Nicotine aerosols diminish airway CFTR function and mucociliary clearance

Electronic cigarettes (e-cigs) are often promoted as safe alternatives to smoking based on the faulty perception that inhaling nic-otine is safe until other harmful chemicals in cigarette smoke are absent. Previously, others and we have reported that, similar to cigarette smoke, e-cig aerosols decrease CFTR-mediated ion transport across airway epithelium. However, it is unclear whether such defective epithelial ion transport by e-cig aerosols occurs in vivo and what the singular contribution of inhaled nicotine is to impairments in mucociliary clearance (MCC), the primary physiologic defense of the airways. Here, we tested the effects of nicotine aerosols from e-cigs in primary human bronchial epithelial (HBE) cells and two animal models, rats and ferrets, known for their increasing physiologic complexity and potential for clinical translation, followed by in vitro and in vivo electrophysiologic assays for CFTR activity and micro-optical coherence tomography (mu OCT) image analyses for alterations in airway mucus physiol-ogy. Data presented in this report indicate nicotine in e-cig aerosols causes 1) reduced CFTR and epithelial Na thorn channel (ENaC)-mediated ion transport, 2) delayed MCC, and 3) diminished airway surface hydration, as determined by periciliary liquid depth analysis. Interestingly, the common e-cig vehicles vegetable glycerin and propylene glycol did not affect CFTR function or MCC in vivo despite their significant adverse effects in vitro. Overall, our studies contribute to an improved understanding of inhaled nicotine effects on lung health among e-cig users and inform pathologic mechanisms involved in altered host defense and increased risk for tobacco-associated lung diseases.

Automated summary

Electronic cigarettes (e-cigs) are mistakenly believed to be a safe alternative to smoking, but research shows that e-cig aerosols containing nicotine reduce ion transport, delay mucociliary clearance (MCC), and decrease airway surface hydration. The effects were observed in human bronchial epithelial (HBE) cells, as well as in rats and ferrets. Surprisingly, e-cig vehicles such as vegetable glycerin and propylene glycol did not have the same adverse effects. This study provides insight into the negative effects of inhaled nicotine on lung health and the mechanisms behind tobacco-associated lung diseases.