Diesel exhaust exposure and nasal response to attenuated influenza in normal and allergic volunteers.
Am J Respir Crit Care Med. 2012 Jan 15 ;185(2):179-85. Epub 2011 Oct 27. PMID: 22071326
Terry L Noah
RATIONALE: Diesel exhaust enhances allergic inflammation, and pollutants are associated with heightened susceptibility to viral respiratory infections. The effects of combined diesel and virus exposure in humans are unknown.
OBJECTIVES: Test whether acute exposure to diesel modifies inflammatory responses to influenza virus in normal humans and those with allergies.
METHODS: We conducted a double-blind, randomized, placebo-controlled study of nasal responses to live attenuated influenza virus in normal volunteers and those with allergic rhinitis exposed to diesel (100μg/m(3)) or clean air for 2 hours, followed by standard dose of virus and serial nasal lavages. Endpoints were inflammatory mediators (ELISA) and virus quantity (quantitative reverse-transcriptase polymerase chain reaction). To test for exposure effect, we used multiple regression with exposure group (diesel vs. air) as the main explanatory variable and allergic status as an additional factor.
MEASUREMENTS AND MAIN RESULTS: Baseline levels of mediators did not differ among groups. For most postvirus nasal cytokine responses, there was no significant diesel effect, and no significant interaction with allergy. However, diesel was associated with significantly increased IFN-γ responses (P = 0.02), with no interaction with allergy in the regression model. Eotaxin-1 (P = 0.01), eosinophil cationic protein (P<0.01), and influenza RNA sequences in nasal cells (P = 0.03) were significantly increased with diesel exposure, linked to allergy.
CONCLUSIONS: Short-term exposure to diesel exhaust leads to increased eosinophil activation and increased virus quantity after virus inoculation in those with allergic rhinitis. This is consistent with previous literature suggesting a diesel"adjuvant"effect promoting allergic inflammation, and our data further suggest this change may be associated with reduced virus clearance.Clinical trial registered with www.clinicaltrials.gov (NCT00617110).