E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion

Reidel, Boris; Radicioni, Giorgia; Clapp, Phillip W.; Ford, Amina A.; Abdelwahab, Sabri H.; Rebuli, Meghan E.; Haridass, Prashamsha; Alexis, Neil E.; Jaspers, Ilona; Kesımer, Mehmet

doi:10.1164/rccm.201708-1590oc

Cited by 301 publications

(294 citation statements)

References 51 publications

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“…3 However, while e-cigarettes are believed to be less harmful to health than tobacco cigarettes, e-cigarettes are not harmless to users and recent evidence suggests that e-cigarettes could be more harmful than initially believed. For example, e-cigarette ingredients may cause cancer (Yu et al, 2016) and serious problems with lung function (Reidel et al, 2017). Moreover, e-cigarette use is linked with a range of adverse health outcomes such as coughing, nausea, chest pain, and increased blood pressure 4 (Grana, Benowitz, & Glantz, 2014;Orellana-barrios, Payne, Mulkey, & Nugent, 2015).…”

Section: Controversy Surrounding E-cigarette Use and Public Healthmentioning

confidence: 99%

What factors predict the passage of state‐level e‐cigarette regulations?

et al. 2018

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E-cigarettes are controversial products. They may help addicted smokers to consume nicotine in a less harmful manner or to quit tobacco cigarettes entirely, but these products may also entice youth into smoking. This controversy complicates e-cigarette regulation as any regulation may lead to health improvements for some populations, and health declines for other populations. Using data from 2007 to 2016, we examine factors that are plausibly linked with U.S. state e-cigarette regulations. We find that less conservative states are more likely to regulate e-cigarettes and that states with stronger tobacco lobbies are less likely to regulate e-cigarettes. This information can help policymakers as they determine how best to promote public health through regulation.

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Section: Controversy Surrounding E-cigarette Use and Public Healthmentioning

confidence: 99%

What factors predict the passage of state‐level e‐cigarette regulations?

et al. 2018

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“…Between factors such as wattage settings for the heating element, PG/VG composition, and a user's experience with a device, a single session of inhaled vape can deliver nicotine doses that exceed those in smoke from 1 cigarette (8). Furthermore, recent efforts have partially demonstrated how PG/VG and various e-cig flavorings cause negative outcomes in vitro and in vivo such as cell death, airway inflammation, and impaired airway hydration (9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

Chung

Baumlin

Dennis

et al. 2019

Am J Respir Crit Care Med

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of Health (NIH) -F32-HL140729 (to S.C.) and R01 HL139365 (to M.S.) RUNNING TITLE: Vaped nicotine impairs mucociliary function preferentially via TRPA1 SUBJECT CATEGORY DESCRIPTOR: 6.17 Smoking Health Effects TOTAL WORD COUNT: 3985 AT A GLANCE COMMENTARY: Scientific Knowledge on the Subject E-cigarettes are marketed as safer alternatives to conventional cigarettes due to their defined composition and noncombustible nature. However, it is unclear how exposure to e-cigarette vapor, colloquially referred to as "vape", affects naïve airway epithelia. It is largely unknown to what extent individual constituents of vape, such as nicotine and flavoring agents, influence pulmonary function, if at all. The transient receptor potential ankyrin 1 (TRPA1) is a molecular target for vape effects due to its expression in airway epithelia and its reported gating by nicotine, reactive oxidants, and flavors, especially cinnamaldehyde. What This Study Adds to the FieldThis study implicates nicotine as a key "vape" constituent that acutely impairs airway mucociliary functions in vitro and in vivo (sheep). A functional, nicotine-sensitive TRPA1 receptor is natively expressed in human and sheep bronchial epithelial cells and mediates the effects of nicotine and e-cigarette vapors. Importantly, its inhibition prevents mucociliary dysfunction in vitro and in vivo. These findings implicate TRPA1 as a driver of mucociliary dysfunction induced by nicotine-containing e-cigarette vapor.ABSTRACT RATIONALE: Electronic cigarette (e-cig) use has been widely adopted under the perception of safety. However, possibly adverse effects of e-cig vapor in never-smokers are not well understood. OBJECTIVES:Effects of nicotine-containing e-cig vapors on airway mucociliary function were tested in differentiated human bronchial epithelial cells (HBECs) isolated from never-smokers and in the airways of a novel, ovine large animal model. METHODS:Mucociliary parameters were measured in HBECs and in sheep. Systemic nicotine delivery to sheep was quantified using plasma cotinine levels, measured by ELISA. MEASUREMENTS AND MAIN RESULTS:In vitro, exposure to e-cig vapor reduced airway surface liquid hydration and increased mucus viscosity of HBECs in a nicotinedependent manner. Acute nicotine exposure increased intracellular calcium levels, an effect primarily dependent on transient receptor potential ankyrin 1 (TRPA1). TRPA1 inhibition with A967079 restored nicotine-mediated impairment of mucociliary parameters including mucus transport in vitro. Sheep tracheal mucus velocity (TMV), an in vivo measure of mucociliary clearance, was also reduced by e-cig vapor. Nebulized e-cig liquid containing nicotine also reduced TMV in a dose-dependent manner and elevated plasma cotinine levels. Importantly, nebulized A967079 reversed the effects of e-cig liquid on sheep TMV. CONCLUSIONS:Our findings show that inhalation of e-cig vapor causes airway mucociliary dysfunction in vitro and in vivo. Furthermore, they suggest that the main Page 4 of 64 2 nicotine effect on mucociliary ...

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“…Such a pattern would indicate a potential for e-cigarettes to narrow inequalities in smoking (and therefore health). However, vaping instead of smoking could still carry some residual health risk [35] relative to using neither, so socioeconomic patterning of vaping among ex-smokers, may still represent some residual potential to widen health inequalities.…”

Section: Introductionmentioning

confidence: 99%

Socioeconomic patterning of vaping by smoking status among UK adults and youth

et al. 2020

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Background:Smoking contributes significantly to socioeconomic health inequalities. Vaping has captured much interest as a less harmful alternative to smoking, but may be harmful relative to non-smoking. Examining inequalities in vaping by smoking status, may offer insights into potential impacts of vaping on socioeconomic inequalities in health. Methods: Data were from 3291 youth (aged 10-15) and 35,367 adults (aged 16+) from wave 7 (2015-17) of the UK Household Longitudinal Study. In order to adjust for biases that could be introduced by stratifying on smoking status, marginal structural models were used to estimate controlled direct effects of an index of socioeconomic disadvantage (incorporating household education, occupation and income) on vaping by smoking status (among adults and youth), adjusting for relevant confounders and for selection into smoking states. We also estimated controlled direct effects of socioeconomic disadvantage on being an ex-smoker by vaping status (among adult ever-smokers; n = 18,128). Results: Socioeconomic disadvantage was associated with vaping among never smoking youth (OR for a unit increase in the socioeconomic index: 1.17; 95%: 1.03-1.34), and among ex-smoking adults (OR: 1.17; 95% CI: 1.09-1.26), with little to no association among never smoking (OR: 0.98; 95% CI: 0.91-1.07) and current smoking (OR: 1.00; 95% CI: 0.93-1.07) adults. Socioeconomic disadvantage was also associated with reduced odds of being an exsmoker among adult ever-smokers, but this association was moderately weaker among those who vaped (OR: 0.88; 95% CI: 0.82-0.95) than those who did not (OR: 0.82; 95% CI: 0.80-0.84; p-value for difference = 0.081). Conclusions: Inequalities in vaping among never smoking youth and adult ex-smokers, suggest potential to widen health inequalities, while weaker inequalities in smoking cessation among adult vapers indicate e-cigarettes could help narrow inequalities. Further research is needed to understand the balance of these opposing potential impacts, and how any benefits can be maximised whilst protecting the vulnerable.

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E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion

Abstract: Together, our results indicate that e-cigarette use alters the profile of innate defense proteins in airway secretions, inducing similar and unique changes relative to cigarette smoking. These data challenge the concept that e-cigarettes are a healthier alternative to cigarettes.

Cited by 301 publications

References 51 publications

What factors predict the passage of state‐level e‐cigarette regulations?

What factors predict the passage of state‐level e‐cigarette regulations?

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

Socioeconomic patterning of vaping by smoking status among UK adults and youth

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