Tobacco smoke exposure and altered nasal responses to live attenuated infuenza virus

Abstract

Background: Epidemiologic evidence links tobacco smoke and increased risk for infuenza in humans, but the specifc host defense pathways involved are unclear. oB je c t iv e: We developed a model to examine influenza-induced innate immune responses in humans and test the hypothesis that exposure to cigarette smoke alters nasal infammatory and antiviral responses to live attenuated infuenza virus (LAIV). Methods: Tis was an observational cohort study comparing nasal mucosal responses to LAIV among young adult active smokers (n = 17), nonsmokers exposed to secondhand smoke (SHS; n = 20), and unexposed controls (n = 23). Virus RNA and infammatory factors were measured in nasal lavage fuids (NLF) serially after LAIV inoculation. For key end points, peak and total (area under curve) responses were compared among groups. re su l t s: Compared with controls, NLF interleukin-6 (IL-6) responses to LAIV (peak and total) were suppressed in smokers. Virus RNA in NLF cells was signifcantly increased in smokers, as were interferon-inducible protein 10:virus ratios. Responses in SHS-exposed subjects were generally intermediate between controls and smokers. We observed signifcant associations between urine cotinine and NLF IL-6 responses (negative correlation) or virus RNA in NLF cells (positive correlation) for all subjects combined. co n c l u sio n s: Nasal inoculation with LAIV results in measurable inflammatory and antiviral responses in human volunteers, thus providing a model for investigating environmental efects on infuenza infections in humans. Exposure to cigarette smoke was associated with suppression of specifc nasal infammatory and antiviral responses, as well as increased virus quantity, after nasal inoculation with LAIV. Tese data suggest mechanisms for increased susceptibility to infuenza infection among persons exposed to tobacco smoke.