Multiple Tobacco Product Use Among Youth E-Cigarette Users: National Youth Tobacco Survey, 2020.

PURPOSE: Limited information exists on multiple tobacco product use, particularly among youth. This study assessed the prevalence of current youth use of e-cigarettes with other tobacco products and their associated characteristics using 2020 National Youth Tobacco Survey data. METHODS: Prevalence estimates were calculated for current e-cigarette users, by multiple tobacco product use status and product combination. Demographic characteristics, e-cigarette use behaviors, age at first combustible tobacco use, and tobacco dependence symptoms were compared between current users of both e-cigarettes and combustible tobacco (dual users) and current exclusive e-cigarette users. RESULTS: In 2020, 61.1% of all current e-cigarette users reported exclusive e-cigarette use, and 38.9% used e-cigarettes with other tobacco products. Among those who used e-cigarettes with other tobacco products, 85.0% used combustible tobacco, with cigarettes being the most commonly used other tobacco product. Compared with current exclusive e-cigarette users, higher proportions of dual users reported the following: frequent e-cigarette use; obtaining e-cigarettes from gas stations, persons other than a family member/friend, vape shops, or the internet; and having any tobacco dependence symptoms. Among dual users, 31.2% reported first combustible product use after e-cigarette initiation, and 34.3% reported first combustible product use prior to e-cigarette initiation. DISCUSSION: Approximately four in 10 youth current e-cigarette users reported using multiple tobacco products, with a majority using combustible tobacco. Frequent e-cigarette use and tobacco dependence symptoms were more prevalent among dual users of e-cigarettes and combustible tobacco.

Cardiovascular Outcomes among Combustible-Tobacco and Electronic Nicotine Delivery System (ENDS) Users in Waves 1 through 5 of the Population Assessment of Tobacco and Health (PATH) Study, 2013-2019.

BACKGROUND: Prior studies have not clearly established risk of cardiovascular disease (CVD) among smokers who switch to exclusive use of electronic nicotine delivery systems (ENDS). We compared cardiovascular disease incidence in combustible-tobacco users, those who transitioned to ENDS use, and those who quit tobacco with never tobacco users. METHODS: This prospective cohort study analyzes five waves of Population Assessment of Tobacco and Health (PATH) Study data, Wave 1 (2013-2014) through Wave 5 (2018-2019). Cardiovascular disease (CVD) incidence was captured over three intervals (Waves 1 to 3, Waves 2 to 4, and Waves 3 to 5). Participants were adults (40+ years old) without a history of CVD for the first two waves of any interval. Change in tobacco use status, from exclusive past 30 day use of any combustible-tobacco product to either exclusive past 30 day ENDS use, dual past 30 day use of ENDS and combustible-tobacco, or no past 30 day use of any tobacco, between the first two waves of an interval was used to predict onset of CVD between the second and third waves in the interval. CVD incidence was defined as a new self-report of being told by a health professional that they had congestive heart failure, stroke, or a myocardial infarction. Generalized estimating equation (GEE) analyses combined 10,548 observations across intervals from 7820 eligible respondents. RESULTS: Overall, there were 191 observations of CVD among 10,548 total observations (1.7%, standard error (SE) = 0.2), with 40 among 3014 never users of tobacco (1.5%, SE = 0.3). In multivariable models, CVD incidence was not significantly different for any tobacco user groups compared to never users. There were 126 observations of CVD among 6263 continuing exclusive combustible-tobacco users (adjusted odds ratio [AOR] = 1.44; 95% confidence interval (CI) 0.87-2.39), 15 observations of CVD among 565 who transitioned to dual use (AOR = 1.85; 0.78-4.37), and 10 observations of CVD among 654 who quit using tobacco (AOR = 1.18; 0.33-4.26). There were no observations of CVD among 53 who transitioned to exclusive ENDS use. CONCLUSIONS: This study found no difference in CVD incidence by tobacco status over three 3 year intervals, even for tobacco quitters. It is possible that additional waves of PATH Study data, combined with information from other large longitudinal cohorts with careful tracking of ENDS use patterns may help to further clarify this relationship.

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.

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.

Biomarkers of Potential Harm among Adult Cigarette and Smokeless Tobacco Users in the PATH Study Wave 1 (2013-2014): A Cross-sectional Analysis.

BACKGROUND: While smokeless tobacco (ST) causes oral cancer and is associated with cardiovascular diseases, less is known about how its effects differ from other tobacco use. Biomarkers of potential harm (BOPH) can measure short-term health effects such as inflammation and oxidative stress. METHODS: We compared BOPH concentrations [IL6, high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), and F2-isoprostane] across 3,460 adults in wave 1 of the Population Assessment of Tobacco and Health study (2013-2014) by tobacco use groups: primary ST users (current exclusive ST use among never smokers), secondary ST users (current exclusive ST use among former smokers), exclusive cigarette smokers, dual users of ST and cigarettes, former smokers, and never tobacco users. We estimated geometric mean ratios using never tobacco users, cigarette smokers, and former smokers as referents, adjusting for demographic and health conditions, creatinine (for F2-isoprostane), and pack-years in smoker referent models. RESULTS: BOPH levels among primary ST users were similar to both never tobacco users and former smokers. Most BOPH levels were lower among ST users compared with current smokers. Compared with never tobacco users, dual users had significantly higher sICAM-1, IL6, and F2-isoprostane. However, compared with smokers, dual users had similar biomarker levels. Former smokers and secondary ST users had similar levels of all five biomarkers. CONCLUSIONS: ST users have lower levels of inflammatory and oxidative stress biomarkers than smokers. IMPACT: ST use alone and in combination with smoking may result in different levels of inflammatory and oxidative stress levels.

Dose-Response Association of Low-Intensity and Nondaily Smoking With Mortality in the United States.

Importance: An increasing proportion of US smokers smoke at low intensity and not every day. Some nondaily smokers have always had this pattern, whereas others previously smoked daily. The effect of reducing the level of smoking from daily to nondaily smoking and the dose response at low smoking levels are poorly understood. Objective: To evaluate risk of all-cause and cause-specific mortality among nondaily and daily cigarette smokers, by cigarettes per month, years after reducing from daily to nondaily smoking, and years since quitting. Design, Setting, and Participants: A prospective cohort study using harmonized data from multiple cycles of the Tobacco Use Supplements to the Current Population Survey (TUS-CPS), linked to the National Death Index, were analyzed during the period from 2018 to 2020. Adults completed the 1992-1993, 1995-1996, 1998-1999, 2000, 2001-2002, 2003, 2006-2007, or 2010-2011 TUS-CPS. Cigarette smokers were classified as daily or nondaily users; current nondaily smokers were further categorized by whether they previously smoked every day. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for risks of mortality vs never smoking. Age was the underlying time metric, adjusted for sex, race/ethnicity, education, survey year, and household income. Results: Among 505 500 participants (aged 18-103 years), approximately 47 000 deaths occurred. The median number of cigarettes smoked per month was 600 (interquartile range, 300-600) (20 cigarettes per day [interquartile range, 10-20 cigarettes per day]) for daily cigarette smokers and 40 (interquartile range, 15-90) for lifelong nondaily smokers. Nevertheless, both current daily (HR, 2.32; 95% CI, 2.25-2.38) and lifelong nondaily (HR, 1.82; 95% CI, 1.65-2.01) smokers had higher all-cause mortality risks than never smokers. Associations were observed for 6 to 10 cigarettes per month and increased with greater-intensity use. Nondaily smokers who previously smoked every day had lower mortality risks than daily smokers, with similar HRs after 10 or more years of nondaily smoking as lifelong nondaily smokers (HR vs never smokers, 1.73; 95% CI, 1.56-1.92). Yet, their risks were higher than former smokers who quit 10 or more years before (HR vs never smokers, 1.18; 95% CI, 1.15-1.22). Conclusions and Relevance: Although reducing smoking from daily to nondaily was associated with decreased mortality risk, cessation was associated with far greater benefit. Lifelong nondaily smokers have higher mortality risks than never smokers, even among those smoking 6 to 10 cigarettes per month. Thus, all smokers should quit, regardless of how infrequently they smoke.

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

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.

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.

Association of Cigarette, Cigar, and Pipe Use With Mortality Risk in the US Population.

Importance: Tobacco products have changed in recent years. Contemporary mortality risk estimates of combustible tobacco product use are needed. Objective: To investigate the mortality risks associated with current and former use of cigars, pipes, and cigarettes. Design, Setting, and Participants: The National Longitudinal Mortality Study is a longitudinal population-based, nationally representative health survey with mortality follow-up that includes demographic and other information from the Current Population Survey, tobacco product use information from the Tobacco Use Supplement, and mortality data from the National Death Index. In this study, participants provided tobacco use information at baseline in surveys starting from 1985 and were followed for mortality through the end of 2011. The study includes 357 420 participants who reported exclusively using cigar, pipes, or cigarettes or reported never using any type of tobacco product. Exposures: Current or former exclusive use of any cigar (little cigar, cigarillos, large cigar), traditional pipe, or cigarette and never tobacco use. Information on current daily and nondaily use was also collected. Estimates adjusted for age, sex, race/ethnicity, education, and survey year. Main Outcomes and Measures: All-cause and cause-specific mortality as identified as the primary cause of death from death certificate information. Results: Of the 357 420 persons included in the analysis, the majority of current and former cigar and pipe smokers were male (79.3%-98.0%), and smokers were more evenly divided by sex (46% of current daily smokers were male). There were 51 150 recorded deaths during follow-up. Exclusive current cigarette smokers (hazard ratio [HR], 1.98; 95% CI, 1.93-2.02) and exclusive current cigar smokers (HR, 1.20; 95% CI, 1.03-1.38) had higher all-cause mortality risks than never tobacco users. Exclusive current cigarette smokers (HR, 4.06; 95% CI, 3.84-4.29), exclusive current cigar smokers (HR, 1.61; 95% CI, 1.11-2.32), and exclusive current pipe smokers (HR, 1.58; 95% CI, 1.05-2.38) had an elevated risk of dying from a tobacco-related cancer (including bladder, esophagus, larynx, lung, oral cavity, and pancreas). Among current nondaily cigarette users, statistically significant associations were observed with deaths from lung cancer (HR, 6.24; 95% CI, 5.17-7.54), oral cancer (HR, 4.62; 95% CI, 1.84-11.58), circulatory death (HR, 1.43; 95% CI, 1.30-1.57), cardiovascular death (HR, 1.24; 95% CI, 1.11-1.39), cerebrovascular death (stroke) (HR, 1.39; 95% CI, 1.12-1.74), and chronic obstructive pulmonary disease (HR, 7.66; 95% CI, 6.09-9.64) as well as for daily smokers. Conclusions and Relevance: This study provides further evidence that exclusive use of cigar, pipes, and cigarettes each confers significant mortality risks.

Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case-Control Study within the Agricultural Health Study.

Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation, and the risk of hormone-related cancers. Here, we evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide-SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism or regulation (N = 1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N = 17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction = 4.0 × 10-5; q-value = 0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR = 0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR = 0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.

Coumaphos exposure and incident cancer among male participants in the Agricultural Health Study (AHS).

BACKGROUND: Coumaphos is an organophosphate livestock insecticide. Previous research in the Agricultural Health Study (AHS) cohort observed a positive association between coumaphos and prostate cancer in men with a family history of prostate cancer. OBJECTIVES: This study was performed to determine the association between coumaphos and other major cancer sites and to explore the consistency of the association with prostate cancer early (1993-1999) and later (2000-2005) in AHS follow-up. METHODS: This study included 47,822 male licensed pesticide applicators. Incident cases were ascertained by linkage to state cancer registries, and exposure data were collected by enrollment questionnaire. Poisson regression was used to estimate rate ratio (RR) and 95% confidence interval (CI) of cancer for coumaphos exposure controlling for potentially confounding variables. RESULTS: Approximately 8% of applicators reported use of coumaphos; 8.5% reported a family history of prostate cancer. Cumulative exposure to coumaphos was not associated with cancer risk overall or with any major cancer site including prostate. In men with a family history of prostate cancer, we observed a positive association between ever use of coumaphos and prostate cancer in both early (RR = 2.07; 95% CI, 1.19-3.62, p-interaction = 0.005) and later (RR = 1.46; 95% CI, 0.89-2.40; p-interaction = 0.11) periods of follow-up. Across all years, this association was statistically significant (RR = 1.65; 95% CI, 1.13-2.38; p-interaction = 0.004). CONCLUSION: Coumaphos was not associated with any cancer evaluated here. In men with a family history of disease, there was evidence of an association between coumaphos and prostate cancer, possibly due to genetic susceptibility; however, other explanations, including chance, are plausible.

Heterocyclic aromatic amine pesticide use and human cancer risk: results from the U.S. Agricultural Health Study.

Imazethapyr, a heterocyclic aromatic amine, is a widely used crop herbicide first registered for use in the United States in 1989. We evaluated cancer incidence among imazethapyr-exposed pesticide applicators enrolled in the Agricultural Health Study (AHS). The AHS is a prospective cohort of 57,311 licensed pesticide applicators in the U.S., enrolled from 1993-1997. Among the 49,398 licensed pesticide applicators eligible for analysis, 20,646 applicators reported use of imazethapyr and 2,907 incident cancers developed through 2004. Imazethapyr exposure was classified by intensity-weighted lifetime exposure days calculated as [years of use x days per year x intensity level]. Poisson regression analysis was used to evaluate the relationship between imazethapyr exposure and cancer incidence. We found significant trends in risk with increasing lifetime exposure for bladder cancer (p for trend 0.01) and colon cancer (p for trend 0.02). Rate ratios (RRs) were increased by 137% for bladder cancer and 78% for colon cancer when the highest exposed were compared to the nonexposed. The excess risk for colon cancer was limited to proximal cancers, (RR = 2.73, 95% confidence intervals 1.42, 5.25, p for trend 0.001). No association was observed for prostate, lung, rectum, kidney, oral, pancreas, lymphohematopoietic cancers or melanoma. These findings provide new evidence that exposure to aromatic amine pesticides may be an overlooked exposure in the etiology of bladder and colon cancer. The use of imazethapyr and other imidazolinone compounds should continue to be evaluated for potential risk to humans.