Blunt Talk on "Blunts": The Increasingly Popular Tobacco Product That Is Potentially Exacerbating Tobacco-Related Health Disparities.

A "blunt" is a hollowed-out cigar/cigarillo from which much of the loose tobacco has been removed, and the remaining tobacco wrapper filled with cannabis. Although blunts contain significant levels of tobacco/nicotine, they are often treated as if they were exclusive cannabis products and omitted from surveys of tobacco products. Whereas the prevalence of virtually all other tobacco products is on the decline in the USA, available data suggest that the prevalence of blunt smoking is not - and in fact, it may be increasing. Blunts are most frequently used by people who self-identify as Black. As a result of misperceptions and perhaps biases, there is a dearth of scientific investigation, hence knowledge, surrounding the health effects associated with blunt smoking. Co-use of tobacco and cannabis has been reported to have additive and even synergistic adverse health effects. Lack of investigations into the health effects of tobacco products most frequently used by Black people may contribute to tobacco-related health disparities. We argue that the scientific and public health communities must treat blunts as the potentially lethal tobacco product that they are, studying their prevalence and use patterns, and investigating their adverse health effects, both short and long term.

Arrhythmogenic effects of acute electronic cigarette compared to tobacco cigarette smoking in people living with HIV.

The leading cause of death in people living with HIV (PLWH) is cardiovascular disease, and the high prevalence of tobacco cigarette (TC) smoking is a major contributor. Switching to electronic cigarettes (ECs) has been promoted as a harm reduction strategy. We sought to determine if acute EC compared to TC smoking had less harmful effects on arrhythmogenic risk factors including acute changes in hemodynamics, heart rate variability (HRV), and ventricular repolarization (VR). In PLWH who smoke, changes in hemodynamics, HRV, and VR were compared pre/post acutely using an EC, TC, or puffing on an empty straw on different days in random order, in a crossover study. Thirty-seven PLWH (36 males, mean age 40.5 ± 9.1 years) participated. Plasma nicotine was greater after TC versus EC use (10.12 ± 0.96 vs. 6.18 ± 0.99 ng/mL, respectively, p = 0.004). HR increased significantly, and similarly, after acute EC and TC smoking compared to control. Changes in HRV that confer increased cardiac risk (LF/HF ratio) were significantly smaller after acute EC versus TC use, consistent with a harm reduction effect. In a post-hoc analysis of PLWH with and without positive concurrent recreational drug use as indicated by point of care urine toxicology testing, this differential effect was only seen in PLWH not currently using recreational drugs. Changes in VR were not different among the three exposures. In PLWH who smoke, EC compared to TC smoking resulted in smaller adverse changes in HRV. This differential effect was accompanied by a smaller increase in plasma nicotine, and was negated by concurrent recreational drug use. Additional studies are warranted in this vulnerable population disproportionately affected by tobacco-related health disparities.

Acute cardiovascular effects of 4th generation electronic cigarettes and combusted cigarettes: implications for harm reduction.

The health consequences associated with using electronic cigarettes (ECs) are of great public interest because of their potential role in smoking cessation. In 110 participants, including 41 nonusers, 34 people who exclusively use ECs (EC group), and 35 people who smoke tobacco cigarettes (TCs) including 12 dual users (collectively called the TC-D group), the heart rate (HR), blood pressure (BP), and heart rate variability (HRV) were compared at baseline. People in the EC or the TC-D groups were also compared after using a 4th generation EC with or without nicotine, a TC with or without nicotine (TC-D group only), and a straw-control. Baseline HR, BP, and HRV parameters were not different among the EC, the TC-D, and nonuser groups. In people who exclusively use ECs, acute nicotine-EC use increased HR and BP, and produced changes in HRV patterns suggestive of increased cardiac sympathetic influence. In people in the TC-D group, BP increased similarly after acutely smoking a nicotine-TC or a nicotine-EC. However, the increase in HR was significantly greater after smoking a TC compared with the nicotine-EC despite similar acute increases in plasma nicotine. Overall, all exposures containing nicotine significantly increased HR and BP in both cohorts when compared with non-nicotine exposures. Since acute EC use 1) produces an abnormal HRV pattern associated with increased cardiac sympathetic tone in people who chronically use ECs, and 2) similar hemodynamic increases compared with acute TC smoking in people who chronically smoke TCs including dual users, the role of ECs as part of a harm reduction strategy is questioned.NEW & NOTEWORTHY We found that nicotine, not the non-nicotine constituents in tobacco cigarette (TC) or electronic cigarette (EC) emissions, may be the instigator of the acute, potentially adverse, changes in hemodynamics and heart rate variability (HRV) that were recorded several minutes after tobacco product use. Furthermore, acute EC use produced an abnormal HRV pattern associated with increased cardiac risk in people who chronically smoke ECs and produced similar hemodynamic increases compared with acute TC use in people who chronically smoke TCs, including people who are dual users.

Chronic Electronic Cigarette Use and Atherosclerosis Risk in Young People: A Cross-Sectional Study-Brief Report.

BACKGROUND: Little is known whether electronic cigarettes (ECIG) increase vulnerability to future atherosclerotic cardiovascular disease. We determined, using an ex vivo mechanistic atherogenesis assay, whether proatherogenic changes including monocyte transendothelial migration and monocyte-derived foam cell formation are increased in people who use ECIGs. METHODS: In a cross-sectional single-center study using plasma and peripheral blood mononuclear cells from healthy participants who are nonsmokers or with exclusive use of ECIGs or tobacco cigarettes (TCIGs), autologous peripheral blood mononuclear cells with patient plasma and pooled peripheral blood mononuclear cells from healthy nonsmokers with patient plasma were utilized to dissect patient-specific ex vivo proatherogenic circulating factors present in plasma and cellular factors present in monocytes. Our main outcomes were monocyte transendothelial migration (% of blood monocyte cells that undergo transendothelial migration through a collagen gel) and monocyte-derived foam cell formation as determined by flow cytometry and the median fluorescence intensity of the lipid-staining fluorochrome BODIPY in monocytes of participants in the setting of an ex vivo model of atherogenesis. RESULTS: Study participants (N=60) had median age of 24.0 years (interquartile range [IQR], 22.0-25.0 years), and 31 were females. Monocyte transendothelial migration was increased in people who exclusively used TCIGs (n=18; median [IQR], 2.30 [ 1.29-2.82]; P<0.001) and in people who exclusively used ECIGs (n=21; median [IQR], 1.42 [ 0.96-1.91]; P<0.01) compared with nonsmoking controls (n=21; median [IQR], 1.05 [0.66-1.24]). Monocyte-derived foam cell formation was increased in people who exclusively used TCIGs (median [IQR], 2.01 [ 1.59-2.49]; P<0.001) and in people who exclusively used ECIGs (median [IQR], 1.54 [ 1.10-1.86]; P<0.001) compared with nonsmoker controls (median [IQR], 0.97 [0.86-1.22]). Both monocyte transendothelial migration and monocyte-derived foam cell formation were higher in TCIG smokers compared with ECIG users and in ECIG users who were former smokers versus ECIG users who were never smokers (P<0.05 for all comparisons). CONCLUSIONS: The finding of alterations in proatherogenic properties of blood monocytes and plasma in TCIG smokers compared with nonsmokers validates this assay as a strong ex vivo mechanistic tool with which to measure proatherogenic changes in people who use ECIGs. Similar yet significantly less severe alterations in proatherogenic properties of monocytes and plasma were detected in the blood from ECIG users. Future studies are necessary to determine whether these findings are attributable to a residual effect of prior smoking or are a direct effect of current ECIG use.

Electronic cigarettes prolong ventricular repolarization in people who smoke tobacco cigarettes: implications for harm reduction.

Electronic cigarettes are often used for smoking cessation as a harm reduction strategy, but studies comparing risks of electronic cigarettes (ECs) and tobacco cigarettes (TCs) are scarce. Ventricular repolarization in people who smoke TCs is abnormal. Baseline repolarization was compared among nonusers (people who do not use TCs or ECs) and people who use ECs or TCs. The acute effects of ECs and TCs on metrics of ventricular repolarization were then compared in people who chronically smoke. A total of 110 participants (59 female), including 35 people (21 females) in the TC cohort, 34 people (17 females) in the EC cohort, and 41 people (21 females) in the nonuser cohort, were included. None of the primary outcomes, Tpeak-end (Tp-e), Tp-e/QT, and Tp-e/QTc, were different among the three cohorts at supine baseline, even when adjusted for sex. When compared with the control exposure standing after acutely using the EC but not the TC, significantly prolonged all three primary indices of ventricular repolarization in people who smoke TCs. The major new finding in this study is that in people who smoke TCs, using an EC compared with a TC significantly prolongs ventricular repolarization. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers. In summary, chronic TC smoking is the most prevalent, modifiable risk factor for cardiovascular death, including sudden cardiac death. If used for smoking cessation, ECs should only be used in the short term since they too carry their own risks; this risk appears to be greatest in males compared with females who smoke.NEW & NOTEWORTHY The major new finding in this study is that in people who smoke tobacco cigarettes, using an electronic cigarette but not a tobacco cigarette acutely and significantly prolongs several metrics of ventricular repolarization, including Tpeak-Tend, Tpeak-Tend/QT, and Tpeak-Tend/QTc. Furthermore, in our subgroup analysis by sex, this adverse effect on repolarization is found only in male, not female, smokers.

Electronic Cigarettes: an Overlooked Tool to Alleviate Disparities in Tobacco Use Disorder Among People with Mental Health and Substance Use Disorders.

The remarkable decline in cigarette smoking since 1964 has plateaued; approximately 12.5% of Americans still smoke. People who continue to smoke are largely members of marginalized groups, such as people with behavioral health conditions (BHC), encompassing both mental health and substance use disorders. Certified smoking cessation interventions can increase smoking abstinence in trials in people with BHC, yet smoking rates remain markedly increased, leading to increased mortality from smoking-related diseases, and worsening health disparities. A novel approach tailored to the unique needs, characteristics, and circumstances of people with BHC is mandated. One promising approach, the electronic cigarette, has not been embraced in the USA, likely due to an understandable concern for non-smoking young people among whom electronic cigarettes have been popular. Recent data confirm that electronic cigarette use is declining among young people, yet cigarette smoking is not declining among people with BHC. We propose smoking cessation trials utilizing electronic cigarettes in people with BHC. To this goal, the UK has already begun allowing companies to submit their products for approval as medically licensed electronic cigarettes that can be prescribed as smoking cessation aids. Our proposal is timely, backed by evidence, and aims to save hundreds of thousands of American lives.

Ectodomain shedding of proteins important for SARS-CoV-2 pathogenesis in plasma of tobacco cigarette smokers compared to electronic cigarette vapers: a cross-sectional study.

The impact of tobacco cigarette (TCIG) smoking and electronic cigarette (ECIG) vaping on the risk of development of severe COVID-19 is controversial. The present study investigated levels of proteins important for SARS-CoV-2 pathogenesis present in plasma because of ectodomain shedding in smokers, ECIG vapers, and non-smokers (NSs). Protein levels of soluble angiotensin-converting enzyme 2 (ACE2), angiotensin (Ang) II (the ligand of ACE2), Ang 1-7 (the main peptide generated from Ang II by ACE2 activity), furin (a protease that increases the affinity of the SARS-CoV-2 spike protein for ACE2), and products of ADAM17 shedding activity that predict morbidity in COVID-19 (IL-6/IL-6R alpha (IL-6/IL-6Rα) complex, soluble CD163 (sCD163), L-selectin) were determined in plasma from 45 NSs, 30 ECIG vapers, and 29 TCIG smokers using ELISA. Baseline characteristics of study participants did not differ among groups. TCIG smokers had increased sCD163, L-selectin compared to NSs and ECIG vapers (p < 0.001 for all comparisons). ECIG vapers had higher plasma furin compared to both NSs (p < 0.001) and TCIG smokers (p < 0.05). ECIG vaping and TCIG smoking did not impact plasma ACE2, Ang 1-7, Ang II, and IL-6 levels compared to NSs (p > 0.1 for all comparisons). Further studies are needed to determine if increased furin activity and ADAM17 shedding activity that is associated with increased plasma levels of sCD163 and L-selectin in healthy young TCIG smokers may contribute to the future development of severe COVID-19 and cardiovascular complications of post-acute COVID-19 syndrome.

Neural-hematopoietic-inflammatory axis in nonsmokers, electronic cigarette users, and tobacco smokers.

Amygdala activity in context of the splenocardiac model has not been investigated in healthy, young adults and has not been compared between nonsmokers, electronic cigarette users, and smokers. The purpose of the current study was to determine whether fluorodeoxyglucose positron emission tomography/computer tomography (FDG PET/CT) scans would demonstrate positively correlated metabolic activity in the amygdala, bone marrow, spleen, and aorta, elucidating activation of the splenocardiac axis in otherwise healthy young people who use tobacco products compared to nonusers. Moreover, the study was conducted to evaluate whether electronic cigarette users and tobacco smokers have similar levels of inflammation compared to nonusers. In 45 healthy adults (mean age = 25 years), including nonsmoker (n = 15), electronic cigarette user (n = 16), and smoker (n = 14) groups, metabolic activity in the amygdala, spleen, aorta, bone marrow of thoracic vertebrae, and adjacent erector spinae skeletal muscle was quantified through visualization of radioactive glucose (18 FDG) uptake by FDG-PET/CT. The maximum standardized uptake value for each region was calculated for correlation analyses and comparisons between groups. In correlation analyses, metabolic activity of the amygdala correlated with metabolic activity in the aorta (r = 0.757), bone marrow (r = 0.750), and spleen (r = 0.665), respectively. Metabolic activity in the aorta correlated with 18 FDG uptake in the thoracic vertebrae (r = 0.703) and spleen (r = 0.594), respectively. Metabolic activity in the spleen also correlated with 18 FDG uptake in the bone marrow (r = 0.620). Metabolic activity in the adjacent erector spinae skeletal muscle (our control tissue) was not positively correlated with any other region of interest. Finally, there were no statistically significant mean differences in metabolic activity between the three groups: nonsmokers, electronic cigarette users, and smokers in any target tissue. Amygdala metabolic activity, as measured by 18 FDG uptake in FDG-PET/CT scans, positively correlated with inflammation in the splenocardiac tissues, including: the aorta, bone marrow, and spleen, underscoring the existence of a neural-hematopoietic-inflammatory axis in healthy, young adults.

Optimizing ECG lead selection for detection of prolongation of ventricular repolarization as measured by the Tpeak-end interval.

BACKGROUND: The Tpeak-end(Tp-e) has not been compared in all 12 ECG leads in healthy adults to determine if the Tp-e varies across leads. If there is variation, it remains uncertain, which lead(s) are preferred for recording in order to capture the maximal Tp-e value. OBJECTIVE: The purpose of the current study was to determine the optimal leads, if any, to capture the maximal Tp-e interval in healthy young adults. METHODS: In 88 healthy adults (ages 21-38 years), including derivation (n = 21), validation (n = 20), and smoker/vaper (n = 47) cohorts, the Tp-e was measured using commercial computer software (LabChart Pro 8 with ECG module, ADInstruments) in all 12 leads at rest and following a provocative maneuver, abrupt standing. Tp-e was compared to determine which lead(s) most frequently captured the maximal Tp-e interval. RESULTS: In the rest and abrupt standing positions, the Tp-e was not uniform among the 12 leads; the maximal Tp-e was most frequently captured in the precordial leads. At rest, grouping leads V2-V4 resulted in detection of the maximum Tp-e in 85.7% of participants (CI 70.7, 99.9%) versus all other leads (p < .001). Upon abrupt standing, grouping leads V2-V6 together, resulted in detection of the maximum Tp-e 85.0% of participants (CI 69.4, 99.9% versus all other leads; p < .001). These findings were confirmed in the validation cohort, and extended to the smoking/vaping cohort. CONCLUSION: If only a subset of ECG leads will be recorded or analyzed for the Tp-e interval, selection of the precordial leads is preferred since these leads are most likely to capture the maximal Tp-e value.

Drugs of Misuse: Focus on Vascular Dysfunction.

Common drugs of misuse, including cannabis, opioids, stimulants, alcohol, and anabolic steroids, have strikingly disparate acute and chronic vascular effects, leading to a wide range of clinical cardiovascular presentations. Acute cannabis smoking has been associated with increased risk for myocardial infarction and ischemic stroke in otherwise healthy young people. However, it remains uncertain if people who exclusively smoke cannabis have increased risk for accelerated atherosclerosis similar to that found in people who exclusively smoke tobacco cigarettes. Cocaine and methamphetamines, both stimulants, increase risk for stroke, myocardial infarction, aortic dissection, and accelerated atherosclerosis, but only methamphetamine use is strongly linked to pulmonary hypertension. Chronic alcohol use is strongly associated with chronic hypertension and hemorrhagic stroke, but perhaps confers a lower risk for myocardial infarction. Finally, anabolic steroid use, presumably through adverse effects on circulating lipids and the hematopoietic system, is associated with increased risk for accelerated atherosclerosis and myocardial infarction. Physicians, especially cardiologists, emergency medicine, and internal medicine physicians, should be familiar with the short- and long-term vascular consequences of use of these substances, thereby ensuring appropriate, specific, and informed counselling and treatment.

Instigators of COVID-19 in Immune Cells Are Increased in Tobacco Cigarette Smokers and Electronic Cigarette Vapers Compared With Nonsmokers.

INTRODUCTION: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, gains entry into the host cell when its Spike protein is cleaved by host proteases TMPRSS2 and furin, thereby markedly increasing viral affinity for its receptor, angiotensin-converting enzyme-2 (ACE2). In rodent and diseased human lungs, tobacco cigarette (TCIG) smoke increases ACE2, but the effect of electronic cigarette vaping (ECIG) is unknown. It is unknown whether nicotine (in both TCIGs and ECIGs) or non-nicotine constituents unique to TCIG smoke increase expression of key proteins in COVID-19 pathogenesis. METHODS: Immune (CD45+) cells collected before the pandemic in otherwise healthy young people, including TCIG smokers (n = 9), ECIG vapers (n = 12), or nonsmokers (NS) (n = 12), were studied. Using flow cytometry, expression of key proteins in COVID-19 pathogenesis were compared among these groups. RESULTS: TCIG smokers and ECIG vapers had similar smoking or vaping burdens as indicated by similar plasma cotinine levels. TCIG smokers compared with NS had a significantly increased percentage of cells that were positive for ACE2 (10-fold, p < .001), TMPRSS2 (5-fold, p < .001), and ADAM17 (2.5-fold, p < .001). Additionally, the mean fluorescence intensity (MFI) consistently showed greater mean ACE2 (2.2-fold, p < .001), TMPRSS2 (1.5-fold, p < .001), furin (1.1-fold, p < .05), and ADAM17 (2-fold, p < .001) in TCIG smokers compared with NS. In ECIG vapers, furin MFI was increased (1.15-fold, p < .05) and TMPRSS2 MFI tended to be increased (1.1-fold, p = .077) compared with NS. CONCLUSIONS: The finding that key instigators of COVID-19 infection are lower in ECIG vapers compared with TCIG smokers is intriguing and warrants additional investigation to determine if switching to ECIGs is an effective harm reduction strategy. However, the trend toward increased proteases in ECIG vapers remains concerning. IMPLICATIONS: (1) This is the first human study to report a marked increase in proteins critical for COVID-19 infection, including ACE2, TMPRSS2, and ADAM17, in immune cells from healthy tobacco cigarette smokers without lung disease compared with e-cigarette vapers and nonsmokers. (2) These findings warrant additional investigation to determine whether switching to electronic cigarettes may be an effective harm reduction strategy in smokers addicted to nicotine who are unable or unwilling to quit. (3) The increase in proteases in electronic cigarette vapers remains concerning.

Electronic and Tobacco Cigarettes Alter Polyunsaturated Fatty Acids and Oxidative Biomarkers.

[Figure: see text].

Increased Expression of Proatherogenic Proteins in Immune Cell Subtypes in Tobacco Cigarette Smokers But Not in Electronic Cigarette Vapers.

It is unclear how oxidative stress triggered by smoking and vaping may alter specific immune cell subsets. In this study, we showed that tobacco cigarette smoking, but not electronic-cigarette vaping, is associated with increased expression of major proteins in the toll-like receptor 4 (TLR4) inflammasome-interleukin (IL)-6 signalling axis in monocyte subtypes and T cells. TLR4 senses oxidative stress in immune cells caspase-1 is a key protein of inflammasome activation, and IL-6R-α is the receptor for IL-6 that drives proatherogenic IL-6 signalling. These findings implicate the non-nicotine, pro-oxidant toxicants in tobacco cigarette smoke as instigators of increased expression of key proteins in the TLR4-inflammasome-IL-6 axis that contribute to atherogenesis.

Vaping and cardiac disease.

Tobacco cigarette smoking is the most prevalent reversible risk factor for cardiovascular disease in the USA. Electronic cigarettes, invented as an alternative nicotine source for smokers unable or unwilling to stop smoking, have gained skyrocketing popularity, but their cardiovascular risk remains uncertain. Although data recently analysed in a Cochran report do support their superior effectiveness to other forms of nicotine replacement therapies for smoking cessation, electronic cigarettes are also frequently used by non-smokers-especially high school students. There are no long-term outcome studies on the cardiovascular risk of vaping electronic cigarettes, but the effects of electronic cigarettes on known risk factors for cardiovascular disease, including neurohumoural activation, oxidative stress and inflammation, endothelial function and thrombosis, have been studied. In this review, we summarise evidence in humans that supports the notion that while electronic cigarettes may be less harmful than traditional cigarettes, they are not harmless. Additionally, the increasing popularity of vaping marijuana with its unknown cardiovascular risks as well as the outbreak in 2019 of EVALI (electronic cigarette, or vaping, product use-associated lung injury) related to bootlegged vaping products raise further concerns. Before physicians can confidently advise their smoking patients about the role of electronic cigarettes as a means of smoking cessation to lower cardiovascular risk, improved regulation and quality control is necessary.

Changes in lipid composition associated with electronic cigarette use.

BACKGROUND: Electronic cigarette use is on the rise despite a number of reports linking electronic cigarettes with adverse health outcomes. Recent studies have suggested that alterations in lipid signaling may be one mechanism by which electronic cigarettes contribute to lung pulmonary function. Vitamin E acetate, for example, is synthetic form of Vitamin E transported via lipids, found to be associated with electronic cigarette associated lung injury. Lipids are absolutely critical for normal lung physiology and perturbations in a number of lipid pathways have been associated with respiratory illness. Is it conceivable that electronic cigarette use even in seemingly healthy cohorts are associated with alterations in lipid pathways? METHODS: To investigate quantitative alterations in the plasma lipidome associated with electronic cigarette use in healthy we obtained plasma samples from 119 male and female participants with who were either: (1) chronic tobacco cigarette (TC) smokers (> 12 months of self-reported TC use), (2) chronic Electronic cigarette (EC) users (> 12 months of self-reported EC use), or (3) non-users. We measured quantitative lipid species across different lipid sub-classes from plasma samples using the Sciex Lipidyzer. RESULTS: We found that male and female tobacco and electronic cigarette users had distinct lipidome signatures across a number of lipid species although the vast majority of lipids were unchanged when compared to non-users. Intriguingly, we found that female but not male electronic cigarette users had lower levels of plasmalogens, critical glycerophospholipids secreted by alveoli and required for normal surfactant function. CONCLUSIONS: In summary, our study does not reveal striking changes associated with electronic cigarette use but we observed sex-specific changes in lipids known to be critical for lung function.

Elevated Cellular Oxidative Stress in Circulating Immune Cells in Otherwise Healthy Young People Who Use Electronic Cigarettes in a Cross-Sectional Single-Center Study: Implications for Future Cardiovascular Risk.

Background Tobacco cigarettes (TCs) increase oxidative stress and inflammation, both instigators of atherosclerotic cardiac disease. It is unknown if electronic cigarettes (ECs) also increase immune cell oxidative stress. We hypothesized an ordered, "dose-response" relationship, with tobacco-product type as "dose" (lowest in nonsmokers, intermediate in EC vapers, and highest in TC smokers), and the "response" being cellular oxidative stress (COS) in immune cell subtypes, in otherwise, healthy young people. Methods and Results Using flow cytometry and fluorescent probes, COS was determined in immune cell subtypes in 33 otherwise healthy young people: nonsmokers (n=12), EC vapers (n=12), and TC smokers (n=9). Study groups had similar baseline characteristics, including age, sex, race, and education level. A dose-response increase in proinflammatory monocytes and lymphocytes, and their COS content among the 3 study groups was found: lowest in nonsmokers, intermediate in EC vapers, and highest in TC smokers. These findings were most striking in CD14dimCD16+ and CD14++CD16+ proinflammatory monocytes and were reproduced with 2 independent fluorescent probes of COS. Conclusions These findings portend the development of premature cardiovascular disease in otherwise healthy young people who chronically vape ECs. On the other hand, that the COS is lower in EC vapers compared with TC smokers warrants additional investigation to determine if switching to ECs may form part of a harm-reduction strategy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03823885.

Differential effects of tobacco cigarettes and electronic cigarettes on endothelial function in healthy young people.

Tobacco cigarette (TC) smoking has never been lower in the United States, but electronic cigarette (EC) vaping has reached epidemic proportions among our youth. Endothelial dysfunction, as measured by flow-mediated vasodilation (FMD) is a predictor of future atherosclerosis and adverse cardiovascular events and is impaired in young TC smokers, but whether FMD is also reduced in young EC vapers is uncertain. The aim of this study in otherwise healthy young people was to compare the effects of acute and chronic tobacco cigarette (TC) smoking and electronic cigarette (EC) vaping on FMD. FMD was compared in 47 nonsmokers (NS), 49 chronic EC vapers, and 40 chronic TC smokers at baseline and then after EC vapers (n = 31) and nonsmokers (n = 47) acutely used an EC with nicotine (ECN), EC without nicotine (EC0), and nicotine inhaler (NI) at ~4-wk intervals and after TC smokers (n = 33) acutely smoked a TC, compared with sham control. Mean age (NS, 26.3 ± 5.2 vs. EC, 27.4 ± 5.45 vs. TC, 27.1 ± 5.51 yr, P = 0.53) was similar among the groups, but there were more female nonsmokers. Baseline FMD was not different among the groups (NS, 7.7 ± 4.5 vs. EC:6.6 ± 3.6 vs. TC, 7.9 ± 3.7%∆, P = 0.35), even when compared by group and sex. Acute TC smoking versus control impaired FMD (FMD pre-/postsmoking, -2.52 ± 0.92 vs. 0.65 ± 0.93%∆, P = 0.02). Although the increase in plasma nicotine was similar after EC vapers used the ECN versus TC smokers smoked the TC (5.75 ± 0.74 vs. 5.88 ± 0.69 ng/mL, P = 0.47), acute EC vaping did not impair FMD. In otherwise healthy young people who regularly smoke TCs or ECs, impaired FMD compared with that in nonsmokers was not present at baseline. However, FMD was significantly impaired after smoking one TC, but not after vaping an equivalent "dose" (estimated by change in plasma nicotine) of an EC, consistent with the notion that non-nicotine constituents in TC smoke mediate the impairment. Although it is reassuring that acute EC vaping did not acutely impair FMD, it would be dangerous and premature to conclude that ECs do not lead to atherosclerosis.NEW & NOTEWORTHY In our study of otherwise healthy young people, baseline flow-mediated dilation (FMD), a predictor of atherosclerosis and increased cardiovascular risk, was not different among tobacco cigarette (TC) smokers or electronic cigarette (EC) vapers who had refrained from smoking, compared with nonsmokers. However, acutely smoking one TC impaired FMD in smokers, whereas vaping a similar EC "dose" (as estimated by change in plasma nicotine levels) did not. Finally, although it is reassuring that acute EC vaping did not acutely impair FMD, it would be premature and dangerous to conclude that ECs do not lead to atherosclerosis or increase cardiovascular risk.