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Am J Respir Crit Care Med. 2019 Jun 7. doi: 10.1164/rccm.201811-2087OC. [Epub ahead of print]

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

Author information

1
University of Kansas Medical Center Department of Internal Medicine, 189695, Pulmonary and Critical Care Medicine, Kansas City, Kansas, United States.
2
University of Miami School of Medicine, 12235, Division of Pulmonary, Critical Care, and Sleep Medicine, Miami, Florida, United States.
3
University of Miami School of Medicine, 12235, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Miami, Florida, United States.
4
Mount Sinai Medical Center, 5258, Miami Beach, Florida, United States.
5
University of Miami School of Medicine, 12235, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Miami, Florida, United States ; msalathe@kumc.edu.

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 nicotine-dependent 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 nicotine effect on mucociliary function is mediated by TRPA1 and not nicotinic acetylcholine receptors.

KEYWORDS:

Airway Epithelium; Electronic Nicotine Delivery Systems; Mucociliary Transport; Mucus; TRPA1

PMID:
31170808
DOI:
10.1164/rccm.201811-2087OC

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