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Effects of environmental tobacco smoke on nasal responses to live attenuated influenza virus
NOAH, T., P. Murphy, W. Zhang, M. Herbst, AND I. JASPERS. Effects of environmental tobacco smoke on nasal responses to live attenuated influenza virus. Presented at American Thoracic Society Annual Meeting, Toronto, ON, CANADA, May 16 - 28, 2008.
Background: Published and preliminary data in our laboratory suggest that airborne pollutants including tobacco smoke increase susceptibility of respiratory epithelium to infection with influenza A. However, no studies have specifically looked at the interaction between tobacco smoke (TS) exposure and the effects of influenza virus in human volunteers. We hypothesize that exposure to TS results in increased susceptibility to infection with influenza virus and its effects in nasal epithelium in humans. Methods: This is a prospective, descriptive comparison of the effects of nasal inoculation of live attenuated influenza virus (LAIY) on viral replication and nasal inflammation, in healthy young adults who are not exposed to TS (control), vs. subjects actively or passively exposed to TS. Subjects are classified by smoking and TS exposure history, then undergo 3 baseline nasal lavages followed by administration of LAIV (FluMist®; MedImmune, used according to manufacturer's recommendations) and serial nasal lavages on days 1-4,9, and 21 post LAIV. Results: Urinary cotinine levels were significantly elevated in TS-exposed subjects (N = 8) compared to controls (N= 20). TS subjects had 7-fold higher peak viral hemagglutinin mRNA in NLF cells during days 1-4 post LAIV, compared to controls. Study groups had similar baseline NLF inflammatory markers, and both groups had transiently increased NLF inflammation (% neutrophils, cytokines) during days 1-4 following LAIV. However, TS subjects showed blunted responses compared to controls for change in % neutrophils from baseline (median increase TS = 24% vs. C =35%), and fold increase in cytokines IL-6 (median increase TS = 1.8x vs. C = 8.lx) and IP-10 (median increase TS = 3.3x vs. C = l6.0x). Conclusions: LAIV and serial sampling of nasal secretions can be used to safely and effectively investigate respiratory mucosal responses to viral infection in healthy human volunteers. LAIV replicates transiently and induces a measurable inflammatory response in the nasal passages. Preliminary results suggest that TS-exposed individuals have increased viral replication but blunted early inflammatory responses to virus. We speculate that chronic exposure to tobacco smoke or other oxidant agents induces alterations in susceptibility to viral infection, and in resulting host defense responses at the mucosal surface.