Sequence of pathologic changes in the airway mucosa of guinea pigs during ozone-induced bronchial hyperreactivity.

We assessed the nature and progression of airway mucosal disease and muscarinic bronchial reactivity in guinea pigs studied in groups of 4 at 2 h, 6 h, 14 h, 1 day, 2 days, or 4 days after ozone exposure (3.0 ppm for 2 h), and in 1 control group. Muscarinic reactivity was determined by measuring specific airway resistance as a function of increasing doses of intravenous acetylcholine in 31 intact, unanesthetized, spontaneously breathing animals. After testing, each group was killed to obtain tracheal tissue for light microscopic examination. We found that airway hyperreactivity to acetylcholine occurred in 96% of the animals exposed to ozone. Its degree at 2 h was substantial. Complete remission was not observed until the fourth day. In association with the acute bronchial hyperreactivity found at 2 h, a marked decrease in airway mucosal goblet cells and an increase in mucosal mast cells occurred. Neutrophilic infiltration occurred later and lasted longer, despite remission of the hyperreactivity. Our results indicate that acute, ozone-induced bronchial hyperreactivity is related to signs of airway mucosal injury and mast cell infiltration. After this early phase of airway damage, neutrophilic infiltration occurs and persists, suggesting that it is a consequence of the damage rather than a cause of the increased airway reactivity after ozone exposure.