EFFECTS OF E-CIGARETTES AND THEIR COMPONENTS ON RESPIRATORY DYSFUNCTION, INFLAMMATION, AND REPAIR

EFFECTS OF E-CIGARETTES AND THEIR COMPONENTS ON RESPIRATORY DYSFUNCTION, INFLAMMATION, AND REPAIR

A4170 / 702 – Nasal Mucosal Immune Response to Infection with Live-Attenuated Influenza Virus (LAIV) Is Altered with Exposure to E-cigarettes and Cigarettes

 May 20, 2019, 2:15 PM – 4:15 PM

ParticipantM. E. Rebuli1, E. Glista-Baker2, A. M. Speen1, J. R. Hoffman3, P. F. Duffney1, E. Pawlak2, H. Dang4, A. Ghosh5, R. Tarran5, T. L. Noah6, I. Jaspers2;
1Curriculum in Toxicology & Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 2Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 3Curriculum for the Environment and Ecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 4Cystic Fibrosis and Pulmonary Diseases Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 5Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 6Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.AbstractIntroduction: Inhalation of tobacco smoke has been linked to an increased risk of viral infection, such as influenza, in humans. Inhalation of new and emerging tobacco products, such as e-cigarettes, has also recently been linked to immune suppression within the respiratory tract, specifically the nasal mucosa. We propose that innate immune suppression in the respiratory tract modifies antiviral host defense responses in e-cigarette users.
Methods: We used inoculation of human volunteers with live attenuated influenza virus (LAIV) to safely examine innate immune response to influenza infection. Subjects were categorized as non-smokers, cigarette smokers, and e-cigarette users based on self-reported tobacco product use, smoking/vaping diaries, and biomarkers of exposure to nicotine and tobacco products. Before and after LAIV, we collected epithelial lining fluid (ELF), nasal lavage fluid (NLF), nasal biopsies, and blood. Endpoints examined include cytokines/chemokines, influenza-specific IgA, influenza peptide cleavage activity, immune gene expression, and markers of viral replication.
Results: Response to LAIV differed in e-cigarette users and cigarette smokers as compared to non-smokers. At baseline in smokers, influenza peptide cleavage activity was increased, which correlated with increased levels of viral mRNA after LAIV, as compared to non-smokers. No difference was observed in e-cigarette users. However, IFNɣ pathway genes and proteins essential for innate immune cell recruitment and antiviral responses were suppressed in e-cigarette users and not in cigarette smokers, as compared to non-smokers. LAIV-induced NLF and ELF levels of IFNɣ and IFNɣ-inducible chemokines were suppressed after LAIV in e-cigarette users. IFNɣ antiviral response pathway genes were also suppressed after LAIV in e-cigarette users. Similarly, we found that e-cigarette users had lower levels of influenza-specific IgA compared to non-users while cigarette smokers had no difference in nasal IgA levels.
Conclusion: Together these data suggest that e-cigarette use and cigarette smoking differentially modify the respiratory antiviral host defense system. Specifically, in e-cigarette users, the IFNɣ antiviral pathway and influenza-specific IgA levels were reduced were significantly reduced following infection with LAIV. Considering the role of IFNɣ and downstream signaling molecules in recruitment and activation of lymphocytes, e-cigarette use may impair the adaptive antiviral immune response.
Disclaimer: Research reported in this abstract was in part supported by the NIH and the FDA Center for Tobacco Products (CTP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration. Funding sources: P50 HL12010004 and T32 ES00712634.

Source: AMERICAN THORACIC SOCIETY

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