Vaping and Lung Inflammation and Injury.

The use of electronic (e)-cigarettes was initially considered a beneficial solution to conventional cigarette smoking cessation. However, paradoxically, e-cigarette use is rapidly growing among nonsmokers, including youth and young adults. In 2019, this rapid growth resulted in an epidemic of hospitalizations and deaths of e-cigarette users (vapers) due to acute lung injury; this novel disease was termed e-cigarette or vaping use-associated lung injury (EVALI). Pathophysiologic mechanisms of EVALI likely involve cytotoxicity and neutrophilic inflammation caused by inhaled chemicals, but further details remain unknown. The undiscovered mechanisms of EVALI are a barrier to identifying biomarkers and developing therapeutics. Furthermore, adverse effects of e-cigarette use have been linked to chronic lung diseases and systemic effects on multiple organs. In this comprehensive review, we discuss the diverse spectrum of vaping exposures, epidemiological and clinical reports, and experimental findings to provide a better understanding of EVALI and the adverse health effects of chronic e-cigarette exposure.

Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products: A Scientific Statement From the American Heart Association.

Vaping and electronic cigarette (e-cigarette) use have grown exponentially in the past decade, particularly among youth and young adults. Cigarette smoking is a risk factor for both cardiovascular and pulmonary disease. Because of their more limited ingredients and the absence of combustion, e-cigarettes and vaping products are often touted as safer alternative and potential tobacco-cessation products. The outbreak of e-cigarette or vaping product use-associated lung injury in the United States in 2019, which led to >2800 hospitalizations, highlighted the risks of e-cigarettes and vaping products. Currently, all e-cigarettes are regulated as tobacco products and thus do not undergo the premarket animal and human safety studies required of a drug product or medical device. Because youth prevalence of e-cigarette and vaping product use was as high as 27.5% in high school students in 2019 in the United States, it is critical to assess the short-term and long-term health effects of these products, as well as the development of interventional and public health efforts to reduce youth use. The objectives of this scientific statement are (1) to describe and discuss e-cigarettes and vaping products use patterns among youth and adults; (2) to identify harmful and potentially harmful constituents in vaping aerosols; (3) to critically assess the molecular, animal, and clinical evidence on the acute and chronic cardiovascular and pulmonary risks of e-cigarette and vaping products use; (4) to describe the current evidence of e-cigarettes and vaping products as potential tobacco-cessation products; and (5) to summarize current public health and regulatory efforts of e-cigarettes and vaping products. It is timely, therefore, to review the short-term and especially the long-term implications of e-cigarettes and vaping products on cardiopulmonary health. Early molecular and clinical evidence suggests various acute physiological effects from electronic nicotine delivery systems, particularly those containing nicotine. Additional clinical and animal-exposure model research is critically needed as the use of these products continues to grow.

Electronic Cigarette Vape Exposure Exacerbates Post-Ischemic Outcomes in Female but Not in Male Rats.

BACKGROUND: Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current exploratory study aims to evaluate the sex-dependent effects of EC exposure on brain energy metabolism and stroke outcomes. METHODS: Adult Sprague-Dawley rats of both sexes were randomly assigned to air/EC vapor (5% nicotine Juul pods) exposure for 16 nights, followed by randomization into 3 cohorts. The first cohort underwent exposure to air/EC preceding randomization to transient middle cerebral artery occlusion (90 minutes) or sham surgery, followed by survival for 21 days. During the survival period, rats underwent sensorimotor and Morris water maze testing. Subsequently, brains were collected for histopathology. A second cohort was exposed to air/EC after which brains were collected for unbiased metabolomics analysis. The third cohort of animals was exposed to air/EC and received transient middle cerebral artery occlusion/sham surgery, and brain tissue was collected 24 hours later for biochemical analysis. RESULTS: In females, EC significantly increased (P<0.05) infarct volumes by 94% as compared with air-exposed rats, 165±50 mm3 in EC-exposed rats, and 85±29 mm3 in air-exposed rats, respectively, while in males such a difference was not apparent. Morris water maze data showed significant deficits in spatial learning and working memory in the EC sham or transient middle cerebral artery occlusion groups compared with the respective air groups in rats of both sexes (P<0.05). Thirty-two metabolites of carbohydrate, glycolysis, tricarboxylic acid cycle, and lipid metabolism were significantly altered (P≤0.05) due to EC, 23 of which were specific for females. Steady-state protein levels of hexokinase significantly decreased (P<0.05) in EC-exposed females; however, these changes were not seen in males. CONCLUSIONS: Even brief EC exposure over 2 weeks impacts brain energy metabolism, exacerbates infarction, and worsens poststroke cognitive deficits in working memory more in female than male rats.

Cardiopulmonary Consequences of Vaping in Adolescents: A Scientific Statement From the American Heart Association.

Although the US Food and Drug Administration has not approved e-cigarettes as a cessation aid, industry has at times positioned their products in that way for adults trying to quit traditional cigarettes; however, their novelty and customizability have driven them into the hands of unintended users, particularly adolescents. Most new users of e-cigarette products have never smoked traditional cigarettes; therefore, understanding the respiratory and cardiovascular consequences of e-cigarette use has become of increasing interest to the research community. Most studies have been performed on adult e-cigarette users, but the majority of these study participants are either former traditional smokers or smokers who have used e-cigarettes to switch from traditional smoking. Therefore, the respiratory and cardiovascular consequences in this population are not attributable to e-cigarette use alone. Preclinical studies have been used to study the effects of naive e-cigarette use on various organ systems; however, almost all of these studies have used adult animals, which makes translation of health effects to adolescents problematic. Given that inhalation of any foreign substance can have effects on the respiratory and cardiovascular systems, a more holistic understanding of the pathways involved in toxicity could help to guide researchers to novel therapeutic treatment strategies. The goals of this scientific statement are to provide salient background information on the cardiopulmonary consequences of e-cigarette use (vaping) in adolescents, to guide therapeutic and preventive strategies and future research directions, and to inform public policymakers on the risks, both short and long term, of vaping.

Factors associated with child and adolescent electronic nicotine and non-nicotine delivery systems use: A scoping review.

OBJECTIVES: To identify, characterise and broadly synthesise factors associated with child and adolescent electronic nicotine delivery systems (ENDS) and/or electronic non-nicotine delivery systems (ENNDS) ever-use and/or current use. METHODS: Four electronic databases were searched from inception to 3rd June 2022. Non-experimental studies that provided quantitative factors associated with adolescent and/or child ENDS or ENNDS ever-use and/or current use were included. Factors associated with ever-use (any lifetime use) and/or current use (use in past 30 days) were included. All screening and data extraction was conducted independently by paired review authors. Frequencies for country, study design, sample size, measure of ENDS/ENNDS use and factors examined were calculated. Factors were categorised according to the Theory of Triadic Influence domains and sub-domains. RESULTS: The search of electronic databases identified 4756 records, 240 of which were included. The majority of studies examined factors categorised within the Biology and Personality domain of the Theory of Triadic Influence (89.2%; 95%CI 84.6, 82.5), followed by the Social Context (50.8%; 95%CI 44.5, 57.2) and Broader Environment domains (30.4%; 95%CI 24.6, 36.3). The proportion of factors significantly associated with ENDS/ENNDS use was >75% for the Behavioural (78.0%; factors included use of tobacco, other drugs and alcohol), Peer Attitudes and Behaviours (80.0%; factors included peer use of ENDS/ENNDS and tobacco), and Legislation/Policy sub-domains (78.6%; factors included accessibility and advertising). CONCLUSIONS: The evidence base on factors associated with ENDS/ENNDS use in children and adolescents is rapidly developing, predominately by research concentrated in high income regions and focused on behavioural- and personality-related factors.

Electronic nicotine delivery system use and its relation to waterpipe smoking among youth in seven Arab countries.

OBJECTIVES: Electronic Nicotine Delivery System (ENDS) use and Waterpipe Tobacco Smoking (WTS) are reported to be a growing strain of tobacco epidemic among youth in the Arab world. Therefore, we aimed to: (1) estimate the regional prevalence of ENDS use among youth in 7 Arab countries and, (2) to explore the bidirectional relationship between ENDS use and WTS among Arab adolescents. METHODS: We analyzed data from the World Health Organization Global Youth Tobacco Survey (GYTS 2014-2018) of 18,536 schoolchildren aged 12-16 from Iraq, Mauritania, Morocco, Oman, Qatar, Tunisia, and Yemen. The weighted prevalence was calculated to generate nationally representative estimates. Adjusted multilevel logistic regression models were conducted to assess the association between ENDS use and WTS. RESULTS: The pooled weighted prevalence of ENDS use was 9.5%. Higher odds of ENDS use were significantly associated with WTS (AOR: 5.26, 95%CI: 4.28-6.46), smoking conventional cigarettes (AOR: 1.54, 95%CI: 1.23-1.94) and first tobacco use prior to the age of 12 (AOR: 1.40, 95%CI: 1.14-1.72). Females and children who were taught in school the dangers of tobacco had less odds of using ENDS. CONCLUSION: WTS was associated with increased odds of ENDS use by >5 folds, and vice versa. Tobacco consumption at age younger than 12 years was associated with higher odds of ENDS use, but less odds of WTS. Females and those who were taught in school the dangers of tobacco were less likely to report ENDS use.

Use patterns of flavored non-cigarette tobacco products among US adults, 2010-2019.

OBJECTIVE: Flavored non-cigarette tobacco product (NCTP) use is common among US adult tobacco users. To update the estimates of use patterns of flavored NCTPs, this study assessed current NCTP use among adults by flavor use and flavor categories from 2010 to 2019. METHODS: We analyzed data from the 2010-2019 Tobacco Use Supplement to the Current Population Survey to estimate the weighted proportion of adult NCTP users by flavor use across survey waves. Flavor use was defined as past 30-day use of any menthol/mint or fruit/other flavors. We used the 2018-2019 data to examine the differences in demographic characteristics and tobacco use patterns among users of menthol/mint or fruit/other flavors compared to exclusive users of tobacco flavor, by product type. RESULTS: Compared to 2014-2015, electronic nicotine delivery system (ENDS) users were more likely (79.0% vs. 66.6%, p < 0.001) to report flavor use in 2018-2019, whereas cigar (26.9% vs. 31.2%, p = 0.030) and pipe (56.3% vs. 65.5%, p = 0.015) smokers were less likely to report flavor use in 2018-2019. In 2018-2019, the most prevalent flavor categories were exclusive use of tobacco flavor among cigar (73.1%) and smokeless tobacco (48.3%) users, and use of fruit/other flavors among ENDS (64.9%) and pipe (48.4%) users. Flavored users were more likely to be young adults aged 18-24 years (cigars, ENDS, smokeless tobacco) and Non-Hispanic Black or Hispanic persons (cigars, ENDS, pipes) compared to tobacco-flavored users. CONCLUSIONS: Flavored product use increased among adult ENDS users but decreased among cigar and pipe smokers. These findings could inform tobacco regulatory efforts concerning flavored NCTPs.

Sex differences in tobacco use, attempts to quit smoking, and cessation among dual users of cigarettes and e-cigarettes: Longitudinal findings from the US Population Assessment of Tobacco and Health Study.

SIGNIFICANCE: A growing number of adults use more than one tobacco product, with dual use of cigarettes and e-cigarettes being the most common combination. Monitoring sex disparities in tobacco use is a public health priority. However, little is known regarding whether dual users differ by sex. METHODS: Data came from Waves 4-6 (12/2016-11/2021) of the Population Assessment of Tobacco and Health Study, a US nationally-representative longitudinal survey. This analysis included current adult dual users of cigarettes and e-cigarettes. We used weighted generalized estimating equations to assess the association between sex and (1) making a cigarette quit attempt (n = 1882 observations from n = 1526 individuals) and (2) smoking cessation (n = 2081 observations from n = 1688 individuals) across two wave pairs, adjusting for age, education, ethnicity, time-to-first cigarette after waking, and e-cigarette use frequency. RESULTS: Among US dual users, 14.1% (95% Confidence Intervals [Cl] = 11.9-16.4) of females and 23.4% (20.0-26.9) of males were young adults (aged 18-24), 11.7% (9.2-14.2) of females and 14.4% (11.6-17.2) of males had

Sex differences in tobacco use, attempts to quit smoking, and cessation among dual users of cigarettes and e-cigarettes: Longitudinal findings from the US Population Assessment of Tobacco and Health Study.

SIGNIFICANCE: A growing number of adults use more than one tobacco product, with dual use of cigarettes and e-cigarettes being the most common combination. Monitoring sex disparities in tobacco use is a public health priority. However, little is known regarding whether dual users differ by sex. METHODS: Data came from Waves 4-6 (12/2016-11/2021) of the Population Assessment of Tobacco and Health Study, a US nationally-representative longitudinal survey. This analysis included current adult dual users of cigarettes and e-cigarettes. We used weighted generalized estimating equations to assess the association between sex and (1) making a cigarette quit attempt (n = 1882 observations from n = 1526 individuals) and (2) smoking cessation (n = 2081 observations from n = 1688 individuals) across two wave pairs, adjusting for age, education, ethnicity, time-to-first cigarette after waking, and e-cigarette use frequency. RESULTS: Among US dual users, 14.1% (95% Confidence Intervals [Cl] = 11.9-16.4) of females and 23.4% (20.0-26.9) of males were young adults (aged 18-24), 11.7% (9.2-14.2) of females and 14.4% (11.6-17.2) of males had

E-Cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) Continues: An Opportunity for Pharmacist Intervention.

Electronic cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) was first identified and reported in 2019, but media coverage and reporting of cases drastically decreased when the COVID-19 pandemic started in early 2020. The syndrome has continued to occur since that time and it is critical that pharmacists are aware of how EVALI presents, and when it should be considered as a potential diagnosis. Inpatient and outpatient pharmacists play a vital role in the treatment of EVALI, and should be knowledgeable of the utility of corticosteroids, even though data are extremely limited. Pharmacists should understand the importance of collecting detailed and accurate information about vaping from patient interviews. Pharmacists also play a leading role in cessation counseling and treatment, selecting medications that can be used to treat nicotine addiction from vaping, and assisting with transitions of care and follow-up.

The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis.

INTRODUCTION: The effects of combustible cigarettes (CCs) and electronic nicotine delivery systems (ENDS) on immune cell-driven colon inflammation and intestinal healing of patients with ulcerative colitis (UC) are still unknown and, therefore, were examined in this study. METHODS: Intracellular staining and flow cytometry analysis of immune cells isolated from UC patients who used ENDS (UCENDS), CCs (UCCC) and who were non-smokers (UCAIR) were performed to elucidate cellular mechanisms which were responsible for CCs and ENDS-dependent modulation of immune response during UC progression. Additionally, dextran sulfate sodium (DSS)-colitis was induced in ENDS/CC/air-exposed mice (DSSENDS/ DSSCC/DSSAIR groups) to support clinical findings. RESULTS: Significantly increased number of immunosuppressive, IL-10, TGF-ß and IL-35-producing, FoxP3-expressing CD3+CD4+T regulatory cells (Tregs) was observed in the blood of UCENDS patients while reduced presence of inflammatory, TNF-α and IFN-γ-producing, Tbx21-expressing CD3+CD4+ Th1, IL-4-producing Gata3-expresing Th2 and IL-17, IL-22-producing, RORγT, IL-23R-expressing Th17 cells were noticed in the blood of UCCC patients. Exposure to either CCs or ENDS was associated with enhanced mucosal healing, ameliorated spontaneous recovery and improved survival of DSS-treated mice. An expansion of immunosuppressive cells (IL-10-producing tolerogenic CD11c+ dendritic cells, alternatively activated CD206, Arginase 1-expressing, IL-10-producing F4/80+macrophages, IL-10-producing FoxP3-expressing Tregs) was noticed in the colons of DSSENDS-treated mice, while reduced number of inflammatory, IL-17- and IL-4-producing T lymphocytes was observed in the colons of DSSCC-compared to DSSAIR-treated mice. CONCLUSIONS: Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients. IMPLICATIONS: This is the first study that compared the effects of CCs and ENDS on immune cells of patients suffering from ulcerative colitis, providing new information about molecular and cellular mechanisms which were responsible for ENDS and CCs-dependent modulation of immune cell-driven colon injury and inflammation. Obtained results showed that both ENDS and CCs had capacity to attenuate detrimental immune response, enhanced healing and ameliorated recovery of injured intestines.

Effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation: Evidences from diabetic patients and multiple low dose streptozotocin-treated diabetic mice.

Considering detrimental impacts of combustible cigarettes (CCs) on the exacerbation of diabetes mellitus (DM), a significant number of DM patients have substituted CCs with electronic nicotine delivery systems (ENDS). Herewith, we compared CCs and ENDS-dependent modulation of immune cell-driven inflammation in DM patients who used ENDS (DMENDS), CCs (DMCC) or were non-smokers (DMAIR), paving the way for the better understanding of ENDS-induced biological effects. Multiple low dose streptozotocin (MLD-STZ)-induced mice model of DM was used to support clinical findings. Both CCs and ENDS aggravated MLD-STZ-induced DM. Pancreatic injury and inflammation were more severe in CC-exposed than in ENDS-exposed diabetic mice. CCs promoted activation of NLRP3 inflammasome, enhanced production of inflammatory cytokines in neutrophils, macrophages and remarkably improved antigen presenting capacity of dendritic cells which resulted in the expansion of TNF-α, IFN-γ and IL-17-producing Th1 and Th17 lymphocytes, NK and NKT cells. Compared to CCs, ENDS more intensively promoted expansion of FoxP3-expressing, IL-10-producing NK and NKT cells and triggered less intense systemic inflammatory response in diabetic animals. Similar findings were observed in DM patients. The highest numbers of inflammatory, TNF-α and IL-1ß-producing neutrophils and monocytes, TNF-α and IFN-γ-producing T lymphocytes, NK and NKT cells were determined in the blood of DMCC patients, while total number of immunosuppressive, TGF-ß-producing CD3 + CD4 + T cells was the highest in the blood of DMENDS patients. In conclusion, although both CC and ENDS aggravate on-going inflammation in DM, ENDS have weaker capacity to induce production of inflammatory cytokines in immune cells than CCs.

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.

Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette.

Background: Electronic nicotine delivery systems (ENDS) have the potential to benefit public health if smokers completely switch from cigarettes to ENDS. Methods: A cohort of adult smokers (age ≥ 21) who purchased a JUUL Starter Kit was followed for 12 months after the initial purchase. We defined "switching" as past-30-day abstinence from smoking (even if JUUL use had stopped), and analyzed factors associated with achievement and maintenance of self-reported repeated point-prevalence switching (RPPS) at three follow-ups, i.e., no past-30-day smoking at months 6, 9, and 12. Results: RPPS was reported by 21.6% of the 12,537 evaluable smokers. Smokers with lighter smoking history and lower cigarette dependence at baseline were more likely to report RPPS. RPPS was also associated with daily use of JUUL (Month-3: OR = 2.32, 95% CI = 2.02-2.68; Month-6: OR = 1.73, 95% CI = 1.42-2.10), and with greater subjective reinforcing effects from JUUL use (assessed by the mCEQ, Month-3: OR = 1.46, 95% CI = 1.38-1.56; Month-6: OR = 1.11; 95% CI = 1.02-1.20). Even among smokers who did not meet the criteria of RPPS (i.e., who smoked at least once), 35.5% reported past 30-day point-prevalence switching on at least one follow-up, and their cigarette consumption was substantially reduced compared to baseline. Conclusions: Approximately one-fifth of adult smokers reported 30-day point-prevalence abstinence at 6, 9, and 12 months after purchasing JUUL. Greater use of JUUL and stronger subjective reinforcing effects were associated with nonsmoking, validating the potential for ENDS to substitute for smoking, with potential for positive impacts on individual and population health.

Vaping Frequency in Young Users: The Role of Gender and Age Among Regular Users.

Background: Vaping is popular among adolescents and emerging adults; however, little is known about regular vaping patterns in older adolescents and emerging adults. Objective: The current study explored whether gender and age are associated with nicotine-based vaping frequency to ascertain ascertaining which subgroups of youth are most at-risk for frequent use. Methods: In a cross-sectional survey, participants using nicotine-based vaping devices (N=535, age range 16-24) reported frequency measured as vaping days in a week, number of episodes during which participants vaped, and puff numbers for each episode. A two-way multivariate analysis of variance was used to test the effects and interactions of gender and age groups on the three frequency outcomes. Results: Emerging adults and males vaped more frequently than their older adolescent and female counterparts, respectively. Specifically, emerging adults vaped more days per week in comparison to older adolescents, whereas males vaped more days per week and had more vaping episodes per day relative to females. Further, emerging adult males had more vaping episodes in comparison to other subgroups, and adolescent females as well as emerging adult males took more puffs per episode in comparison to emerging adult females. Conclusion: Vaping differences among subgroups suggests the need for policies to reduce regular nicotine vaping targeted toward specific gender and age groups.

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.

Flavored Tobacco User Characteristics in U.S. young Adults: Wave 5 of the Population Assessment of Tobacco and Health Study.

Introduction: Flavorings are one of the major appealing factors of current tobacco products, especially for young adults. They constantly evolve, and new flavorings are introduced to the market every year, but little is known about user profiles of flavored tobacco products (FTPs). Methods: We analyzed young adult (ages 18-24) tobacco product users (N = 4,707) from Wave 5 of the Population Assessment of Tobacco and Health Study. We applied bivariate analyses to compare individuals who use FTP and non-FTPs by different flavor types (i.e., menthol/mint, fruit, candy/sweets, and tobacco). Parameter estimates were weighted by applying the sample and replicate weights for the complex study design to produce population-representative estimates. Results: Sixty percent of the current combustible tobacco users and 90% of electronic nicotine delivery systems (ENDS) users were FTP users. FTP users were more likely to be multiple product users than non-FTP users. Being non-Hispanic White, drinking alcohol in the past year, experiencing internalizing problems in the past month, and having tobacco dependence were associated with FTP use. Flavored ENDS users had different sociodemographic characteristics by flavor types but did not differ significantly in vaping-related behaviors (e.g., frequency). Also, preferred flavors differed among tobacco user groups (i.e., ENDS, hookah, and cigars). Conclusions: FTPs appear to be gaining popularity among young adults and tend to show co-use with multiple tobacco products and other substances. Future studies are warranted to monitor the risk factors of young adult FTP use, especially in the context of flavor ban on ENDS products.

Reply to Commentary on "Adult Smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months After Initially Purchasing a JUUL e-Cigarette" and the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study.

BACKGROUND: This is authors' reply to the Commentary on our publication entitled "Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette." METHODS AND RESULTS: Analyses addressed questions about follow-up rates and missed responses in the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study. Results demonstrate limited potential for selection bias, as participants who missed surveys were similar to those with complete data, and re-contact of participants who missed a follow-up indicated almost half were not smoking. Imputing smoking behavior for missing data would likely introduce bias and is not appropriate. The study demonstrated that JUUL products can facilitate high rates of complete switching away from cigarettes as suggested in previous experimental and observational studies. The ADJUSST cohort, including baseline nonsmokers, demonstrates a net reduction in smoking prevalence. Moreover, population modeling considering both benefits and harms demonstrated a net population benefit. CONCLUSION: While the ADJUSST Study is not without limitations, the findings are consistent with multiple streams of real-world evidence that indicate that ENDS can facilitate switching among adults who smoke, and provide population benefits.

Tobacco industry strategies to influence the regulation of new and emerging tobacco and nicotine products in Latin America and the Caribbean.

Objective: To document tobacco industry strategies to influence regulation of new and emerging tobacco and nicotine products (NETNPs) in Latin America and the Caribbean. Methods: We analyzed industry websites, advocacy reports, news media and government documents related to NETNPs, focusing on electronic cigarettes and heated tobacco products. We also conducted a survey of leading health advocates. We applied the policy dystopia model to analyze industry action and argument-based strategies on NETNP regulations. Results: Industry actors engaged in four instrumental strategies to influence NETNP regulation - coalition management, information management, direct involvement in and access to the policy process, and litigation. Their actions included: lobbying key policy-makers, academics and vaping associations; providing grants to media groups to disseminate favorable NETNP information; participating in public consultations; presenting at public hearings; inserting industry-inspired language into draft NETNP legislation; and filing lawsuits to challenge NETNP bans. The industry disseminated its so-called harm reduction argument through large/influential countries (e.g., Argentina, Brazil, and Mexico). Industry discursive strategies claimed NETNPs were less harmful, provided safer alternatives, and should be regulated as so-called harm reduction products or have fewer restrictions on their sale and use than those currently in place. Conclusion: Our analysis provides a better understanding of industry strategies to undermine tobacco and nicotine control. To help counter industry efforts, health advocates should proactively strengthen government capacities and alert policy-makers to industry attempts to create new regulatory categories (so-called reduced-risk products), provide misleading information of government authorizations of NETNPs, and co-opt so-called harm-reduction messages that serve the industry's agenda.

Key Challenges for In Vitro Testing of Tobacco Products for Regulatory Applications: Recommendations for the In Vitro Mouse Lymphoma Assay.

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting in vitro assays to assess potential toxicity within and across traditional tobacco and various tobacco and nicotine next-generation products (NGPs), including Heated Tobacco Products (HTPs) and Electronic Nicotine Delivery Systems (ENDS). This report was developed by a working group composed of attendees of the seventh IIVS workshop, 'Approaches and recommendations for conducting the mouse lymphoma gene mutation assay (MLA) and introduction to in vitro disease models', which was held virtually on 21-23 June 2022. This publication provides a background overview of the MLA, and includes the description of assay conduct and data interpretation, key challenges and recommended best practices for evaluating tobacco and nicotine products, with a focus on the evaluation of NGPs, and a summary of how the assay has been used to evaluate and compare tobacco and nicotine products.