Chronic bronchiolitis in nonhuman primates after prolonged ozone exposure.

Bonnet monkeys (Macaca radiata) were exposed to 0.0, 0.5, or 0.8 ppm ozone for 7, 28, or 90 consecutive days, 8 hours per day. The pulmonary response was evaluated by means of pulmonary function testing, light microscopy, scanning electron microscopy, transmission microscopy, autoradiography, and morphometry. Pulmonary function values obtained before exposure did not statistically differ from values obtained after exposure. A general trend of increased quasistatic compliance of the lung was observed in both groups of exposed monkeys. Morphologic changes were principally characterized as low-grade chronic respiratory bronchiolitis. Major features were intraluminal accumulations of macrophages and hypertrophy and hyperplasia of cuboidal bronchiolar epithelial cells. The intensity of this inflammatory response was determined by counting the number of intraluminal inflammatory cells per millimeter of respiratory bronchiolar surface. The magnitude of inflammation was greatest at the 0.8 ppm ozone concentration at each exposure period; however, the number of inflammatory cells present at 90 days was less than one half that observed at 7 days, in spite of persistent ozone insult. Tritiated thymidine labeling and counts of respiratory bronchiolar epithelium demonstrated up to a 37-fold increase in labeling index at 7 days but only a sevenfold increase at 90 days. Differential cell counts demonstrated an increase in the proportion of cuboidal bronchiolar cells constituting the respiratory bronchiolar epithelium. In control monkeys, 60% of the epithelial cells were cuboidal bronchiolar cells. At 90 days of exposure, more than 90% of the respiratory bronchiolar cells were cuboidal in appearance. The cuboidal bronchiolar cell in control monkeys does not appear secretory, but membrane-bound electron-dense secretory granules are present in this cell type from exposed monkeys. Epithelial hyperplasia (increased number of cells per millimeter of airway length) persisted through 90 days of exposure at a level slightly above that present at 7 days.