Nitric Acid-Induced Bronchiolitis in Rats Mimics Childhood Bronchiolitis obliterans

Abstract

Background: Childhood bronchiolitis obliterans (CBO) is an infrequent but severe disease, characterized by persistent obstructive respiratory symptoms after an acute episode of bronchiolitis. Its etiology is mostly postviral, especially in developing countries. Pathologically, CBO is characterized as constrictive-type BO. The pathogenesis of this disease is poorly understood and there is no specific treatment. Animal models could help to better understand the sequence of events culminating in bronchiolar obliteration and serve as basis for experimental therapeutic research. Objectives: In this study, we adapted the nitric acid (NA) technique to develop a suitable model to study CBO in rats. Methods: We have intratracheally instilled 0.5% NA or saline and studied the histological lesions on days 2, 7, 14 and 30. NA-instilled animals developed a sequence of bronchiolar lesions that included necrotizing bronchiolitis, proliferative (PROL) bronchiolar lesions and constricitive (CONS) bronchiolar lesions with bronchiectasis, mucostasis and macrophagic accumulation. Results: The frequency of PROL lesions decreased and that of the CONS lesions increased, with a statistically significant difference at the sacrifice days, except for day 7 (PROL vs. CONS lesions day 2: p = 0.001; PROL vs. CONS lesions day 7: p = 0.38; PROL vs. CONS lesions day 14: p < 0.001; PROL vs. CONS lesions day 30: p < 0.001). Conclusions: We conclude that this model presents histological similarities with the histological picture of CBO, being suitable for further developmental and therapeutic experimental research in this field.