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Epigenetic alterations, including DNA methylation, microRNA, and long noncoding RNA, play important roles in the pathogenesis of numerous respiratory health conditions and diseases. Exposure to tobacco smoking has been found to be associated with epigenetic changes in the respiratory tract. Marketed as a less harmful alternative to combustible cigarettes, electronic cigarette (e-cigarette) has rapidly gained popularity in recent years, especially among youth and young adults. Accumulative evidence from both animal and human studies has shown that e-cigarette use (vaping) is also linked to similar respiratory health conditions as observed with cigarette smoking, including wheezing, asthma, and COPD. This review aims to provide an overview of current studies on associations of smoking and vaping with epigenetic alterations in respiratory cells and provide future research directions in epigenetic studies related to vaping. [ABSTRACT FROM AUTHOR]

Introduction: Emerging heated tobacco products (HTPs) were designed to reduce exposure to toxicants from cigarette smoke (CS) by avoiding burning tobacco and instead heating tobacco. We studied the effects of short-term inhalation of aerosols emitted from HTP called IQOS, on lung damage and immune-cell recruitment to the lungs in mice.Methods: Numerous markers of lung damage and inflammation including albumin and lung immune-cell infiltrates, proinflammatory cytokines, and chemokines were quantified in lungs and bronchoalveolar (BAL) fluid from IQOS, CS, or air-exposed (negative control) mice.Results: Importantly, as a surrogate marker of lung epithelial-cell damage, we detected significantly increased levels of albumin in the BAL fluid of both HTP- and CS-exposed mice compared with negative controls. Total numbers of leukocytes infiltrating the lungs were equivalent following both IQOS aerosols and CS inhalation and significantly increased compared with air-exposed controls. We also observed significantly increased numbers of CD4+IL-17A+ T cells, a marker of a T-cell immune response, in both groups compared with air controls; however, numbers were the highest following CS exposure. Finally, the numbers of CD4+RORγt+ T cells, an inflammatory T-cell subtype expressing the transcription factor that is essential for promoting differentiation into proinflammatory Th17 cells, were significantly augmented in both groups compared with air-exposed controls. Levels of several cytokines in BAL were significantly elevated, reflecting a proinflammatory milieu.Conclusions: Our study demonstrates that short-term inhalation of aerosols from IQOS generates damage and proinflammatory changes in the lung that are substantially similar to that elicited by CS exposure.Implications: Exposure of mice to IQOS, one of the candidate modified-risk tobacco products, induces inflammatory immune-cell accumulation in the lungs and augments the levels of proinflammatory cytokines and chemokines in the BAL fluid. Such an exacerbated pulmonary proinflammatory microenvironment is associated with lung epithelial-cell damage in IQOS-exposed mice, suggesting a potential association with the impairment of lung function. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

INTRODUCTION Flavors other than tobacco flavor have been identified as a major reason for electronic nicotine delivery system (ENDS) initiation in youth and are thought to contribute to the continued use of ENDS in users of all ages. Our previous research showed a significant association between overall ENDS use and COPD. This study aims to identify the association of ENDS flavor categories with self-reported COPD. METHODS The data analysis included 4909 adults from Population Assessment of Tobacco and Health (PATH) Wave 4 data who were ever established ENDS users and responded to an item about diagnosis of COPD. Weighted multivariable logistic regression models were used to examine the association between different ENDS flavors and self-reported COPD considering complex sampling design. RESULTS Among 4909 ever established ENDS users, 418 adults (weighted percentage 9.8%) had self-reported COPD. Self-reported COPD prevalence differed between different ENDS flavor categories, with the highest (weighted percentage 19.9%) occurring among tobacco flavor users. Compared to non-tobacco flavor categories, tobacco flavor category showed significantly higher association with self-reported COPD (AOR=2.05; 95% CI: 1.20-3.53), after adjusting for potential confounding variables. No significant associations with self-reported COPD were found for other examined ENDS flavor categories including menthol/mint, fruit, candy/ desserts/other-sweets, and other flavors, compared to their corresponding non-users. CONCLUSIONS Tobacco flavored ENDS use was significantly associated with self-reported COPD. Future studies are needed to confirm the biological and epidemiological association of flavored ENDS use with COPD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 non-cannabis 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. [ABSTRACT FROM AUTHOR]

Rationale: There is limited understanding regarding how various e-cigarette flavorings may influence the behavior of non-regular e-cigarette users who are regular cigarette smokers. Objectives: To assess differences in nicotine delivery, puffing topography, subjective effects, and user satisfaction from different flavored e-liquids. Methods: Eighteen daily smokers (average age, 44.1 ± 7.0; 9 males; average CPD, 13.0 ± 5.8) smoked their tobacco cigarettes during an initial visit and returned five times to try an e-cigarette (eGo type) refilled with a nicotine solution (24 mg/ml) of five different flavors: cherry, tobacco, espresso, menthol, and vanilla (randomized order). Assessments at each visit included puffing topography, blood samples for nicotine analysis, and subjective reports of nicotine effects and flavor satisfaction. Results: Vaping different flavors resulted in different levels of plasma nicotine. The flavor producing the highest plasma nicotine concentration (Cmax) was cherry (median 21.2 ng/ml), which was not significantly different than nicotine delivery from a combustible cigarette (29.2 ng/ml, p >.05). Vanilla e-liquid produced the lowest Cmax (9.7 ng/ml), and participants tended to puff less frequently on vanilla compared to tobacco flavor (p =.013). Flavors did not differ significantly in the speed of nicotine delivery (Tmax). During controlled use, puff duration for all flavors was significantly longer than a combustible cigarette (p < 0.05). After controlling for nicotine delivery, significant differences in flavor enjoyment were detected. Menthol flavored e-liquid was rated as more enjoyable than vanilla and tobacco flavored e-liquids (p < 0.05). Conclusions: Flavors tested in this study yielded different patterns of nicotine delivery and led to differences in reduction in smoking urges. Trial registration: ClinicalTrials.gov Identifier: #NCT02575885 [ABSTRACT FROM AUTHOR]