Canine model of chronic bronchial injury. Lung mechanics and pathologic changes

Bronchial injury was induced in 7 dogs by exposure to nebulized 1% nitric acid 3 days per week for 4 weeks. Lung mechanics were measured prior to exposure, at the completion of exposure, and at 1, 3, and 5 months postexposure. Airway obstruction persisted unabated throughout the postexposure period, with significant reductions in maximal expiratory flows. Pulmonary resistance, the slope of phase III, and the volume of isoflow were increased. Hyperresponsiveness to histamine developed between 3 and 5 months. Histologically, there was minimal damage to the cartilaginous airways. Widespread chronic inflammation with minimal fibrosis was seen in the membranous bronchi and respiratory bronchioles. Pathology scores for cartilaginous and noncartilaginous (small) airways were developed and correlated with tests of airway function. Small airways pathology scores correlated with flows at 50 and 25% of the vital capacity and with pulmonary resistance. Density dependence of maximal expiratory flow, closing volume, and closing capacity failed to correlate with either the airway obstruction or the small airways pathology scores.