Ozone-induced lung function decrements do not correlate with early airway inflammatory or antioxidant responses

This study sought to clarify the early events occurring within the airways of healthy human subjects performing moderate intermittent exercise followi ng ozone challenge. Thirteen healthy nonsmoking subjects were exposed in a single blinded, cros sover control fashion to 0.2 parts per million ppm) O-3 and filtered ail fo r 2 h, using a standard intermittent exercise and rest protocol, Lung funct ion was assessed pre- and immediately post-exposure; Bronchoscopy was perfo rmed,with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoal veolar lavage (BAL) 1.5 h after the end of the exposure period. Respiratory tract lining fluid (RTLF) redox status was assessed by measuring a range o f antioxidants and oxidative damage markers in BW and BAL fluid samples. There was a significant upregulation after O-3 exposure in the expression o f vascular endothelial P-selectin (p<0.005) and intercellular adhesion mole cule-1 (p<0.005). This was associated with a 2-fold increase in submucosal mast cells (p<0.005) in biopsy samples,without evidence of neutrophilic inf lammation, and a decrease in BAL fluid macrophage numbers (1.6-fold, p<0.00 5), with an activation of the remaining macrophage subset (2.5-fold increas e in % human leukocyte antigen (HLA)-DR+ cells, p<0.005). In addition, expo sure led to a 4.5-fold and 3.1-fold increase of reduced glutathione (GSH) c oncentrations, in BW and BAL fluid respectively (p<0.05), with alterations in urate and alpha-tocopherol plasma/RTLF partitioning ratios (p<0.05). Spi rometry showed reductions in forced vital capacity (p<0.05) and forced expi ratory volume in one second (p<0.01), with evidence of small airway narrowi ng using forced expiratory flow values (p<0.005). Evidence was found of O-3-induced early adhesion molecule upregulation, inc reased submucosal mast cell numbers and alterations to the respiratory trac t lining fluid redox status. No clear relationship was demonstrable between changes in these early markers and the lung function decrements observed, The results therefore indicate that the initial lung function decrements ar e not predictive of, or causally related to the O-3-induced inflammatory ev ents in normal human subjects.