The tar reduction study: randomised trial of the effect of cigarette tar yield reduction on compensatory smoking.

BACKGROUND--Observational and short term intervention studies have reported that smokers of low tar cigarettes inhale more deeply (that is, compensate) than those who smoke high tar cigarettes. To quantify this effect a long term randomised trial was conducted on the effects of switching to low tar cigarettes. METHODS--The trial was carried out between April 1985 and March 1988 among cigarette smokers in the British Civil Service, measuring blood carboxyhaemoglobin (COHb) levels and serum cotinine levels as markers of tobacco smoke intake. Volunteers first switched to a cigarette brand yielding around 10% less tar than their usual brand to identify smokers able to change brand. The 434 subjects who successfully switched were then randomly allocated to one of three groups: (a) "fast reduction" group which changed to a brand of cigarettes with a tar yield of about half that of their usual brand; (b) "slow reduction" group which reduced to the same level in steps over several months; and (c) a control group which continued smoking cigarettes with a tar yield 10% lower than their usual brand. RESULTS--Over the course of the trial cigarette consumption declined slightly in all three groups. In both the "fast reduction" and the "slow reduction" groups, intake of COHb and cotinine was reduced, though not to the same extent as the yield reduction. Comparison of the results before randomisation with those at the end of the trial showed that a reduction in carbon monoxide yield of 45% was associated with a decrease in carbon monoxide intake of 19% (95% confidence interval 14% to 24%) and that a reduction in nicotine yield of 40% was associated with an 11% (6% to 16%) reduction in nicotine intake, reflecting relative intakes of about 1.5 for both carbon monoxide and nicotine in the "fast reduction" group. Results were similar in the "slow reduction" group with a 42% reduction in carbon monoxide yield, a 16% (11% to 22%) reduction in carbon monoxide intake, a 37% reduction in nicotine yield, and a 6% (0% to 13%) reduction in nicotine intake. Estimates of compensation derived from these results were 65% for carbon monoxide, 79% for nicotine, and 62% for tar. CONCLUSIONS--Compensation, demonstrated when switching from a high tar cigarette to a low tar one, was incomplete. Advising people who have failed to give up smoking to switch to low tar cigarettes will reduce the intake of smoke constituents to a small extent. This would be expected to decrease their risk of smoking-related diseases, although by a smaller amount than would be achieved by giving up smoking altogether.     

Relative intakes of tar, nicotine, and carbon monoxide from cigarettes of different yields

The relative intakes of tar, nicotine, and carbon monoxide were estimated in 2455 cigarette smokers, who freely smoked their usual brands of cigarette. The estimates were derived by using an objective index of inhaling based on the measurement of carboxyhaemoglobin divided by the carbon monoxide yield of the cigarettes smoked, after background and carry over carboxyhaemoglobin effects had been allowed for. Separate analyses were performed according to the yield and type (plain, filter, etc) of cigarette smoked. The analyses based on yield indicated that the extent of inhaling was adjusted sufficiently to achieve similar intakes of nicotine/carbon monoxide regardless of the nicotine/carbon monoxide yield. It was not, however, sufficiently increased to achieve a similar intake of tar as the tar yield of the cigarette decreased. The analyses based on type of cigarette indicated that the extent of inhaling was adjusted to achieve similar intakes of tar and nicotine regardless of the type of cigarette smoked, but that this led to a greater intake of carbon monoxide among filter cigarette smokers than that among smokers of plain cigarettes--more so than would have been expected from their relative carbon monoxide yields. Two conclusions arise from these results. Firstly, any harmful effects of nicotine/carbon monoxide are unlikely to be materially reduced by smoking cigarettes with lower yields of nicotine/carbon monoxide, but the harmful effects of tar are likely to be reduced by smoking cigarettes with lower tar yields. These predictions appear to be borne out by epidemiological observations. Secondly, any harmful effects of carbon monoxide on the cardiovascular system will be greater in smokers of modern filter cigarettes than in smokers of modern plain cigarettes, provided that these two groups of smokers are otherwise similar with respect to risk of cardiovascular disease.     

The effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the arterial wall

The association between cigarette smoking and the development of atherosclerosis is well established, but the mechanism that makes cigarettes such a potent "risk factor" is not understood. There is normally a constant insudation of plasma macromolecules into the arterial wall. Fibrinogen and lipids are two of the large molecules involved in atherosclerosis. Therefore we studied the effect of cigarette smoke, nicotine, and carbon monoxide on the permeability of the canine arterial wall to 125I-labeled fibrinogen. The results show that inhaled cigarette smoke significantly and rapidly increases the permeability of the arterial wall to fibrinogen and that this effect can be produced with carbon monoxide alone but not with intravenous nicotine.     

Recent smoking behavior and postoperative nausea and vomiting

The risk of postoperative nausea and vomiting (PONV) is reduced in cigarette smokers by unknown mechanisms. If protection is related to an acute effect of smoke constituents, smokers with the most recent exposure to cigarette smoke would be most protected. We tested the hypothesis that in cigarette smokers, postoperative nausea is correlated with recent exposure to cigarette smoke as quantified by exhaled carbon monoxide (CO) concentrations. In this observational study, exhaled CO levels were measured in 140 female smokers preoperatively. PONV was assessed over the first 24 h after surgery. There was no correlation (assessed with Spearman rank correlation) between preoperative CO and nausea scores at recovery room discharge. Significant correlations were found between nausea assessed over the first 24 h postoperatively and a history of PONV or motion sickness, the use of intraoperative antiemetic prophylaxis, duration of anesthesia, and use of opioids in the postanesthesia care unit. However, there was no correlation between preoperative CO and nausea over the first 24 h. These preliminary data suggest that the effect of smoking in reduced PONV is not directly related to preoperative exhaled CO levels.     

Effect of nicotine, silver acetate, and ordinary chewing gum in combination with group counselling on smoking cessation.

Four hundred and ninety six smokers participated in a randomised comparison of the effect of silver acetate, nicotine, and ordinary chewing gum on smoking cessation. All were motivated to stop smoking abruptly and all had smoked at least 10 cigarettes a day for at least five years. Side effects and taste acceptability were related to outcome after six months. The participants attended nine meetings over a year, at which lectures, support, and advice about stopping smoking were given. Tobacco abstinence was confirmed by measurement of carbon monoxide in expired air. The chewing gums were used for 12 weeks. After 12 weeks there was a trend towards more abstainers in the nicotine group (59%) than in the silver acetate (50%) and ordinary (45%) chewing gum groups that was not quite significant (p = 0.07). At 26 and 52 weeks the number of cigarette abstainers was similar in the three treatment groups. Subjects in the nicotine chewing gum group had a longer mean time before relapse than those in the silver acetate and ordinary chewing gum groups. Mean success rates for all subjects combined at 12, 26, and 52 weeks were 52.8%, 39.7%, and 23.3%. The side effects of nicotine and silver acetate chewing gum were generally mild and transient, and unimportant except for mouth irritation from silver acetate, which had a negative effect on outcome, and the low taste acceptability of nicotine, which had a strong negative influence on the success rate. The results suggest a short term effect on nicotine chewing gum on smoking cessation, but the abstinence rates after one year were generally disappointing.     

Glycerol particle cigarettes: a less harmful option for chronic smokers.

In 20 smokers who switched to a new type of virtually tar free cigarette for three days, average nicotine intake was reduced by 44%, carbon monoxide intake increased by 19%, while estimated tar intake was reduced by about 90%. Such cigarettes pose substantially less risk of cancer and chronic obstructive lung disease than conventional cigarettes, and their acceptability and safety could be improved by increasing nicotine yield, reducing carbon monoxide yield, and improving the flavour.     

Inhaling habits among smokers of different types of cigarette.

Inhaling habits were studied in 1316 men who freely smoked their usual brands of cigarette. An index of inhaling was calculated for each person by dividing the estimated increase in carboxyhaemoglobin level from a standard number of cigarettes by the carbon monoxide yield of the cigarette smoked. Smokers of ventilated filter cigarettes inhaled 82% more than smokers of plain cigarettes (p less than 0.001) and those who smoked unventilated filter cigarettes inhaled 36% more (p less than 0.001). Cigarette consumption was similar among smokers of each type of cigarette. Assuming that the intake of tar and nicotine is proportional to the inhaling index, the intake in either group of filter cigarette smokers would have been less than that in plain cigarette smokers. Among smokers of unventilated cigarettes, however, the intake would not have been much less.     

Trends in sales weighted tar, nicotine, and carbon monoxide yields of UK cigarettes

BACKGROUND: Reducing tar yields of manufactured cigarettes has been an important plank of government policy on tobacco, but sale weighted yields are not routinely published. METHODS: Tar, nicotine, and carbon monoxide yields measured by the Laboratory of the Government Chemist were combined with cigarette brand market shares from national surveys of smoking behaviour to generate sales weighted yield estimates for the period 1972-99. RESULTS: Sales weighted mean tar yields have declined steadily and in 1999 were 9.6 mg per cigarette, less than half their level in 1972. Over the same period nicotine yields have come down from 1.33 mg to 0.79 mg per cigarette. Carbon monoxide yields have shown smaller declines. At the same time as absolute yields have declined, there have also been changes in tar to nicotine ratios. Smokers in 1999 were exposed to 22% less tar per unit of nicotine than in 1973, and smokers of low tar brands have consistently been exposed to less tar per unit of nicotine than smokers of other brands. CONCLUSIONS: The value of reducing cigarette tar and nicotine yields has been questioned, since the tendency of smokers to compensate for reductions in nicotine delivery undermines the policy. The favourable trends in tar to nicotine ratios suggest that, despite this, there may have been some modest public health benefit. It cannot be assumed that future reductions from present levels would necessarily result in further improvement in tar to nicotine ratios. An explicit focus on the ratio of tar to nicotine may provide a metric of greater relevance for public health than the present emphasis on absolute tar yields.     

Carboxyhaemoglobin and pulmonary epithelial permeability in man.

The effect of cigarette smoke exposure on pulmonary epithelial permeability was studied in 45 smokers and 22 non-smokers. An index of cigarette smoke exposure was obtained from the carboxyhaemoglobin concentration (HbCO%). Pulmonary epithelial permeability was proportional to the half-time clearance rate of technetium-99m-labelled diethylene triamine pentacetate (99mTc DTPA) from lung to blood (T1/2LB). The relationship between T1/2LB and HbCO% was hyperbolic in form and the data could be fitted to the quadratic formula (formula; see text) where the parameters a0, a1, and a2 represent respectively the asymptotic T1/2LB value at large carboxyhaemoglobin values and the slope and shape of the curve. The values of these parameters were a0 4.4 (2.6), a1 = 77.8 (15.5), and a2 -25.5 (9.7) (SE). This is the first demonstration of a dose-response relationship between carboxyhaemoglobin and an increased permeability of the lungs in man and provides a technique for identifying the roles of carbon monoxide and other cigarette smoke constituents in causing increased pulmonary epithelial permeability.     

Differential effects of nicotine and smoke condensate on bone cell metabolic activity

OBJECTIVE: Delayed or impaired healing of skeletal trauma in patients who smoke has been attributed to vascular responses of nicotine absorption and/or a direct effect of nicotine or other smoke components on bone cells. In vivo studies indicate variability in osteosynthetic response to nicotine versus smoke inhalation. We tested the hypothesis that components of cigarette smoke other than nicotine may be responsible for the adverse skeletal effects of smoking. DESIGN: In vitro cultures of MC3T3-E1 osteoblastlike cells were exposed to varying doses of nicotine or condensates of cigarette smoke. Metabolic assays included alkaline phosphatase activity, collagen synthesis, and total protein synthesis as well as cell proliferation. RESULTS: Variations in the degree of response were noted between bone cell preparations. Nicotine elicited a significant dose-dependent stimulation of bone cell metabolism in all studies. This was detected as increases in alkaline phosphatase activity and increases in total protein and collagen synthesis. Responses were noted with nicotine doses as low as 12.5 ng/mL (half the nicotine level circulating in smokers). In one study, maximum stimulation occurred at 250 ng/mL with levels reaching 74% (total protein) and 104% (collagen) greater than control cultures. In a second study, 222% and 627% stimulation of protein and collagen synthesis over controls was noted using 100 ng/mL. Addition of the nicotine receptor antagonist mecamylamine reduced the nicotine stimulation. Preparations of smoke condensate with equivalent nicotine concentrations reduced all indices of metabolic activity. Cell proliferation was stimulated by both nicotine (20-25%) and smoke condensate (38-46%). CONCLUSION: The data suggest that nicotine acts as a direct stimulant of bone cell metabolic activity. Smoke condensate containing equivalent levels of nicotine elicits an inhibitory effect. A probable speculation is that the delay in clinical healing of skeletal trauma in smoking patients may in part be a result of absorption of components of smoke other than nicotine.     

Response and acclimatisation of symptomless smokers on changing to a low tar, low nicotine cigarette.

Ten symptomless smokers were switched from their usual cigarette to a low tar, low nicotine test cigarette for two weeks to investigate their immediate response and subsequent acclimatisation to the test cigarette. The tar (T) and nicotine (N) yields of the test cigarettes were T = 3.8 mg, N = 0.6 mg; the median yields of the usual cigarettes were T = 16.4 mg, N = 1.4 mg. The subjects were monitored over a six week period comprising a control period (usual cigarette), a test period (test cigarette), and a return period (usual cigarette), each lasting two weeks. The inhaled smoke volume (smoke from the burning tip of the cigarette which is subsequently inhaled) was measured with a non-invasive radiotracer technique. Puffing indices were recorded using an electronic smoking analyser and flowhead cigarette holder. Measurements were made at the beginning of the control period, at the beginning and end of the test period, and at the end of the return period. Subjects kept records of their cigarette consumption during each of the three periods. Apart from a small change in puff duration, cigarettes were smoked in the same way during the control and return periods. Mean and total puff volumes increased with the low tar, low nicotine cigarette but did not change from the beginning to the end of the test period. There was no significant change between the control, test, and return periods for mean inhaled smoke volume, total inhaled smoke volume, or cigarette consumption. It is concluded that when smokers are switched to a low tar, low nicotine cigarette the puff volume increases but there is no change in the inhaled smoke volume or daily consumption.     

Cigarette smoke inhalation and the acute airway response.

The acute airway response to smoking varying numbers (one to four) of identical cigarettes in rapid succession and smoking single cigarettes of differing tar/nicotine yields was assessed repeatedly in 13 healthy smokers. The airway response was variable, indicating airway narrowing consistently in only three subjects. There appeared no difference between forced spirometry and measurement of airway resistance in detecting the airway response. No relationship was observed between the airway response and amount of smoke inhaled into the lungs as measured either by changes in venous blood nicotine or percentage carboxyhaemoglobin. When five smokers inhaled smoke directly from a cigarette acute airway narrowing was consistently observed. A normal smoking pattern consisting of an initial drag of smoke into the mouth, followed after a pause by inhalation of smoke diluted with air, did not consistently cause airway narrowing although similar amounts of smoke as the direct drag were inhaled as assessed by changes in venous blood nicotine. The manner of smoke inhalation affects the relative concentrations of the different constituents of smoke reaching the lungs and also appears to be the main determinant of the acute airway response to smoking, which was unrelated to the number of cigarettes smoked or the tar content of the smoke. This suggests that patterns of smoke inhalation may influence the pathogenesis of bronchial disease associated with smoking.     

Urinary cotinine as an objective measure of cigarette smoking in chronic kidney disease.

BACKGROUND: Smoking is a modifiable behaviour that may hasten the progression of chronic kidney disease (CKD). Cotinine, a nicotine metabolite, is measurable in body fluids, including urine, and can be utilized as an objective measure of smoking exposure. Its use has not been examined in the CKD population. METHODS: In this cross-sectional study, we evaluated use of 24-h urinary cotinine excretion (Ucot) as a quantitative index of smoking exposure in a CKD population. Methods of comparison included self-report and expired air carbon monoxide (eCO) as standard measures of smoking exposure. Assessments of kidney function included estimated glomerular filtration rate (eGFR) and 24-h urinary protein (Uprot) excretion. RESULTS: Sixty-one patients were enrolled, of whom 12 were excluded for incomplete urine collections. Of the remaining, 77% were active current smokers (mean cigarettes smoked: 12+/-7 per day). The mean eGFR was 47+/-25 ml/min/1.73 m2 with no significant differences among non-smokers. The mean eCO and Ucot were significantly higher in smokers vs non-smokers (12.5+/-6.9 ppm and 1.3+/-1.1 ppm and 1685.87+/-922.77 microg/d and 134.18+/-445.03 microg/d, respectively, P<0.001 for both). Ucot was weakly correlated with eGFR (R=0.40, P=0.005), but not with Uprot (R=0.09, P=0.54). In multivariate analyses, daily cigarette consumption and eCO were the only significant predictors of Ucot (P<0.05 for both). CONCLUSION: In this CKD cohort, Ucot is correlated with commonly used measures of smoking exposure and is minimally influenced by underlying renal function, demonstrating its potential utility in clinical trials examining change in smoking behaviour and effects on renal injury.     

Distribution of carboxyhaemoglobin concentrations in smokers and non-smokers.

Carboxyhaemoglobin concentrations were measured in 3487 subjects comprising 1255 non-smokers, 1933 cigarette smokers, 193 cigar smokers (39 primary, 154 secondary), and 106 pipe smokers (30 primary, 76 secondary). In cigarette smokers the mean carboxyhaemoglobin concentration was 4.78% of the total haemoglobin and 94.7% of smokers had a concentration greater than 1.7%. Primary cigar smokers had a much lower mean carboxyhaemoglobin concentration (0.93%), and only 10.3% had concentrations greater than 1.7%. Primary pipe smokers also had a low mean carboxyhaemoglobin concentration (1.36%) and none had a concentration above 1.7%. Secondary cigar smokers had a high mean concentration (6.80%) and 97.4% had values above 1.7%; the findings in secondary pipe smokers were similar--the mean concentration was 3.39%, 94.7% having values greater than 1.7%. The lower carboxyhaemoglobin concentrations in primary pipe and cigar smokers suggest that in general they do not inhale, and the raised concentrations in cigarette smokers who change to pipes or cigars suggest that they usually continue to inhale and to absorb large amounts of carbon monoxide and other constituents of tobacco smoke.     

Carbon monoxide in breath in relation to smoking and carboxyhaemoglobin levels.

Carboxyhaemoglobin (COHb) levels were studied in 11 249 men. The distribution among the 2613 men who smoked cigarettes was well separated from that in 6641 non-smokers (including ex-smokers). The distribution for 2005 cigar and pipe smokers was intermediate, though some of the highest COHb levels occurred in cigar smokers. Using a COHb cut-off level of 2%, 81% of cigarette smokers, 35% of cigar and pipe smokers, and 1.0% of non-smokers had raised COHb levels. In a subsidiary experiment alveolar air samples were collected from 162 smokers and 25 non-smokers using a simple breath sampling technique. Carbon monoxide concentrations in alveolar breath were highly correlated with COHb levels (r = 0.97) indicating that COHb levels can be estimated reliably by measuring the concentration of carbon monoxide in breath. Alveolar carbon monoxide measurement is thus a simple method of estimating whether a person is likely to be a smoker.     

The first published chemical analyses of smoke from South African cigarettes.

The smoke of 69 brands of cigarettes sold in South Africa in March 1978 was analysed for its content of tar, nicotine, carbon monoxide and carbon dioxide. The average yield of tar per cigarette varied between 30 and 38,5 mg in 27 brands and between 20 and 30 mg in all but one of the other 42 brands. The nicotine yields with one exception varied between 1,0 and 2,40 mg per cigarette and generally correlated well with those of tar (r = 0,75). The yields of carbon monoxide per cigarette generally ranged from about 14 to 32 mg, and those of carbon dioxide from about 50 to 85 mg. The results of this analysis, the first to be published with regard to South African cigarettes, are very disturbing. In particular, the tar yields are unacceptably high by international standards. They demand urgent action including (a) regular cigarette analyses by the Government, and publication of the results by the mass media, especially the SABC; (b) compulsory printing of the results of analyses on every cigarette pack and advertisement; (c) education of the public with regard to the meaning of the analyses; and (d) a programme designed to replace more dangerous cigarettes with less hazardous ones. Most important, all these measures must be implemented within the framework of a really meaningful, systematic, continuous and appropriate campaign aimed at combating the tobacco hazard at every level in all population groups.     

Urinary point-of-care test for smoking in the pre-operative assessment of patients undergoing elective plastic surgery.

Self-reported information about smoking habit and cigarette consumption can be inaccurate and subject to bias in the clinical setting. Accurate assessment of a given smoking history at point-of-care is valuable. We describe the use of a comprehensive smoking questionnaire and the use of a disposable biomarker test to verify and quantify the exposure to tobacco smoke. This point-of-care test (SmokeScreen) is a 6-min, easy-to-use urine test that measures nicotine and its breakdown products. One hundred consecutive patients attending plastic surgery pre-assessment clinic filled in the questionnaire and gave a consented urine sample. Qualitative and semi-quantitative assessment of tobacco consumption was observed by a simple sample colour change set against a standardised colorimetric chart for nicotine metabolite containing urine. The questionnaire self-reported smoking prevalence was 30% with 98% test specificity. The cotinine validated smoking prevalence was 54% with a 26% self-denial rate. Half the patients (n = 15) who admitted smoking on the questionnaire underreported the amount they smoked daily, as quantified by biochemical measurement. Objective biochemical assessment shows that 26% of self-reporting non-smokers via self-completed questionnaire studies are actual smokers attending this pre-assessment clinic. When patients did report smoking there was consistent underreporting of cigarette consumption.     

Acute smoking increases ST depression in humans during general anesthesia.

We tested the hypothesis that acute smoking is associated with ST segment depression during general anesthesia in patients without ischemic heart disease. The carbon monoxide (CO) concentration in expired gas and hemodynamic data was measured during general anesthesia for noncardiac or nonperipheral vascular surgery in patients without symptoms or evidence of ischemic heart disease. Increased expired CO concentrations are indicators of recent smoking. Logistic regression analysis identified significant predictors of ST segment depression > or = 1 mm. Both rate pressure product (odds ratio 1.20 for each increase of 1000, 95% confidence interval = 1.04-1.41, P = 0.007) and expired CO concentration (odds ratio 1.05 for each part per million increase, 95% confidence interval = 1.03-1.08, P = 0.001) were significant predictors of ST segment depression when considered simultaneously. Males demonstrated a lower probability of having an episode of ST depression (odds ratio = 0.16, P = 0.01), but this did not change the relationship between rate pressure product and CO as predictors of ST depression. Approximately 25% of chronically smoking patients smoked on the morning of surgery despite instructions not to smoke. IMPLICATIONS: Patients under age 65 without symptoms of ischemic heart disease who smoked shortly before surgery had more episodes of rate pressure product-related ST segment depression than nonsmokers, prior smokers, or chronic smokers who did not smoke before surgery. Females were at greater risk of ST depression than males.     

Urinary nicotine concentrations in cigarette and pipe smokers

Urinary concentrations of nicotine were studied in men who did not smoke (27) and in men who smoked cigarettes only (145) or pipes only (48). The median urinary nicotine concentrations were less than 50 ng/ml (the detection limit of the assay for urine tests) in the non-smokers, 1393 ng/ml in the cigarette smokers, and 1048 ng/ml in the pipe smokers. These values were standardised for urinary pH and creatinine concentration to allow for the fact that nicotine excretion is influenced by the acidity of the urine and by urinary flow rate. The high urinary nicotine concentrations in the pipe and cigarette smokers indicated that both types of smoker have relatively high systemic nicotine concentrations. This observation, together with the fact that large prospective studies have shown that pipe smokers have no material excess risk of coronary heart disease whereas cigarette smokers do, provides evidence that nicotine is unlikely to be the major cause of the excess deaths from coronary heart disease in cigarette smokers. This conclusion is consistent with earlier observations based on serum cotinine concentrations in smokers and non-smokers.     

Use of carboxyhaemoglobin levels to predict the development of diseases associated with cigarette smoking.

Carboxyhaemoglobin (COHb) levels in tobacco smokers vary throughout the day since they are affected by the pattern of tobacco consumption and the rate at which COHb is eliminated. A method is described whereby a single COHb measurement together with a recent smoking history may be used to estimate the average COHb "boost" produced by each cigarette, the total daily carbon monoxide (CO) uptake from smoking, and the mean COHb level throughout the day. These three indices of tobacco smoke absorption were estimated in nine healthy cigarette smokers on different days, each set of three estimations being derived from separate COHb determinations. The indices were reasonably reproducible within the same person, and the differences between people were statistically highly significant (P less than 0-001). For example, the estimates of mean daily COHb level resulting from smoking ranged from 0-7% to 9-3% in smokers who smoked 15 to 40 cigarettes a day. These differences are sufficiently large to distinguish possible differences in the risk of developing diseases such as ischaemic heart disease which may result from the inhalation and absorption of tobacco smoke. The suggested indices also depend less on the time of the blood test and on the daily pattern of smoking than a COHb level alone. The ratio of the COHb boost to the CO yield of a cigarrette may reflect depth of inhalation more accurately than a smoker's self-assessment. Moreover there was little correlation between these two measures of inhalation in the nine subjects studied.