2020 design and methods of the Population Assessment of Tobacco and Health (PATH) study during the COVID-19 pandemic.

The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative, longitudinal study of the US population on tobacco use and its effects on health, collecting data annually since 2013. The COVID-19 pandemic interrupted in-person survey data collections around the world. In the USA, this included a PATH Study data collection focused on youth (13-17) and young adults (18-19) as well as other US surveys on tobacco use. Given that it was necessary to pause data collection and considering that tobacco-use behaviours could be expected to change along with pandemic-related changes in the social environment, the original design for the 2020 PATH Study data collection for youth and young adults was modified. Also, the PATH Study Adult Telephone Survey was developed to address the need for adult tobacco use monitoring in this unprecedented time. This article describes the modifications made to the 2020 PATH Study design and protocol to provide nationally representative data for youth and adults after the onset of the COVID-19 pandemic as well as the implications of these modifications for researchers.

Update to the design and methods of the PATH Study, Wave 4 (2016-2017).

The Population Assessment of Tobacco and Health (PATH) Study is a nationally representative study of the US population on tobacco use and its effects on health, with four waves of data collection between 2013 and 2017. Prior work described the methods of the first three waves. In this paper, we describe the methods of Wave 4, during which a replenishment sample was added to the ongoing cohort. We describe the design and estimation methods of the continuing Wave 1 cohort (with four waves of data) and the Wave 4 cohort (the new cohort created at Wave 4). We provide survey quality metrics, including response rates for both cohorts and a panel conditioning analysis, and guidance on understanding the target populations for both cohorts.

Association between tobacco product use and asthma among US adults from the Population Assessment of Tobacco and Health (PATH) Study waves 2-4.

BACKGROUND: Research on cigarettes and adult asthma offers mixed findings, perhaps due to overlap with chronic obstructive pulmonary disease (COPD) and inadequate adjustment for other smoke exposures. Associations between other tobacco products, including e-cigarettes, and asthma are also understudied. RESEARCH QUESTION: Using Population Assessment of Tobacco and Health Study waves 2-4 (2014/2015-2016/2017) data, we assessed the relation between tobacco product use and asthma in persons unlikely to have COPD. STUDY DESIGN AND METHODS: Prospective study of 10 267 adults aged 18-39 years without COPD diagnoses. Past-month tobacco use at wave 2 was modelled first as combustible versus non-combustible use and second as specific product categories (former, cigarettes, e-cigarettes, cigars, hookah, smokeless tobacco). Outcomes included lifetime asthma prevalence at wave 2, incidence (waves 3 and 4) and Asthma Control Test score (lower=worse). Multivariable regressions adjusted for predictors of asthma, including other smoke exposures: cigarette pack-years, secondhand smoke and marijuana use. Sensitivity analyses examined findings when persons >39 years and those with both COPD and asthma were added, and when smoke exposure adjustments were removed. RESULTS: No product, including cigarettes and e-cigarettes, was associated with prevalence or incidence of asthma. Among people with asthma at wave 2, combustible tobacco (beta=-0.86, 95% CI (-1.32 to -0.39)) and cigarettes (beta=-1.14, 95% CI (-1.66 to -0.62)) were associated with worse asthma control. No tobacco product was associated with asthma control over time. In sensitivity analyses, tobacco use became associated with incident asthma as adults >39 years and those with asthma+COPD were added, and as adjustments for other smoke exposures were omitted. INTERPRETATION: Although cigarette use was associated with worse asthma control, there were no longitudinal associations between combustible tobacco or e-cigarette use and new onset or worsening asthma in these preliminary analyses. Research on tobacco and asthma should exclude COPD and adjust for smoking history and other smoke exposures.

Variability in Urinary Nicotine Exposure Biomarker Levels Between Waves 1 (2013-2014) and 2 (2014-2015) in the Population Assessment of Tobacco and Health Study.

INTRODUCTION: To date, no studies have evaluated the consistency of biomarker levels in people who smoke over a long-time period in real-world conditions with a large number of subjects and included use behavior and measures of nicotine metabolism. We evaluated the variability of biomarkers of nicotine exposure over approximately a 1-year period in people who exclusively smoke cigarettes, including intensity and recency of use and brand switching to assess impact on understanding associations with product characteristics. AIMS AND METHODS: Multivariate regression analysis of longitudinal repeated measures of urinary biomarkers of nicotine exposure from 916 adults in the Population Assessment of Tobacco and Health (PATH) Study with demographic characteristics and use behavior variables. Intraclass correlation coefficients (ICCs) were calculated to examine individual variation of nicotine biomarkers and the uncertainty of repeat measures at two time points (Waves 1 and 2). RESULTS: Age, race, and urinary creatinine were significant covariates of urinary cotinine. When including use behavior, recency, and intensity of use were highly significant and variance decreased to a higher extent between than within subjects. The ICC for urinary cotinine decreased from 0.7530 with no use behavior variables in the model to 0.5763 when included. Similar results were found for total nicotine equivalents. CONCLUSIONS: Urinary nicotine biomarkers in the PATH Study showed good consistency between Waves 1 and 2. Use behavior measures such as time since last smoked a cigarette and number of cigarettes smoked in the past 30 days are important to include when assessing factors that may influence biomarker concentrations. IMPLICATIONS: The results of this study show that the consistency of the nicotine biomarkers cotinine and total nicotine equivalents in spot urine samples from Waves 1 to 2 of the PATH Study is high enough that these data are useful to evaluate the association of cigarette characteristics with biomarkers of exposure under real-world use conditions.

Predictors of E-cigarette and Cigarette Use Trajectory Classes from Early Adolescence to Emerging Adulthood Across Four Years (2013-2017) of the PATH Study.

INTRODUCTION: This study examines predictors of trajectories of cigarette and e-cigarette use among a cohort of US adolescents transitioning into young adulthood. Comparing trajectories of each tobacco product is important to determine if different intervention targets are needed to prevent progression to daily use. METHODS: Latent trajectory class analyses identified cigarette and e-cigarette use (never, ever excluding past 12-month, past 12-month (excluding past 30-day (P30D)), P30D 1-5 days, P30D 6+ days) trajectory classes, separately, among US youth (12-17; N = 10,086) using the first 4 waves (2013-2017) of data from the nationally representative PATH Study. Weighted descriptive analyses described the class characteristics. Weighted multinomial logistic regression analyses examined demographic, psychosocial, and behavioral predictors of class membership. RESULTS: Younger adolescents 12-15 years had lower tobacco use compared to 16-17 year olds and less stable classes. In the 16-17 year group, there were five unique trajectories of cigarette smoking, including a Persistent High Frequency class. Four e-cigarette use trajectories were identified; but not a persistent use class. Shared predictors of class membership for cigarettes and e-cigarettes included mental health problems, other tobacco use, marijuana use, and poorer academic achievement. Male sex and household tobacco use were unique e-cigarette trajectory class predictors. CONCLUSIONS: There was no evidence that initiation with e-cigarettes as the first product tried was associated with cigarette progression (nor cigarettes as first product and e-cigarette progression). Interventions should focus on well-established risk factors such as mental health and other substance use to prevent progression of use for both tobacco products. IMPLICATIONS: Using nationally representative data and definitions of use that take into account frequency and recency of use, longitudinal 4-year trajectories of e-cigarette and cigarette use among US adolescents transitioning into young adulthood were identified. Results among 16-17-year olds revealed a class of persistent high frequency cigarette smoking that was not identified for e-cigarette use. Cigarette use progression was not associated with e-cigarettes as the first product tried. Risk factors for progression of use of both products included mental health and other substance use, which are important prevention targets for both tobacco products.

Correlates of tobacco product initiation among youth and young adults between waves 1-4 of the population assessment of tobacco and Health (PATH) study (2013-2018).

INTRODUCTION: While risk factors for cigarette smoking among youth and young adults are well-documented, less is known about the correlates of initiation of other tobacco products. This study aims to provide estimates and correlates of initiation among U.S. youth and young adults. METHODS: Data on youth aged 12-17 (n = 10,072) and young adults aged 18-24 (N = 5,727) who provided information on cigarettes, electronic nicotine delivery systems (ENDS), cigars, pipe, hookah and smokeless tobacco use in Wave 1 (W1: 2013-2014)-Wave 4 (W4: 2016-2018) of the nationally-representative PATH Study were used to calculate ever use initiation and correlates of initiation by W4. RESULTS: Nearly 6 million youth and 2.5 million young adults used tobacco for the first time between W1-W4. Approximately one quarter of youth and young adult ENDS never users initiated ENDS between W1-W4 of the PATH Study. Among youth, use of other tobacco products, ever substance use, and high externalizing problems were associated with initiation of most products. Among young adults, use of other tobacco products and ever substance use were associated with initiation of most products. In both youth and young adults, Hispanics were more likely to initiate hookah use than their non-Hispanic White counterparts. While male sex was a risk factor for most tobacco product initiation across both age groups, it was not associated with hookah initiation. CONCLUSIONS: Cigarette and non-cigarette products shared many correlates of initiation, although there are noteworthy demographic differences. Findings can help tailor product specific interventions to reach populations at risk during preliminary stages of use.

Tobacco Use and Respiratory Symptoms Among Adults: Findings From the Longitudinal Population Assessment of Tobacco and Health (PATH) Study 2014-2016.

INTRODUCTION: We examined the relationship between current tobacco use and functionally important respiratory symptoms. METHODS: Longitudinal cohort study of 16 295 US adults without COPD in Waves 2-3 (W2-3, 2014-2016) of the Population Assessment of Tobacco and Health Study. Exposure-Ten mutually exclusive categories of tobacco use including single product, multiple product, former, and never use (reference). Outcome-Seven questions assessing wheezing/cough were summed to create a respiratory symptom index; cutoffs of ≥2 and ≥3 were associated with functional limitations and poorer health. Multivariable regressions examined both cutoffs cross-sectionally and change over approximately 12 months, adjusting for confounders. RESULTS: All tobacco use categories featuring cigarettes (>2/3's of users) were associated with higher risk (vs. never users) for functionally important respiratory symptoms at W2, for example, at symptom severity ≥ 3, risk ratio for exclusive cigarette use was 2.34 [95% CI, 1.92, 2.85] and for worsening symptoms at W3 was 2.80 [2.08, 3.76]. There was largely no increased symptom risk for exclusive use of cigars, smokeless tobacco, hookah, or e-cigarettes (adjustment for pack-years and marijuana attenuated the cross-sectional e-cigarette association from 1.53(95% CI 0.98, 2.40) to 1.05 (0.67, 1.63); RRs for these products were also significantly lower compared to exclusive use of cigarettes. The longitudinal e-cigarette-respiratory symptom association was sensitive to the respiratory index cutoff level; exclusive e-cigarette use was associated with worsening symptoms at an index cutoff ≥ 2 (RR = 1.63 [1.02, 2.59]) and with symptom improvement at an index cutoff of ≥ 3 (RR = 1.64 [1.04, 2.58]). CONCLUSIONS: Past and current cigarette smoking drove functionally important respiratory symptoms, while exclusive use of other tobacco products was largely not associated. However, the relationship between e-cigarette use and symptoms was sensitive to adjustment for pack-years and symptom severity. IMPLICATIONS: How noncigarette tobacco products affect respiratory symptoms is not clear; some studies implicate e-cigarettes. We examined functionally important respiratory symptoms (wheezing/nighttime cough) among US adults without COPD. The majority of adult tobacco users smoke cigarettes and have higher risk of respiratory symptoms and worsening of symptoms, regardless of other products used with them. Exclusive use of other tobacco products (e-cigarettes, cigars, smokeless, hookah) was largely not associated with functionally important respiratory symptoms and risks associated with their use was significantly lower than for cigarettes. The association for e-cigarettes was greatly attenuated by adjustment for cigarette pack-years and sensitive to how symptoms were defined.

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.

Tobacco Product Use and Functionally Important Respiratory Symptoms Among US Adolescents/Young Adults.

OBJECTIVE: The relation between respiratory symptoms and the range of tobacco product use among US adolescents/young adults is not yet clear. This cross-sectional analysis examines tobacco product use and respiratory symptoms in a nationally representative sample of 21,057 adolescents/young adults aged 12-24 years from Wave 4 (2016-17) of the Population Assessment of Tobacco and Health Study. METHODS: Presence of functionally important respiratory symptoms was defined by questions regarding wheezing and nighttime cough at a cutoff score associated with poorer functional health status. Past-30-day tobacco use was analyzed 2 ways: never-tobacco users (reference) versus combustible users, noncombustible-only users, and former users; or frequency of use of cigarettes and/or e-cigarettes. Weighted Poisson regression adjusted for past-30-day marijuana use, secondhand smoke exposure, and asthma. RESULTS: Functionally important respiratory symptoms were present in 10.0% overall: 13.8% of combustible users, 9.0% of noncombustible users, 8.2% of noncurrent users and 9.7% of never users. Functionally important respiratory symptoms were associated with combustible tobacco use (relative risk [RR] = 1.52[95% CI 1.29, 1.80]), marijuana use (RR = 1.54[1.34, 1.77]) and secondhand smoke exposure (RR = 1.04[1.03, 1.05]). Higher cigarette smoking frequency was also associated with functionally important respiratory symptoms for frequency categories >14 days/month (eg, RR = 1.93[1.50, 2.49] for 15-29 days/month). Frequency of e-cigarette use was not associated with functionally important respiratory symptoms. CONCLUSIONS: During 2016-17, smoking cigarettes, marijuana use, and secondhand smoke exposure were cross-sectionally associated with functionally important respiratory symptoms in adolescents/young adults. Risk increased with increased frequency of cigarette use but not e-cigarette use. Given changes to contemporary e-cigarettes and use, findings may not generalize to newer products.

Changes in Biomarkers of Tobacco Exposure among Cigarette Smokers Transitioning to ENDS Use: The Population Assessment of Tobacco and Health Study, 2013-2015.

Limited data are available for how biomarkers of tobacco exposure (BOE) change when cigarette smokers transition to using electronic nicotine delivery systems (ENDS). Using biomarker data from Waves 1 (2013-2014) and 2 (2014-2015) of the PATH Study, we examined how mean BOE concentrations, including metabolites of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOC) and metals, changed when 2475 adult smokers transitioned to using ENDS or quit tobacco products. Exclusive smokers who transitioned to dual use had a significant decrease in NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), but not nicotine metabolites, most PAHs, metals, or VOCs. Exclusive smokers who became dual users had significant reductions in total nicotine equivalents, NNAL, and 2CyEMA (acrylonitrile metabolite), but only in those who reduced cigarettes per day (CPD) by >=50%. Smokers who transitioned to exclusive ENDS use had significant reductions in most TSNAs, PAHs, and VOCs; however, nicotine metabolites did not decrease in dual users who became exclusive ENDS users. Smokers who quit tobacco use had significant decreases in nicotine metabolites, all TSNAs, most PAHs, and most VOCs. Cigarette smokers who became dual users did not experience significant reductions in most BOEs. Reductions were impacted by changes in CPD. However, transitioning from smoking to no tobacco or exclusive ENDS use was associated with reduced exposure to most BOEs measured. Future analyses could incorporate additional waves of PATH data and examine changes in biomarker exposure by ENDS device type and CPD.

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.

Validation of an Index for Functionally Important Respiratory Symptoms among Adults in the Nationally Representative Population Assessment of Tobacco and Health Study, 2014-2016.

The purpose of this study is to validate the seven-item wheezing module from the International Study of Asthma and Allergies in Children (ISAAC) in the nationally representative Population Assessment of Tobacco and Health Study. Adult participants with complete Wave 2-3 data were selected, including those with asthma but excluding those with COPD and other respiratory diseases (n = 16,295). We created a nine-point respiratory symptom index from the ISAAC questions, assessed the reliability of the index, and examined associations with self-reported asthma diagnosis. Threshold values were assessed for association with functional outcomes. The weighted prevalence for one or more respiratory symptom was 18.0% (SE = 0.5) for adults without asthma, 70.1% (SE = 1.3) for those with lifetime asthma, 75.7% (SE = 3.7) for adults with past-year asthma not on medications, and 92.6% (SE = 1.6) for those on medications. Cronbach's alpha for the respiratory symptom index was 0.86. Index scores of ≥2 or ≥3 yielded functionally important respiratory symptom prevalence of 7-10%, adequate sensitivity and specificity for identifying asthma, and consistent independent associations with all functional outcomes and tobacco use variables. Respiratory symptom index scores of ≥2 or ≥3 are indicative of functionally important respiratory symptoms and could be used to assess the relationship between tobacco use and respiratory health.

Biomarkers of Inflammation and Oxidative Stress among Adult Former Smoker, Current E-Cigarette Users-Results from Wave 1 PATH Study.

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 e-cigarettes 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.

Cardiovascular Risk Factor and Disease Measures from the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: Cardiovascular disease is a key health condition associated with tobacco use; however, clinical measures are not typically possible in population-based studies. In this paper, we assess the reliability and validity of self-reported cardiovascular risk factors and diseases in a large nationally representative study of tobacco use and health outcomes. METHODS: This paper analyzes self-reported cardiovascular risk factors and disease among adults age 40 years and older based on U.S. nationally representative data from the Population Assessment of Tobacco and Health (PATH) Study. Prevalence of cardiovascular risk factors (self-reported high blood pressure, high cholesterol, diabetes and family history of premature heart disease, BMI ≥ 35, and tobacco use) and cardiovascular disease (self-reported heart attack, stroke and/or congestive heart failure (CHF)) were considered along with ratings of physical functioning, fatigue, and general health. RESULTS: Self-reported cardiovascular disease was found to be associated with functional health measures (walking up a flight of stairs) and general ratings of health. Prospective analyses found strong correlations between sequential data collection waves for history of hypertension, elevated cholesterol and CHF, while more modest correlations were noted for stroke and heart attack. The overall prevalence of cardiovascular disease and hypertension was comparable to those from the National Health and Nutrition Examination Survey (NHANES). CONCLUSIONS: These analyses suggest reliability and concurrent validity regarding self-reported cardiovascular risk factors and disease assessed in the PATH Study.

Exposure to Nicotine and Toxicants Among Dual Users of Tobacco Cigarettes and E-Cigarettes: Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

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.

Tobacco-Specific Nitrosamines (NNAL, NNN, NAT, and NAB) Exposures in the US Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

INTRODUCTION: The tobacco-specific nitrosamines (TSNAs) are an important group of carcinogens found in tobacco and tobacco smoke. To describe and characterize the levels of TSNAs in the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014), we present four biomarkers of TSNA exposure: N'-nitrosonornicotine, N'-nitrosoanabasine, N'-nitrosoanatabine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which is the primary urinary metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. METHODS: We measured total TSNAs in 11 522 adults who provided urine using automated solid-phase extraction coupled to isotope dilution liquid chromatography-tandem mass spectrometry. After exclusions in this current analysis, we selected 11 004 NNAL results, 10 753 N'-nitrosonornicotine results, 10 919 N'-nitrosoanatabine results, and 10 996 N'-nitrosoanabasine results for data analysis. Geometric means and correlations were calculated using SAS and SUDAAN. RESULTS: TSNA concentrations were associated with choice of tobacco product and frequency of use. Among established, every day, exclusive tobacco product users, the geometric mean urinary NNAL concentration was highest for smokeless tobacco users (993.3; 95% confidence interval [CI: 839.2, 1147.3] ng/g creatinine), followed by all types of combustible tobacco product users (285.4; 95% CI: [267.9, 303.0] ng/g creatinine), poly tobacco users (278.6; 95% CI: [254.9, 302.2] ng/g creatinine), and e-cigarette product users (6.3; 95% CI: [4.7, 7.9] ng/g creatinine). TSNA concentrations were higher in every day users than in intermittent users for all the tobacco product groups. Among single product users, exposure to TSNAs differed by sex, age, race/ethnicity, and education. Urinary TSNAs and nicotine metabolite biomarkers were also highly correlated. CONCLUSIONS: We have provided PATH Study estimates of TSNA exposure among US adult users of a variety of tobacco products. These data can inform future tobacco product and human exposure evaluations and related regulatory activities.

Association of Electronic Nicotine Delivery System Use With Cigarette Smoking Progression or Reduction Among Young Adults.

Importance: The 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. Objective: To 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 Participants: This 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. Exposures: Never 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 Measures: The 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. Results: The 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 Relevance: In 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.

Role of e-cigarettes and pharmacotherapy during attempts to quit cigarette smoking: The PATH Study 2013-16.

BACKGROUND: More smokers report using e-cigarettes to help them quit than FDA-approved pharmacotherapy. OBJECTIVE: To assess the association of e-cigarettes with future abstinence from cigarette and tobacco use. DESIGN: Cohort study of US sample, with annual follow-up. PARTICIPANTS: US adult (ages 18+) daily cigarette smokers identified at Wave 1 (W1; 2013-14) of the PATH Study, who reported a quit attempt before W2 and completed W3 (n = 2443). EXPOSURES: Use of e-cigarettes, pharmacotherapy (including nicotine replacement therapy), or no product for last quit attempt (LQA), and current daily e-cigarette use at W2. ANALYSIS: Propensity score matching (PSM) of groups using different methods to quit. OUTCOME MEASURES: 12+ months abstinence at W3 from cigarettes and from all tobacco (including e-cigarettes). 30+ days abstinence at W3 was a secondary outcome. RESULTS: Among daily smokers with an LQA, 23.5% used e-cigarettes, 19.3% used pharmacotherapy only (including NRT) and 57.2% used no product. Cigarette abstinence for 12+ months at W3 was ~10% in each group. Half of the cigarette abstainers in the e-cigarette group were using e-cigarettes at W3. Different methods to help quitting had statistically comparable 12+ month cigarette abstinence at W3 (e-cigarettes vs no product: Risk Difference (RD) = 0.01, 95% CI: -0.04 to 0.06; e-cigarettes vs pharmacotherapy: RD = 0.02, 95% CI:-0.04 to 0.09). Likewise, daily e-cigarette users at W2 did not show a cessation benefit over comparable no-e-cigarette users and this finding was robust to sensitivity analyses. Abstinence for 30+ days at W3 was also similar across products. LIMITATIONS: The frequency of e-cigarette use during the LQA was not assessed, nor was it possible to assess continuous abstinence from the LQA. CONCLUSION: Among US daily smokers who quit cigarettes in 2014-15, use of e-cigarettes in that attempt compared to approved cessation aids or no products showed similar abstinence rates 1-2 years later.

Longitudinal pathways of exclusive and polytobacco cigarette use among youth, young adults and adults in the USA: findings from the PATH Study Waves 1-3 (2013-2016).

OBJECTIVE: Cigarettes are the most harmful and most prevalent tobacco product in the USA. This study examines cross-sectional prevalence and longitudinal pathways of cigarette use among US youth (12-17 years), young adults (18-24 years) and adults 25+ (25 years and older). DESIGN: Data were drawn from the first three waves (2013-2016) of the Population Assessment of Tobacco and Health Study, a nationally representative, longitudinal cohort study of US adults and youth. Respondents with data at all three waves (youth, N=11 046; young adults, N=6478; adults 25+, N=17 188) were included in longitudinal analyses. RESULTS: Among Wave 1 (W1) any past 30-day (P30D) cigarette users, more than 60%, persistently used cigarettes across three waves in all age groups. Exclusive cigarette use was more common among adult 25+ W1 P30D cigarette users (62.6%), while cigarette polytobacco use was more common among youth (57.1%) and young adults (65.2%). Persistent exclusive cigarette use was the most common pathway among adults 25+ and young adults; transitioning from exclusive cigarette use to cigarette polytobacco use was most common among youth W1 exclusive cigarette users. For W1 youth and young adult cigarette polytobacco users, the most common pattern of use was persistent cigarette polytobacco use. CONCLUSIONS: Cigarette use remains persistent across time, regardless of age, with most W1 P30D smokers continuing to smoke at all three waves. Policy efforts need to continue focusing on cigarettes, in addition to products such as electronic nicotine delivery systems that are becoming more prevalent.