Pulmonary fibrosis with small-airway disease: A model in nonhuman primates

Bleomycin was administered intrabronchially to four baboons in doses of 1 mg/kg for four consecutive weeks. At necropsy 6 months later, the lesions produced differed markedly from those resulting from parenteral administration of bleomycin and consisted of diffuse foci of inflammation and fibrosis of the lung parenchyma associated with small airway lesions. Airway lesions were found in respiratory bronchioles and consisted of bronchiolar wall inflammation, hyper-plasia of smooth muscle, and epithelial bronchiolization of adjacent alveolated structures. Many bronchioles were obliterated by the fibrotic process. Physiologically, these animals demonstrated findings of both lung fibrosis and obstruction of small airways. Biochemical measurements confirmed the histologic appearance of increased lung collagen in three of four animals. These findings indicate that obstruction of small airways by processes which cause lung fibrosis may be separable physiologically from processes which affect only the lung parenchyma.