Exposure to e-cigarette vapor extract induces vocal fold epithelial injury and triggers intense mucosal remodeling.

Introduction:
This article presents a study on the effects of e-cigarette vapor extract (ECVE) on human engineered vocal fold (VF) mucosae. The study aimed to investigate the impact of ECVE on VF mucosal structure and function during exposure and subsequent VF mucosal regeneration. The larynx and VFs are involved in voice production and are directly exposed to inhaled vaporized e-liquids. VF epithelial cells are particularly vulnerable as they serve as the first line of defense against inorganic, organic, and microbial intruders and protect the VF lamina propria beneath. Disruption in the VF epithelial barrier can cause acute laryngeal inflammation and swelling of laryngeal structures, which can rapidly lead to life-threatening airway obstruction.

Key Points:

* The study utilized a three-dimensional (3D) model of human VF mucosa, which was exposed to 0.5% and 5% ECVE for 1 week.
* Exposure to ECVE induced cellular damage in VF apical epithelial cells, disrupting mucosal homeostasis and innate barrier function, and triggered epithelial remodeling during VF epithelial recovery.
* ECVE exposure affected compactness of apical epithelial cell layers and altered the expression of cytokeratin and E-cadherin.
* ECVE exposure led to increased expression of luminal MUC1 and the formation of mucus clots that can accumulate in the laryngeal/airway lumen and impair mucus clearance.
* Exposure to ECVE caused moderate VF mucosal inflammation, with significantly upregulated expression of BMP4 and BMP7 in the PG/VG group and with significant reduction of BMP4 and BMP7 in VF mucosae exposed to PG/VG+N and PG/VG+FN.
* ECVE exposure led to inefficient clearance of lipid/solvent particles that gather in the cytosol and intercellular spaces, causing chemical epithelial injury.
* Lipid particles can be derived from the nicotine and flavorings added to e-liquids to intensify the taste and/or enhance the vaping experience.

Main Message:
The study highlights the potential risks associated with e-cigarette use, particularly for the larynx and VFs. Exposure to ECVE disrupts VF mucosal homeostasis and innate barrier function, triggers epithelial remodeling, and causes moderate VF mucosal inflammation. The study also suggests that lipid particles derived from nicotine and flavorings added to e-liquids can cause chemical epithelial injury. These findings raise concerns about the safety of e-cigarette use and emphasize the need for further research to understand the long-term effects of ECVE on VF mucosal health.

Lungova V, Wendt K, Thibeault SL. Exposure to e-cigarette vapor extract induces vocal fold epithelial injury and triggers intense mucosal remodeling. Disease models & mechanisms. 2022;15(8). doi:10.1242/dmm.049476