The Effects of Individual Components of E-Cigarettes on Ion Transport and Airway Surface Liquid Height in Human Bronchial Epithelial Cells.

Background and objectives: The rising popularity of new-generation electronic cigarettes (e-cig) like JUUL necessitates a better understanding of their impact on respiratory and other body systems, as the effects of JUUL's components remain unclear. This study aimed to investigate the effects of JUUL components on ion channels and airway surface liquid (ASL) height in human bronchial epithelial cells (HBECs). Furthermore, the cytotoxic effects of these components were investigated in human embryonic kidney 293T (HEK293T) cells.

Materials and methods: The components tested included nicotine salt (NicSalt), benzoic acid (BA), sodium hydrogen tartrate (NaTar), propylene glycol/vegetable glycerin (PG/VG), freebase nicotine (FBNic) and nicotine salt+benzoic acid (NicSalt+BA). Each component was prepared at 100 µM, and HBECs were exposed for 24 h to measure ASL height, short-circuit current (I_sc), and transepithelial electrical resistance (TEER).

Results: Initial exposure (0 h) to these substances did not significantly alter ASL height. However, after 2 h, FBNic-treated HBECs exhibited a significant reduction in ASL height compared to NicSalt and other tested substances, with the most pronounced decrease observed at the 6th hour. This effect persisted over prolonged exposure, suggesting a cumulative impact on airway hydration and epithelial function. Additionally, adenosine administration did not induce a significant increase in ASL height. NicSalt, BA, and FBNic were found to disrupt ion balance in HBECs, affecting ion channels and ASL homeostasis while significantly decreasing TEER. In terms of cytotoxicity, NicSalt, and benzoic acid demonstrated minimal cytotoxicity at low concentrations, whereas FBNic showed significantly higher cytotoxicity at moderate levels.

Conclusions: In conclusion, this study highlights that e-cigarette components can disrupt airway surface liquid homeostasis by affecting ion channel activity, compromise epithelial barrier integrity by reducing transepithelial electrical resistance, and emphasize the importance of their cytotoxic effects.