Journal Article

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial

Dhingra, Radhika, Noah, Terry L., Hoffman, Jessica R., Jaspers, Ilona, Glista-Baker, Ellen, Robinette, Carole, Duffney, Parker F., Speen, Adam M., Pawlak, Erica A., Rebuli, Meghan E.

2021

Overview

Inhalation of tobacco smoke has been linked to increased risk of viral infection, such as influenza. Inhalation of electronic-cigarette (e-cigarette) aerosol has also recently been linked to immune suppression within the respiratory tract, specifically the nasal mucosa. We propose that changes in the nasal mucosal immune response modify antiviral host-defense responses in e-cigarette users. Nonsmokers, cigarette smokers, and e-cigarette users were inoculated with live-attenuated influenza virus (LAIV) to safely examine the innate immune response to influenza infection. Before and after LAIV inoculation, we collected nasal epithelial-lining fluid, nasal lavage fluid, nasal-scrape biopsy specimens, urine, and blood. Endpoints examined include cytokines and chemokines, influenza-specific IgA, immune-gene expression, and markers of viral load. Statistical analysis included primary comparisons of cigarette and e-cigarette groups with nonsmokers, as well as secondary analysis of demographic factors as potential modifiers. Markers of viral load did not differ among the three groups. Nasal-lavage-fluid anti-LAIV IgA levels increased in nonsmokers after LAIV inoculation but did not increase in e-cigarette users and cigarette smokers. LAIV-induced gene-expression changes in nasal biopsy specimens differed in cigarette smokers and e-cigarette users as compared with nonsmokers, with a greater number of genes changed in e-cigarette users, mostly resulting in decreased expression. The top downregulated genes in cigarette smokers were SMPD3, NOS2A, and KLRB1, and the top downregulated genes in e-cigarette users were MR1, NT5E, and HRAS. Similarly, LAIV-induced cytokine levels in nasal epithelial-lining fluid differed among the three groups, including decreased antiviral host-defense mediators (IFNγ, IL6, and IL12p40). We also detected that sex interacted with tobacco-product exposure to modify LAIV-induced immune-gene expression. Our results demonstrate that e-cigarette use altered nasal LAIV-induced immune responses, including gene expression, cytokine and chemokine release, and LAIV-specific IgA levels. Together, these data suggest that e-cigarette use induces changes in the nasal mucosa that are consistent with the potential for altered respiratory antiviral host-defense function. Clinical trial registered with www.clinicaltrials.gov (NCT 02019745).

• Publisher: Oxford University Press,American Thoracic Society
• Subject: Adult / Antiviral drugs / Biopsy / Chemokines / Cigarette smoking / Clinical trials / Cytokines / Cytokines - immunology / Down-regulation / Electronic cigarettes / Female / Gene expression / Humans / Immune response / Immune system / Immunity, Innate - drug effects / Immunity, Innate - immunology / Immunity, Mucosal - drug effects / Immunity, Mucosal - immunology / Immunoglobulin A / Inflammation - immunology / Inflammation - virology / Influenza / Influenza Vaccines - immunology / Influenza, Human - immunology / Influenza, Human - virology / Inhalation / Innate immunity / Inoculation / Male / Mucosal immunity / Nasal Lavage Fluid - immunology / Nasal Lavage Fluid - virology / Nasal Mucosa - drug effects / Nasal Mucosa - immunology / Original Research / Respiratory tract / Smoke - adverse effects / Smoking / Statistical analysis / Studies / Tobacco Products - adverse effects / Vaccines, Attenuated - immunology / Vaping / Vaping - adverse effects / Vaping - immunology / Viral infections / Young Adult / γ-Interferon