title: Atopic asthmatic subjects but not atopic subjects without asthma have enhanced inflammatory response to ozone.
abstract: BACKGROUND
  Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined.
  
  
  OBJECTIVE
  We sought to determine whether atopic status modulates ozone response phenotypes in human subjects.
  
  
  METHODS
  Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations.
  
  
  RESULTS
  All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significantly change in any group with ozone. All groups had similar levels of hyaluronic acid at baseline, with increased levels after ozone exposure in atopic and atopic asthmatic subjects.
  
  
  CONCLUSIONS
  Atopic asthmatic subjects have increased airway inflammatory responses to ozone. Increased Toll-like receptor 4 expression suggests a potential pathway through which ozone generates the inflammatory response in allergic asthmatic subjects but not in atopic subjects without asthma.
authors.affiliation: Center for Environmental Medicine Asthma and Lung Biology, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, NC 27599-7310, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Hernandez
authors.forename: John C
authors.initials: JC
authors.lastname: Lay
authors.forename: Bradford
authors.initials: B
authors.lastname: Harris
authors.forename: Charles R
authors.initials: CR
authors.lastname: Esther
authors.forename: W June
authors.initials: WJ
authors.lastname: Brickey
authors.forename: Philip A
authors.initials: PA
authors.lastname: Bromberg
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
authors.forename: Robert B
authors.initials: RB
authors.lastname: Devlin
authors.forename: Steven R
authors.initials: SR
authors.lastname: Kleeberger
authors.forename: Neil E
authors.initials: NE
authors.lastname: Alexis
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications* / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008297:Male; D010126:Ozone / Q000494:pharmacology*; D012129:Respiratory Function Tests; D055815:Young Adult
chemical_list: D010126:Ozone
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