Nicotine and carbon monoxide content of cigarette smoke and the risk of myocardial infarction in young men

To evaluate whether the nicotine and carbon monoxide content of cigarette smoke is related to the risk of nonfatal first myocardial infarction in young men, we compared 502 cases with 835 hospital controls, all between the ages of 30 and 54 years. As expected, the estimated risk of myocardial infarction increased with the number of cigarettes smoked; overall, the relative-risk estimate for current smokers was 2.8 (95 per cent confidence interval, 2.0 to 4.0). The risk did not appear to vary according to the amount of nicotine or carbon monoxide in the cigarette, and the mean amounts of both substances per cigarette were similar for the cases and controls. The results suggest that men who smoke the newer cigarettes with reduced amounts of nicotine and carbon monoxide do not have a lower risk of myocardial infarction than those who smoke cigarettes containing larger amounts of these substances.     

The contributions of cigarette yield,consumption, inhalation and puffing behaviour to the prediction of smoke exposure

Summary The overall predictability of smoke exposure indicators and the importance of different influencing factors were assessed in a cross-sectional study (n = 144), using multiple linear regression and bivariate correlation analyses. Respiratory CO, and plasma nicotine and cotinine concentrations were measured before and after smoking, for lip or holder smoking, and natural or standardized (30 puffs) puffing. The prediction of smoke exposure measures varied considerably across sampling times, smoking conditions, and dependent variables. The variance of plasma cotinine and nicotine were predictable to a considerable extent (30%; 19–41 %) by cigarette yield, consumption and self-reported inhalation, whereas respiratory CO was less predictable (15–27%). Generally, consumption was the most important predictor, surpassed by nicotine yield for post-smoking plasma nicotine. Smoke exposure from a single smoking period could be predicted to a variable degree (CO, 11–42%; nicotine, 33–54%) by a subset of smoker's sex, cigarette yield, self-reported inhalation and puffing characteristics. The highest prediction was found under standardized smoking conditions (30 puffs through a holder), the lowest under natural smoking conditions. The best subset of predictors, especially with respect to puffing parameters, was found to vary considerably across smoking conditions and dependent variables.Abbreviations CED cigarettes on experimental day - CO carbon monoxide - CPD cigarettes per day - H holder smoking - L lip smoking - N natural puffing - S standardized puffing     

"Low yield" cigarettes and the risk of nonfatal myocardial infarction in women

Newer brands of cigarettes with reduced yields of nicotine and carbon monoxide have been promoted as being less hazardous than others. We evaluated the effect of smoking "low yield" cigarettes on the risk of nonfatal myocardial infarction in women under 65 years of age. The data were obtained in a case-control study of 910 women with a first myocardial infarction and 2375 hospital controls. The estimated relative risk for current smokers as compared with those who had never smoked increased with the number of cigarettes smoked. The estimated overall relative risk was 3.7 (95 percent confidence interval, 3.0 to 4.7). The estimated risks did not vary according to the nicotine or carbon monoxide yield of the cigarette. The estimated relative risk (4.7) in women who smoked brands with the lowest levels of nicotine (less than 0.40 mg per cigarette) was similar to that (4.2) in smokers of the higher-yield brands (greater than 1.30 mg). For exsmokers, the estimated relative risk was 1.4 (95 percent confidence interval, 1.0 to 1.8). These data suggest that women who smoke low-yield cigarettes do not have a lower risk of a first nonfatal myocardial infarction than women who smoke higher-yield brands. For smokers who wish to reduce their risk, switching to low-yield brands is a poor alternative to quitting.     

African-American menthol and nonmenthol smokers: differences in smoking and cessation experiences

BACKGROUND: Despite smoking fewer cigarettes per day, African Americans have lower cessation rates and experience disproportionately higher rates of smoking-related health consequences. Because of their high preference for menthol cigarettes, it has been suggested that smoking menthol cigarettes may contribute to the excess smoking-related morbidity experienced by African Americans. Smoking menthol cigarettes could increase health risks from smoking if smokers of menthol cigarettes have lower cessation rates and thereby have longer duration of smoking compared to smokers of nonmentholated cigarettes. Few studies have examined associations between smoking of mentholated cigarettes and smoking cessation among African Americans. This study examined the smoking patterns of menthol cigarette smokers and their smoking cessation experiences. METHODS: A cross-sectional survey of 480 African-American smokers at an inner-city health center. Survey examined sociodemographics, smoking characteristics, and smoking cessation experiences of participants. Menthol smokers (n = 407) were compared to nonmenthol smokers (n = 73) in these characteristics. RESULTS: Menthol smokers were younger and more likely to smoke cigarettes with longer rod length, with filters, and those high in nicotine and tar. Although both groups did not differ by number of past quit attempts, time since most recent quit attempt was shorter for menthol smokers. The durations of most recent and longest-ever quit attempts were nonsignificantly shorter for menthol, compared to nonmenthol smokers. CONCLUSIONS: These data suggest that African-American menthol smokers are less successful with smoking cessation. Prospective studies are needed to confirm these findings and examine mechanisms underlying such differences.     

Smoking rate,carboxyhemoglobin, and body mass in the Second National Health and Nutrition Examination Survey (NHANES II)

The relationship of body mass and triceps skinfold thickness to both reported number of cigarettes smoked per day and carboxyhemoglobin levels was examined in healthy cigarette smokers in the NHANES II. Among both men and women, higher carboxyhemoglobin levels were related to lower body mass and thinner skinfolds, whereas higher levels of reported daily cigarette smoking were related to increased body mass and thicker skinfolds among men only. These relationships were independent of age, education, caloric intake, physical activity, and exercise. The opposite effects of number of cigarettes smoked per day and a biological index of cigarette smoke exposure on body mass suggest that increased cigarette smoking may covary with factors that would favor increased body weight among men, whereas decreases in body weight with increases in carboxyhemoglobin may reflect the effects of nicotine exposure on energy expenditure in both men and women.This research was supported by National Heart, Lung, and Blood Institute Grant HL38414.     

Exposure level to cigarette tar or nicotine is associated with leukocyte DNA damage in male Japanese smokers

We investigated the number of cigarettes smoked daily, years of smoking, cigarette pack-years, levels of daily exposure to cigarette tar (LECT, mg/day) or nicotine (LECN, mg/day) in 53 male Japanese smokers using a questionnaire and measured each participant's baseline leukocyte DNA damage using the alkaline comet assay. The results showed that the baseline value of peripheral leukocyte DNA strand breaks was significantly associated with LECT (P < 0.05), LECN (P < 0.05), years of smoking or cigarette pack-years (P < 0.05) but not with the number of cigarettes smoked per day. Stepwise multiple regression analyses of factors including age, occupation, years of employment, alcohol drinking behaviour, physical activity, nutritional balance and cigarette smoking parameters showed that LECT was a positively significant predictor (Partial r = 0.0005, P < 0.05) of the comet tail moment. In consideration of the high correlation between LECT and LECN (Y(tar) = 12.53 X(nicotine) -7.23, r = 0.995, P < 0.0001), these results suggest that levels of exposure to cigarette tar or nicotine (mg/day) would be a sensitive parameter in appreciation of genotoxicity of cigarette smoking in these male Japanese smokers.     

Cardiomyopathy produced by cigarette smoke. Ultrastructural observations in guinea pigs.

Guinea pigs were restrained in a smoking machine and were exposed to the smoke of eight cigarettes a day, five days a week for 12 to 15 weeks. One group of animals inhaled filtered smoke from which most of the tar and nicotine had been removed. Heart weight of the smoking animals was found to be significantly increased in both the filtered and unfiltered groups. Toxic changes were evident in myocardial mitochondria that were associated with edema, increased lipid and enhanced autophagolysosomal activity. The observed cardiomyopathy is probably caused by carbon monoxide and resembles the changes of chronic intermittent hypoxia.     

Biomarkers of tobacco smoke exposure

Tobacco smoking is a major risk factor for cancer, cardiovascular diseases and respiratory illnesses. Smoking is increasing among children and adolescents with subsequent consequences on the health. Furthermore, maternal tobacco smoking during pregnancy adversely affects prenatal growth. Nicotine, the most important tobacco alkaloid, is responsible for maintaining tobacco addiction. According to a recent Circulaire de la direction générale de la santé, nicotine dependence should be determined through questionnaires and quantitative estimate of nicotine metabolites. Nicotine blood level fluctuates and urinary nicotine excretion is of short duration. Nicotine is intensively metabolized in the liver and oxidized into cotinine. Urinary measurement of cotinine appears to be highly related with the degree of intoxication and to allow the differentiation between non exposed and exposed non-smokers. In order to check the present application of nicotine metabolites measurement, a survey was conducted in 340 smoking cessation units. Forty percent physicians (n = 137) answered the survey. For 17% of them, the quantification of nicotine metabolites is included in their daily practise and for 79%, guidelines about cotinine measurement should be given in France. Sixty-seven biologists answered the survey. Recommendations for immunoassay and HPLC determination of cotinine should be given as reported by 66 and 44% of them respectively. Indeed, urinary cotinine measurement with high performance liquid chromatography is highly sensitive and specific. However, immunoassays are more convenient. These two approaches are presently under investigation in order to provide guidelines for optimal use in various clinical situations. Traditional measures for nicotine dependence are the number of cigarettes smoked per day, nicotine intake expressed as mg per day, Fagerstr m questionnaire, expired air carbon monoxide, thiocyanates and cotinine levels in biological fluids. Urinary cotinine measurement is the most useful for the follow-up of smoking cessation including adjustment of nicotine replacement therapy, especially after a clinical event or for the follow-up of smoking pregnant women. It allows the detection of passive smoke exposure in children who are hospitalized for recurrent respiratory illnesses.     

Tobacco smoke: Unraveling a controversial subject

Cigarettes are a modern and industrial form of tobacco use and obviously involve more than just tobacco. A multitude of physical processes and chemical reactions occur inside the burning zone of a cigarette. Cigarette smoke is an aerosol of liquid droplets (the particulate phase) suspended within a mixture of gases and semi-volatile compounds. Two kinds of smoke with different composition and properties are produced during smoking: mainstream smoke inhaled by the smoker and sidestream smoke, which is released into the environment between puffs from the lit end of the cigarette. Several techniques and modifications have altered the design of the cigarette during the last 50 years and changed smoke composition, with the effect of lower tar and nicotine smoke yields. An enormous amount of research has been done since the 1950s on smoke composition. With regard to the numerous toxic or carcinogenic constituents identified in tobacco smoke, there is a strong focus in the industry and with the authorities on the over 40 compounds, called "Hoffmann analytes". The yields of tar and nicotine in mainstream smoke of a cigarette brand as printed on the pack are measured with smoking machines under highly standardized conditions. Yields must comply with regulatory limits set in a number of countries. Smoking by machine is different from the smoking behavior of humans. There is a growing movement to develop more "realistic" methods to estimate smoke yields. But it is unclear whether alternative smoking regimens are more representative of human smoking behavior and provide better predictions of human exposure. Tobacco smoke has strong biological and toxicological effects in vitro and in vivo. There is an obvious need for developing a unified and validated testing approach particularly for the assessment of additives and the evaluation of new potentially reduced exposure products (PREPs). This paper gives a comprehensive overview of cigarette design, the composition and toxicity testing of smoke, and the way machines and people smoke - with links to the more detailed literature.     

Parental bad habits breed bad behaviors in youth: Exposure to gestational smoke and child impulsivity

In utero exposure to cigarette smoke has been shown to have an adverse effect on healthy brain development in childhood. In the present study, we examine whether fetal exposure to mild and heavy smoking is associated with lower levels of impulsivity and cognitive control at age 10. Using a sample of 2120 children from the Québec Longitudinal Study of Child Development, we examine the association between gestational cigarette smoke exposure and fourth grade teacher reports of impulsivity and classroom engagement which represent behavioral indicators of executive functions. When compared to children of non-smokers, children of mothers who reported smoking heavily during pregnancy (10 or more cigarettes per day) were rated by their fourth grade teachers as displaying higher levels of impulsive behavior, scoring.112 standard deviation units higher than children of non-smokers. Children of mothers who smoked heavily were also less engaged in the classroom, scoring.057 standard deviation units lower than children of women who did not smoke. These analyses were adjusted for many potentially confounding child and family variables. Exposure to perinatal nicotine may compromise subsequent brain development. In particular, fetal nicotine may be associated with impairment in areas recruited for the effortful control of behavior in later childhood, a time when task-orientation and industriousness are imperative for academic success.     

Impact of smoking on the frequencies of micronuclei and other nuclear abnormalities in exfoliated oral cells: a comparative study with different cigarette types

The primary aim of the study was to investigate the impact of tar and nicotine contents of cigarettes on chromosomal damage in oral mucosa cells of smokers. We monitored the effect of smoking different cigarette types (i.e., of ultralight filter, light filter, medium filter and unfiltered cigarettes) on induction of nuclear anomalies including micronuclei (MN), broken eggs (BE), binucleates (BN), condensed chromatin (CC), karyorrhexis (KR), karyolysis (KL) and pyknosis (P) in exfoliated buccal cells. The cells were collected from 83 healthy heavy smokers (n=15-25/group) consuming a similar number of cigarettes (26-33) per day and from never smokers as controls (n=20). The frequencies of KR, CC, KL, BE and BN were increased significantly only in smokers of medium (MF) and non-filtered (NF) types of cigarettes while MN levels were only elevated (p < 0.0001) in the group that smoked NF cigarettes. Since BN and BE were increased (p < 00001) as a consequence of exposure to lower levels of toxic constituents in tobacco, it suggests that these endpoints, which both reflect DNA damage, are more sensitive than MN, which is the only parameter scored in most earlier studies. The induction of MN, BN, KR and KL increased significantly with daily tar exposure and decreased simultaneously with daily nicotine uptake (in all cases, P was < 0.0001). These findings also suggest that nicotine potentially protects cells against DNA reactive carcinogens contained in tobacco smoke although earlier in vitro and animal studies showed that the alkaloid induces DNA damage per se. A significant inverse correlation between the frequencies of endpoints such as cells with MN (- 1.56), MN (-1.69), BN (-1.36), KR (-1.10) and KL (-1.87) with the nicotine levels in cigarettes was found. However, this observation requires further verification by a controlled intervention study. In case it can be substantiated it will have an impact on the ongoing discussion of the health risks associated with nicotine replacement therapy.     

Smoking behaviour and increase in nicotine and carboxyhaemoglobin in venous blood

Summary The connection between smoking behaviour (number of puffs, puff volume, depth of inhalation, duration of inhalation) and the increase in both nicotine and carboxyhaemoglobin (COHb) in venous blood was investigated with methods developed especially for measurement of the puff volume, the depth of inhalation, and the duration of inhalation in 28 inhaling cigarette smokers. A significant correlation could be demonstrated between the smoking parameters and the nicotine and carboxyhaemoglobin increase. The weighting obtained shows that the number of puffs is the most important parameter affecting the increase in nicotine, whereas the depth of inhalation and the puff volume are of much less relevance. The duration of inhalation does not affect the nicotine level. A significant increase in nicotine cannot be attained in non-inhalatioe smoking of cigarettes with an acid mainstream smoke (n=14). The increase in COHb is most affected by the puff volume, and slightly less by the number of puffs and the depth of inhalation. The duration of inhalation does not affect the COHb level.Abbreviations C compliance of the lung - C_sta static compliance of the lung - CO carbon monoxide - COHb carboxyhaemoglobin - D_coa diffusion of carbon monoxide in the lung - Hb haemoglobin - P_ACO alveolar partial pressure of carbon monoxide - P_cCO partial pressure of carbon monoxide in the pulmonary capillaries - P_A-cNCO difference in partial pressure between the alveolar cavity and the pulmonary capillaries - VC vital capacity - V_coa amount of diffusion of carbon monoxide per unit of time     

Markers for smoking]

Quantitative and objective measurement of exposure to cigarette smoke by assays of chemical markers is desirable, especially in preventive medicine, since the negative health effects of tobacco smoke are well documented. Chemical markers include nicotine and cotinine in plasma, urine, and saliva; carbon monoxide in exhaled air; carboxyhemoglobin in blood and thiocyanate in biological fluids. Ease of use, cost, specificity, and sensitivity vary across markers. Determination of the thiocyanate/creatinine ratio in urine is a reliable, noninvasive, and inexpensive test for evaluating exposure to cigarette smoke. No marker for cumulative exposure to cigarette smoke is available to date. The plasma level of fluorescent lipoperoxides may provide an estimation of the in vivo toxicity of exposure to cigarette smoke.     

Effects of cigarette smoke and nicotine on feeding and energy

Much evidence has accumulated indicating that cigarette smokers weigh less than non-smokers and that smokers gain weight when they cease smoking. In the present study we evaluated the effects of cigarette smoke and nicotine on food intake, weight gain, resting energy output, brown fat mass and opiate binding (opiates initiate feeding in sated rats) in rats. Chronic smoke exposure slightly suppressed growth rate and food intake after 14 days of smoke exposure. Blood glucose levels and intrascapular brown adipose mase were increased as a result of smoke exposure. Hamsters chronically exposed to cigarette smoke decreased body weight; however, food intake was not significantly suppressed. Short term (5 day) exposure to nicotine (4 and 2 mg/kg/day) suppressed growth rate and food intake. Nicotine (4 and 2 mg/kg) significantly suppressed water ingestion in water-deprived rats and altered the quantities of flavored solutions ingested by rats compared with those ingested by rats receiving no nicotine. Thus cigarette smoke and nicotine exposure affects food intake, energy utilization and taste perception; all parameters which contribute to overall body mass; however, these parameters change in a complex manner with only small changes occurring at specific time intervals.     

Nocturnal sleep-disturbing nicotine craving: a newly described symptom of extreme nicotine dependence

In our research on smoking and nicotine dependence we have noticed a sleep disturbance, which is a further symptom of extreme nicotine dependence. We call this symptom "nocturnal sleep-disturbing nicotine craving" (NSDNC). NSDNC is characterised by craving for cigarettes during the individual sleep times. The smoker awakes (one or several times per week) during his regular sleep time, and has to smoke a cigarette before he/she continues sleeping. This symptom can be explained by the decreasing nicotine levels during the sleep time, which results in nicotine craving. However, NSDNC should be carefully separated from other sleep disturbances, or sleep disturbing events (nycturia, medication side effects), when nicotine craving is not the main reason for awakening.     

Interaction and pH dependence of effects of nicotine and carbon monoxide in cigarette smoke inhalation experiments with rats

In view of subacute inhalation studies with cigarette smoke at high concentrations, the toxic properties of combinations of carbon monoxide and nicotine were investigated. Treating rats with fresh diluted cigarette smoke in an inhalation chamber, we established a smoking schedule that resulted in a certain death rate after 13 days. The mortality under the experimental conditions was taken as a measure for the toxicity of different combinations of carbon monoxide and nicotine. Since the absorption and therefore the toxicity of nicotine is pH dependent, the factorial experiments were performed under two pH conditions. The first experiments were conducted between pH 6.5 and 6.9 and then between pH 6.6 and 7.8 where the higher pH is due to the addition of nicotine base to the cigarette filler. After extensive mathematical treatment of the data, the following results were established:

1. Equations for the dose-response surface of CO and nicotine were computed.
2. R ² values (square of the multiple correlation coefficient) for the respective dose-response surfaces were between 87% and 94%.
3. From the respective equations the dose-response surfaces were drawn in the form of several computer plots.

From the equations it becomes evident that, under the experimental conditions, there are no synergistic effects between carbon monoxide and nicotine. A simple additivity of the toxic effects was therefore postulated. On the other hand, it has been demonstrated that smoke pH plays an important role, because only from alkaline smoke does the absorption of nicotine seem sufficiently rapid for it to add to the acute toxicity of CO. The total particulate matter apparently does not contribute significantly to the toxicity of the smoke aerosol.     

Nicotine regulation among heavy and light smokers in a non-stressful environment

The purpose of this study was to assess nicotine regulation among "heavy" and "light" smokers. Previous studies supporting the nicotine regulation model of smoking behavior have suggested that smokers compensate for a reduction in the amount of nicotine available in their cigarette by altering smoking frequency, puff volume, or other aspects of smoking topography. However, little is known about a smoker's decision to smoke a specific cigarette, and the concurrent changes in their blood nicotine. Manipulation of nicotine levels in the blood could play a critical role in smoking maintenance, by regulating the extent and quality of the CNS effects of smoking. In this study, 24 heavy and light smokers (cotinine above or below 260 ng/ml) smoked high- (1.0 mg) or low- (0.5 mg) dose nicotine cigarettes while watching non-stressful movies. Blood nicotine was assessed before and after smoking a preload and free operant cigarette. The results showed that blood nicotine levels after smoking the free operant cigarette were significantly more consistent (lower standard error) for the heavy smokers, following a low dose, as opposed to a high-dose preload. Light smokers showed a non-significant trend towards being more consistent when the high-dose nicotine preload was used. This suggests that heavy smokers may have maximized their dose of nicotine whenever available nicotine was in relatively short supply (low dose condition). However, light smokers may have minimized their exposure when available nicotine was relatively more plentiful (high dose condition).     

Nicotine and cigarette smoking: effects on the ultrastructure of aortic endothelium

The aortic endothelium from rats has been examined by scanning (SEM) and transmission electron microscopy (TEM) following nicotine administration or cigarette smoking. Nicotine was administered to rats by subcutaneous injections at concentrations of 1, 5, 10 and 20 mg/kg or by continuous subcutaneous pumps delivering a solution of 0.54 g/ml of nicotine at the rate of 1 microliter/h for 7 days. Animals were exposed to fresh smoke from eight cigarettes, each yielding 19 mg tar and 1.5 mg nicotine. Twenty minutes after subcutaneous injections, no endothelial abnormalities were evident by SEM, apart from at the high dose where minimal endothelial damage was seen. Limited endothelial damage was discerned following nicotine infusion and this consisted of microvillus formation, platelet adhesion and some cell separation. TEM revealed no endothelial changes in any of the animals. Cigarette smoking, however, resulted in considerable endothelial morphological changes consisting of the formation of blebs, microvillus-like projections, increased numbers of plasmalemmal vesicles and an increase in the numbers of Weibel-Palade bodies. The results suggest that components of cigarette smoke other than nicotine are responsible for the endothelial cell changes associated with smoking.     

Pulmonary hazards of smoking marijuana as compared with tobacco

To compare the pulmonary hazards of smoking marijuana and tobacco, we quantified the relative burden to the lung of insoluble particulates (tar) and carbon monoxide from the smoke of similar quantities of marijuana and tobacco. The 15 subjects, all men, had smoked both marijuana and tobacco habitually for at least five years. We measured each subject's blood carboxyhemoglobin level before and after smoking and the amount of tar inhaled and deposited in the respiratory tract from the smoke of single filter-tipped tobacco cigarettes (900 to 1200 mg) and marijuana cigarettes (741 to 985 mg) containing 0.004 percent or 1.24 percent delta 9-tetrahydrocanabinol. As compared with smoking tobacco, smoking marijuana was associated with a nearly fivefold greater increment in the blood carboxyhemoglobin level, an approximately threefold increase in the amount of tar inhaled, and retention in the respiratory tract of one third more inhaled tar (P less than 0.001). Significant differences were also noted in the dynamics of smoking marijuana and tobacco, among them an approximately two-thirds larger puff volume, a one-third greater depth of inhalation, and a fourfold longer breath-holding time with marijuana than with tobacco (P less than 0.01). Smoking dynamics and the delivery of tar during marijuana smoking were only slightly influenced by the percentage of tetrahydrocanabinol. We conclude that smoking marijuana, regardless of tetrahydrocannabinol content, results in a substantially greater respiratory burden of carbon monoxide and tar than smoking a similar quantity of tobacco.