Ozone-Induced Structural Changes in Monkey Respiratory System

Abstract

Abstract The principal sites of ozone-induced damage in the respiratory tracts of monkeys are the anterior nasal cavity and respiratory bronchioles. Intermittent exposures (8 h/day) for 6 or 90 days to 0.15 or 0.30 ppm ozone resulted in ciliated cell necrosis, shortened cilia, and secretory cell hyperplasia with less stored glycoconjugates in the nasal region. Respiratory bronchiolitis was also observed in these monkeys at 6 days and persisted to 90 days of exposure. Even at the lower concentration of 0.15 ppm O s nonciliated bronchiolar cells appeared hypertrophied and increased in abundance in respiratory bronchioles. The response of respiratory bronchioles to intermittent (8 h/day), long-term ozone exposure of 0.4 or 0.64 ppm included the following morphometric changes: 1) a thicker wall and narrower lumen, 2) thicker epithelial compartment and a much thicker interstitial compartment, 3) shifts in epithelial cell populations with many more nonciliated bronchiolar epithelial cells and fewer squamous type I epithelial cells, 4) larger nonciliated bronchiolar epithelial cells with a larger compliment of cellular organelles associated with protein synthesis, 5) greater volumes of interstitial fibers and amorphous ground substance and 6) greater numbers of interstitial smooth muscle cells, neutrophils, macrophages and mast cells per surface area of epithelial basal lamina. Following cessation of exposure there was persistence of some degree of the hyperplastic and metaplastic epithelial changes, but worsening of interstitial fibrosis. The principal lesion in response to intermittent (8 h/day) O s exposure of 0.25 ppm daily or to cyclical exposures (9 cycles of 1 month of O s followed by 1 month of filtered air) for 18 months was respiratory bronchiolitis. Cyclically exposed monkeys, but not those exposed daily, had significantly increased total lung collagen content, chest wall compliance and inspiratory capacity. The conclusions of this study are: 1) there is persistent epithelial injury in the anterior nasal cavity and respiratory bronchiole by as low as 0.15 ppm 0 3 , 2) there is worsening of the respiratory bronchiole lesion in monkeys in the post-exposure period and 3) cyclical exposures cause more severe injury than continued daily exposures.