E-cigarette vaping with nicotine appears to hamper mucus clearance from the airways, according to a study (“Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors“) published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

A team of researchers from the University of Kansas, University of Miami, and Mt. Sinai Medical Center in Miami Beach reported that exposing human airway cells to e-cigarette vapor containing nicotine in culture resulted in a decreased ability to move mucus or phlegm across the surface. This phenomenon is called “mucociliary dysfunction.” The researchers report the same finding in vivo in sheep, whose airways mimic those of humans when exposed to e-cigarette vapor.

Electronic cigarette (e-cig) use has been widely adopted under the perception of safety. However, possible adverse effects of e-cig vapor in never-smokers are not well understood. 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,” the investigators wrote.

“Mucociliary parameters were measured in HBECs and in sheep. Systemic nicotine delivery to sheep was quantified using plasma cotinine levels, measured by ELISA. 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.

“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.”

“This study grew out of our team’s research on the influence of tobacco smoke on mucus clearance from the airways,” said senior author Matthias Salathe, MD, chair of internal medicine and a professor of pulmonary and critical care medicine at the University of Kansas Medical Center. “The question was whether vape containing nicotine had negative effects on the ability to clear secretions from the airways similar to tobacco smoke.”

Mucociliary dysfunction is a feature of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Specifically, the study found that vaping with nicotine impairs ciliary beat frequency, dehydrates airway fluid, and makes mucus more viscous or sticky. These changes make it more difficult for the bronchi, the main passageways to the lung, to defend themselves from infection and injury.

The researchers note that a recent report found that young e-cigarette users who never smoked were at increased risk to develop chronic bronchitis, a condition characterized by chronic production of phlegm that is also seen in tobacco smokers.

Salathe said the newly published data not only support the earlier clinical report but help explain it. A single session of vaping can deliver more nicotine to the airways than smoking one cigarette. Moreover, according to Salathe, absorption into the bloodstream is lower, possibly exposing the airways to high nicotine concentrations for prolonged periods of time.

The study also found that nicotine produced these negative effects by stimulating the ion channel transient receptor potential ankyrin 1 (TRPA1). Blocking TRPA1 reduced the effects of nicotine on clearance in both the human cells in culture and in the sheep.

“Vaping with nicotine is not harmless as commonly assumed by those who start vaping. At the very least, it increases the risk of chronic bronchitis,” Salathe said. “Our study, along with others, might even question e-cigarettes as a harm reduction approach for current smokers with respect to chronic bronchitis/COPD.”

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