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E-cigarette nicotine may impede airway mucus clearance

Exposure to nicotine in vapor from electronic cigarettes appears to contribute to mucociliary dysfunction that is often seen with respiratory diseases such as COPD and asthma, according to in vitro and in vivo data published in the American Journal of Respiratory and Critical Care Medicine.

Matthias Salathe, MD, Peter T. Bohan Professor and Chair of the department of internal medicine and associate director of the Adult Cystic Fibrosis Center at the University of Kansas Medical Center, and colleagues performed the study to “see whether e-cigarettes have the same detrimental effects like tobacco on the clearing mechanisms of the airways (also called mucociliary clearance as part of the innate defense system),” Salathe told Healio Pulmonology.

For the in vitro component of the study, the researchers exposed differentiated human bronchial epithelial cells isolated from de-identified donor lungs of 18 men (mean age, 26 years) and 13 women (mean age, 25.5 years) who never smoked to e-cigarette vapor. Using the researchers’ delivery method, the e-cigarette deposited the nicotine expected from 1-2 smoked cigarettes in the airway surface liquid.

Results showed that exposure to e-cigarette vapor containing nicotine vs. air or e-cigarette vapor containing no nicotine reduced airway surface liquid hydration and increased mucus viscosity of the human bronchial epithelial cells. Nicotine exposure also increased intracellular calcium levels through transient receptor potential ankyrin 1 (TRPA1). TRPA1 inhibition with A967079, however, mitigated the adverse effects of nicotine.

“We suspected that e-cigarettes have detrimental effects, but this was the first proof. Mechanism through a special receptor (TRPA1) rather than nicotinic receptors was unexpected,” Salathe wrote in an email to Healio Pulmonology.

The researchers reported comparable results in vivo in sheep. Exposure to e-cigarette vapor reduced sheep’s tracheal mucus velocity, a measure of mucociliary clearance, and nebulized e-cigarette liquid containing nicotine reduced tracheal mucus velocity in a dose-dependent manner. Plasma cotinine levels showed that the exposure was similar to two smoked cigarettes.  Similar to the in vitro experiments, the effects of e-cigarette liquid were reversed with nebulized A967079.  

These findings have prompted new questions that Salathe and colleagues would like to see studied further, Salathe said. For instance, they would like to assess how the components of e-cigarette liquid aside from nicotine.

“We need to examine now what propylene glycol and/or vegetable glycerin and e-cigarette flavors are doing,” he said.

Overall, the data indicate that e-cigarettes have the potential to cause harm and contradict certain claims made by others.

“E-cigarettes are not innocuous, as suggested by many. The detrimental effects on clearance of mucus from the airway can lead to cough productive of phlegm like tobacco cigarettes do,” Salathe told Healio Pulmonology. – by Melissa Foster

For more information:
Matthias Salathe, MD, can be reached at msalathe@kumc.edu.

Disclosure: The study was funded by the Flight Attendant Medical Research Institute, the James and Esther King Florida Biomedical Research Program and the NIH.