Comparison of the impacts of an acute exposure to electronic cigarette aerosol and cigarette smoke on small airway epithelial cultures: In vitro systems toxicology assessment

      Iskandar, A. R.; Kondylis, A.; Martin, F.; Steiner, S.; Majeed, S.; Leroy, P.; Guedj, E.; Merg, C.; Trivedi, K.; Frentzel, S.; Ivanov, N. V.; Doshi, U.; Lee, K. M.; McKinney, W. J.; Peitsch, M. C.; Hoeng, J.

      Conference date
      Mar 12, 2019
      Conference name
      Society of Toxicology (SOT) 2019

      With increasing popularity of electronic cigarettes (ECs), it is important to assess the potential toxicity of EC aerosol exposure. In the context of a harm reduction approach, we examined the effects of whole EC aerosol exposure relative to the effects of mainstream cigarette smoke (CS) exposure using human organotypic small airway cultures. Cultures were exposed at the air-liquid interface to 112 puffs of either undiluted aerosols generated from a MarkTen® cartridge containing various eliquids (with aerosol formers alone (CARRIER), with 4% nicotine (BASE), with 4% nicotine and flavors “TEST” ) or to diluted CS, in Vitrocell® exposure systems. We conducted a series of independent exposure repetitions to strengthen the accuracy of the observation. Concentrations of the deposited nicotine and carbonyls in the exposure chamber were measured as markers of exposure. Biological endpoints investigated included histology, cytotoxicity, inflammatory mediators, and gene microarray. Alterations in morphology or cytotoxicity were not observed in small airway cultures exposed to undiluted EC aerosols despite resulting in higher nicotine deposition in the chamber than that found following CS exposure. Increased loss of cilia was recorded in cultures exposed to CS but not in cultures exposed to any EC aerosol. Media of cultures exposed to CS had numerous inflammatory mediators that were significantly altered in comparison to cultures exposed to EC aerosols. CS exposure also elicited a greater number of differentially expressed genes. Based on a network-based enrichment analysis, the transcriptome data showed that the exposures impacted different cellular processes (e.g., cell fate, proliferation, stress, and inflammatory response) with greater impacts following CS exposure than following EC aerosol exposure. These collective endpoints demonstrated that EC aerosols had significantly lower biological impact in small airway cultures, in comparison to CS exposure.