Ozone exposure and the production of reactive oxygen species by bronchoalveolar cells in humans

Exposure to ozone injures respiratory epithelium, and the mechanisms may in volve the generation of reactive oxygen species (ROS). This study tested th e hypothesis that ozone exposure increases the airway burden of ROS to a gr eater degree in smokers than nonsmokers, and that this effect is independen t of ozone-induced changes in spirometry. Healthy subjects were selected as either responders (decrement in FEV1 > 15%) or non-responders (decrement i n FEV1 < 5%) to ozone; each underwent 2 exposures to ozone and 1 to air, wi th bronchoalveolar lavage (BAL) performed 30 min ( early) and 18 h (late) a fter exposure. Release of superoxide anion (O-2(-)) was used as a measure o f ROS release by all BAL cells, and flow cytometry was used to detect ROS p roduction in alveolar macrophages (AM) only. Recovery of AM was approximate ly threefold greater in smokers than nonsmokers. Unstimulated, but not stim ulated, cells obtained by BAL from smokers released approximately twofold g reater amounts of O-2(-) than cells from non-smokers, both early and late a fter ozone exposure (p = .012 and p = .046, respectively). Stimulated, but not unstimulated, ROS generation by AM from smokers increased following ozo ne exposure, but the ozone effect was not significant. ROS production by AM decreased in nonsmokers (air vs. ozone late, p = .014). Total protein, alb umin, and immunoglobulin M (IgM) increased in BAL fluid, consistent with an increase in epithelial permeability. In addition, the concentration of alp ha (2)-macroglobulin increased approximately threefold 18 h after exposure in nonsmokers (p < .001). No relationship was found between measures of ROS production and lung function responsiveness to ozone. These studies sugges t the airways of smokers experience a greater burden of ROS than those of n onsmokers following ozone exposure.