B cell immune repertoire sequencing in tobacco cigarette smoking, vaping, and chronic obstructive pulmonary disease in the COPDGene cohort.

Rationale: Cigarette smoking (CS) impairs B cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B cell activity is unclear. Objective: To examine B cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, dual-use, COPD-related outcomes, and demographic factors. Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V-segment usage, and clonal expansion) with CS, vaping, dual-use, COPD severity, age, sex, and race. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at 5% FDR and suggestive associations at 10% FDR. Results: Among 234 non-Hispanic white (NHW) and African American (AA) participants, CS and dual-use were significantly positively associated with increased secretory IgA production, with dual-use showing the strongest associations. Dual-use was positively associated with class switching and B cell clonal expansion, indicating increased B cell activation, with similar trends in those only smoking or only vaping. We observed significant associations between race and IgG antibody usage. AA participants had higher IgG subclass proportions and lower IgM usage compared to NHW participants. Conclusions: CS and vaping additively enhance B cell activation, most notably in dual-users. Self-reported race was strongly associated with IgG isotype usage. These findings highlight associations between B cell activation and antibody transcription, suggesting potential differences in immune and vaccine responses linked to CS, vaping, and race.

E-cigarettes increase the risk of adenoma formation in murine colorectal cancer model.

Background: E-cigarettes (E.cigs) cause inflammation and damage to human organs, including the lungs and heart. In the gut, E.cig vaping promotes inflammation and gut leakiness. Further, E.cig vaping increases tumorigenesis in oral and lung epithelial cells by inducing mutations and suppressing host DNA repair enzymes. It is well known that cigarette (cig) smoking increases the risk of colorectal cancer (CRC). To date, it is unknown whether E.cig vaping impacts CRC development. Methods: A mouse model of human familial adenomatous polyposis (CPC-APC) was utilized wherein a mutation in the adenomatous polyposis coli (APC) gene, CDX2-Cre-APCMin/+, leads to the development of colon adenomas within 16 weeks. Mice were exposed to air (controls), E.cig vaping, cig, or both (dual exposure). After 4 weeks of 2-hour exposures per day (1 hour of each for dual exposures), the colon was collected and assessed for polyp number and pathology scores by microscopy. Expression of inflammatory cytokines and cancer stem cell markers were quantified. DNA damage such as double-strand DNA breaks was evaluated by immunofluorescence, western blot and gene-specific long amplicon qPCR. DNA repair enzyme levels (NEIL-2, NEIL-1, NTH1, and OGG1) were quantified by western blot. Proliferation markers were assessed by RT-qPCR and ELISA. Results: CPC-APC mice exposed to E.cig, cig, and dual exposure developed a higher number of polyps compared to controls. Inflammatory proteins, DNA damage, and cancer stemness markers were higher in E-cig, cig, and dual-exposed mice as well. DNA damage was found to be associated with the suppression of DNA glycosylases, particularly with NEIL-2 and NTH1. E.cig and dual exposure both stimulated cancer cell stem markers (CD44, Lgr-5, DCLK1, and Ki67). The effect of E.cigs on polyp formation and CRC development was less than that of cigs, while dual exposure was more tumorigenic than either of the inhalants alone. Conclusion: E.cig vaping promotes CRC by stimulating inflammatory pathways, mediating DNA damage, and upregulating transcription of cancer stem cell markers. Critically, combining E.cig vaping with cig smoking leads to higher levels of tumorigenesis. Thus, while the chemical composition of these two inhalants, E.cigs and cigs, is highly disparate, they both drive the development of cancer and when combined, a highly common pattern of use, they can have additive or synergistic effects.

Dual Use of Cannabis with Tobacco Is Associated with Increased Sugary Food and Drink Intake in Young People.

Rates of cannabis initiation among teenagers and young adults are increasing. Further, the use of various forms of cannabis (smoked or vaped) with nicotine (dual use) is increasingly common among young people. The health effects of dual use are lesser known, particularly in the context of high-potency cannabis products and across different routes of administration, which is ominous in terms of predicting future health outcomes. There is a long history of cannabis use being associated with decreased activity and increased snacking, both of which could portend an increased risk of metabolic and cardiovascular disease, particularly when these habits begin during formative years. However, modern forms of cannabis may not have these same effects. Here, we assess whether cannabis use alone and dual use of cannabis with nicotine impact dietary and exercise habits in young people. An anonymous, social media-based survey was designed based on the UC San Diego Inhalant Questionnaire and published diet and exercise questionnaires. A total of 457 surveys were completed. Young sole cannabis users represented 29% of responders, 16% were dual users of cannabis and nicotine, and 55% were non-users of either drug. Although the sole use of cannabis was not associated with dietary or activity differences relative to non-users, dual users of cannabis and nicotine reported higher consumption of unhealthy sugars. This novel finding of dual use being associated with increased sugar intake in young people raises concerns for an increased risk of metabolic syndrome and cardiovascular disease in this population.

E-cigarette Vapor Extract Alters Human Eosinophil Gene Expression in an Effect Mediated by Propylene glycol, Glycerin, and Nicotine.

E-cigarette use has become widespread, and its effects on airway inflammation and disease are not fully delineated. E-cigarette vapor extract (EVE) profoundly affects neutrophil function. We hypothesized that EVE also alters eosinophil function and thus could impact allergic airways disease. We employed RNA-sequencing to measure the ex vivo effect of EVE components on human eosinophil transcription. Blood eosinophils from 9 non-vaping subjects without asthma were isolated by negative selection. Cells were incubated for 48 hours with EVE consisting of glycerin, propylene glycol and nicotine (EVE+), EVE without nicotine ("EVE-"), air-exposed media termed Extract Buffer (EB), or untreated media. Bulk RNA-sequencing was performed. Transcriptomic analysis revealed that the EB, EVE-, and EVE+ conditions showed highly variable gene expression with respect to No Treatment and each other. Differential gene expression analysis comparing a combination of EVE+, EVE-, and EB revealed 3,030 differentially expressed genes (DEG) with adjusted p value < 0.05 and log2 fold change >0.5 or <0.5. There were 645 DEG between EB and EVE-, 1,713 between EB and EVE+, and 404 between EVE- and EVE+. Gene set enrichment analysis demonstrated that DEG between both EVE+ and EVE- and the EB control were positively enriched for heme metabolism and apoptosis and negatively enriched TNFα signaling, IFNγ signaling, and inflammatory response. Thus, EVE significantly alters eosinophil metabolic and inflammatory pathways, mediated by propylene glycol and glycerin with both enhancing and unique effects of nicotine. This study motivates further research into the pathogenic effects of vaping on airway eosinophils and allergic airways disease.

The paradox of the safer cigarette: understanding the pulmonary effects of electronic cigarettes.

Electronic cigarette (e-cigarette) use continues to rise globally. E-cigarettes have been presented as safer alternatives to combustion cigarettes that can mitigate the harm associated with tobacco products; however, the degree to which e-cigarette use itself can lead to morbidity and mortality is not fully defined. Herein we describe how e-cigarettes function; discuss the current knowledge of the effects of e-cigarette aerosol on lung cell cytotoxicity, inflammation, antipathogen immune response, mucociliary clearance, oxidative stress, DNA damage, carcinogenesis, matrix remodelling and airway hyperresponsiveness; and summarise the impact on lung diseases, including COPD, respiratory infection, lung cancer and asthma. We highlight how the inclusion of nicotine or flavouring compounds in e-liquids can impact lung toxicity. Finally, we consider the paradox of the safer cigarette: the toxicities of e-cigarettes that can mitigate their potential to serve as a harm reduction tool in the fight against traditional cigarettes, and we summarise the research needed in this underinvestigated area.

Through the Looking Glass: Revisiting Smoking and Health.

January 11, 2024, marked the 60th anniversary of the initial U.S. Surgeon General report "Smoking and Health," which definitively linked cigarette smoking and lung cancer.1 Similar to the old Virginia Slims slogan "you've come a long way, baby," smoking rates have diminished greatly since the release of that report.2 However, smoking still represents the leading cause of preventable deaths.3 Numerous countries have enacted policies aimed at decreasing conventional cigarette use, such as including warning labels on tobacco products, limiting advertising, and imposing bans on particular products. Such measures have contributed to significant reductions in cigarette use.

Duration of intermittent hypoxia impacts metabolic outcomes and severity of murine NAFLD.

Rationale: Obstructive sleep apnea (OSA) is associated with metabolic dysfunction, including progression of nonalcoholic fatty liver disease (NAFLD). Chronic intermittent hypoxia (IH) as a model of OSA worsens hepatic steatosis and fibrosis in rodents with diet induced obesity. However, IH also causes weight loss, thus complicating attempts to co-model OSA and NAFLD. We sought to determine the effect of various durations of IH exposure on metabolic and liver-related outcomes in a murine NAFLD model. We hypothesized that longer IH duration would worsen the NAFLD phenotype. Methods: Male C57BL/6J mice (n = 32) were fed a high trans-fat diet for 24 weeks, to induce NAFLD with severe steatohepatitis. Mice were exposed to an IH profile modeling severe OSA, for variable durations (0, 6, 12, or 18 weeks). Intraperitoneal glucose tolerance test was measured at baseline and at six-week intervals. Liver triglycerides, collagen and other markers of NAFLD were measured at sacrifice. Results: Mice exposed to IH for 12 weeks gained less weight (p = 0.023), and had lower liver weight (p = 0.008) relative to room air controls. These effects were not observed in the other IH groups. IH of longer duration transiently worsened glucose tolerance, but this effect was not seen in the groups exposed to shorter durations of IH. IH exposure for 12 or 18 weeks exacerbated liver fibrosis, with the largest increase in hepatic collagen observed in mice exposed to IH for 12 weeks. Discussion: Duration of IH significantly impacts clinically relevant outcomes in a NAFLD model, including body weight, fasting glucose, glucose tolerance, and liver fibrosis.

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection.

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5'-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.

Transcriptomic responses in the blood and sputum of cigarette smokers compared to e-cigarette vapers.

RATIONALE: Electronic (e)-cigarettes are popular among youth and cigarette smokers attempting to quit. Studies to date have focused on the utility of e-cigarettes as a smoking cessation tool, but the biological effects are largely unknown. OBJECTIVES: To identify transcriptomic differences in the blood and sputum of e-cigarette users compared to conventional cigarettes smokers and healthy controls and describe biological pathways affected by these tobacco products. METHODS: Cross-sectional analysis of whole blood and sputum RNA-sequencing data from 8 smokers, 9 e-cigarette users (e-cigs) and 4 controls. Weighted gene co-network analysis (WGCNA) identified gene module associations. Ingenuity Pathway Analysis (IPA) identified canonical pathways associated with tobacco products. MAIN RESULTS: In blood, a three-group comparison showed 16 differentially expressed genes (DEGs); pair-wise comparison showed 7 DEGs between e-cigs and controls, 35 DEGs between smokers and controls, and 13 DEGs between smokers and e-cigs. In sputum, 438 DEGs were in the three-group comparison. In pair-wise comparisons, there were 2 DEGs between e-cigs and controls, 270 DEGs between smokers and controls, and 468 DEGs between smokers and e-cigs. Only 2 genes in the smokers vs. control comparison overlapped between blood and sputum. Most gene modules identified through WGCNA associated with tobacco product exposures also were associated with cotinine and exhaled CO levels. IPA showed more canonical pathways altered by conventional cigarette smoking than by e-cigarette use. CONCLUSION: Cigarette smoking and e-cigarette use led to transcriptomic changes in both blood and sputum. However, conventional cigarettes induced much stronger transcriptomic responses in both compartments.

Inflammation biomarkers in OSA, chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease/OSA overlap syndrome.

STUDY OBJECTIVES: The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in a single individual, also known as overlap syndrome (OVS), is associated with higher cardiovascular risk and mortality than either OSA or COPD alone. However, the underlying mechanisms remain unclear. We hypothesized that patients with OVS have elevated systemic inflammatory biomarkers relative to patients with either disease alone, which could explain greater cardiovascular risk observed in OVS. METHODS: We included 255 participants in the study, 55 with COPD alone, 100 with OSA alone, 50 with OVS, and 50 healthy controls. All participants underwent a home sleep study, spirometry, and a blood draw for high-sensitivity C-reactive protein and total blood count analysis. In a randomly selected subset of 186 participants, inflammatory protein profiling was performed using Bio-Rad Bio-Plex Pro Human Cytokine 27-Plex Assays. Biomarker level differences across groups were identified using a mixed linear model. RESULTS: Levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and granulocyte colony stimulating factor (G-CSF) were higher in participants with OVS and COPD compared with healthy controls and participants with OSA. Furthermore, participants with OVS had higher circulating levels of leukocytes and neutrophils than those with COPD, OSA, and controls. CONCLUSIONS: COPD and OVS are associated with higher systemic inflammation relative to OSA and healthy controls. This work proposes the potential utilization of interleukin 6, granulocyte colony stimulating factor, and high-sensitivity C-reactive protein as screening biomarkers for COPD in patients with OSA. Inflammatory pathways may not fully explain the higher cardiovascular risk observed in OVS, indicating the need for further investigation. CITATION: Sanchez-Azofra A, Gu W, Masso-Silva JA, et al. Inflammation biomarkers in OSA, chronic obstructive pulmonary disease, and chronic obstructive pulmonary disease/OSA overlap syndrome. J Clin Sleep Med. 2023;19(8):1447-1456.

Dynamic activity in cis-regulatory elements of leukocytes identifies transcription factor activation and stratifies COVID-19 severity in ICU patients.

Transcription factor programs mediating the immune response to coronavirus disease 2019 (COVID-19) are not fully understood. Capturing active transcription initiation from cis-regulatory elements such as enhancers and promoters by capped small RNA sequencing (csRNA-seq), in contrast to capturing steady-state transcripts by conventional RNA-seq, allows unbiased identification of the underlying transcription factor activity and regulatory pathways. Here, we profile transcription initiation in critically ill COVID-19 patients, identifying transcription factor motifs that correlate with clinical lung injury and disease severity. Unbiased clustering reveals distinct subsets of cis-regulatory elements that delineate the cell type, pathway-specific, and combinatorial transcription factor activity. We find evidence of critical roles of regulatory networks, showing that STAT/BCL6 and E2F/MYB regulatory programs from myeloid cell populations are activated in patients with poor disease outcomes and associated with COVID-19 susceptibility genetic variants. More broadly, we demonstrate how capturing acute, disease-mediated changes in transcription initiation can provide insight into the underlying molecular mechanisms and stratify patient disease severity.

Assessing Barriers to Implementation of Machine Learning and Artificial Intelligence-Based Tools in Critical Care: Web-Based Survey Study.

BACKGROUND: Although there is considerable interest in machine learning (ML) and artificial intelligence (AI) in critical care, the implementation of effective algorithms into practice has been limited. OBJECTIVE: We sought to understand physician perspectives of a novel intubation prediction tool. Further, we sought to understand health care provider and nonprovider perspectives on the use of ML in health care. We aim to use the data gathered to elucidate implementation barriers and determinants of this intubation prediction tool, as well as ML/AI-based algorithms in critical care and health care in general. METHODS: We developed 2 anonymous surveys in Qualtrics, 1 single-center survey distributed to 99 critical care physicians via email, and 1 social media survey distributed via Facebook and Twitter with branching logic to tailor questions for providers and nonproviders. The surveys included a mixture of categorical, Likert scale, and free-text items. Likert scale means with SD were reported from 1 to 5. We used student t tests to examine the differences between groups. In addition, Likert scale responses were converted into 3 categories, and percentage values were reported in order to demonstrate the distribution of responses. Qualitative free-text responses were reviewed by a member of the study team to determine validity, and content analysis was performed to determine common themes in responses. RESULTS: Out of 99 critical care physicians, 47 (48%) completed the single-center survey. Perceived knowledge of ML was low with a mean Likert score of 2.4 out of 5 (SD 0.96), with 7.5% of respondents rating their knowledge as a 4 or 5. The willingness to use the ML-based algorithm was 3.32 out of 5 (SD 0.95), with 75% of respondents answering 3 out of 5. The social media survey had 770 total responses with 605 (79%) providers and 165 (21%) nonproviders. We found no difference in providers' perceived knowledge based on level of experience in either survey. We found that nonproviders had significantly less perceived knowledge of ML (mean 3.04 out of 5, SD 1.53 vs mean 3.43, SD 0.941; P<.001) and comfort with ML (mean 3.28 out of 5, SD 1.02 vs mean 3.53, SD 0.935; P=.004) than providers. Free-text responses revealed multiple shared concerns, including accuracy/reliability, data bias, patient safety, and privacy/security risks. CONCLUSIONS: These data suggest that providers and nonproviders have positive perceptions of ML-based tools, and that a tool to predict the need for intubation would be of interest to critical care providers. There were many shared concerns about ML/AI in health care elucidated by the surveys. These results provide a baseline evaluation of implementation barriers and determinants of ML/AI-based tools that will be important in their optimal implementation and adoption in the critical care setting and health care in general.

The E-cigarette or Vaping Product Use-Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report.

E-cigarette or vaping product use-associated lung injury (EVALI) is a severe pulmonary illness associated with the use of e-cigarettes or vaping products that was officially identified and named in 2019. This American Thoracic Society workshop was convened in 2021 to identify and prioritize research and regulatory needs to adequately respond to the EVALI outbreak and to prevent similar instances of disease associated with e-cigarette or vaping product use. An interdisciplinary group of 26 experts in adult and pediatric clinical care, public health, regulatory oversight, and toxicology were convened for the workshop. Four major topics were examined: 1) the public health and regulatory response to EVALI; 2) EVALI clinical care; 3) mechanisms contributing to EVALI; and 4) needed actions to address the health effects of EVALI. Oral presentations and group discussion were the primary modes used to identify top priorities for addressing EVALI. Initiatives including a national EVALI case registry and biorepository, integrated electronic medical record coding system, U.S. Food and Drug Administration regulation and enforcement of nicotine e-cigarette standards, regulatory authority over nontobacco-derived e-cigarettes, training in evaluating exogenous exposures, prospective clinical studies, standardized clinical follow-up assessments, ability to more readily study effects of cannabinoid e-cigarettes, and research to identify biomarkers of exposure and disease were identified as critical needs. These initiatives will require substantial federal investment as well as changes to regulatory policy. Overall, the workshop identified the need to address the root causes of EVALI to prevent future outbreaks. An integrated approach from multiple perspectives is required, including public health; clinical, basic, and translational research; regulators; and users of e-cigarettes. Improving the public health response to reduce the risk of another substantial disease-inducing event depends on coordinated actions to better understand the inhalational toxicity of these products, informing the public of the risks, and developing and enforcing regulatory standards for all e-cigarettes.

Implementing Holistic Review Practices in a Pulmonary and Critical Care Fellowship.

Background: Medical schools have used holistic review in admissions to increase mission-aligned enrollment of students from backgrounds underrepresented in medicine. Graduate medical education programs have increasingly followed suit. However, there is a paucity of literature regarding holistic review at the fellowship level. Objective: Here, we share our experience implementing the Association of American Medical Colleges core principles of holistic review during the 2021 recruitment cycle. Methods: We used a partially asynchronous and online learning strategy to train division members on the principles of holistic review. Following the match, we conducted a survey of faculty members and fellows to understand their opinions on our holistic review training and implementation. Results: Although few of our colleagues clearly understood holistic review before the training, they were able to identify broad-based criteria that aligned with our division's mission and balanced applicants' experiences, attributes, competencies, and metrics. These were viewed as better selection criteria than traditional measures and were incorporated into the individualized consideration of applicants. Our survey had a 41.5% response rate, with 10 of 22 fellows and 24 of 60 faculty members responding. Most faculty members and fellows agreed that holistic review decreases socioeconomic disparities in fellowship recruitment (79.2% and 80.0%, respectively) and promotes inclusion and diversity (83.3% and 90.0%, respectively). Faculty members appeared more confident than fellows that our training efforts had influenced recruitment. All respondents agreed that it would be critical for such training to be repeated yearly. Conclusion: Although this was a single-institution experience, implementing holistic review was feasible and well received by faculty and fellows.

Abrogation of neutrophil inflammatory pathways and potential reduction of neutrophil-related factors in COVID-19 by intravenous immunoglobulin.

Pathogenesis of lung injury in COVID-19 is not completely understood, leaving gaps in understanding how current treatments modulate the course of COVID-19. Neutrophil numbers and activation state in circulation have been found to correlate with COVID-19 severity, and neutrophil extracellular traps (NETs) have been found in the lung parenchyma of patients with acute respiratory distress syndrome (ARDS) in COVID-19. Targeting the pro-inflammatory functions of neutrophils may diminish lung injury in COVID-19 and ARDS. Neutrophils were isolated from peripheral blood of healthy donors, treated ex vivo with dexamethasone, tocilizumab and intravenous immunoglobulin (IVIG) and NET formation, oxidative burst, and phagocytosis were assessed. Plasma from critically ill COVID-19 patients before and after clinical treatment with IVIG and from healthy donors was assessed for neutrophil activation-related proteins. While dexamethasone and tocilizumab did not affect PMA- and nigericin-induced NET production ex vivo, IVIG induced a dose-dependent abrogation of NET production in both activation models. IVIG also reduced PMA-elicited reactive oxygen species production, but did not alter phagocytosis. COVID-19 patients were found to have elevated levels of cell-free DNA, neutrophil elastase and IL-8 as compared to healthy controls. Levels of both cell-free DNA and neutrophil elastase were lower 5 days after 4 days of daily treatment with IVIG. The lack of impact of dexamethasone or tocilizumab on these neutrophil functions suggests that these therapeutic agents may not act through suppression of neutrophil functions, indicating that the door might still be open for the addition of a neutrophil modulator to the COVID-19 therapeutic repertoire.

Learning Outcomes in a Live Virtual versus In-Person Curriculum for Medical and Pharmacy Students.

Background: The coronavirus disease (COVID-19) pandemic has been a source of disruption, changing the face of medical education. In response to infection control measures at the University of California, San Diego, the hybrid in-person and recorded preclerkship curriculum was converted to a completely virtual format. The impact of this exclusive virtual teaching platform on the quality of trainee education is unknown. Objective: To determine the efficacy of a virtual course, relative to traditional hybrid in-person and recorded teaching, and to assess the impact of supplementary educational material on knowledge acquisition. Methods: A retrospective observational cohort study was performed to assess an introductory course, held mostly in person in 2019 versus completely virtual in 2020, for first-year medical students and second-year pharmacy students at the University of California, San Diego, School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. Results: The midterm and final examination scores were similar for the hybrid and virtual courses. There was no association between the hours of recorded lectures watched and final examination scores for either course. In the 2019 in-person and recorded course, students who demonstrated consistent on-time use of practice quizzes scored statistically higher on the final examination (P = 0.0066). In the 2020 virtual course, students who downloaded quizzes regularly had statistically higher scores on the midterm examination (P < 0.0001). Conclusion: The similar examination scores for the hybrid in-person and recorded and exclusively virtual courses suggest that the short-term knowledge acquired was equivalent, independent of the modality with which the content was delivered. Consistent on-time use of practice quizzes was associated with higher examination scores. Future studies are needed to assess the difference between a completely in-person versus virtual curriculum.

Electronic Cigarettes: A Pro-Con Review of the Current Literature.

Electronic cigarettes (e-cigarettes, e-cigs, or electronic nicotine delivery systems) are battery-operated devices typically containing glycerol and/or propylene glycol-based solutions with varying nicotine content, known as e-liquids. Although e-cigarettes were originally developed as a potentially less harmful alternative to traditional combustible tobacco cigarette smokers, several factors have driven their popularity among smokers and nonsmokers alike, including their sleek product designs, innumerable appealing flavors, lack of combustible smoke and odor, and high potential nicotine concentrations. Furthermore, many advocates have promoted the idea that e-cigarettes are safe to use, or at least safer than conventional tobacco, despite limited longitudinal data to support these claims. Here, we examine what is known about the impacts of e-cigarette use on traditional cigarette smoking cessation, lung health, and youth and young adult tobacco product exposure. Upon review of the currently available literature, the negative effects of e-cigarette use seem to outweigh any potential benefit, because the available evidence does not confirm the use of e-cigarettes as an effective strategy for supporting traditional combustible tobacco cigarette smoking cessation, particularly given the emerging adverse effects on lung health and the potential future public health effects of e-cigarette adoption among a burgeoning new generation of tobacco product users.

Electronic cigarette use and perceptions during COVID-19.

This study was designed to examine how the COVID-19 pandemic changed e-cigarette user habits and risk perceptions. A nationally distributed 52-item questionnaire assessed nicotine e-cigarette use, perceptions, COVID-19 diagnosis, demographic data, and vaping habits among respondents aged 16-96 years (n = 565). Questions were developed in-house to assess vaping habits of users and risk perceptions of nicotine containing e-cigarette users and non-users both before and during the COVID-19 pandemic. Seventy-six percent of non-users believed that e-cigarette use would lead to worse COVID-19 symptoms, compared to 40% of e-cigarette users (P < 0.001). Twenty-eight percent of non-users also believed that e-cigarette users were more likely to be infected with SARS-CoV-2, versus 11% of e-cigarette users (P < 0.001). Fifty-eight percent of e-cigarette users described themselves as making no change in their e-cigarette usage, 10% decreased e-cigarette use, and 32% increased e-cigarette use during the pandemic. Twenty-five percent of users switched to vaping non-socially during the pandemic (P < 0.001). Sixty-seven percent of e-cigarette users replied that they would decrease or stop vaping if diagnosed with COVID and 31% said they would continue (P < 0.001). These findings reveal there are large differences in risk perception of e-cigarette use between users and non-users. Additionally, our findings characterize the habits of e-cigarette users during the COVID-19 pandemic, revealing users report steady to increased use, more caution in social settings, and would reduce usage if diagnosed with COVID-19.

Cardiopulmonary Consequences of Vaping in Adolescents: A Scientific Statement From the American Heart Association.

Although the US Food and Drug Administration has not approved e-cigarettes as a cessation aid, industry has at times positioned their products in that way for adults trying to quit traditional cigarettes; however, their novelty and customizability have driven them into the hands of unintended users, particularly adolescents. Most new users of e-cigarette products have never smoked traditional cigarettes; therefore, understanding the respiratory and cardiovascular consequences of e-cigarette use has become of increasing interest to the research community. Most studies have been performed on adult e-cigarette users, but the majority of these study participants are either former traditional smokers or smokers who have used e-cigarettes to switch from traditional smoking. Therefore, the respiratory and cardiovascular consequences in this population are not attributable to e-cigarette use alone. Preclinical studies have been used to study the effects of naive e-cigarette use on various organ systems; however, almost all of these studies have used adult animals, which makes translation of health effects to adolescents problematic. Given that inhalation of any foreign substance can have effects on the respiratory and cardiovascular systems, a more holistic understanding of the pathways involved in toxicity could help to guide researchers to novel therapeutic treatment strategies. The goals of this scientific statement are to provide salient background information on the cardiopulmonary consequences of e-cigarette use (vaping) in adolescents, to guide therapeutic and preventive strategies and future research directions, and to inform public policymakers on the risks, both short and long term, of vaping.