Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers.

Blood nicotine and carboxyhaemoglobin (COHb) concentrations were studied in 330 smokers (206 women and 124 men). Blood nicotine concentrations in individual smokers varied from 25 to 444 nmol/l (4 to 72 ng/ml). The average concentration, 203 nmol/l (33 ng/ml), was the same in the men and the women, although cigarette consumption was higher in the men. Despite large differences in nicotine yield, there was no relation between blood nicotine concentration and the type of cigarette smoked: smokers of plain, untipped cigarettes (1.9 mg nicotine), cigarettes with unventilated filters (1.3 mg nicotine), and cigarettes with ventilated filters (0.8 mg nicotine) had similar blood nicotine concentrations. Cigarette consumption was also similar in these three groups. The correlation between blood nicotine concentration and nicotine yield of cigarette, though significant, was low (0.21, p < 0.001), showing that the nicotine yield of the cigarettes accounted for only 4.4% of the variation in blood nicotine concentrations. Similarly, the low correlation of 0.30 between COHb concentration and cigarette consumption suggests that cigarette consumption accounted for only 9% of the variation in the amount of smoke taken into the smokers'' lungs. These results suggest that the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation. The findings of epidemiological studies showing lower risks with filter-tipped cigarettes may be attributable to other factors such as biases in the samples and changes in the quality and carcinogenicity of tobacco tar, rather than to reduced tar intake.     

Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts.

OBJECTIVE--To investigate relation between tar yield of manufactured cigarettes and mortality from smoking related diseases. DESIGN--Prospective epidemiological study of four cohorts of men studied between 1967 and 1982. SETTING--Combined data from British United Provident Association (BUPA) study (London), Whitehall study (London), Paisley-Renfrew study (Scotland), and United Kingdom heart disease prevention project (England and Wales). SUBJECTS--Of the 56,255 men aged over 35 who were included in the studies, 2742 deaths occurred among 12,400 smokers. Average follow up was 13 years. MAIN OUTCOME MEASURES--Relative mortality from smoking related diseases according to tar yields of cigarettes smoked. RESULTS--Age adjusted mortality from smoking related diseases in smokers of filter cigarettes was 9% lower (95% confidence interval 1% to 17%) than in smokers related diseases consistently decreased with decreasing tar yield. Relative mortality in cigarette smokers for a 15 mg decrease in tar yield per cigarette was 0.75 (0.52 to 1.09) for lung cancer, 0.77 (0.61 to 0.97) for coronary heart disease, 0.86 (0.50 to 1.50) for stroke, 0.78 (0.40 to 1.48) for chronic obstructive lung diseases, 0.78 (0.65 to 0.93) for these smoking related diseases combined, and 0.77 (0.65 to 0.90) for all smoking related diseases. CONCLUSION--About a quarter of deaths from lung cancer, coronary heart disease, and possibly other smoking related diseases would have been avoided by lowering tar yield from 30 mg per cigarette to 15 mg. Reducing cigarette tar yields in Britain has had a modest effect in reducing smoking related mortality.     

Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8

Objective To assess the risk of lung cancer in smokers of medium tar filter cigarettes compared with smokers of low tar and very low tar filter cigarettes.Design Analysis of the association between the tar rating of the brand of cigarette smoked in 1982 and mortality from lung cancer over the next six years. Multivariate proportional hazards analyses used to assess hazard ratios, with adjustment for age at enrolment, race, educational level, marital status, blue collar employment, occupational exposure to asbestos, intake of vegetables, citrus fruits, and vitamins, and, in analyses of current and former smokers, for age when they started to smoke and number of cigarettes smoked per day.Setting Cancer prevention study II (CPS-II).Participants 364 239 men and 576 535 women, aged ≥ 30 years, who had either never smoked, were former smokers, or were currently smoking a specific brand of cigarette when they were enrolled in the cancer prevention study.Main outcome measure Death from primary cancer of the lung among participants who had never smoked, former smokers, smokers of very low tar (≤ 7 mg tar/cigarette) filter, low tar (8-14 mg) filter, high tar (≥ 22 mg) non-filter brands and medium tar conventional filter brands (15-21 mg).Results Irrespective of the tar level of their current brand, all current smokers had a far greater risk of lung cancer than people who had stopped smoking or had never smoked. Compared with smokers of medium tar (15-21 mg) filter cigarettes, risk was higher among men and women who smoked high tar (≥ 22 mg) non-filter brands (hazard ratio 1.44, 95% confidence interval 1.20 to 1.73, and 1.64, 1.26 to 2.15, respectively). There was no difference in risk among men who smoked brands rated as very low tar (1.17, 0.95 to 1.45) or low tar (1.02, 0.90 to 1.16) compared with those who smoked medium tar brands. The same was seen for women (0.98, 0.80 to 1.21, and 0.95, 0.82 to 1.11, respectively).Conclusion The increase in lung cancer risk is similar in people who smoke medium tar cigarettes (15-21 mg), low tar cigarettes (8-14 mg), or very low tar cigarettes (≤ 7 mg). Men and women who smoke non-filtered cigarettes with tar ratings ≥ 22 mg have an even higher risk of lung cancer.     

Relationship between cigarette yields,puffing patterns,and smoke intake: evidence for tar compensation?

The relationship between cigarette yields (of nicotine, tar, and carbon monoxide), puffing patterns, and smoke intake was studied by determining puffing patterns and measuring blood concentrations of nicotine and carboxy-haemoglobin (COHb) in a sample of 55 smokers smoking their usual brand of cigarette. Regression analyses showed that the total volume of smoke puffed from a cigarette was a more important determinant of peak blood nicotine concentration than the nicotine or tar yield of the cigarette, its length, or the reported number of cigarettes smoked on the test day. There was evidence of compensation for a lower tar yield over and above any compensation for nicotine. When nicotine yield was controlled for, smokers of lower-tar cigarettes not only puffed more smoke from their cigarettes than smokers of higher-tar cigarettes but they also had higher plasma nicotine concentrations, suggesting that they were compensating for the reduced delivery of tar by puffing and inhaling a greater volume of smoke. The results based on the COHb concentrations were consistent with this interpretation. If an adequate intake of tar proves to be one of the main motives for smoking, then developing a cigarette that is acceptable to smokers and also less harmful to their health will be much more difficult.     

A comparison of the free radical chemistry of tobacco-burning cigarettes and cigarettes that only heat tobacco

Cigarette smoke contains free radicals both in the particulate matter (tar) and in vapor-phase smoke. Vapor-phase smoke decreases the activity of alpha-1-proteinase inhibitor (alpha 1PI) in vitro. The free radical content of the tar and vapor-phase smoke from a cigarette that heats rather than burns tobacco has been compared with data on a standard 1R4F cigarette. No radicals were detected in the tar from the new cigarette and radicals in its vapor-phase smoke are lower by more than 99% relative to the 1R4F standard cigarettes. The vapor-phase smoke from the new cigarette causes essentially no reduction of alpha 1PI activity in vitro. These findings support our previously published mechanisms for the production of radicals in tar and in vapor-phase smoke.     

Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases.

OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.     

Cigarette smoking and serum soluble Fas levels: Findings from the JACC study

Cigarette smoking enhances low-grade systemic inflammation in the lung and other organs. Activated immune cells play an important role at early and late stages of inflammation, and in recent years, soluble Fas (sFas), an isoform of death molecule Fas, was found to interfere with the apoptotic pathways of these activated immune cells. The aim of this study was to confirm the association between cigarette smoking and sFas levels in healthy male subjects. We measured serum sFas levels of 4415 male subjects selected as controls for a nested case-control study within the large-scale cohort study conducted in Japan, called the JACC Study. Smoking status at baseline was evaluated by a self-administered questionnaire. Least square means of sFas according to smoking status and numbers of cigarettes smoked per day among smokers were calculated and adjusted for possible confounding factors. Mean sFas levels showed an increasing trend across never smokers, past smokers and current smokers, as 2.21 (95% CI: 2.14–2.27) ng/ml, 2.29 (2.22–2.36) ng/ml, and 2.36 (2.30–2.43) ng/ml, respectively. However, no dose-response relationship was observed between the number of cigarettes smoked per day and sFas levels among smokers.     

A Simple and Rapid Method for Standard Preparation of Gas Phase Extract of Cigarette Smoke

Cigarette smoke consists of tar and gas phase: the latter is toxicologically important because it can pass through lung alveolar epithelium to enter the circulation. Here we attempt to establish a standard method for preparation of gas phase extract of cigarette smoke (CSE). CSE was prepared by continuously sucking cigarette smoke through a Cambridge filter to remove tar, followed by bubbling it into phosphate-buffered saline (PBS). An increase in dry weight of the filter was defined as tar weight. Characteristically, concentrations of CSEs were represented as virtual tar concentrations, assuming that tar on the filter was dissolved in PBS. CSEs prepared from smaller numbers of cigarettes (original tar concentrations ≤15 mg/ml) showed similar concentration-response curves for cytotoxicity versus virtual tar concentrations, but with CSEs from larger numbers (tar ≥20 mg/ml), the curves were shifted rightward. Accordingly, the cytotoxic activity was detected in PBS of the second reservoir downstream of the first one with larger numbers of cigarettes. CSEs prepared from various cigarette brands showed comparable concentration-response curves for cytotoxicity. Two types of CSEs prepared by continuous and puff smoking protocols were similar regarding concentration-response curves for cytotoxicity, pharmacology of their cytotoxicity, and concentrations of cytotoxic compounds. These data show that concentrations of CSEs expressed by virtual tar concentrations can be a reference value to normalize their cytotoxicity, irrespective of numbers of combusted cigarettes, cigarette brands and smoking protocols, if original tar concentrations are ≤15 mg/ml.     

Increased risk of respiratory symptoms in young smokers of low tar cigarettes.

The effect of cigarettes yielding less than 10 mg tar was investigated in a representative sample (n = 4729) of 16 and 18 year old Finns. The rate of response was 80%. Cough and phlegm were significantly increased in young people smoking low tar cigarettes. When more than nine cigarettes were smoked daily respiratory symptoms were 2.4-6.2 times more prevalent among those who smoked low tar cigarettes than among those who never smoked. No differences were found between the smokers of low tar and medium tar cigarettes (yielding tar 10-18 mg). These data disagree with the hypothesis that the new low tar brands of cigarettes are less likely to cause respiratory symptoms than the old medium tar brands.     

Human urine mutagenicity study comparing cigarettes which burn or only heat tobacco

Cigarette smokers have been reported to void urine which is more mutagenic, as measured in the Ames bacterial mutation assay, than urine voided by non-smokers. Condensate from the mainstream smoke of a cigarette which heats, but does not burn tobacco (test cigarette) showed no evidence of mutagenicity in a battery of in vitro genotoxicity assays under conditions in which condensate from the mainstream smoke of cigarettes that burn tobacco was mutagenic. The objective of this study was to determine whether the absence of mutagenic activity observed in the in vitro assays would be reflected in the urine of smokers of the test cigarette. 72 subjects (31 smokers and 41 non-smokers) were enrolled in a 6-week study, with the smokers randomly divided into 2 groups. The study was designed as a double crossover, with each smoker smoking both test (tobacco-heating) and reference (tobacco-burning) cigarettes. This design allowed each smoker to serve as his or her own control while at the same time allowing comparisons between groups of non-smokers and smokers of both test and reference cigarettes. 24-h urine samples were collected twice a week and concentrated using XAD-2 resin. Urine concentrates were tested in Ames bacterial strains TA98 and TA100, with and without metabolic activation and with and without beta-glucuronidase/aryl sulfatase. Individuals who smoked the test cigarette voided urine which was significantly less mutagenic than that voided when they smoked reference cigarettes. The mutagenicity of urine from smokers who smoked the test cigarette and non-smokers did not differ under any of the assay conditions used in this study.     

Smoking Habits of Men Employed in Industry,and Mortality

A study of the relation between smoking habits and lung cancer in male industrial workers over a period of three years has confirmed the earlier findings in doctors that the death-rate from lung cancer correlates closely with the number of cigarettes smoked. Of 54,460 men studied 68.7% were current cigarette smokers. The annual mortality rate from lung cancer was 0.33 per thousand in non-smokers and ex-smokers, and 1.2 per thousand for all cigarette smokers, and higher in heavy smokers.Heavy cigarette smokers who retained the cigarette in the mouth between puffs (“drooping” cigarette habit) had an annual mortality rate of 4.1 per thousand.The mortality from coronary thrombosis in smokers was nearly three times that in non-smokers. A mortality gradient with rising consumption of cigarettes was observed.Some correlation between smoking and cancer of other sites and from non-neoplastic lung disease was observed in older men, but no correlation was found with other cardiovascular diseases and cerebrovascular diseases.     

Hormones, nicotine, and cocaine: Clinical studies

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (< 20 min), ratings of “high” and “rush” began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.     

Would a medium-nicotine,low-tar cigarette be less hazardous to health?

Smoking behaviour and exposure to carbon monoxide, nicotine, and tar were studied in 19 middle-tar smokers. All smoked their own brands for three weeks and then switched to either a conventional low-nicotine, low-tar brand (control) or a medium-nicotine, low-tar cigarette for a further three weeks, the order then being reversed. The medium-nicotine, low-tar brand also had a low delivery of carbon monoxide. With the medium-nicotine, low-tar cigarette mouth-level delivery and intake of nicotine was similar to that with the smokers'' usual brands, and significantly greater than with the control low-tar cigarette. Intake of carbon monoxide from the medium-nicotine, low-tar cigarette was significantly less than with either own or control brands. With both low-tar brands mouth-level exposure to tar was reduced relative to smokers'' usual cigarettes. There was no evidence, however, that the reduction in tar exposure was greater with the medium-nicotine brand than with the control low-tar cigarette. Both low tar brands were "''oversmoked" relative to subjects'' usual middle-tar cigarettes. The medium-nicotine, low-tar cigarette was marginally more acceptable than the control brand, and the particular design used in the study resulted in a lower intake of carbon monoxide. In terms of reducing mouth-level exposure to tar, however, the medium-nicotine, low-tar cigarette had no advantage over the control low-tar product. In part this was because of the ratio of tar to nicotine delivery obtained by human smokers was not the same as that obtained by smoking machine.     

Cigarette smoking and aneuploidy in human sperm

Cigarette smoke contains chemicals which are capable of inducing aneuploidy in experimental systems. These chemicals have been shown to reach the male reproductive system, increasing oxidative DNA damage in human sperm and lowering semen quality. We have examined the association between smoking and aneuploid sperm by studying 31 Chinese men with similar demographic characteristics and lifestyle factors except for cigarette smoking. None of the men drank alcohol. These men were divided into three groups: nonsmokers (10 men), light smokers (< 20 cigarettes/day, 11 men), and heavy smokers (> or = 20 cigarettes/day, 10 men). There were no significant differences in semen parameters or in age across groups. Two multi-color fluorescence in situ hybridizations (FISH) were performed: two-color FISH for chromosomes 13 and 21, and three-color FISH for the sex chromosomes using chromosome 1 as an internal autosomal control for diploidy and lack of hybridization. The mean hybridization efficiency was 99.78%. The frequency of disomy 13 was significantly higher in light and heavy smokers than in non-smokers, while no significant differences in the frequency of disomy 21, X or Y were observed across groups. Significant inter-donor heterogeneity in every category of disomic sperm examined was found in both light and heavy smokers, while in nonsmokers only XY disomy showed significant inter-donor differences. Thus, we conclude that cigarette smoking may increase the risk of aneuploidy only for certain chromosomes and that men may have different susceptibilities to aneuploidy in germ cells induced by cigarette smoking. Mol. Reprod. Dev. 59: 417-421, 2001.     

Tar yield of cigarettes and risk of acute myocardial infarction. GISSI-EFRIM Investigators.

OBJECTIVE--To analyse the relation between tar and nicotine yield of cigarettes smoked in the recent past and the risk of myocardial infarction. DESIGN--Multicentre case-control study conducted between September 1988 and June 1989. SETTING--Over 80 coronary care units in various Italian regions. SUBJECTS--916 patients with acute myocardial infarction without history of ischaemic heart disease and 1106 controls admitted to hospital for acute conditions not related to known or suspected risk factors for ischaemic heart disease. MAIN OUTCOME MEASURES--Relative risk of myocardial infarction according to type of cigarette smoked adjusted for identified potential confounding factors. Brands of cigarettes classified according to yield of tar and nicotine. RESULTS--Patients with acute myocardial infarction were more often smokers and among smokers they tended to smoke more cigarettes. Compared with non-smokers their estimated relative risks were 3.8, 4.3, 3.2, and 3.7 in the four categories of tar yield (< 10, 10-15, > 15-20, and > 20 mg, respectively). No trend in risk across yields was evident when analysis was restricted to smokers and allowance was made for number of cigarettes. Compared with risks in subjects in the lowest category of tar yield the relative risks were 1.2, 0.8, and 1.0 for the subsequent yields. Compared with risks in non-smokers the relative risks ranged from 9.3 to 12.6 below the age of 50 but no trend was observed with increasing yield. CONCLUSIONS--Changing to cigarettes with a lower tar yield is not an effective means of reducing tobacco related morbidity from myocardial infarction.     

Effect of cigarette smoking on gastric emptying.

Gastric emptying after a test meal was studied in 17 normal volunteers--10 habitual smokers and seven non-smokers. The solid component of the test meal was labelled with technetium and the liquid component with indium. After one meal the habitual smokers smoked two cigarettes. Emptying curves were produced for both technetium and indium, and the differences between curves for meals with and without cigarettes were analysed. Cigarette smoking accelerated the rate at which the liquid component of a meal left the stomach. This may be important in the pathogenesis of duodneal ulcer and the delay in healing caused by cigarette smoking.     

Self-titration by cigarette smokers

An 11-week crossover study was carried out in which 12 subjects smoked high-nicotine (1·84 mg standard yield) and low-nicotine (0·6 mg) cigarettes after an initial period of smoking their usual brands with a medium-nicotine yield (mean 1·4 mg). Plasma and urine nicotine concentrations, carboxyhaemoglobin (COHb) concentration, puffing behaviour, 24-hour cigarette consumption, and butt nicotine content were measured. The changes in plasma nicotine and blood COHb concentrations showed that the smokers compensated for about two-thirds of the difference in standard yields when switched to either high- or low-nicotine cigarettes. Thus, compared with the medium-nicotine brand, the intake of nicotine and carbon monoxide was only about 10% higher when subjects smoked the high-nicotine cigarettes, which had a standard yield 30-40% higher than the medium brands; and only about 15% lower when they smoked the low-nicotine cigarettes, which had a standard yield about 50% lower than the medium brands. But nicotine content and urine nicotine concentrations followed a similar pattern. Changes in puffing behaviour and in 24-hour cigarette consumption were only slight.The results show clear evidence of both upward and downward self-titration of nicotine and carbon monoxide (and tar) intakes when smokers change to cigarettes with standard yields that differ over the range studied.     

Tobacco and pregnancy: overview of exposures and effects

This opening article will review the epidemiology of the effects of cigarette smoking and other forms of tobacco exposure on human development. Sources of exposure described include cigarettes and other forms of smoked tobacco, secondhand (environmental) tobacco smoke, several forms of smokeless tobacco, and nicotine from nicotine replacement therapy. Exposure is immense and worldwide, most of it due to smoking, but in some parts of the world and in some populations, smoking is exceeded by smokeless tobacco use. Nicotine and carbon monoxide exposure are of large concern, but cigarette smoke contains over 4000 chemical constituents and additives including known carcinogens, toxic heavy metals, and many chemicals untested for developmental toxicity. The impact of tobacco on human development will be reviewed. Fertility, conception, survival of the conceptus, most phases and aspects of development studied to date, as well as postnatal survival and health are adversely impacted by maternal tobacco use or exposure. Effects in surviving offspring are probably life-long, and are still being elucidated. It is hoped that this review and those to follow in this issue will serve to keep a focus on the critical and continuing problem of tobacco use impacting human development.     

Inhaling and lung cancer: an anomaly explained.

An objective index of inhaling cigarette smoke based on carboxyhaemoglobin concentrations and the carbon monoxide yields of cigarettes was used to investigate possible systematic differences in the extent of inhaling among light and heavy smokers when classified according to their self described inhaling habits. A total of 2108 men who smoked cigarettes were studied. Heavy smokers (20 or more cigarettes a day) had a higher average inhaling index than light smokers (fewer than 20 cigarettes a day) both among those who said that they inhaled and among those who said that they did not. This observation, together with indirect evidence that heavy smokers who inhale deeply may to some extent avoid depositing smoke condensate on their main bronchial epithelium, explains a hitherto unresolved anomaly--namely, that the risk of lung cancer is less among heavy cigarette smokers who say that they inhale than it is among those who say that they do not inhale.     

Bronchial Reactivity to Cigarette and Cigar Smoke

The change in specific airway conductance produced by smoking a cigarette under standard conditions was measured in 91 heavy smokers. Subsequently 19 of the most reactive subjects smoked two cigarettes with different filters and another containing cigar tobacco. The results indicated that reactivity to cigarette smoke was reduced significantly by increasing the retention efficiency of the filter and that reactivity to inhaled cigar-tobacco smoke was no less than that to cigarette smoke.