Nicotine inhalation and metabolism triggers AOX-mediated superoxide generation with oxidative lung injury.

With the increasing use of vaping devices that deliver high levels of nicotine (NIC) to the lungs, sporadic lung injury has been observed. Commercial vaping solutions can contain high NIC concentrations of 150 mM or more. With high NIC levels, its metabolic products may induce toxicity. NIC is primarily metabolized to form NIC iminium (NICI) which is further metabolized by aldehyde oxidase (AOX) to cotinine. We determine that NICI in the presence of AOX is a potent trigger of superoxide generation. NICI stimulated superoxide generation from AOX with Km = 2.7 µM and Vmax = 794 nmol/min/mg measured by cytochrome-c reduction. EPR spin-trapping confirmed that NICI in the presence of AOX is a potent source of superoxide. AOX is expressed in the lungs and chronic e-cigarette exposure in mice greatly increased AOX expression. NICI or NIC stimulated superoxide production in the lungs of control mice with an even greater increase after chronic e-cigarette exposure. This superoxide production was quenched by AOX inhibition. Furthermore, e-cigarette-mediated NIC delivery triggered oxidative lung damage that was blocked by AOX inhibition. Thus, NIC metabolism triggers AOX-mediated superoxide generation that can cause lung injury. Therefore, high uncontrolled levels of NIC inhalation, as occur with e-cigarette use, can induce oxidative lung damage.

E-Cigarette Toxicology.

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic cigarette (e-cigarette) vaping has surpassed conventional cigarette smoking among adolescents and young adults in the United States and beyond. This review describes the experimental and clinical evidence of e-cigarette toxicity and deleterious health effects. Adverse health effects related to e-cigarette aerosols are influenced by several factors, including e-liquid components, physical device factors, chemical changes related to heating, and health of the e-cigarette user (e.g., asthmatic). Federal, state, and local regulations have attempted to govern e-cigarette flavors, manufacturing, distribution, and availability, particularly to underaged youths. However, the evolving e-cigarette landscape continues to impede timely toxicological studies and hinder progress made toward our understanding of the long-term health consequence of e-cigarettes.

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

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

Does vaping increase the likelihood of SARS-CoV-2 infection? Paradoxically yes and no.

Data on the relationship between electronic cigarettes (ECs) and SARS-CoV-2 infection are limited and contradictory. Our objectives were to investigate the impact of EC aerosols on SARS-CoV-2 infection of human bronchial epithelial cells and identify the causative chemical(s). Fully differentiated human bronchial epithelial tissues (hBETs) were exposed at the air-liquid interface (ALI) to aerosols produced from JUUL "Virginia Tobacco" and BLU ECs, as well as nicotine, propylene glycol (PG), vegetable glycerin (VG), and benzoic acid, and infection was then evaluated with SARS-CoV-2 pseudoparticles. Pseudoparticle infection of hBETs increased with aerosols produced from PG/VG, PG/VG plus nicotine, or BLU ECs; however, JUUL EC aerosols did not increase infection compared with controls. Increased infection in PG/VG alone was due to enhanced endocytosis, whereas increased infection in PG/VG plus nicotine or in BLU ECs was caused by nicotine-induced elevation of the aerosol's pH, which correlated with increased transmembrane protease, serine 2 (TMPRSS2) activity. Notably, benzoic acid in JUUL aerosols mitigated the enhanced infection caused by PG/VG or nicotine, offering protection that lasted for at least 48 h after exposure. In conclusion, the study demonstrates that EC aerosols can impact susceptibility to SARS-CoV-2 infection depending on their specific ingredients. PG/VG alone or PG/VG plus nicotine enhanced infection through different mechanisms, whereas benzoic acid in JUUL aerosols mitigated the increased infection caused by certain ingredients. These findings highlight the complex relationship between ECs and SARS-CoV-2 susceptibility, emphasizing the importance of considering the specific aerosol ingredients when evaluating the potential effects of ECs on infection risk.NEW & NOTEWORTHY Data on the relationship between electronic cigarettes (ECs) and SARS-CoV-2 infection are limited and contradictory. We investigated the impact of EC aerosols and their ingredients on SARS-CoV-2 infection of human bronchial epithelial cells. Our data show that specific ingredients in EC aerosols impact the susceptibility to SARS-CoV-2 infection. Propylene glycol (PG)/vegetable glycerin (VG) alone or PG/VG plus nicotine enhanced infection through different mechanisms, whereas benzoic acid in JUUL aerosols mitigated the increased infection caused by these ingredients.

Electronic vape fluid activates the pulmonary endothelium and disrupts vascular integrity in vitro through an ARF6-dependent pathway.

The use of e-cigarettes or vapes is increasingly popular amongst a range of different demographics however the research in this area is surprisingly sparse. Clinical reports of e-cigarette- or vaping use-associated lung injury (EVALI) and vascular disruption, in both nicotine-containing and nicotine-free e-cigarette smokers, prompts the need for further research with a focus on the pulmonary endothelium. Using a common brand of e-cigarette (eVape) and an in vitro model of the human lung microvasculature, we investigated the effect of nicotine-free eVape fluid on pulmonary endothelial barrier integrity, oxidative stress and inflammation profile. Findings demonstrate reactive oxygen species-dependent breakdown of the pulmonary endothelium and release of inflammatory cytokines. These phenotypic changes, following exposure to nicotine-free eVape fluid, were accompanied by dysregulation of a number of adheren junctions-related genes of which ARF6 was most abundantly overexpressed. Further investigation of ARF6 identified it as a key regulator in eVape-induced barrier disruption and ROS accumulation. This study demonstrates, for the first time, the barrier disruptive effect of nicotine-free e-cigarette fluid on the pulmonary microvasculature and the ARF6 and ROS-dependent molecular mechanisms underlying this damage. Whilst these studies focus on a human in vitro model of the pulmonary microvasculature, the results support clinical case studies on EVALI and demonstrate a need for further investigation of the impact of nicotine-free e-cigarettes on the lung.

Demographic characteristics, perinatal smoking patterns, and risk for neonatal health complications among pregnant smokers in the United States who begin using electronic cigarettes during pregnancy: A descriptive study using population-based surveillance data.

INTRODUCTION: Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (a) characteristics of smokers who begin using ECs during pregnancy, (b) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (c) risk for neonatal health complications among smokers who initiate ECs during pregnancy. METHODS: Pregnant women using CCs exclusively pre-pregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified as dual users (used both ECs and CCs) or EC replacers (used ECs exclusively). RESULTS: Of 29,505 pregnant smokers, 1.5% reported using ECs during the last 3 pregnancy months. Among them, 29.7% became EC-exclusive users. EC initiators were disproportionately non-Hispanic White. Relative to quitters, EC initiators had lower income, were less likely to be married, have intended pregnancies, receive first-trimester prenatal care, and participate in a federal assistance program. Compared to CC-exclusive users, EC initiators overall, and dual users specifically, were more likely to reduce pre- and post-natal CC usage relative to pre-pregnancy levels. EC initiators' risk for neonatal health complications fell between quitters and CC-exclusive users, though differences were not statistically significant. CONCLUSIONS: Although EC initiators reduced CC use more than CC-exclusive users, only 29.7% reported complete CC cessation, and there was insufficient evidence of reduction in neonatal health complications relative to CC-exclusive users. Currently, ECs should not be considered a viable gestational smoking cessation strategy. IMPLICATIONS: Health agencies have identified a critical need for research evaluating the use of e-cigarettes in supporting prenatal smoking cessation. Using the US Pregnancy Risk Assessment Monitoring System surveillance study data, we provide real-world evidence that prenatal e-cigarette initiation as a smoking cessation tool is used infrequently among pregnant combustible cigarettes smokers. Most using e-cigarettes in the last three months of pregnancy also used combustible cigarettes.

National Health and Medical Research Council statement on electronic cigarettes: 2022 update.

INTRODUCTION: Electronic cigarette (e-cigarette) use in Australia has rapidly increased since the 2017 National Health and Medical Research Council (NHMRC) Chief Executive Officer (CEO) statement on e-cigarettes. The type of products available and the demographic characteristics of people using these products have changed. New evidence has been published and there is growing concern among public health professionals about the increased use, particularly among young people who do not currently smoke combustible cigarettes. The combination of these issues led NHMRC to review the current evidence and provide an updated statement on e-cigarettes. In this article, we describe the comprehensive process used to review the evidence and develop the 2022 NHMRC CEO statement on electronic cigarettes. MAIN RECOMMENDATIONS: E-cigarettes can be harmful; all e-cigarette users are exposed to chemicals and toxins that have the potential to cause adverse health effects. There are no health benefits of using e-cigarettes if you do not currently smoke tobacco cigarettes. Adolescents are more likely to try e-cigarettes if they are exposed to e-cigarettes on social media. Short term e-cigarette use may help some smokers to quit who have been previously unsuccessful with other smoking cessation aids. There are other proven safe and effective options available to help smokers to quit. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: The evidence base for the harms of e-cigarette use has strengthened since the previous NHMRC statement. Significant gaps in the evidence base remain, especially about the longer term health harms of using e-cigarettes and the toxicity of many chemicals in e-cigarettes inhaled as an aerosol.

Association of electronic cigarette use and suicidal behaviors: a systematic review and meta-analysis.

BACKGROUND: The proliferation of electronic cigarettes (e-cigarettes) has presented new challenges in public health, particularly among adolescents and young adults. While marketed as safer than tobacco and as cessation aids, e-cigarettes have raised concerns about their long-term health and psychosocial impacts, including potential links to increased suicidal behaviors. This study aims to evaluate the relationship between e-cigarette use and suicidal behaviors by conducting a systematic review of the current literature. METHODS: We searched PubMed, Web of Science, and EMBASE for studies up to March 10, 2024, examining the relationship between e-cigarette use and suicidal behaviors. Eligible studies included cross-sectional, longitudinal, retrospective, prospective, and case-control designs. Meta-analysis was performed to calculate pooled odds ratios (ORs). Newcastle Ottawa scale was used to assess the quality of studies. R software (V 4.3) was used to perform the meta-analysis. RESULTS: Our analysis included fourteen studies, predominantly from the US and Korea, with participants ranging from 1,151 to 255,887. The meta-analysis identified a significant association between e-cigarette use and an increased risk of suicidal ideation (OR = 1.489, 95% CI: 1.357 to 1.621), suicide attempts (OR = 2.497, 95% CI: 1.999 to 3.996), and suicidal planning (OR = 2.310, 95% CI: 1.810 to 2.810). Heterogeneity was noted among the studies. CONCLUSION: E-cigarette use is significantly associated with the risk of suicidal behaviors, particularly among adolescents. The findings underscore the necessity for caution in endorsing e-cigarettes as a safer smoking alternative and call for more extensive research to understand the underlying mechanisms. Public health strategies should be developed to address and mitigate the risks of suicidal behaviors among e-cigarette users.

Vaping during pregnancy: a systematic review of health outcomes.

INTRODUCTION: Smoking during pregnancy is harmful to maternal and child health. Vaping is used for smoking cessation but evidence on health effects during pregnancy is scarce. We conducted a systematic review of health outcomes of vaping during pregnancy. METHODS: We searched six databases for maternal/fetal/infant outcomes and vaping, including quantitative, English language, human studies of vaping during pregnancy, to November 10th, 2023. We assessed study quality with the Mixed-Methods Appraisal Tool. We focused on comparisons of exclusive-vaping with non-use of nicotine and tobacco products and with smoking. Presentation is narrative as the studies were of insufficient quality to conduct meta-analysis. RESULTS: We included 26 studies, with 765,527 women, with one randomised controlled trial (RCT) comparing vaping and nicotine replacement therapy for smoking cessation, 23 cohort studies and two case-control studies. While the RCT met 4/5 quality criteria, the quality of the cohort studies and case-control studies was poor; none adequately assessed exposure to smoking and vaping. For studies comparing exclusive-vaping with 'non-use', more reported no increased risk for vaping (three studies) than reported increased risk for maternal pregnancy/postpartum outcomes (one study) and for fetal and infant outcomes (20 studies no increased risk, four increased risk), except for birth-weight and neurological outcomes where two studies each observed increased and no increased risk. When the RCT compared non-users with those not smoking but vaping or using NRT, irrespective of randomisation, they reported no evidence of risk for vaping/NRT. For studies comparing exclusive-vaping and exclusive-smoking, most studies provided evidence for a comparable risk for different outcomes. One maternal biomarker study revealed a lower risk for vaping. For small-for-gestational-age/mean-birth-centile equal numbers of studies found lower risk for vaping than for smoking as found similar risk for the two groups (two each). CONCLUSIONS: While more studies found no evidence of increased risk of exclusive-vaping compared with non-use and evidence of comparable risk for exclusive-vaping and exclusive-smoking, the quality of the evidence limits conclusions. Without adequate assessment of exposure to vaping and smoking, findings cannot be attributed to behaviour as many who vape will have smoked and many who vape may do so at low levels. STUDY REGISTRATION: https://osf.io/rfx4q/ .

Altered executive control network and default model network topology are linked to acute electronic cigarette use: A resting-state fNIRS study.

In recent years, electronic cigarettes (e-cigs) have gained popularity as stylish, safe, and effective smoking cessation aids, leading to widespread consumer acceptance. Although previous research has explored the acute effects of combustible cigarettes or nicotine replacement therapy on brain functional activities, studies on e-cigs have been limited. Using fNIRS, we conducted graph theory analysis on the resting-state functional connectivity of 61 male abstinent smokers both before and after vaping e-cigs. And we performed Pearson correlation analysis to investigate the relationship between alterations in network metrics and changes in craving. E-cig use resulted in increased degree centrality, nodal efficiency, and local efficiency within the executive control network (ECN), while causing a decrease in these properties within the default model network (DMN). These alterations were found to be correlated with reductions in craving, indicating a relationship between differing network topologies in the ECN and DMN and decreased craving. These findings suggest that the impact of e-cig usage on network topologies observed in male smokers resembles the effects observed with traditional cigarettes and other forms of nicotine delivery, providing valuable insights into their addictive potential and effectiveness as aids for smoking cessation.