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Rationale: While tobacco industry data suggests that switching from combustible cigarettes to heated tobacco products (HTPs), like IQOS, may reduce the users' exposure to respiratory toxicants, it is not known if using HTPs impacts the outcomes of acute respiratory infections., Objectives: Does switching from cigarettes to HTPs improve responses to pulmonary infection., Methods: We conducted experiments in which 3 groups of mice were pre-exposed to cigarette smoke for 8 weeks, followed by 8-week exposure to (1) HTPs (tobacco product switching), (2) air (smoking cessation), or (3) continued exposure to cigarette smoke. Pulmonary bacterial clearance and surrogate markers of lung damage were assessed as study outcomes., Main Results: Significantly compromised clearance of bacteria from the lungs post-acute challenge occurred in both the switching group and in mice continuously exposed to cigarette smoke. Bacterial clearance, inflammatory T-cell infiltration into the lungs, and albumin leak improved at 12 h post-acute challenge in the switching group compared to mice continuously exposed to cigarette smoke. Bacterial clearance, total lung immune-cell infiltration, inflammatory T-cell infiltration into the lungs, the content of total proteins in the BAL, and albumin leak measured post-acute challenge were compromised in the switching group compared to mice in the cessation group. Switching from cigarettes to HTPs did not improve lung myeloperoxidase and neutrophil elastase levels (markers for lung inflammation and damage), which, however, were significantly reduced in the cessation group., Conclusions: This study reveals only a modest improvement in respiratory infection outcomes after switching exposure from cigarettes to HTPs and significantly compromised outcomes compared to a complete cessation of exposure to all tobacco products., (© 2024. The Author(s).)

Importance: Population-level health outcomes associated with e-cigarettes depend in part on the association between e-cigarettes and combustible cigarette cessation. The US Food and Drug Administration has authority to regulate e-cigarette characteristics, including flavor and device type., Objective: To investigate whether e-cigarette characteristics are associated with cigarette cessation behaviors among adults in the US population who use e-cigarettes., Design, Setting, and Participants: This cohort study was conducted using longitudinal data collected in 2014 to 2021 by the Population Assessment of Tobacco and Health Study, a population-based, US nationally representative study. Participants were sampled from the civilian noninstitutionalized population using a 4-staged, stratified sampling design. Data were weighted and analyzed from 1985 adults ages 21 or older who smoked cigarettes daily and had used e-cigarettes in the past 30 days. Data were analyzed in May 2021 to May 2024., Exposures: The following e-cigarette characteristics were assessed: use frequency (daily and nondaily), flavor type (tobacco, menthol or mint, sweet, and combination), device type (disposable, cartridge, and tank), and year of data collection as a proxy for the evolving e-cigarette marketplace., Main Outcomes and Measures: The following cigarette cessation behaviors were assessed: making a cigarette quit attempt, cigarette cessation among individuals who made a quit attempt, and overall cigarette discontinuation regardless of quit attempts. Associations were evaluated between e-cigarette characteristics (assessed at baseline in 1 approach and assessed at follow-up in another approach) and cigarette cessation outcomes, controlling for demographic, cigarette smoking, and other e-cigarette use characteristics., Results: The study sample consisted of 1985 participants representing adults in the population (mean age, 40.0 years [95% CI, 39.2-40.9 years]; 49.4% [95% CI, 46.3%-52.6%] male; 11.4% [95% CI, 9.6%-13.4%] Black, 80.7% [95% CI, 77.8%-83.3%] White, and 8.0% [95% CI, 6.3%-10.0%] other race; 9.2% [95% CI, 7.5%-11.2%] Hispanic). Daily vs nondaily e-cigarette use was associated with greater overall cigarette discontinuation rates (12.8% [95% CI, 9.1%-17.7%] vs 6.1% [95% CI, 4.8%-7.7%]; adjusted odds ratio [aOR], 2.26 [95% CI, 1.34-3.81]), and use of e-cigarettes in 2019 to 2021 vs 2014-2015 to 2015-2016 was also associated with greater overall cigarette discontinuation rates (12.0% [95% CI, 8.8%-16.0%] vs 5.3% [95% CI, 2.9%-9.3%]; aOR, 2.75 [95% CI, 1.13-6.67]). Use of menthol or mint vs tobacco flavor e-cigarettes was associated with greater overall cigarette discontinuation rates (9.2% [95% CI, 6.6%-12.8%] vs 4.7% [95% CI, 3.0%-7.1%]; aOR, 2.63 [95% CI, 1.32-5.27]) only when assessing e-cigarette use at baseline. E-cigarette device type was not associated with cigarette discontinuation rates in adjusted analyses., Conclusions and Relevance: In this study, daily e-cigarette use and use of e-cigarettes in 2019 to 2021 were consistently associated with greater cigarette discontinuation rates. These findings suggest that research focused on e-cigarettes marketed in recent years is needed to inform product regulation and public health policy decisions.

E-liquids contain combinations of chemicals, with many enhancing the sensory attractiveness of the product. Studies are needed to understand and characterize e-liquid ingredients, particularly flavorings, to inform future research and regulations of these products. We identified common flavor ingredients in a convenience sample of commercial e-liquids using gas chromatography-mass spectrometry. E-liquid flavors were categorized by flavor descriptors provided on the product packaging. A Flavor Ingredient Wheel was developed to link e-liquid flavor ingredients with flavor categories. An analysis of 109 samples identified 48 flavor ingredients. Consistency between the labeled flavor and ingredients used to produce such flavor was found. Our novel Flavor Ingredient Wheel organizes e-liquids by flavor and ingredients, enabling efficient analysis of the link between ingredients and their flavor profiles and allowing for quick assessment of an e-liquid ingredient's flavor profile. Investigating ingredient profiles and identifying and classifying commonly used chemicals in e-liquids may assist with future studies and improve the ability to regulate these products.

Heated Tobacco Products (HTPs) purport to reduce exposure to tobacco-related toxicants compared to combustible cigarettes. This cross-sectional study examined the content of nicotine, two humectants (propylene glycol (PG) and vegetable glycerin (VG)), and four tobacco-specific nitrosamines (TSNAs: NNN, NNK, NAT, and NAB) in the tobacco filler of a popular HTP brand (IQOS). Non-menthol and menthol IQOS sticks were purchased from nine countries between 2017 and 2020 and were classified into two versions ("Bold" and "Light") using Philip Morris's flavor descriptors. The average nicotine concentration was 4.7 ± 0.5 mg/stick, and the highest nicotine concentration was found in products from Japan (5.1 ± 0.2 mg/stick). VG was the dominant humectant found in all sticks, with an average concentration of (31.5 ± 2.3 mg/stick). NNN, NNK, and NAT were substantially higher in the "Bold" sticks than the "Light" sticks. Significant differences between countries for TSNAs were also observed: the NAT and NAB contents were the highest in the "Light" products from Canada (192.5 ± 24.1 and 22.9 ± 1.0 ng/stick, respectively); the NNK concentration was the highest in the "Bold" products from Poland (64.8 ± 7.9 ng/stick); and the highest NNN concentrations were observed in the "Bold" products from South Africa (488.9 ± 26.7 ng/stick). As NNN and NNK are known human carcinogens, and as humectants like PG and VG can degrade into toxic carbonyl compounds upon heating, monitoring the concentration of these chemicals in HTPs is important for protecting users' health and ensuring compliance with regulations.

Nicotine vaping products (NVPs) and heated tobacco products (HTPs) are designed to replicate the sensory and behavioural aspects of smoking cigarettes while avoiding combustion. The success of these products as harm reduction tools will partially depend on their ability to satisfy smokers and alleviate nicotine-related withdrawal symptoms. This study aims to compare short-term effects of NVPs (Juul and Aspire PockeX) versus HTPs (IQOS) on smoking-related withdrawal relief, product satisfaction, intention to switch to NVP/HTP, perceptions and attitudes in UK adult cigarette smokers naïve to these products. In a randomized cross-over study, 45 participants visited the lab twice, at each visit trying one of the two products (NVP/HTP) and completing a questionnaire. Responses were normalized on a 0-100% scale and mean differences (MD) between NVP and HTP scores computed, with positive and negative MD values indicating greater endorsement for NVP and HTP, respectively. Cigarette cravings were reduced similarly (~ 20.0%) by both products (MD = 4.5%, 95%Confidence Interval (CI) - 4.8, 13.8). Direct positive effects (MD = - 3.5%, 95%CI - 7.2, 0.2) and adverse side effects (MD = 1.8%, 95%CI - 0.3, 3.8) were comparable after each product use, though marginally favouring HTPs. HTPs were perceived as more satisfying overall (MD = - 13.2%, 95%CI - 20.3 - 6.1) than NVPs but both were perceived as similarly addictive (MD = 3.6%, 95%CI - 4.6, 11.8), relative to cigarettes. Intention to switch to either product was comparable (MD = 4.0%, 95%CI - 5.7, 13.8). Comparison of acute use of NVP versus HTP in a sample of UK smokers naïve to these products suggests that HTPs are perceived as more satisfying than NVPs, though still less satisfying than cigarettes.Registration: The analysis plan was pre-registered, and it is available at https://osf.io/6ymdu., (© 2023. The Author(s).)

Importance: Pregnant adolescents sometimes use cigarettes; however, little is known about e-cigarette use among pregnant adolescents, a population with increased health vulnerability., Objective: To examine yearly trends, sociodemographic and pregnancy-related determinants, and the association with small-for-gestational-age (SGA) birth of e-cigarette and/or cigarette use during late pregnancy among adolescents., Design, Setting, and Participants: This cohort study used existing data from the 2016-2021 Pregnancy Risk Assessment Monitoring System on 10 428 US adolescents aged 10 to 19 years who had a singleton birth with complete data on e-cigarette or cigarette use and SGA birth., Exposure: Adolescents reported e-cigarette and cigarette use during the last 3 months of pregnancy., Main Outcomes and Measures: SGA birth (birth weight below the 10th percentile for the same sex and gestational duration) was determined from birth certificates. Multivariable logistic regression was used to compare the odds of SGA birth across pregnant adolescents who exclusively used e-cigarettes, exclusively used cigarettes, used e-cigarettes and cigarettes, or did not use either., Results: Of the 10 428 pregnant adolescents, 72.7% were aged 18 or 19 years; 58.9% self-identified as White and 23.3% as Black; and 69.8% were non-Hispanic. The weighted prevalence of exclusive e-cigarette use during late pregnancy increased from 0.8% in 2016 to 4.1% in 2021, while the prevalence of exclusive cigarette use decreased from 9.2% in 2017 to 3.2% in 2021. The prevalence of dual use fluctuated, ranging from 0.6% to 1.6%. White pregnant adolescents were more likely than those who self-identified as another race and ethnicity to use e-cigarettes (2.7% vs 1.0% for American Indian or Alaska Native adolescents, 0.8% for Asian or other race adolescents, 0.6% for Black adolescents, and 0.7% for multiracial adolescents). Compared with those who did not use either product, adolescents who exclusively used e-cigarettes (16.8% vs 12.9%; confounder-adjusted odds ratio [AOR], 1.68 [95% CI, 0.89-3.18]) or who used cigarettes and e-cigarettes (17.6% vs 12.9%; AOR, 1.68 [95% CI, 0.79-3.53]) had no statistically significant difference in risk of SGA birth. However, adolescents who exclusively used cigarettes had a more than 2-fold higher risk of SGA birth (24.6% vs 12.9%; AOR, 2.51 [95% CI, 1.79-3.52])., Conclusions and Relevance: This cohort study suggests that pregnant adolescents increasingly used e-cigarettes, with the highest use among White adolescents. Results from this analysis found that, unlike cigarette use, e-cigarette use during late pregnancy was not statistically significantly associated with an increased risk of SGA birth among adolescents. Due to the uncertainty of this nonsignificant association, future research could benefit from a larger sample size.

Rationale: Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding of their long-term respiratory health effects. We therefore undertook the first-ever side-by-side comparison of the impact of chronic inhalation of aerosols emitted from electronic cigarettes (EC) and heated tobacco products (HTP), and combustible cigarettes (CC) smoke., Objectives: To evaluate the potential differential effects of alternative tobacco products on lung inflammatory responses and efficacy of vaccination in comparison to CC., Methods: Mice were exposed to emissions from EC, HTP, CC, or air for 8 weeks. BAL and lung tissue were analyzed for markers of inflammation, lung damage, and oxidative stress. Another group was exposed for 12 weeks and vaccinated and challenged with a bacterial respiratory infection. Antibody titers in BAL and sera and pulmonary bacterial clearance were assessed., Main Results: EC- and HTP-aerosols significantly augmented lung immune cell infiltrates equivalent to that achieved following CC-exposure. HTP and CC significantly increased neutrophil numbers compared to EC. All products augmented numbers of B cells, T cells, and pro-inflammatory IL17A + T cells in the lungs. Decreased lung antioxidant activity and lung epithelial and endothelial damage was induced by all products. EC and HTP differentially augmented inflammatory cytokines/chemokines in the BAL. Generation of immunity following vaccination was impaired by EC and HTP but to a lesser extent than CC, with a CC > HTP > EC hierarchy of suppression of pulmonary bacterial clearance., Conclusions: HTP and EC-aerosols induced a proinflammatory pulmonary microenvironment, lung damage, and suppressed efficacy of vaccination., (© 2023. The Author(s).)

Importance: Smoking cigarettes during pregnancy can impair maternal and child health, and pregnant individuals have increasingly used electronic cigarettes (e-cigarettes) for various reasons, including quitting smoking., Objective: To assess smoking abstinence rates among pregnant individuals who used e-cigarettes compared with those who used nicotine replacement therapy (NRT)., Design, Setting, and Participants: This cohort study is a secondary data analysis of phase 8 of the US Pregnancy Risk Assessment Monitoring System, conducted between 2016 and 2020. Eligible participants included pregnant individuals who smoked combustible cigarettes within the 3 months before pregnancy and either used e-cigarettes or NRT during pregnancy. Data analysis was conducted from March 2022 to April 2023., Exposures: Combustible cigarette use within 3 months before pregnancy and use of either e-cigarettes or NRT during pregnancy., Main Outcomes and Measures: The primary outcome was the individual's self-reported smoking abstinence status during the last 3 months of pregnancy. Weighted percentages were reported and weighted multivariable logistic regression models were used to examine the association of e-cigarette use vs NRT with smoking abstinence. A propensity score was used to control for confounding by sociodemographics, pregnancy characteristics, prepregnancy smoking intensity, depression, behavioral support, and hookah use., Results: The cohort included 1329 pregnant individuals (759 ≥25 years [60.2%]; 766 non-Hispanic White individuals [79.8%]) of whom 781 had an education level of high school or lower (61.4%), and 952 had an annual household income of $48 000 or less (81.5%). Of the 1329 individuals, 890 (unweighted percentage, 67.0%) were existing e-cigarette users, 67 (unweighted percentage, 5.0%) were new e-cigarette users, and 372 (unweighted percentage, 28.0%) were NRT users. Compared with individuals who used NRT during pregnancy, individuals who used e-cigarettes had a higher rate of smoking abstinence in late pregnancy (456 individuals [50.8%] vs 67 individuals [19.4%]; propensity score adjusted odds ratio [OR], 2.47; 95% CI, 1.17-5.20; P = .02). In the secondary analysis stratified by the timing of e-cigarette use initiation, existing users of e-cigarettes who initiated before pregnancy had a higher smoking abstinence rate than NRT users (446 users [53.1%] vs 67 users [19.4%]; adjusted OR, 2.61; 95% CI, 1.23-5.51; P = .01). However, new e-cigarette users who initiated use during pregnancy had a similar smoking abstinence rate in late pregnancy when compared with NRT users (10 users [20.6%] vs 67 users [19.4%]; adjusted OR, 1.13; 95% CI, 0.22-5.87; P = .88)., Conclusions and Relevance: These findings suggest that individuals who used e-cigarettes during pregnancy had a higher smoking abstinence rate in late pregnancy than individuals who used NRT, especially for those who initiated e-cigarette use before pregnancy, indicating that replacement of cigarettes with e-cigarettes during pregnancy may be a viable strategy for harm reduction.

Background: Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use., Methods: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1., Results: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%-4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1-62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5-66.4)], among most demographic subgroups., Conclusions: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4., Impact: Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status., (©2023 American Association for Cancer Research.)

Background: As summarised in the most recent Cochrane review, the few clinical trials on e-cigarettes are largely focused on smoking cessation. We aimed to determine the naturalistic uptake, use, and impact of e-cigarettes among adults who may or may not want to stop smoking., Methods: In this naturalistic, randomised, controlled clinical trial, adult smokers, across the motivational spectrum and with minimal history of e-cigarette use, were recruited online from the general community within 11 cities across the USA. Participants were randomly assigned (2:1) to either receive either a free 4-week supply of flavoured, tank-style e-cigarette, or not. E-cigarette group participants received a battery and device with up to 30 pre-filled tanks, offered among five flavours, with minimal instructions on use. The study's primary purpose was to descriptively assess naturalistic uptake and usage of the e-cigarette, and to secondarily assess its impact on smoking behavior. The latter, assessed through six months of follow-up, included: a) self-reported 7-day point prevalence abstinence, b) incidence of quit attempts, and c) smoking reduction. This trial is registered at ClinicalTrials.gov, NCT03453385., Findings: Between 5/2018 and 3/2022, 638 adult smokers were enrolled and randomly assigned (427 in the e-cigarette group and 211 in the no-product control group). Uptake of e-cigarettes was robust: approximately 70% of participants used the product, with average usage exceeding 4 days per week during the initial 30 days. Based on an intent-to-treat approach where missing data is imputed as smoking, almost all behavioral outcomes favored the e-cigarette group relative to no-product control, including point prevalence abstinence at six months (Odds Ratio [OR] = 1.8; 95% Confidence Interval [CI] = 1.0-3.1), cumulative incidence of 24-hr quit attempts (OR = 1.5; 95% CI = 1.0-2.2), and having reduced smoking by at least 50% since baseline (OR = 1.8; 95% CI = 1.2-2.7). Results were similar under an alternative imputation., Interpretation: Complementing cessation-focused trials, results suggest that unguided e-cigarette use also leads to smoking cessation, allaying the notion that causal effects of e-cigarettes on cessation are not reflective of real-world scenario of self-determined use. For smokers who may not be able to quit using existing pharmacologic approaches, e-cigarettes may be considered to achive that purpose., Funding: National Cancer Institute., Competing Interests: KMC has served as a paid expert witness in litigation filed against the tobacco industry. KMG has provided consultation to Jazz Pharmaceuticals and has received research funding from Aelis Farma. MLG has served as a member of the Scientific Advisory Board to Johnson & Johnson; he has also consulted with both the World Health Organization and Campaign for Tobacco Free Kids on toxicity of tobacco products and tobacco control products; MLG is also a Member of the IASLC Tobacco Control and Smoking Cessation Committee; and a leadership role with the American Association for Cancer Research. JD is a co-owner of Behavioral Activation Tech LLC, a small business that develops digital interventions for behavioral health treatment. E-cigarette products (tanks and liquids) were purchased directly from NJoy; no study support provided from industry. All other authors declare no competing interests., (© 2023 The Author(s).)

This perspective summarizes available evidence on biomarkers of exposure in electronic nicotine delivery system (ENDS) users to aid the overall assessment of the health consequences of using ENDS. Identification of novel biomarkers of exposure specific to ENDS use remains challenging because chemicals emitted from ENDS devices have many familiar sources. The biomarker levels of many tobacco-related toxicants measured in biological samples collected from ENDS users did not differ significantly from non-users, except for nicotine metabolites and a small number of biomarkers of exposure to volatile organic compounds and tobacco-specific tobacco nitrosamines. Several studies have shown that while exposed to nicotine, long-term exclusive ENDS users showed significantly lower levels of toxicant biomarkers than cigarette smokers. Studies have also shown that concurrent users of ENDS and combustible cigarettes ('dual users') are not reducing overall exposure to harmful toxicants compared to exclusive cigarette smokers. Because of an absence of validated ENDS-specific biomarkers, we recommend combining several biomarkers to differentiate tobacco product user groups in population-based studies and monitor ENDS compliance in randomized controlled trials. Using a panel of biomarkers would provide a better understanding of health effects related to ENDS use.

South Korea is the world's second-largest heated tobacco product (HTP) market after Japan. HTP sales in South Korea have increased rapidly since May 2017, accounting for 10.6% of the total tobacco market in 2020. Despite this, little is known as to why HTP consumers who were current and former smokers started using HTPs and used them regularly. We analyzed cross-sectional data for 1815 adults (aged 19+) who participated in the 2020 International Tobacco Control (ITC) Korea Survey, of whom 1650 were HTP-cigarette consumers (those who reported smoking cigarettes and using HTPs ≥ weekly) and 165 were exclusive HTP consumers (using HTPs ≥ weekly) who were former or occasional smokers (smoking cigarette < weekly). Respondents were asked to report the reason(s) they used HTPs, with 25 possible reasons for HTP-cigarette consumers and 22 for exclusive HTP consumers. The most common reasons for initiating HTP use among all HTP consumers were out of curiosity (58.9%), family and friends use HTPs (45.5%), and they like the HTP technology (35.9%). The most common reasons for regularly using HTPs among all HTP consumers were that they were less smelly than cigarettes (71.3%), HTPs are less harmful to own health than cigarettes (48.6%), and stress reduction (47.4%). Overall, 35.4% of HTP-cigarette consumers reported using HTPs to quit smoking, 14.7% to reduce smoking but not to quit, and 49.7% for other reasons besides quitting or reducing smoking. In conclusion, several common reasons for initiating and regularly using HTPs were endorsed by all HTP consumers who were smoking, had quit smoking completely, or occasionally smoked. Notably, only about one-third of HTP-cigarette consumers said they were using HTPs to quit smoking, suggesting that most had no intention of using HTPs as an aid to quit smoking in South Korea.

Introduction: Novel tobacco-free oral nicotine products are not combusted, easy to conceal, available in flavors, and do not contain tobacco leaf. Since 2016, oral nicotine product sales have increased and may be gaining popularity among youth. This study aims to examine the trends in the prevalence and correlates of oral nicotine product use among U.S. youth., Methods: Data from participants aged 16-19 years in the U.S. International Tobacco Control Policy Evaluation Project Youth Tobacco and Vaping Survey were analyzed cross-sectionally from August 2019, February 2020, August 2020, February 2021, and August 2021. Weighted descriptive statistics and logistic regressions were used to describe the use and correlates of oral nicotine products., Results: Oral nicotine product use significantly increased from 3.5% in August 2019 to 4.1% in August 2021. Oral nicotine product use was most prevalent among those aged 18 years, male, and non-Hispanic White. Those who used cigarettes (AOR=2.18, 95% CI=19.37, 40.88), nicotine vaping products (AOR=4.27, 95% CI=3.02, 6.04), and smokeless tobacco (AOR=28.14, 95% CI=19.37, 40.88) in the past 30 days were more likely to report recent use of oral nicotine products., Conclusions: Although oral nicotine products are less popular among U.S. youth than cigarettes, nicotine vaping products, and smokeless tobacco, their prevalence of use significantly increased. Oral nicotine product users are more likely to use other nicotine products, but the availability of flavors and easy-to-conceal design may be appealing to those who may not use nicotine products. Researchers should continue to observe the behaviors associated with oral nicotine product use to inform the need for future regulatory efforts., (© 2023 The Authors.)

RNA-seq is a high-throughput sequencing technology widely used for gene transcript discovery and quantification under different biological or biomedical conditions. A fundamental research question in most RNA-seq experiments is the identification of differentially expressed genes among experimental conditions or sample groups. Numerous statistical methods for RNA-seq differential analysis have been proposed since the emergence of the RNA-seq assay. To evaluate popular differential analysis methods used in the open source R and Bioconductor packages, we conducted multiple simulation studies to compare the performance of eight RNA-seq differential analysis methods used in RNA-seq data analysis (edgeR, DESeq, DESeq2, baySeq, EBSeq, NOISeq, SAMSeq, Voom). The comparisons were across different scenarios with either equal or unequal library sizes, different distribution assumptions and sample sizes. We measured performance using false discovery rate (FDR) control, power, and stability. No significant differences were observed for FDR control, power, or stability across methods, whether with equal or unequal library sizes. For RNA-seq count data with negative binomial distribution, when sample size is 3 in each group, EBSeq performed better than the other methods as indicated by FDR control, power, and stability. When sample sizes increase to 6 or 12 in each group, DESeq2 performed slightly better than other methods. All methods have improved performance when sample size increases to 12 in each group except DESeq. For RNA-seq count data with log-normal distribution, both DESeq and DESeq2 methods performed better than other methods in terms of FDR control, power, and stability across all sample sizes. Real RNA-seq experimental data were also used to compare the total number of discoveries and stability of discoveries for each method. For RNA-seq data analysis, the EBSeq method is recommended for studies with sample size as small as 3 in each group, and the DESeq2 method is recommended for sample size of 6 or higher in each group when the data follow the negative binomial distribution. Both DESeq and DESeq2 methods are recommended when the data follow the log-normal distribution., Competing Interests: The authors have declared that no competing interests exist.

The health benefits of switching from tobacco to electronic cigarettes (ECs) are neither confirmed nor well characterized. To address this problem, we used RNA-seq analysis to compare the nasal epithelium transcriptome from the following groups ( n = 3 for each group): (1) former smokers who completely switched to second generation ECs for at least 6 months, (2) current tobacco cigarette smokers (CS), and (3) non-smokers (NS). Group three included one former cigarette smoker. The nasal epithelial biopsies from the EC users vs. NS had a higher number of differentially expressed genes (DEGs) than biopsies from the CS vs. NS and CS vs. EC sets (1817 DEGs total for the EC vs. NS, 407 DEGs for the CS vs. NS, and 116 DEGs for the CS vs. EC comparison). In the EC vs. NS comparison, enriched gene ontology terms for the downregulated DEGs included cilium assembly and organization, whereas gene ontologies for upregulated DEGs included immune response, keratinization, and NADPH oxidase. Similarly, ontologies for cilium movement were enriched in the downregulated DEGs for the CS vs. NS group. Reactome pathway analysis gave similar results and also identified keratinization and cornified envelope in the upregulated DEGs in the EC vs. NS comparison. In the CS vs. NS comparison, the enriched Reactome pathways for upregulated DEGs included biological oxidations and several metabolic processes. Regulator effects identified for the EC vs. NS comparison were inflammatory response, cell movement of phagocytes and degranulation of phagocytes. Disease Ontology Sematic Enrichment analysis identified lung disease, mouth disease, periodontal disease and pulmonary fibrosis in the EC vs. NS comparison. Squamous metaplasia associated markers, keratin 10, keratin 13 and involucrin, were increased in the EC vs. NS comparison. Our transcriptomic analysis showed that gene expression profiles associated with EC use are not equivalent to those from non-smokers. EC use may interfere with airway epithelium recovery by promoting increased oxidative stress, inhibition of ciliogenesis, and maintaining an inflammatory response. These transcriptomic alterations may contribute to the progression of diseases with chronic EC use.

Background: Electronic cigarettes (e-cigarettes) are relatively new tobacco products that are attracting public attention due to their unique features, especially their many flavor options and their potential as an alternative to cigarettes. However, uncertainties remain regarding the determinants and consequences of e-cigarette use because current research on e-cigarettes is made more difficult due to the lack of psychometrically sound instruments that measure e-cigarette related constructs. This systematic review therefore seeks to identify the instruments in the field that are designed to assess various aspects of e-cigarette use or its related constructs and analyze the evidence presented regarding the psychometric properties of the identified instruments., Methods: This systematic review utilized six search engines: PubMed, Medline, CINAHL, PsycINFO, Web of Science, and EMBASE, to identify articles published in the peer-reviewed journals from inception to February 2022 that contained development or validation processes for these instruments., Results: Eighteen articles describing the development or validation of 22 unique instruments were identified. Beliefs, perceptions, motives, e-cigarette use, and dependence, were the most commonly assessed e-cigarette related constructs. The included studies reported either construct or criterion validity, with 14 studies reporting both. Most studies did not report the content validity; for reliability, most reported internal consistencies using Cronbach's alpha, with 15 instruments reporting Cronbach's alpha > 0.70 for the scale or its subscales., Conclusions: Twenty-two instruments with a reported development or validation process to measure e-cigarette related constructs are currently available for practitioners and researchers. This review provides a guide for practitioners and researchers seeking to identify the most appropriate existing instruments on e-cigarette use based on the constructs examined, target population, psychometric properties, and instrument length. The gaps identified in the existing e-cigarette related instruments indicate that future studies should seek to extend the validity of the instruments for diverse populations, including adolescents. Instruments that explore additional aspects of e-cigarette use and e-cigarette related constructs to help build a strong theoretical background and expand our current understanding of e-cigarette use and its related constructs, should also be developed., (© 2022. The Author(s).)

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.

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.

Numerous flavoring chemicals are added to e-cigarette liquids to create various flavors. Flavorings provide sensory experience to users and increase product appeal; however, concerns have been raised about their potential inhalation toxicity. Estimating potential health risk of inhaling these chemicals has been challenging since little is known about their actual concentrations in e-cigarette products. To date, a limited number of analytical methods exist to measure the concentrations of flavoring chemicals in e-cigarette products. We have developed an analytical method that accurately and precisely measures the concentrations of 20 flavoring chemicals of potential inhalation risk concerns: 2,3,5-trimethylpyrazine, acetoin, benzaldehyde, benzyl alcohol, butanoic acid, dl-limonene, ethyl maltol, ethyl salicylate, ethyl vanillin, eucalyptol, eugenol, furaneol, isovanillin, l-menthol, maltol, methyl salicylate, pulegone, trans -cinnamaldehyde, triacetin, and vanillin. Calibration and QC solutions were prepared in 50:50 propylene glycol (PG):vegetable glycerin (VG) and 5% H 2 O and flavoring concentrations ranging from 0.02 to 10.00 mg/ml. Samples of commercial e-cigarette liquids, calibration and QC solutions were combined with 30 µL of an internal standard mix (benzene-d6, pyridine-d5, chlorobenzene-d5, naphthalene-d8 and acenaphthene-d10; 1 mg/ml each) and were diluted 100-fold into methanol. Analysis was performed on an Agilent 7890B/7250 GC/Q-TOF using a DB-624UI column (30 m x 0.25 mmID x 1.4 μm film thickness), with a total runtime of 13.5 min. Calibration curves were fit using a weighted quadratic model and correlations of determination ( r ) values exceeded 0.990 for all chemicals. Bias and precision tests yielded values less than 20% and lower limits of quantitation (LLOQ) ranged from 0.02 to 0.63 mg/ml. Over 200 commercially available products, purchased or collected from adult e-cigarette users and spanning a range of flavor categories, were evaluated with this method. Concentrations of pulegone, a suspected carcinogen, varied from below limit of quantitation (BLOQ) to 0.32 mg/ml, while acetoin and vanillin, known precursors to more cytotoxic byproducts, ranged from BLOQ to 1.52 mg/ml and from BLOQ to 16.22 mg/ml, respectively. This method features a wide dynamic working range and allows for a rapid routine analysis of flavoring additives in commercial e-cigarette liquids.2 ) values exceeded 0.990 for all chemicals. Bias and precision tests yielded values less than 20% and lower limits of quantitation (LLOQ) ranged from 0.02 to 0.63 mg/ml. Over 200 commercially available products, purchased or collected from adult e-cigarette users and spanning a range of flavor categories, were evaluated with this method. Concentrations of pulegone, a suspected carcinogen, varied from below limit of quantitation (BLOQ) to 0.32 mg/ml, while acetoin and vanillin, known precursors to more cytotoxic byproducts, ranged from BLOQ to 1.52 mg/ml and from BLOQ to 16.22 mg/ml, respectively. This method features a wide dynamic working range and allows for a rapid routine analysis of flavoring additives in commercial e-cigarette liquids., Competing Interests: MG received a research grant from Pfizer and is a member of advisory board to Johnson and Johnson. The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Page and Goniewicz.)

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., (©2021 American Association for Cancer Research.)

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.

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.

Background: Determine the overall, sex-, and racially/ethnically-appropriate population-level cotinine and total nicotine equivalents (TNE-2, the molar sum of the two major nicotine metabolites) cut-points to distinguish tobacco users from nonusers across multiple definitions of use (e.g., exclusive vs. polytobacco, and daily vs. non-daily)., Methods: Using Wave 1 (2013-2014) of the U.S. Population Assessment of Tobacco and Health (PATH) Study, we conducted weighted Receiver Operating Characteristic (ROC) analysis to determine the optimal urinary cotinine and TNE-2 cut-points, stratified by sex and race/ethnicity., Results: For past 30-day exclusive cigarette users, the cotinine cut-point that distinguished them from nonusers was 40.5 ng/mL, with considerable variation by sex (male: 22.2 ng/mL; female: 43.1 ng/mL) and between racial/ethnic groups (non-Hispanic other: 5.2 ng/mL; non-Hispanic black: 297.0 ng/mL). A similar, but attenuated, pattern emerged when assessing polytobacco cigarette users (overall cut-point = 39.1 ng/mL, range = 5.5 ng/mL-80.4 ng/mL) and any tobacco users (overall cut-point = 39.1 ng/mL, range = 4.8 ng/mL-40.0 ng/mL). Using TNE-2, which is less impacted by racial differences in nicotine metabolism, produced a comparable pattern of results although reduced the range magnitude., Conclusions: Because of similar frequency of cigarette use among polytobacco users, overall cut-points for exclusive cigarette use were not substantially different from cut-points that included polytobacco cigarette use or any tobacco use. Results revealed important differences in sex and race/ethnicity appropriate cut-points when evaluating tobacco use status and established novel urinary TNE-2 cut-points., Impact: These cut-points may be used for biochemical verification of self-reported tobacco use in epidemiologic studies and clinical trials., (©2021 American Association for Cancer Research.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Physiological Society.)

Potential mechanisms by which e-cigarette use may relate to combustible cigarette smoking cessation are not well-understood. We used U.S. nationally representative data to prospectively evaluate the relationship between e-cigarette flavor use and frequency of e-cigarette use among adult cigarette/e-cigarette dual users who attempted to quit smoking cigarettes. Analyses used Population Assessment of Tobacco and Health (PATH) Study data from adult dual users (2015/16) who attempted to quit smoking between 2015/16 and 2016/17 (Wave 3-Wave 4, n = 685, including those who did/did not quit by 2016/17). E-cigarette flavor use (usual/last flavor, past 30-day flavor; assessed in 2015/16) was categorized into Only tobacco; Only menthol/mint; Only non-tobacco, non-menthol/mint; and Any combination of tobacco, menthol/mint, other flavor(s). The key outcome, evaluated at follow-up in 2016/17, was frequent e-cigarette use, which was defined as use on 20+ of past 30 days. Logistic regression was used to evaluate associations between e-cigarette flavor use in 2015/16 and frequent e-cigarette use at follow-up in 2016/17. Dual users who attempted to quit smoking had greater odds of frequent e-cigarette use at follow-up when they used only non-tobacco, non-menthol/mint flavor than when they used only tobacco flavor as their regular/last e-cigarette flavor (OR = 1.9, 95% CI: 1.1-3.4); findings were no longer significant when adjusted for factors including e-cigarette device type (AOR = 1.4, 95% CI: 0.7-2.8). Past 30-day e-cigarette flavor use results were generally similar, although frequent e-cigarette use at follow-up was highest among those who used any combination of tobacco, menthol/mint, or other flavors. Findings indicate that e-cigarette flavor use among dual users who attempt to quit smoking may be related to e-cigarette use frequency overall, which may indicate a mechanism underlying findings for e-cigarette use and smoking cessation. Further longitudinal research may help to disentangle how e-cigarette characteristics uniquely impact e-cigarette use frequency and smoking cessation/sustained use.

Following their introduction a decade ago, electronic cigarettes (e-cigarettes) have grown in popularity. Given their novelty, knowledge of the health consequences of e-cigarette use remains limited. Epidemiologic studies have not comprehensively explored associations between e-cigarette use and hypertension, a highly prevalent health condition and major contributor to cardiovascular disease burden. In this study, cross-sectional associations of cigarette smoking and e-cigarette use (vaping) with self-reported diagnosed hypertension were evaluated among 19,147 18-55 year old respondents in Wave 3 (2015-2016) of the Population Assessment of Tobacco and Health Study. Multivariable analyses first modeled smoking and vaping as separate 2-category variables, then as a 6-category composite variable accounting for former smoking. After adjusting for potential confounders, current vaping (aOR = 1.31; 95%CI: 1.05-1.63) and current smoking (aOR = 1.27; 95%CI: 1.10-1.47) were both associated with higher odds of hypertension. In analyses modeling smoking and vaping compositely, respondents who were concurrently smoking and vaping had the highest odds of hypertension (aOR = 1.77; 95%CI: 1.32-2.39 [referent: never smokers]). These results differ somewhat from prior epidemiologic studies of vaping and respiratory outcomes, which consistently report smaller point estimates for current vaping than for current smoking. Our findings reinforce the uncertainty surrounding long-term health consequences of vaping, as well as highlight important distinctions between respiratory and cardiovascular outcomes when considering the harm reduction potential of e-cigarettes.

E-cigarettes have surged in popularity over the last few years, particularly among youth and young adults. These battery-powered devices aerosolize e-liquids, comprised of propylene glycol and vegetable glycerin, typically with nicotine, flavors, and stabilizers/humectants. Although the use of combustible cigarettes is associated with several adverse health effects including multiple pulmonary and cardiovascular diseases, the effects of e-cigarettes on both short- and long-term health have only begun to be investigated. Given the recent increase in the popularity of e-cigarettes, there is an urgent need for studies to address their potential adverse health effects, particularly as many researchers have suggested that e-cigarettes may pose less of a health risk than traditional combustible cigarettes and should be used as nicotine replacements. This report is prepared for clinicians, researchers, and other health care providers to provide the current state of knowledge on how e-cigarette use might affect cardiopulmonary health, along with research gaps to be addressed in future studies., (Published by Oxford University Press on behalf of American Physiological Society 2021. This work is written by US Government employees and is in the public domain in the US.)

Nicotine and cannabis use are common among adolescents and may be associated with behavioral problems, poor academic outcomes and use disorders. The goals of this analysis were the following: (1) Describe the influence of friends' nicotine and cannabis smoking and vaping on self-reported use. (2) Describe the relationship between friends' nicotine and cannabis use on participants' urinary biomarkers of nicotine (cotinine) and cannabis (11-nor-9-carboxy-Δ⁸tetrahydrocannabinol=THC-COOH). This is a secondary analysis of survey and biomarker data collected in adolescents aged 12-21 between April 2017 and April 2018, in Long Island, New York. Bivariate and multivariable analyses were conducted using SPSS 26. A cutoff value of ≥10 ng/mL was used to signify recent usage for urinary cotinine and THC-COOH levels. Over one-third of the 517 surveyed adolescents reported using tobacco and one-third reported using cannabis. A significant relationship between friends' substance use and self-use was found. For both tobacco and cannabis, over 90% ( p < 0.01) of participants with urinary biomarker levels above cutoff had friends who used the respective substance. Friends' nicotine and friends' cannabis use were each independently associated with urinary biomarker levels for those substances (for nicotine, beta = 88.29, p = 0.03; for cannabis, beta = 163.58, p = 0.03). Friends' use of nicotine and cannabis is associated with adolescents' intake, as well as the physiological exposure to those substances. These findings underscore the importance of including peer influence in the discussion with adolescents about tobacco and cannabis use.

Background: Multiple cases of e-cigarette or vaping product use-associated lung injury (EVALI) have been reported in the USA, which have been attributed to informally obtained cannabis oil vaping devices. This report estimated whether cumulative incidence of EVALI differed according to state-level cannabis policy., Methods: Publicly available information was used to estimate the cumulative incidence of EVALI. Odds of incident EVALI were calculated according to policy status (active, legal adult-use recreational policy vs. no legal access). Figures were statistically compared using chi-square tests., Results: Estimated cumulative incidence of EVALI was 5.19 per 100,000 cannabis users across all states with recreational cannabis policies (95% CI 4.70-5.72), and 15.89 per 100,000 cannabis users across all states with no legal access to cannabis (95% CI 14.88-16.96). Odds of EVALI were 3.06 times higher (95% CI 2.71-3.45) among users living in states with no legal access to cannabis compared to users in states with active recreational policies, with significant differences detected according to policy exposure (χ 2 = 385.57, p < 0.0001)., Conclusions: Estimates suggest there may have been a protective effect of state-level, recreational adult-use cannabis policies on incident EVALI. Effects of specific state-level regulations (e.g., laboratory testing, product quality standards, tracking systems) should be considered alongside additional geographic indices in future assessments of EVALI causes.

Background: Electronic cigarettes (e-cigarettes) are widely promoted as harm-reduction products for smokers, and smokers commonly perceive them as less harmful than combustible cigarettes. One of the key questions regarding public health consequences of e-cigarettes is the magnitude of harm reduction achievable by smokers who switch from combustible cigarettes to e-cigarettes. We conducted a systematic literature review of epidemiological studies that estimated odds of respiratory and cardiovascular outcomes among former smokers who use e-cigarettes compared to current smokers., Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched the PubMed and Embase databases in September 2020 to identify epidemiological studies that compared odds of cardiovascular and respiratory outcomes among former smokers who transitioned to e-cigarettes relative to odds among current smokers not using e-cigarettes (current exclusive smokers). We included studies that provided direct estimates of relevant odds ratios (ORs). We also included studies where indirect estimates of relevant ORs could be calculated based on published results. Two reviewers independently extracted data and conducted quality appraisals., Results: Six population-based studies with sample sizes ranging from 19,475 to 161,529 respondents met review inclusion criteria, five of which were cross-sectional and one longitudinal. Three studies reported respiratory outcomes and three reported cardiovascular outcomes. ORs of respiratory outcomes (including chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma, and wheezing) in former smokers who transitioned to e-cigarettes versus current exclusive smokers were below 1.0, ranging from 0.58 (95%CI 0.36-0.94) to 0.66 (95%CI 0.50-0.87; all p < 0.05). All ORs for cardiovascular outcomes (including stroke, myocardial infarction, and coronary heart disease) did not differ significantly from 1.0., Conclusion: Though our review included a small number of studies, it provided consistent results. Former smokers who transitioned to e-cigarettes showed ~ 40% lower odds of respiratory outcomes compared to current exclusive smokers. Switching from smoking to e-cigarette does not appear to significantly lower odds of cardiovascular outcomes. Since the utility of cross-sectional studies for causal inference remains limited, both randomized controlled trials and prospective cohort studies are needed to better evaluate contributions of e-cigarettes as harm reduction tools for smokers.

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.

Introduction : Although electronic cigarettes (e-cigarettes) were originally developed to deliver aerosolized nicotine to lungs, recent data have shown that consumers also use them for inhalation of other drugs, including cannabidiol (CBD). The aim of this study was to test the acute inhalation toxicity of flavored CBD-containing aerosols emitted from e-cigarettes. Methods : Bronchial epithelial cells (H292) cells were exposed to aerosol generated from e-cigarettes refilled either with (1) propylene glycol solvent only (PG, control), (2) commercially purchased unflavored solution with CBD, or (3) commercially purchased solutions with and without CBD and with different flavors. The in vitro toxicological effects were assessed using the following methods: (1) trypan blue exclusion assay (cell viability), (2) neutral red uptake assay (metabolic activity), and (3) ELISA (concentrations of inflammatory mediators). Results : Most flavored products with or without CBD were cytotoxic as compared to the air control. Overall, aerosols with CBD were more cytotoxic than aerosols without CBD irrelevant of the flavoring used in the product. Although, unflavored aerosols containing CBD in PG were significantly more cytotoxic than aerosols containing only PG, not all flavored products containing CBD were significantly more toxic than the same flavored products without CBD. Most CBD containing products significantly increase the concentration of cytokines released as compared to the same flavored products without CBD. Conclusion : Different flavors show different cytotoxic effects in CBD-containing e-cigarettes. Aerosols emitted from CBD containing e-cigarettes were more cytotoxic than those emitted from CBD-free e-cigarettes., (Copyright © 2020 Leigh and Goniewicz.)

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

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., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. M.L. Goniewicz reports personal fees from Johnson & Johnson, outside the submitted work. R.J. O'Connor reports grants from National Institutes of Health during the conduct of the study, personal fees and non-financial support from Food and Drug Administration, and from World Health Organization, and personal fees from National Institutes of Health, outside the submitted work., (© 2020 Shi H. et al.)

This descriptive study of smokers (smoked at least monthly) and recent ex-smokers (quit for ≤2 years) examined transitions over an 18 month period in their smoking and vaping behaviors. Data are from Waves 1 (W1: 2016) and 2 (W2: 2018) of the ITC Four Country Smoking and Vaping Survey, a cohort study of adult (≥18+) smokers, concurrent users (smoke and vape), and recent ex-smokers from Australia, Canada, England, and the United States (US). Respondents (N = 5016) were classified according to their smoking and vaping status, which resulted in eight subgroups: (1) exclusive daily smokers (2) exclusive non-daily smokers; (3-6) concurrent users (subdivided into four groups by each combination of daily/non-daily smoking and daily/non-daily vaping); (7) ex-smokers who vape; (8) ex-smokers not vaping. The analyses focused first on describing changes between groups from W1 to W2. Second, transition outcomes were assessed based on changes in smoking and vaping between W1 and W2. Transitions focused on smoking were: no change in smoking (continued smoking at the same frequency); decreased smoking; increased smoking; discontinued smoking; relapsed (ex-smokers at W1 who were smoking at W2). Transitions focused on vaping were: initiated vaping; switched from smoking to vaping. Overall, this study found that the vast majority of smokers were smoking 18 months later. Non-daily smokers were more likely than daily smokers to have discontinued smoking ( p < 0.0001) and to have switched to exclusive vaping ( p = 0.034). Exclusive non-daily smokers were more likely than exclusive daily smokers to have initiated vaping ( p = 0.04). Among all W1 daily smokers, there were no differences in discontinued smoking between daily smokers who vaped (concurrent users) and exclusive daily smokers; however, concurrent users were more likely than exclusive daily smokers to have decreased to non-daily smoking ( p < 0.001) or to have switched to vaping by W2 ( p < 0.001). Among all W1 non-daily smokers, there were no significant differences in increased smoking or discontinued smoking between concurrent users or exclusive smokers. Most ex-smokers remained abstinent from smoking, and there was no difference in relapse back to smoking between those who vaped and those who did not., Competing Interests: KMC has received payment as a consultant to Pfizer, Inc., for service on an external advisory panel to assess ways to improve smoking cessation delivery in healthcare settings. KMC also has served as paid expert witness in litigation filed against cigarette manufacturers. GTF, DH, and JFT have served as expert witnesses on behalf of governments in litigation involving the tobacco industry. MLG has received a research grant from Pfizer and served as a member of scientific advisory board to Johnson and Johnson. AM is a UK National Institute for Health Research (NIHR) Senior Investigator. The views expressed in this article are those of the authors and not necessarily those of the NIHR, or the UK Department of Health and Social Care. All other authors have no conflicts of interest to declare.

Introduction: Tobacco companies have introduced heated tobacco products (HTPs), such as IQOS, which may compete with e-cigarettes among smokers interested in switching to potentially reduced-risk products. Non-smokers may also start using IQOS if they believe this product is less harmful than other nicotine products. Smokers' and non-smokers' decisions may be driven by relative harm perceptions of emerging nicotine products. We aimed to examine relative harm perceptions between IQOS, e-cigarettes, and cigarettes, among nicotine product users and non-users., Methods: We conducted a web survey with Canadian respondents (aged ≥20 years; n=268) in September-October 2018. Perceptions about relative harm between IQOS (available for sale since 2017 and subject to the same comprehensive marketing restrictions as cigarettes in Canada), e-cigarettes, and cigarettes, were assessed among non-users (n=79), exclusive smokers (n=78), exclusive e-cigarette users (n=32), and dual users (n=79). Multiple logistic regression explored the association between relative harm perceptions and nicotine-use status, adjusting for sociodemographic variables., Results: Over half of respondents perceived IQOS as equally or more harmful than e-cigarettes (53.7%), while almost a quarter either reported IQOS as less harmful than e-cigarettes or were uncertain (22.7% and 23.5%, respectively). Two-thirds of respondents (65.7%) perceived e-cigarettes as less harmful than cigarettes, yet only half (48.1%) perceived IQOS as less harmful than cigarettes. Both exclusive and dual e-cigarette users, but not exclusive smokers, had higher odds of perceiving IQOS as more harmful than e-cigarettes and less harmful than cigarettes compared to non-users., Conclusions: Most nicotine users and non-users perceive differential health risk across IQOS, e-cigarettes, and cigarettes. Although e-cigarettes are generally viewed as less harmful than cigarettes, the perceived harm of IQOS was unclear., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. R.J. O’Connor reports personal fees and non-financial support from World Health Organization and from Food and Drug Administration. In addition, he reports grants, personal fees and non-financial support from the National Institutes of Health, outside the submitted work. D. Hammond reports that he has received research grants from public health and government agencies to study tobacco and nicotine use, and has provided expert testimony on behalf of governments and public health authorities in response to legal challenges from tobacco, cannabis and e-cigarette companies. K.M. Cummings reports having received payments as an expert witness on behalf of plaintiff’s in litigation against cigarette manufacturers. G.T. Fong reports that he has served as an expert witness on behalf of governments in litigation involving the tobacco industry. Finally, M.L. Goniewicz reports personal fees from Johnson & Johnson, outside the submitted work., (© 2020 Sutanto E. et al.)

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.

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., Competing Interests: KMC has received payment as a consultant to Pfizer, Inc., for service on an external advisory panel to assess ways to improve smoking cessation delivery in health care settings. KMC also has served as paid expert witness in litigation filed against the tobacco industry. MG receives fees for serving on an advisory board from Johnson & Johnson and grant support from Pfizer. WC reports long-term stock holdings in General Electric Company, 3M Company, and Pfizer Incorporated, unrelated to this manuscript. Westat is a commercial, employee-owned research corporation. This does not alter our adherence to PLOS ONE policies on sharing data and materials.