Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes

Abstract

Background: Little is known about health risks associated with electronic cigarette (EC) use although EC are rising in popularity and have been advocated as a means to quit smoking cigarettes.

Methods: Ten never-smokers, without exposure history to tobacco products or EC, were assessed at baseline with questionnaire, chest X-ray, lung function, plasma levels of endothelial microparticles (EMP), and bronchoscopy to obtain small airway epithelium (SAE) and alveolar macrophages (AM). One week later, subjects inhaled 10 puffs of "Blu" brand EC, waited 30 min, then another 10 puff; n = 7 were randomized to EC with nicotine and n = 3 to EC without nicotine to assess biological responses in healthy, naive individuals.

Results: Two hr. post-EC exposure, subjects were again assessed as at baseline. No significant changes in clinical parameters were observed. Biological changes were observed compared to baseline, including altered transcriptomes of SAE and AM for all subjects and elevated plasma EMP levels following inhalation of EC with nicotine.

Conclusions: This study provides in vivo human data demonstrating that acute inhalation of EC aerosols dysregulates normal human lung homeostasis in a limited cohort of healthy naïve individuals. These observations have implications to new EC users, nonsmokers exposed to secondhand EC aerosols and cigarette smokers using EC to quit smoking.

Trial registration: ClinicalTrials.gov NCT01776398 (registered 10/12/12), NCT02188511 (registered 7/2/14).

Conflict of interest statement

Ethics approval and consent to participate

Weill Cornell Medicine (WCM) Institutional Review Board approved the protocols. Research subjects were evaluated and consented at the Weill Cornell Medical College Clinical Translational and Science Center and the Department of Genetic Medicine Clinical Research Facility.

IACUC approval not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Plasma endothelial microparticle levels. Shown are data at baseline and 1 week following acute E-cigarette exposure. a CD42b−CD31+ EMP levels of never-smokers who were exposed acutely to inhalation of EC without nicotine (n = 3). b CD42b−CD31+ EMP levels of never-smokers who were exposed to acute inhalation of EC with nicotine (n = 7). For all groups before and after, the %EMP that were ACE+ was 76 ± 6%. Data shown are the mean ± standard error of the mean; p values were determined using paired, two-tailed t-test

Fig. 2

Effect of acute E-cigarette aerosol inhalation on small airway epithelium genome-wide transcriptome profiles. a Volcano plot showing expression of all genes comparing baseline to post-EC exposure visit from SAE of never-smokers who were exposed to acute inhalation of EC with nicotine (n = 7 subjects). Significance determined by p value < 0.05 (horizontal dashed line) and fold-change of post-EC exposure to baseline > 1.5 (vertical dashed lines). b Hierarchical clustering of differentially expressed genes from SAE of never-smokers who were exposed to acute inhalation of EC with nicotine (n = 7 subjects). c Volcano plot showing expression of all genes comparing baseline to post-EC exposure visit from SAE of never-smokers who were exposed to acute inhalation of EC without nicotine (n = 3 subjects). Significance determined by p value < 0.05 (horizontal dashed line) and fold-change of post-EC exposure to baseline > 1.5 (vertical dashed lines). d Hierarchical clustering of differentially expressed genes from SAE of never-smokers who were exposed to acute inhalation of EC without nicotine (n = 3 subjects)

Fig. 3

Effect of acute E-cigarette aerosol inhalation on alveolar macrophage genome-wide transcriptome profiles. a Volcano plot showing expression of all genes comparing baseline to post-EC exposure visit from AM of never-smokers who were exposed to acute inhalation of EC with nicotine (n = 7 subjects). Significance determined by p value < 0.05 (horizontal dashed line) and fold-change of post-EC exposure to baseline > 1.5 (vertical dashed lines). b Hierarchical clustering of differentially expressed genes from AM of never-smokers who were exposed to acute inhalation of EC with nicotine (n = 7 subjects). c Volcano plot showing expression of all genes comparing baseline to post-EC exposure visit from AM of never-smokers who were exposed to acute inhalation of EC without nicotine (n = 3 subjects). Significance determined by p value < 0.05 (horizontal dashed line) and fold-change of post-EC exposure to baseline > 1.5 (vertical dashed lines). d Hierarchical clustering of differentially expressed genes from AM of never-smokers who were exposed to acute inhalation of EC without nicotine (n = 3 subjects)