Urinary tobacco-specific nitrosamines and 4-aminobiphenyl hemoglobin adducts measured in smokers of either regular or light cigarettes.

Cigarette brands may differ in their reported yields of "tar" as determined by the Federal Trade Commission smoking-machine method. Brands with relatively lower tar and nicotine yields often are described as light cigarettes. Smokers of light cigarettes generally maintain a nicotine intake comparable to that of smokers of regular cigarettes through compensatory smoking behaviors, but similar data have not been reported for carcinogen biomarkers. In the present study we measured serum cotinine concentrations (a marker of nicotine exposure), urinary levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a tobacco-specific nitrosamine [TSNA]), and hemoglobin adducts of 4-aminobiphenyl (4-ABP) in 150 smokers of either regular or light cigarettes. The TSNA and aromatic amines are known carcinogens in tobacco smoke. Multiple regression models were developed for each of the analytes and used to calculate adjusted geometric means. We found no significant differences in the levels of these biomarkers between customary users of light and regular cigarettes. Thus the concentrations of the carcinogen biomarkers NNAL and 4-ABP in the smokers who regularly smoked light cigarettes were essentially the same as those in the smokers who chose regular cigarettes.     

Smokeless tobacco reduction: preliminary study of tobacco-free snuff versus no snuff.

This preliminary study examined the effects of tobacco-free snuff (intervention, n = 52) compared with no snuff (control, n = 54) for reducing tobacco use among smokeless tobacco (ST) users not interested in quitting. Both groups received behavioral instructions, and intervention subjects received tobacco-free snuff for 8 weeks. Participants were required to reduce their intake by 50% during the first 4 weeks and by 75% during the subsequent 4 weeks. Follow-up occurred at 12 weeks. Significant reductions were observed from baseline to week 8 (end of treatment) for both treatment groups in the amount of ST use (tins/week and dips/day, p<.001); mean urinary cotinine (p<.001); and mean urinary total NNAL, a carcinogen biomarker (p<.001). At week 8 the intervention resulted in a lower mean total NNAL (p = .048). Compared with the control condition, the intervention resulted in a higher percentage of subjects achieving at least a 50% reduction in cotinine (p = .046) and total NNAL (p = .002) at the end of treatment, more quit attempts (p = .030), and a longer mean duration of abstinence (p = .013) through follow-up. An ST reduction intervention incorporating tobacco-free snuff could potentially reduce risk for ST-related disease beyond that achieved with no snuff by increasing the number of patients who achieve significant reductions in carcinogen exposure and, more important, by facilitating tobacco abstinence by increasing quit attempts and abstinence duration.     

Smoking reduction fails to improve clinical and biological markers of cardiac disease: a randomized controlled trial.

Cigarette reduction has been proposed as a treatment goal for smokers who are not interested in stopping completely. This randomized controlled trial was designed to determine the effect of a smoking reduction intervention on smoking behavior, symptoms of heart disease, and biomarkers of tobacco exposure. It included 152 patients with heart disease who did not intend to stop smoking in the next 30 days. Participants were randomly assigned to smoking reduction (SR) or usual care (UC). SR subjects received counseling and nicotine replacement therapy to encourage > or =50% reduction in cigarettes per day (CPD). They were followed at 1, 3, 6, 12 and 18 months to assess smoking, heart disease symptoms, quality of life and nicotine, cotinine, carbon monoxide (CO), white blood cell (WBC) count, fibrinogen, hs-C-reactive protein (hs-CRP), F2-isoprostane, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), and 1-hydroxypyrene (1-HOP). At 6 months SR participants reduced by 10.9 CPD, compared with 7.4 CPD in UC (difference NS). At 18 months, 9/78 SR vs. 9/74 UC participants quit smoking. There were no significant differences between treatment groups in angina, quality of life or adverse events, nicotine, cotinine, CO, WBC count, fibrinogen, hs-CRP, F2-isoprostane, total NNAL or 1-HOP levels at any time point. To determine if smoking reduction, regardless of treatment condition, was associated with improved outcomes, we compared all subjects at 6 months to baseline (mean reduction in CPD from 27.4 to 18.1, p<.01). There were no significant changes in outcome variables except CO, which decreased by 5.5 ppm (p<.01). There were also no significant improvements considering only subjects who reduced by > or =50%, or those who had no history of reduction prior to enrollment in the study. The SR intervention did not significantly reduce CPD or toxin exposure, or improve smoking cessation or clinical outcomes compared to UC. These results emphasize the importance of abstinence for smokers with heart disease to minimize health risks from tobacco.     

Smoking behaviour and toxin exposure during six weeks use of a potential reduced exposure product: Omni

Objective: To determine smoking behaviour, acceptability, and toxin exposure when smokers switch to the potential reduced exposure product—Omni cigarette.

Design: 12 week randomised, crossover study of Omni versus own cigarettes.

Participants: 19 light/ultralight and 15 regular smokers.

Outcomes: Cigarettes/day, smoking topography, craving, withdrawal symptoms, urinary cotinine plus its glucuronide (total cotinine), nicotine plus its glucuronide (total nicotine), and carcinogen metabolites (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol plus its glucuronides and 1-hydroxypyrene).

Results: When switched to Omni, smokers smoked the same number of cigarettes/day, smoked Omni cigarettes less intensely (total puff volume = –11%) and had slightly lower total cotinine (–18%) levels than their own cigarettes, but had a slightly greater carbon monoxide boost/cig (+21%). Craving and withdrawal ratings were similar with Omni and own cigarettes. Carcinogen metabolite levels were somewhat but not significantly lower with Omni. About half of smokers rated Omni as better for their health and about two thirds stated it was weaker and worse tasting than their own cigarettes.

Conclusions: Although Omni may be an adequate behavioural and pharmacological substitute for traditional cigarettes, it may not decrease carcinogen exposure and may increase carbon monoxide. Replications with larger sample sizes and longer follow up are needed. These results indicate the need for regulation of reduced exposure and reduced risk claims.

     

Tobacco specific nitrosamines and potential reduced exposure products for smokers: a preliminary evaluation of Advance

Objective: To develop a method for evaluating the carcinogen delivery of potential reduced exposure products (PREPs) like Advance^TM, a PREP marketed to reduce smokers' exposure to one tobacco specific nitrosamine (TSN), NNK, a potent lung carcinogen.

Design, setting, and participants: Latin square ordered, three condition, outpatient, crossover design with 12 smokers of light or ultra-light cigarettes (15 or more cigarettes/day). In each five day condition, participants either smoked own brand, Advance^TM, or no cigarettes. Also, on the first and last day of each condition, participants smoked one cigarette in the laboratory.

Main outcome measures: Subject rated measures of tobacco/nicotine withdrawal, expired air carbon monoxide, urine concentrations of cotinine and NNAL (one TSN biomarker), puff volume, duration, number, and interpuff interval.

Results: Relative to own brand, Advance^TM produced similar withdrawal suppression, slightly lower carbon monoxide, equivalent cotinine, and 51% lower NNAL concentrations. The lowest cotinine and NNAL concentrations were observed in the no cigarette condition. Participants took fewer puffs when smoking Advance^TM.

Conclusions: Past experience with PREPs that failed to reduce smoking's harm demonstrates the need for clinical methods in PREP evaluation. This study shows how assessing PREP induced changes in withdrawal and exposure to carbon monoxide, nicotine, and carcinogens may help predict PREP harm reduction potential. Adequate withdrawal suppression, slightly lower concentrations of carbon monoxide, and reduction of one TSN biomarker were observed for Advance^TM. In the future, clinical methods like those described here may be valuable for evaluating PREPs before they are marketed publicly.

     

Smoke constituent exposure and smoking topography of adolescent daily cigarette smokers.

Adolescent smoking prevalence is a major health concern, with 24.4% reporting smoking in the past 30 days and 15.8% considered daily smokers. The purpose of this study was to characterize biobehavioral nicotine dependence, smoke constituent exposure and smoking topography in adolescent daily smokers. Relationships among biological markers of nicotine dependence (nicotine boost, carbon monoxide [CO] boost and cotinine levels) with existing self-report measures (modified Fagerstr?m Tolerance Questionnaire [mFTQ] and the motivations for smoking scale) were examined. Gender differences were characterized. Fifty adolescents 13-18 years old were recruited for the study, 50% female. CO, plasma nicotine levels pre- and postcigarette, cotinine, and smoking topography were measured during a smoking bout with participant's usual cigarette. Average CO boost, pre- to postcigarette was 7.2 + 3.6 ppm, baseline cotinine level averaged 224.0 +/- 169.6 ng/ml and nicotine boost averaged 23.4 +/- 21.7 ng/ml. Mean puffs per cigarette was 14.2 +/- 6.3. Males had significantly higher total puff volumes, but similar smoke constituent exposure to females, and higher handling of cigarettes as smoking motive. In regression analysis, 35% of variance in tobacco use, as indicated by baseline cotinine concentration, was explained by maximum puff duration, postcigarette CO level, and nicotine dependence, as measured by the mFTQ. Results indicated adolescents had considerable smoke constituent exposure and nicotine dependence suggesting the importance of appropriate smoking cessation treatment.     

An association of CYP2A6 genotype and smoking topography.

Nicotine is metabolized into biologically inactive cotinine primarily by the cytochrome P450 enzyme CYP2A6. CYP2A6 genetic variations have been phenotypically grouped as slow, intermediate, and normal metabolizers. Slow metabolizers smoke fewer cigarettes daily and weekly, and have lower carbon monoxide (CO) and plasma nicotine levels, suggesting a reduced smoking rate compared with normal metabolizers. CYP2A6 also is involved in the metabolic activation of tobacco-specific procarcinogenic nitrosamines, such as 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). NNK is one of the most abundant and potent procarcinogens in cigarette smoke. The present study investigated the association of CYP2A6 genotype with smoking topography, a quantifiable measure of smoking behavior, in a sample of treatment-seeking smokers prior to treatment. Smoking topography measures indicative of quantity of smoke exposure--number of puffs, mean puff volume, and total puff volume--were the outcome variables. Covariates associated with smoking topography were included in the analyses. Results indicated that CYP2A6 genotype group had a significant effect on mean puff volume and total puff volume, but not number of puffs, such that slow metabolizers exhibited reduced puffing compared with others. Smokers having CYP2A6 variants resulting in low activity metabolize nicotine more slowly, and convert procarcinogen nitrosamines to carcinogens more slowly, than do normal metabolizers. The results from this study also suggest a behavioral mechanism that may account for reduced cancer risk in slow metabolizers.     

Pilot study on lower nitrosamine smokeless tobacco products compared with medicinal nicotine.

Smokeless tobacco (ST) products have the potential to be used as a harm reduction method for cigarette smokers. These products can deliver significantly less toxicants than cigarettes, although they are not toxicant free nor harmless. It is important to examine potential health risks and benefits of these products. These two small pilot studies examined the effects of two different ST products (Exalt and Ariva) compared with medicinal nicotine, another potential harm reduction product. Dependent, healthy adult cigarette smokers, who were motivated to quit smoking, underwent 1 week of baseline smoking measurement. They were then asked to quit smoking and were randomly assigned to use either an ST product or a medicinal nicotine lozenge (MNL, Commit) for 2 weeks, then crossed over to use the other product for 2 weeks. In the last week, following the sampling phase, subjects could choose the product they wished to use. Assessments were made repeatedly during baseline cigarette use and throughout the 5 weeks of treatment. Outcome measures included biomarkers for tobacco exposure and subjective, physiological, and behavioral responses. Tobacco-specific carcinogen uptake was greater from Exalt than from the MNL, and was comparable between the MNL and Ariva. Physiological effects and subjective effects on withdrawal and craving were comparable among Exalt, Ariva, and the MNL. Ariva was preferred over the MNL, which was preferred over Exalt. With the exception of medicinal nicotine products, low-nitrosamine ST products have the greatest potential to result in reduced toxicant exposure compared with other combustible reduced exposure products and have promise for reducing individual risk for disease. However, the population effect of marketing of such products as reduced exposure/reduced risk is unknown. The need for further research in this area and regulation of tobacco products is evident.     

吸烟者转抽加热卷烟的抽吸行为和烟碱暴露

为研究吸烟者转抽加热卷烟后抽吸行为和烟碱暴露水平的变化,招募50名抽吸卷烟的志愿者,分为两组,分别转抽加热卷烟IQOS和国内加热卷烟M。转抽前后通过问卷调查获得志愿者的基线资料,使用CReSS吸烟行为记录仪测试吸烟行为参数,采用HPLC-MS/MS测定志愿者基线和转抽后尿样中的烟碱暴露生物标志物。结果表明:①志愿者转抽加热卷烟后抽吸行为基本保持不变,抽吸容量和抽吸时间均未发生显著性改变,但抽吸间隔明显缩短,两组志愿者抽吸卷烟时抽吸间隔分别为（14.3±8.0）s和（15.3±9.0）s,转抽加热卷烟后抽吸间隔分别为（9.8±8.3）s和（9.7±5.4）s。②转抽后志愿者尿液中烟碱总代谢物和可替宁等烟碱暴露生物标志物的浓度水平也未发生显著性改变。③转抽IQOS后志愿者的抽吸行为与转抽M后的志愿者没有明显差异,两组志愿者尿液中烟碱总代谢物和可替宁的水平也近似。      

The influence of gender, race, and menthol content on tobacco exposure measures.

Research has suggested that race, gender, and menthol cigarette use influence tobacco-smoke exposure measures and smoking-related disease risk. For example, a high proportion of Black smokers prefer menthol cigarettes and, despite smoking fewer cigarettes per day (CPD) than do Whites, tend to have higher cotinine levels. Additionally, Black males are more at risk for smoking-related lung cancer. High cotinine levels and smoking menthol cigarettes may lead to higher toxin intake, which contributes to increased disease risk. We explored the relationship between tobacco exposure variables (i.e., cotinine, CPD, carbon monoxide [CO], nicotine content, and nicotine dependence) with respect to race, gender, and menthol content in a sample of 307 smokers recruited from the greater Boston area to participate in a smoking cessation treatment trial. The pattern of correlations between tobacco exposure measures and cotinine showed a consistently positive correlation between cotinine and CO in all smokers and a correlation between cotinine and CPD in those who smoked nonmenthol cigarettes. Cotinine and CPD correlations varied by gender and race among menthol cigarette smokers. Consistently, we found a significant gender x race x menthol interaction on salivary cotinine level as well as cotinine/CPD ratio. These findings suggest that the relationship between number of cigarettes consumed and salivary cotinine is more complex than previously believed. It is not sufficient to look at race alone; researchers and clinicians need to look at race and gender concurrently, as well as type of cigarette consumed.     

Sex-related differences in serum cotinine concentrations in daily cigarette smokers

Self-reported use of cigarettes generally underestimates the true cigarette exposure of smokers. Serum cotinine is considered the best biomarker to evaluate tobacco exposure. This study determined whether or not there were any significant differences in serum cotinine concentrations between men and women when they reported smoking the same number of cigarettes per day. We analyzed cotinine and tobacco consumption data on 680 women and 840 men, aged 20 years or older, who smoked at least 100 cigarettes during their lifetime and were still actively smoking at the time of the National Health and Nutrition Examination Surveys (1999-2002). Overall, compared with men, women reported smoking fewer cigarettes per day (16.1 vs. 18.7, p<.001) and had lower serum cotinine concentrations (1163.3 nmol/L vs. 1343.9 nmol/L, p<.001). Women were more likely than men to smoke filtered (p = .018) and mentholated (p<.001) cigarettes. After adjustment for the number of cigarettes smoked per day, age, race, body mass index, poverty status, the use of either menthol or regular cigarettes, and the nicotine content in cigarettes, female compared with male smokers had lower serum cotinine concentrations (difference of 117.6 nmol/L; 95% CI = 42.6-192.6, p = .003). The difference was particularly notable in moderate to heavy smokers (i.e., those who smoked more than 15 cigarettes/day). These findings indicate that significant sex-related differences exist in serum cotinine levels among smokers, which suggests that self-reports may overestimate cigarette exposure in women compared with men.     

Waterpipe smoking and nicotine exposure: a review of the current evidence.

The waterpipe, also known as shisha, hookah, narghile, goza, and hubble bubble, has long been used for tobacco consumption in the Middle East, India, and parts of Asia, and more recently has been introduced into the smokeless tobacco market in western nations. We reviewed the published literature on waterpipe use to estimate daily nicotine exposure among adult waterpipe smokers. We identified six recent studies that measured the nicotine or cotinine levels associated with waterpipe smoking in four countries (Lebanon, Jordan, Kuwait, and India). Four of these studies directly measured nicotine or cotinine levels in human subjects. The remaining two studies used smoking machines to measure the nicotine yield in smoking condensate produced by the waterpipe. Meta-analysis of the human data indicated that daily use of the waterpipe produced a 24-hr urinary cotinine level of 0.785 microg/ml (95% CI = 0.578-0.991 microg/ml), a nicotine absorption rate equivalent to smoking 10 cigarettes/day (95% CI = 7-13 cigarettes/day). Even among subjects who were not daily waterpipe smokers, a single session of waterpipe use produced a urinary cotinine level that was equivalent to smoking two cigarettes in one day. Estimates of the nicotine produced by waterpipe use can vary because of burn temperature, type of tobacco, waterpipe design, individual smoking pattern, and duration of the waterpipe smoking habit. Our quantitative synthesis of the limited human data from four nations indicates that daily use of waterpipes produces nicotine absorption of a magnitude similar to that produced by daily cigarette use.     

Behavioral counseling for reducing children's ETS exposure: implementation in community clinics.

The present randomized controlled trial tested the effectiveness of a behavioral counseling program for reducing children's exposure to environmental tobacco smoke (ETS). Counseling was delivered by clinic staff as part of well-child health care services in a community clinic setting. A total of 150 mothers with children aged 4 years or younger were recruited. Parent-reported and children's urinary cotinine measures of ETS exposure were obtained at baseline, 3 months, 6 months (post-test), and 12 months (follow-up). Saliva samples were obtained from mothers who reported quitting smoking, for objective verification by thiocyanate analysis. After baseline, mothers were randomly assigned to a measures-only control condition or an intervention consisting of seven behavioral counseling sessions over 6 months. Counseling included behavioral contracting, self-monitoring, problem solving, and positive reinforcement. Results indicated acceptable test-retest reliability and validity of measures. Parent-reported measures indicated that, in both groups, children's exposure to their mothers' tobacco smoke in the home and to all tobacco smoke declined steeply from baseline to 6 months post-test, and remained essentially level during follow-up. Mothers' smoking rates followed the same pattern. Children's urinary cotinine concentrations did not show significant change over time in either group. Findings on the fidelity of treatment implementation suggest that the structure and funding of the community clinic health care system and associated staff turnover and training issues resulted in participants receiving a less efficacious intervention than in our past efficacy trials. Implications for future effectiveness trials are discussed.     

Sensitivity and specificity of a reagent-impregnated test strip in identifying smokeless tobacco users.

This study was designed to determine the sensitivity and specificity of a reagent-impregnated test strip in identifying habitual snuff users and tobacco chewers. Urine specimens were obtained from smokeless tobacco users and controls and blind tested on-site using a reagent-impregnated test strip. Samples also were sent to our university hospital lab for cotinine and nicotine analysis by gas chromatography (GC). The test strip results were compared with GC results and self-reported use of snuff and chewing tobacco. A total of 61 subjects enrolled in the study: 26 snuff users, 25 tobacco chewers, and 10 nonconsumers of nicotine. Using GC assessment of nicotine and cotinine (>or=200 ng/ml) as the standard, we found the sensitivity of the test strip to be 96% (25/26) for snuff users and 96% (24/25) for tobacco chewers. When compared with self-report, the sensitivity of the test strip was 92.3% (24/26) for snuff users and 84% (21/25) for tobacco chewers. The specificity for nonusers of nicotine was 100% (10/10) for both the self-report and GC conditions. These results suggest that a reagent-impregnated test strip is a rapid, valid, and user-friendly means of differentiating smokeless tobacco users from nonconsumers of tobacco. The intensity of the pink color on the test strip is proportional to the amount of nicotine or its metabolites present in urine and therefore offers a semiquantitative measure of nicotine consumption.     

Cotinine levels in relation to smoking behavior and addiction in young adolescent smokers.

The goal of this study was to identify associations among self-reported nicotine exposure, nicotine addiction, and actual nicotine intake as measured by salivary cotinine levels in adolescent smokers. A total of 170 adolescent smokers with a mean age of 15 years were recruited from seven northern Californian public high schools. Data were collected on smoking behaviors, addiction, craving, and withdrawal. Nicotine dependence was assessed using a modified teen Fagerstr?m Tolerance Questionnaire (mtFTQ), a modified Nicotine Dependence Syndrome Scale (mNDSS), and a simple self-rating. Withdrawal was assessed using the Minnesota Withdrawal Questionnaire, and craving was assessed using a survey created by the authors. Salivary cotinine levels were collected from and analysed in participants who self-identified as smokers; data from the 54 participants who smoked in the past 4 days and whose salivary cotinine levels were greater than 0.1 ng/ml were used in the analysis. Among this group of adolescent smokers, the mean number of cigarettes smoked per day was 3.51 (SD = 3.44) and the mean level of salivary cotinine was 44.1 ng/ml (Mdn = 24.2). Even at this low level of nicotine exposure, cotinine was highly correlated with measures of nicotine dependence such as the mtFTQ (r = 0.497, p = .001), NDSS (r = 0.439, p = .002), timing of craving in the morning (r = -0.601, p = .000), and self-rated addiction (r = 0.562, p = .000). Most interesting, cotinine levels reached a plateau at around 4-5 cigarettes/day.     

The variability of urinary cotinine levels in young children: implications for measuring ETS exposure.

This study examined the within-subject variability of urinary cotinine levels in young children (aged = 0.6-7.2 years) of smoking parents to determine the number of urine samples needed to provide accurate estimates of exposure to environmental tobacco smoke (ETS) for different time intervals. Secondary analyses were conducted of five independent studies (N = 376), in which multiple urinary cotinine measures had been collected over time periods up to 13 months. Over measurement periods of 4-15 days, the within-subject cotinine levels varied 3-5 times more than would be expected based on measurement error alone. Over 7-13 months, the within-subject variability was 10-20 times higher than would be expected based on the measurement error. Findings indicated that cotinine measures from single urine samples provided highly accurate estimates of only recent exposure (i.e., 2-3 days; rho = 0.99). To achieve similarly precise estimates of the mean cotinine level of an individual child over 4-15 days, up to nine urine samples may be necessary. Up to 12 urine samples may be required to achieve similarly precise estimates of ETS exposure over a 4- to 13-month period. Epidemiologic and clinical research on ETS exposure in children can benefit from multiple urine samples (a) to accurately measure average exposure at the level of the individual child, (b) to describe temporal patterns, (c) to detect incidences of peak exposure that would remain underrecognized if monitoring is limited to a single time point, and (d) to establish stable baseline levels and endpoints based on urine samples collected over clinically relevant time periods.     

Salivary cotinine concentration versus self-reported cigarette smoking: Three patterns of inconsistency in adolescence.

The present study examined the extent and sources of discrepancies between self-reported cigarette smoking and salivary cotinine concentration among adolescents. The data are from household interviews with a cohort of 1,024 adolescents from an urban school system. Histories of tobacco use in the last 7 days and saliva samples were obtained. Logistic regressions identified correlates of three inconsistent patterns: (a) Pattern 1-self-reported nonsmoking among adolescents with cotinine concentration above the 11.4 ng/mg cutpoint (n = 176), (b) Pattern 2-low cotinine concentration (below cutpoint) among adolescents reporting having smoked within the last 3 days (n = 155), and (c) Pattern 3-high cotinine concentration (above cutpoint) among adolescents reporting not having smoked within the last 3 days (n = 869). Rates of inconsistency were high among smokers defined by cotinine levels or self-reports (Pattern 1 = 49.1%; Pattern 2 = 42.0%). Controlling for other covariates, we found that reports of nonsmoking among those with high cotinine (Pattern 1) were associated with younger age, having few friends smoking, little recent exposure to smokers, and being interviewed by the same interviewer as the parent and on the same day. Low cotinine concentration among self-reported smokers (Pattern 2) was negatively associated with older age, being African American, number of cigarettes smoked, depth of inhalation, and exposure to passive smoke but positively associated with less recent smoking and depressive symptoms. High cotinine concentrations among self-reported nonsmokers was positively associated with exposure to passive smoke (Pattern 3). The data are consonant with laboratory findings regarding ethnic differences in nicotine metabolism rate. The inverse relationship of cotinine concentration with depressive symptoms has not previously been reported. Depressed adolescent smokers may take in smaller doses of nicotine than nondepressed smokers; alternatively, depressed adolescents may metabolize nicotine more rapidly.     

Japanese spousal smoking study revisited: how a tobacco industry funded paper reached erroneous conclusions

Objectives: To provide a participant''s account of the development of a paper commissioned by the tobacco industry examining the reliability of self reported smoking status; to redress the distorted report of this Japanese spousal smoking study which evaluated the reliability and validity of self reported smoking status, and estimated confounding by diet and lifestyle factors. Design: Repeated interviews on smoking status and its verification by environmental and biological markers for environmental tobacco smoke (ETS) exposure. Setting: Urban wives in Osaka City and Sizuoka City, Japan Participants: Semi-random sampling of 200 wives in each city. From the Osaka subjects, 100 non-smoking wives were selected for the validity study. Main outcome measures: Kappa coefficient for reliability of self reported smoking status. Correlation coefficients between environmental nicotine concentration, cotinine in saliva and urine, and self reported smoking status. Results: The κ coefficient for the repeated interview was high suggesting sufficient reliability of the response. The proportion of self reported current smokers misclassified as non-smokers was equivalent to the misclassified self reported non-smokers. Ambient concentration of nicotine and personal exposure to nicotine correlated with each other and also with salivary cotinine and self reported ETS exposure but not with urinary cotinine/creatinine ratio (CCR). There was no major difference in diet and lifestyle related to husband''s smoking status. Conclusion: Self reported smoking status by Japanese wives shows high reliability. It also shows high validity when verified by both nicotine exposure and salivary cotinine, but not by CCR. A previous report questioning the credibility of self reported smoking status, based on questionable CCR, could thus be of dubious validity. In addition, possible dietary and lifestyle confounding factors associated with smoking husbands were not demonstrable, a finding not reported previously. Using all the data from this project changes the conclusion of the previous published report. In addition to the distortion of scientific findings by a tobacco industry affiliated researcher, anti-smoking campaigners made attempts to intimidate and suppress scientific activities. These distortions of science should be counteracted.     

Acute effects of Advance: a potential reduced exposure product for smokers

OBJECTIVE: To examine the acute effects of Advance, a potential reduced exposure product (PREP) for smokers marketed as a means to reduce exposure to toxic gases and tobacco specific nitrosamines. Design, setting, participants: Latin square ordered, three condition, laboratory based, crossover design with 20 smokers of light or ultra-light cigarettes (15 or more cigarettes/day). In each 2.5 hour condition, participants completed an 8-puff smoking bout from their own brand, Advance, or an unlit cigarette (that is, sham smoking) every 30 minutes for a total of four bouts. MAIN OUTCOME MEASURES: Subject rated measures of tobacco/nicotine withdrawal; carbon monoxide (CO), and heart rate; plasma nicotine concentrations. RESULTS: Relative to own brand, Advance produced similar withdrawal suppression and heart rate increase, lower CO boost, and higher plasma nicotine concentrations. CONCLUSIONS: PREPs for smokers need to be evaluated using a comprehensive strategy that includes empirical examination of acute and long term effects. Adequate withdrawal suppression and potentially lower concentrations of CO associated with Advance use are positive factors, although higher nicotine concentrations do not constitute "reduced exposure". Overall, longer exposure periods are necessary to determine carcinogen delivery. PREP evaluation is complex and should be completed objectively.     

Nicotine lozenges for the treatment of smokeless tobacco use.

Nicotine lozenges have been shown to increase tobacco abstinence rates in cigarette smokers, but they have not been evaluated in smokeless tobacco (ST) users. We conducted an open-label, one-arm, phase II clinical trial to evaluate the efficacy of the 4-mg nicotine lozenge for the treatment of withdrawal and craving associated with tobacco abstinence among ST users. Eligible subjects received 4-mg nicotine lozenges for 6 weeks followed by a 6-week taper. Subjects completed daily tobacco withdrawal diaries, and data on lozenge use, adverse events, and lozenge acceptability were collected. Urine anabasine was collected at 3 and 6 months for biochemical confirmation of self-reported tobacco abstinence. Participants were 30 ST users with a mean age of 35.4 years (SD=6.5) using an average of 4.2 cans or pouches (SD=3.2) of ST per week for a mean of 15.1 years (SD=6.5). Among subjects continuously tobacco abstinent for the first 2 weeks, no significant increases in composite withdrawal symptoms were observed, compared with baseline symptoms, whereas craving decreased significantly. Biochemically confirmed 7-day point-prevalence tobacco abstinence was 53% (95% CI=34%-72%) at 12 weeks (end of treatment) and 47% (95% CI=28%-66%) at 6 months. Few adverse events attributable to the nicotine lozenge occurred, and the lozenge was perceived as helpful in assisting subjects quit ST. The use of the 4-mg nicotine lozenge appears promising for the clinical treatment of withdrawal symptoms and craving associated with tobacco abstinence in ST users. Future phase III clinical trials investigating the efficacy of nicotine lozenges are warranted.