ANIMAL MODELS OF CHRONIC BRONCHITIS AND THEIR RELEVANCE TO STUDIES OF PARTICLE-INDUCED DISEASE

Abstract

Chronic bronchitis is a significant cause of morbidity and mortality. Chronic irritation of the conducting airways by inhaled substances, most importantly cigarette smoke, air pollution, and occupational exposures, is thought to be a key factor in the pathogenesis of chronic bronchitis. Microbial infections have been implicated in acute exacerbations of bronchitis and in its progression. Several animal models of chronic bronchitis have been developed. This review examines similarities and dissimilarities among commonly used animal models of bronchitis and the human disease. The most commonly used animal models of chronic bronchitis are those employing SO2, tobacco smoke, lipopolysaccharide (endotoxin), proteases, and secretagogues. Bronchiolitis induced by nickel and nitric acid have also been reported. Rats, hamsters, and dogs are the species most frequently used; sheep and monkeys have been used less frequently. These models vary in the extent or location of mucouscell hyperplasia and metaplasia, airway inflammation, chronicity, ease of induction, and reproducibility. Frequently, the deficiencies in these models are attributable to anatomic differences between human and animal airways, differences in the severity or chronicity of inflammation or fibrosis, or lack of complete characterization of the responses and their time course in the animal model. These animal models may be useful for investigating how, and under what exposure conditions, ambient pollutants might exacerbate airway inflammation, mucus hypersecretion, and airflow limitation.