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Item Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome(American Thoracic Society, 2021) Zeng, Zhenguo; Chen, Weiguo; Moshensky, Alexander; Shakir, Zaid; Khan, Raheel; Crotty Alexander, Laura E.; Ware, Lorraine B.; Aldaz, C.M.; Jacobson, Jeffrey R.; Dudek, Steven M.; Natarajan, Viswanathan; Machado, Roberto F.; Singla, Sunit; Medicine, School of MedicineA history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31+ CD45-cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant Staphylococcus aureus or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant S. aureus or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.Item Clinical Perspective: Treatment of adolescent e-cigarette use – limitations of existing nicotine use disorder treatment and future directions for e-cigarette use cessation(Elsevier, 2021) Adams, Zachary W.; Kwon, Elizabeth; Aalsma, Matthew C.; Zapolski, Tamika C.B.; Dir, Allyson; Hulvershorn, Leslie A.; Psychiatry, School of MedicineElectronic cigarette use ("vaping") has surged in the United States since the mid-2010s. From 2011 to 2018, current e-cigarette use among high school students escalated from 1.5% to 20.8% (∼3.05 million youths),1 countering downward trends in combustible nicotine product use (21.8% in 2011 to 13.9% in 2018).1 Although preventing the initial uptake of vaping is crucial, for the millions of adolescents who have taken up this behavior-many of whom express interest in quitting (eg, 44.5% of current, adolescent non-light e-cigarette users in one US national representative sample)2-it is critically important to help them quit vaping so as to curtail future substance use disorders and other health consequences. Here, we discuss several challenges around adolescent vaping treatment, and highlight research areas in urgent need of attention.Item Prohibition of e-cigarettes in the US: Are prohibitions where alcohol is consumed related to lower alcohol consumption?(Palgrave Macmillan, 2016-12) Hershberger, Alexandra R.; Karyadi, Kenny A.; Cyders, Melissa A.; Psychology, School of ScienceRecently, research has suggested negative consequences related to electronic cigarette (e-cig) use, including the increased risk for alcohol use and abuse. Previous work found that cigarette smoking ban legislation lowered overall smoking and alcohol use rates; however, researchers have not yet examined the potential effects of prohibiting e-cig use. The present study surveyed 617 individuals from a community-based online sample in the US (mean age = 33.33, SD = 10.50, 54.7 per cent female) who reported their smoking/e-cig use status, alcohol consumption, and the presence of e-cig prohibitions where they consume alcohol. E-cig prohibition was associated with a lower likelihood of being an e-cig user (OR = 0.12, p < 0.001) or dual user (use both cigarettes and e-cigs) (OR = 0.07, p < 0.001). Alcohol Use Disorder Identification Test scores (b = -1.92, p < 0.001), total drinks consumed over 14 days (b = -4.58, p = 0.002), and average drinks per drinking day (b = -0.71, p < 0.001) were all lower when e-cigs were prohibited. Findings are an initial step in this line of research and suggest important future work examining implications of e-cig prohibition recommendations and policy.Item The Relationship Between Electronic Nicotine Delivery System Use and Alcohol Consumption: A Neurocognitive and Behavioral Investigation(2019-08) Hershberger, Alexandra Raemin; Cyders, Melissa A.; Stewart, Jesse C.; Lapish, Christopher C.; Zapolski, Tamika C.B.Increasing research shows that the use of electronic nicotine delivery systems (ENDS) is associated with higher rates and quantity of alcohol consumption; however, no research to date experimentally examines the relationship between ENDS use and alcohol use. The present study uses a two-session within-subjects design to examine 1) the relationship between ENDS use prime and attentional bias for alcohol related cues and 2) the relationship between ENDS use and laboratory ad libitum alcohol consumption. A total of N = 31 (mean age = 28.71, SD = 11.17; 45.2% women; 54.8% White/Caucasian) healthy users of ENDS who endorsed liking beer completed the present study, which included 1) a dot-probe and eye-tracking task that assessed attentional bias (reaction time, initial orientation, and delayed disengagement) to alcohol images following ENDS prime or no prime and 2) an ad libitum beer consumption task that assessed mL of beer consumed by the participants when concurrent use of ENDS was allowed or not allowed. All analyses controlled for age, race, and gender. Results of repeated measure ANCOVA’s indicate that attentional bias for alcohol does not differ between the ENDS prime or control conditions (F’s 0.01 to 0.12, ηp2’s 0.001 to 0.01). There is a large interactive effect of self-reported days of concurrent use of ENDS and alcohol over the last 14 days (ηp2’s 0.35 to 0.85), small to medium effects of alcohol craving preceding eye-tracking (ηp2’s 0.02 to 0.09), and small to medium effects of ENDS craving preceding eye-tracking (ηp2’s 0.06 to 0.13), all of which show increases in attentional bias following the ENDS prime; however, these results were limited by data quality issues that preclude strong support of these effects. Results of repeated measure ANCOVA’s demonstrate that amount of beer consumed does not differ by ENDS condition, F (4, 26) = 0.03, p = .86, ηp2 = 0.001. Results of a hierarchical linear regression show that amount of ENDS weight change (g) is not significantly related to mL of beer consumed in the ENDS session (b = -86.48, t = -0.90, p = 0.38, ∆R2 = 0.03). Results of linear mixed modeling testing the effect of ENDS puffs on alcohol sips temporally across the ad lib task show puffs are significantly related to sips (estimate = 0.23, SE = 0.07, p = .002) and number ENDS puffs account for some variability in slope of participant sips across participants. Results of repeated measure ANCOVA’s do not demonstrate significant interactions between mL of beer consumed by session and concurrent self-reported ENDS use over the past two weeks (ηp2 = 0.45), alcohol craving, or ENDS craving (ηp2’s = 0.002). Overall, results indicate that increased frequency of ENDS use is related to an increased frequency of beer consumption in real time. Since ENDS is related to alcohol use in time and place, individuals at risk for alcohol use problems should take care in their ENDS use. This study suggests that research should more fully measure and compare event-level and meta-level data on ENDS and alcohol use and that patterns based in the cigarette literature may not always generalize to ENDS.Item Thirdhand vaping exposures are associated with pulmonary and systemic inflammation in a mouse model(OAE, 2023) Commodore, Sarah; Sharma, Shikha; Ekpruke, Carolyn Damilola; Pepin, Robert; Hansen, Angela M.; Rousselle, Dustin; Babayev, Maksat; Ndeke, Jonas M.; Alford, Rachel; Parker, Erik; Dickinson, Stephanie; Sharma, Sunita; Silveyra, Patricia; Medicine, School of MedicineThirdhand smoke (THS) is the accumulation of secondhand smoke on surfaces that ages with time. THS exposure is a potential health threat to children, partners of smokers, and workers in environments with current or past smoking, and needs further investigation. In this study, we hypothesized that thirdhand Electronic Nicotine Delivery Systems (ENDS) exposures elicit lung and systemic inflammation due to resuspended particulate matter (PM) and inorganic compounds that remain after active vaping has ceased. To test our hypothesis, we exposed C57BL/6J mice to cotton towels contaminated with ENDS aerosols from unflavored vape fluid (6 mg nicotine in 50/50 propylene glycol/vegetable glycerin) for 1h/day, five days/week, for three weeks. We assessed protein levels in serum and bronchoalveolar lavage fluid (BALF) using a multiplex protein assay. The mean ± sd for PM10 and PM2.5 measurements in exposed mouse cages were 8.3 ± 14.0 and 4.6 ± 7.5 μg/m3, compared to 6.1 ± 11.2 and 3.7 ± 6.6 μg/m3 in control cages respectively. Two compounds, 4-methyl-1, 2-dioxolane and 4-methyl-cyclohexanol, were detected in vape fluid and on ENDS-contaminated towels, but not on control towels. Mice exposed to ENDS-contaminated towels had lower levels of serum Il-7 (P = 0.022, n = 7), and higher levels of Il-13 in the BALF (P = 0.006, n = 7) than those exposed to control towels (n = 6). After adjusting for sex and age, Il-7 and Il-13 levels were still associated with thirdhand vaping exposure (P = 0.010 and P = 0.017, respectively). This study provides further evidence that thirdhand ENDS aerosols can contaminate surfaces, and subsequently influence lung and systemic health upon exposure.