E-cigarette vapor renders neutrophils dysfunctional due to filamentous actin accumulation.

BACKGROUND: Electronic cigarette (e-cigarette) use continues to rise despite concerns of long-term effects, especially the risk of developing lung diseases such as chronic obstructive pulmonary disease. Neutrophils are central to the pathogenesis of chronic obstructive pulmonary disease, with changes in phenotype and function implicated in tissue damage. OBJECTIVE: We sought to measure the impact of direct exposure to nicotine-containing and nicotine-free e-cigarette vapor on human neutrophil function and phenotype. METHODS: Neutrophils were isolated from the whole blood of self-reported nonsmoking, nonvaping healthy volunteers. Neutrophils were exposed to 40 puffs of e-cigarette vapor generated from e-cigarette devices using flavorless e-cigarette liquids with and without nicotine before functions, deformability, and phenotype were assessed. RESULTS: Neutrophil surface marker expression was altered, with CD62L and CXCR2 expression significantly reduced in neutrophils treated with e-cigarette vapor containing nicotine. Neutrophil migration to IL-8, phagocytosis of Escherichia coli and Staphylococcus aureus pHrodo bioparticles, oxidative burst response, and phorbol 12-myristate 13-acetate-stimulated neutrophil extracellular trap formation were all significantly reduced by e-cigarette vapor treatments, independent of nicotine content. E-cigarette vapor induced increased levels of baseline polymerized filamentous actin levels in the cytoplasm, compared with untreated controls. CONCLUSIONS: The significant reduction in effector neutrophil functions after exposure to high-power e-cigarette devices, even in the absence of nicotine, is associated with excessive filamentous actin polymerization. This highlights the potentially damaging impact of vaping on respiratory health and reinforces the urgency of research to uncover the long-term health implications of e-cigarettes.

Electronic cigarettes and cardiovascular disease: epidemiological and biological links.

Electronic cigarettes (e-cigarettes), as alternative nicotine delivery methods, has rapidly increased among youth and adults in recent years. However, cardiovascular safety is an important consideration regarding e-cigarettes usage. e-cigarette emissions, including nicotine, propylene glycol, flavorings, nitrosamine, and metals, might have adverse effects on cardiovascular health. A large body of epidemiological evidence has indicated that e-cigarettes are considered an independent risk factor for increased rates of cardiovascular disease occurrence and death. The incidence and mortality of various types of cardiovascular disease, such as cardiac arrhythmia, hypertension, acute coronary syndromes, and heart failure, have a modest growth in vapers (users of e-cigarettes). Although the underlying biological mechanisms have not been fully understood, studies have validated that oxidative stress, inflammation, endothelial dysfunction, atherosclerosis, hemodynamic effects, and platelet function play important roles in which e-cigarettes work in the human body. This minireview consolidates and discusses the epidemiological and biological links between e-cigarettes and various types of cardiovascular disease.

Evidence of premature vascular dysfunction in young adults who regularly use e-cigarettes and the impact of usage length.

BACKGROUND: Electronic (e-) cigarettes are increasingly popular tobacco products on the US market. Traditional tobacco products are known to cause vascular dysfunction, one of the earliest indicators of cardiovascular disease (CVD) development. However, little is known about the effect of regular e-cigarette use on vascular function. The purpose of this study was to investigate the impact of regular e-cigarette use on vascular function and cardiovascular health in young, healthy adults. METHODS: Twenty-one regular users of e-cigarettes (ECU) and twenty-one demographically matched non-users (NU) completed this study. Vascular health was assessed in the cutaneous microcirculation through different reactivity tests to evaluate overall functionality, endothelium-dependent vasodilation (EDD), and endothelium-independent vasodilation (EID). Macrovascular function was assessed using flow-mediated dilation (FMD). RESULTS: Our results suggest that regular users of e-cigarettes present with premature microvascular impairment when compared to non-users. Specifically, they exhibit lower hyperemic (p = 0.003), thermal (p = 0.010), and EDD (p = 0.004) responses. No differences in EID between the groups were identified. We also identified that individuals who use e-cigarettes for longer than 3 years also present with systemic manifestations, as observed by significantly reduced macrovascular (p = 0.002) and microvascular (p ≤ 0.044) function. CONCLUSIONS: Our novel data suggests that young, apparently healthy, regular users of e-cigarettes present with premature vascular dysfunction in the microcirculation when compared to non-users. We have also identified systemic vascular dysfunction affecting both the micro and macrovasculature in those young individuals who used e-cigarettes for longer than 3 years. Taken together, these findings associate regular e-cigarette use with premature vascular dysfunctions and adverse cardiovascular outcomes.

Nicotine Impairs Smooth Muscle cAMP Signaling and Vascular Reactivity.

OBJECTIVE: This study aimed to determine nicotine's impact on receptor-mediated cyclic adenosine monophosphate (cAMP) synthesis in vascular smooth muscle (VSM). We hypothesize that nicotine impairs ß adrenergic-mediated cAMP signaling in VSM, leading to altered vascular reactivity. METHODS: The effects of nicotine on cAMP signaling and vascular function were systematically tested in aortic VSM cells and acutely isolated aortas from mice expressing the cAMP sensor TEpacVV (Camper), specifically in VSM (e.g., CamperSM). RESULTS: Isoproterenol (ISO)-induced ß-adrenergic production of cAMP in VSM was significantly reduced in cells from second-hand smoke (SHS)-exposed mice and cultured wild-type VSM treated with nicotine. The decrease in cAMP synthesis caused by nicotine was verified in freshly isolated arteries from a mouse that had cAMP sensor expression in VSM (e.g., CamperSM mouse). Functionally, the changes in cAMP signaling in response to nicotine hindered ISO-induced vasodilation, but this was reversed by immediate PDE3 inhibition. CONCLUSIONS: These results imply that nicotine alters VSM ß adrenergic-mediated cAMP signaling and vasodilation, which may contribute to the dysregulation of vascular reactivity and the development of vascular complications for nicotine-containing product users.

Adapting E-cigarette prevention programming to reach the latinx community.

PURPOSE: E-cigarettes are the most commonly used tobacco product among youth in the United States. Yet evidence-based prevention programming is limited due to the rapid onset of this threat. Community-based efforts to address vaping largely target youth in school settings. Although parents can play an important role in youth tobacco control efforts, messages about the dangers of vaping, use among adolescents, and strategies for intervening have not reached many Spanish-speaking parents in low-income Latinx communities. Our community-academic team developed e-cigarette prevention programming for use by promotor/as de salud to address this unmet need. METHODS: During the 1-year project, the team worked closely with a Project Advisory Committee to: review existing evidence-informed materials; conduct focus groups with parents, youth and promotor/as to guide program development; develop a curriculum to prepare promotor/as to educate low-literacy, Spanish-speaking parents about vaping; craft Spanish language resources for promotor/as to use in community education sessions; train 61 promotor/as to deliver the program; and support program delivery to 657 community members. RESULTS: Focus groups with promotor/as and community members, key-informant interviews, and brief surveys informed program development and assessment. Community member feedback was essential to development of appropriate materials. Promotor/as demonstrated significant pre- to post- training increases in e-cigarette knowledge and confidence in delivering vaping prevention education. Community members demonstrated a mastery of basic e-cigarette concepts and expressed intention to discuss vaping with their children. CONCLUSIONS: Promotor/a-led programming for parents represents a promising approach to vaping prevention and control in the Latinx community.

E-cigarettes Induce Dysregulation of Autophagy Leading to Endothelial Dysfunction in Pulmonary Arterial Hypertension.

Given the increasing popularity of electronic cigarettes (e-cigs), it is imperative to evaluate the potential health risks of e-cigs, especially in users with preexisting health concerns such as pulmonary arterial hypertension (PAH). The aim of the present study was to investigate whether differential susceptibility exists between healthy and patients with PAH to e-cig exposure and the molecular mechanisms contributing to it. Patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from healthy individuals and patients with PAH were used to investigate whether e-cig contributes to the pathophysiology of PAH and affects EC homeostasis in PAH. Our results showed that PAH iPSC-ECs showed a greater amount of damage than healthy iPSC-ECs upon e-cig exposure. Transcriptomic analyses revealed that differential expression of Akt3 may be responsible for increased autophagic flux impairment in PAH iPSC-ECs, which underlies increased susceptibility upon e-cig exposure. Moreover, knockdown of Akt3 in healthy iPSC-ECs significantly induced autophagic flux impairment and endothelial dysfunction, which further increased with e-cig treatment, thus mimicking the PAH cell phenotype after e-cig exposure. In addition, functional disruption of mTORC2 by knocking down Rictor in PAH iPSC-ECs caused autophagic flux impairment, which was mediated by downregulation of Akt3. Finally, pharmacological induction of autophagy via direct inhibition of mTORC1 and indirect activation of mTORC2 with rapamycin reverses e-cig-induced decreased Akt3 expression, endothelial dysfunction, autophagic flux impairment, and decreased cell viability, and migration in PAH iPSC-ECs. Taken together, these data suggest a potential link between autophagy and Akt3-mediated increased susceptibility to e-cig in PAH.

Feasibility of restricting e-cigarettes to prescription only for smoking cessation.

E-cigarette use among youth in Canada has risen to epidemic proportions. E-cigarettes are also moderately useful smoking cessations aids. Restricting e-cigarettes to prescription only smoking cessation aids could help limit youth's access to them while keeping them available as therapies for patients who smoke conventional cigarettes. In Canada, drugs or devices must be approved by regulatory bodies such as Health Canada in order to become licensed prescription medications. A similar situation is underway in Australia, where e-cigarettes have been restricted to prescription only. This commentary explores the feasibility of a similar regulation for e-cigarettes in Canada as prescription smoking cessation aids.

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung.

BACKGROUND: Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) aerosolize an e-liquid composed of propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with tobacco-derived nicotine (TDN) composed of S-nicotine, and tobacco-free/synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently, there is limited knowledge of the potential differences in the toxicity of TFN versus TDN. We hypothesized that exposure of TFN and TDN salts to C57BL/6J mice would result in a differential response in lung inflammation and protease/ antiprotease imbalance. METHODS: Five-week-old male and female C57BL/6J mice were exposed to air, PG/VG, PG/VG with TFN salts (TFN), or PG/VG with TDN salts (TDN) by nose-only exposure. Lung inflammatory cell counts, cytokine/chemokine levels, and matrix metalloproteinase (MMP) protein abundance and activity levels were determined by flow cytometry, ELISA, immunoblotting, and gel zymography, respectively. RESULTS: Exposure to the humectants (PG/VG) alone increased cytokine levels- IL-6, KC, and MCP-1 in the BALF and KC levels in lung homogenate of exposed mice. While no change was observed in the cytokine levels in lung homogenate of TDN aerosol exposed mice, exposure to TFN aerosols resulted in an increase in KC levels in the lungs of these mice compared to air controls. Interestingly, exposure to TDN aerosols increased MMP-9 protein abundance in the lungs of female mice, while exposure to TFN aerosol showed no change. The metabolism of nicotine or the clearance of cotinine for TFN exposure may differ from that for TDN. CONCLUSION: Exposure to humectants, PG/VG alone, induces an inflammatory response in C57BL/6J mice. TFN and TDN salts show distinct changes in inflammatory responses and lung proteases on acute exposures. These data suggest variable toxicological profiles of the two forms of nicotine in vivo. Future work is thus warranted to delineate the harmful effects of synthetic/natural nicotine with humectants to determine the potential toxicological risks for users.

Using Eye tracking to Examine Young Adults' Visual Attention to E-cigarette Advertising Features and Associated Positive E-cigarette Perceptions.

BACKGROUND: Little is known about the influence of e-cigarette marketing features on the antecedents of e-cigarette use. PURPOSE: Using an eye-tracking experiment, we examined visual attention to common features in e-cigarette ads and its associations with positive e-cigarette perceptions among young adults. METHODS: Young adults (ages 18-29) who smoke cigarettes (n = 40) or do not use tobacco (n = 71) viewed 30 e-cigarette ads on a computer screen. Eye-tracking technology measured dwell time (fixation duration) and entry time (time to first fixation) for 14 pre-defined ad features. Participants then completed a survey about perceptions of e-cigarettes shown in the ads. We used regression models to examine the associations between ad features and standardized attention metrics among all participants and by tobacco-use status and person-aggregated standardized attention for each ad feature and positive e-cigarette perceptions. RESULTS: Dwell time was the longest for smoker-targeted claims, positive experience claims, and price promotions. Entry time was the shortest for multiple flavor descriptions, nicotine warnings, and people. Those who do not use tobacco had a longer dwell time for minor sales restrictions and longer entry time for purchasing information than those who smoke. Longer dwell time for multiple flavor descriptions was associated with e-cigarette appeal. A shorter entry time for fruit flavor description was associated with positive e-cigarette-use expectancies. CONCLUSIONS: Young adults allocated attention differently to various e-cigarette ad features, and such viewing patterns were largely similar by tobacco-use statuses. Multiple or fruit flavors may be the features that contribute to the positive influence of e-cigarette marketing among young adults.

E-cigarette marketing exposure is associated with e-cigarette use among young adults. However, little is known about the influence of e-cigarette marketing features among this population. This study used eye-tracking technology to objectively measure dwell time and entry time for 14 pre-defined e-cigarette ad features. Young adults (ages 18­29) who smoke cigarettes (n = 40) or do not use tobacco (n = 71) viewed 30 e-cigarette ads on a computer screen and completed an online survey about positive e-cigarette perceptions. The study found that dwell time was the longest for smoker-targeted claims, positive experience claims, and price promotions. Entry time was the shortest for multiple flavor descriptions, nicotine warnings, and people. Those who do not use tobacco had a longer dwell time for minor sales restrictions and longer entry time for purchasing information than those who smoke. Longer dwell time for multiple flavor descriptions was associated with e-cigarette appeal. A shorter entry time for fruit flavor description was associated with positive e-cigarette-use expectancies. The results suggest that young adults allocated attention differently to various e-cigarette ad features, and such viewing patterns were largely similar by tobacco-use statuses. Multiple or fruit flavors may be the features that contribute to the positive influence of e-cigarette marketing among young adults.

Association of cigarette and electronic cigarette use patterns with all-cause mortality: A national cohort study of 145,390 US adults.

OBJECTIVE: While e-cigarette use is associated with adverse cardiopulmonary health effects, the mortality risks associated with e-cigarette use alone and combined with smoking remain unexamined. METHODS: Data between 2014 and 2018 were obtained from the National Health Interview Survey (NHIS), an annual cross-sectional survey of US adults. All-cause mortality and date of death were obtained via linkage of the NHIS to the National Death Index through December 31, 2019. A 6-category composite cigarette (never, former, current) and e-cigarette (current, non-current) exposure variable was created. We examined the association of cigarette and e-cigarette use patterns with all-cause mortality using adjusted Cox models. RESULTS: Among 145,390 participants (79,294 women [51.5%]; 60,560 aged 18-44 [47.4%]), 5220 deaths were observed over a median follow-up of 3.5 years (508,545 total person-years). Dual use of cigarettes and e-cigarettes was associated with higher mortality risk compared with non-current e-cigarette use in combination with never smoking (hazard ratio [HR] 2.44; 95% CI, 1.90-3.13) and had a risk that did not differ from current exclusive smoking (HR, 1.06; 95% CI, 0.83-1.37). Current e-cigarette use in combination with former smoking was associated with a lower mortality risk than current exclusive cigarette smoking (HR 0.64; 95% CI, 0.41-0.99). CONCLUSIONS: The addition of e-cigarette use to smoking does not reduce mortality risk compared with exclusive smoking. However, transitioning completely from cigarettes to e-cigarettes may be associated with mortality risk reduction. Further research is needed to verify these findings in larger cohorts and over longer periods of follow-up.

Parenting practices, mental health, and electronic cigarette use among U.S. young adolescents: A longitudinal panel analysis, 2013-2018.

PURPOSE: This study examined prospective association of parenting practices related to tobacco use with adolescent e-cigarette use and the moderating role of mental health among U.S. young adolescents. METHODS: We study used multi-wave longitudinal data (2013-2018) drawn from the Population Assessment of Tobacco and Health Study. A total of 5114 young adolescents (12-14 years) who were not lost to follow-ups across four waves (Wave 1-4) comprised the study sample. Weighted logistic regression models along with generalized linear mixed modeling assessed the within-subject associations of parenting practices related to tobacco use (tobacco availability at parent/guardian's home, past-year parent talk about tobacco use, and rules about non-combustible tobacco use at home) with adolescent current e-cigarette use. RESULTS: Prevalence of having home rules about non-combustible tobacco use increased (74.5%-80.2%) and that of parent talk about tobacco use decreased (52.0%-33.9%) over time while tobacco availability at home did not show a specific trend. Tobacco availability at home was associated with increased odds of adolescent e-cigarette use (adjusted odd ratio[OR] = 2.25, 95% confidence interval[CI] = 1.72-2.95), and having home rules about non-combustible tobacco use was linked to decreased likelihood of e-cigarette use (adjusted OR = 0.72, 95% CI = 0.55-0.92). The magnitude of negative association between having rules about non-combustible tobacco and adolescent e-cigarette use was stronger among adolescents with internalizing problems but weaker among those with externalizing problems. CONCLUSIONS: Our findings highlight the important role of home-based interventions in discouraging young adolescents from e-cigarette use. Parents/guardians should consider adolescents' mental health to provide more efficient home- and/or clinical-based e-cigarette use prevention.

Would banning menthol cigarettes, flavored cigars, and flavored e-cigarettes prompt users to seek illicit channels for obtaining them in the United States?

BACKGROUND: Banning flavors in tobacco and nicotine products may reduce youth initiation and prompt quit attempts but such bans may lead to illicit markets. We examined how likely current users would be to seek flavored products from illicit channels under various ban scenarios. METHODS: Cross-sectional surveys of 2552 current users of menthol cigarettes or flavored cigars and 2347 users of flavored e-cigarettes were conducted between 2021 and 2022 in the United States. For each ban scenario, respondents reported if they would have intentions to seek the banned flavored products from any illicit channels and identified the specific illicit channel they would consider. Logistic regressions were used to estimate how the likelihood of having intentions to seek illicit channels was associated with demographics, ban scenarios, and status of tobacco use. RESULTS: Under various ban scenarios, 24-30% of people who smoked said they would seek illicit channels to obtain the banned products compared with 21-41% of dual users and 35-39% of users of flavored e-cigarettes. Online retailers were favored by people who smoked while users of flavored e-cigarettes favored local retailers. Heavy users were more likely to say they would try illicit channels. Under bans restricting more types of flavored tobacco products, users would be less likely to try illegal channels. CONCLUSIONS: A significant proportion of users of flavored tobacco and nicotine products would not reject using illicit banned products. Tailored programs are needed to apply to the groups with a higher risk of seeking illicit channels for banned products.

Serious psychological distress and higher associations with tobacco and cannabis use among college students in the United States.

OBJECTIVE: To examine associations between serious psychological distress (SPD) and tobacco and cannabis use among college students in the United States. METHODS: This cross-sectional study included 257,626 college students from the 2019-2022 National College Health Assessment survey. SPD was defined as having symptoms in the past month. Current tobacco (i.e., cigarettes, e-cigarettes) and cannabis use was defined as past month use. Multiple product use was categorized for single, dual, or triple products. Adjusted logistic regression models were used to examine associations between SPD, tobacco, cannabis, and multiple product use. RESULTS: SPD increased over time (18.4% to 23.8%) among students and nearly 30% of tobacco or cannabis users reported SPD. Cigarette, e-cigarette, or cannabis use was associated with about a 50-60% increased likelihood of reporting SPD than non-current use of each product, with the highest associations in Fall 2020. Triple product users had double the likelihood of reporting SPD, followed by dual users at 70% and single users at 47%, relative to non-current users. Daily users also had nearly twice the likelihood of reporting SPD, followed by non-daily users at 13-35%, relative to non-current users. CONCLUSIONS: College students have an increasing burden of SPD which is significantly associated with tobacco and cannabis use. There is a dose-response relationship between the number of tobacco and cannabis products used, as well as the frequency of use, and SPD among U.S. college students. Colleges addressing student mental health should prioritize the implementation of screening and treatment support for tobacco, cannabis, and multiple product use.

Socioecological factors associated with multiple nicotine product use among U.S. youth: Findings from the population assessment of tobacco and health (PATH) study 2013-2018.

OBJECTIVE: This study utilized a socioecological approach to prospectively identify intrapersonal, familial, and environmental factors associated with single nicotine product use (NPU) and multiple NPU among U.S. youth. METHODS: Participants were 10,029 youths (ages 12-17 years) who had completed the Population Assessment of Tobacco Health study's Wave 1 (2013-2014) and Wave 4 (2016-2018) assessments and data on past 30-day nicotine product use. Multinomial logistic regression was fit for the 3-level outcome (no use, single NPU, multiple NPU) to estimate adjusted associations between the predictors and the outcome. RESULTS: The current study found that intrapersonal (sex, age, race/ethnicity, internalizing symptoms, sensation seeking, harm perceptions, lifetime history of using two or more tobacco products), familial (parental discussion about not using tobacco and living with someone who uses tobacco products) and environmental factors (exposure to tobacco advertising) commonly associated with tobacco use differentiated between individuals who later reported past 30-day NPU (either multiple or single NPU) from those who did not report past 30-day NPU. One familial factor only differentiated between lifetime users who were single NPUs from those who reported no NPU: non-combustible tobacco product use allowed anywhere in the home. Intrapersonal factors differentiated multiple NPU from single NPU: older age, being male, lifetime history of using nicotine product and less harm perceptions. CONCLUSIONS: This study identified factors that may be studied to prevent any NPU, along with factors that may be studied to promote harm reduction by preventing escalation of single NPU to problematic patterns of multiple NPU.

Non-tobacco nicotine E-cigarette use and flavored E-cigarette use among young adults in the United States.

BACKGROUND: E-cigarette flavors can create sensations of sweetness and coolness while masking the aversiveness of nicotine. Recently, non-tobacco nicotine (NTN) products were introduced to the market, but little is known about flavors in NTN e-cigarette use. We examined associations between flavors (i.e., sweet, mint/menthol) and susceptibility to and use of NTN e-cigarettes. METHODS: 1239 US young adults (18-25 years) completed an anonymous, online survey in Fall 2021. The analytic sample included 520 participants who had used e-cigarettes and heard of NTN. Multinomial logistic regression models analyzed associations of flavored e-cigarette use (sweet and mint/menthol) with NTN e-cigarette use status (i.e., current [past-month] use, past [ever but not current] use, susceptible to use, and non-susceptible to use [reference]). RESULTS: Overall, 46.2% of participants reported current NTN use, 14.8% reported past use, 16.7% were susceptible to use, and 22.3% reported no susceptibility. Participants reported dual-use of sweet and mint/menthol NTN e-cigarette flavors (56.5%), sweet flavors use (24.8%), and mint/menthol flavor use (1.7%). Ever dual use of sweet and mint/menthol flavors was associated with current (OR = 9.64, 95%CI: 3.21-28.98) and past NTN e-cigarette use (8.30, [2.10-32.80]). Ever sweet flavor use was associated with current NTN use (3.80, 95%CI: 1.44-10.03) and susceptibility to future use (4.25, [1.53-11.81]). Similar findings were observed for mint/menthol flavors (current: 5.03, [1.41-17.99]; susceptible: 5.65, [1.64-19.51]). CONCLUSION: The use of sweet and mint/menthol flavors was significantly associated with NTN e-cigarette use among US young adults, highlighting the need for ongoing surveillance of flavored NTN e-cigarettes and appropriate regulations to discourage use.

Electronic nicotine delivery systems (ENDS): Frequency of use and smoking-cessation efforts among U.S. women of reproductive age.

OBJECTIVE: Reducing harm from combustible cigarette use among women of reproductive age (WRA) is critical given their potential vulnerability to multigenerational adverse impacts of cigarette smoking. Although electronic nicotine delivery systems (ENDS) are not approved smoking cessation aids in the US, many WRA who smoke report using ENDS to help quit smoking. Associations between ENDS use patterns and smoking-cessation efforts among US WRA remain unclear. METHODS: Using the Population Assessment of Tobacco and Health (PATH) Study, we examined whether baseline (Wave 3 or 4) ENDS use frequency predicted (a) making a cigarette quit attempt (QA) and (b) successful quitting by follow-up (Wave 4 or 5, respectively) among WRA (N = 2834; 72.1% non-Hispanic White). RESULTS: Daily ENDS use predicted greater adjusted odds of making a QA than non-daily (AOR = 1.63, 95% CI = 1.03, 2.59) and no ENDS use (AOR = 1.97, 95% CI = 1.23, 3.14), and greater odds of successful smoking cessation than non-daily use (AOR = 2.37, 95% CI = 1.31, 4.26). Daily ENDS use did not significantly improve odds of successful smoking cessation compared to no ENDS use (AOR = 1.62, 95% CI = 0.97, 2.69). Non-daily ENDS use did not significantly improve odds of making a QA (AOR = 1.21, 95% CI = 0.94, 1.56) and hindered successful smoking cessation compared to no ENDS use (AOR = 0.68, 95% CI = 0.48, 0.98). CONCLUSIONS: These findings suggest that benefits of ENDS for smoking cessation in WRA may be greatest among those who use ENDS daily. WRA who choose to use ENDS to help quit would be well-informed by evidence that non-daily ENDS use may impede smoking cessation.

Sex differences in appeal, reward, and sensory experience of E-cigarette flavors among adults who smoke cigarettes.

OBJECTIVE: Flavors enhance nicotine e-cigarette appeal by altering sensory experience. Females may be more sensitive to tobacco-associated cues and uniquely affected by flavor. The current study is an exploratory analysis to examine differences by sex on reward, appeal, and sensory experience of popular e-cigarette flavors. METHODS: Adults (N = 121) who use cigarettes (≥1 cigarette/day) were enrolled in a laboratory study in which they vaped four e-cigarette flavors (tobacco, cherry, menthol, vanilla; in separate lab sessions) in one of two freebase nicotine concentrations (6 mg/ml,18 mg/ml). Following exposures, participants rated e-cigarette reward using the Drug Effects Questionnaire (DEQ), flavor and overall e-cigarette appeal using Labeled Hedonic Scales (LHS), and intensity of flavor, irritation, coolness, fruitiness, and sweetness using Generalized Labeled Magnitude Scales (gLMS). Linear mixed models were conducted for outcomes to analyze effects of sex, flavor, and sex x flavor interaction. RESULTS: For DEQ ratings, there was a trend (p = .08) toward a sex x flavor interaction, in which menthol flavor produced more reward than other flavors for females, but not males. For LHS ratings, there was a significant sex x flavor interaction (p = .03) for overall e-cigarette experience with females but not males rating menthol higher than other flavors. All gLMS scales but irritation showed that females generally had greater differences between flavors compared to males (ps ≤ 0.03). CONCLUSION: Menthol in e-cigarettes may play an important role in mediating appeal and/or reward among females. This may be due in part to their ability to better detect sensory effects of e-cigarettes.

Exposure to Aldehyde Cherry e-Liquid Flavoring and Its Vaping Byproduct Disrupt Pulmonary Surfactant Biophysical Function.

Over the past decade, there has been a significant rise in the use of vaping devices, particularly among adolescents, raising concerns for effects on respiratory health. Pressingly, many recent vaping-related lung injuries are unexplained by current knowledge, and the overall implications of vaping for respiratory health are poorly understood. This study investigates the effect of hydrophobic vaping liquid chemicals on the pulmonary surfactant biophysical function. We focus on the commonly used flavoring benzaldehyde and its vaping byproduct, benzaldehyde propylene glycol acetal. The study involves rigorous testing of the surfactant biophysical function in Langmuir trough and constrained sessile drop surfactometer experiments with both protein-free synthetic surfactant and hydrophobic protein-containing clinical surfactant models. The study reveals that exposure to these vaping chemicals significantly interferes with the synthetic and clinical surfactant biophysical function. Further atomistic simulations reveal preferential interactions with SP-B and SP-C surfactant proteins. Additionally, data show surfactant lipid-vaping chemical interactions and suggest significant transfer of vaping chemicals to the experimental subphase, indicating a toxicological mechanism for the alveolar epithelium. Our study, therefore, reveals novel mechanisms for the inhalational toxicity of vaping. This highlights the need to reassess the safety of vaping liquids for respiratory health, particularly the use of aldehyde chemicals as vaping flavorings.

Categorizing Vaping Intensity among Youth.

INTRODUCTION: Increasing electronic cigarette use among youth has led to a need for a novel intensity measure of e-cigarette use and its association with nicotine addiction variables. METHODS: Using a cross sectional study of the 2018-2019 PATH Wave 5 Youth survey, a new intensity metric of e-cigarette use, the average number of puffs per month as a function of frequency (days of use per month), number of uses per day and number of puffs per use, was developed for adolescent e-cigarette users. Using logistic regression, standard addiction measures were tested for association with higher quartile (Q) of e-cigarette intensity: Q1 (1-5 puffs), Q2 (6-50 puffs), Q3 (51-528 puffs), and Q4 (529+ puffs). RESULTS: Among 1,051 current youth e-cigarette users, cravings were associated with greater intensity of use (Q2: aOR= 1.90, 95% CI: 0.94-3.87; Q3: aOR = 6.91, 95% CI: 3.25-14.69; Q4: aOR =21.48, 95% CI 10.03-45.97). Craving associations exceeded the corresponding aORs for the identical regression using frequency of use. Higher intensity was significantly associated with being an older adolescent (aOR=1.85), best friend use (aOR: 3.35), not thinking about quitting (aOR: 2.51), and lower perceived addiction (aOR: 1.95). CONCLUSIONS: This study found that an intensity metric (puffs per month) was strongly associated with cravings, best friend use, harm perception, and lack of intention to quit. This metric provides a more accurate picture of the intensity of youth e-cigarette use than other commonly used measures and may be important for understanding the current and future impact of the youth e-cigarette epidemic. IMPLICATIONS: Adolescent addiction to e-cigarettes affects learning, memory, and attention. However, it is unknown whether intensity of use, puffs per month, differs from frequency, days of use per month, in relation to addiction measures. This study provides evidence that high intensity use characterized by puffs per month has a stronger association to cravings compared to frequency, which suggests puffs per month may be a better measure of nicotine exposure. This new intensity metric may give insights into youth e-cigarette use patterns, addiction, and appropriate treatment of intense but intermittent users.

Using pod based e-cigarettes and nicotine pouches to reduce harm for adults with low socioeconomic status who smoke: A pilot randomized controlled trial.

INTRODUCTION: Alternative Nicotine Delivery Systems (ANDS) such as e-cigarettes (EC) and oral nicotine pouches (ONP) may facilitate the substitution of smoking for those unwilling to quit. This pilot study assesses the harm reduction potential of EC and ONP among smokers with low socioeconomic status (SES). METHODS: Adults who smoked daily in the past 6 months, had a household income < 250% federal poverty level and had no intention of quitting smoking in the next 30 days were randomized 2:2:1 to 8 Weeks of 5% nicotine EC; 4mg ONP or assessment-only control (CC). The primary outcome was a within-group change in cigarettes per day (CPD) from Baseline to Week 8. RESULTS: 45 individuals were randomized (EC: N=18; ONP: N=18; CC: N=9). Analyses included 33 participants who completed the Week 8 visit. Mean age was 50.2 years (SD:10.7) and average CPD at baseline was 13.9 (SD: 10.1). For those randomized to EC, average CPD decreased from 14.7 (95%CI: 10.3; 19.1) at Baseline to 2.9 (95%CI: 0.09; 5.79) at Week 8 (p-value <0.001). For those randomized to ONP, average CPD decreased from 15.0 (95%CI: 5.02; 24.93) to 8.3 (95%CI: 1.34; 15.18) by Week 8 (p-value =0.01). In the EC and ONP groups, respectively, 4 (28.6%) and 1 (8.3%) participant fully switched from smoking to the ANDS product by Week 8. CONCLUSIONS: Individuals with low SES who smoke had lower CPD after switching to EC or ONP. These findings show the potential of ANDS in helping smokers switch to less harmful devices. IMPLICATIONS: This study provides novel evidence that e-cigarettes and nicotine pouches can be a harm reduction tool for individuals with lower SES who smoke and are not willing to quit smoking, contributing to reducing tobacco-related disparities in this population.