Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone: a comparison of healthy and mild asthmatic subjects

Free Radic Biol Med. 2001 Oct 15;31(8):962-74. doi: 10.1016/s0891-5849(01)00671-2.


The air pollutant ozone induces both airway inflammation and restrictions in lung function. These responses have been proposed to arise as a consequence of the oxidizing nature of ozone, depleting endogenous antioxidant defenses with ensuing tissue injury. In this study we examined the impact of an environmentally relevant ozone challenge on the antioxidant defenses present at the surface of the lung in two groups known to have profound differences in their antioxidant defense network: healthy control (HC) and mild asthmatic (MA) subjects. We hypothesized that baseline differences in antioxidant concentrations within the respiratory tract lining fluid (RTLF), as well as induced responses, would predict the magnitude of individual responsiveness. We observed a significant loss of ascorbate (ASC) from proximal (-45.1%, p <.01) and distal RTLFs (-11.7%, p <.05) in healthy subjects 6 h after the end of the ozone challenge. This was associated (Rs, -0.71, p <.01) with increased glutathione disulphide (GSSG) in these compartments (p =.01 and p <.05). Corresponding responses were not seen in asthmatics, where basal ASC concentrations were significantly lower (p <.01) and associated with elevated concentrations of GSSG (p <.05). In neither group was any evidence of lipid oxidation seen following ozone. Despite differences in antioxidant levels and response, the magnitude of ozone-induced neutrophilia (+20.6%, p <.01 [HC] vs. +15.2%, p =.01 [MA]) and decrements in FEV(1) (-8.0%, p <.01 [HC] vs. -3.2%, p <.05 [MA]) did not differ between the two groups. These data demonstrate significant differences between the interaction of ozone with RTLF antioxidants in MA and HC subjects. These responses and variations in basal antioxidant defense were not, however, useful predictive markers of group or individual responsiveness to ozone.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antioxidants / metabolism*
  • Ascorbic Acid / antagonists & inhibitors
  • Ascorbic Acid / metabolism
  • Asthma / chemically induced
  • Asthma / diagnosis
  • Asthma / metabolism*
  • Bronchial Provocation Tests
  • Bronchoscopy
  • Double-Blind Method
  • Female
  • Glutathione Disulfide / agonists*
  • Glutathione Disulfide / metabolism
  • Humans
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism*
  • Male
  • Middle Aged
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Ozone* / adverse effects
  • Predictive Value of Tests
  • Respiratory Function Tests
  • Respiratory System / cytology
  • Respiratory System / drug effects
  • Respiratory System / metabolism


  • Antioxidants
  • Ozone
  • Ascorbic Acid
  • Glutathione Disulfide