E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion

Introduction:
This text discusses a study that aimed to determine the effects of e-cigarette use on the human airways. The study used induced sputum samples from cigarette smokers, e-cigarette users, and healthy never-smokers and compared them to validate the quantitative approach to identifying the effects on airways. The key points and main message of the study are summarized below.

Key Points:

* The study confirmed changes in the levels of numerous proteins that are established markers of cigarette smoke exposure, suggesting that e-cigarette exposure might be harmful for the lung as well.
* The elevated levels of markers known to be associated with cigarette smoke and lung disease/inflammation, such as thioredoxin and MMP9, in the sputum of both cigarette smokers and e-cigarette users indicates commonality in the impacts of these products on airway physiology.
* The levels of innate defense proteins, such as DMBTl, trefoil factor 3, lactoferrin, and LYSC, were observed to be increased in cigarette smokers but decreased in e-cigarette users, suggesting an altered innate immune response in the latter group.
* The sputum of e-cigarette users displayed a significant increase in calprotectin, coronin-1, and peptidylarginine deiminase 4, indicating increased NET formation in e-cigarette users' airways.
* Peripheral blood neutrophils isolated from e-cigarette users were significantly more susceptible to PMA-induced NET formation at 2 hours, suggesting systemic effects of e-cigarette use.
* The total mucin concentrations in sputum samples were significantly increased in cigarette smokers compared with nonsmokers, and MUCSAC concentrations were significantly increased in cigarette smokers and e-cigarette users compared with nonsmokers.
* The MUCSAC/MUC5B ratio was significantly increased in cigarette smokers and e-cigarette users compared with nonsmokers.

Main Message:
The study suggests that e-cigarette use alters the airway innate immune response, causing an increase in the release of neutrophil extracellular trap-associated proteins, proteins involved in maintaining the redox balance of the airways, and the ratio of the building blocks of airway mucus, namely, the mucins MUC5AC and MUC5B. The findings challenge the concept that e-cigarettes are a healthier alternative to cigarettes and suggest potential systemic harm beyond the lung. Further research is needed to elucidate the functional consequences of these alterations for the antibacterial and antioxidant defense mechanisms of the lung and their contributions to the pathogenesis of chronic lung diseases.

Reidel, Boris, Giorgia Radicioni, Phillip W. Clapp, Amina A. Ford, Sabri Abdelwahab, Meghan E. Rebuli, Prashamsha Haridass, Neil E. Alexis, Ilona Jaspers, and Mehmet Kesimer. “E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion.” American Journal of Respiratory and Critical Care Medicine 197, no. 4 (February 15, 2018): 492–501. https://doi.org/10.1164/rccm.201708-1590OC.