Biomarkers Of Tobacco Exposure Research Articles

Exposure to secondhand smoke is associated with increased left ventricular mass.

INTRODUCTIONChronic hypertension is associated with left ventricular hypertrophy. Recent evidence suggests that secondhand smoke (SHS) exposure is associated with chronic hypertension, so we sought to examine the relationship between secondhand smoke exposure and electrocardiographic left ventricular (LV) mass among non-smokers.METHODSThis analysis included 4982 non-smoker participants from the Third National Health and Nutrition Examination (NHANES-III). Non-smoking was defined by self-report and serum cotinine ≤10 ng/mL, a biomarker for tobacco exposure. SHS exposure was defined as serum cotinine level ≥1 ng/mL. LV mass was estimated using an electrocardiographic model developed and applied in NHANES-III then validated in the Cardiovascular Health Study. Multivariable linear regression was used to examine the cross-sectional association between SHS exposure (vs no exposure) with estimated LV mass index. In similar models, we also examined the associations of LV mass index across quartiles of serum cotinine (reference group, 1st quartile) and in subgroups stratified by age, race, sex, hypertension, and obesity.RESULTSAbout 9.8% (n=489) of the participants were exposed to SHS. Exposure to SHS was associated with an estimated 2.9 g/m2 increase in LV mass index, with a dose-response relationship between higher serum cotinine and LV mass index. These results were consistent in men and women, Whites and non-Whites, elderly and non-elderly, and those with and without hypertension. Significant effect modification was present among obese individuals with an estimated 4.8 g/m2 increase in LV mass index (interaction p=0.01).CONCLUSIONSIn a racially diverse sample of non-smokers, SHS is associated with increased LV mass with a dose-response relationship between level of exposure and LV mass. Effect modification was present among obese individuals. These findings underscore the harmful effect of passive smoking on the cardiovascular system and highlight the need for more restrictions on smoking in public areas, especially in countries or regions with less-stringent public health policies.

Association between cotinine-verified smoking status and moderately increased albuminuria in the middle-aged and older population in Korea: A nationwide population-based study.

ObjectivesAlthough several self-reported questionnaire-based studies have found an association between smoking and moderately increased albuminuria, this result remains controversial. We investigated whether moderately increased albuminuria was associated with smoking status, verified by urinary cotinine (an objective biomarker of tobacco exposure), using population-based, nationally representative data.MethodsThis study included 2059 participants aged ≥ 50 years from the 2014 Korean National Health and Nutrition Examination Survey. Individuals with a urinary cotinine level ≥ 50 ng/mL were identified as cotinine-verified smokers. Moderately increased albuminuria was defined as a urine albumin-to-creatinine ratio ranging between ≥ 30 mg/g and < 300 mg/g. Multivariable logistic regression was used to evaluate the association between cotinine-verified smoking status and moderately increased albuminuria.ResultsAmong the study participants, 16.9% were cotinine-verified smokers, 84.8% of whom were men. After adjustment for multiple covariates, cotinine-verified smokers showed a significant positive association with moderately increased albuminuria (adjusted odds ratio: 4.37, 95% confidence interval: 1.63–11.71) compared with cotinine-verified non-smokers. The association between urinary cotinine and moderately increased albuminuria did not differ with age, sex, obesity, or comorbidities (P-value for interaction > 0.05 in all cases).ConclusionThis large-scale observational study showed that cotinine-verified smoking is associated with moderately increased albuminuria in the Korean middle-aged and older general population, suggesting that smoking must be strictly controlled to reduce the risk of moderately increased albuminuria.

Relationship Between Nicotine Dependence Scores and Nicotine, Cotinine, 3′-Hydroxycotinine and Nicotine Metabolite Ratio in Chinese Male Smokers

Summary Smoking is mainly sustained by nicotine dependence (ND), which varies across ethnic groups principally due to genetic as well as environmental factors. The Fagerström Test for Nicotine Dependence (FTND) and biomarkers of tobacco exposure are two important approaches to assess ND. However, the relationship between ND and FTND of Chinese smokers has not been studied. The aim of this study was to assess the relationship between FTND scores and nicotine, cotinine, 3′-hydroxycotinine (3HC) and nicotine metabolite ratio (NMR, the concentration ratio of 3HC to cotinine) in Chinese smokers. FTND was carried out and general characteristics were collected using a self-administered smoking questionnaire with 289 smokers. Nicotine, cotinine and 3HC in urine were simultaneously determined by liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS). The concentrations of nicotine, cotinine and 3HC in the urine of smokers with a high FTND score were higher than in the urine of those with a low FTND score. There were significant correlations between urinary biomarker and FTND scores. Except for FTND item 2 (difficulty to refrain), the other items showed significant associations with the urinary biomarkers. No relationship was found between the nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) and FTND scores or general characteristics of the participants. In conclusion, biomarkers of tobacco exposure levels are significantly associated with FTND scores. However, FTND Item 2 and NMR were not found to be associated with nicotine dependence in Chinese smokers.

Abstract 15034: Exposure to Secondhand Smoke is Associated With Increased Left Ventricular Mass

Background: Exposure to secondhand smoke (SHS), or passive smoking, has been associated with chronic hypertension. However, little is known about the relationship between SHS and left ventricular (LV) hypertrophy, the most common complication of hypertension and a manifestation of cardiac end-organ damage. Hypothesis: SHS exposure is independently associated with LV mass. Methods: This analysis included 4,982 non-smoker participants (age 60.8±13.6 years, 57.8% women, 77.7% whites) from the Third National Health and Nutrition Examination (NHANES-III). Non-smoking was defined by self-report and serum cotinine ≤ 10 ng/dL, a biomarker for tobacco exposure. SHS was defined as serum cotinine level &gt;1 ng/dL. LV mass was estimated using an electrocardiographic model developed and applied in NHANES-III then validated in the Cardiovascular Health Study. Multivariable linear regression was used to examine the cross-sectional association between SHS exposure (vs. no exposure) with estimated LV mass. In similar models, we also examined the associations of LV mass across quartiles of serum cotinine (reference group, 1 st quartile) and in subgroups stratified by race, sex, and hypertension status. Results: About 9.8% (n=489) of the participants were exposed to SHS. Exposure to SHS was associated with an estimated 2.9 gram increase in LV mass, with a dose-response relationship between higher serum cotinine and LV mass ( Table ). These results were consistent in men and women (interaction p-value= 0.31), whites and non-whites (interaction p-value= 0.21), and those with and without hypertension (interaction p-value= 0.88) Conclusion: In a racially diverse sample of non-smokers, SHS is associated with increased LV mass with a dose-response relationship between level of exposure and LV mass. These findings underscore the harmful effect of passive smoking on the cardiovascular system and highlight the need for more restrictions on smoking in public areas.

UGT2B10 Genotype Influences Serum Cotinine Levels and Is a Primary Determinant of Higher Cotinine in African American Smokers.

Cotinine is the most widely used biomarker of tobacco exposure. At similar smoking levels, African Americans have higher serum cotinine than Whites. UGT2B10-catalyzed cotinine glucuronidation impacts these levels, and African Americans often have low UGT2B10 activity due to a high prevalence of a UGT2B10 splice variant (rs2942857). Two UGT2B10 SNPs (rs6175900 and rs2942857) were genotyped in 289 African Americans and 627 White smokers. Each smoker was assigned a genetic score of 0, 1, or 2 based on the number of variant alleles. Total nicotine equivalents (TNE), the sum of nicotine and six metabolites, and serum cotinine and 3'-hydroxycotinine were quantified. The contribution of UGT2B10 genetic score to cotinine concentration was determined. Serum cotinine was significantly higher in smokers with UGT2B10 genetic scores of 2 versus 0 (327 ng/mL vs. 221 ng/mL; P < 0.001); TNEs were not different. In a linear regression model adjusted for age, gender, cigarettes per day, TNE, race, and CYP2A6 activity, geometric mean cotinine increased 43% between genetic score 2 versus 0 (P < 0.001). A 0.1 increase in the CYP2A6 activity ratio, 3'-hydroxycotinine/cotinine, resulted in a 6% decrease in cotinine. After adjustment for UGT2B10 genotype and the other covariants, there was no significant difference in serum cotinine by race. UGT2B10 genotype is a major contributor to cotinine levels and explains the majority of high serum cotinine in African American smokers. Cotinine levels in smokers may greatly overestimate tobacco exposure and potentially misinform our understanding of ethnic/racial difference in tobacco-related disease if UGT2B10 genotype is not taken into account.

Smoking status and second-hand smoke biomarkers in COPD, asthma and healthy controls.

IntroductionTobacco smoke worsens COPD and asthma. For healthy individuals, quantifying active and second-hand smoke (SHS) exposure clarifies the epidemiology of tobacco consumption and the efficacy of nonsmoking measures. Identifying tobacco exposure biomarkers and cut-offs might allow the creation of sensitive and specific tests.AimWe describe the state-of-the-art serum, urinary cotinine and exhaled carbon monoxide (CO) cut-offs for assessing smoking status and SHS exposure in adult patients with COPD or asthma, and healthy controls.MethodologyAfter a keyword research in the PubMed database, we included papers reporting on the cut-offs of the investigated biomarkers in one of the populations of interest. Papers published before 2000, not in English, or reporting only data on nonadult subjects or on pregnant women were excluded from the analysis. 14 papers were included in the final analysis. We summarised diagnostic cut-offs for smoking status or SHS exposure in COPD, asthmatic and healthy control cohorts, reporting sensitivity and specificity when available.ConclusionSerum and urinary cotinine and exhaled CO are easy-to-standardise, affordable and objective tests for assessing smoking status and SHS exposure. Evidence on cut-offs with good sensitivity and specificity values is available mainly for healthy controls. For COPD and asthmatic patients, most of the currently available evidence focuses on exhaled CO, while studies on the use of cotinine with definite sensitivity and specificity values are still missing. Solid evidence on SHS exposure is available only for healthy controls. An integrated approach with a combination of these markers still needs evaluation.

Biomarkers of Exposure among Adult Smokeless Tobacco Users in the Population Assessment of Tobacco and Health Study (Wave 1, 2013-2014).

Monitoring population-level toxicant exposures from smokeless tobacco (SLT) use is important for assessing population health risks due to product use. In this study, we assessed tobacco biomarkers of exposure (BOE) among SLT users from the Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study. Urinary biospecimens were collected from adults ages 18 and older. Biomarkers of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), metals, and inorganic arsenic were analyzed and reported among exclusive current established SLT users in comparison with exclusive current established cigarette smokers, dual SLT and cigarette users, and never tobacco users. In general, SLT users (n = 448) have significantly higher concentrations of BOE to nicotine, TSNAs, and PAHs compared with never tobacco users; significant dose-response relationships between frequency of SLT use and biomarker concentrations were also reported among exclusive SLT daily users. Exclusive SLT daily users have higher geometric mean concentrations of total nicotine equivalent-2 (TNE2) and TSNAs than exclusive cigarette daily smokers. In contrast, geometric mean concentrations of PAHs and VOCs were substantially lower among exclusive SLT daily users than exclusive cigarette daily smokers. Our study produced a comprehensive assessment of SLT product use and 52 biomarkers of tobacco exposure. Compared with cigarette smokers, SLT users experience greater concentrations of some tobacco toxicants, including nicotine and TSNAs. Our data add information on the risk assessment of exposure to SLT-related toxicants. High levels of harmful constituents in SLT remain a health concern.

Time to First Cigarette: A Potential Clinical Screening Tool for Nicotine Dependence

The time to first cigarette (TTFC) of the day has been identified as the best single-item indicator of nicotine dependence. However, TTFC has not been extensively used in clinical settings and is not a criterion for tobacco use disorder, perhaps due to a lack of information about TTFC's predictive value. This review provides a synthesis of the accumulating literature on TTFC's relationships with nicotine dependence, identify gaps, and inform future clinical and epidemiologic research of potential uses of TTFC. A systematic review of the literature was conducted using PubMed, Google Scholar, and Web of Science ISI databases. We identified 16 articles examining the relation between TTFC and negative outcomes associated with high levels of nicotine addiction and Tobacco Use Disorders (eg, high levels of nicotine and toxicant exposure, progressive use over time, failed cessation, head-and-neck cancers). Earlier TTFC was consistently associated with greater likelihood of cessation failure and relapse, and higher levels of biomarkers of tobacco exposure. Several of these associations were found among both adult and adolescent smokers, and remained even after accounting for smoking behaviors (eg, cigarettes/day). Earlier TTFC is a key indicator of greater nicotine dependence. Knowledge of a smoker's TTFC may allow clinicians to accurately inform smokers of health risks and assign greater resources during cessation attempts. Smokers may be able to use TTFC to self-select cessation aids and accurately assess their unique smoking-related health risks. TTFC may be a better item than cigarettes/day for accurately quantifying dependence and risk in epidemiologic studies.

Biomarkers of Exposure for Dual Use of Electronic Cigarettes and Combustible Cigarettes: Nicotelline, NNAL, and Total Nicotine Equivalents.

Dual use of electronic cigarettes (e-cigarettes) and combustible cigarettes is a major public health issue. It is generally accepted that exclusive e-cigarette use is less harmful than exclusive combustible cigarette use, but most e-cigarette users continue to smoke combustible cigarettes as well. To what extent the use of e-cigarettes reduces harm in people who continue to smoke combustible cigarettes has been debated. The aim of this study was to explore the utility of biomarkers as measures of dual use. In two human studies of participants who used e-cigarettes only or both combustible cigarettes and e-cigarettes, we measured urine concentrations of the metabolites of nicotine (total nicotine equivalents) as well as two biomarkers of tobacco exposure: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen metabolite, and nicotelline, a tobacco alkaloid not found in significant concentrations in e-cigarette products. The presence of nicotine metabolites indicates either e-cigarette or combustible cigarette use. Nicotelline (half-life of 2-3 hours) indicates recent combustible cigarette use and NNAL (half-life of 10 days or more), indicates combustible cigarette use occurring within several weeks prior to sample collection. Nicotelline and NNAL are useful biomarkers for combustible tobacco use in users e-cigarettes. The application of these biomarkers provides a tool to help assess whether, or to what extent, dual use of e-cigarettes and combustible cigarettes reduces harm compared to sole use of combustible cigarettes. These biomarkers can also verify exclusive use of e-cigarettes over short (24 hour) or long (several week) time periods. To what extent dual use of e-cigarettes and combustible cigarettes reduce harm compared to smoking combustible cigarettes only is of considerable public health interest. We show that the levels of the minor tobacco alkaloid nicotelline and the nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are extremely low in electronic cigarette fluids. The urine biomarkers nicotelline and the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are indicative of cigarette smoking and can be used to assess recent and past smoking in dual users.

Preparing the new generation of Romanian experts in tobacco control: PhD studies in the field

Scientific progresses and new regulatory global context about tobacco use and cessation have created attractive opportunities for young researchers seeking for a PhD in the field. As such, three most relevant ongoing PhD research topics at the University of Medicine and Pharmacy “Grigore T. Popa” Iasi were selected for presentation: 1. “Air pollution and tobacco smoke interactions in COPD” (to investigate cumulated effect of tobacco smoking and air pollution on clinical course and benefits in COPD, in the actual upsetting increased local environmental pollution frame). 2. “Smoking and oxidative stress in mixed anxious and depressive disorder”( to reveal interactions between oxidative stress and tobacco smoking in mixed anxious an depressive disorders, to ascertain clinical practice benefits of tobacco exposure biomarkers in use and propose new such markers 1 to improve disease management). 3. “Personalized tobacco treatment algorithms for smokers at high respiratory risk” (to develop and implement clinical practice personalized algorithms to treat tobacco dependence in smokers at high risk for respiratory disease and to test their feasibility in a real life respiratory disease clinical setting).

ASSOCIATION BETWEEN SERUM COTININE LEVELS AND PR AND QT INTERVALS AND THEIR COMPONENTS

Serum cotinine is a highly sensitive and specific biomarker for tobacco exposure and is a more accurate measure of tobacco exposure than self-reported smoking status. Few studies have reported its association to electrophysiological dysfunction but may have overlooked key endpoints and covariates.

Association Between Cotinine-verified Smoking Status and Risk of Colorectal Neoplasia.

We evaluated the association of urinary cotinine-verified smoking status with the risk of colorectal neoplasia (CRN). Many studies have reported the association between the risk of CRN and smoking status, based on self-reported questionnaires. Although self-reported smoking status may be inaccurate, to our knowledge, no study has yet assessed the association between objective biomarkers of tobacco exposure and the risk of CRN. A cross-sectional study was conducted on 96,806 asymptomatic examinees who underwent colonoscopy and urinary cotinine measurements as part of a health check-up. Cotinine-verified current smokers were participants having a urinary cotinine level ≥50 ng/mL. The mean participant age was 38.4 years, and the proportion of cotinine-verified current smokers was 23.0%. Cotinine-verified current smoking was an independent risk factor for CRN [adjusted odds ratio (AOR), 1.49; 95% confidence interval (CI), 1.42-1.56] and advanced CRN (ACRN) (AOR, 1.79; 95% CI, 1.57-2.05). Moreover, the risk of CRN and ACRN increased with increasing cotinine levels. Among self-reported never smokers, cotinine-verified current smokers had a higher risk of CRN (AOR, 1.77; 95% CI, 1.57-2.00) and ACRN (AOR, 1.94; 95% CI, 1.37-2.74) than cotinine-verified never smokers did, whereas among self-reported current smokers, cotinine-verified never smokers had a lower risk of CRN (AOR, 0.78; 95% CI, 0.70-0.87) and ACRN (AOR, 0.71; 95% CI, 0.52-0.98) than cotinine-verified current smokers did. Cotinine-captured smoking status and metabolic variation exhibit associations with CRN more accurately and objectively than self-reporting does, providing clearer evidence for the role of tobacco in the development of CRN.

Randomized trial of nicotine inhaler for pregnant smokers

Smoking during pregnancy is a serious public health problem in need of better treatments. Nicotine replacement treatment (NRT) (patch or gum) has not been shown in randomized placebo-controlled trials to be efficacious for smoking cessation during pregnancy. However, the nicotine inhaler may have advantages over other NRTs as it replicates some of the sensory effects of smoking. The purpose of the study was examine the efficacy and safety of the nicotine inhaler for smoking cessation during pregnancy. We hypothesized that the nicotine inhaler compared to placebo would increase quit rates and reduce smoking during treatment and at the end of pregnancy, result in a higher birth weight and gestational age in the offspring, and reduce the incidence of preterm birth and low birth weight infants. We conducted a randomized, double-blind, placebo-controlled trial of the nicotine inhaler for smoking cessation during pregnancy. Pregnant women who smoked ≥5 cigarettes daily received behavioral counseling and random assignment to a 6-week treatment with nicotine or placebo inhaler, followed by a 6-week taper period. Throughout treatment, we assessed tobacco exposure biomarkers, cessation rates, and adverse events. We also obtained information on birth outcomes. The primary outcome was smoking cessation at 32-34 weeks gestation; secondary outcomes were smoking reduction, birth weight and gestational age, and the incidence of preterm birth or low birth weight infants. We compared treatment groups on these measures using t-tests, Fisher's exact tests, and multivariate linear and logistic regression. Participants in the placebo (n=67) and nicotine (n=70) groups were comparable on baseline characteristics, though women in the placebo group reported a higher motivation to quit (p=0.016). Biochemically-validated smoking cessation rates were similar with nicotine and placebo (after 6 weeks of treatment: 4% (3/70) vs. 3% (2/67), respectively, p< 0.99, and at 32-34 weeks gestation: 10% (7/70) vs. 18% (12/67), respectively, p=0.220). Cigarettes per day (CPD) decreased over time in both groups (p< 0.001), with the nicotine inhaler group having a greater decrease than the placebo group two (p=0.022) and six weeks after the quit date (p=0.042), but not at 32-34 weeks gestation (p=0.108). Serum cotinine levels, birth weight, gestational age and reductions in carbon monoxide did not differ by group. However, the incidence of preterm delivery was higher in the placebo than the nicotine group: 15% (10/67) vs. 4% (3/67), respectively, p=0.030). The incidence of delivering a low birth weight infant was also higher in the placebo than the nicotine group: 15% (10/67) vs. 6% (4/67), respectively, p=0.035, but not after adjusting for preterm delivery p=0.268. Although the nicotine inhaler group did not have a higher quit rate during pregnancy than the placebo group, the outcome of preterm delivery occurred less frequently in the nicotine group.

E-cigarettes and Tobacco Exposure Biomarkers among American Indian Smokers.

Objective We assessed associations between electronic cigarette (e-cigarette) use and smoking-related measures among American Indians (AIs) who smoke. MethodsWe collected baseline survey and smoking biomarker data in a cohort of 375 adult AI smokers at a Cherokee Nation healthcare facility in Oklahoma. We used multivariate logistic and linear regression analyses to determine associations between e-cigarette use and smoking-related characteristics, including biomarkers. ResultsCurrent e-cigarette users were more likely than never users to report a quit attempt in the past 12 months (current vs never adjusted odds ratio (AOR) = 2.24 [95% CI 1.20-4.16]). Current and past e-cigarette users were more likely than never users to report a likelihood to quit smoking (current vs never AOR = 2.97 [95% CI 1.34-6.56]; past vs never AOR = 1.77 [95% CI 1.08-2.91]). E-cigarette use was not significantly associated with confidence to quit smoking, cigarette packs smoked per day, or cotinine levels. ConclusionsE-cigarette use was associated with previous and future quit attempts, but not with reductions in cigarette smoking or confidence in quitting. This suggests that many dual users might benefit from the addition of evidence-based smoking cessation treatments.

Biomarkers of Tobacco Exposure Decrease After Smokers Switch to an E-Cigarette or Nicotine Gum.

IntroductionThe aerosol composition of electronic cigarettes (ECs) suggests that exposure to toxicants during use is greatly reduced compared to exposure from combustible cigarettes (CCs).MethodsThis randomized, parallel-group, clinical study enrolled smokers to switch to Vuse Solo (VS) Digital Vapor Cigarettes (Original or Menthol) or Nicorette 4 mg nicotine gum (NG) in a controlled setting. Subjects who smoked CCs ad libitum for 2 days during a baseline period were then randomized to ad libitum use of either VS or NG for 5 days. Biomarkers of 23 toxicants were measured in 24-hour urine samples and blood collected at baseline and following product switch.ResultsA total of 153 subjects completed the study. Total nicotine equivalents decreased in all groups, but higher levels were observed in the VS groups compared to the NG groups, with decreases of 38% and 60%–67%, respectively. All other biomarkers were significantly decreased in subjects switched to VS, and the magnitude of biomarker decreases was similar to subjects switched to NG. Decreases ranged from 30% to greater than 85% for constituents such as benzene and acrylonitrile.ConclusionsThese results indicate that exposure to toxicants when using VS is significantly reduced compared to CC smoking, and these reductions are similar to those observed with use of NG. Although statistically significantly decreased, nicotine exposure is maintained closer to CC smoking with VS use compared to NG use. This research suggests that use of VS exposes consumers to fewer and lower levels of smoke toxicants than CCs while still providing nicotine to the consumer.ImplicationsThis is the first study to report changes in nicotine delivery and biomarkers of tobacco exposure following a short-term product switch from CCs to either an EC or NG in a controlled environment. The study shows that nicotine exposure decreased in both groups but was maintained closer to CC smoking with the EC groups. Biomarkers of tobacco combustion decreased to similar levels in both EC and gum groups.

Collaborative Method Performance Study of the Measurement of Nicotine, Its Metabolites, and Total Nicotine Equivalents in Human Urine.

Background: Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements.Methods: This report presents the results from a method performance study involving 11 laboratories from 6 countries that are currently active in this area. Each laboratory assayed blind replicates of seven human urine pools at various concentrations on three separate days. The samples included five pools blended from smoker and nonsmoker urine sources, and two additional blank urine samples fortified with pure nicotine, cotinine, and hydroxycotinine standards. All laboratories used their own methods, and all were based on some form of liquid chromatography/tandem mass spectrometry.Results: Overall, good agreement was found among the laboratories in this study. Intralaboratory precision was good, and in the fortified pools, the mean bias observed was < + 3.5% for nicotine, approximately 1.2% for hydroxycotinine, and less than 1% for cotinine (1 outlier excluded in each case). Both indirect and direct methods for analyzing the glucuronides gave comparable results.Conclusions: This evaluation indicates that the experienced laboratories participating in this study can produce reliable and comparable human urinary nicotine metabolic profiles in samples from people with significant recent exposure to nicotine.Impact: This work supports the reliability and agreement of an international group of established laboratories measuring nicotine and its metabolites in urine in support of nicotine exposure studies. Cancer Epidemiol Biomarkers Prev; 27(9); 1083-90. ©2018 AACR.

Comparison of Biomarkers of Tobacco Exposure between Premium and Discount Brand Cigarette Smokers in the NHANES 2011–2012 Special Sample

Background: Increased cigarette costs have inadvertently strengthened the appeal of discounted brands to price-sensitive smokers. Although smokers perceive discounted brands as having poorer quality, little is known about their delivery of toxic tobacco smoke constituents compared with premium-branded tobacco products.Methods: We investigated the differences between discount and premium brand smokers using the National Health and Nutrition Examination Survey 2011-2012 Special Smoker Sample. Our analyses focused on demographic differences and 27 biomarkers of harmful and potentially harmful constituents (HPHC) listed by the FDA, including volatile organic compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide; reported as total NNAL (tNNAL)], metals, and polycyclic aromatic hydrocarbons (PAHs). Data were analyzed using linear regression models adjusting for potential confounders.Results: A total of 976 non-tobacco users and 578 recent cigarette smokers were eligible for analysis, of which 141 (26.0% weighted) smoked discount brand cigarettes and 437 (74.0% weighted) smoked premium. Discount brand smokers were older, predominantly non-Hispanic white, and had higher serum cotinine. Discount brand smokers had significantly higher levels of 13 smoking-related biomarkers, including tNNAL, uranium, styrene, xylene, and biomarkers of exposure to PAHs (naphthalene, fluorene, and phenanthrene), compared with premium brand smokers.Conclusions: These findings suggest that discount cigarette use is associated with higher exposure to several carcinogenic and toxic HPHCs.Impact: These results may have important regulatory implications for product standards, as higher exposures could lead to a greater degree of harm. Cancer Epidemiol Biomarkers Prev; 27(5); 601-9. ©2018 AACR.

Salivary thiocyanate as a biomarker for tobacco exposure - implications in diagnosis and tobacco cessation

Salivary thiocyanate as a biomarker for tobacco exposure - implications in diagnosis and tobacco cessation

Association between cotinine-verified smoking status and risk of nonalcoholic fatty liver disease.

The relationship between cigarette smoking and nonalcoholic fatty liver disease (NAFLD) has been controversial. Most relevant studies have relied on self-reported questionnaires. We aimed to elucidate the association between smoking status and NAFLD using an objective biomarker of tobacco exposure (urinary cotinine) and self-reported questionnaire. A cross-sectional study was conducted on 160862 asymptomatic examinees who underwent abdominal ultrasonography and urinary cotinine measurements between April 2011 and December 2015. Cotinine-verified current smokers were defined as participants with urinary cotinine levels ≥50ng/mL. The mean age of the study population was 36.1years, and the proportion of men was 51.7%. The proportions of self-reported and cotinine-verified current smokers were 17.6% and 17.7% respectively. After adjusting for confounding factors, self-reported current smoking was associated with an increased risk of NAFLD (adjusted odds ratio [AOR], 1.10; 95% confidence interval [CI], 1.06-1.14). Moreover, among the current smokers, the risk of NAFLD increased with an increase in the amount of cigarette smoking (<10 and ≥10 pack-years vs never smokers; AOR, 1.04 and 1.11; 95% CI, 1.01-1.08 and 1.05-1.16 respectively). Cotinine-verified current smoking was also associated with an increased risk of NAFLD (AOR, 1.10; 95% CI, 1.06-1.14). Cotinine-verified current smoking and self-reported current smoking were independent risk factors for NAFLD. Further longitudinal studies are needed to more clearly elucidate the impact of smoking on the development of NAFLD.

Urine 4-(methylnitrosamino)-1-(3) pyridyl-1-butanol and cotinine in Alaska native postpartum women and neonates comparing smokers and smokeless tobacco users

ABSTRACTObjective: Foetuses and neonates of women who use tobacco are exposed to nicotine and tobacco-derived carcinogens. We determined the relationship between urine biomarkers of tobacco toxicant exposure postpartum and in the neonates of Alaska Native (AN) women, comparing smokers and smokeless tobacco (ST) users, including iqmik, a homemade ST product.Methods: AN women, including 36 smokers, 9 commercial ST and 16 iqmik users their neonates participated. Urine from the woman at the time of delivery and her neonate’s first urine were analysed for cotinine, the major metabolite of nicotine, and 4-(methylnitrosamino)-1-(3) pyridyl-1-butanol (NNAL), a tobacco-specific carcinogen biomarker.Results: Maternal urine cotinine and neonatal urine cotinine were strongly correlated in all tobacco use groups (r from 0.83 to 0.9, p < 0.002). Correlations between maternal cotinine and neonatal NNAL were moderately strong for cigarettes and commercial smokeless but weaker for iqmik users (r 0.73, 0.6 and 0.36, respectively).Conclusion: Correlations between maternal and neonatal biomarkers of tobacco toxicant exposure vary, dependent on tobacco product use.Significance: This study provides novel data on biomarkers of tobacco exposure among postpartum AN women and their neonates. The results could be useful to guide future epidemiological studies of health risks associated with use of various tobacco products during pregnancy.