Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation.
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ABSTRACT:
SUBMITTER: Lee AC
PROVIDER: S-EPMC7432384 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Electronic cigarettes (e-cigarettes) have gained their popularity as a substitute for cigarettes or cigars. Despite the widespread use of flavoring chemicals in e-cigarettes, the health impacts of the flavoring compounds, in particular their effects on critical cellular function in the lung, remain largely unknown. The goal of this study was to identify transcriptomic changes and impacted biological pathways in primary human bronchial epithelial cells (HBECs) exposed to flavoring chemicals (diacetyl or 2,3-pentanedione) and to flavored e-cigarette smoke. An airway-liquid interface culturing method was used to differentiate primary human bronchial epithelial cells (HBECs) into mature epithelial cells, which were then treated with 25 ppm diacetyl, 100 ppm 2,3 pentanedione, or e-cigarette smoke solution containing 2 ppm diacetyl. Poly(A)-selected RNA-Seq libraries were prepared with the PrepX RNA-Seq for Illumina Library kit. An Illumina HiSeq 2500 instrument was used to generate 50 base pair single-end reads. STAR was used to align sequencing reads to the hg38 reference genome, and HTSeq was used to quantify transcript levels. DESeq2 was used to perform differential expression analysis.
2019-08-21 | GSE118431 | GEO
Project description:The public health impact of e-cigarettes may depend on their substitutability for tobacco cigarettes. Dual users of e-cigarettes and tobacco cigarettes completed purchasing tasks in which they specified daily use levels under hypothetical conditions that varied the availability and price of e-cigarettes, tobacco cigarettes, and nicotine gum (for those with nicotine gum experience). When either e-cigarettes or tobacco cigarettes were the only available commodity, as price per puff increased, purchasing decreased, revealing similar reinforcement profiles. When available concurrently, as the price of tobacco puffs increased, purchasing of tobacco puffs decreased while purchasing of fixed-price e-cigarette puffs increased. Among those with nicotine gum experience, when the price of tobacco puffs was closest to the actual market value of tobacco puffs, e-cigarette availability decreased median tobacco puff purchases by 44% compared to when tobacco was available alone. In contrast, nicotine gum availability caused no decrease in tobacco puff purchases. E-cigarettes may serve as a behavioral economic substitute for tobacco cigarettes, and may be a superior substitute compared to nicotine gum in their ability to decrease tobacco use. Although important questions remain regarding the health impacts of e-cigarettes, these data are consistent with the possibility that e-cigarettes may serve as smoking cessation/reduction aids.
| S-EPMC6668913 | biostudies-literature
Project description:BACKGROUND:E-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD. OBJECTIVES:This study sought to determine the early vascular impact of switching from TC to EC in chronic smokers. METHODS:The authors conducted a prospective, randomized control trial with a parallel nonrandomized preference cohort and blinded endpoint of smokers ?18 years of age who had smoked ?15 cigarettes/day for ?2 years and were free from established cardiovascular disease. Participants were randomized to EC with nicotine or EC without nicotine for 1 month. Those unwilling to quit continued with TC in a parallel preference arm. A propensity score analysis was done to adjust for differences between the randomized and preference arms. Vascular function was assessed by FMD and pulse wave velocity. Compliance with EC was measured by carbon monoxide levels. RESULTS:Within 1 month of switching from TC to EC, there was a significant improvement in endothelial function (linear trend ? = 0.73%; 95% confidence interval [CI]: 0.41 to 1.05; p < 0.0001; TC vs. EC combined: 1.49%; 95% CI: 0.93 to 2.04; p < 0.0001) and vascular stiffness (-0.529 m/s; 95% CI: -0.946 to -0.112; p = 0.014). Females benefited from switching more than males did in every between-group comparison. Those who complied best with EC switch demonstrated the largest improvement. There was no difference in vascular effects between EC with and without nicotine within the study timeframe. CONCLUSIONS:TC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use [VESUVIUS]; NCT02878421; ISRCTN59133298).
| S-EPMC6928567 | biostudies-literature
Project description:IntroductionMost e-cigarettes contain highly addictive nicotine. This study assessed trends in nicotine strength in e-cigarettes sold in the United States during January 2017-March 2022.Aims and methodsWe obtained January 2017-March 2022 national retail e-cigarette sales data from NielsenIQ. We assessed monthly average nicotine strength overall, by e-cigarette product and flavor type, and manufacturer. A Joinpoint regression model assessed the magnitude and significance of changes in nicotine strength.ResultsDuring January 2017-March 2022, monthly average nicotine strength of e-cigarette products increased from 2.5% to 4.4%, an average of 0.8% per month (p < .001). Monthly average nicotine strength of disposable e-cigarettes increased the most (average monthly percentage change [AMPC] = 1.26%, p < .001) as compared to prefilled pods (AMPC = 0.6%, p < .001) and e-liquids (AMPC = 0.5%, p = .218). Monthly average nicotine strength for all flavors of e-cigarette products increased except for mint-flavored products. Increases were greatest for beverage-flavored products (AMPC = 2.1%, p < .001), followed by menthol-flavored products (AMPC = 1.2%, p < .001). Among the top 10 e-cigarette manufacturers assessed, monthly average nicotine strength decreased for Juul Labs products from 5% to 4.7% (AMPC = -0.1%, p < .001) but increased significantly for five manufacturers' products and remained unchanged at 5%-6% for four manufacturers' products.ConclusionsMonthly average nicotine strength of e-cigarette products increased overall, for most product and flavor types, and for some manufacturers in the United States during the study period. Imposing maximum limits on nicotine strength of e-cigarettes together with other evidence-based tobacco control strategies can help reduce the use of e-cigarettes among youth and increase tobacco product cessation among adults.ImplicationsFrom January 2017 to March 2022, the monthly average nicotine strength of disposable e-cigarettes increased substantially and exceeded prefilled pods since May 2020. E-cigarettes with menthol flavor and youth-appealing flavors, like fruit, also had sharp increases in monthly average nicotine strength. Among the top 10 e-cigarette manufacturers, monthly average nicotine strength increased or remained unchanged at a high nicotine level for all manufacturers' products, except Juul Lab's products. Comprehensive strategies including restricting sales of all flavored e-cigarettes, restricting youth tobacco product access, and imposing maximum limits on nicotine strength may help reduce youth e-cigarette use and increase tobacco cessation.
| S-EPMC10461184 | biostudies-literature
Project description:IntroductionNicotine can robustly increase responding for conditioned reinforcers (CRs), stimuli that acquire reinforcing properties based on association with primary reinforcers. Menthol and licorice are tobacco flavoring agents also found in sweet foods (eg, candy and ice cream), making them putative CRs before they are consumed in tobacco. We sought to determine if intravenous self-administration (IVSA) of nicotine was enhanced by the inclusion of oral tobacco flavor CRs.MethodsMenthol (160 or 320 µM) or licorice root extract (0.1% or 1%) were established as CRs (paired with 20% sucrose) or "neutral" stimuli (paired with water) in separate groups. During subsequent IVSA tests, nicotine was delivered in conjunction with oral presentations of the CR.ResultsIn experiment 1, a menthol CR significantly shifted the peak nicotine dose from 15 µg/kg/infusion (Neutral group) to 3.25 µg/kg/infusion (CR group). In experiment 2, a menthol CR significantly increased operant licks for nicotine (3 µg/kg/infusion) relative to control groups. In experiment 3, both licorice and menthol CRs significantly increased operant licks for nicotine (7.5 µg/kg/infusion) relative to an "inactive" sipper. The licorice CR increased nicotine IVSA in proportion to the strength of the flavor, but both menthol concentrations increased nicotine IVSA to a similar extent.ConclusionTobacco flavor additives with conditioned reinforcing properties promote acquisition of nicotine self-administration at low unit doses and may have robust impact on tobacco consumption when nicotine yield is low.ImplicationsTobacco flavor additives are found in rewarding foods (eg, ice cream) and gain palatability based on associations with primary rewards (eg, sugar) making them "conditioned reinforcers." Nicotine increases the motivation for flavor conditioned reinforcers and the present studies show that tobacco flavor additives can interact with nicotine to promote more nicotine self-administration. The interaction between flavors additives and nicotine may promote nicotine exposure and subsequently dependence.
| S-EPMC7297109 | biostudies-literature
Project description:BackgroundElectronic cigarette (e-cig) vaping has increased in the past decade in the US, and e-cig use is misleadingly marketed as a safe cessation for quitting smoking. The main constituents in e-liquid are humectants, such as propylene glycol (PG) and vegetable glycerine (VG), but different flavoring chemicals are also used. However, the toxicology profile of flavored e-cigs in the pulmonary tract is lacking. We hypothesized that menthol and tobacco-flavored e-cig (nicotine-free) exposure results in inflammatory responses and dysregulated repair in lung fibroblast and epithelium.MethodWe exposed lung fibroblast (HFL-1) and epithelium (BEAS-2B) to Air, PG/VG, menthol flavored, or tobacco-flavored e-cig, and determined the cytotoxicity, inflammation, and wound healing ability in 2D cells and 3D microtissue chip models.ResultsAfter exposure, HFL-1 showed decreased cell number with increased IL-8 levels in the tobacco flavor group compared to air. BEAS-2B also showed increased IL-8 secretion after PG/VG and tobacco flavor exposure, while menthol flavor exposure showed no change. Both menthol and tobacco-flavored e-cig exposure showed decreased protein abundance of type 1 collagen α 1 (COL1A1), α-smooth-muscle actin (αSMA), and fibronectin as well as decreased gene expression level of αSMA (Acta2) in HFL-1. After tobacco flavor e-cig exposure, HFL-1 mediated wound healing and tissue contractility were inhibited. Furthermore, BEAS-2B exposed to menthol flavor showed significantly decreased tight junction gene expressions, such as CDH1, OCLN, and TJP1.ConclusionOverall, tobacco-flavored e-cig exposure induces inflammation in both epithelium and fibroblasts, and tobacco-flavored e-cig inhibits wound healing ability in fibroblasts.
| S-EPMC10777495 | biostudies-literature
Project description:ImportanceUse of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product users.ObjectivesTo estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users.Design, setting, and participantsA population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N = 5105).ExposuresThe primary exposure was tobacco use, including current exclusive e-cigarette users (n = 247), current exclusive cigarette smokers (n = 2411), and users of both products (dual users) (n = 792) compared with never tobacco users (n = 1655).Main outcomes and measuresGeometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs).ResultsOf the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure.Conclusions and relevanceExclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.
| S-EPMC6324349 | biostudies-literature
Project description:Electronic nicotine delivery systems (ENDS) are rapidly increasing in popularity due to the perception that they may represent a safe alternative to conventional cigarettes. However, a growing body of evidence indicates that ENDS exposure can disrupt maintenance of pulmonary immune homeostasis and antimicrobial immunity. In this issue of the JCI, Madison et al. demonstrate that in mice, chronic ENDS exposure induces profound alterations in lipid homeostasis. ENDS-exposed mice showed irregularities in the surfactant-secreting lamellar bodies within type 2 alveolar cells and increased intracellular phospholipid accumulation within alveolar macrophages. Moreover, ENDS-exposed mice displayed greater inflammation and tissue damage in response to influenza A, which may be due to downregulated expression of a viral pattern-recognition receptor in alveolar macrophages. Collectively, the results of this study identify previously unrecognized adverse effects of ENDS exposure on pulmonary lipid metabolism, although the implication of these effects on long-term respiratory health requires future exploration.
| S-EPMC6763218 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:Electronic cigarettes (e-cigarettes) are a recent technology that has gained rapid acceptance. Still, little is known about them in terms of safety and effectiveness. A basic question is how effectively they deliver nicotine; however, the literature is surprisingly unclear on this point. Here, a population pharmacokinetic model was developed for nicotine and its major metabolite cotinine with the aim to provide a reliable framework for the simulation of nicotine and cotinine concentrations over time, based solely on inhalation airflow recordings and individual covariates [i.e., weight and breath carbon monoxide (CO) levels]. METHODS:This study included ten adults self-identified as heavy smokers (at least one pack of cigarettes per day). Plasma nicotine and cotinine concentrations were measured at regular 10-min intervals for 90 min while human subjects inhaled nicotine vapor from a modified e-cigarette. Airflow measurements were recorded every 200 ms throughout the session. A population pharmacokinetic model for nicotine and cotinine was developed based on previously published pharmacokinetic parameters and the airflow recordings. All of the analyses were performed with the non-linear mixed-effect modeling software NONMEM(®) version 7.2. RESULTS:The results show that e-cigarettes deliver nicotine effectively, although the pharmacokinetic profiles are lower than those achieved with regular cigarettes. Our pharmacokinetic model effectively predicts plasma nicotine and cotinine concentrations from the inhalation volume, and initial breath CO. CONCLUSION:E-cigarettes are effective at delivering nicotine. This new pharmacokinetic model of e-cigarette usage might be used for pharmacodynamic analysis where the pharmacokinetic profiles are not available.
| S-EPMC4450108 | biostudies-literature