E-cigarette Aerosol Research Articles

Maternal electronic cigarette use during pregnancy affects long-term arterial function in offspring.

Vaping, or electronic cigarette (ecig) use, is prevalent among pregnant women, although little is known about the effects of perinatal ecig use on cardiovascular health of the progeny (even when using nicotine-free e-liquid). Maternal toxicant inhalation may adversely affect vital conduit vessel development. We tested the hypothesis that perinatal exposure to maternal vaping would lead to a dose-dependent dysfunction that would persist into later life of offspring. Pregnant Sprague-Dawley rats were exposed to either nicotine-free (ecig0) or nicotine-containing ecig aerosol (18 mg/mL, ecig18) starting on gestational day 2 and continued until pups were weaned (postnatal day 21). Pups were never directly exposed. Conduit artery function (stiffness and reactivity) and structure were assessed in 3- and 7-mo-old offspring. At 3 mo, pulse wave velocity (PWV) in the ecig0 and ecig18 offspring was significantly higher than controls in both the 20 puffs/day (6.6 ± 2.1 and 4.8 ± 1.3 vs. 3.2 ± 0.7 m/s, respectively, P < 0.05, means ± SD) and in 60 puffs/day exposure cohort (7.5 ± 2.8 and 7.5 ± 2.5 vs. 3.2 ± 0.5 m/s, respectively, P < 0.01). Wire myography revealed (range of 23%-31%) impaired aortic relaxation in all ecig exposure groups (with or without nicotine). Incubation of vessels with TEMPOL or Febuxostat reversed the aortic dysfunction, implicating the involvement of reactive oxygen species. Nearly identical changes and pattern was seen in vascular outcomes of 7-mo-old offspring. The take-home message from this preclinical study is that maternal vaping during pregnancy, with or without nicotine, leads to maladaptations in vascular (aortic) development that persist into adult life of offspring.NEW & NOTEWORTHY We observe a significant alteration in arterial structure and function in adolescent and adult offspring due to developmental exposure to toxicants resulting from perinatal maternal vaping. Taken together with previous work that described lasting dysfunction in cerebral microvasculature in offspring, these data underscore the adverse consequences of maternal exposure to electronic cigarette aerosol in conduit and resistance vessels alike, irrespective of nicotine content.

Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions.

We review the literature on laboratory studies quantifying the production of potentially toxic organic byproducts (carbonyls, carbon monoxide, free radicals and some nontargeted compounds) in e-cigarette (EC) aerosol emissions, focusing on the consistency between their experimental design and a realistic usage of the devices, as determined by the power ranges of an optimal regime fulfilling a thermodynamically efficient process of aerosol generation that avoids overheating and "dry puffs". The majority of the reviewed studies failed in various degrees to comply with this consistency criterion or supplied insufficient information to verify it. Consequently, most of the experimental outcomes and risk assessments are either partially or totally unreliable and/or of various degrees of questionable relevance to end users. Studies testing the devices under reasonable approximation to realistic conditions detected levels of all organic byproducts that are either negligible or orders of magnitude lower than in tobacco smoke. Our review reinforces the pressing need to update and improve current laboratory standards by an appropriate selection of testing parameters and the logistical incorporation of end users in the experimental design.

Oral epithelium response of electronic cigarette users to electronic cigarette.

Electronic cigarettes are increasing in popularity, but there is only little information on their biologic effects on the oral epithelium, the initial site exposed to electronic cigarette smoke. We assessed the oral epithelium response to electronic cigarettes by comparing the histology and RNA transcriptome (mRNA and miRNA) of healthy electronic cigarette vapers to nonsmokers. mRNA was assessed based on: (1) genome-wide; (2) genes previously identified as dysregulated in the oral epithelium of electronic cigarette vapers versus nonsmokers; (3) immune and inflammatory-related genes previously identified as dysregulated in the nasal epithelium of electronic cigarette vapers compared to nonsmokers; (4) genes previously identified as dysregulated in the small airway epithelium of nonsmokers following an acute exposure to electronic cigarette; and (5) genes related to the initial steps of COVID-19 infection. In addition, miRNA was assessed genome-wide. Comparisons were performed using analysis of variance, and Benajmini-Hochberg corrected p< 0.05 was considered significant. The histology of the epithelium, lamina propria and basal layer in electronic cigarette vapers appeared normal. Assessment of mRNA and miRNA, based on all gene lists, did not identify any genes significantly modified in the oral epithelium of electronic cigarette vapers in response to electronic cigarette use. An average history of 2 years of vaping results in no detectable histologic or transcriptome abnormalities in the buccal mucosa.

E-Cigarette Vapour Increases ACE2 and TMPRSS2 Expression in a Flavour- and Nicotine-Dependent Manner.

COVID-19 infects via the respiratory system, but it can affect multiple systems and lead to multi system failure. There is growing evidence that smoking may be associated with higher rates of COVID-19 infections and worse outcomes due to increased levels of ACE2 in lung epithelial cells, but it is unknown whether E-cigarette use may lead to increased risk of COVID-19 infection from the SARS-CoV-2 virus. In this study, healthy donor bronchial epithelial cells (NHBE) and monocyte-derived macrophages (MDM) were exposed to cigarette smoke extract (CSE) or nicotine or flavoured E-cigarette vapour extract (EVE) before the assessment of SARS-CoV-2 recognition receptors ACE2 and TMPRSS2 genes. MDMs exposed to CSE and Tobacco EVE showed increased ACE2 expression; however, no treatment altered the TMPRSS2 expression. ACE2 was found to be upregulated by >2-fold in NHBE cells exposed to CSE, as well as nicotine, banana, or chocolate EVE, while TMPRSS2 was only upregulated by CSE or nicotine EVE exposure. These findings suggesting that flavourings can increase ACE2 expression in multiple cell types, while TMPRSS2 expression increases are limited to the epithelial cells in airways and may be limited to nicotine and/or cigarette smoke exposure. Therefore, increased risk of COVID-19 infection cannot be ruled out for vapers.

E-cigarette aerosol exposure of pulmonary surfactant impairs its surface tension reducing function.

E-cigarette (EC) and vaping use continue to remain popular amongst teenage and young adult populations, despite several reports of vaping associated lung injury. One of the first compounds that EC aerosols comes into contact within the lungs during a deep inhalation is pulmonary surfactant. Impairment of surfactant's critical surface tension reducing activity can contribute to lung dysfunction. Currently, information on how EC aerosols impacts pulmonary surfactant remains limited. We hypothesized that exposure to EC aerosol impairs the surface tension reducing ability of surfactant. Bovine Lipid Extract Surfactant (BLES) was used as a model surfactant in a direct exposure syringe system. BLES (2ml) was placed in a syringe (30ml) attached to an EC. The generated aerosol was drawn into the syringe and then expelled, repeated 30 times. Biophysical analysis after exposure was completed using a constrained drop surfactometer (CDS). Minimum surface tensions increased significantly after exposure to the EC aerosol across 20 compression/expansion cycles. Mixing of non-aerosolized e-liquid did not result in significant changes. Variation in device used, addition of nicotine, or temperature of the aerosol had no additional effect. Two e-liquid flavours, menthol and red wedding, had further detrimental effects, resulting in significantly higher surface tension than the vehicle exposed BLES. Menthol exposed BLES has the highest minimum surface tensions across all 20 compression/expansion cycles. Alteration of surfactant properties through interaction with the produced aerosol was observed with a basic e-liquid vehicle, however additional compounds produced by added flavourings appeared to be able to increase inhibition. EC aerosols alter surfactant function through increases in minimum surface tension. This impairment may contribute to lung dysfunction and susceptibility to further injury.

Abstract 12922: Detection of the Effect of Nicotine Delivered by E-Cigarettes or Standard Cigarettes on Cardiovascular System From a Carotid Waveform Using a Physics-Based Machine Learning Approach

Introduction: We have recently shown (Alavi et al. Circulation, (2021)144: A13745-A13745) that adverse effects of nicotine delivered chronically by electronic cigarette (EC) vapor or standard cigarettes on left ventricular systolic function can be captured using intrinsic frequency (IF) method applied on carotid waveforms. Here, we propose a hybrid IF-machine learning (ML) method to detect nicotine effect on cardiovascular system using a carotid waveform. Methods: Total number of n=117 young healthy adult male and female Sprague Dawley rats (49% (n=57) female, weight ~200-250 g) were randomized and exposed to: 1) purified air, n=32; 2) EC vapor without nicotine (EC NIC-), n=26; 3) EC vapor plus nicotine (EC NIC+), n=27; and 4) standard cigarette smoke from reference combustion cigarettes (3R4F), n=32. All the exposures (nose-only) took place for duration of 5 hours/day, 4 days/week for total of 8 weeks. Third-generation type EC from VaporFi, tank model: Volt 2 was used. E-liquid was tobacco flavored with a 50/50 propylene glycol/glycerin ratio. Similar nicotine amount as the standard cigarette was delivered to the rats of EC NIC+ group. After 8 weeks of exposure, IFs were computed from invasively measured carotid waveforms. A support vector machine (SVM) classifier with radial basis function kernel was trained using IF data from 83 rats to detect (non)-nicotine groups. The k -fold cross-validation ( k =10) was used to avoid overfitting. The remaining rats were used for generalization test (n=14) and stratified blind test (n=20). Results: Our SVM model showed positive and negative predictive values of 66.7% and 76.9%, respectively. Sensitivity and specificity were 82.4% and 58.8% for test data (Fig1). Conclusions: Our results suggest that nicotine delivered by ECs or cigarettes can be detected by a physics-based ML model from a single carotid waveform. This method can potentially be used for detecting adverse effect of nicotine on cardiovascular system noninvasively.

Abstract 13315: Differences in Infarct Size and No-Reflow by Sex in Young Adult Rats in an Electronic Cigarette Exposure Study

Purpose: We investigated the effects of chronic exposure to electronic cigarettes (e-cig) on myocardial infarct size and the size of the no-reflow zone in a rat model of both sexes. Methods and Results: Sprague Dawley rats (6 weeks old) were randomized to 4 exposure groups: (1) Purified air (n=16 male/16 female); (2) e-cig vapor with 15mg/mL nicotine (n=13 male/15 female); (3) e-cig vapor without nicotine (n=16 male/12 female); and (4) Standard nicotine-containing combustion cigarette smoke (n=16 male/16 female). All rats were exposed to inhalation exposure for 8 weeks, prior to being subjected to 30 minutes of left coronary artery occlusion followed by 3 hours of reperfusion. Two-way analysis of variance (that factors sex and treatment) demonstrated that chronic exposure to e-cig vapor (with or without nicotine) or to standard cigarettes did not alter myocardial infarct or no-reflow size compared to air. However, as shown in the figure, infarct size was significantly smaller (40.7 ± 2.7% vs 54.5 ± 2.6%; p=0.0004) and no-reflow size was smaller (18.1 ± 2.0% vs 26.8 ± 2.2%; p=0.0042) in female rats compared to male rats. Conclusions: Long-term e-cig exposure did not affect the cardiac sensitivity to ischemia/reperfusion injury in young rats. Female rats are more tolerance to ischemia/reperfusion injury than males. This sex difference phenomena was not observed in our previous study [Li et al. J Thromb Thrombolysis. 1995;2(3):221-225.] that examined the tolerance between males and females subjected to 90 mins of left coronary artery occlusion followed by 4 hours of reperfusion in 1-year-old SD rats and found the myocardial infarct size to be similar between the sexes. The different findings between the 2 studies may be due to the age difference (which implies possible hormonal effects in the younger rats) or different coronary artery occlusion and reperfusion times.

Abstract 13324: Impact of Chronic Electronic Cigarette Vapor Exposure on the Recovery of Cardiovascular Function in Experimental Rat Myocardial Ischemia/Reperfusion Model

Background: The impact of long-term electronic cigarettes (E-cig) vaping on cardiovascular function in rats were investigated. Methods: Sprague Dawley rats (both sex, 6 weeks old) were randomly exposed to filtered air (n=32), E-cig with nicotine (E-cig Nic + , n=26), E-cig without nicotine (E-cig Nic - , n=26), or standard cigarette smoke (n=31). After exposure to inhalation exposure for 8 weeks, the rats were subjected to 30 minutes of left coronary artery occlusion followed by 3 hours of reperfusion. Cardiovascular function was measured with intracavitary Millar catheters and echocardiography during the surgical procedure. Results: As the data shown in the Table, at 2.5 hours after coronary artery reperfusion, heart rate, cardiac output and positive/negative LV dp/dt were lower in the E-cig Nic + group compared to the air and/or cigarette group. LVFS in the cigarette group was higher than compared to E-cig Nic + or air group. There was a significantly higher systemic arterial resistance in the E-cig Nic + group compared to the cigarette group. Conclusions: Chronic E-cig Nic + exposure impairs the cardiovascular function recovery during the phase of coronary artery reperfusion after heart attack, indicated by reductions of heart rate, cardiac output, LV positive and negative dp/dt (suggesting a reduction in contractility and relaxation); and increase in systemic arterial resistance in the setting of experimental acute myocardial infarction compared to air and/or standard cigarette smoke.

Abstract 13745: Electronic Cigarette-Derived Aerosols Induce Endothelial Dysfunction: Role of Aldehydes and Transient Receptor Potential Ankyrin-1 in Mice

Introduction: Electronic cigarettes (e-cigs) threaten to reverse the decline in rates of nicotine dependence and smoking. While some believe that e-cigarettes are less harmful than combustible cigarettes, e-cig use is associated with respiratory symptoms (cough, wheeze) and endothelial dysfunction (ED) indicating a potential to increase the risk of cardiovascular disease (CVD) with chronic use. ED is sine qua non of multiple CVD, yet the mechanism of e-cig-induced ED is unknown. Hypothesis: E-cigs generate levels of irritants that activate the Transient Receptor Potential Ankyrin-1 (TRPA1) to trigger nocifensive reflexes and induce ED in mice. Methods: Wild type (WT) and TRPA1-null C57BL/6J male and female mice were exposed to: filtered air (control), aerosols of JUUL e-cig liquid, e-cig solvents without nicotine (propylene glycol:glycerin, PG:G), or irritant gases alone (acrolein, formaldehyde). Urinary levels of nicotine and aldehyde metabolites were measured by UPLC-MS/MS. During acute exposures, respiratory irritant responses were monitored by radiotelemetry. Following short-term exposure (4d), aortic endothelial function, blood/plasma markers of organ toxicity, and platelet activation were measured. Results: Exposure of WT mice to e-cig aerosols increased urine levels of the acrolein, but not formaldehyde, metabolite (3HPMA), to that of exposures to 1 ppm acrolein alone. In WT mice, exposure to either PG:G (30:70), formaldehyde (5 ppm), or acrolein (1 ppm) induced respiratory braking. In female WT mice (n=5-18), exposure to PG:G (-61.8±4.2 % ACh relaxation) and formaldehyde (–56.3 ± 4.5 %) but not acrolein (-80.0±3.2 %) induced ED vs control group (-77.8±1.5 %). In female TRPA1-null mice (n=5-14), neither PG:G (-77.6±3.6 %), formaldehyde (-85.9±7.8 %) nor acrolein (-86.6±2.8 %) exposure induced ED vs control (-81.3±5.4 %). Acrolein exposure enhanced aortic sensitivity to an NO donor similarly in female WT and TRPA1-null mice. Conclusions: Formaldehyde and acrolein generated from the PG:G in e-cigs provoked pulmonary irritant reflexes, and formaldehyde exposure alone induced ED in female mice. Irritant aldehydes in e-cig-derived aerosols activate the TRPA1 receptor to promote ED that could increase CVD risk.

Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors

The size and chemical content of particles in electronic cigarette vapors (e-vapors) dictate their fate in the human body. Understanding how particles in e-vapors are formed and their size is critical to identifying and mitigating the adverse consequences of vaping. Thermal decomposition and reactions of the refill liquid (e-liquid) components play a key role in new particles formation. Here we report the evolution of particle number concentration in e-vapors over time for variable mixtures of refill e-liquids and operating conditions. Particle with aerodynamic diameter < 300 nm accounted for up to 17% (or 780 μg/m3) of e-vapors particles. Two events of increasing particle number concentration were observed, 2–3 s after puff completion and a second 4–5 s later. The intensity of each event varied by the abundance of propylene glycol, glycerol, and flavorings in e-liquids. Propylene glycol and glycerol were associated with the first event. Flavorings containing aromatic and aliphatic unsaturated functional groups were strongly associated with the second event and to a lesser extent with the first one. The results indicate that particles in e-vapors may be formed through the heteromolecular condensation of propylene glycol, glycerol, and flavorings, including both parent chemicals and/or their thermal decomposition products.

Social environment exposure to electronic cigarettes and its association with e-cigarette use among adolescents in Shanghai, China.

This study investigated adolescents' social-environmental exposure to e-cigarettes in association with e-cigarette use in Shanghai, China. We also explored these differences by gender and school type. Sixteen thousand one hundred twenty-three students were included by a stratified random cluster sampling, and the number was weighted according to selection probability. Association between social environment exposure and e-cigarette use was examined by multivariate logistic regressions. There were 35.07, 63.49, 75.19, 9.44, and 18.99% students exposed to secondhand e-cigarette aerosol (SHA), e-cigarette sales, e-cigarette information, parents' and friends' e-cigarette use. Students exposed to SHA (aOR = 1.73, 95% CI 1.40-2.14), e-cigarette sales from ≥2 sources (aOR = 1.55, 95% CI 1.18-2.03), e-cigarette information exposure from ≥2 sources (aOR = 1.39, 95% CI 1.05-1.83), and having a social e-smoking environment (friends' e-cigarette use: aOR = 2.56, 95% CI 2.07-3.16; parents' e-cigarette use: aOR = 1.54, 95% CI 1.17-2.02) were significantly associated with their intention to use e-cigarettes. More girls were exposed to e-cigarette sales in the malls, e-cigarette information at points of sale and on social media (P < 0.01), and exposure to sales from ≥2 sources were associated with girls' intention to use e-cigarettes (aOR = 1.84, 95% CI 1.22-2.78). However, boys were more likely to be exposed to friends' e-cigarette use (P < 0.001), and having friends using e-cigarettes was associated with greater intention to use them in boys (aOR = 2.64, 95% CI 1.97-3.55). Less vocational high school students were exposed to parents' e-cigarette use (P < 0.001), but they were more likely to use e-cigarettes in the future after being exposed (aOR = 2.27, 95% CI 1.50-3.43). A similar phenomenon was observed between junior high students and their exposure to SHA. This study reported adolescents' high exposure rates to the social environment of e-cigarettes. Exposure to SHA, e-cigarette sales from ≥2 sources, e-cigarette information from ≥2 sources and having a social e-smoking environment were related to adolescents' intention to use e-cigarettes. Differences in gender and school type were observed. More attention should be paid to girls, and different interventions should be designed for different types of school students. Additionally, comprehensive tobacco control policies are needed.

RF32 | PSUN45 Nicotine E-Cigarette Vapors Exposure Disturbs 11β-Hydroxysteroid Dehydrogenase Type 2 Expression in the Kidney May Contribute to E-Cigarette-Induced Blood Pressure Elevation in Mice

Abstract Inhalation of electronic (e)-cigarettes containing nicotine may elevate blood pressure (BP), but the underlying mechanisms are poorly understood. 11β-HSD2 is crucial for BP regulation by inactivating glucocorticoids in the kidney. Little is known about the effect of e-cigarettes on 11β-HSD2 and their contribution to the process of BP elevation. To examine the possible effects of e-cigarette vapor exposures on renal 11β-HSD2 and BP, four groups of mice were exposed to aerosolized PBS, nicotine-free or nicotine-containing e-cigarettes, with concurrent exposure to either saline or the nicotine antagonist hexamethonium (Hex). Mouse renal M1 CCD cells were used to identify the effects of nicotine on 11β-HSD2 and its transcription factor C/EBPβ. Our results showed that mice exposed to e-cigarettes containing nicotine for 4 weeks markedly decreased the expression and activity of renal 11β-HSD2 and elevated the systolic BP in C57BL/6J mice. Reduction of 11β-HSD2 by nicotine inhalation was accompanied by reduction of renal C/EBPβ and responded to elevated plasma nicotine levels. In contrast, these effects were not observed in mice exposed to e-cigarettes vapor without nicotine compared to PBS controls. Treatment with Hex significantly decreased the elevated ratio of urinary corticosterone to 11-DHC along with stimulation of renal C/EBPβ and prevented the raised BP in mice exposed to e-cigarette vapor containing nicotine. Treating CCD M1 cells with vaporized e-cigarettes containing nicotine extract showed comparable effects with those of pure nicotine for suppression of C/EBPβ and 11β-HSD2, and these effects are blocked by Hex, indicating a mechanistic specificity. Our results indicate that the inhalation of nicotine e-cigarette vapors has potential adverse effects on renal health suggesting that disturbance of renal 11β-HSD2 may contribute to e-cigarette nicotine-induced BP elevation. These findings highlight the potential health risk of e-cigarettes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.

Impairment of Endothelial Function by Cigarette Smoke Is Not Caused by a Specific Smoke Constituent, but by Vagal Input From the Airway.

Exposure to tobacco or marijuana smoke, or e-cigarette aerosols, causes vascular endothelial dysfunction in humans and rats. We aimed to determine what constituent, or class of constituents, of smoke is responsible for endothelial functional impairment. We investigated several smoke constituents that we hypothesized to mediate this effect by exposing rats and measuring arterial flow-mediated dilation (FMD) pre- and post-exposure. We measured FMD before and after inhalation of sidestream smoke from research cigarettes containing normal and reduced nicotine level with and without menthol, as well as 2 of the main aldehyde gases found in both smoke and e-cigarette aerosol (acrolein and acetaldehyde), and inert carbon nanoparticles. FMD was reduced by all 4 kinds of research cigarettes, with extent of reduction ranging from 20% to 46% depending on the cigarette type. While nicotine was not required for the impairment, higher nicotine levels in smoke were associated with a greater percent reduction of FMD (41.1±4.5% reduction versus 19.2±9.5%; P=0.047). Lower menthol levels were also associated with a greater percent reduction of FMD (18.5±9.8% versus 40.5±4.8%; P=0.048). Inhalation of acrolein or acetaldehyde gases at smoke-relevant concentrations impaired FMD by roughly 50% (P=0.001). However, inhalation of inert carbon nanoparticles at smoke-relevant concentrations with no gas phase also impaired FMD by a comparable amount (P<0.001). Bilateral cervical vagotomy blocked the impairment of FMD by tobacco smoke. There is no single constituent or class of constituents responsible for acute impairment of endothelial function by smoke; rather, we propose that acute endothelial dysfunction by disparate inhaled products is caused by vagus nerve signaling initiated by airway irritation.

Electronic cigarette vaping product use is associated with lung injury in a 15-year-old adolescent.

A 15-year-2-month-old boy presented with progressive and persistent upper abdominal pain and productive cough for 3 days before admission. A physical examination revealed crackles in the right lung, a distended abdomen, and tenderness over the upper abdomen. A chest radiograph (Fig. S1a) and chest computed tomography scan revealed blunting of bilateral costophrenic angles and multiple infiltrative nodules in both lungs with sparing of the left upper lobe (Fig. S1b and c). Laboratory tests showed leukocytosis and an elevated C-reactive protein level.

Maternal Inhalation of Electronic Cigarette Vapor Increases XOR Activity in the Dam and Her Offspring

Maternal Inhalation of Electronic Cigarette Vapor Increases XOR Activity in the Dam and Her Offspring

Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels.

The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function. Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants' sera, or e-cigarette aerosol condensate, on NO and H2O2 release and cell permeability in cultured endothelial cells (ECs). E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production. Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.

Harm perceptions of secondhand e-cigarette aerosol among youth in the United States

E-cigarette use among youth remains a public health concern. Although extant literature has examined the perceived harms of cigarette use and secondhand smoke, perceptions of harms associated with secondhand e-cigarette aerosol (SHA) are not well understood. Therefore, we used data from the 2020 U.S. National Youth Tobacco Survey (n = 13,292) in which participants indicated whether SHA caused no harm, little harm, some harm, or a lot of harm. We dichotomized SHA harm perceptions as harmless vs harmful. We included sociodemographics (i.e., age, sex, race/ethnicity, sexual orientation, urbanicity), e-cigarette use characteristics, and SHA exposure as covariates and estimated associations between SHA harm perceptions and each covariate using adjusted logistic regression. Most youth perceived SHA as harmful (87.9 %) compared to harmless (12.1 %). Older youth (vs younger youth) had higher odds of perceiving SHA as harmless, whereas male (vs female) youth had 49 % higher odds (95 % CI: 1.29–1.72) of perceiving SHA as harmless. As the number of days of e-cigarette use in the past 30 days increased (vs non-users), odds of perceiving SHA as harmless increased. Youth exposed to SHA (vs no exposure) in the past 30 days had 35 % higher odds of perceiving SHA as harmless (95 % CI: 1.16–1.57). To conclude, youth SHA harm perceptions varied overall and by sociodemographic characteristics, e-cigarette use, and SHA exposure. Educational campaigns to inform youth of the health risks associated with e-cigarettes and SHA are needed to reduce overall nicotine intake and disparities in nicotine exposure.

E-cigarettes and their lone constituents induce cardiac arrhythmia and conduction defects in mice

E-cigarette use has surged, but the long-term health effects remain unknown. E-cigarette aerosols containing nicotine and acrolein, a combustion and e-cigarette byproduct, may impair cardiac electrophysiology through autonomic imbalance. Here we show in mouse electrocardiograms that acute inhalation of e-cigarette aerosols disturbs cardiac conduction, in part through parasympathetic modulation. We demonstrate that, similar to acrolein or combustible cigarette smoke, aerosols from e-cigarette solvents (vegetable glycerin and propylene glycol) induce bradycardia, bradyarrhythmias, and elevations in heart rate variability during inhalation exposure, with inverse post-exposure effects. These effects are slighter with tobacco- or menthol-flavored aerosols containing nicotine, and in female mice. Yet, menthol-flavored and PG aerosols also increase ventricular arrhythmias and augment early ventricular repolarization (J amplitude), while menthol uniquely alters atrial and atrioventricular conduction. Exposure to e-cigarette aerosols from vegetable glycerin and its byproduct, acrolein, diminish heart rate and early repolarization. The pro-arrhythmic effects of solvent aerosols on ventricular repolarization and heart rate variability depend partly on parasympathetic modulation, whereas ventricular arrhythmias positively associate with early repolarization dependent on the presence of nicotine. Our study indicates that chemical constituents of e-cigarettes could contribute to cardiac risk by provoking pro-arrhythmic changes and stimulating autonomic reflexes.

E-cigarette aerosol impairs male mouse skeletal muscle force development and prevents recovery from injury.

To date, there has been a lag between the rise in E-cigarette use and an understanding of the long-term health effects. Inhalation of E-cigarette aerosol delivers high doses of nicotine, raises systemic cytokine levels, and compromises cardiopulmonary function. The consequences for muscle function have not been thoroughly investigated. The present study tests the hypothesis that exposure to nicotine-containing aerosol impairs locomotor muscle function, limits exercise tolerance, and interferes with muscle repair in male mice. Nicotine-containing aerosol reduced the maximal force produced by the extensor digitorum longus (EDL) by 30%-40% and, the speed achieved in treadmill running by 8%. Nicotine aerosol exposure also decreased adrenal and increased plasma epinephrine and norepinephrine levels, and these changes in catecholamines manifested as increased muscle and liver glycogen stores. In nicotine aerosol exposed mice, muscle regenerating from overuse injury only recovered force to 80% of noninjured levels. However, the structure of neuromuscular junctions (NMJs) was not affected by e-cigarette aerosols. Interestingly, the vehicle used to dissolve nicotine in these vaping devices, polyethylene glycol (PG) and vegetable glycerin (VG), decreased running speed by 11% and prevented full recovery from a lengthening contraction protocol (LCP) injury. In both types of aerosol exposures, cardiac left ventricular systolic function was preserved, but left ventricular myocardial relaxation was altered. These data suggest that E-cigarette use may have a negative impact on muscle force and regeneration due to compromised glucose metabolism and contractile function in male mice.NEW & NOTEWORTHY In male mice, nicotine-containing E-cigarette aerosol compromises muscle contractile function, regeneration from injury, and whole body running speeds. The vehicle used to deliver nicotine, propylene glycol, and vegetable glycerin, also reduces running speed and impairs the restoration of muscle function in injured muscle. However, the predominant effects of nicotine in this inhaled aerosol are evident in altered catecholamine levels, increased glycogen content, decreased running capacity, and impaired recovery of force following an overuse injury.

E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring.

The in utero environment is sensitive to toxicant exposure, altering the health and growth of the fetus, and thus sensitive to contaminant exposure. Though recent clinical data suggest that e-cigarette use does no further harm to birth outcomes than a nicotine patch, this does not account for the effects of vaping during pregnancy on the long-term health of offspring. Pregnant mice were exposed to: 1) e-cigarette vapor with nicotine (PV + Nic; 2% Nic in 50:50 propylene glycol: vegetable glycerin), 2) e-cigarette vapor without nicotine [PV; (50:50 propylene glycol:vegetable glycerin)], or 3) HEPA filtered air (FA). Dams were removed from exposure upon giving birth. At 5 mo of age, pulmonary function tests on the offspring revealed female and male mice from the PV group had greater lung stiffness (Ers) and alveolar stiffness (H) compared with the FA group. Furthermore, baseline compliance (Crs) was reduced in female mice from the PV group and in male mice from the PV and PV + Nic groups. Lastly, female mice had decreased forced expiratory volume (FEV0.1) in the PV group, but not in the male groups, compared with the FA group. Lung histology revealed increased collagen deposition around the vessels/airways and in alveolar tissue in PV and PV + Nic groups. Furthermore, goblet hyperplasia was observed in PV male and PV/PV + Nic female mice. Our work shows that in utero exposure to e-cigarette vapor, regardless of nicotine presence, causes lung dysfunction and structural impairments that persist in the offspring to adulthood.