Dataset Information

Tobacco and menthol flavored nicotine-free electronic cigarettes induced inflammation and dysregulated repair in lung fibroblast and epithelium.

ABSTRACT:

Background

Electronic 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.

Method

We 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.

Results

After 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.

Conclusion

Overall, tobacco-flavored e-cig exposure induces inflammation in both epithelium and fibroblasts, and tobacco-flavored e-cig inhibits wound healing ability in fibroblasts.

SUBMITTER: Wang Q

PROVIDER: S-EPMC10777495 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Tobacco and menthol flavored nicotine-free electronic cigarettes induced inflammation and dysregulated repair in lung fibroblast and epithelium.

Wang Qixin Q Lucas Joseph H JH Pang Cortney C Zhao Ruogang R Rahman Irfan I

Respiratory research 20240110 1

<h4>Background</h4>Electronic 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) exp ...[more]

PMID: 38200492

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Project description:IntroductionIQOS was authorized by the U.S. Food and Drug Administration (FDA) as a modified-risk tobacco product. We conducted a pharmacokinetic study evaluating the nicotine delivery and subjective effects of IQOS use among current menthol cigarette smokers to better understand if IQOS is an acceptable cigarette alternative in light of the proposed menthol cigarette ban.Aims and methodsParticipants were adult smokers of >4 menthol cigarettes per day. After 14-hour nicotine abstinence, participants were provided an IQOS device and menthol heatstick to puff every 20 seconds for a total of 14 puffs. Blood samples were collected at baseline and during active use to calculate nicotine boost from baseline to peak concentration. Nicotine withdrawal symptoms were collected before and after IQOS use. In addition, a modified Product Evaluation Scale for IQOS was collected after use.ResultsParticipants (n = 8) were a mean age of 43.9 years, 63% were female, 88% identified as White, and they smoked a mean of 17.1 menthol cigarettes per day. After IQOS use, the mean nicotine boost obtained was 15.96 ng/mL (SD = 6.91) (range 9.31 to 30.55 ng/mL). Most (75%) participants reported enjoying use of the product "a lot" or greater and more than half (62.5%) reported reduced cigarette cravings. Most participants reported no side effects after use; however, two experienced dry mouth, three experienced dizziness, one experienced throat irritation, and one experienced headache.ConclusionWe found that directed use (14 puffs) of menthol IQOS delivered a mean nicotine boost of 15.96 ng/mL which reduced craving for a cigarette. The majority of participants enjoyed use of IQOS and reported mild side effects.ImplicationsMenthol IQOS delivered a sufficient dose of nicotine perceived as satisfying by menthol cigarette smokers and it reduced craving with mild side effects. Menthol IQOS has potential to serve as a less harmful alternative for menthol cigarette smokers. The availability of modified risk products like IQOS should be considered by FDA's Comprehensive Plan for Tobacco and Nicotine Regulation.

Project description:BackgroundSweet/fruit disposable e-cigarettes (ECs) are cheap, easy to use, and look like inconspicuous colored markers, which encourages young people and young adults to use them. This work attempts to summarize current knowledge about the effect of sweet/fruit-flavor disposable ECs on early nicotine initiation.MethodsThe literature search was performed in June 2024 in Pub Med, Scopus, Web of Science and Science Direct databases by the terms 'ends', 'electronic nicotine delivery system', 'disposable electronic cigarette', 'disposable e-cigarette', 'cig-a-like e-cigarette', 'cig-a-like electronic cigarette', 'nicotine initiation'.ResultsThis systematic review analyzes findings from four heterogenous US studies. All analyzed studies highlighted that sweet/fruit-flavored ECs, compared to mint/menthol- or tobacco-flavors, were the most commonly chosen by youths and young adults during initiation and progression of vaping, regardless of the device type. Furthermore, two studies determined that never-smokers mostly start vaping by using modifiable ECs compared to disposable EC devices. Moreover, all studies showed that initiation by using disposable ECs was lower in people who had never previously vaped or smoked compared to current/former ECs users and former tobacco cigarettes (TCs) smokers or dual users.ConclusionsDue to limited number of studies, their limited location, scope (mostly ever users aged ≥ 18), and moderate quality of the studies, it is difficult to clearly determine the effect of sweet/fruit-flavored disposable ECs on early nicotine initiation. Moreover, it is difficult to determine if sweet/fruit-flavored disposable EC have a role in the avoiding the initiation of tobacco cigarettes or delaying the initiation by the effect of competition. The findings from this systematic review are preliminary and require validation through high-quality, global studies among youth and young adult never-smokers/never-vapers who initiated using tobacco products with sweet/fruit-flavored disposable ECs and continue vaping and/or smoking any tobacco products (and any flavors).Trial registrationThe study protocol of this systematic review was registered in International Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42024585153.

Project description:IntroductionA ban on menthol cigarettes and flavored cigars may reduce smoking and tobacco-related disparities.Aims and methodsWe aimed to examine the response of current smokers to a hypothetical ban on menthol cigarettes and flavored cigars. Current smokers were recruited online and reported the alternative products that they may switch to under a hypothetical ban, if they would try to obtain the banned products from illicit channels, and their support to the ban.Results51% of current smokers would use nonflavored cigarettes and cigars as alternatives, 45% would switch to flavored heated tobacco products or e-cigarettes or quit smoking. 17% would try to obtain the banned flavored products from illicit markets. A majority of menthol only smokers opposed the ban. Daily smokers would be more likely to switch to nonflavored smoking, to try illicit market products, and were less supportive of the ban. Black smokers would be less likely to switch to nonflavored smoking and were more supportive of the ban. Smokers who used menthol cigarettes only would be more likely to switch to nonflavored smoking, less likely to try illicit market sellers, and were the least supportive of the ban.ConclusionsIn response to a ban of all added flavors for cigarettes or cigars, nearly half of the current smokers would quit smoking, largely by switching to nonsmoking products. However, smokers with more chronic use and those who used only menthol cigarettes would be more likely to switch to nonflavored smoking, diminishing the harm reduction potential. The ban may decrease the relatively higher prevalence of menthol cigarette smoking among Blacks compared with other groups.ImplicationsA ban on the sale of menthol cigarettes and flavored cigars may decrease the prevalence of smoking because some current smokers may quit smoking and switch to nonsmoking products. However, smokers with more chronic use and those who used menthol cigarettes only were more likely to switch to nonflavored cigarettes or cigars, diminishing the harm reduction potential of the ban. Black smokers would be more likely to switch to products other than cigarettes and cigars thus decreasing their relatively higher prevalence of smoking compared with other groups.

Project description:Background and objectivesFlavored non-tobacco oral nicotine products (eg, nicotine pouches and nontherapeutic nicotine gum, lozenges, tablets, gummies), are increasingly marketed in the United States. Prevalence of non-tobacco oral nicotine product use among adolescents is unknown.MethodsWe calculated prevalence of ever and past 6-month use of nicotine pouches, other non-tobacco oral nicotine products (ie, gum, lozenges, tablets, and/or gummies), e-cigarettes, cigarettes, hookah or waterpipe, cigars, cigarillos, and snus among high school students in Southern California between September and December 2021. Generalized linear mixed models tested associations of sociodemographic factors and tobacco-product use with use of any non-tobacco oral nicotine product.ResultsAmong the sample (n = 3516), prevalence was highest for e-cigarettes (ever: 9.6%, past 6-month: 5.5%), followed by non-tobacco oral nicotine products (ever: 3.4%, past 6-month: 1.7%), and <1% for other products. Ever users of combustible tobacco (adjusted odds ratio [aOR] = 77.6; 95% confidence interval [CI] = 39.7-152) and ever users of noncombustible tobacco (aOR = 40.4; 95% CI= 24.3-67.0) had higher odds of ever using non-tobacco oral nicotine products, compared to never users of combustible and noncombustible tobacco. Use of any non-tobacco oral nicotine product was greater for Hispanic (versus all other races/ethnicities except Asian, aOR = 2.58; 95% CI = 1.36-4.87), sexual minority (versus heterosexual, aOR=1.63; 95% CI = 1.03-2.57), gender minority (versus male, aOR = 2.83; 95% CI = 1.29-6.19), and female (versus male, aOR=1.92, 95% CI = 1.20-3.06) participants.ConclusionsNon-tobacco oral nicotine products were the second most prevalent nicotine product used by adolescents. They were disproportionately used by certain racial or ethnic, sexual, or gender minority groups, and those with a history of nicotine use. Adolescent non-tobacco oral nicotine product use surveillance should be a public health priority.

Project description:Electronic cigarettes (e-cigarettes) are the most widely used electronic nicotine delivery systems and are designed to imitate smoking and aid in smoking cessation. Although the number of e-cigarette users is increasing rapidly, especially among young adults and adolescents, the potential health impacts and biologic effects of e-cigarettes still need to be elucidated. Our previous study demonstrated the cytotoxic effects of electronic liquids (e-liquids) in a human middle ear epithelial cell (HMEEC-1) line, which were affected by the manufacturer and flavoring agents regardless of the presence of nicotine. In this study, we aimed to evaluate the gene expression profile and identify potential molecular modulator genes and pathways in HMEEC-1 exposed to two different e-liquids (tobacco- and menthol-flavored). HMEEC-1 was exposed to e-liquids, and RNA sequencing, functional analysis, and pathway analysis were conducted to identify the resultant transcriptomic changes. A total of 843 genes were differentially expressed following exposure to the tobacco-flavored e-liquid, among which 262 genes were upregulated and 581 were downregulated. Upon exposure to the menthol-flavored e-liquid, a total of 589 genes were differentially expressed, among which 228 genes were upregulated and 361 were downregulated. Among the signaling pathways associated with the differentially expressed genes mediated by tobacco-flavored e-liquid exposure, several key molecular genes were identified, including IL6 (interleukin 6), PTGS2 (prostaglandin-endoperoxide synthase 2), CXCL8 (C-X-C motif chemokine ligand 8), JUN (Jun proto-oncogene), FOS (Fos proto-oncogene), and TP53 (tumor protein 53). Under menthol-flavored e-liquid treatment, MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), MYC (MYC proto-oncogene, bHLH transcription factor), HMOX1 (heme oxygenase 1), NOS3 (nitric oxide synthase 3), and CAV1 (caveolin 1) were predicted as key genes. In addition, we identified related cellular processes, including inflammatory responses, oxidative stress and carcinogenesis, under exposure to tobacco- and menthol-flavored e-liquids. We identified differentially expressed genes and related cellular processes and gene signaling pathways after e-cigarette exposure in human middle ear cells. These findings may provide useful evidence for understanding the effect of e-cigarette exposure.

Dataset Information

Tobacco and menthol flavored nicotine-free electronic cigarettes induced inflammation and dysregulated repair in lung fibroblast and epithelium.

Background

Method

Results

Conclusion

Publications

Tobacco and menthol flavored nicotine-free electronic cigarettes induced inflammation and dysregulated repair in lung fibroblast and epithelium.

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