Nicotine & Tobacco Research

ObjectivesUptake of evidence-based smoking cessation support remains limited. Digital interventions offer the prospect of scalable and highly accessible support. Smoke Free, a digital mobile application using established behaviour change techniques, has shown promise, but no large-scale randomised controlled efficacy trial has yet been conducted. We assessed its effectiveness for smoking cessation. DesignIn this prospective, randomised, controlled, two-arm, parallel clinical trial with 6-month follow-up, study personnel and patients were blinded. SettingThe trial was conducted nationwide in Germany, utilising a decentralised, fully remote trial design. Enrolment took place digitally after receiving brief advice from a healthcare professional, following guidelines for primary care. ParticipantsOut of a volunteer sample of 1850 patients assessed for eligibility, 1466 adult cigarette smokers who had at least moderate cigarette dependence (F17.2, FTCD[&ge;]3) were recruited between August 2023 and February 2024; 84.1% (1233 participants) completed the primary outcome measure. InterventionsThe intervention group (IG) received the Smoke Free app including behaviour-change missions and gamification elements, while the control group (CG) received a text-only cessation information app. Both groups received brief advice from a healthcare professional. Main outcome measuresThe prespecified primary outcome was self-reported 7-day point-prevalence abstinence from combustible tobacco at 6 months post-randomisation; secondary outcomes included biochemical validation of abstinence in participants providing a saliva sample (59% of eligible participants). ResultsSelf-reported abstinence (primary outcome) was significantly higher in the IG compared with the CG (283 [39.3%] vs. 182 [24.4%], OR=2.01, 95% CI 1.60 to 2.50, p<0.0001). The NNT was 6.7 (5.1 to 9.8). The effect was consistent with biochemical validation (OR=1.76, 95% CI 1.27 to 2.44, p<0.0001) and across secondary outcomes and sensitivity analyses. The 6-month follow-up rates for the primary outcome did not differ between groups (IG: 601 [83.5%]; CG: 632 [84.7%]; p=0.52). Eighty-four serious adverse events were reported by 75 participants (IG: 31, 4.3%; CG: 44, 5.9%; p=0.53); none were treatment-related. ConclusionsThe Smoke Free app is effective for aiding smoking cessation in at least moderately dependent cigarette smokers compared with an informational app when provided as an adjunct to brief advice from a healthcare professional. Trial registrationThe trial was registered with the German Clinical Trials Register (DRKS00031140). FundingSmoke Free 23 GmbH (for-profit company).

IntroductionMonitoring trends in transitions in the use of electronic nicotine delivery systems (ENDS) and cigarettes among youth is important for understanding the potential public health impacts of these products. MethodsUsing a weighted Markov multistate transition model accounting for complex survey design, we estimated transition rates and one-year transition probabilities between never, non-current, ENDS-only, and cigarette use (with or without dual use of ENDS) among 26,744 youth aged 12-17 years who participated in at least two consecutive waves from Waves 2-7.5 (approximately 2015-2023) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. We also estimated transitions stratified by ages 12-14 and 15-17 years. ResultsThe one-year probability of ENDS-only initiation from never use among youth peaked in 2017-19 (Waves 4-5) at 4.0% (95%CI: 3.6-4.3%) and was higher for 15-17-year-olds at 5.8% (95%CI: 5.2-6.4%) than 12-14-year-olds at 2.2% (95%CI: 1.8-2.6%). In the following years, ENDS-only initiation rates declined and plateaued, with 2.6% (95%CI: 2.3-3.0%) initiation in 2022-23. Cigarette initiation from never use decreased over 2015- 23 from 0.8% (95%CI: 0.6-1.0%) in 2015-16 to 0.1% (95%CI: 0.0-0.2%) in 2022-23. There was an increase in the fraction of youth who transitioned from non-current product use to ENDS-only use from 13.7% (95%CI: 7.5-20.0%) in 2015-16 to 35.1% (95%CI: 25.4-44.8%) in 2022-23, paired with a decrease in non-current use to cigarette use from 20.9% (95%CI: 11.8-30.0%) to 6.3% (95%CI: 1.7-10.8%). Transitions from ENDS-only or cigarette use to non-current use remained relatively constant over time at around 25% and 15% per year, respectively. ConclusionENDS-only use initiation has changed over time, peaking around 2019 and subsequently decreasing and plateauing, but cessation rates for both ENDS and cigarettes have remained relatively stable. Thus, interruption of tobacco product initiation may be the most effective approach to reducing tobacco product use among youth. What this paper addsWhat is already known on this topic: O_LITransitions in cigarette and ENDS use have changed over time, with youth more likely to adopt ENDS and less likely to adopt cigarettes than older age groups. C_LI What this study adds O_LIWe found that ENDS initiation among youth peaked around 2019 and was higher for those 15-17 years than 12-14 years. There were few significant differences between the two age groups for other transitions. C_LIO_LICigarette initiation among youth declined over this period. Cessation rates for both ENDS and cigarettes have remained relatively stable. C_LI How this study might affect research, practice or policy O_LITobacco control efforts should prioritize preventing all tobacco and nicotine product initiation among youth. C_LI

"Dry Hitting" is a unique phenomenon of e-cigarette use that has been shown to produce toxic chemical degradants and byproducts. Although it is widely understood that nicotine exposure during adolescence impacts neurobiological and behavioral function, little is known about how dry hitting may impact users. We hypothesized that subjects repeatedly exposed to nicotine dry hit vapor would exhibit distinct behavioral responses compared with saturated nicotine vapor and would differentially alter the expression of perineuronal nets (PNNs) in the rodent brain. Using a customized system of e-cigarette vapor inhalation, adolescent male Wistar rats (PND 31-40) received vaporized nicotine (30 or 60 mg/mL; [~]2.5-3 mL/cage), nicotine with dry hits (60 mg/mL; 1.75-2 mL/cage), or propylene glycol (PG) vehicle for 30 minutes over 7 daily sessions. Locomotor activity, antinociception, and elevated plus maze testing were used to assess behavioral response to drug intoxication and tolerance. Immunohistochemistry was used to identify Wisteria Floribunda Agglutinin (WFA)-positive PNN structures in the amygdala and insular cortex. Rats exposed to dry hits exhibited behavioral responses (locomotor sensitization, antinociception) similar to those of rats exposed to saturated nicotine vapor, but spent more time in the open arms of the elevated plus maze. Immunohistochemical analyses confirmed significantly greater WFA intensity in the central nucleus of the amygdala, but not the basolateral amygdala or insular cortex, of rats exposed to dry hits. Overall, these data confirm the impact of dry hit vapor on behavioral responses and perineuronal net expression in rats during adolescence.

Background The clinical safety profile of e-cigarette use for smoking reduction remains poorly characterized. This study compared the relative safety and tolerability of nicotine e-cigarette use with non-nicotine e-cigarettes or a non-aerosol cigarette substitute (CS) among adults interested in reducing their smoking. Methods We conducted a secondary analysis of adverse events (AEs) reported in a 6-month, double-blind RCT involving 520 participants assigned to either e-cigarettes with 0, 8, or 36 mg/mL nicotine or a CS. AEs were coded using CTCAE V4.0 and assessed for frequency, severity, seriousness and relatedness across groups. Cumulative incidence was calculated over 24 weeks. We estimated risk differences (RDs) and 95% confidence intervals (CIs) for frequently reported AEs (>=1% of participants overall) comparing e-cigarette vs. CS and nicotine versus non-nicotine e-cigarette groups. Fisher's exact test, with adjustment for multiple comparisons, was used to assess statistical significance. Results Most study-related AEs (those rated as possibly, probably, or definitely related by medical monitor) were mild in severity and none were classified as serious. At 24 weeks, cumulative incidence of first study-related AE was highest in the 36 mg/mL (37.0%) and 8 mg/mL (35.2%) e-cigarette groups, followed by 0 mg/mL (23.4%), and lowest in CS group (2.5%). E-cigarette users experienced significantly greater risks of cough (RD [95%CI]: 8.5% [5.6-11.3]), headache (RD [95%CI]: 5.4% [3.3-7.6]) and sore throat (RD [95%CI]: 5.4% [3.2-7.6]) as compared with the CS group. Cough was also more common in those randomized to nicotine versus non-nicotine e-cigarettes (RD [95%CI]: 8.1% [3.4-12.8]). Conclusion All study products were generally well-tolerated; however, AEs were more common in e-cigarette groups, especially with nicotine. Findings highlight the need to monitor common symptoms such as cough, headache, and sore throat in clinical and regulatory evaluations of e-cigarette safety.

BackgroundDespite their potential to serve as a reduced-harm alternative to combustible tobacco, e-cigarette take-up remains low among older (45+) adult smokers, especially in the U.S. While social media is a known driver of vaping attitudes and behaviors in younger populations, its influence on older smokers is poorly understood. This paper provides the first focused analysis of e-cigarette-related social media exposure in this population, documenting its prevalence, characteristics, and attitudinal correlates. MethodsData come from an opt-in survey of U.S. adults (N = 974) recruited via Prolific, comprising three groups: (i) non-vaping smokers aged 45+ (N = 484), (ii) former-smoking vapers aged 45+ (N = 149), and (iii) any-vaping-status smokers aged 18-35 (N = 341). Descriptive statistics, weighted to U.S. population benchmarks, characterize self-reported exposure to e-cigarette-related content on social media. Logistic regressions estimate associations between exposure and intentions for future e-cigarette use, e-cigarette harm perceptions, and related attitudes. ResultsOlder smokers (35.3%) reported exposure to e-cigarette-related content on social media less frequently than both older vapers (44.0%) and younger smokers (72.0%). For older smokers, e-cigarette health risks were the most frequently reported topic of content viewed, followed by youth vaping and e-cigarette addiction. Among this group, exposure was positively associated with stated intentions for future e-cigarette use. Exposure was not significantly associated with perceived e-cigarette harms for any group. ConclusionsFindings provide suggestive evidence that social media exposure may promote e-cigarette adoption among older smokers. However, the cross-sectional design limits causal inference, and the observed associations may reflect selection bias or reverse causality. If a causal relationship exists, the patterns observed suggest that exposure influences e-cigarette adoption through mechanisms other than updating beliefs about e-cigarette risks. While these results tentatively support the potential of social media as a channel for older-smoker harm reduction, any policy applications must carefully weigh privacy concerns and risks to youth. Rigorous experimental studies are needed to confirm these findings and clarify how social media might be leveraged to improve public health outcomes among older smokers.

Abstract Importance: The overall prevalence of youth nicotine and tobacco product use has declined over recent years, but the product landscape continues to evolve rapidly, particularly with new disposable e-cigarettes and oral nicotine pouches. Objective: To examine changes between 2024 and 2025 in the prevalence of nicotine and tobacco product use among US middle and high school students and describe shifts in product characteristics among current e-cigarette and nicotine pouch users. Design, Setting, and Participants: Repeated cross-sectional study using nationally representative data from the 2024 and 2025 National Youth Tobacco Survey (NYTS), a school-based survey of US students in grades 6-12 (approximately ages 11-18). The analytic sample included 29,678 students in 2024 and 23,557 students in 2025. Exposures: Survey year (2025 vs 2024). Main Outcomes and Measures: Past 30-day use of nicotine/tobacco products, including e-cigarettes, nicotine pouches, cigarettes, and other combustible and non-combustible products. Among current e-cigarette and nicotine pouch users, frequency of use, device type, brands, and flavors were assessed. Results: In 2025, 7.2% (95% CI, 6.4-8.2%) of US middle and high school students reported past 30-day use of any nicotine/tobacco product, compared with 8.1% (7.4-8.9%) in 2024. E-cigarettes remained the most commonly used product (5.2%, 4.5-5.9%); 1.7% (1.4-2.1%) used nicotine pouches, 1.7% (1.4-1.9%) smoked cigarettes, and 2.7% (2.4-3.1%) smoked any combustible tobacco product. Among current e-cigarette users, 40.7% (36.7-44.9%) reported frequent use and 27.0% (24.0-30.2%) reported daily use in 2025. Disposable e-cigarette use increased from 55.8% (52.6-59.0%) in 2024 to 66.7% (62.5-70.7%) in 2025, while pod/cartridge device use declined. Flavored product use was reported by 90.0% of e-cigarette users and 88.0% of nicotine pouch users. The most commonly reported brands were Geek Bar among e-cigarette users (61.1%) and ZYN among nicotine pouch users (69.4%). Conclusions and Relevance: Overall youth nicotine and tobacco use remains relatively low, but the product landscape is evolving rapidly, with increasing disposable device use and shifting brand preferences. These findings highlight the importance of ongoing, product-specific surveillance to inform public health strategies and regulatory policies.

ABSTRACT Background and aims: Mental and behavioral disorders due to use of tobacco (MBDT) present a critical challenge to global health, yet modifiable lifestyle factors for reducing its risk remain poorly understood. Given that dietary fibre can affect mental health through gut-brain communication, we sought to explore how fibre intake relates to MBDT risks in smokers. Methods: We specifically evaluated the link between dietary fibre intake and MBDT within a smoking population. Utilizing the UK Biobank (UKB) database, we performed cross-sectional (N=19,943) and prospective cohort (N=19,885) evaluations applying logistic and Cox proportional hazards models, respectively. To determine potential causality, two-sample Mendelian randomization (MR) was applied, relying on GWAS summary data derived from the IEU Open GWAS Project and FinnGen repositories. Results: Cross-sectional findings indicated that individuals in the top quartile (Q4) of fibre intake exhibited decreased MBDT risks relative to the bottom quartile (Q1) (OR: 0.32, 95% CI: 0.13-0.79). Over a median observation time of 12.84 years, the prospective evaluation demonstrated a notable inverse correlation (Q4 HR: 0.46, 95% CI: 0.40-0.54). Non-linear modeling via restricted cubic splines uncovered an L-shaped dose-response curve. Furthermore, MR results confirmed a genetically predicted protective causality (IVW OR: 0.68, 95% CI: 0.49-0.95), which remained consistent across sensitivity validations. Conclusions: Among smokers, higher dietary fibre intake is robustly associated with a reduced risk of mental and behavioral disorders due to the use of tobacco, offering a modifiable dietary target for public health interventions.

BackgroundThe initiation of tobacco and nicotine product use often occurs in adolescents. This necessitates monitoring of this behaviour in this population, particularly in countries such as the Democratic Republic of the Congo (DRC) where approximately 58% of the population is under 19 years of age. Our study assessed the prevalence of, and factors associated with use in the DRC. MethodsWe conducted a nationally representative, cross-sectional, household survey between March and May 2024 among adolescents aged 10 to 17 years. We estimated the prevalence of use of smoked and smokeless tobacco products, heated tobacco products, and nicotine products (i.e., electronic cigarettes and nicotine pouches). We used logistic regression to identify factors associated with current use of any tobacco product, smoked tobacco, and smokeless tobacco using adjusted odd ratios. All analyses included 95% confidence intervals (CI). ResultsOf the 4,675 adolescents who completed the survey, the prevalence of current use of any tobacco or nicotine product was 11.87% (95% CI: 6.93-19.58). This was 7.98% (95% CI: 4.23-14.55) for smoked tobacco products, 5.86% (95% CI: 3.42-9.87) for smokeless tobacco products, 0.11% (95% CI: 0.11-0.11) for heated tobacco products and 0.60% (95% CI: 0.10-3.40) for nicotine products. Boys were more likely to use tobacco than girls. Being enrolled in school and having both parents alive were protective from tobacco use. Having a male household head, a household head education level of at least secondary school, and exposure to tobacco smoking in public places increased the odds of being a tobacco user. ConclusionsThe DRC should strengthen policies that make tobacco and nicotine products less accessible or appealing to adolescents. This includes raising excise taxes; banning the sale of single cigarette sticks, small packets and flavoured products; and comprehensive smoke-free laws. Policies should account for factors that make adolescents more vulnerable product use. Key messagesO_ST_ABSWhat is already known on the topicC_ST_ABSO_LIThe last survey on tobacco use among adolescents in the DRC was a school-based survey among 13-15-year-olds conducted in 2008, and only covered Kinshasa and Lubumbashi. C_LI What this study addsO_LIThis survey provided national-level estimates that cover adolescents aged 10-17years, includes out-of-school adolescents, and covers both tobacco and nicotine products. C_LIO_LIIt also identifies individual-, household-, and environmental-level factors that are associated with tobacco and nicotine product use among adolescents in the DRC. C_LI How this study might affect research, practice or policyO_LIBy providing current and more comprehensive data, our study enhances policymakers ability to design evidence-based tobacco control interventions that are aimed at preventing the initiation and use of tobacco and nicotine products among adolescents in the DRC and other similar settings. C_LI

IntroductionAlthough prior studies suggest e-cigarette use is associated with worse mental health, it remains unclear whether these associations persist independent of diagnosed depression and how tobacco use and depression jointly affect health-related quality of life. Although the long-term health risks of vaping are still unknown, self-reported health is a reliable measure of quality of life. This study provides the first health utility estimates of the independent and combined effects of cigarette use, e-cigarette use, and depression on health-related quality of life. MethodsWe analyzed 2022-2023 Behavioral Risk Factor Surveillance System data on health-related quality of life as measured by self-reported physically or mentally unhealthy days in the past 30 days. The average number of unhealthy days was estimated by age, gender, smoking status (current versus non-smoking), depression status (received a prior diagnosis), and current e-cigarette use status (every day or some day use). We converted the number of overall healthy days into EQ-5D utility scores by age-specific percentile matching of BRFSS and MEPS distributions, a method developed by Jia and Lubetkin. ResultsCigarette use, e-cigarette use, and depression were each associated with worse health-related quality of life. Mentally unhealthy days increased with the accumulation of these conditions. Associations with physically unhealthy days followed a similar pattern, particularly among younger adults, although the magnitude of association was smaller. E-cigarette use alone was associated with 2.0-4.2 (95% CI: 2.0-4.6) additional mentally unhealthy days per month across all age groups. Notably, e-cigarette use was independently associated with poorer mental health among adults aged 18-64 with or without diagnosed depression. After accounting for smoking and depression status, e-cigarette use was associated with disutility scores of 0.011 in men and 0.015 in women among young adults, with the largest losses observed when multiple conditions co-occurred. ConclusionE-cigarette use is associated with poorer health-related quality of life, particularly among younger adults, and these effects are amplified when combined with cigarette use and depression. Quantifying these joint impacts as health utility losses highlights the importance of addressing e-cigarette use within integrated tobacco control and mental health policies, especially for young populations.

BackgroundSecondhand smoke (SHS) exposure remains a major public health concern among adolescents, particularly in low- and middle-income countries. Evidence from Zambia is limited, despite increasing tobacco use and existing tobacco control policies. This study examined the prevalence and correlates of SHS exposure among adolescents in Zambia. MethodsWe analyzed data from the 2021 Zambia Global Youth Tobacco Survey (GYTS), a nationally representative, school-based survey. The sample included 6,499 adolescents aged 11-17 years enrolled in grades 7-9. The primary outcome was any SHS exposure, defined as exposure to tobacco smoke at home, school, enclosed public places, or outdoor public places. Weighted prevalence estimates were calculated, and multivariable logistic regression was used to identify factors associated with SHS exposure, adjusting for demographic, social, environmental, and socioeconomic variables. ResultsOverall, 66.0% of adolescents reported exposure to SHS. Adolescents living with a parent or guardian who smoked had nearly three times higher odds of SHS exposure (adjusted odds ratio [AOR] = 2.76; 95% CI: 2.12-3.62; p < 0.001). Having friends who smoked tobacco (AOR = 1.86; 95% CI: 1.52-2.30; p < 0.001) and seeing teachers smoking at school (AOR = 1.88; 95% CI: 1.40-2.56; p < 0.001) were also significant predictors. Media exposure was important: seeing people use tobacco on television (AOR = 1.88; 95% CI: 1.63-2.17; p < 0.001) and exposure to tobacco advertisements (AOR = 1.38; 95% CI: 1.14-1.67; p = 0.001) increased odds of SHS exposure. Adolescents who had smoked cigarettes had higher odds of exposure (AOR = 2.80; 95% CI: 1.70-4.67; p < 0.001), as did those intending to use tobacco in the next five years (AOR = 1.64; 95% CI: 1.21-2.24; p = 0.002). Age, sex, and grade level were not independently associated with SHS exposure. ConclusionsSHS exposure among adolescents in Zambia is widespread and is largely driven by household smoking, peer influence, school environments, and media exposure. Strengthening enforcement of smoke-free policies, promoting smoke-free homes, and addressing social and media influences are critical to reducing adolescent SHS exposure.

E-cigarettes have attracted significant attention as a safer substitute for conventional tobacco smoking. However, they have introduced new inhalable toxicants, including benzaldehyde-propylene glycol acetal (BPGA)--a chemical adduct produced by cherry-flavoured e-cigarettes. The health risks associated with such flavour-derived acetals remain insufficiently elucidated at the cellular level. This study investigated the role of BPGA in the progression of epithelial-to-mesenchymal transition (EMT)-like changes in alveolar epithelial cells (A549 cells). A549 cells exposed to various concentrations of BPGA were analysed for cell viability, morphology, mitochondrial function, lysosomal health, and cytoskeletal integrity using viability assays and fluorescence imaging. Intracellular reactive oxygen species (ROS) production was quantified using the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Antioxidant enzyme expression, inflammatory responses, and EMT-associated phenotypic alterations were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence (IF) assays. Exposure of alveolar epithelial cells to BPGA caused a concentration-dependent decrease in cell viability. BPGA exposure resulted in mitochondrial membrane depolarisation, lysosomal damage, cytoskeletal changes, and stress fibre formation, which altered cell morphology. It significantly increased intracellular ROS production. As a result, antioxidant enzyme levels were upregulated as a protective response. However, during severe oxidative stress, this response was overwhelmed. Excess ROS disrupted cellular homeostasis and initiated apoptosis, though not completely. ROS also acted as a signalling molecule, promoting the upregulation of inflammatory mediators. These changes were associated with altered EMT marker expression, suggesting that BPGA might drive EMT-like remodelling. In conclusion, BPGA, a chemical adduct from e-cigarette vapour, induces alveolar injury by promoting oxidative stress, inflammation, and EMT-related changes, which may explain a mechanism by which e-cigarette exposure could lead to lung injury and pulmonary fibrosis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/724520v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@f7739dorg.highwire.dtl.DTLVardef@1c74f11org.highwire.dtl.DTLVardef@180aeeorg.highwire.dtl.DTLVardef@75ae14_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG

Tobacco use disorder is a chronic condition characterized by compulsive nicotine use, withdrawal, and relapse following abstinence. Impulsivity contributes to persistent nicotine use and poor cessation outcomes. This study examined whether nicotinic acetylcholine receptor (nAChR) modulators alter impulsive action in a nicotine self-administration Go/No-Go task in male and female rats. Rats acquired intravenous nicotine self-administration and were then trained in a Go/No-Go procedure in which active lever presses were reinforced during Go periods but not during No-Go periods. We then assessed the effects of varenicline (0.1-3 mg/kg), nicotine (0.1-0.6 mg/kg), and the nAChR antagonist mecamylamine (0.5-2 mg/kg) in the Go/No-Go procedure. Varenicline and nicotine pretreatment reduced active responding during both Go and No-Go periods, whereas mecamylamine selectively reduced responding during No-Go periods. Mecamylamine decreased the percentage of active responses during No-Go trials, indicating reduced bias toward the nicotine-associated lever. In contrast, nicotine and varenicline did not alter response allocation, suggesting that their effects reflected nonspecific reductions in responding rather than changes in impulsive action. No sex differences were observed. Substituting saline for nicotine during self-administration did not alter active responding during Go periods, but rats in the saline group had fewer active responses during No-Go periods than rats in the nicotine group. These results show that chronic nicotine self-administration increases impulsive action and that nAChR antagonism, but not agonism or partial agonism, reduces nicotine-related impulsive action. This work supports the utility of the Go/No-Go self-administration task for investigating nAChR-dependent mechanisms underlying nicotine-induced impulsivity.

Importance: Understanding patterns of substance use and environmental exposures to tobacco, cannabis, and electronic nicotine delivery systems (ENDS) among youth is critical for developing targeted prevention strategies, particularly as co-use of tobacco, ENDS, and cannabis becomes more prevalent. Objective: To identify latent classes of tobacco, ENDS, and cannabis use, and environmental exposures to these products among adolescents and emerging adults. Design, Setting, and Participants: Data from the Environmental influences on Child Health Outcomes (ECHO) consortium (3rd data release, 2018 to 2022) were analyzed from March 2025 to January 2026. The sample (N=2,786) included early adolescents (ages 11 to 13; n=226, 7.9%), middle adolescents (ages 14 to 17; n=1,248, 43.4%), and late adolescents/emerging adults (ages 18 to 24; n=1,402, 48.7%) from 19 ECHO cohorts. Main Outcomes and Measures: The Youth Risk Behavior Survey, Substance Use module measured experimental and current use of cannabis, ENDS, and tobacco products, as well as daily environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke within home and social contexts. A multiple group latent class analysis was used to identify distinct latent classes of substance use and environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke and compared class prevalences across early, middle, and late adolescence. Results: Four latent classes were identified, including: No Use/No Exposure (53%), No Use, Polyexposure (10%), Experimental Use/Low Exposure (22%), and Polysubstance Use/High Polyexposure (14%). Cannabis was the most used substance (34% experimental or current use) and the most common source of environmental exposure (20%), followed by ENDS use (26% experimental or current use; 19% environmental exposure) and combustible tobacco (15% use; 19% environmental exposure). The No Use/No Exposure and No Use/Polyexposure classes were primarily made up of early and middle-aged adolescents, whereas the Experimental Use/Low Exposure and Polysubstance Use/High Polyexposure classes primarily consisted of late adolescents and emerging adults. Conclusions: Our study revealed distinct, developmentally patterned groupings of substance use and environmental exposure among US adolescents and emerging adults, highlighting the need for developmentally tailored interventions, messaging, and policies that address both active use and environmental exposure across adolescence.

Abstract Aims To examine which demographic groups nicotine pouch advertisers chose to target on social media, and which groups Meta's algorithms actually delivered the adverts to. Design Cross-sectional analysis of advert-level data from the Meta Ad Library. Setting Meta social media platforms (including Facebook and Instagram) in the UK. Cases A random sample of 741 nicotine pouch adverts shown in the 12 months up to December 2025, and a comparison sample of 1,125 general adverts. Analyses of reach were restricted to adverts eligible for all genders and adult ages (444 pouch adverts; 674 general). Measurements Outcomes were advertiser-set gender and age-group targeting criteria (i.e., groups eligible to be shown each advert) and estimated advert reach to each group (i.e., number of people who saw each advert). Male-to-female reach ratios within age groups, and reach ratios comparing age groups, were calculated per advert and summarised using geometric means. To assess whether patterns were pouch-specific, comparisons with general adverts were made using ratios of reach ratios (RRR). Findings Advertisers of nicotine pouches targeted a broad sample; most adverts (79.1%; 586/741) were eligible to be shown to all genders, the remainder were restricted to men only. All were restricted to adults (minimum age 18 years) and most (95.6%; 708/741) had no upper age limit. Despite this, of pouch adverts eligible to be shown to all adults, adverts were more likely to reach men, particularly among younger men. Among 18-24-year-olds, pouch adverts reached around ten times as many men as women (RR 10.0, 95% CI 8.7-11.5), compared with a slight skew towards women for general adverts (RR 0.81, 95% CI 0.71-0.94), corresponding to an RRR of 12.3 (95% CI 10.0-15.1). Pouch adverts also showed a skew in reach towards younger age groups. Relative to those aged 35-44 years, reach was higher among 18-24-year-olds for nicotine pouch adverts (RR 1.33, 95% CI 1.17-1.51) but much lower for general adverts (RR 0.19, 95% CI 0.17-0.21), corresponding to an RRR of 7.0 (95% CI 6.0-8.2). Conclusions Nicotine pouch adverts on social media are often eligible to be shown broadly to all demographic groups but are disproportionately delivered to young men.

ObjectiveTo evaluate the effectiveness of various Large Language Models (LLMs) in identifying reliable predictors of Electronic Nicotine Delivery Systems (ENDS) initiation among adolescents, using solely large-scale survey variable descriptions. MethodsA cohort of 7,943 tobacco-naive adolescents aged 12-16 years from the Population Assessment of Tobacco and Health (PATH) Study was analyzed to predict ENDS use at wave 5. Four instruction-tuned LLMs - GPT-4o, LLaMA 3.1-70B, Qwen 2.5-72B-Instruct, and DeepSeek-V3 - were systematically evaluated for text-based feature selection using only variable descriptions from wave 4.5. Selected features were used to train LightGBM classifiers, with model performance compared to a baseline. ResultsOur findings reveal notable consistency among the four instruction-tuned LLMs, with substantial overlap in the top predictors each model identified. These selected variables spanned critical domains such as peer and household influence, risk perception, and exposure to tobacco-related cues. LightGBM classifiers trained on PATH wave 4.5-5 data using features selected by the LLMs demonstrated strong predictive performance. Notably, Qwen 2.5-72B-Instruct achieved an AUC of 0.791 with 30 predictors, surpassing the baseline AUC of 0.768. DiscussionThe substantial overlap among the top predictors identified by different LLMs suggests a shared reasoning process, despite variations in model architecture and training. LightGBM classifiers trained on these LLM-selected features achieved performance comparable to, or exceeding, models trained on the full set of survey variables, underscoring the high quality of features selected solely from textual descriptions. Moreover, these findings are consistent with previous tobacco regulatory research, further validating the effectiveness of LLM-driven feature selection. ConclusionInstruction-tuned large language models can effectively perform text-based feature selection using survey variable descriptions alone, without accessing raw survey data. This scalable, interpretable, and privacy-preserving framework holds promise for behavioral health research and tobacco use surveillance.

BackgroundThis study aimed to investigate whether retinal fractal dimension (Df), a measure of microvascular branching complexity from fundus images, together with plasma metabolites, can help identify pathways linking microvascular changes to cardiovascular disease (CVD) events. MethodsWe analyzed longitudinal data from a subset of 4,781 participants from the Comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA), free of CVD at baseline (mean age 58.74 {+/-} 8.39; 47% male), and with 811 plasma metabolites measured at baseline and retinal imaging. Total, arterial and venular Df were derived from fundus photographs using the Vessel Assessment and Measurement Platform for Images of the Retina. Incident CVD was defined as one or more of self-reported physician-diagnosed myocardial infarction, angina, coronary heart disease, stroke, transient ischemic attack, or peripheral vascular disease during follow-up. Regression models tested associations among Df, plasma metabolites and incident CVD. ResultsOver a median follow-up of 5.75 years (IQR 5.48-6.04), 546 participants (11.42%) developed CVD. Higher total, arterial and venular Df were associated with lower CVD risk in unadjusted analyses (Odds Ratio (OR)=0.62, 95% CI:0.53-0.72 for total Df; OR=0.78, 95% CI:0.70-0.86 for arterial Df; OR=0.74, 95% CI:0.67-0.82 for venular Df). Total Df demonstrated the strongest predictive value for incident CVD but not independently of established CVD risk factors. Nine plasma metabolites, including amino acids, lipids, and xenobiotics, were associated with both incident CVD and one Df measure (p < 0.05), with cotinine and hydroxycotinine satisfying a false discovery rate adjustment (q < 0.05). Consistent with these findings the Total Nicotine Equivalent (TNE-3) was also associated with both lower arterial Df and increased CVD risk. ConclusionsRetinal microvascular complexity is associated with incident CVD. Nicotine metabolism from tobacco smoking exposures emerged as the strongest association linking microvascular changes and CVD events. Clinical PerspectiveO_ST_ABSWhat is New?C_ST_ABSO_LILower retinal branching complexity, as measured through Df, is significantly associated with incident cardiovascular disease (CVD) in unadjusted analyses. C_LIO_LIIn a population-based sample, we found nine plasma metabolites associated with both retinal vascular complexity and incident CVD, but only nicotine metabolites were significant after multiple testing correction. C_LIO_LINicotine metabolites, particularly cotinine and hydroxycotinine, remained significantly associated with incident CVD even after adjustment for self-reported smoking status. C_LI What Are the Clinical Implications?O_LIRetinal Df measures could be used as a predictor of CVD event, although not independently of age and traditional cardiovascular risk factors. C_LIO_LIMicrovascular changes may lie on the pathway linking nicotine metabolites to CVD events. C_LIO_LIPlasma nicotine metabolites may provide additional cardiovascular risk information beyond self-reported smoking, reflecting individual exposure, metabolism and passive smoke exposure. C_LI

Chronic pain and nicotine use frequently co-occur, and individuals with chronic pain often experience greater difficulty quitting. Therefore, we examined nicotine withdrawal behaviors and analgesic-like effects in pain-naive and chronic pain conditions. Adult male and female rats underwent chronic constriction injury or sham surgery. After pain establishment, rats received twice-daily subcutaneous nicotine (0.3 or 0.7 mg/kg) or saline for 14 days. 24 h after the final injection, withdrawal was assessed, including physical signs and anxiety-like behavior. Depressive-like responses were evaluated at 72 h. Pain sensitivity and nicotines analgesic-like effects were assessed throughout. Chronic pain increased physical signs of withdrawal in both sexes, with greater effects in females. It also induced anxiety-like behavior in controls of both sexes. In rats with comorbid chronic pain and withdrawal, anxiety-like behavior was further enhanced in males, whereas females showed variable responses across assays, with increases or decreases depending on the test. Chronic pain induced depressive-like behavior in males but not in females. During withdrawal, depressive-like responses in males with chronic pain were not greater than those in the chronic pain alone group, while chronic nicotine exposure reduced depressive-like behavior in females. Nicotine produced acute analgesic-like effects that diminished over time in both pain-naive and chronic pain conditions, indicating tolerance. In pain-naive rats, repeated nicotine exposure induced mechanical hypersensitivity. Chronic pain intensified nicotine withdrawal severity in a nicotine concentration- and sex-dependent manner. These findings highlight the importance of considering pain status and sex when developing effective cessation strategies, particularly for individuals with comorbid chronic pain. SummaryChronic pain exacerbates nicotine withdrawal severity. Chronic nicotine exposure induces pain hypersensitivity and tolerance to analgesic effects. These effects vary by nicotine concentration and sex.

BackgroundIntentional inhalation of 1,1-difluoroethane (DFE), the propellant in aerosol duster products, is a leading cause of inhalant-abuse death in the United States. The CPSC has cited death counts from its Clearinghouse in regulatory proceedings, yet no peer-reviewed publication has described the methods used to identify these cases. ObjectivesTo estimate DFE- and duster-related deaths in the CPSC Clearinghouse for 2011-2021, characterize reporting patterns, and assess classification reliability against an independently coded dataset. MethodsDeath records (N = 6,316) were identified from 261,076 Clearinghouse records using CPSC product codes for chemicals, aerosols, gases, and related products. Each record was classified through narrative review and substance coding. Inter-rater reliability was assessed against an independently coded dataset from Families United Against Inhalant Abuse (FUAIA) using Cohens kappa and Gwets AC1. ResultsOf 2,451 inhalant-abuse deaths identified (70.8% male; mean age 36.9 years), 2,097 (85.6%) involved DFE or aerosol duster products. DFE/duster deaths rose from 110 (2011) to 266 (2016). Only 17% of cases were received in the same calendar year as the incident. Prior to reconciliation, comparison with the FUAIA dataset yielded Cohens kappa of 0.90 (95% CI [0.89, 0.91]); all discrepancies were subsequently resolved through joint review. ConclusionAerosol duster products account for approximately 86% of inhalant-abuse deaths reported to the CPSC Clearinghouse; however, these counts significantly underestimate true prevalence. The concentration of mortality in a single, widely available product class supports targeted product-level interventions and provides the first peer-reviewed baseline for evaluating the impact of regulatory and prevention efforts.

BackgroundOur group previously reported that lung cancer (LC) screening history results and subsequent timing of diagnosis are associated with significant differences in survival outcomes. As a follow-up study, we sought to develop novel personalized risk models that considered screening history for incidence cancers, interval LCs, and prevalence LCs. MethodsUsing data from the CT-arm of the NLST, four independent case-control analyses were conducted to develop parsimonious risk models. Controls (n=26,038) were those never diagnosed with LC. The four LC case groups were 270 prevalence LCs, 44 interval LCs, 206 screen-detected LCs (SDLCs) that had a baseline positive screen, and 164 SDLCs that had a baseline negative screen. For each case-control analysis, univariable analyses identified statistically significant covariates from 48 variables and then significant covariates were included into a stepwise backward selection approach to identify a model with the most informative covariates. ResultsFor prevalence LCs, the model (AUC=0.711) included age, pack-years smoked, BMI, smoking status, smoking onset age, personal history of cancer, family history of LC, alcohol consumption, and milling occupation. For interval LCs, the model (AUC=0.734) included age, smoking status, smoking onset age, cigar smoking, marital status, and asbestos occupation. For baseline positive SDLCs, the model (AUC=0.685) included age, pack-years smoked, BMI, emphysema, chemicals/plastics exposure, and milling occupation. For baseline negative SDLCs, the model (AUC=0.701) included age, pack-years smoked, BMI, smoking status, emphysema, sarcoidosis, and sandblasting occupation. ConclusionsBesides smoking and age, which are inclusion criteria for screening, these models identified other important risk factors which could be used to provide personalized LC risk assessment and screening management.

IntroductionSmoking cessation after acute coronary syndrome (ACS) is a Class I recommendation, yet prescription pharmacotherapy use remains low and its real-world cardiovascular effectiveness when added to nicotine replacement therapy (NRT) is poorly characterized. MethodsWe conducted a retrospective cohort study using the TriNetX US Collaborative Network (67 healthcare organizations). Adults hospitalized with ACS who received NRT within one month, serving as a proxy for active smoking status, were identified. Two co-primary propensity-matched (1:1, 50 covariates, caliper 0.10 SD) comparisons evaluated bupropion + NRT and varenicline + NRT individually versus NRT alone; a supportive analysis evaluated combined pharmacotherapy versus NRT alone. All-cause mortality was the primary endpoint. Secondary outcomes included MACE, heart failure exacerbations, major bleeding, TIA/stroke, emergency rehospitalizations, and cardiac rehabilitation utilization, assessed at 6 months and 1 year via Kaplan-Meier analysis. Hazard ratios (HRs) greater than 1.0 indicate higher hazard in the NRT-only group. ResultsAfter matching, the combined analysis comprised 8,574 pairs, the bupropion analysis 4,654 pairs, and the varenicline analysis 2,126 pairs. At 1 year, the combined pharmacotherapy group had significantly lower all-cause mortality (HR 1.26, 95% CI 1.16-1.37), MACE (HR 1.16, 95% CI 1.12-1.21), heart failure exacerbations (HR 1.16, 95% CI 1.08-1.25), major bleeding (HR 1.18, 95% CI 1.08-1.28), and greater cardiac rehabilitation utilization (HR 0.82, 95% CI 0.74-0.92; all p < 0.001). TIA/stroke did not differ significantly. Six-month results were consistent. Both varenicline and bupropion individually showed lower mortality and MACE. A urinary tract infection falsification endpoint showed no between-group differences, supporting matching validity. The pharmacotherapy group had higher rates of new-onset depression, driven predominantly by bupropion recipients. ConclusionsIn this propensity-matched real-world analysis, adding prescription smoking cessation pharmacotherapy to NRT after ACS was associated with lower mortality and fewer adverse cardiovascular events, supporting broader integration into post-ACS care pathways.