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Electronic Nicotine Delivery System Aerosol-induced Cell Death and Dysfunction in Macrophages and Lung Epithelial Cells.

ABSTRACT: Electronic nicotine delivery system (ENDS) use is outpacing our understanding of its potential harmful effects. Homeostasis of the lung is maintained through proper balance of cell death, efferocytic clearance, and phagocytosis of pathogens. To investigate whether ENDS use has the potential to alter this balance, we developed physiologically relevant ENDS exposure paradigms for lung epithelial cells and primary macrophages. In our studies, cells were exposed directly to aerosol made from carefully controlled components with and without nicotine. We found that ENDS aerosol exposure led to apoptosis, secondary necrosis, and necrosis in lung epithelial cell models. In contrast, macrophages died mostly by apoptosis and inflammatory caspase-mediated cell death when exposed to ENDS aerosol. The clearance of dead cells and pathogens by efferocytosis and phagocytosis, respectively, is an important process in maintaining a healthy lung. To investigate the impact of ENDS aerosol on macrophage function independent of general toxicity, we used an exposure time that did not induce cell death in primary macrophages. Exposure to ENDS aerosol containing nicotine inhibited nearly all phagocytic and greatly reduced the efferocytic abilities of primary macrophages. When challenged with a bacterial pathogen, there was decreased bacterial clearance. The presence of nicotine in the ENDS aerosol increased its toxicity and functional impact; however, nicotine exposure alone did not have any deleterious effects. These data demonstrate that ENDS aerosol exposure could lead to increased epithelial cell and macrophage death in the lung and impair important macrophage functions that are essential for maintenance of lung function.

SUBMITTER: Serpa GL

PROVIDER: S-EPMC7462344 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AIMS:To estimate the effect of potential regulations of electronic nicotine delivery systems (ENDS) among adult smokers, including increasing taxes, reducing flavor availability and adding warning labels communicating various levels of risk. DESIGN:We performed a discrete choice experiment (DCE) among a national sample of 1200 adult smokers. We examined heterogeneity in policy responses by age, cigarette quitting interest and current ENDS use. Our experiment overlapped January 2015 by design, providing exogenous variation in cigarette quitting interest from New Year resolutions. SETTING:KnowledgePanel, an online panel of recruited respondents. PARTICIPANTS:A total of 1200 adult smokers from the United States. MEASUREMENTS:Hypothetical purchase choice of cigarettes, nicotine replacement therapy and a disposable ENDS. FINDINGS:Increasing ENDS prices from $3 to $6 was associated with a 13.6 percentage point reduction in ENDS selection (P < 0.001). Restricting flavor availability in ENDS to tobacco and menthol was associated with a 2.1 percentage point reduction in ENDS selection (P < 0.001). The proposed Food and Drug Administration (FDA) warning label was associated with a 1.1 percentage point reduction in ENDS selection (P < 0.05) and the MarkTen warning label with a 5.1 percentage point reduction (P < 0.001). We estimated an ENDS price elasticity of -1.8 (P < 0.001) among adult smokers. Statistically significant interaction terms (P < 0.001) imply that price responsiveness was higher among adult smokers 18-24 years of age, smokers who have vaped over the last month and smokers with above the median quitting interest. Young adult smokers were 3.7 percentage points more likely to choose ENDS when multiple flavors were available than older adults (P < 0.001). Young adult smokers and those with above the median cigarette quitting interest were also more likely to reduce cigarette selection and increase ENDS selection in January 2015 (P < 0.001), potentially in response to New Year's resolutions to quit smoking. CONCLUSIONS:Increased taxes, a proposed US Food and Drug Administration warning label for electronic nicotine delivery systems and a more severe warning label may discourage adult smokers from switching to electronic nicotine delivery systems. Reducing the availability of flavors may reduce ENDS use by young adult smokers.

Project description:IntroductionSecond generation electronic nicotine delivery systems (ENDS; also known as e-cigarettes, vaporizers or vape pens) are designed for a customized nicotine delivery experience and have less resemblance to regular cigarettes than first generation "cigalikes." The present study examined whether they generalize as a conditioned cue and evoke smoking urges or behavior in persons exposed to their use.MethodsData were analyzed in N = 108 young adult smokers (?5 cigarettes per week) randomized to either a traditional combustible cigarette smoking cue or a second generation ENDS vaping cue in a controlled laboratory setting. Cigarette and e-cigarette urge and desire were assessed pre- and post-cue exposure. Smoking behavior was also explored in a subsample undergoing a smoking latency phase after cue exposure (N = 26).ResultsThe ENDS vape pen cue evoked both urge and desire for a regular cigarette to a similar extent as that produced by the combustible cigarette cue. Both cues produced similar time to initiate smoking during the smoking latency phase. The ENDS vape pen cue elicited smoking urge and desire regardless of ENDS use history, that is, across ENDS na?ve, lifetime or current users. Inclusion of past ENDS or cigarette use as covariates did not significantly alter the results.ConclusionsThese findings demonstrate that observation of vape pen ENDS use generalizes as a conditioned cue to produce smoking urge, desire, and behavior in young adult smokers. As the popularity of these devices may eventually overtake those of first generation ENDS cigalikes, exposure effects will be of increasing importance.ImplicationsThis study shows that passive exposure to a second generation ENDS vape pen cue evoked smoking urge, desire, and behavior across a range of daily and non-daily young adult smokers. Smoking urge and desire increases after vape pen exposure were similar to those produced by exposure to a first generation ENDS cigalike and a combustible cigarette, a known potent cue. Given the increasing popularity of ENDS tank system products, passive exposures to these devices will no doubt increase, and may contribute to tobacco use in young adult smokers.

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Electronic Nicotine Delivery System Aerosol-induced Cell Death and Dysfunction in Macrophages and Lung Epithelial Cells.

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