicarettc has been smoked may be obtained by ~ calculating the ratio of't'he smoker's mainstream smoke nicqtiine value to the main- 0' stream smoke nicoitine measured on machine smoking. We have calltd this the ~ nicotine coimpensation ratio whichL because it relates the.smokers value to the O standard machine smoking fiigure, may be compared both betwecn subjects and across product ty v 1 pes , . tN .~s~ ~'

S Venous HDCOSaturation .o w ., ~ w. ~.. ~~~ 1 1 r l r r ~ N \ r 1 m r W_ m ~ ~. < ~ m w ..: :::.:. .::. :. . . .:. .....:.; . .: .. . ..... ~::::.:.. .. .... . . .. ... ... .. O .. ...::.: ~ ~.:.. ; . '. ^ i~, Fig. 14.9 Variatioins in alvuol2r carbon monoxide parrtiai1pncsaunc with cigarette smoking throughowt a 13'•hour period in two subjccas (A ana BD1 The verticaa bars indicaae periods of ciearetue smnk;n.. 1005053000

IN1tALATIbN AND .aBSOAtI'TIION OF TO&ACCD SMOKE 181 A comparison between the increment in alveolar carbon monoxide and butt nicotine analysis Two indicators of a, subject's'dose of tobacco smoke' have now been described - measurement of the increment in alveolar carbon monoxidie from smoking a single cigarette reflects the 'dosc" absorbed whilst the derivation of mainstream smoke nicotine reflects the'diose"presented to the subject. It is of'interest to compare these two measurements. Forty-seven subjetts took part in a study where each wass asked' tochain-smoke frve cigarettes. Carbon monoxide measurcmcntsmere made before and 15' minutes after the smoking period andl each subject's cigarette buttss were collected'and pooled for nicotine! analysi's, in this way, min'inaising,errors due to analytic technique. Bothithe increment in carbon monoxide and the nicotine presented to the smoker have been related to machine smoked values to allow irsterr subject and inter-product comparisons and the results are shown in Fig. 14:10 as a scattergram i 1.0 0.5 0 . .~ .1 • • . ® I 0 . • .. • . . •~ . 0 • .. .. 1! •~, •~, 0 0.5 1.0 1.5' 2.0 NICOTINE PRESEMtED TO SMOKER I MACHINE' NIICOTINE; Fig. 14.10 A scattergrarn of the increment inialvcoGrrcarbon monoxide parrtial! pressurrJmachine smoked carbon monoxide yield versus the dk•rived nicotine presentedtiolthe smokerl'machine smoked nicptine value (nicotine eompensatio,n ratio) in 48 suibjects (k0:28, p)0:05'):

184: SMOKING BEHAWIIt)U6i' lt can be seen that there is no significant ref ationship between the two measurements, (r-0.28,,p 0.05).. The'dose' of tobacco smoke presented'to the smoker (as measured by butt nicotine) is not therefore equal to or even proportional to tihe'dose' of tobacco smoke absorbed by the smoker (as measured by the carbon monoxide increment)'and themajor factior inidetermining the differences is probably related to: inhalation.of the smoke from the mouth into the lungs. The relationship between the abveolaresrbon monoxide! increment and the smoke exposure index If inhalationiis the major determinant of differences between the 'dbse"of tobacco smoke presented to a subjiect during the smoking of a cigarette and the 'dose' absorbed duritog,smoking; then a relationship might be expected between the smoke exposure index (reflecting the depth of inhalation of smoke:and the time which this smoke remains in the llangs) and the increment inialveolar carbon monoxide (reflecting the. 'dose' of smoke absoribed). Habitual middle tar smokers In Fig. 14.11 the carbon monoxide: incretmenr has been pl'otted against' the smoke exposure index for ten habitual middle tar smokers smoking one cigarctte of their usual brand. x Normal smoking ® Defined smoking Fig: 14.11 The relationship bctween the incremenrin alveolar carbon monoxide partial pressure and tihe smoke exposure indez in haibitual'middle tar smokers. x, normal smoking;, ®, defiined unoiking,einher witih, maximal inhataition and!breathhplding or no in'hal'a4ion. Thle tinear'rCg!fessiolfliliil'e for ailllmeasuTemienila i4t ahn+vn lir.A O6

186' SFCOK'ING BENA'V10t1iR' s A comparison between habitiual middle tar smokers and habi'tuai low tar smokers Inhalation Fig; 14.12'shows„inadidition to thc Iinear. regression line for ltDw tar smokers, the regression line for the middle tar smokers prcviously discusscd and shown in Fig. 14.11. These two lines are significantly different at the 5'7eJcvel. The significant relationships between the increment in carbon monoxide and the smoke exposure index for both middle~and low tar smokers is pcrhaps surprising; for within each, tar group there is a range ofi products of differing carbon monoxide yietd! Nibre important however. is the implication of the demonstrated relationship, that all smokers of the satne product type inhale an amount of carbon monoxide which falls within relatively narrow limits, such that the inhalation pattern is the major determinant of the carbon monoxide increment. Although the 'dose' of tobacco smoke presented to srnokers differs widel'y from subjqct tiolsubject, the 'dose' inhaled and available, for absorption tends towards~a constant. Ifs in Fig. 14.12, the slope of the middle tar regression line is set toirepresent thee relationships between inhalation pattern and rise in alveolzrcarbon monoxide :or an average middle tar product: containing 20mg carbon monoxideper cigarette„ then the relationship for an average low tar product, which contains 110mg carbon monoxide, can be predicted. The predicted line for such a product is as shown in Fig. 14.12 and it is not, significantly d'ifferenr from the actual line obtained itorn habitual low tar smokers (p )0;05); Furthermore, as can be seen from.Fig;. 14.11 and' 14.12; the values~for the smoke exposure index of the middle tar, smokers overlap the values for the low tar smokers and statistically there is no difference between the two groups (p )'0.05): One must therefore conclude thart there.is no difference between the inhalation patterns of habit~ual middle tar and habitual low tar smokers, and, at any given level of,smoke exposure index, diflferences in carbon monoxide increment can be accounted fpr by the differences in carbon monoxide content of the d'ifferent product types. Alveolar carbon monoxide increments Itt ttie previous studies investigating the relationships of alveolar, ccarbon monoxide increments with the smoke exposure index, subjects were studied at randbm times during the working day. IU is possible that the increments in carbon.monoxide with smoking may show a changing pattern;' other than rand'om variation, during, the day. Pn order to investigate between-product differences therefore, measure- ments of carbon monoxide were made in relation to the first cigarette of the day. Nine middle and nine low tar smokers were studied before and after their first cigarette of, the day on three separate days over a period of tltree weeks. The results are shown in Table 14.2 as the mean group levels~i Table 14.2 The mesn,alveolar carbom.monoxide partial pressures before and after smoking the firsicigarette of'the day in groups of habitual!middle and low tar smokers:, Wliddle Tar Group Low Tar Group L'evclio[ Sitnifirance Pre s!moking .0I06'3I + .0068 t NS IcveHmm1Hg) .000669 .001045 t ~ Post smoking .01094 t .0086 `- NS L ' Ievell(mmfH6)' Increment .0I00840 nnlt ± .001085 nntT t

I88' SMOKING BEHAVIOUR the differences in nicotine yield' of the two product groups. Habitual middle tar and habitual low tar smokers Both the studies ofinhalation patterns and'smoking parameters presented would ~~• . appear to suggest that there are no differences between habitual middle and low tar smokers in the way iniwhich they smoke and inhale theu respective products. ~.. Differences in carbon monoxide, nicotine and presumably tar presented to smokers are merely a reflection of the differences between the products and not modified by smoking. This conclusion would appear to be contrary to a lot of published experience •~ `:. . '• -~ ~'. the two sequential smoking periods. but such studies are predominantly switching studies where middle tar smokers are studied smoking low tar products and, vice versa, comparisons being made between Cigarette switchingstudies Smoking, paramerers An experiment, to examine the effects on smoking parameters of subjects switching from middle to low tar cigarettes was conducted in nine habitual middle tar smokers. ,n;;•.. The original experimental desigmwas for the subjects to smoke their own middle tar product for the first two weeks of the study and then switch to a defined low tar product for four weeks. Following this second period, on a low tar product, subjects were expected to switch back to their middle tar product for the third study period which would last a further four weeks: Duringthe studyhowever„atthe completion of the second period, fsve subjects declined to switch back to thcir original middle tar product„electing to remain at the low tar level. This is presumably a reflection of the bias of subjects volunteering for such smoking stvdies! As a consequence, the original study population consists of two potentially different groups and for the analyses presented here these groups have been treated separately. Group1A are those subjects who, in the thirdl period, switched back to their original middle tar prodtzct ('n=4) whilst group B are those subjects who elected to remain on the low tar product (n=5): Response measurements were obtained weeklyduringthe ten week study period. Smoking parameters were recorded Crom the smoking of a single cigarette, butt lengthiand butt nicotine analyses were the average from a?4 hour butt collection and cigarette consumption was the mean daily consumption from a weekly record. For the summary results presented the mean response for all subjects in each of the two groups is given for each of the three smoking periods. Examination for differences between the groups has been carried out using the unpaired t test. Tablk 14.4 presents the results from Group A where subjects have switchedback to the middletar product for the final smoking period! There are no significant differences for any parameter betweenithe first and third smoking periods when subjects were smoking the middle tar products. The nicotine compensation ratio would indicate however that the low tar product is being significantly'oversmokedl when compared! to the middle tar product and from the puff parameters this would seem to be the result of taking larger puff vollrmes. Despite this `oversmoking' of the low tar product, eompensation, in terms of nicotine, is nut complcte. Althuughithe decrease in nicotine presented to the smoker is not significant when switching to the low tar product, thereis a significant increase wheni switching,bzck to midrllc tarin the third