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EFFECT OF SHORT TERM DIESEL EXHAUST EXPOSURE ON NASAL RESPONSES TO INFLUENZA IN ALLERGIC RHINITICS.
Citation:
Noah, T., K. Horvath, C. Robinette, D. DIAZ-SANCHEZ, H. Zhang, H. Zhou, AND I. JASPERS. EFFECT OF SHORT TERM DIESEL EXHAUST EXPOSURE ON NASAL RESPONSES TO INFLUENZA IN ALLERGIC RHINITICS. Presented at American Thoracic Society (ATS) meeting, Denver, CO, May 13 - 18, 2011.
Impact/Purpose:
We conducted a randomized, prospective study describing nasal responses to live attenuated influenza virus (LAIV) in normal or allergic rhinitic (AR) volunteers exposed to either DE (100 ug/m3) or clean air for 2 hr, followed by a standard dose of LAIV and serial sampling of nasal lavage fluids (NLF). Measured NLF endpoints were virus quantity by qRTPCR and multiple inflammatory or immune mediators by multiplex ELISA. Area under curve data for 9 days post-exposure were analyzed for diesel effect and the impact of allergy status, using nonparametric ANOVA for subgroup comparisons and multiple regression models for the entire study population.
Description:
Introduction: Recently published data suggest that diesel exhaust (DE) has special impact on allergic inflammation, suppressing Th1 and augmenting Th2 responses to allergen via oxidant stress effects on airway cells. Exposures to particulate air pollutants including DE are also associated with heightened susceptibility to viral respiratory infections in humans, but mechanisms remain unclear. Our previous studies conducted in mice demonstrated that exposure to DE particles increased virus-induced allergic inflammation. We hypothesized that acute exposure to DE modifies inflammatory responses to influenza virus in allergic humans, shifting to a more allergic phenotype. Study Design: We conducted a randomized, prospective study describing nasal responses to live attenuated influenza virus (LAIV) in normal or allergic rhinitic (AR) volunteers exposed to either DE (100 ug/m3) or clean air for 2 hr, followed by a standard dose of LAIV and serial sampling of nasal lavage fluids (NLF). Measured NLF endpoints were virus quantity by qRTPCR and multiple inflammatory or immune mediators by multiplex ELISA. Area under curve data for 9 days post-exposure were analyzed for diesel effect and the impact of allergy status, using nonparametric ANOVA for subgroup comparisons and multiple regression models for the entire study population. Results: Baseline levels of mediators did not differ between exposure groups. Virus quantity was markedly increased with DE exposure, driven by the AR subgroup. DE was associated with increased IL-8 and ECP, and decreased IP-10, in the AR subgroup. DE increased IFNy overall, but this did not reach significance in AR. Mean ± SE (area under curve) data for these endpoints are shown in the Table: In the multiple regression model including demographic, nutritional and allergy status, a significant DE effect was confirmed for virus quantity, as well as an interaction effect between DE exposure and allergy status for ECP and eotaxin-1. No significant DE effect was seen for multiple other cytokines and chemokines in any of the analyses. Conclusions: Short term exposure to DE leads to increased virus quantity after LAIV inoculation. Allergic individuals appear to be more susceptible than normals to diesel-induced IL-8 production, suppressed IP-10, and increased eosinophil activation after LAIV infection. We speculate that in the allergic respiratory tract, DE induces mucosal anti-viral responses favoring poor virus clearance and increased Th2-like inflammation. Acknowledgments: Supported by NIH R01 ES013611, NIEHS (P30ES1 0126), and US EPA Cooperative Agreement CR83346301 (not subject EPA review and does not necessarily reflect EPA policy).