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

The air pollutant ozone induces both airway inflammation and restrictions i n lung function. These responses have been proposed to arise as a consequen ce of the oxidizing nature of ozone, depleting endogenous antioxidant defen ses with ensuing tissue injury. In this study we examined the impact of an environmentally relevant ozone challenge on the antioxidant defenses presen t at the surface of the lung in two groups known to have profound differenc es in their antioxidant defense network: healthy control (HC) and mild asth matic (MA) subjects. We hypothesized that baseline differences in antioxida nt concentrations within the respiratory tract lining fluid (RTLF), as well as induced responses, would predict the magnitude of individual responsive ness. 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 aft er the end of the ozone challenge. This was associated (Rs, -0.71, p < .01) with increased glutathione disulphide (GSSG) in these compartments (p = .0 1 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 ev idence of lipid oxidation seen following ozone. Despite differences in anti oxidant levels and response, the magnitude of ozone-induced neutrophilia (20.6%, p < .01 [HC] vs. +15.2%, p = .01 [MA]) and decrements in FEV1 (-8.0% , p < .01 [HC] vs. -3.2%, p < .05 [MA]) did not differ between the two grou ps. 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 predictiv e markers of group or individual responsiveness to ozone. (C) 2001 Elsevier Science Inc.