Evaluation of urinary 1-hydroxypyrene, S-phenylmercapturic acid, trans,trans-muconic acid, 3-methyladenine, 3-ethyladenine, 8-hydroxy-2'-deoxyguanosine and thioethers as biomarkers of exposure to cigarette smoke

The objective was to evaluate the utility of urinary 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (S-PMA), trans,trans-muconic acid (t,t-MA), 3-methyladenine (3-MeAd), 3-ethyladenine (3-EtAd), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and thioethers as biomarkers for assessing the exposure in adult smokers who switched from smoking conventional cigarettes to candidate potential reduced exposure products (PREP) or who stopped smoking. Two electrically heated smoking systems (EHCSS) were used as prototype cigarettes that have significant reductions in a number of mainstream smoke constituents as measured by smoking machines relative to those from conventional cigarettes. Urine samples were collected from a randomized, controlled, forced-switching study in which 110 adult smokers of a conventional cigarette brand (CC1) were randomly assigned to five study groups. The groups included the CC1 smoking group, a lower-tar conventional cigarette (CC2) smoking group, EHCSS1 group, EHCSS2 group and a no smoking group that were monitored for 8 days. Biomarkers were measured at baseline and day 8. The daily excretion levels of these biomarkers were compared among the groups before and after switching, and the relationships between the daily excretion levels of these biomarkers and cigarette smoking-related exposure were investigated using Pearson product-moment correlation and multiple regression analyses. It was concluded that under controlled study conditions: (1) 1-OHP, S-PMA and t,t-MA are useful biomarkers that could differentiate exposure between smoking conventional and EHCSS cigarettes or between smoking conventional cigarettes and no smoking; between S-PMA and t,t-MA, the former appeared to be more sensitive; (2) 3-MeAd could only differentiate between smoking conventional cigarettes and no smoking; the results for 3-EtAd were not conclusive because contradictory results were observed; (3) 8-OHdG had a questionable association with smoking and therefore the utility of this biomarker for smoking-related exposure could not be established; and (4) urinary excretion of thioethers as a biomarker lacked sensitivity to demonstrate a clear dose-response relationship in conventional cigarette smokers, although it could differentiate the excretion levels between those subjects who smoked a conventional cigarette and those who stopped smoking.     

Nicotine increases sucrose self-administration and seeking in rats

Associations between nicotine in cigarettes and food consumption may alter the incentive value of food such that food cue-reactivity is exaggerated during abstinence from smoking. This effect may contribute to the weight gain associated with cessation of smoking. We examined the effects of nicotine (0.4 mg/kg base subcutaneous) paired (NPD) or unpaired (NUP) with 10% sucrose self-administration (SA; 0.2 ml/delivery, 1 h/day for 10 days) on SA response rate and intake as well as sucrose cue-reactivity following either 1 or 30 days of forced abstinence. Rats were administered the training dose of nicotine prior to a second, consecutive cue-reactivity session. NPD rats responded at over three times the rate for sucrose and earned nearly twice the number of sucrose deliveries as NUP rats or saline controls. Sucrose cue-reactivity was greater after 30 days versus 1 day of forced abstinence for all groups. History of nicotine exposure had no effect on sucrose cue-reactivity. However, the subsequent injection of nicotine increased sucrose cue-reactivity only in the NPD groups. There were no abstinent-dependent effects of nicotine challenge on sucrose cue-reactivity. A study conducted in parallel with water as the reinforcer revealed a less dramatic effect of nicotine on intake. There was no history or abstinence-dependent effects of nicotine on water cue-reactivity. Nicotine increases the reinforcing effects of sucrose and sucrose-paired cues when nicotine is present. An implication of these findings is that relapse to nicotine (cigarettes) could substantially elevate food cue-reactivity.     

Evaluation of urinary 1-hydroxypyrene,S-phenylmercapturic acid,trans,trans-muconic acid, 3-methyladenine, 3-ethyladenine, 8-hydroxy-2′-deoxyguanosine and thioethers as biomarkers of exposure to cigarette smoke

The objective was to evaluate the utility of urinary 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (S-PMA), trans,trans-muconic acid (t,t-MA), 3-methyladenine (3-MeAd), 3-ethyladenine (3-EtAd), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and thioethers as biomarkers for assessing the exposure in adult smokers who switched from smoking conventional cigarettes to candidate potential reduced exposure products (PREP) or who stopped smoking. Two electrically heated smoking systems (EHCSS) were used as prototype cigarettes that have significant reductions in a number of mainstream smoke constituents as measured by smoking machines relative to those from conventional cigarettes. Urine samples were collected from a randomized, controlled, forced-switching study in which 110 adult smokers of a conventional cigarette brand (CC1) were randomly assigned to five study groups. The groups included the CC1 smoking group, a lower-tar conventional cigarette (CC2) smoking group, EHCSS1 group, EHCSS2 group and a no smoking group that were monitored for 8 days. Biomarkers were measured at baseline and day 8. The daily excretion levels of these biomarkers were compared among the groups before and after switching, and the relationships between the daily excretion levels of these biomarkers and cigarette smoking-related exposure were investigated using Pearson product-moment correlation and multiple regression analyses. It was concluded that under controlled study conditions: (1) 1-OHP, S-PMA and t,t-MA are useful biomarkers that could differentiate exposure between smoking conventional and EHCSS cigarettes or between smoking conventional cigarettes and no smoking; between S-PMA and t,t-MA, the former appeared to be more sensitive; (2) 3-MeAd could only differentiate between smoking conventional cigarettes and no smoking; the results for 3-EtAd were not conclusive because contradictory results were observed; (3) 8-OHdG had a questionable association with smoking and therefore the utility of this biomarker for smoking-related exposure could not be established; and (4) urinary excretion of thioethers as a biomarker lacked sensitivity to demonstrate a clear dose–response relationship in conventional cigarette smokers, although it could differentiate the excretion levels between those subjects who smoked a conventional cigarette and those who stopped smoking.     

Should intake of carbon monoxide be used as a guide to intake of other smoke constituents?

The relation between blood carboxyhaemoglobin (COHb) and plasma nicotine concentrations was studied in a group of 12 smokers smoking cigarettes of three levels of standard delivery. While the intake of carbon monoxide from a single cigarette was unrelated to the intake of nicotine, presmoking "trough" concentrations of the two substances (reflecting longer-term exposure) were highly correlated. Various other measures of nicotine exposure were at best only moderately correlated with blood nicotine concentrations. Thus trough COHb concentrations might be used to provide a reliable indication of the exposure to nicotine of individual smokers smoking the same type of cigarette, and of the relative exposure to nicotine of populations smoking cigarettes of different standard deliveries.     

Meta-analysis of relation between cigarette smoking and stroke.

There is a lack of consensus among studies on the possible risks of stroke from cigarette smoking; because of this a meta-analysis was conducted. All published data on the association were sought and the relative risk for each study obtained whenever possible. The pooled relative risks were calculated by using estimates of the precision of the individual relative risks to weight their contribution to the meta-analysis. Thirty two separate studies were analysed. The overall relative risk of stroke associated with cigarette smoking was 1.5 (95% confidence interval 1.4 to 1.6). Considerable differences were seen in relative risks among the subtypes: cerebral infarction 1.9, cerebral haemorrhage 0.7, and subarachnoid haemorrhage 2.9. An effect of age on the relative risk was also noted; less than 55 years 2.9, 55-74 years 1.8, and greater than or equal to 75 years 1.1. A dose response between the number of cigarettes smoked and relative risk was noted, and there was a small increased risk in women compared with men. Ex-smokers under the age of 75 seemed to retain an appreciably increased risk of stroke (1.5); for all ages the relative risk in ex-smokers was 1.2. The meta-analysis provides strong evidence of an excess risk of stroke among cigarette smokers. Stroke should therefore be added to the list of diseases related to smoking.     

Respiratory effects of non-tobacco cigarettes.

Data from the Tucson epidemiological study of airways obstructive disease on smoking of non-tobacco cigarettes such as marijuana were analysed to determine the effect of such smoking on respiratory symptoms and pulmonary function. Among adults aged under 40, 14% had smoked non-tobacco cigarettes at some time and 9% were current users. The prevalence of respiratory symptoms was increased in smokers of non-tobacco cigarettes. After tobacco smoking had been controlled for men who smoked non-tobacco cigarettes showed significant decreases in expiratory flow rates at low lung volumes and in the ratio of the forced expiratory volume in one second to the vital capacity. This effect on pulmonary function in male non-tobacco cigarette smokers was greater than the effect of tobacco cigarette smoking. These data suggest that non-tobacco cigarette smoking may be an important risk factor in young adults with respiratory symptoms or evidence of airways obstruction.     

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.     

Phlegm and Filters

Male mass radiography volunteers aged 40 or more were questioned about their sputum production and cigarette consumption in relation to type (filter or plain) smoked. Of 10,414 volunteers, 3,045 smoked filter cigarettes and 2,393 smoked plain cigarettes. The rate of persistent daily sputum of filter smokers (31·9%) was significantly lower than that of plain cigarette smokers (37·2%). A similar pattern was maintained when age and cigarette consumption were standardized. These figures are thought to understate the less injurious nature of filter cigarettes, since more than half of the filter smokers with persistent sputum developed this while previously smoking plain cigarettes.Whatever the reasons for the less injurious nature of filter cigarettes, it seems that cigarette smokers unable to stop smoking might suffer less from chronic bronchitis if they changed to filter cigarettes.     

Quantitative analyses of methamphetamine's effects on self-control choices: implications for elucidating behavioral mechanisms of drug action

The purpose of the present research was to utilize quantitative methods to identify behavioral mechanisms involved in the effects of stimulant drugs on choice in a self-control procedure. A logarithmic equation based upon a combination of the matching law and hyperbolic discounting was used to separate drug-induced changes in sensitivity to reinforcement delay from drug-induced changes in sensitivity to reinforcement amount. Pigeons responded under a concurrent-chains schedule. In the initial link, two keys were illuminated simultaneously and access to the terminal link was controlled by a single random-interval (RI) schedule; pecks on one or the other key lead to its terminal link with a 0.5 probability. In the terminal links, one alternative provided 1-s access to food (the smaller reinforcer) and the other alternative provided 4-s access to food (the larger reinforcer). The signaled delay to the smaller reinforcer always was 2s, whereas the signaled delay to the larger reinforcer increased from 2 to 40s within each session, across 10-min blocks. In general, intermediate doses of methamphetamine increased preference for the larger more delayed reinforcer. Quantitative analyses indicated that, in most cases, methamphetamine decreased sensitivity to reinforcement delay. In a few instances, concomitant decreases in sensitivity to reinforcement amount also occurred. These results suggest that a reduced sensitivity to reinforcement delay may be important behavioral mechanism of the effects of stimulants on self-control choices, and that this effect sometimes can be accompanied by a decreased sensitivity to reinforcement amount.     

Developing human laboratory models of smoking lapse behavior for medication screening

Use of human laboratory analogues of smoking behavior can provide an efficient, cost-effective mechanistic evaluation of a medication signal on smoking behavior, with the result of facilitating translational work in medications development. Although a number of human laboratory models exist to investigate various aspects of smoking behavior and nicotine dependence phenomena, none have yet modeled smoking lapse behavior. The first instance of smoking during a quit attempt (i.e. smoking lapse) is highly predictive of relapse and represents an important target for medications development. Focusing on an abstinence outcome is critical for medication screening as the US Food and Drug Administration approval for cessation medications is contingent on demonstrating effects on smoking abstinence. This paper outlines a three-stage process for the development of a smoking lapse model for the purpose of medication screening. The smoking lapse paradigm models two critical features of lapse behavior: the ability to resist the first cigarette and subsequent ad libitum smoking. Within the context of the model, smokers are first exposed to known precipitants of smoking relapse (e.g. nicotine deprivation, alcohol, stress), and then presented their preferred brand of cigarettes. Their ability to resist smoking is then modeled and once smokers 'give in' and decide to smoke, they participate in a tobacco self-administration session. Ongoing and completed work developing and validating these models for the purpose of medication screening is discussed.     

The role of glutathione in the toxicity of smoke condensates from cigarettes that burn or heat tobacco

Inhalation of cigarette smoke aerosol via active smoking is associated with the development of pulmonary inflammation. The cytotoxic potential of cigarette smoke has been hypothetically related to development of pulmonary inflammation since the release of intracellular contents from dead and dying cells has been reported to induce inflammatory foci. In this study, cigarette smoke condensates (CSCs) were prepared from Kentucky 1R4F reference cigarettes and cigarettes that primarily heat tobacco (Eclipse). The two CSCs were then compared for their ability to induce killing in human-hamster A_L hybrid cells. CSCs prepared from Eclipse were much less cytotoxic than those prepared from reference cigarettes. At 60 μg CSC/ml culture medium, survival for CSC from Eclipse cigarettes was approximately 70% compared with 1% for CSC from burned K1R4F cigarettes. The observed reduction in CSC-Eclipse cytotoxicity toward these mammalian cells is consistent with the previously published observation of a 30% decline in pulmonary white cell count and 40% reduction in visual bronchitis index in human smokers who switched to Eclipse for 2 months. Results with N-acetylcysteine and buthionine-S-R-sulfoximine indicate that glutathione markedly reduces the cytoxicity of both CSCs.     

Nicotine and the behavioral mechanisms of intertemporal choice

Nicotine has been found to produce dose-dependent increases in impulsive choice (preference for smaller, sooner reinforcers relative to larger, later reinforcers) in rats. Such increases could be produced by either of two behavioral mechanisms: (1) an increase in delay discounting (i.e., exacerbating the impact of differences in reinforcer delays) which would increase the value of a sooner reinforcer relative to a later one, or (2) a decrease in magnitude sensitivity (i.e., diminishing the impact of differences in reinforcer magnitudes) which would increase the value of a smaller reinforcer relative to a larger one. To isolate which of these two behavioral mechanisms was likely responsible for nicotine's effect on impulsive choice, we manipulated reinforcer delay and magnitude using a concurrent, variable interval (VI 30 s, VI 30 s) schedule of reinforcement with 2 groups of Long-Evans rats (n = 6 per group). For one group, choices were made between a 1-s delay and a 9-s delay to 2 food pellets. For a second group, choices were made between 1 pellet and 3 pellets. Nicotine (vehicle, 0.03, 0.1, 0.3, 0.56 and 0.74 mg/kg) produced dose-dependent decreases in preference for large versus small magnitude reinforcers and had no consistent effect on preference for short versus long delays. This suggests that nicotine decreases sensitivity to reinforcer magnitude.     

Passive exposure to tobacco smoke: saliva cotinine concentrations in a representative population sample of non-smoking schoolchildren.

Saliva cotinine concentrations in 569 non-smoking schoolchildren were strongly related to the smoking habits of their parents. When neither parent smoked the mean concentration was 0.44 ng/ml, rising to 3.38 ng/ml when both parents were cigarette smokers. Mothers'' smoking had a stronger influence than did fathers'' (p less than 0.01). In addition, there was a small independent effect of number of siblings who smoked (p less than 0.01). The dose of nicotine received from fathers'' smoking was estimated as equivalent to the active smoking of 30 cigarettes a year, that from mothers'' smoking as equivalent to smoking 50 cigarettes a year, and that from both parents smoking as equivalent to smoking 80 cigarettes a year. This unsolicited burden may be prolonged throughout childhood and poses a definite risk to health.     

A comparative study by electron paramagnetic resonance of free radical species in the mainstream and sidestream smoke of cigarettes with conventional acetate filters and 'bio-filters'

Tobacco smoking is the most important extrinsic cause, after the diet, for increasing morbidity and mortality in humans. Unless current tobacco smoking patterns in industrialised and non-industrialised countries change, cigarettes will kill prematurely 10 million people a year by 2025. Greece is at the top of the list of European countries in cigarette consumption. In 1997, a Greek tobacco company introduced a new 'bio-filter' (BF) claiming that it reduces substantially the risks of smoking. In a recent publication [Deliconstantinos G, Villiotou V, Stavrides J. Scavenging effects of hemoglobin and related heme containing compounds on nitric oxide, reactive oxidants and carcinogenic volatile nitrosocompounds of cigarette smoke. A new method for protection against the dangerous cigarette constituents. Anticancer Res 1994; 14: 2717-2726] it was claimed that the new 'bio-filter' (activated carbon impregnated with dry hemoglobin) reduces certain toxic substances and oxidants (like NO, CO, NOx, H2O2, aldehydes, trace elements and nitroso-compounds) in the gas-phase of the mainstream smoke. We have investigated by electron paramagnetic resonance (EPR) the mainstream and sidestream smoke of the BF cigarette, in comparison with three other cigarettes with similar tar and nicotine contents, that have conventional acetate filters. We found that BF cigarette smoke has similar tar radical species with the same intensity EPR signals to those of the other cigarettes. The ability of the aqueous cigarette tar extracts to produce hydroxyl radicals (HO*), which were spin trapped by DMPO, was very similar to, or even higher than, the other 3 brands. The gas-phase of the mainstream smoke of the BF cigarette showed a 30-35% reduction in the production of oxygen-centered radicals (spin trapped with PBN). In the case of the sidestream smoke, BF cigarettes produced substantially higher concentrations of gas-phase radicals, compared to the other brands. These results suggest that BF is partially effective at removing some of the gas-phase oxidants but not effective in the reduction of tar and its radical species in the mainstream and sidestream smoke. It is well known from epidemiological studies that tar content is strongly associated with increasing risk to smokers of lung cancer. In our experiments, BF cigarettes produce a higher amount of tar and stable free radical species than the other 3 brands in the sidestream smoke (between puffs), thus potentially increasing risk to the smoker and passive smoker.     

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.     

Smoking habits of men and women.

The smoking habits of 1501 cigarette smokers attending 28 general practitioners in five group practices in London were assessed. Prevalence of smoking, daily cigarette consumption, and the use of cigars, untipped cigarettes, and hand-rolled cigarettes were lower in the women. After controlling for consumption the proportions of men and women who smoked every day were similar. Women who smoked 20 or more a day were similar to men in their self-reported inhaling habits and use of low-nicotine cigarettes. The results suggest that women differ from men in those aspects of smoking that are determined predominantly by social factors but that their smoking habits become similar when pharmacological motivation takes over. This apparently occurs when consumption reaches about 20 cigarettes a day, when smoking almost inevitably becomes a regular event and the sex differences disappear.     

Blood carboxyhaemoglobin,plasma thiocyanate,and cigarette consumption: implications for epidemiological studies in smokers.

Carboxyhaemoglobin and plasma thiocyanate concentrations were found to be significantly correlated with self-reported daily cigarette consumption in 360 smokers (r = 0.416 and 0.412 respectively; p less than 0.001). The extent to which inhalation patterns affected the intake of cigarette smoke constituents was determined from the partial correlation between carboxyhaemoglobin and plasma thiocyanate concentrations after the number of cigarettes smoke per day had been allowed for (r = 0.48). Thus 23% of the variation in carboxyhaemoglobin and thiocyanate concentrations was accounted for by the was a cigarette was smoked and a further 21% by the number smoked a day. Furthermore, the relation between carboxyhaemoglobin or plasma thiocyanate and daily cigarette consumption was not linear but reached an asymptote at consumption rates above 25 cigarettes a day. These results suggest that by itself daily cigarette consumption will not identify those smokers most at risk and will also underestimate and dose-response relationship between smoking and selected diseases.     

APPLICATIONS OF SENSORY SCIENCE WITHIN THE TOBACCO INDUSTRY

Sensory testing of cigarette smoke presents some unique problems to the sensory specialist. This is due to a variety of reasons including the high degree of similarity between blended cigarettes and a high degree of variability between individual cigarettes. In the cigarette industry, a large effort has been placed on adapting and developing new methods of collecting and analyzing sensory-data on both flavorants and cigarette smoke. These methods include odor profiling and multidimensional scaling based on attributes and acceptability scales. In addition, extensive research has been conducted to determine the number of relevent dimensions to smoking and the types of changes that could affect consumer acceptance or purchase behavior.     

Effects of acute cigarette smoke exposure on macrophage kinetics and release of tumour necrosis factor alpha in rats

Some biological parameters before and after an acute episode of cigarette smoking in rats have been evaluated. The carboxyhaemoglobin levels depended either on the number of cigarettes, or on the time of exposure to cigarette smoke and returned to pre-smoking values in about 2 h. The evaluation of the kinetics of alveolar and peritoneal macrophages in rats after a smoking session of three cigarettes within an hour, indicated that alveolar macrophages in the bronchoalveolar lavage fluid significantly increased 8 h after the smoking, whereas the number of peritoneal macrophages remained practically constant. The incubation of these cells for various times at 37( degrees )C in a humidified atmosphere, resulted in a spontaneous release, 24 h thereafter, of variable amounts of tumour necrosis factor alpha (TNFalpha), which remained practically constant during the following days. Neither alveolar macrophages of control rats, nor peritoneal macrophages of both control and smoking rats were able to release TNFalpha. Moreover, after lipopolysaccharide induction of alveolar macrophages of both control and smoking rats, an increased release of TNFalpha was observed, indicating that these cells were in an active state.     

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.