Wood Smoke Exposure Alters Human Inflammatory Responses to Viral Infection in a Sex-Specific Manner. A Randomized, Placebo-controlled Study

Abstract

Rationale: Exposure to particulates from burning biomass is an increasing global health issue. Burning biomass, including wood smoke, is associated with increased lower respiratory infections. Objectives: To determine whether acute exposure to wood smoke modifies nasal inflammatory responses to influenza. Methods: Healthy young adults (N=39) were randomized to a 2-hr controlled chamber exposure to wood smoke, where exposure levels were controlled to particulate number, (WSP) (500 μg/cm3), or filtered air (FA), followed by nasal inoculation with a vaccine dose of live attenuated influenza virus (LAIV). Nasal lavage was performed on pre-exposure (day 0) and days 1 and 2 post-exposure. Nasal lavage fluid cells were analyzed for inflammatory gene expression profiles and cell-free fluid was assayed for cytokines. Measurements and Main Results: Only IP-10 protein levels were affected, suppressed, by WSP exposure in aggregate analysis. Subsequent analysis indicated an exposure*sex interaction, prompting additional analyses of WSP- and LAIV-induced changes in males and females. Inflammation-related gene expression profiles differed between the sexes, at baseline (males greater than females), after LAIV inoculation (females greater than males), and after WSP exposure (increase in males and decrease in females), demonstrating that WSP-and LAIV-induced changes in antiviral defense responses in the nasal mucosa occur in a sex-specific manner. Conclusions: WSP exposure resulted in minimal modification of LAIV-induced responses in aggregate analysis. In contrast, analyzing WSP-induced modification of LAIV responses in the sexes separately unmasked sex-specific differences in response to exposure. These data highlight the need for additional studies to understand sex-specific pollutant-induced effects. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02183753.