Exposure to polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines and incidence of esophageal cancer.

BACKGROUND: Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. METHODS: The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma. RESULTS: Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N'-Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users. CONCLUSION: These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.

Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study.

BACKGROUND: Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use. METHODS: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1. RESULTS: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%-4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1-62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5-66.4)], among most demographic subgroups. CONCLUSIONS: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4. IMPACT: Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status.

Anabasine and Anatabine Exposure Attributable to Cigarette Smoking: National Health and Nutrition Examination Survey (NHANES) 2013-2014.

Anabasine and anatabine are minor alkaloids in tobacco products and are precursors for tobacco-specific nitrosamines (TSNAs). The levels of these two compounds have been used to differentiate tobacco product sources, monitor compliance with smoking cessation programs, and for biomonitoring in TSNA-related studies. The concentrations of urinary anabasine and anatabine were measured in a representative sample of U.S. adults who smoked cigarettes (N = 770) during the 2013−2014 National Health and Nutrition Examination Survey (NHANES) study cycle, which was the first cycle where urinary anabasine and anatabine data became available. Weighted geometric means (GM) and geometric least squares means (LSM) with 95% confidence intervals were calculated for urinary anabasine and anatabine categorized by tobacco-use status [cigarettes per day (CPD) and smoking frequency] and demographic characteristics. Smoking ≥20 CPD was associated with 3.6× higher anabasine GM and 4.8× higher anatabine GM compared with smoking <10 CPD. Compared with non-daily smoking, daily smoking was associated with higher GMs for urinary anabasine (1.41 ng/mL vs. 6.28 ng/mL) and anatabine (1.62 ng/mL vs. 9.24 ng/mL). Urinary anabasine and anatabine concentrations exceeded the 2 ng/mL cut point in 86% and 91% of urine samples from people who smoke (PWS) daily, respectively; in comparison, 100% of them had serum cotinine concentrations greater than the established 10 ng/mL cut point. We compared these minor tobacco alkaloid levels to those of serum cotinine to assess their suitability as indicators of recent tobacco use at established cut points and found that their optimal cut point values would be lower than the established values. This is the first time that anabasine and anatabine are reported for urine collected from a U.S. population-representative sample of NHANES study participants, providing a snapshot of exposure levels for adults who smoked during 2013−2014. The results of this study serve as an initial reference point for future analysis of NHANES cycles, where changes in the national level of urinary anabasine and anatabine can be monitored among people who smoke to show the effect of changes in tobacco policy.

Geometric Mean Serum Cotinine Concentrations Confirm a Continued Decline in Secondhand Smoke Exposure among U.S. Nonsmokers-NHANES 2003 to 2018.

The objective of this study was to examine long-term trends in serum cotinine (COT) concentrations, as a measure of secondhand smoke (SHS) exposure, in U.S. nonsmokers using data from the National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2018. We analyzed NHANES serum COT results from 8 continuous NHANES 2 year cycles from 2003 to 2018 using a liquid chromatography−tandem mass spectrometry assay that has been maintained continuously at the Centers for Disease Control and Prevention (CDC) since 1992. Serum COT concentrations (based on the geometric means) among nonsmokers in the U.S. decreased by an average of 11.0% (95% confidence interval (CI) [8.8%, 13.1%]; p < 0.0001) every 2 year cycle. From 2003 to 2018, serum COT concentrations in U.S. nonsmokers declined by 55.0%, from 0.065 ng/mL in 2003−2004 to 0.029 ng/mL in 2017−2018 (p < 0.0001). Significant decreases in serum COT concentrations were observed in all demographic groups. While disparities between these groups seems to be shrinking over time, several previously observed disparities in SHS exposure remain in 2017−2018. Serum COT concentrations of the non-Hispanic Black population remained higher than those of non-Hispanic Whites and Mexican Americans (p < 0.0001). Additionally, serum COT concentrations were significantly higher for children aged 3−5 years than other age groups (p ≤ 0.0002), and men continued to have significantly higher serum COT concentrations than women (p = 0.0384). While there is no safe level of exposure to SHS, the decrease in serum COT concentrations in the U.S. population as well as across demographic groupings represents a positive public health outcome and supports the importance of comprehensive smoke-free laws and policies for workplaces, public places, homes, and vehicles to protect nonsmokers from SHS exposure.

Urinary Nicotine Metabolites and Self-Reported Tobacco Use Among Adults in the Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

INTRODUCTION: The Population Assessment of Tobacco and Health (PATH) Study is a longitudinal cohort study on tobacco use behavior, attitudes and beliefs, and tobacco-related health outcomes, including biomarkers of tobacco exposure in the U.S. population. In this report we provide a summary of urinary nicotine metabolite measurements among adult users and non-users of tobacco from Wave 1 (2013-2014) of the PATH Study. METHODS: Total nicotine and its metabolites including cotinine, trans-3'-hydroxycotinine (HCTT), and other minor metabolites were measured in more than 11 500 adult participants by liquid chromatography tandem mass spectrometry methods. Weighted geometric means (GM) and least square means from statistical modeling were calculated for non-users and users of various tobacco products. RESULTS: Among daily users, the highest GM concentrations of nicotine, cotinine and HCTT were found in exclusive smokeless tobacco users, and the lowest in exclusive e-cigarette users. Exclusive combustible product users had intermediate concentrations, similar to those found in users of multiple products (polyusers). Concentrations increased with age within the categories of tobacco users, and differences associated with gender, race/ethnicity and educational attainment were also noted among user categories. Recent (past 12 months) former users had GM cotinine concentrations that were more than threefold greater than never users. CONCLUSIONS: These urinary nicotine metabolite data provide quantification of nicotine exposure representative of the entire US adult population during 2013-2014 and may serve as a reference for similar analyses in future measurements within this study. IMPLICATIONS: Nicotine and its metabolites in urine provide perhaps the most fundamental biomarkers of recent nicotine exposure. This report, based on Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study, provides the first nationally representative data describing urinary nicotine biomarker concentrations in both non-users, and users of a variety of tobacco products including combustible, e-cigarette and smokeless products. These data provide a urinary biomarker concentration snapshot in time for the entire US population during 2013-2014, and will provide a basis for comparison with future results from continuing, periodic evaluations in the PATH Study.

Nicotine Exposure in the U.S. Population: Total Urinary Nicotine Biomarkers in NHANES 2015-2016.

We characterize nicotine exposure in the U.S. population by measuring urinary nicotine and its major (cotinine, trans-3'-hydroxycotinine) and minor (nicotine 1'-oxide, cotinine N-oxide, and 1-(3-pyridyl)-1-butanol-4-carboxylic acid, nornicotine) metabolites in participants from the 2015−2016 National Health and Nutrition Examination Survey. This is one of the first U.S. population-based urinary nicotine biomarker reports using the derived total nicotine equivalents (i.e., TNEs) to characterize exposure. Serum cotinine data is used to stratify tobacco non-users with no detectable serum cotinine (−sCOT), non-users with detectable serum cotinine (+sCOT), and individuals who use tobacco (users). The molar concentration sum of cotinine and trans-3'-hydroxycotinine was calculated to derive the TNE2 for non-users. Additionally, for users, the molar concentration sum of nicotine and TNE2 was calculated to derive the TNE3, and the molar concentration sum of the minor metabolites and TNE3 was calculated to derive the TNE7. Sample-weighted summary statistics are reported. We also generated multiple linear regression models to analyze the association between biomarker concentrations and tobacco use status, after adjusting for select demographic factors. We found TNE7 is positively correlated with TNE3 and TNE2 (r = 0.99 and 0.98, respectively), and TNE3 is positively correlated with TNE2 (r = 0.98). The mean TNE2 concentration was elevated for the +sCOT compared with the −sCOT group (0.0143 [0.0120, 0.0172] µmol/g creatinine and 0.00188 [0.00172, 0.00205] µmol/g creatinine, respectively), and highest among users (33.5 [29.6, 37.9] µmol/g creatinine). Non-daily tobacco use was associated with 50% lower TNE7 concentrations (p < 0.0001) compared with daily use. In this report, we show tobacco use frequency and passive exposure to nicotine are important sources of nicotine exposure. Furthermore, this report provides more information on non-users than a serum biomarker report, which underscores the value of urinary nicotine biomarkers in extending the range of trace-level exposures that can be characterized.

Rapid Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method to Measure Cannabinoids in Bronchoalveolar-Lavage Fluid of Patients with e-Cigarette, or Vaping, Product Use-Associated Lung Injury.

In 2019, the Centers for Disease Control and Prevention responded to an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). Bronchoalveolar-lavage (BAL) fluid from EVALI patients was available for analysis to investigate a range of potential toxicants that might be present at the presumed site of lung injury. Our laboratory developed and validated a novel method to measure cannabinoids and their metabolites in BAL fluid to aid in the investigation of the toxicants that might be the cause of EVALI. In this paper, we describe a sensitive liquid chromatography-tandem mass spectrometry method to measure the following six cannabinoids: Δ9-tetrahydrocannabinol (THC), THC metabolites 11-nor-9-carboxy-THC and 11-hydroxy-THC, cannabinol, cannabidiol (CBD), and CBD metabolite 7-nor-7-carboxycannabidiol. Cannabinoids were extracted from BAL fluid using solid-phase extraction. Accuracy, precision, stability, and limits of detection were determined from replicate analyses of spiked BAL pools. The lower limits of detection ranged from 0.019 to 0.153 ng/mL for a sample volume of 150 µL. Overall accuracy ranged from 71.0 to 100.8%. Within-run imprecision (measured by the coefficient of variation) was below 8%, and between-run imprecision was below 21% for all analytes and concentrations tested. The method was applied to samples from 59 EVALI case patients. We identified THC, CBD, or their metabolites in 76% of EVALI patient samples. These findings support previous evidence that THC-containing products played a major role in the EVALI outbreak and help to inform public health recommendations.

Serum Concentrations of Cotinine and Trans-3'-Hydroxycotinine in US Adults: Results From Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative cohort of tobacco product users and nonusers. The study's main purpose is to obtain longitudinal epidemiologic data on tobacco use and exposure among the US population. AIMS AND METHODS: Nicotine biomarkers-cotinine (COT) and trans-3'-hydroxycotinine (HCT)-were measured in blood samples collected from adult daily tobacco users and nonusers during Wave 1 of the PATH Study (2013-2014; n = 5012; one sample per participant). Participants' tobacco product use and exposure to secondhand smoke were categorized based on questionnaire responses. Nonusers were subdivided into never users and recent former users. Daily tobacco users were classified into seven tobacco product use categories: exclusive users of cigarette, smokeless tobacco, electronic cigarette, cigar, pipe, and hookah, as well as polyusers. We calculated sample-weighted geometric mean (GM) concentrations of cotinine, HCT, and the nicotine metabolite ratio (NMR) and evaluated their associations with tobacco use with adjustment for potential confounders. RESULTS: The GMs (95% confidence intervals) of COT and HCT concentrations for daily tobacco users were 196 (184 to 208) and 72.5 (67.8 to 77.4) ng/mL, and for nonusers they were 0.033 (0.028 to 0.037) and 0.021 (0.018 to 0.023) ng/mL. Exclusive smokeless tobacco users had the highest COT concentrations of all user groups examined. The GM NMR in daily users was 0.339 (95% confidence interval: 0.330 to 0.350). CONCLUSIONS: These nationally representative estimates of serum nicotine biomarkers could be the basis for reference ranges characterizing nicotine exposure for daily tobacco users and nonusers in the US adult population. IMPLICATIONS: This report summarizes the serum nicotine biomarker measurements in Wave 1 of the PATH Study. We are reporting the first estimates of HCT in serum for daily tobacco users and nonusers in the noninstitutionalized, civilian US adult population; the first nationally representative serum COT estimates for daily exclusive users of different tobacco products and daily polyusers; and the first nationally representative estimate of the serum NMR in daily tobacco users by age, race/ethnicity, and sex.

Trends in Secondhand Smoke Exposure, 2011-2018: Impact and Implications of Expanding Serum Cotinine Range.

INTRODUCTION: The impact of defining secondhand smoke exposure among nonsmokers using an expanded serum cotinine range is currently unknown. METHODS: This study assessed the trends in secondhand smoke exposure prevalence among a nationally representative sample of 23,753 U.S. nonsmokers aged ≥3 years. Serum cotinine ranges of 0.05-10 ng/mL (established) and of 0.015-10 ng/mL (expanded) were analyzed in 2021 using data from the 2011-2018 National Health and Nutrition Examination Survey. RESULTS: During 2011-2018, the percentage of people with a serum cotinine range of 0.05-10 ng/mL remained stable (25.3% to 24.6%) across most sociodemographic subgroups but declined significantly among adult Mexican Americans aged ≥20 years (23.9% to 14.1%). However, the percentage of people with serum cotinine range of 0.015-10 ng/mL significantly declined (58.3% to 52.3%) among male individuals (60.9% to 55.0%), among female individuals (56.2% to 50.0%), among adults aged ≥20 years (55.8% to 49.2%), among Mexican Americans (60.9% to 41.2%), among people with a college degree or higher (44.4% to 36.0%), among those who rented their housing (71.7% to 62.5%), among people not living with someone who smoked inside the home (56.1% to 50.0%), and among Mexican Americans aged ≥20 years (60.9% to 39.1%) (all p<0.05 for linear trend test). CONCLUSIONS: Expanding the serum cotinine range to 0.015-10 ng/mL more than doubles the estimated proportion of U.S. nonsmokers exposed to secondhand smoke. In contrast to a serum cotinine range of 0.05-10 ng/mL, it suggests that progress has been made in reducing population-level secondhand smoke exposure during 2011-2018, especially among nonsmokers experiencing lower exposure levels.

Urinary Cotinine and Cotinine + Trans-3'-Hydroxycotinine (TNE-2) Cut-points for Distinguishing Tobacco Use from Nonuse in the United States: PATH Study (2013-2014).

BACKGROUND: Determine the overall, sex-, and racially/ethnically-appropriate population-level cotinine and total nicotine equivalents (TNE-2, the molar sum of the two major nicotine metabolites) cut-points to distinguish tobacco users from nonusers across multiple definitions of use (e.g., exclusive vs. polytobacco, and daily vs. non-daily). METHODS: Using Wave 1 (2013-2014) of the U.S. Population Assessment of Tobacco and Health (PATH) Study, we conducted weighted Receiver Operating Characteristic (ROC) analysis to determine the optimal urinary cotinine and TNE-2 cut-points, stratified by sex and race/ethnicity. RESULTS: For past 30-day exclusive cigarette users, the cotinine cut-point that distinguished them from nonusers was 40.5 ng/mL, with considerable variation by sex (male: 22.2 ng/mL; female: 43.1 ng/mL) and between racial/ethnic groups (non-Hispanic other: 5.2 ng/mL; non-Hispanic black: 297.0 ng/mL). A similar, but attenuated, pattern emerged when assessing polytobacco cigarette users (overall cut-point = 39.1 ng/mL, range = 5.5 ng/mL-80.4 ng/mL) and any tobacco users (overall cut-point = 39.1 ng/mL, range = 4.8 ng/mL-40.0 ng/mL). Using TNE-2, which is less impacted by racial differences in nicotine metabolism, produced a comparable pattern of results although reduced the range magnitude. CONCLUSIONS: Because of similar frequency of cigarette use among polytobacco users, overall cut-points for exclusive cigarette use were not substantially different from cut-points that included polytobacco cigarette use or any tobacco use. Results revealed important differences in sex and race/ethnicity appropriate cut-points when evaluating tobacco use status and established novel urinary TNE-2 cut-points. IMPACT: These cut-points may be used for biochemical verification of self-reported tobacco use in epidemiologic studies and clinical trials.

Concentrations of Cotinine and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol (NNAL) in U.S. Non-Daily Cigarette Smokers.

BACKGROUND: Accumulating evidence suggests that non-daily smokers have higher disease and mortality risks than never smokers. Yet, the accuracy of self-reported non-daily cigarette smoking is poorly understood. METHODS: We examined the concordance between self-reported non-daily smoking and serum cotinine in 18,835 adult participants (20 years or older) of the 2007 to 2014 National Health and Nutrition Examination Surveys, in comparison with daily smokers and nonsmokers. We also analyzed concentrations of the urinary biomarker 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by smoking status. RESULTS: In the study sample, 77.8% (14,660) reported currently not smoking (nonsmokers), 18.3% (3,446) smoked every day (daily smokers), and 3.9% (729) smoked on some days of the past month (non-daily smokers). Just 2.1% of nonsmokers had cotinine concentrations in the active smoking range (>10 ng/mL), compared with 70.4% of non-daily and 98.8% of daily smokers. Non-daily smokers reported smoking a median of 24 cigarettes per month [interquartile range (IQR) = 9-60] and had substantially higher concentrations of NNAL (median = 72.5; IQR = 14.8-211.0 pg/mL) than nonsmokers (median = 0.4; IQR = 0.4-2.1 pg/mL), although lower than daily smokers (median = 294.0; IQR = 148.0-542.0 pg/mL). Among non-daily smokers, concentrations of cotinine and NNAL were positively correlated with days and cigarettes smoked per month (P < 0.001). CONCLUSIONS: We observed excellent concordance between self-reported non-daily cigarette smoking and concentrations of serum cotinine. IMPACT: These results provide evidence for the validity of self-reported non-daily smoking and indicate that non-daily smokers are exposed to substantial concentrations of carcinogenic nitrosamines regardless of the low number of cigarettes they smoke per month.

Secondhand marijuana exposure in a convenience sample of young children in New York City.

BACKGROUND: Biomarkers of exposure to marijuana smoke can be detected in the urine of children with exposure to secondhand marijuana smoke, but the prevalence is unclear. METHODS: We studied children between the ages of 0 to 3 years who were coming in for well-child visits or hospitalized on the inpatient general pediatric unit between 2017 and 2018 at Kravis Children's Hospital at Mount Sinai. Parents completed an anonymous survey, and urine samples were analyzed for cotinine and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (COOH-THC), a metabolite of Δ9-tetrahydrocannabinol. RESULTS: Fifty-three children had urine samples available for analysis. COOH-THC was detectable in 20.8% of the samples analyzed and urinary cotinine was detectable in 90.2%. High levels of tobacco exposure (defined as cotinine ≥2.0 ng/ml) were significantly associated with COOH-THC detection (p < 0.01). We found that 34.8% of children who lived in attached housing where smoking was allowed within the property had detectable COOH-THC compared to 13.0% of children who lived in housing where smoking was not allowed at all. CONCLUSIONS: This study adds to the growing evidence that children are being exposed to marijuana smoke, even in places where recreational marijuana use is illegal. It is critical that more research be done on the impact of marijuana smoke exposure on children's health and development. IMPACT: We found that 20.8% of the 53 children recruited from Mount Sinai Hospital had detectable marijuana metabolites in their urine. Children with household tobacco smoke exposure and children who lived in attached housing where smoking was allowed on the premises were more likely to have detectable marijuana smoke metabolites. This study adds to the growing evidence that children are being exposed to marijuana smoke, even in places where marijuana remains illegal by state law. As states consider marijuana legalization, it is critical that the potential adverse health effects from marijuana exposure in children be taken into account.

Differences in Exposure to Nicotine, Tobacco-Specific Nitrosamines, and Volatile Organic Compounds among Electronic Cigarette Users, Tobacco Smokers, and Dual Users from Three Countries.

Country-level differences in nicotine vaping products used and biomarkers of exposure among long-term e-cigarette users and dual users remain understudied. This cross-sectional study was conducted in 2014 in the United States (n = 166), United Kingdom (n = 129), and Poland (n = 161). We compared patterns of tobacco product use and nicotine and toxicant exposure among cigarette-only smokers (n = 127); e-cigarette-only users (n = 124); dual users of tobacco cigarettes and e-cigarettes (n = 95); and non-users (control group, n = 110) across three countries using mixed-effects linear regression. Compared with cigarette smokers, e-cigarette-only users had lower levels of toxicant biomarkers, but higher levels of nicotine biomarkers. Dual users had higher levels of toxicant biomarkers than e-cigarette-only users but similar levels to cigarette-only smokers. E-cigarette users in Poland, who overwhelmingly used refillable tank devices, exhibited greater levels of nicotine, and toxicant biomarkers relative to e-cigarette users in US/UK. Despite smoking fewer cigarettes, dual users from Poland exhibited similar levels of nicotine biomarkers compared with UK dual users, but higher than US dual users. Country-level differences in e-cigarette devices used and smoking behaviors (e.g., intensity) may contribute to differences in biomarker levels among users of the same products residing in different countries.

Biomarkers of Exposure among USA Adult Hookah Users: Results from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2014).

Hookah smoking has become common in the USA, especially among young adults. This study measured biomarkers of exposure to known tobacco product toxicants in a population-based sample of exclusive, established hookah users. Urinary biomarker data from 1753 adults in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study were used to compare geometric mean concentrations of biomarkers of exposure in exclusive, established past 30-day hookah users to never users of tobacco. Geometric mean ratios were calculated comparing hookah user groups with never users adjusting for age, sex, race/ethnicity, education, past 30-day marijuana use, secondhand smoke exposure and creatinine. Past 30-day hookah users (n = 98) had 10.6 times the urinary cotinine level of never tobacco users. Compared to never tobacco users, past 30-day hookah users had 2.3 times the level of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 1.3 times higher polycyclic aromatic hydrocarbons (PAHs) 3-hydroxyfluorene and 1-hydroxypyrene, 1.8 times higher levels of acrylonitrile, 1.3 times higher levels of acrylamide, and 1.2 times higher levels of acrolein exposure. These data indicate that hookah use is a significant source of exposure to nicotine, carcinogens, and respiratory toxicants.

Opiate and Tobacco Use and Exposure to Carcinogens and Toxicants in the Golestan Cohort Study.

BACKGROUND: There is little information on human exposure to carcinogens and other toxicants related to opiate use, alone or in combination with tobacco. METHODS: Among male participants of the Golestan Cohort Study in Northeast Iran, we studied 28 never users of either opiates or tobacco, 33 exclusive cigarette smokers, 23 exclusive users of smoked opiates, and 30 opiate users who also smoked cigarettes (dual users; 21 smoked opiates and 9 ingested them). We quantified urinary concentrations of 39 exposure biomarkers, including tobacco alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC), and used decomposition to parse out the share of the biomarker concentrations explained by opiate use and nicotine dose. RESULTS: Dual users had the highest concentrations of all biomarkers, but exclusive cigarette smokers and exclusive opiate users had substantially higher concentrations of PAH and VOC biomarkers than never users of either product. Decomposition analysis showed that opiate use contributed a larger part of the PAH concentrations than nicotine dose, and the sum of 2- and 3-hydroxyphenanthrene (∑2,3-phe) resulted almost completely from opiate use. Concentrations of most VOC biomarkers were explained by both nicotine dose and opiate use. Two acrylamide metabolites, a 1,3-butadiene metabolite and a dimethylformamide metabolite, were more strongly explained by opiate use. Acrylamide metabolites and ∑2,3-phe were significantly higher in opiate smokers than opiate eaters; other biomarkers did not vary by the route of opiate intake. CONCLUSIONS: Both cigarette smokers and opiate users (by smoking or ingestion) were exposed to many toxicants and carcinogens. IMPACT: This high exposure, particularly among dual opiate and cigarette users, can have a substantial global public health impact.

Evaluation of Tobacco Smoke and Diet as Sources of Exposure to Two Heterocyclic Aromatic Amines for the U.S. Population: NHANES 2013-2014.

BACKGROUND: Heterocyclic aromatic amines (HAA) are a group of hazardous substances produced during combustion of tobacco or high-temperature cooking of meats. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is a major carcinogenic HAA in tobacco smoke. METHODS: Urinary AαC, used as a marker of AαC exposure, was analyzed on spot urine samples from adult participants of the 2013-2014 cycle of the National Health and Nutrition Examination Survey (N = 1,792). AαC was measured using isotope-dilution liquid chromatography-tandem mass spectrometry. Exclusive combusted tobacco smokers were differentiated from nonusers of tobacco products through both self-report and serum cotinine data. RESULTS: Among exclusive smokers, sample-weighted median urinary AαC was 40 times higher than nonusers. Sample-weighted regression models showed that urinary AαC increased significantly with serum cotinine among both exclusive tobacco users and nonusers with secondhand smoke exposure. Among nonusers, eating beef cooked at high temperature was associated with a significant increase in urinary AαC, whereas consuming vegetables was associated with decreased AαC. In addition, smoking one-half pack of cigarettes per day was associated with a significant increase of 23.6 pg AαC/mL calculated at geometric mean of AαC, controlling for potential confounders. In comparison, increase in AαC attributable to consuming the 99th percentile of beef cooked at high temperature was 0.99 pg AαC/mL. CONCLUSIONS: Both exclusive smokers and nonusers of tobacco in the general U.S. population are exposed to AαC from tobacco smoke, with additional, lesser contributions from certain dietary components. IMPACT: AαC is an important biomarker that is associated with tobacco smoke exposure.

Environmental Tobacco Smoke Exposure in Relation to Family Characteristics, Stressors and Chemical Co-Exposures in California Girls.

Childhood environmental tobacco smoke (ETS) exposure is a risk factor for adverse health outcomes and may disproportionately burden lower socioeconomic status groups, exacerbating health disparities. We explored associations of demographic factors, stressful life events, and chemical co-exposures, with cotinine levels, among girls in the CYGNET Study. Data were collected from families of girls aged 6-8 years old in Northern California, through clinic exams, questionnaires and biospecimens (n = 421). Linear regression and factor analysis were conducted to explore predictors of urinary cotinine and co-exposure body burdens, respectively. In unadjusted models, geometric mean cotinine concentrations were higher among Black (0.59 ug/g creatinine) than non-Hispanic white (0.27), Asian (0.32), or Hispanic (0.34) participants. Following adjustment, living in a rented home, lower primary caregiver education, and lack of two biologic parents in the home were associated with higher cotinine concentrations. Girls who experienced parental separation or unemployment in the family had higher unadjusted cotinine concentrations. Higher cotinine was also associated with higher polybrominated diphenyl ether and metals concentrations. Our findings have environmental justice implications as Black and socio-economically disadvantaged young girls experienced higher ETS exposure, also associated with higher exposure to other chemicals. Efforts to reduce ETS and co-exposures should account for other disparity-related factors.

Biomarkers of Exposure among U.S. Adult Cigar Smokers: Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

BACKGROUND: Given the diverse cigar market and limited data on biomarker patterns by cigar type, we compared biomarkers of nicotine and tobacco toxicants among cigar smokers and other groups. METHODS: Using Wave 1 urinary biomarker data from 5,604 adults in the Population Assessment of Tobacco and Health (PATH) Study, we compared geometric mean concentrations among cigar-only smokers (all cigars and separately for traditional, cigarillo, and filtered cigars), cigarette-only smokers, dual cigar/cigarette smokers, and never users of tobacco. We calculated geometric mean ratios comparing groups with never users adjusting for sex, age, race/ethnicity, education and creatinine. RESULTS: Some day cigar-only smokers had lower biomarker concentrations than every day cigar-only smokers, but higher than never users. Every day cigar-only smokers (n = 61) had lower TNE-2 (cotinine+trans-3'-hydroxycotinine) compared to every day cigarette-only (n = 2217; P < 0.0001) and dual cigar/cigarette smokers (n = 601; P < 0.0001). Several biomarkers, including NNAL (NNK metabolite) and CYMA (metabolite of acrylonitrile), were comparable in these groups. In exploratory analyses, every day filtered cigar-only (n = 7) smokers had higher biomarker concentrations compared with every day traditional cigar-only smokers (n = 12) and cigarillo-only smokers (n = 24). Every day smokers of each cigar type were similar to exclusive cigarette smokers. For some biomarkers, particularly for every day filtered cigar-only smokers, concentrations were higher. CONCLUSIONS: For some biomarkers, every day cigar-only smokers were comparable with every day cigarette-only smokers. Exploratory analyses suggest that biomarkers vary by cigar type with every day filtered cigar-only smokers having the highest concentrations. IMPACT: High exposure to harmful constituents among cigar smokers is a continuing health issue.

Urinary Biomarkers of Carcinogenic Exposure among Cigarette, Waterpipe, and Smokeless Tobacco Users and Never Users of Tobacco in the Golestan Cohort Study.

BACKGROUND: How carcinogen exposure varies across users of different, particularly noncigarette, tobacco products remains poorly understood. METHODS: We randomly selected 165 participants of the Golestan Cohort Study from northeastern Iran: 60 never users of any tobacco, 35 exclusive cigarette, 40 exclusive (78% daily) waterpipe, and 30 exclusive smokeless tobacco (nass) users. We measured concentrations of 39 biomarkers of exposure in 4 chemical classes in baseline urine samples: tobacco alkaloids, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC). We also quantified the same biomarkers in a second urine sample, obtained 5 years later, among continuing cigarette smokers and never tobacco users. RESULTS: Nass users had the highest concentrations of tobacco alkaloids. All tobacco users had elevated TSNA concentrations, which correlated with nicotine dose. In both cigarette and waterpipe smokers, PAH and VOC biomarkers were higher than never tobacco users and nass users, and highly correlated with nicotine dose. PAH biomarkers of phenanthrene and pyrene and two VOC metabolites (phenylmercapturic acid and phenylglyoxylic acid) were higher in waterpipe smokers than in all other groups. PAH biomarkers among Golestan never tobacco users were comparable to those in U.S. cigarette smokers. All biomarkers had moderate to good correlations over 5 years, particularly in continuing cigarette smokers. CONCLUSIONS: We observed two patterns of exposure biomarkers that differentiated the use of the combustible products (cigarettes and waterpipe) from the smokeless product. Environmental exposure from nontobacco sources appeared to contribute to the presence of high levels of PAH metabolites in the Golestan Cohort. IMPACT: Most of these biomarkers would be useful for exposure assessment in a longitudinal study.

Exposure to Secondhand Smoke Among Nonsmokers - United States, 1988-2014.

Exposure to secondhand smoke from burning tobacco products can cause sudden infant death syndrome, respiratory infections, ear infections, and asthma attacks in infants and children, and coronary heart disease, stroke, and lung cancer in adult nonsmokers (1). There is no risk-free level of secondhand smoke exposure (2). CDC analyzed questionnaire and laboratory data from the National Health and Nutrition Examination Survey (NHANES) to assess patterns of secondhand smoke exposure among U.S. nonsmokers. The prevalence of secondhand smoke exposure among U.S. nonsmokers declined substantially during 1988-2014, from 87.5% to 25.2%. However, no change in exposure occurred between 2011-2012 and 2013-2014, and an estimated one in four nonsmokers, or approximately 58 million persons, were still exposed to secondhand smoke during 2013-2014. Moreover, marked disparities persisted across population groups. Exposure prevalence was highest among nonsmokers aged 3-11 years (37.9%), non-Hispanic blacks (50.3%), and those who were living in poverty (47.9%), in rental housing (38.6%), or with someone who smoked inside the home (73.0%), or among persons who had less than a high school education (30.7%). Comprehensive smoke-free laws and policies for workplaces and public places and smoke-free rules for homes and vehicles can further reduce secondhand smoke exposure among all nonsmokers.