Relationships Between Race, Gender, and Spot Urine Levels of Biomarkers of Tobacco Exposure Vary Based on How Creatinine Is Handled in Analyses.

INTRODUCTION: We illustrate the differential impact of common analysis approaches to handling urinary creatinine, a measure for urine dilution, on relationships between race, gender, and biomarkers of exposure measured in spot urine. METHODS: In smokers, spot urine levels of total nicotine equivalents (TNE, sum of total nicotine, total cotinine, and total 3'-hydroxycotinine) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) overall and per cigarette were examined. Relationships between race (African Americans [AA] n = 373, Whites n = 758) or gender (males n = 629, females n = 502) and TNE or NNAL were examined using the following approaches to handling creatinine: (1) unadjusted/unstandardized; (2) standardization; (3) adjustment as a covariate. Significance was considered at p < .05. RESULTS: Creatinine was higher in AA versus Whites (1.19 vs. 0.96 mg/mL; p < .0001) and in males versus females (1.21 vs. 0.84 mg/mL; p < .0001). Independent of how creatinine was handled, TNE was lower among AA than Whites (TNE ratios AA vs. Whites: 0.67-0.84; p's < .05). Unadjusted TNE per cigarette was higher among AA versus Whites (ratio 1.12; p = .0411); however, the relationship flipped with standardization (ratio 0.90; p = .0360) and adjustment (ratio 0.95; p = .3165). Regarding gender, unadjusted TNE was higher among males versus females (ratio 1.13; p = .0063), but the relationship flipped with standardization (ratio 0.79; p < .0001) or adjustment (ratio 0.89; p = .0018). Unadjusted TNE per cigarette did not differ across gender (ratio 0.98; p = .6591), but lower levels were found in males versus females with standardization (ratio 0.68; p < .0001) and adjustment (ratio 0.74; p < .0001). NNAL displayed similar patterns. CONCLUSIONS: Relationships between race, gender, and spot urine levels of biomarkers of exposure can vary greatly based on how creatinine is handled in analyses. IMPLICATIONS: Lack of appropriate methods can lead to discrepancies across reports on variability of urinary biomarkers by race and gender. We recommend that for any analyses of biomarkers of exposure measure in spot urine samples across race, gender, or other population subgroups that differ in urinary creatinine levels, sensitivity analyses comparing the different methods for handling urinary creatinine should be conducted. If methods result in discrepant findings, this should be clearly noted and discussed.

Urinary Cyanoethyl Mercapturic Acid, a Biomarker of the Smoke Toxicant Acrylonitrile, Clearly Distinguishes Smokers From Nonsmokers.

INTRODUCTION: Cyanoethyl mercapturic acid (CEMA) is a urinary metabolite of acrylonitrile, a toxicant found in substantial quantities in cigarette smoke, but not in non-combusted products such as e-cigarettes or smokeless tobacco and rarely in the diet or in the general human environment. Thus, we hypothesized that CEMA is an excellent biomarker of combusted tobacco product use. AIMS AND METHODS: We tested this hypothesis by analyzing CEMA in the urine of 1259 cigarette smokers (urinary cotinine ≥25 ng/mL) and 1191 nonsmokers. The analyses of CEMA and cotinine were performed by validated liquid chromatography-tandem mass spectrometry methods. Logistic regression was fit for log-transformed CEMA to construct the receiver operating characteristic curve. RESULTS: We found that a CEMA cutpoint of 27 pmol/mL urine differentiated cigarette smokers from nonsmokers with sensitivity and specificity greater than 99%. The use of different cotinine cutpoints to define smokers (10-30 ng/mL) had little effect on the results. CONCLUSIONS: CEMA is a highly reliable urinary biomarker to identify users of combusted tobacco products such as cigarettes as opposed to users of non-combusted products, medicinal nicotine, or nonusers of tobacco products. IMPLICATIONS: CEMA can be used to distinguish users of combusted tobacco products from non-combusted products such as e-cigarettes, smokeless tobacco, and medicinal nicotine. Levels of CEMA in the urine of people who use these non-combusted products are extremely low, in contrast to cotinine.

Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers.

BACKGROUND: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers. METHODS: Secondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers. NMR was modeled continuously in secondary analysis. RESULTS: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant. CONCLUSIONS: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers. IMPACT: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco-related disease.

Effect of Cotinine-Verified Change in Smoking Status on Risk of Metachronous Colorectal Neoplasia After Polypectomy.

BACKGROUND & AIMS: Previous assessments of colorectal neoplasia (CRN) recurrence after polypectomy used self-report to determine smoking status. We evaluated the association between change in smoking status and metachronous CRN risk after polypectomy using cotinine level in urine to determine tobacco exposure. METHODS: We performed a retrospective study of participants in the Kangbuk Samsung Health Study in Korea who underwent a screening colonoscopy examination and measurement of cotinine in urine samples. Our analysis included 4762 patients who had 1 or more adenomas detected in an index colonoscopy performed between January 2010 and December 2014, and underwent a surveillance colonoscopy, 6 or more months later, until December 2017. RESULTS: Patients were classified into 4 groups based on the change in cotinine-verified smoking status from index to follow-up colonoscopy (mean interval, 3.2 ± 1.3 y), as follows: remained nonsmokers (n = 2962; group 1), smokers changed to nonsmokers (n = 600; group 2), nonsmokers changed to smokers (n = 138; group 3), and remained smokers (n = 1062; group 4). After adjustment for confounding factors, group 4 had a significantly higher risk of metachronous CRN than group 1 (hazard ratio [HR], 1.54; 95% CI, 1.36-1.73) and group 2 (HR, 1.63; 95% CI, 1.39-1.99). Group 4 also had a higher risk of metachronous advanced CRN than group 1 (HR, 2.84; 95% CI, 1.79-4.53) and group 2 (HR, 2.10; 95% CI, 1.13-3.89). Group 3 had a higher risk of metachronous CRN than group 1 (HR, 1.50; 95% CI, 1.14-1.97) and group 2 (HR, 1.62; 95% CI, 1.20-2.20). CONCLUSIONS: In a retrospective study of individuals with at least 1 adenoma, we found that cotinine-verified changes in smoking status between index and follow-up colonoscopy are associated with a risk of metachronous CRN. Helping patients quit smoking is important for effective prevention of colorectal cancer.

Black Light Smokers: How Nicotine Intake and Carcinogen Exposure Differ Across Various Biobehavioral Factors.

OBJECTIVE: The study objective was to identify biobehavioral variables associated with greater intake of nicotine and a tobacco carcinogen among Black light smokers who smoke 1 to 10 cigarettes per day (CPD). METHODS: We analyzed baseline data collected from 426 Black light smokers enrolled in Kick It at Swope III (KIS III), a smoking cessation trial for Black smokers. We examined differences in concentrations of tobacco biomarkers, including urinary total nicotine equivalents (TNE) and total 4-(methylnitrosamino)-1-(3)pyridyl-1-butanonol (NNAL; a human carcinogen), across gender, age, plasma nicotine metabolite ratio (NMR), CPD, and measures of tobacco dependence, including time to first cigarette (TFC), using ANOVA. RESULTS: Tobacco biomarker levels were significantly higher among those who smoked more CPD (6-10 vs 1-5 CPD) and those with greater reported physical dependence on tobacco. Concurrently, those who smoked 1-5 CPD smoked each cigarette more intensely than those who smoked 6-10 CPD. While we found no gender differences overall, among those who smoked 1-5 CPD, women had higher NNAL levels compared to men. The rate of nicotine metabolism, measured by the nicotine metabolite ratio, was not significantly related to TNE or NNAL levels. CONCLUSION: Among Black Light smokers, higher cigarette consumption and greater physical dependence-but not rate of nicotine metabolism, menthol use, or socioeconomic status-were associated with greater toxicant exposure and thus a likely increased risk of tobacco-related diseases. The lack of data on light smokers, and specifically on Blacks, make this observation important given the disproportionate burden of lung cancer in this population.

Effects of Menthol Flavor Cigarettes or Total Urinary Menthol on Biomarkers of Nicotine and Carcinogenic Exposure and Behavioral Measures.

INTRODUCTION: The effects of either menthol flavor cigarettes or total urinary menthol on nicotine dependence, biomarkers of addictive and carcinogenic exposure, and behavioral measures may inform differences and similarities of these two approaches. METHODS: Stratified recruitment by cigarette (menthol flavor or regular) and race (African American and white) yielded a balanced sample of 136 adult smokers in a 36-hour inpatient protocol. Exposure measures assessed during 24-hour data collection included urinary menthol, total NNAL [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol], 10 polycyclic aromatic hydrocarbon metabolites, baseline plasma cotinine, plasma nicotine pre- and post-smoking, exhaled carbon monoxide pre- and post-smoking, and cigarette puff volumes. The latter three were measured at four specified timepoints throughout the day. RESULTS: There were no significant differences between menthol flavor and regular cigarette smokers in measures of nicotine dependence, biomarkers of addictive and carcinogenic exposures, or behavioral measures. Significant race × cigarette type interaction effects were found for two biomarkers: plasma nicotine and 3-hydroxyphenanthrene. Total urinary menthol was significantly associated with higher levels of nearly all dependent variables including puff volume, exhaled carbon monoxide, plasma nicotine and cotinine, NNAL, and polycyclic aromatic hydrocarbons. The significant effects of total urinary menthol were sustained after adjusting for menthol flavor and regular cigarette type and other covariates (eg, number of cigarettes per day, baseline cotinine, and baseline nicotine). CONCLUSIONS: Urinary menthol is an independent predictive biomarker for nicotine dependence, addictive and carcinogenic exposure, and behaviors. IMPLICATIONS: Comparison of the effects of menthol flavor and total urinary menthol on nicotine dependence, biomarkers of addictive and carcinogenic exposure, and behavioral measures emphasizes the important significant contribution of total urinary menthol concentrations in contrast to no significant associations by dichotomous cigarette type with these biomarkers.

Effects of omega-3 fatty acid supplementation on cigarette craving and oxidative stress index in heavy-smoker males: A double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Smoking-induced oxidative stress is thought to contribute to lower levels of omega-3 fatty acids in plasma and brain tissue. This lower level leads to impaired function in a dopaminergic system related to dependence and craving. AIMS: The aim of this study was to evaluate the effects of omega-3 fatty acid supplementation on cigarette craving and oxidative stress index in heavy-smoker males. METHODS: In this double-blind, randomized clinical trial, 54 heavy-smoker males (smoke ⩾20 cigarettes per day) were randomly selected to receive either five capsules of fish-oil-derived omega-3 fatty acid supplements ( n = 27, each 1 g capsule containing 180 mg of eicosapentaenoic acid and 120 mg of docosahexanoic acid) or a placebo ( n = 27) for 3 months. The psychometric evaluations (nicotine dependence and cigarette craving), biochemical markers (urinary cotinine, serum total antioxidant capacity and total oxidant status) and self-reported smoking status were used to assess the cigarette craving and oxidative stress index (oxidative stress index = total oxidant status/total antioxidant capacity). RESULTS: There was a greater reduction in levels of nicotine dependence, cigarette craving and cigarettes smoked per day in the omega-3 fatty acid group compared to the placebo group, and the difference between the two groups increased from baseline to 3-month follow up. The model estimated that these differences were statistically significant ( p < 0.001, p < 0.001 and p < 0.001, respectively). Also, a significant decrease was observed in levels of total oxidant status ( p = 0.008) and oxidative stress index ( p = 0.011) in the omega-3 fatty acid group after intervention. CONCLUSIONS: This study showed that high-dose omega-3 fatty acid supplementation appears to be useful in reducing cigarette craving and oxidative stress index in heavy-smoker males.

Effects of galantamine on smoking behavior and cognitive performance in treatment-seeking smokers prior to a quit attempt.

OBJECTIVE: Drugs that enhance cholinergic transmission have demonstrated promise treating addictive disorders. Galantamine, an acetylcholinesterase inhibitor, may reduce cigarette smoking in otherwise healthy treatment-seeking smokers. METHODS: The current study is a double-blind, placebo-controlled, study that randomized daily smokers (n = 60) to receive one of two doses of galantamine extended release (8 or 16 mg/day), or a placebo treatment. Participants completed a smoking choice task as well as study measures and cognitive tasks in the laboratory and daily life using ecological momentary assessment. Analysis focused on smoking behavior and satisfaction, cognitive performance, and decision to smoke prior to a quit attempt. RESULTS: Linear mixed models demonstrated that, compared with placebo, both doses of galantamine reduced smoking in a laboratory choice task (p = 0.006) and decreased urine cotinine levels, but not self-reported cigarettes, during the pre-quit period (p = 0.007). Treatment had minimal effect on smoking satisfaction or cognitive performance. CONCLUSIONS: The results suggest that galantamine reduces nicotine intake but it is unlikely that galantamine improves cognitive performance in otherwise healthy, treatment-seeking smokers. Larger randomized clinical trials can determine if galantamine adjunctive to addiction treatment can improve smoking treatment outcomes.

Smoking Exposure in Early Pregnancy and Adverse Pregnancy Outcomes: Usefulness of Urinary Tobacco-Specific Nitrosamine Metabolite 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol Levels.

OBJECTIVES: The aim was to investigate the effect of -maternal smoking exposure assessed by urinary tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-a1-butanol (NNAL) with adverse pregnancy outcomes. METHODS: A total of 251 pregnant women were recruited. Urinary cotinine and NNAL were measured. Participants' sociodemographics were obtained by questionnaire and pregnancy outcomes were collected by charts review after delivery. RESULTS: The prevalence of smoking was 8.4% (21 of 249), 1.2% (3 of 241), and 3.7% (9 of 241) in pregnant women according to questionnaire, cotinine, and NNAL, respectively. As compared with questionnaire positivity and cotinine levels, women with positive NNAL were independent determinants for spontaneous abortion (adjusted OR 12.357, 95% CI 2.053-74.368), preterm birth (adjusted OR 22.239, 95% CI 3.737-132.357), and small for gestational age (adjusted OR 6.915, 95% CI 1.385-34.524). CONCLUSIONS: Urinary NNAL might be a useful biomarker in detection of maternal smoking status in association with adverse pregnancy outcomes. Use of this marker in preconception and pregnancy counselling before planning pregnancy may allow prevention of several adverse pregnancy outcomes.

Nicotine Dependence and Urinary Nicotine, Cotinine and Hydroxycotinine Levels in Daily Smokers.

INTRODUCTION: Nicotine dependence and smoking frequency are critical factors for smoking cessation. The aims of this study are (1) to determine if nicotine dependence Fagerström Test for Nicotine Dependence (FTND) scores are associated with urinary levels of nicotine metabolites, (2) to assess the relationship of hydroxycotinine/cotinine ratio with FTND score and cigarettes smoked per day (CPD), and (3) to identify significant predictors of cigarettes per day among biomarker concentrations and individual FTND items. METHODS: Urine samples and questionnaire data of 239 daily smokers were obtained. Nicotine, cotinine and hydroxycotinine urinary levels were determined by UPLC MS/MS.Multiple linear regression models were developed to explore the relationship between nicotine, cotinine, hydroxycotinine levels and separate FTND scores (for all six items). RESULTS: We found significant correlations between the different urinary biomarker concentrations, and the FTND score. The time before the first cigarette after waking (TTFC) was significantly associated with the nicotine, cotinine and hydroxycotinine concentrations. No association was found between the ratio of hydroxycotinine to cotinine and either the FTND or the CPD. A model including four FTND questions, sex, age, and the cotinine concentration, accounted for 45% of the variance of CPD. CONCLUSIONS: There are significant relationships between urinary levels of nicotine, cotinine, and hydroxycotinine and the FTND score. Especially the FTND question about TTFC is relevant for explaining the biomarker concentrations. CPD (below 15) was significantly explained by four FTND dependence items and urinary cotinine levels in a regression model. IMPLICATIONS: We investigated associations between urinary levels of nicotine, cotinine, and hydroxycotinine in daily smokers and the FTND scores for nicotine dependence. We did not find association between the hydroxycotinine/cotinine ratio and CPD. We developed a model that explains the cigarettes smoked daily (CPD) in a group of light smokers by combining FTND items, urinary cotinine levels, sex, and age. Our results might be of importance for clinical use or future studies on larger smoking populations.

Three Decades of High-Dose Nicotine Gum Dependence Treated With Nicotine Patches.

INTRODUCTION: Some long-term nicotine gum users are addicted to nicotine and may need assistance to stop. There is no published evidence on the use of nicotine patches for this purpose. CASE DESCRIPTION: A 45-year old man presented with a 30-year history of high-dose nicotine gum use (up to 200mg nicotine per day). He was highly nicotine dependent and had failed repeatedly to stop using nicotine gum use in the past. Within a week of commencing nicotine patches he was able to cease nicotine gum with minimal discomfort and has remained nicotine-free for 6 months, with abstinence confirmed biochemically. His severe sweating disorder rapidly resolved with cessation of the gum. CONCLUSION: Nicotine patches may be an effective treatment for long-term nicotine gum addiction.

Association between cotinine-verified smoking status and metabolic syndrome: analyses of Korean National Health and Nutrition Examination Surveys 2008-2010.

BACKGROUND: The association between smoking and metabolic syndrome has not been clarified, especially for women, probably because of the inaccurate self-reported smoking status. This study aimed to investigate the association between cotinine-verified smoking status and metabolic syndrome. METHODS: A total of 11,559 participants from the Korean National Health and Nutrition Examination Surveys were included in this cross-sectional study. Metabolic syndrome was determined according to revised National Cholesterol Education Program Adult Treatment Panel III criteria. Smokers were distinguished from nonsmokers by a urinary cotinine level above 50 ng/mL. Multivariable adjusted logistic regression analysis was used to evaluate the association between cotinine-verified smoking status and metabolic syndrome. RESULTS: Prevalence of metabolic syndrome was 28.2% in men and 24.6% in women. Self-reported smoking status was much less consistent with cotinine-verified smoking status in women (kappa values=43.0%) compared with men (kappa value=88.6%). Risk of metabolic syndrome was significantly higher in cotinine-verified smokers than in nonsmokers for both men and women. Among the components of metabolic syndrome, smokers had an increased risk of high triglycerides (TGs), low high-density lipoprotein cholesterol, and decreased risk of high blood pressure compared with nonsmokers in men. In women, smokers had a higher risk of abdominal obesity and high TGs compared with nonsmokers. CONCLUSIONS: This population-based study showed that smoking was associated with increased risk for metabolic syndrome in men as well as in women and this association is mainly due to the association between smoking and dyslipidemia.

Spontaneous reductions in smoking during double-blind buprenorphine detoxification.

OBJECTIVE: Evidence suggests a positive association between administration of psychoactive drugs and rates of cigarette smoking. Prevalence of smoking among opioid-dependent individuals, for example, is four times greater than the general population. We recently completed a randomized double-blind trial evaluating outpatient buprenorphine taper for prescription opioid (PO) abusers, which provided a unique opportunity to examine naturalistic changes in smoking among participants who detoxified without resumption of illicit opioid use. METHOD: Participants received no smoking-cessation services and were not encouraged to alter their smoking in any way. A subset of 10 opioid-dependent smokers, who were randomized to receive the same 4-week buprenorphine taper and successfully completed detoxification, were included in the present study. They provided staff-observed urine specimens thrice-weekly throughout the 12-week trial. Specimens were analyzed on-site via enzyme-multiplied immunoassay for urinary cotinine, a metabolite of nicotine that provides a sensitive biochemical measure of smoking status. RESULTS: Mean cotinine levels were significantly different across study phases, with significantly lower cotinine levels during taper (1317.5 ng/ml) and post-taper (1015.8 ng/ml) vs. intake (1648.5 ng/ml) phases (p''s<.05). Overall, mean cotinine levels decreased by 38% between intake and end-of-study, reflecting a reduction of approximately eight cigarettes per day. CONCLUSIONS: These data provide additional evidence that opioids influence smoking and extend prior findings to include primary PO abusers, rigorous double-blind opioid dosing conditions and urinary cotinine. These results also suggest that, while likely insufficient for complete cessation, patients who successfully taper from opioids may also experience concurrent reductions in smoking and thus may be ideal candidates for smoking cessation services.

The accuracy of urinary cotinine immunoassay test strip as an add-on test to self-reported smoking before major elective surgery.

INTRODUCTION: Smoking is a preventable cause of perioperative complications. An accurate and rapid classification of smoking status is essential as up to 35% of smokers deny smoking before surgery. We compared the diagnostic performance of a preoperative urinary cotinine immunoassay test strip (NicAlert®) as an add-on test to patient's self-reported smoking status. METHODS: Four hundred and sixty-five patients undergoing major elective surgery self-reported their smoking history and provided a sample for measuring urinary cotinine concentration by liquid chromatography tandem mass spectrometry (reference standard) and NicAlert®. Using the "either test positive" rule, the gain in diagnostic performance for NicAlert® add-on test was assessed using relative positive and negative likelihood ratios (LRs) and area under the receiver operating characteristic curve (AUROC) with 95% CIs. RESULTS: Of the 60 patients with a positive reference standard (adjusted cotinine ≥ 50 ng/ml), 10 (16.7%) denied current cigarette smoking. The NicAlert® add-on test had better test performance measures (sensitivity = 95.0%, specificity = 94.8%) than self-reported smoking history alone (sensitivity = 83.3%, specificity = 95.0%). The relative positive and negative LRs were 1.09 (95% CI = 0.95-1.24) and 0.30 (95% CI = 0.12-0.78), respectively. The AUROC for the NicAlert® add-on test (0.90; 95% CI = 0.84-0.96) was significantly higher than for the self-reported smoking history alone (0.78; 95% CI = 0.69-0.88) (p = .006). CONCLUSION: The NicAlert® add-on test strategy had excellent diagnostic test performance for identifying current smokers who are expected to have a high risk of perioperative complications.

Prenatal cigarette smoking: Long-term effects on young adult behavior problems and smoking behavior.

We examined the long-term effects of prenatal cigarette smoke exposure (PCSE) on the behavior problems and smoking behavior of 22-year-old offspring. The mothers of these offspring were interviewed about their tobacco and other drug use during pregnancy at the fourth and seventh gestational months, and at delivery. Data on the offspring are from interviews at age 22 (n=608). Behavior problems were measured by the Adult Self-Report (ASR) with the following outcome scales: total behavior problems, externalizing, internalizing, attention, anxiety/depression, withdrawn, thought, intrusive, aggression, somatic and rule breaking behavioral problems. Young adult smoking behavior was measured using self-reported average daily cigarettes, and was validated with urine cotinine. Nicotine dependence was measured with the Fagerström Tobacco and Nicotine Dependence (FTND) scale. Regression analyses tested the relations between trimester-specific PCSE and young adult's behavioral problems and smoking behavior, adjusting for demographic and maternal psychological characteristics, and other prenatal substance exposures. Exposed young adults had significantly higher scores on the externalizing, internalizing, aggression, and somatic scales of the ASR. These young adults were also more likely to have a history of arrests. Young adults with PCSE also had a higher rate of smoking and nicotine dependence. Our previous findings of the relations between PCSE and aggressive behavior in early childhood and PCSE and smoking behavior in early adolescence extend into young adulthood.

Can urinary cotinine predict nicotine dependence level in smokers?

BACKGROUND: Although nicotine dependence plays a role as a main barrier for smoking cessation, there is still a lack of solid evidence on the validity of biomarkers to determine nicotine dependence in clinical settings. This study aimed to investigate whether urinary cotinine levels could reflect the severity of nicotine dependence in active smokers. MATERIALS AND METHODS: Data regarding general characteristics and smoking status was collected using a self-administered smoking questionnaire. The Fagerstrom test for nicotine dependence (FTND) was used to determine nicotine dependence of the participants, and a total of 381 participants were classified into 3 groups of nicotine dependence: low (n=205, 53.8%), moderate (n=127, 33.3%), and high dependence groups (n=49, 12.9%). Stepwise multiple linear regression model and receiver operating characteristic (ROC) curves analyses were used to determine the validity of urinary cotinine for high nicotine dependence. RESULTS: In correlation analysis, urinary cotinine levels increased with FTND score (r=0.567, P<0.001). ROC curves analysis showed that urinary cotinine levels predicted the high-dependence group with reasonable accuracy (optimal cut-off value=1,000 ng/mL; AUC=0.82; P<0.001; sensitivity=71.4%; specificity=74.4%). In stepwise multiple regression analysis, the total smoking period (ß=0.042, P=0.001) and urinary cotinine levels (ß=0.234, P<0.001) were positively associated with nicotine dependence, whereas an inverse association was observed between highest education levels (>16 years) and nicotine dependence (ß=-0.573, P=0.034). CONCLUSIONS: The results of this study support the validity of using urinary cotinine levels for assessment of nicotine dependence in active smokers.

Factors associated with smoking abstinence among smokers and recent-quitters with lung and head and neck cancer.

INTRODUCTION: Smoking cessation among cancer patients is critical for improving outcomes. Understanding factors associated with smoking abstinence after the diagnosis of cancer can provide direction to develop and test interventions to enhance cessation rates. The purpose of this study was to identify determinants of smoking outcomes among cancer patients. METHODS: Standardized questionnaires were used to collect data from 163 smokers or recent-quitters (quit≤6 months) at study entry of which 132 and 121 had data collected at 3 and 6 months. Biochemical verification was conducted with urinary cotinine and carbon monoxide. Descriptive statistics, Cronbach alpha coefficients, Pearson correlations, Fisher's exact test, and multivariable logistic regression were used for analyses. RESULTS: Seven-day-point-prevalence-abstinence (PPA) rates were 90/132 (68%) at 3 months; 46/71 (65%) among lung and 44/61 (72%) among head and neck cancer patients, whereas 7-day-PPA rates were 74/121 (61%) at 6 months; 31/58 (53%) among lung and 43/63 (68%) among head and neck cancer patients. Continuous abstinence rates were 63/89 (71%) at 3 months; 32/45 (71%) among lung and 31/44 (70%) among head and neck cancer patients, whereas continuous abstinence rates were 46/89 (52%) at 6 months; 18/45 (40%) among lung and 28/44 (64%) among head and neck cancer patients. Lower cancer-related, psychological and nicotine withdrawal symptoms were associated with increased 7-D-PPA abstinence rates at 3 and 6 months in univariate models. In multivariable models, however, decreased craving was significantly related with 7-day-PPA at 3 months and decreased craving and increased self-efficacy were associated with 7-D-PPA at 6 months. Decreased craving was the only factor associated with continuous abstinence at 6 months. CONCLUSIONS: Smoking outcomes among lung and head and neck cancer patients appear to have remained the same over the last two decades despite the availability of an increased number of pharmacotherapy options to treat tobacco dependence. Decreased craving and increased self-efficacy were the most consistent factors associated with improved smoking outcomes but symptom control may also play a role in optimal management. Use of combined, and/or higher doses of pharmacotherapy along with behavioral interventions that increase self-efficacy and manage symptoms may promote enhanced cessation rates.

Racial differences in the relationship between number of cigarettes smoked and nicotine and carcinogen exposure.

INTRODUCTION: Black smokers are reported to have higher lung cancer rates and greater tobacco dependence at lower levels of cigarette consumption compared to non-Hispanic White smokers. We studied the relationship between cigarettes per day (CPD) and biomarkers of nicotine and carcinogen exposure in Black and White smokers. METHODS: In 128 Black and White smokers, we measured plasma nicotine and its main proximate metabolite cotinine, urine nicotine equivalents, 4-(methylnitrosamino)-1-(3)pyridyl-1-butanol (NNAL), and polycyclic aromatic hydrocarbon (PAH) metabolites. RESULTS: The dose-response between CPD and nicotine equivalents, and NNAL and PAH was flat for Black but positive for White smokers (Race × CPD interaction, all ps < .05). Regression estimates for the Race × CPD interactions were 0.042 (95% CI 0.013-0.070), 0.054 (0.023-0.086), and 0.028 (0.004-0.052) for urine nicotine equivalents, NNAL, and PAHs, respectively. In contrast there was a strong correlation between nicotine equivalents and NNAL and PAH independent of race. Nicotine and carcinogen exposure per individual cigarette was inversely related to CPD. This inverse correlation was stronger in Black compared to White smokers and stronger in menthol compared to regular cigarette smokers (not mutually adjusted). CONCLUSIONS: Our data indicate that Blacks on average smoke cigarettes differently than White smokers such that CPD predicts smoke intake more poorly in Black than in White smokers.

Nicotine, alcohol, and drug findings in young adults in a population-based postmortem database.

INTRODUCTION: To obtain reliable information on nicotine and drug use through a population-based study, the prevalence of nicotine use in deceased young adults was studied in the Finnish postmortem toxicology database for a 3-year period. The nicotine user and non-nicotine user groups were compared by alcohol, drug, and drug-of-abuse findings and by the manner of death. METHODS: Nicotine users were identified based on detection of nicotine, cotinine, and/or trans-3'-hydroxycotinine in urine from a population-based sample of deceased young adults aged 15-34 years at the time of death (n = 1,623, ∼60% of all fatalities). Background information from case referrals was used to distinguish the abuse of medicines from their therapeutic use. The manner of death was taken from death certificates. RESULTS: Nicotine use was more common in young adults (75%) than among all cases in the database (55%). There were twice as many ethanol-positive cases in nicotine users (60%) than in non-nicotine users (30%). Nicotine use was common (70%-79%) among individuals on antipsychotics, antidepressants, anxiolytics, and/or hypnotics and sedatives. The proportion of nicotine users was also high among the drugs-of-abuse positive cases (85%). There were fewer deaths that were classified as natural in the nicotine users group. CONCLUSIONS: Among deceased young adults, nicotine use was two to three times as common as has been estimated for the corresponding living population (20%-30%). Nicotine use was also strongly associated with substance abuse and mental illnesses requiring pharmacotherapy. This group of young adults usually cannot be reached by traditional health surveys.

Prevalence of tobacco use among young adult males in India: a community-based epidemiological study.

BACKGROUND: Prevalence of tobacco use in India is reaching alarming proportions, despite efforts by both World Health Organization (WHO) and Government of India (GOI) in controlling it. Part of the problem has been lack of available data on tobacco use in various groups. Although Global Youth Tobacco Survey (GYTS) and National Family Health Survey (NFHS) III have focused on adolescents and adults, respectively, data on use among young adults is lacking. Another limitation has been the use of the questionnaire method to determine tobacco use which may not reveal exact prevalence. This study aimed to explore the prevalence of tobacco use among young adult males in Ranchi, as confirmed by serum cotinine levels. METHODS: Five-hundred male students were selected through systematic randomized process to represent 5 universities in Ranchi. After informed consent, the students were administered Tobacco and Other Substance Use questionnaire and then subjected to urine Rapid Nicotine Test to improve sensitivity and biologically confirm prevalence. All tobacco users then were administered Fagerstrom's Scale for Severity of Nicotine Dependence. RESULTS AND CONCLUSION: Biologically confirmed prevalence of tobacco use among male students was 55.6%, revealing high degree of prevalence in this age group. Predominant form of tobacco use was cigarettes (78%) followed by khaini (20%) and gutkha (2%), showing that most young adults use cigarettes possibly due to the 'cool image' associated with it. Seventy-seven percent of all tobacco users want to quit, thereby giving a strong opportunity to carry out cessation services in this group. There was higher mean Fagerstrom's Scale for Severity of Nicotine Dependence (FTND) score in smokers (6.7 +/- 2.2) compared to chewers (4.6 +/- 2.5), revealing higher severity of dependence among smokers than chewers.