title: Diesel exhaust exposure and nasal response to attenuated influenza in normal and allergic volunteers.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 (100 μg/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.
  
  
  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).
authors.affiliation: Department of Pediatrics, University of North Carolina at Chapel Hill, 27599-7310, USA. terry_noah@med.unc.edu
authors.forename: Terry L
authors.initials: TL
authors.lastname: Noah
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhou
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Katie
authors.initials: K
authors.lastname: Horvath
authors.forename: Carole
authors.initials: C
authors.lastname: Robinette
authors.forename: Matthew
authors.initials: M
authors.lastname: Kesic
authors.forename: Megan
authors.initials: M
authors.lastname: Meyer
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D000998:Antiviral Agents / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D054413:Chemokine CCL11 / Q000276:immunology; D004311:Double-Blind Method; D047150:Eosinophil Cationic Protein / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D055556:Nasal Lavage; D009297:Nasal Mucosa / Q000276:immunology*; D009975:Orthomyxoviridae / Q000302:isolation & purification*; D011446:Prospective Studies; D012044:Regression Analysis; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D001335:Vehicle Emissions
chemical_list: D000393:Air Pollutants; D000998:Antiviral Agents; D015415:Biomarkers; D054413:Chemokine CCL11; D007155:Immunologic Factors; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D001335:Vehicle Emissions; D007371:Interferon-gamma; D047150:Eosinophil Cationic Protein
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