Distal Airway Remodeling in Rats Chronically Exposed to Ozone

The morphologic changes in the centriacinar region of lungs from 14 rats exposed to either filtered air (8) or 0.95 ppm ozone (6) 8 hours daily for 90 days were examined morphologically and morphometrically. Rats were killed with an overdose of sodium pentobarbital administered intraperitoneally, the trachea cannulated, and thoracic viscera and lungs removed from the chest. Lungs were fixed via intratracheal instillation of a paraformaldehyde/glutaraldehyde cacodylate buffered fixative at 30 cm water pressure. Lung volumes were determined by weight displacement and the left lung lobe was sectioned transversely into 12 slabs. Three slabs from the cranial, middle, and caudal thirds of the lobe were embedded in paraffin and studied by light microscopy. With these sections, we estimated the volume of proximal bronchiole, terminal bronchiole, respiratory bronchiole, and combined alveolar duct/sac within the lung. Bronchioles dissected from preselected regions of the right middle lobe were studied by transmission electron microscopy. Dissected terminal airways were sectioned in a longitudinal plane through their midlumen. From these dissected airways, 4 subregions of the centriacinus were then examined: (1) terminal bronchiole, (2) respiratory bronchiole, (3) centriacinar alveolar duct wall, and (4) centriacinar alveolar septa. The results of this study showed that after chronic ozone exposure, there was a 13 to 21% decrease in terminal bronchiole luminal diameter but no significant change in total terminal bronchiole volume. The most notable change was a 3.4-fold increase in respiratory bronchiole volume. Analysis of measured volume and diameter changes in the terminal bronchiole, coupled with volume increases in respiratory bronchiole, support the conclusion that respiratory bronchiole (RB) is formed from the centriacinar alveolar duct. Morphologic parameters supporting this conclusion included the presence of fused basement membrane beneath reactive bronchiolar epithelium in the RB, the presence of similar basal laminar changes in both the RB and proximal alveolar duct septal tips, and the observation that most severe epithelial damage and inflammation occurred in the most proximal alveolar duct rather than in the terminal bronchiole. A major conclusion of this study is that the focus of the most severe injury within the acinus appears to shift distally as respiratory bronchiole segments are formed. Hence most of the damage occurs at the tips of alveolar septa at the respiratory bronchiole-alveolar duct junction.