Table S1. Urinary BOEs in PATH Study Wave 1. Table S2. Urinary BOEs of Nicotine Metabolites in PATH Study Wave 1. Table S3. Urinary BOEs of TSNAs in PATH Study Wave 1. Table S4. Urinary BOEs of PAHs in PATH Study Wave 1. Table S5. Urinary BOEs of VOCs in PATH Study Wave 1. Table S6. Urinary BOEs of Metals in PATH Study Wave 1. Table S7. Urinary BOEs of Arsenic in PATH Study Wave 1.

INTRODUCTION:Flavored non-cigarette tobacco product use is widespread in the U.S. The availability of flavor options could be playing a role in recent increases in use, especially for non-cigarette tobacco products, among youth and young adults. Little is known about specific flavor preferences of youth and adult flavored tobacco product users, as well as how preferences may change over time. METHODS:This study analyzes PATH Study data from completed Wave 2 (2014-2015) and Wave 3 (2015-2016) youth (12-17 years), and adult (18 + years) interviews to estimate the prevalence of flavored non-cigarette tobacco product use. We assess flavor switching by examining changes between flavors and characteristics of those who changed flavors between waves. RESULTS:Across age groups, and at both waves, fruit-flavored products were the most frequently used flavor by past 30-day electronic nicotine delivery systems (ENDS), cigar, cigarillo, and hookah users. In the past 30 days, a higher proportion of youth and young adults used candy/sweets-flavored ENDS than adults. Among adult ENDS users, the odds of changing flavors were highest among younger users and decreased with increasing age. CONCLUSIONS:Flavored tobacco product use is prevalent across non-cigarette tobacco products. Stability in the number of flavors used, as well as specific flavors, is higher among adult tobacco users, while the use of multiple flavors, and change in specific flavor, is more prevalent among youth tobacco users. Additional longitudinal research can further examine the role flavors play in appeal, product trial, and switching.

INTRODUCTION:Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS:We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS:Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS:In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS:With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure.

Background: Former smokers who currently use e-cigarettes have lower concentrations of biomarkers of tobacco toxicant exposure than current smokers. It is unclear whether tobacco toxicant exposure reductions may lead to health risk reductions. Methods: We compared inflammatory biomarkers (high-sensitivity C-reactive protein, IL6, fibrinogen, soluble intercellular adhesion molecule-1) and an oxidative stress marker (F2-isoprostane) among 3,712 adult participants in Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study by tobacco user groups: dual users of cigarettes and e-cigarettes; former smokers who currently use e-cigarettes-only; current cigarette-only smokers; former smokers who do not currently use any tobacco; and never tobacco users. We calculated geometric means (GM) and estimated adjusted GM ratios (GMR). Results: Dual users experienced greater concentration of F2-isoprostane than current cigarette-only smokers [GMR 1.09 (95% confidence interval, CI, 1.03-1.15)]. Biomarkers were similar between former smokers who currently use ecigarettes and both former smokers who do not use any tobacco and never tobacco users, but among these groups most biomarkers were lower than those of current cigarette-only smokers. The concentration of F2-isoprostane decreased by time since smoking cessation among both exclusive e-cigarette users (P-trend = 0.03) and former smokers who do not currently use any tobacco (P-trend = 0.0001). Conclusions: Dual users have greater concentration of F2-isoprostane than smokers. Exclusive e-cigarette users have biomarker concentrations that are similar to those of former smokers who do not currently use tobacco, and lower than those of exclusive cigarette smokers. Impact: This study contributes to an understanding of the health effects of e-cigarettes.

Marijuana remains one of the most commonly used psychoactive substances across the globe, yet conclusive evidence about the toxic effects resulting from its exposure is still insufficient. The dearth of high-quality information specific to the toxic effects and thus, potential health implications of marijuana use and related exposures, constitute a critical research need given the emerging liberalization and increasing rates of marijuana use (Glantz et al., 2018 [1]; Hall and Degenhardt, 2009). Marijuana is most commonly smoked, is widely viewed as being less harmful compared to tobacco (Padilla et al., 2014 [3]), and now ranks as the world's second most-popular combustible product following tobacco cigarettes (UNODC, 2018; Murray et al., 2007 [5]; Wei et al., 2016, 2018). Within this context, it is anticipated that the general population's exposure to secondhand marijuana smoke (SHMS) is likely to increase (Wang et al., 2016 [8]). In this chapter, we present an overview of the existing evidence regarding occurrences, biological analyses, and potential adverse health effects of SHMS exposure. We focus our discussion on the recent progress in biomonitoring approaches utilized for assessing SHMS exposure, including selection of biological matrices and exposure biomarkers, and development of the bio-analytical assays. We highlight the challenges that require consideration when interpreting SHMS biomonitoring data in exposure assessments, and provide some suggested directions for future research.

Background: Smoking cannabis may potentially increase exposure to numerous toxic chemicals that are commonly associated with tobacco use. There is a paucity of data related to toxicant exposures among concurrent users of tobacco and cannabis (co-users). Methods: Data are from the Population Assessment of Tobacco and Health Study Wave 1 Biomarker Restricted-Use Files. Analyses focused on adults who provided urine samples (N = 5859). Urine samples were analyzed for biomarkers of exposure to nicotine, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, and volatile organic compounds. Using weighted linear regression, we compared adjusted geometric mean concentrations of 15 biomarkers between user groups of various tobacco product types according to their self-reported past 30-day cannabis use. Results: Past 30-day cannabis use was similar across various types of tobacco product use subgroups (range: 13%-23%) and significantly more common compared to non-tobacco users (1.0%; p < .001). Across all groups of tobacco users, those who co-used cannabis exhibited significantly higher concentrations of the biomarker of exposure to acrylonitrile (CYMA) compared to noncannabis users (by 39%-464%). Tobacco-cannabis co-users also showed significantly elevated levels of the biomarker of exposure to acrylamide (AAMA) compared to exclusive tobacco users, and significantly higher exposure to many polycyclic aromatic hydrocarbons (including fluorene and pyrene). Conclusions: Co-users exhibited higher concentrations for biomarkers of exposure to many combustion byproducts, compared to exclusive tobacco users. More robust measurements of cannabis use can address potential confounding in assessments of exposures to tobacco-related constituents, and potential health effects resulting from co-use. Implications: With disproportionately greater rates of cannabis use occurring among tobacco users, it is critical to consider how concurrent cannabis use may influence health-related outcomes among smokers. Our findings suggest potential additive toxicant exposures among co-users of tobacco and cannabis. Lack of consideration and measurement of cannabis use in assessing tobacco-related exposures may confound estimates thought to be attributable to tobacco, particularly for non-specific biomarkers. Assessing tobacco and cannabis use in tandem will allow for more precise measurement of outcomes related to one or both substances, and can provide additional information on potential health effects related to co-use.

ImportanceThe prevalence of electronic nicotine delivery systems (ENDS) use, including e-cigarettes, among US young adults (YAs) has raised questions about how these products may affect future tobacco and nicotine use among YAs. Given this prevalence and that young adulthood is a critical period for the establishment of tobacco and nicotine use, it is important to consider the association between ENDS use and cigarette smoking specifically in this age group.ObjectiveTo examine whether ENDS use frequency or intensity is associated with changes in cigarette smoking among US YA ever smokers during 1 year.Design, Setting, and ParticipantsThis cohort study used 3 waves of data (2013-2014, 2014-2015, and 2015-2016) from the Population Assessment of Tobacco and Health (PATH) Study, an ongoing longitudinal cohort study of adults and youth. Unweighted 1:6 propensity score matching was used to match participants on wave 1 risk factors for ENDS use at wave 2. The changes in smoking between wave 2 and wave 3 were assessed using the matched sample. In total, 1096 ENDS-naive, ever cigarette–smoking YAs (18-24 years of age) at wave 1 who participated in wave 2 and wave 3 and who had complete data in the PATH Study were included in the analyses, which were conducted from August 2018 to October 2019.ExposuresNever ENDS use (n = 987), any previous 30-day ENDS use (n = 109), 1 to 5 days of ENDS use in the previous 30 days (n = 75), and 6 or more days ENDS use in the previous 30 days at wave 2 (n = 34).Main Outcomes and MeasuresThe analytic sample was selected using multiple variables based on peer-reviewed literature supporting associations with ENDS use. The main outcomes—changes in cigarette smoking behavior between wave 2 and wave 3—were defined using 2 measures: (1) change in smoking frequency, defined as the number of smoking days in the previous 30 days at wave 3 vs wave 2, and (2) change in smoking intensity, defined as the number smoking days in the previous 30 days multiplied by the mean number of cigarettes consumed on smoking days at wave 3 vs wave 2.ResultsThe present cohort analyses included 1096 YA ever smokers who were ENDS naive at wave 1. The majority of the sample were women (609 [55.6%]) and White individuals (698 [63.7%]), and the mean (SD) age was 21.4 (1.9) years. In wave 1, 161 YAs (14.7%) were daily smokers in the previous 30 days. After propensity score matching, no statistically significant associations were observed between any definition of wave 2 ENDS use and changes in either the frequency or intensity of smoking at wave 3.Conclusions and RelevanceIn this cohort study of US YA ever smokers, ENDS use was not associated with either decreased or increased cigarette smoking during a 1-year period. However, it is possible that the rapidly evolving marketplace of vaping products may lead to different trajectories of YA cigarette and ENDS use in the future.

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.

OBJECTIVES:To examine: (1) How perceptions of harm for seven non-cigarette tobacco products predict subsequent use; (2) How change in use is associated with changes in perceptions of product harm; (3) Whether sociodemographic variables moderate the association between perceptions and use. METHODS:Data are from the adult sample (18+) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative longitudinal cohort survey conducted September 2013-December 2014 (Wave 1 (W1) n = 32,320) and October 2014-October 2015 (Wave 2 (W2) n = 28,362). RESULTS:Wave 1 users and non-users of e-cigarettes, filtered cigars, cigarillos, and pipes, who perceived these products as less harmful had greater odds of using the product at W2. For the other products, there was an interaction between W1 perceived harm and W1 use status in predicting W2 product use. At W2, a smaller percentage of U.S. adults rated e-cigarettes as less harmful than cigarettes compared to W1 (41.2% W1, 29.0% W2). Believing non-cigarette products to be less harmful than cigarettes was more strongly associated with subsequent product use in the oldest age group (55+ years) while weaker effects were observed in the youngest age group (18-24 years). This moderating effect of age was significant for e-cigarettes, hookah, traditional cigars, and cigarillos. CONCLUSIONS:Strategies to prevent initiation and promote cessation of these products may benefit from understanding and addressing perceptions of these products.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Impact: 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.

Background: Smoke-free air policies exist to protect users and nonusers from exposure to tobacco smoke. Although electronic nicotine delivery systems (ENDS) may expose passerby to nicotine and particulate matter, few US states regulate indoor use of ENDS. The purpose of this study was to investigate reported rationales for ENDS use and reported ENDS use in public smoke-free places by dual cigarette/ENDS users. Methods: A population of ENDS/cigarette co-users (n = 2051) was drawn from Wave 2 of the Population Assessment of Tobacco and Health (PATH) dataset (2014–2015). Harm reduction beliefs and cessation behavior of co-users were investigated as predictors of ENDS use in public smoke-free places using logistic regression. Results: Fifty-eight percent of dual users reported past 30-day ENDS use in public smoke-free places. Reported use of ENDS to cut down on cigarette smoking (OR: 2.38, 95% CI: 1.86, 3.05), as an alternative to quitting tobacco (OR: 1.71, 95% CI: 1.37, 2.13), or because of belief that ENDS help people to quit cigarettes (OR: 1.52, 95% CI: 1.20, 1.92) were significantly associated with increased odds of ENDS use in smoke-free places. Conclusions: Beliefs that ENDS were useful as cessation tools or posed modified risk to users and nonusers were associated with elevated odds of use ENDS in locations where conventional tobacco is prohibited. Due to limitations in the survey instrument, in-home ENDS use could not be directly assessed in this analysis. However, these self-reported findings suggest that use of ENDS in public places where cigarette use is prohibited is prevalent enough to be of concern for future regulation and enforcement efforts.

BACKGROUND AND AIMS:The prevalence of hookah smoking has increased in the United States since at least 2010, especially among youth and young adults. This study assessed self-reported reasons for hookah smoking cessation and transition to or maintenance of high-frequency hookah smoking among current hookah smokers. DESIGN:Separately analyzed data from the Population Assessment of Tobacco and Health (PATH) study, a longitudinal cohort study. Frequency of and reasons for hookah smoking were ascertained at wave 1 (2013-14); frequency of hookah smoking and past-year cessation were ascertained at wave 2 (2014-15). Weighted multivariable logistic and ordinal logistic regression models were fitted to predict hookah smoking cessation and frequency of hookah smoking at wave 2, respectively, accounting for demographic and behavioral risk factors, reasons for hookah smoking and frequency of hookah smoking at wave 1. SETTING:United States. PARTICIPANTS:A total of 693 youth and 4400 adult past-year hookah smokers. MEASUREMENTS:Self-reported tobacco-use patterns and associated health behaviors were measured via audio computer-assisted self-interviews (ACASI). FINDINGS:At wave 1, 5.9% of youth and 7.5% of adults were past-year hookah smokers. Among all age groups, the leading reasons for hookah smoking were enjoyment of socializing while smoking, the availability of appealing flavors and believing that it was less harmful than cigarette smoking. The odds of cessation were lower for adults who liked hookah flavors [adjusted odds ratio (aOR) = 0.40; 95% confidence interval (CI) = 0.26-0.62] compared with adults who did not like hookah flavors. The odds of transitioning to, or maintaining, monthly or more frequent hookah smoking at wave 2, compared with cessation or less than monthly smoking, were higher for adults who liked hookah flavors [adjusted proportional odds ratio (aPOR) = 2.10; 95% CI = 1.48-2.99 and enjoyed socializing while smoking hookah (aPOR = 1.82; 95% CI =1.13-2.94) compared with adults who did not like hookah flavors or socializing. CONCLUSION:The availability of appealing flavors, affordability and socialization while smoking hookah in the United States are associated with reduced likelihood of cessation and increased likelihood of high-frequency hookah smoking.

BACKGROUND:After North Carolina (NC) fire inspectors detected unsafe carbon monoxide (CO) levels inside several waterpipe cafés, the state fire code was amended to include provisions regulating waterpipe cafés, adding a requirement for air ventilation. These regulations apply to new buildings constructed after 1 January 2016, but can be enforced for older buildings where there exists a distinct hazard to life. We measured air quality at a sample of waterpipe cafés before and after the starting date of this regulation and collected information on presence of air ventilation.METHODS:Air quality (CO, fine particulate matter (PM2.5)) monitoring was conducted inside and outside of six waterpipe cafés in NC in September of 2015 (time 1) and September of 2016 (time 2). In addition, questionnaires were administered to managers from each waterpipe café at time 2 to determine the presence of air ventilation systems.RESULTS:Elevated levels of CO and PM2.5 were found inside waterpipe cafés at time 1 (median CO=42 ppm; median PM2.5=379.3 µg/m3) and time 2 (median CO=65 ppm; median PM2.5=484.0 µg/m3), with no significant differences between time periods (p>0.05). Indoor levels were significantly higher than levels outside cafés at both time periods (p<0.05). All waterpipe cafés reported having an air ventilation system that was installed prior to time 1 air monitoring.CONCLUSIONS:Unsafe levels of CO and PM2.5 were observed in waterpipe cafés in NC, despite reported use of air ventilation systems. Prohibiting indoor waterpipe smoking may be necessary to ensure clean air for employees and patrons.

In the US, youth attribute higher levels of harm and addictiveness to cigarettes relative to other tobacco products. Monitoring harm perceptions across a range of tobacco products is important when forecasting risk for experimentation. This study examined data from US youth (N = 10,081) ages 12-17 from the Population Assessment of Tobacco and Health (PATH) Study who completed both Wave 1 (2013-2014) and Wave 2 (2014-2015) interviews. Analyses assessed: (1) trends in perceived harm and addictiveness of products over time, (2) whether perceived harm and addictiveness of a product at Wave 1 predicted trying that product for the first time by Wave 2, and (3) whether trying a product between Waves 1 and 2 predicted a decrease in one's perceived harm and addictiveness of that product. Levels of perceived harmfulness and addictiveness significantly increased between Wave 1 and Wave 2 for all products (chi(2) (range): 7.8-109.2; p's <= 0.02). Compared to those with "high" perceived harmfulness of a tobacco product at Wave 1, those with "low" and "medium" perceived harmfulness had a significantly increased probability of use of that product at Wave 2. For all products, Wave 1 youth never tobacco users who tried a product (vs. did not) at Wave 2 had a significantly higher probability of being in the "low" category of perceived harmfulness at Wave 2. Among US youth, there is a bidirectional relationship between harm perceptions and product use. Understanding how changes in perceptions translate to changes in tobacco use could inform efforts to prevent tobacco initiation in youth.

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.

Background Evidence is accumulating that youth who try Electronic Nicotine Delivery Systems (ENDS, e-cigarettes) may go on to try cigarettes. This analysis examines the bidirectional patterns of ENDS and cigarette use among US youth over one year and uses propensity score matching (PSM) to examine frequency of ENDS use on changes in cigarette smoking. Methods Our analysis included 11996 participants who had two waves of available data (Wave 1 [W1] 2013-2014; Wave 2 [W2] 2014-2015) drawn from the longitudinal Population Assessment of Tobacco and Health Study. Cross-sectional weighted prevalence estimates are reported for cigarettes and ENDS. We used PSM to estimate the likelihood of ENDS use at W1 and to draw matched analytic samples, then used regression (logistic or linear) models to examine the effect of W1 ENDS use on W2 cigarette smoking. All statistical tests were two-sided. Results In weighted analyses, 69.3% of W1 past-30-day cigarette smokers exhibited past-30-day smoking at W2; 42.2% of W1 past-30-day ENDS users were using ENDS at W2. W1 ever use of either product was similarly associated with W2 new use of the other product. Unweighted PSM models indicated W1 cigarette-naive ENDS use was associated with W2 ever-cigarette smoking (n=676; adjusted odds ratio=3.21, 95% confidence interval [CI]=1.95 to 5.45, P<.001); W1 ever-ENDS use did not affect change in cigarette frequency at W2 (n=1020, beta=0.31, 95% CI=-0.76 to 1.39, P=.57); 1-5days ENDS use compared with ever, no past-30-day ENDS use was associated with a statistically significant decrease of W2 smoking days (n=256, beta=-2.64, 95% CI=-4.96 to -0.32; P=.03); and W1 6+ day ENDS users did not show a decrease in frequency of cigarette smoking. Conclusions Ever-ENDS use predicts future cigarette smoking, and frequency of ENDS use has a differential impact on subsequent cigarette smoking uptake or reduction. These results suggest that both cigarettes and ENDS should be targeted in early tobacco prevention efforts with youth.

IMPORTANCE Use of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product users. OBJECTIVES To estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users. DESIGN, SETTING, AND PARTICIPANTS A population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N = 5105). EXPOSURES The primary exposure was tobacco use, including current exclusive e-cigarette users (n = 247), current exclusive cigarette smokers (n = 2411), and users of both products (dual users) (n = 792) compared with never tobacco users (n = 1655). MAIN OUTCOMES AND MEASURES Geometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). RESULTS Of the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure. CONCLUSIONS AND RELEVANCE Exclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.

Evaluating the safety of e-cigarettes and making informed judgement about developing potential standards require sufficient scientific evidence. Since e-cigarettes are highly engineered products containing plastic, glass and metal parts, and e-liquids are largely different matrices, many toxic compounds which are not typical hazards for the users of combustible tobacco products (e.g., cigarettes), could exist in e-liquids, and consequently, posing potential health risk to e-cigarette users. We combined the measurements of urinary metabolites of organophosphate flame retardants (OPFRs) with questionnaire data collected in the National Health and Nutrition Examination Surveys (NHANES) from 2013 to 2014, and we compared adjusted geometric means (GM) for each biomarker in e-cigarette users with levels in non-users and users of various tobacco products using multiple regression analyses to adjust for potential confounders. We found diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) were detected in all e-cigarette users. The adjusted GM of BCEP, the metabolite of tris(2-chloroethyl) phosphate (TCEP), was 81% higher than nonusers (p = 0.0124) and significantly higher than those for both cigarette and cigar users (p < 0.05). The findings in this pilot study suggest that certain OPFRs may present in e-cigarettes as contaminants, and consequently, resulting in higher exposure levels in e-cigarette users compared to nonusers. As we only identified 14 e-cigarette users in the survey, the findings in this study need to be confirmed in future study at a larger scale. A better examination of the types and levels of FRs and their potential contamination sources in e-cigarettes is also needed.