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Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial.
Am J Respir Cell Mol Biol. 2021 01; 64(1):126-137.AJ

Abstract

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 (NCT02019745).

Authors+Show Affiliations

Curriculum in Toxicology and Environmental Medicine. Center for Environmental Medicine, Asthma and Lung Biology, and. Department of Pediatrics, School of Medicine.Center for Environmental Medicine, Asthma and Lung Biology, and.Curriculum for the Environment and Ecology, College of Arts and Sciences.Curriculum in Toxicology and Environmental Medicine.Center for Environmental Medicine, Asthma and Lung Biology, and.Curriculum in Toxicology and Environmental Medicine.Center for Environmental Medicine, Asthma and Lung Biology, and.Institute for Environmental Health Solutions, and. Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.Center for Environmental Medicine, Asthma and Lung Biology, and. Department of Pediatrics, School of Medicine.Curriculum in Toxicology and Environmental Medicine. Center for Environmental Medicine, Asthma and Lung Biology, and. Department of Pediatrics, School of Medicine. Institute for Environmental Health Solutions, and.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33095645

Citation

Rebuli, Meghan E., et al. "Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. a Clinical Trial." American Journal of Respiratory Cell and Molecular Biology, vol. 64, no. 1, 2021, pp. 126-137.
Rebuli ME, Glista-Baker E, Hoffman JR, et al. Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial. Am J Respir Cell Mol Biol. 2021;64(1):126-137.
Rebuli, M. E., Glista-Baker, E., Hoffman, J. R., Duffney, P. F., Robinette, C., Speen, A. M., Pawlak, E. A., Dhingra, R., Noah, T. L., & Jaspers, I. (2021). Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial. American Journal of Respiratory Cell and Molecular Biology, 64(1), 126-137. https://doi.org/10.1165/rcmb.2020-0164OC
Rebuli ME, et al. Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. a Clinical Trial. Am J Respir Cell Mol Biol. 2021;64(1):126-137. PubMed PMID: 33095645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial. AU - Rebuli,Meghan E, AU - Glista-Baker,Ellen, AU - Hoffman,Jessica R, AU - Duffney,Parker F, AU - Robinette,Carole, AU - Speen,Adam M, AU - Pawlak,Erica A, AU - Dhingra,Radhika, AU - Noah,Terry L, AU - Jaspers,Ilona, PY - 2020/10/24/pubmed PY - 2021/2/2/medline PY - 2020/10/23/entrez KW - e-cigarette KW - immune KW - influenza KW - respiratory KW - virus SP - 126 EP - 137 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 64 IS - 1 N2 - 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 (NCT02019745). SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/33095645/Electronic_Cigarette_Use_Alters_Nasal_Mucosal_Immune_Response_to_Live_attenuated_Influenza_Virus__A_Clinical_Trial_ L2 - https://www.atsjournals.org/doi/10.1165/rcmb.2020-0164OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -