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 mucous-cell 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.

Validation of a new automatic smoking machine to study the effects of cigarette smoke in newborn lambs

“…23 -26 Most studies on the effects of cigarette smoke in adult animals have been performed in rodents. 19 The few studies on the effects of cigarette smoke in adult, non-rodent species were performed either acutely in anaesthetized ewes through a tracheal tube, 27 or chronically in tracheotomized sheep 28,29 and dogs, 19,30 in intact dogs using a mask 31,32 or in baboons taught to inhale through the mouth. 33 Studies in large newborn mammals were also initially performed in lambs as a model of bronchitis, using a tracheostomy tube 29 or an ASM custom-made from a Bird ventilator.…”

Bacterial Lipopolysaccharide Enhances PDGF Signaling and Pulmonary Fibrosis in Rats Exposed to Carbon Nanotubes

“…chronic exposures. The effects of subchronic pulmonary exposure to LPS are similar to chronic bronchitis, and so subchronic treatment of rodents with LPS is used to model this disease (18,19). The lung levels of a variety of secreted pro-inflammatory mediators or their cognate receptors are increased by LPS through activation of Toll-like receptor-4 (TLR4) (20).…”

Lifetime environmental tobacco smoke exposure and the risk of chronic obstructive pulmonary disease

“…Environmental tobacco smoke (ETS) exposure, which appears to cause new cases of asthma, could also cause COPD [6][7][8]. Because it contains potent airway irritants, ETS could lead to chronic airway irritation, inflammation, and obstruction [6,9]. The role of ETS exposure in causing COPD, however, has received limited attention in epidemiologic studies [10,11].…”