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-associated particulate matter emissions.

Waterpipe tobacco smoking is increasingly common worldwide, and evidence about its harmful effects to smokers is emerging. However, no studies have investigated the potential exposure of nonsmokers to waterpipe smoke. We measured particulate matter (PM) emissions (PM2.5, PM10) before and during laboratory sessions in which 20 individuals used a waterpipe to smoke tobacco and 20 individuals smoked a cigarette (10 for each particle-size/smoking-method), as well as 10 waterpipe and 10 cigarette smoldering sessions (i.e., without a smoker). A TSI-SidePak aerosol monitor obtained PM2.5, PM10 background, smoking, and maximum levels. Mean PM2.5 rose 447% for waterpipe (from 48 microg/m3 background to 264 microg/m3 smoking), and by 501% for cigarettes (from 44 microg/m3 to 267 microg/m3), whereas mean PM10 rose by 563% for waterpipe (from 55 microg/m3 to 365 microg/m3), and by 447% for cigarettes (from 52 microg/m3 to 287 microg/m3) (p<.05 for all). The increase in PM during cigarette smoking was due primarily to PM2.5, given that the proportion of PM2.5 from total PM10 increase was 95% compared with 70% for waterpipe (p<.05). Maximum PM2.5 was 908 microg/m3 for waterpipe and 575 microg/m3 for cigarettes, whereas maximum PM10 was 1052 microg/m3 for waterpipe and 653 microg/m3 for cigarettes. Mean PM2.5 and PM10 smoldering levels did not differ from background for waterpipe but were significantly higher for cigarettes (PM2.5: 33-190 microg/m3; PM10: 42-220 microg/m3). Policymakers considering clean air regulations should include waterpipe tobacco smoking, and the public should be warned about this source of smoke exposure.     

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.     

Cigarette and waterpipe smoking among Lebanese adolescents, a cross-sectional study, 2003-2004.

Waterpipe or "argileh" is a form of smoking other than cigarettes that is currently spreading among people of all ages. The objective of the present study was to assess tobacco smoking practices (waterpipe and/or cigarette) among public and private adolescent school students in Beirut, Lebanon. A sample of 2,443 students selected from 10 private and 3 public schools with intermediate/secondary classes filled out a self-administered anonymous questionnaire that inquired about sociodemographic characteristics, and behavior about tobacco smoking. Binary analysis was performed as well as three regression models for the relationship between exclusive cigarettes smoking, exclusive waterpipe smoking and both cigarettes and waterpipe as the dependent variables and gender, type of school, and class as the independent variables. The current prevalence of cigarettes smoking was 11.4%, and that of waterpipe smoking was 29.6%. Gender was significantly associated with cigarettes (OR=3.2, 95% CI 1.8-5.6) but not waterpipe smoking. Public school students were, respectively, 3.2 (95% CI 1.8-5.6) and 1.7 (95% CI 1.4-2.1) times more likely to be exclusive cigarettes smokers, and exclusive waterpipe smokers. Class was not significantly associated with exclusive cigarette smoking; however, students attending secondary classes were 1.3 (95% CI 1.1-1.6) times more likely to be exclusive waterpipe smokers. The reasons behind the high prevalence of both types of smoking are presented and discussed. The present study calls for school-based prevention programs and other types of interventions such as tax increases, and age-restrictions on tobacco sales. More aggressive interventions to disseminate education and awareness among parents and students altogether are warranted.     

Determinants of salivary cotinine levels among current smokers in Mexico.

The present study describes salivary cotinine levels and their relationship to cigarettes smoked per day in Mexican smokers. Using a sampling strategy based on the number of cigarettes per day, we recruited 1,222 smokers from Mexico City and the state of Morelos in Mexico during 1999. Smoking behaviors and other factors known to affect nicotine intake and cotinine level were identified in an interview using a standardized questionnaire. Salivary cotinine was measured by capillary gas chromatography with nitrogen-phosphorus detection. We used generalized additive models to describe the relationship between salivary cotinine levels and variables of interest. The mean age of the population was 39.7 years (SD=15.6 years), with a mean cotinine level of 194.7 ng/ml (SD=134.8; range=10.1-767). Participants smoked a mean of 15.5 cigarettes per day (SD=11.3). Salivary cotinine and cigarettes smoked per day were positively related, although the association was not linear, flattening above 20 cigarettes per day. After adjusting for cigarettes per day, we found that significant predictors of cotinine levels included age, body mass index, cigarette producer, and smoking behavior variables. These results may have implications for dosing with nicotine medications to aid smoking cessation in Mexican smokers and suggest that whether the cigarette is labeled light or regular has no relationship to nicotine dose from smoking cigarettes.     

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.     

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.     

Waterpipe tobacco smoking: knowledge, attitudes, beliefs, and behavior in two U.S. samples.

Despite evidence of increasing waterpipe tobacco smoking prevalence among U.S. young adults, little is known about the knowledge, attitudes, beliefs, and smoking patterns of waterpipe users in this population. To address this lack of knowledge, two convenience samples of U.S. waterpipe users were surveyed--one from a Richmond, Virginia, waterpipe café (n=101), the other from an Internet forum called HookahForum.com (n=100). Sixty percent reported first-time waterpipe use at or before age 18. Daily waterpipe use was reported by 19%, weekly use by 41%, and monthly use by 29%. Waterpipe use was more common during the weekend (75%) than during weekdays (43%). Forty-four percent reported spending >or=60 min smoking tobacco during a waterpipe session. The majority of waterpipe users owned a waterpipe (57%) and purchased it on the Internet (71%). Many waterpipe users smoked the sweetened and flavored tobacco (i.e., maassel), and fruit flavors were the most popular (54%). Past month use of cigarettes, tobacco products other than cigarettes or waterpipe, and alcohol was 54%, 33%, and 80% respectively, and 36% reported past-month marijuana use. Most waterpipe users were confident about their ability to quit (96%), but only a minority (32%) intended to quit. Most waterpipe users believed waterpipe tobacco smoking was less harmful and addictive than cigarettes. These results are from small convenience samples; more detailed study of a larger group of randomly sampled U.S. waterpipe tobacco smokers will be valuable in understanding this behavior and developing effective strategies to prevent it.     

Sex-based and hormonal contraception effects on the metabolism of nicotine among adolescent tobacco-dependent smokers.

Variations in nicotine metabolism influence smoking patterns. Differences between sexes or related to sex hormones may affect nicotine metabolism. Because smoking initiation starts during adolescence, observations gathered from adolescent smokers might broaden our understanding of such sex-based differences. We tested the hypothesis that nicotine metabolism--as indexed primarily by the ratio of trans-3'-hydroxycotinine (3HC) to cotinine--is more rapid among adolescent girl smokers compared with boys and that regular use of hormonal contraceptives influences nicotine and cotinine metabolism. We also hypothesized that more rapid nicotine metabolism is associated with higher nicotine dependence as indexed by smoking frequency and morning urgency. Plasma samples of nicotine, cotinine, and 3HC concentrations were obtained from 120 adolescents (36 boys). Plasma nicotine and cotinine concentrations were similar in boys and girls. Median plasma 3HC concentrations were 44.45 ng/ml for girls versus 35.74 ng/ml for boys (p = .025), and median plasma 3HC-cotinine ratios were significantly higher in girls than in boys (0.317 vs. 0.253, p = .025). After stratifying girls into two groups based on use versus nonuse of hormonal contraception, plasma 3HC-cotinine ratios in girls using hormonal contraception (0.47) were substantially higher (p<.0001) than in boys (0.25) and were significantly higher than in girls not using hormonal contraception (0.28). Controlling for cigarettes smoked per day, ethnicity, and age did not modify these results. Although plasma nicotine, cotinine, or 3HC concentrations were significantly lower in less dependent adolescent smokers, nicotine and cotinine metabolite ratios were similar. This study showed that hormonal contraception in adolescent girls may accelerate cotinine metabolism, an effect likely related to induction of cytochrome P450 2A6 and independent of ethnicity and cigarette consumption. Prospective controlled studies are needed to further evaluate the role of hormonal contraception in patterns of adolescent smoking and nicotine metabolism.     

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.     

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。      

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.

     

Higher nicotine and carbon monoxide levels in menthol cigarette smokers with and without schizophrenia.

This study examined whether smoking menthol cigarettes was associated with increased biochemical measures of smoke intake. Expired carbon monoxide (CO) and serum nicotine and cotinine were measured in 89 smokers with schizophrenia and 53 control smokers immediately after smoking an afternoon cigarette. Serum nicotine levels (27 vs. 22 ng/ml, p = .010), serum cotinine levels (294 vs. 240 ng/ml, p = .041), and expired CO (25 vs. 21 ppm, p = .029) were higher in smokers of menthol compared with nonmenthol cigarettes, with no differences in 3-hydroxycotinine/cotinine ratios between groups when controlling for race. Backward stepwise linear regression models showed that, in addition to having a diagnosis of schizophrenia, smoking menthol cigarettes was a significant predictor of nicotine and cotinine levels. Individuals with schizophrenia or schizoaffective disorder smoked more generic or discount value brands (Basic, Doral, Monarch, USA, Wave, others) compared with control smokers (28% vs. 6%, p = .002) but did not smoke more brands with high nicotine delivery as estimated by the U.S. Federal Trade Commission method. Although rates of mentholated cigarette smoking were not higher in smokers with schizophrenia overall, they were significantly higher in non-Hispanic White people with schizophrenia compared with controls of the same ethnic/racial subgroup (51% vs. 28%, p<.0001). The higher exhaled CO in menthol smokers suggests that the higher nicotine levels are at least partly related to increased intake of smoke from menthol cigarettes, although menthol-mediated inhibition of nicotine metabolism also may be a factor. Menthol is an important cigarette additive that may help explain why some groups have lower quit rates and more smoking-caused disease.     

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.     

Efficacy of the nicotine inhaler in smoking reduction: A double-blind, randomized trial.

Many smokers are not ready to quit but are interested in changing their smoking behavior, particularly if such a change is associated with a reduction in health risk. The present study evaluated the efficacy of the nicotine inhaler in reducing smoking. Exploratory studies assessed whether reduction in smoking was associated with reduction in markers of disease risk. A total of 429 healthy smokers (smoking at least 20 cigarettes/day) were randomly assigned to either nicotine-containing or placebo inhalers, which subjects were allowed to use ad libitum for up to 1 year. The nicotine inhaler was significantly superior to placebo in achieving reduction in daily cigarette consumption by at least 50% after 4 months, compared with baseline (18% vs. 8%, p = .004). Active treatment promoted smoking cessation: 8% of subjects in the nicotine group and 1% in the placebo group were abstinent at month 15. Throughout the study, smoking reduction, per se, independent of treatment group, was associated with a statistically significant decrease in exhaled carbon monoxide and serum cotinine and thiocyanate. Smoking reduction also improved established risk markers for cardiovascular disease over 4 months. The incidence of adverse events did not differ significantly between the active and placebo groups. The most common treatment-related adverse events were throat irritation and cough. In conclusion, the nicotine inhaler can help smokers who are unable or unwilling to quit to reduce daily cigarette consumption, which may be a health benefit on its own and may further promote quitting.     

The relationship between cigarette use, nicotine dependence, and craving in laboratory volunteers.

Data from epidemiological studies suggest that individual differences in cigarettes per day (CPD) and duration of smoking account for only a small portion of the variance in Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) nicotine dependence. However, DSM-IV may be an insensitive measure of nicotine dependence; other measures might better reflect the true nature of the relationship between use and dependence. This paper describes the relationship between cigarettes per day (CPD) and years smoking and the severity of nicotine dependence as measured by the Nicotine Dependence Syndrome Scale (NDSS). Furthermore, we assessed the validity of individual differences in nicotine dependence by determining whether they related to cue-evoked craving during abstinence. Data were pooled from five laboratory studies of 489 regular (i.e., 15+ CPD) smokers. In contrast to previously reported data demonstrating a relatively strong relationship between CPD and dependence in chippers (Shiffman & Sayette, 2005), CPD and years smoking accounted for a statistically significant, but small (<6%), portion of the variance in nicotine dependence in daily smokers. Individual differences in both CPD and years smoking had little or no relationship with craving. However, the magnitude of craving was significantly related to the degree of nicotine dependence even after controlling for use variables and excluding craving-related items on the NDSS. These data suggest that among moderate to heavy daily smokers, meaningful individual differences in nicotine dependence are observed independent of differences in current daily cigarette consumption and duration of smoking. Further research into the sources of this variance is critical to understanding the process of and risk for nicotine dependence.     

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.

     

Active and passive smoking and blood lead levels in U.S. adults: data from the Third National Health and Nutrition Examination Survey.

Lead is a component of tobacco and tobacco smoke. We examined the relationship between current, former, and passive smoking and blood lead levels in a nationally representative sample of 16,458 U.S. adults, aged 17 years or older, who participated in the Third National Health and Nutrition Examination Survey (1988-1994). We used linear and logistic regression modeling, adjusting for known covariates, to determine the relationship between smoking and blood lead levels. Geometric mean blood lead levels were 1.8 microg/dl, 2.1 microg/dl, and 2.3 microg/dl in never-smokers with no, low, and high cotinine levels, respectively. Levels were 2.9 microg/dl in former smokers and 3.5 microg/dl in current smokers. The adjusted linear regression model showed that geometric mean blood lead levels were 30% higher (95% CI = 24%-36%) in adults with high cotinine levels than they were in those with no detectable cotinine. Active and passive smoking is associated with increased blood lead levels in U.S. adults.     

Nicotine, cotinine, withdrawal, and craving patterns during smoking and nicotine nasal spray use: results from a pilot study with African American men.

Nicotine intake via smoking is highly variable. Individualized dosing of nicotine replacement therapy (NRT) may improve product efficacy, but a better understanding of the within-day and within-subject relationships between smoking, NRT use, nicotine and cotinine concentrations in blood, and cravings and withdrawal symptoms is needed to inform dosing algorithms. A pilot study was undertaken to collect data on these relationships and to assess the feasibility of the methods needed for this type of research, including a sophisticated statistical modeling technique (a two-part mixed-effects model with correlated random effects that accounts for clumping at zero). Because nicotine metabolism varies by gender and race, the sample was homogeneous with respect to these characteristics. In a within-subjects study, 27 African American adult male smokers carried a computerized cigarette dispenser for 1 week, capturing the time each cigarette was smoked. Subjects then entered an inpatient setting for 1 day of scheduled smoking (matched to data from the cigarette dispenser to create an ecologically valid schedule) and 4 days of ad libitum nicotine nasal spray use, while tobacco abstinent. Eight times per day, at 2-hour intervals, blood was drawn and ratings of cigarette cravings and withdrawal symptoms were obtained. On average, subjects used less than half of the manufacturer's recommended minimum daily dose of nicotine nasal spray. Large differences in nicotine and cotinine levels were observed between individuals. When predicting nicotine, cotinine, withdrawal, and cravings, we observed significant interactions between route of nicotine intake and a variety of independent variables.     

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.