Airway inflammation despite loss of bronchial hyper-responsiveness after multiple ozone exposures

The effect of single and multiple exposures to ozone (O3) on airway responsiveness and inflammation was examined in guinea pigs. Airway responsiveness, measured as acetylcholine concentration needed to increase baseline airway resistance (RL) by 250% (PC250), increased 1 h after exposure to ozone at 3 ppm for 3 h (-log PC250 from 3.88 +/- 0.17 to 4.78 +/- 0.18; P < 0.05), but returned to baseline at 8 h. An increase in neutrophil numbers was found at 8 h in bronchoalveolar lavage fluid (BALF). After O3 exposure on 4 successive days, baseline RL increased and airway responsiveness decreased at 1, 8 and 72 h (-log PC250 = 2.88 +/- 0.17, 2.83 +/- 0.10 and 3.12 +/- 0.08, respectively, compared to control value of 3.48 +/- 0.05). Repeated exposures to O3 also increased neutrophil numbers in bronchoalveolar lavage fluid and in bronchial submucosa. Thus, single exposure to O3 caused a rapid and transient increase in airway responsiveness, while multiple exposures induced a rapid but prolonged decrease in airway responsiveness associated with persistent bronchoconstriction. Both single and multiple exposures induced airway inflammation as evidenced by an increase in neutrophil influx. These studies demonstrated a dissociation between ozone-induced changes in airway responsiveness and neutrophil influx, and indicate that multiple exposures to O3 induce persistent bronchoconstriction with airway hyporesponsiveness.