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

Mudway, I S, Stenfors, N, Blomberg, A, Helleday, R, Dunster, C, Markland, S L, Frew, Anthony, Sandström, T and Kelly, F J (2001) Differences in basal airway antioxidant concentrations are not predictive of individual responsiveness to ozone: a comparison of healthy and mild asthmatic subjects. Free Radical Biology and Medicine, 31 (8). pp. 962-974. ISSN 0891-5849

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Abstract

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 FEV1 (−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.

Item Type: Article
Depositing User: EPrints Services
Date Deposited: 21 Feb 2012 10:01
Last Modified: 29 Jul 2019 14:01
URI: http://sro.sussex.ac.uk/id/eprint/37643
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