The "Gateway" hypothesis: evaluation of evidence and alternative explanations.

BACKGROUND: Electronic nicotine delivery systems (ENDS) offer a substantial harm reduction opportunity for adults who smoke and are unlikely to quit. However, a major concern about ENDS is their use by non-smoking youth, and particularly whether ENDS are acting as a "gateway" that leads youth to later start smoking cigarettes. However, evidence for the gateway hypothesis can be interpreted in alternative ways, e.g. that youth who have certain characteristics were already predisposed to use both ENDS and cigarettes ("common liability" explanation). AIMS: This commentary provides an evaluation of the gateway hypothesis that is accessible by a lay audience. This paper first reviews and evaluates the evidence interpreted as supporting the gateway hypothesis. Important alternative explanations (i.e., common liability) are discussed, as are different types of evidence (i.e., population-level trends) that can help differentiate between these competing explanations. OVERVIEW: Evidence for the gateway hypothesis is based on the finding that youth who use ENDS are more likely to also smoke cigarettes. However, this evidence suffers from an important flaw: these studies fail to fully account for some youths' pre-existing tendency to use products containing nicotine, and inappropriately interpret the results as ENDS use causing some youth to smoke. Common liability studies suggest that ENDS use does not, in and of itself, directly cause youth to later smoke cigarettes, beyond their pre-existing tendency to use products containing nicotine. Population-level trends show that youth cigarette smoking declined faster after ENDS use became common, which contradicts the central prediction of the gateway hypothesis (i.e. that youth smoking would be more common following ENDS uptake, than otherwise be expected). CONCLUSION: Evidence offered in support of the gateway hypothesis does not establish that ENDS use causes youth to also smoke cigarettes. Instead, this evidence is better interpreted as resulting from a common liability to use both ENDS and cigarettes. Population-level trends are inconsistent with the gateway hypothesis, and instead are consistent with (but do not prove) ENDS displacing cigarettes. Policies based on misinterpreting a causal gateway effect may be ineffective at best, and risk the negative unintended consequence of increased cigarette smoking.

Do Acculturative Gap Conflicts Impact Parenting Practices and Youth E-Cigarette Use? Tests of Moderated Mediation.

BACKGROUND: Latino/a youth are at increased risk of electronic (e)-cigarette or electronic nicotine delivery systems (ENDS) use; thus, identifying factors impacting initiation is critical. Parenting practices reflecting warmth (e.g., relationship quality) and control (e.g., parental monitoring) and substance use-specific parenting (e.g., reactions to use, parenting self-efficacy) may influence youth substance use. For Latino/a youth, tensions from intergenerational acculturative differences are linked to substance use. We investigated ENDS use-specific parenting as a mediator between general parenting and youth ENDS use, examining whether acculturative gap conflict moderated the association between general and ENDS use-specific parenting. We expected mediation among families experiencing low acculturative gap conflicts. METHOD:  Data were analyzed over two waves from a predominantly White and Latino/a sample of caregiver-child dyads (N = 143) who identified with a culture in addition to or distinct from American. Youth (Mage = 14.9 years, SD = 0.67; 62.9% female) reported relationship quality, parental monitoring, caregiver ENDS attitudes and reactions, acculturative gap conflicts, and ENDS use. Caregivers reported on ENDS use-specific parenting self-efficacy. Two moderated multiple mediator regression models (i.e., relationship quality, parental monitoring) were estimated. RESULTS:  Among youth reporting low and mean levels of acculturative gap conflict, ENDS use-specific parenting self-efficacy mediated the association between relationship quality and reduced ENDS use. There was no evidence for an interaction in the parental monitoring model. CONCLUSIONS:  In families experiencing low levels of acculturative gap conflict, relationship quality may impact ENDS use through caregivers' confidence in their ability to prevent child ENDS use.

Electronic Nicotine Delivery Systems (ENDS) use Among Members of a Community Engagement Program.

Electronic nicotine delivery systems (ENDS) are relatively new and ENDS use data from community engagement programs may help us understand usage patterns and facilitate targeted longitudinal studies. Community members in Florida, USA, were asked about ENDS use, tobacco use, and health history/concerns by Community Health Workers. Among 7253 members recruited during 2014 to 2021 into our HealthStreet program, 1177 had ever used ENDS; the proportion increased from 12 to 27% from 2014 to 2021 (adjusted odds ratio (aOR) 2.5; 95% CI 1.7-3.5; Ever versus never used ENDS). Ever tobacco use was strongly associated with ENDS use; 69% of ever users were current tobacco users. Demographic determinants (sex, age, race) and food insecurity were strongest predictors of ENDS use. Most who had ever used ENDS were aged 18-25 (aOR 5.9; 95% CI 4.6-7.6; vs. aged 60 + years), White (aOR 3.7; 95% CI 3.2-4.3; vs. Black/African American), male (aOR 1.5; 95% CI 1.3-1.7; vs. female), and recently food insecure (aOR 1.8; 95% CI 1.5-2.0; vs. not recently food insecure). Those with respiratory issues were more likely to have used ENDS compared to those without (aOR 2.0; 95% CI 1.6-2.6; aOR 1.3; 95% CI 1.1-1.5). Members concerned about hypertension were less likely to have used ENDS (aOR 0.7; 95% CI 0.5-0.9). In this relatively rural, micropolitan sample, tobacco use, socio-economic determinants, and certain health history/concerns were strongly associated with ENDS use. Community outreach approaches are needed to further understand these factors and implement interventions.

Color stability of resin-based composites exposed to smoke. A systematic review.

OBJECTIVE: To conduct a systematic review on color stability of dental resin-based composites (RBC) exposed to conventional and electronic cigarettes. MATERIALS AND METHODS: In vitro studies reporting on the color stability of RBC exposed to conventional cigarettes or to e-cigarettes: both Tobacco Heating Systems (THS) and Electronic Nicotine Delivery Systems (ENDS). The quality of the included studies was assessed with the QUIN tool (risk-of-bias tool for assessing in vitro studies conducted in dentistry). A systematic search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed on four (n = 4) databases (Embase, Medline, Scopus, Web of Science) for articles published until March 28th, 2022. RESULTS: Of the 365 screened articles, 13 were included in this review. All the included articles analyzed conventional cigarette smoke (CS), four analyzed Electronic Nicotine Delivery Systems (ENDS) and two Tobacco Heating Systems (THS). In terms of study design, smoke exposure time, smoke flow, type and number of cigarettes a high variability was reported. CONCLUSIONS: The available evidence suggests that CS smoke significantly affects color stability. Electronic cigarettes show less color change that seems to be easily recovered under clinical acceptability thresholds, although evidence is scarce. CLINICAL SIGNIFICANCE: Clinicians should be aware, and should therefore warn their patients, that RBCs are subjected to irreversible color change if exposed to smoke. Electronic cigarettes (both ENDS and THS) induce less color change that can be recovered with repolishing or whitening procedures.

Exploring the potential neurotoxicity of vaping vitamin E or vitamin E acetate.

Serious adverse health effects have been reported with the use of vaping products, including neurologic disorders and e-cigarette or vaping product use-associated lung injury (EVALI). Vitamin E acetate, likely added as a diluent to cannabis-containing products, was linked to EVALI. Literature searches were performed on vitamin E and vitamin E acetate-associated neurotoxicity. Blood brain barrier (BBB) penetration potential of vitamin E and vitamin E acetate were evaluated using cheminformatic techniques. Review of the literature showed that the neurotoxic potential of inhalation exposures to these compounds in humans is unknown. Physico-chemical properties demonstrate these compounds are lipophilic, and molecular weights indicate vitamin E and vitamin E acetate have the potential for BBB permeability. Computational models also predict both compounds may cross the BBB via passive diffusion. Based on literature search, no experimental nonclinical studies and clinical information on the neurotoxic potential of vitamin E via inhalation. Neurotoxic effects from pyrolysis by-product, phenyl acetate, structurally analogous to vitamin E acetate, suggests vitamin E acetate has potential for central nervous system (CNS) impairment. Cheminformatic model predictions provide a theoretical basis for potential CNS permeability of these inhaled dietary ingredients suggesting prioritization to evaluate for potential hazard to the CNS.

Cigarette smoke preparations, not electronic nicotine delivery system preparations, induce features of lung disease in a 3D lung repeat-dose model.

Cigarette smoking is a risk factor for several lung diseases, including chronic obstructive pulmonary disease, cardiovascular disease, and lung cancer. The potential health effects of chronic use of electronic nicotine delivery systems (ENDS) is unclear. This study utilized fully differentiated primary normal human bronchial epithelial (NHBE) cultures in a repeat-dose exposure to evaluate and compare the effect of combustible cigarette and ENDS preparations. We show that 1-h daily exposure of NHBE cultures over a 10-day period to combustible cigarette whole smoke-conditioned media (WS-CM) increased expression of oxidative stress markers, cell proliferation, airway remodeling, and cellular transformation markers and decreased mucociliary function including ion channel function and airway surface liquid. Conversely, aerosol conditioned media (ACM) from ENDS with similar nicotine concentration (equivalent-nicotine units) as WS-CM and nicotine alone had no effect on those parameters. In conclusion, primary NHBE cultures in a repeat-dose exposure system represent a good model to assess the features of lung disease. This study also reveals that cigarette and ENDS preparations differentially elicit several key endpoints, some of which are potential biomarkers for lung cancer or chronic obstructive pulmonary disease (COPD).

Sub-ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air-liquid interface.

BACKGROUND: Exposure to electronic-cigarette (e-cig) aerosols induces potentially fatal e-cig or vaping-associated lung injury (EVALI). The cellular and molecular mechanisms underlying these effects, however, are unknown. We used an air-liquid interface (ALI) in vitro model to determine the influence of two design characteristics of third-generation tank-style e-cig devices-resistance and voltage-on (1) e-cig aerosol composition and (2) cellular toxicity. METHODS: Human bronchial epithelial cells (H292) were exposed to either butter-flavored or cinnamon-flavored e-cig aerosols at the ALI in a Vitrocell exposure system connected to a third-generation e-cig device. Exposures were conducted following a standard vaping topography profile for 2 h per day, for 1 or 3 consecutive days. 24 h after ALI exposures cellular and molecular outcomes were assessed. RESULTS: We found that butter-flavored e-cig aerosol produced under 'sub-ohm' conditions (< 0.5 Ω) contains high levels of carbonyls (7-15 µg/puff), including formaldehyde, acetaldehyde and acrolein. E-cig aerosol produced under regular vaping conditions (resistance > 1 Ω and voltage > 4.5 V), contains lower carbonyl levels (< 2 µg/puff). We also found that the levels of carbonyls produced in the cinnamon-flavored e-cig aerosols were much lower than that of the butter-flavored aerosols. H292 cells exposed to butter-flavored or cinnamon-flavored e-cig aerosol at the ALI under 'sub-ohm' conditions for 1 or 3 days displayed significant cytotoxicity, decreased tight junction integrity, increased reactive oxygen species production, and dysregulated gene expression related to biotransformation, inflammation and oxidative stress (OS). Additionally, the cinnamon-flavored e-cig aerosol induced pro-oxidant effects as evidenced by increases in 8-hydroxy-2-deoxyguanosine protein levels. Moreover, we confirmed the involvement of OS as a toxicity process for cinnamon-flavored e-cig aerosol by pre-treating the cells with N-acetyl cysteine (NAC), an antioxidant that prevented the cells from the OS-mediated damage induced by the e-cig aerosol. CONCLUSION: The production of high levels of carbonyls may be flavor specific. Overall, inhaling e-cig aerosols produced under 'sub-ohm' conditions is detrimental to lung epithelial cells, potentially via mechanisms associated with OS. This information could help policymakers take the necessary steps to prevent the manufacturing of sub-ohm atomizers for e-cig devices.

Motivations for using electronic cigarettes in young adults: A systematic review.

Background: The most common reasons why adults use e-cigarettes are to stop or reduce tobacco smoking. However, it is unclear if this reason is evenly distributed between young and older adults. Objectives: describe the motivations for e-cigarette use amongst young adults aged 18-25 and compare the reasons for using e-cigarettes of people who currently or formerly used tobacco products to those who had never smoked tobacco prior e-cigarette use. Methods: PubMed®, Scopus®, Cochrane Library®, SocINDEX®, PsycARTICLES®, Psychology and Behavioral Sciences Collection® and PsycINFO® databases were used. English written articles were screened up to March 2018. Depending on study design, quality was assessed using The STROBE or RATS checklists. Results: Six articles were included in the review, all with a moderate quality of evidence. Independently of smoking status, curiosity was the most frequently reported reason for initiating the use of e-cigarettes in young adults. Reasons for continuing to use e-cigarettes were various. The continued use of e-cigarettes could be either a means to replicate smoking habits, or a way for a different and personalized use of nicotine by inhalation. Conclusions: Reasons for using e-cigarettes in young adults are varied and are not limited to stopping smoking.

Socioeconomic Disparities in Vape Shop Density and Proximity to Public Schools in the Conterminous United States, 2018.

We conducted an environmental justice assessment examining the distribution of specialty vape shops in relation to where minority and low-income youth live and attend school. We collated and examined the density of vape shops in public school districts in 2018 throughout the conterminous United States using geographic information systems. We calculated the proximity of vape shops to public middle and high schools through nearest neighbor analysis in QGIS software. We examined the statistical relationships between the density of vape shops in school districts, and proximity to schools, with the proportion of racial/ethnic minorities and those living in poverty. We found that vape shops are more densely distributed, and are in closer proximity to schools, in school districts with higher proportions of Asian and Black or African American populations. However, vape shops were further away from schools in school districts with higher proportions of the population in poverty. The proximity and higher density of vape shops in relationship to schools in Asian and Black or African American communities may result in disproportionate health impacts due to greater access and exposure to vape products and advertisements. Our results may help school district administrators prioritize and target efforts to curb youth vaping (e.g., health education curricula) in these school districts with high density and closer proximity of vape shops to schools. Policy efforts, such as local ordinances restricting the promotion and sale of vaping products close to schools, could help prevent disproportionate human and environmental health impacts to minorities.

Health claims made in vape shops: an observational study and content analysis.

BACKGROUND: Prior to the final deeming rule, federal law in the USA prohibited electronic cigarettes (e-cigarettes) from being marketed as smoking cessation products; for other therapeutic purposes and in ways that conveyed Food and Drug Administration (FDA) approval/endorsement. After August 2016, additional federal prohibitions were added including false/misleading and unauthorised modified risk tobacco product (MRTP) claims. No systematic investigation of e-cigarette health claims has been conducted in the retail environment. We sought to document and characterise claims made in vape shops. METHODS: Between November 2015 and February 2016, before final deeming rule implementation, two trained data collectors conducted unannounced observational assessments of 46 vape shops in North Carolina. Data collectors used wearable imaging technology to document health claims about e-cigarettes. Photos were coded for five claim types: (1) cessation device; (2) drug effect/device; (3) FDA-approved/endorsed; (4) false/misleading and (5) MRTP. Photos were double coded; differences between coders were adjudicated and reviewed by an expert panel. RESULTS: At least one health claim was displayed in 41.3% (n=19) of retailers, ranging from 0 to 27 claims per retailer. All claim types were found. Cessation device claims were the most prevalent (62.2%, n=84), followed by MRTP (27.4%, n=37), drug effect/device (8.1%, n=11), false/misleading (1.5%, n=2), and FDA approved/endorsed (0.7%, n=1). Retail chains made the majority of claims compared with independent shops (88.9% vs 11.1%). CONCLUSIONS: Many vape shops displayed e-cigarette health claims, which are all now FDA prohibited. These claims could mislead consumers and influence behaviour. Findings highlight the need for retailer education, continued surveillance, enforcement specific to advertising and research on consumer perceptions of claims.

Dual use of electronic nicotine delivery systems (ENDS) and smoked tobacco: a qualitative analysis.

INTRODUCTION: Electronic nicotine delivery systems (ENDS) arguably pose fewer health risks than smoking, yet many smokers adopt ENDS without fully relinquishing smoking. Known as 'dual use', this practice is widespread and compromises the health benefits that ENDS may offer. To date, few studies have explored how dual use practices arise and manifest. METHODS: We conducted in-depth, semi-structured interviews with 20 current ENDS users from New Zealand who reported smoking tobacco at least once a month. We explored participants' smoking history, their recent and current smoking, trial, uptake and patterns of ENDS use, and future smoking and vaping intentions. We managed the data using NVivo V.11 and used a thematic analysis approach to interpret the transcripts. RESULTS: Dual use practices among participants evolved in four ways. First, as an attempt to manage the 'inauthenticity' of vaping relative to smoking and to retain meaningful rituals. Second, as complex rationalisations that framed decreased tobacco use, rather than smoking cessation, as 'success'. Third, as a means of alleviating the financial burden smoking imposed and to circumvent smoke-free policies. Lastly, dual use reflected attempts to comply with social group norms and manage stigma. CONCLUSIONS: Dual use reflects both social and physical cues. It assisted participants to navigate smoking restrictions and allowed them to manage divergent norms. Policies that discourage smoking, particularly excise tax increases on smoked tobacco and smoke-free space restrictions, appear important in prompting ENDS use. Future research could explore whether these policies also help foster complete transition from smoking to exclusive ENDS use.

Electronic Nicotine Delivery Systems (E-cigarette/Vape) use and Co-Occurring Health-Risk Behaviors Among an Ethnically Diverse Sample of Young Adults.

BACKGROUND: Prevalence rates of electronic nicotine delivery systems (ENDS; i.e., e-cigarette/vape) use has grown exponentially in the past few years. College students present a particularly vulnerable group for ENDS use. The current study sought to expand the literature by examining the context in which college students use ENDS, co-occurring health risks beyond traditional tobacco use, and the role of ethnicity in ENDS use. METHODS: Health-risk behavior survey data was collected from 452 undergraduates attending a large, public urban university during the 2015-2016 academic year. Ever ENDS users vs. non-ENDS users were compared across potential demographic, health-risk, and other health-related correlates. RESULTS: Almost 40% of participants reported lifetime use of ENDS. No ethnic or sex differences were found. The primary source for obtaining ENDS was friends and ENDS were most often used with friends vs. alone or with others not considered friends. Participants engaging in risky alcohol use and cigarette smoking had a higher likelihood of endorsing ENDS use. Conclusions/Importance: The current study indicated that a large proportion of college students have tried ENDS irrespective of ethnicity or sex. An increasingly normative social context may inform the popularity of ENDS use across ethnicity and sex, but additional research using ethnically diverse samples is warranted. Risky alcohol use appears to be a significant correlate of ENDS use, even after accounting for the robust relationship between ENDS use and cigarette smoking. The robust relationship between alcohol and tobacco use likely extends to ENDS use.

Intention to Experiment With E-Cigarettes in a Cross-Sectional Survey of Undergraduate University Students in Hungary.

BACKGROUND: Electronic cigarettes are often used to promote cessation. Only a few studies have explored the motivations for e-cigarette experimentation among young adults. OBJECTIVES: The goals of this study were to assess the intention to try e-cigarettes among Hungarian university students and to develop a motivational scale to measure vulnerability to e-cigarette experimentation. METHODS: 826 Hungarian university students completed an internet-based survey in 2013 to measure motives for trying e-cigarettes. We conducted exploratory factor analyses and identified factors that promote and deter experimentation. Logistic regression analysis was performed to test the concurrent predictive validity of the identified motivational factors and we used these factors to predict e-cigarette experimentation, controlling for other known correlates of e-cigarette use. RESULTS: 24.9% of the participants have ever tried an e-cigarette and 17.2% of current nonsmokers experimented with the product. Almost 11% of respondents intended to try an e-cigarette in the future, yet only 0.6% were current e-cigarette users. Six factors were identified in the motivational scale for experimentation, four that promote usage (health benefits/smoking cessation; curiosity/taste variety; perceived social norms; convenience when smoking is prohibited) and two that deter usage (chemical hazard; danger of dependence). In a logistic regression analysis, the curiosity/taste factor was the only motivational factor significantly associated with the intention to try e-cigarettes in the future. CONCLUSIONS: This is the first study to test a motivational scale about what motivates e-cigarettes usage among university students. Additional research is needed to better understand these factors and their influence on e-cigarette uptake.

Formaldehyde and the Transient Receptor Potential Ankyrin-1 Contribute to Electronic Cigarette Aerosol-induced Endothelial Dysfunction in Mice.

Electronic Nicotine Delivery Systems (ENDS) aerosol exposures can induce endothelial dysfunction (ED) in healthy young humans and animals. Thermal degradation of ENDS solvents, propylene glycol and vegetable glycerin (PG: VG), generates abundant formaldehyde (FA) and other carbonyls. Because FA can activate the transient receptor potential ankyrin-1 (TRPA1) sensor, we hypothesized that FA in ENDS aerosols provokes TRPA1-mediated changes that include ED and 'respiratory braking' - biomarkers of harm. To test this, wild-type (WT) and TRPA1-null mice were exposed by inhalation to either filtered air, PG: VG-derived aerosol, or formaldehyde (FA, 5 ppm). Short-term exposures to PG: VG and FA induced ED in female WT but not in female TRPA1-null mice. Moreover, acute exposures to PG: VG and FA stimulated respiratory braking in WT but not in TRPA1-null female mice. Urinary metabolites of FA (ie, N  -1,3-thiazolidine-4-carboxylic acid, TCA; N  -1,3-thiazolidine-4-carbonyl glycine, TCG) and monoamines were measured by LC-MS/MS. PG: VG and FA exposures significantly increased urinary excretion of both TCA and TCG in both WT and TRPA1-null mice. To confirm that inhaled FA directly contributed to urinary TCA, mice were exposed to isotopic 13C-FA gas (1 ppm, 6 h).13C-FA exposure significantly increased the urine level of 13C-TCA in the early collection (0-3 h) supporting a direct relationship between inhaled FA and TCA. Collectively, these data suggest that ENDS use may increase CVD risk dependent on FA, TRPA1, and catecholamines, yet independently of either nicotine or flavorants. This study supports that levels of FA in ENDS-derived aerosols should be lowered to mitigate CVD risk in people who use ENDS.

Cigarette smoking, e-cigarette use, and sociodemographic correlates of mental health and tobacco-related disease risk in the All of Us research program.

SIGNIFICANCE: Research on the conditions under which electronic cigarette (EC) use produces a net reduction in the population harm attributable to combusted cigarette (CC) use requires the triangulation of information from cohort(s) of smokers, non-smokers, EC users, and dual-users of all varieties. MATERIALS AND METHODS: This project utilizes data from the All of Us Research Program to contrast a panel of wellness and disease-risk indicators across a range of self-reported tobacco-use profiles, including smokers, current, and former EC users. This article focuses on the tobacco use history and current tobacco use status among All of Us participants enrolled between May 2017 and February 2023 (Registered Controlled Tier Curated Data Repository [CDR] v7). RESULTS: The present analytic sample included an unweighted total of N = 412 211 individuals with information on ever-use of both CC and EC. Among them, 155 901 individuals have a history of CC use, with 65 206 identified as current smokers. EC usage is reported by 64 002 individuals, with 16 619 being current users. Model predicted analyses identified distinct patterns in CC and EC usage across demographic and socioeconomic variables, with younger ages favoring ECs. DISCUSSION: Age was observed to significantly affect EC usage, and gender differences reveal that males were significantly more likely to use CC and/or EC than females or African Americans of any gender. Higher educational achievement and income were associated with lower use of both CC and EC, while lower levels of mental health were observed to increase the likelihood of using CC and EC products. CONCLUSION: Findings suggest the potential for the All of Us Research Program for investigation of causal factors driving both behavioral use transitions and cessation outcomes.

Investigative analysis of blood-brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models.

INTRODUCTION: Seizures are known potential side effects of nicotine toxicity and have been reported in electronic nicotine delivery systems (ENDS, e-cigarettes) users, with the majority involving youth or young adults. AREAS COVERED: Using chemoinformatic computational models, chemicals (including flavors) documented to be present in ENDS were compared to known neuroactive compounds to predict the blood-brain barrier (BBB) penetration potential, central nervous system (CNS) activity, and their structural similarities. The literature search used PubMed/Google Scholar, through September 2023, to identify individual chemicals in ENDS and neuroactive compounds.The results show that ENDS chemicals in this study contain >60% structural similarity to neuroactive compounds based on chemical fingerprint similarity analyses. The majority of ENDS chemicals we studied were predicted to cross the BBB, with approximately 60% confidence, and were also predicted to have CNS activity; those not predicted to passively diffuse through the BBB may be actively transported through the BBB to elicit CNS impacts, although it is currently unknown. EXPERT OPINION: In lieu of in vitro and in vivo testing, this study screens ENDS chemicals for potential CNS activity and predicts BBB penetration potential using computer-based models, allowing for prioritization for further study and potential early identification of CNS toxicity.

Intended and unintended effects of e-cigarette taxes on youth tobacco use.

Over the past decade, rising youth use of e-cigarettes and other electronic nicotine delivery systems (ENDS) has contributed to aggressive regulation by state and local governments. Between 2010 and mid-2019, ten states and two large counties adopted ENDS taxes. We use two large national surveys (Monitoring the Future and the Youth Risk Behavior Surveillance System) to estimate the impact of ENDS taxes on youth tobacco use. We find that ENDS taxes reduce youth ENDS consumption, with estimated ENDS tax elasticities of -0.06 to -0.21. However, we estimate sizable positive cigarette cross-tax effects, suggesting economic substitution between cigarettes and ENDS for youth. These substitution effects are particularly large for frequent cigarette smoking. We conclude that the unintended effects of ENDS taxation may considerably undercut or even outweigh any public health gains.

Longitudinal transitions in e-cigarette and cigarette use among US adults: prospective cohort study.

Background: To support tobacco control efforts, this study sought to characterize longitudinal transitions in use of electronic nicotine delivery systems (ENDS) and cigarettes. Methods: Participants were nationally representative samples of 53,729 US adults from Waves 3-5 (2015-2019) of the Population Assessment of Tobacco and Health Study. We examined behavioral transitions (initiation, relapse, progression, and cessation) in ENDS and cigarette use across waves. Weighted generalized estimating equation models adjusted for sociodemographic variables. Findings: Of never ENDS users at baseline, an estimated 1.7% reported initiating ENDS use by follow-up. Of former ENDS users, an estimated 12.1% relapsed into ENDS use. Of periodic ENDS users at baseline, 13% progressed to established ENDS use. Of baseline current ENDS users, 46.3% discontinued ENDS use. The corresponding transitions for cigarette smoking were 1.6% (initiation), 4.8% (relapse), 21.1% (progression), and 14% (discontinuation). Adults aged 18-24 (vs. older age), Hispanics (vs. non-Hispanic white), and past 12-month cannabis users were more likely to initiate ENDS or cigarettes (all p < 0.05). Having any internalizing mental health symptoms increased the odds of ENDS initiation, while externalizing symptoms increased the odds of cigarette initiation. Those who perceived nicotine as very harmful (vs. none/low harm) were more likely to discontinue ENDS. Current cigarette users (vs. non-users) at baseline were more likely to initiate, relapse, or discontinue ENDS (all p < 0.05) and vice versa. Interpretation: We observed high changeability in ENDS and cigarette use among US adults over time. In absolute terms, ENDS use grew, while smoking fell. Tobacco control programs should focus on priority populations, including young adults and people with internalizing and externalizing mental health symptoms. Funding: National Institutes of Health, R01-CA246606-01A1, R01-DA048390.

e-Cigarettes Used by Adolescents to Try to Quit Smoking Are Associated With Less Quitting: A Cross-Sectional Analysis of the National Youth Tobacco Survey.

PURPOSE: This paper determines the association between youth e-cigarette use "to try to quit using other tobacco products, such as cigarettes" and having stopped smoking cigarettes (defined as an ever cigarette smoker who did not smoke in the past 30 days). METHODS: This study uses data from the NYTS from 2015 through 2021, focusing on youth who started smoking cigarettes before they started using e-cigarettes. Associations between using e-cigarettes to quit and having stopped smoking were computed using logistic regression accounting for the complex survey design and adjusting for level of nicotine dependence, year, age, gender, and race/ethnicity. Sensitivity analyses allowed for having started cigarettes and e-cigarettes in the same year and without regard for starting sequence. RESULTS: The primary analytic subsample included 6435 United States middle and high school students (mean age 15.9 years, 55.4% male). Using e-cigarettes to quit was associated with significantly lower odds of having stopped smoking cigarettes (odds ratio, 0.62; 95% confidence interval, 0.45-0.85), controlling for nicotine dependence and demographics. Youth with higher levels of nicotine dependence also had lower odds of having stopped smoking. The results were stable over time. Sensitivity analyses produced similar results. DISCUSSION: Ever-smoking youth who used e-cigarettes "to try to quit using other tobacco products, such as cigarettes" had lower odds of having stopped smoking cigarettes than those who did not use e-cigarettes as to try to quit. Physicians, regulators, and educators should discourage youth from attempting to use e-cigarettes as a way to stop smoking cigarettes.