Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation in newborn rats

Bronchopulmonary dysplasia is the most common cause of chronic pulmonary di sease in premature infants. Airway inflammation appears to play a major pat hogenetic role together with barotrauma and oxygen toxicity. The aim of the present study was to determine the effect of a 15-d exposure to moderate h yperoxia (Fio(2), 50%) on airway reactivity and inflammatory response in ne onatal and adult rats. We studied in isolated tracheal rings the 1) isometr ic contraction to cumulative concentrations of carbachol (10(-8) to 10(-3) M); 2) epithelial, submucosal, smooth muscle, and connective tissue surface area; and 3) distribution of inflammatory cells (mastocytes, granulocytes, macrophages) by using MAb. Reactivity to carbachol was significantly incre ased in the hyperoxic pups, in which a 13% increase in tracheal smooth musc le surface area was observed. Type-I mast cells and macrophages (submucosa and connective tissue) and granulocytes (connective tissue) were increased in the neonatal hyperoxic group. Hyperoxia did not influence functional, mo rphometric, or cellular data in adult rats. In conclusion, exposure of newb orn rats to moderate hyperoxia induces airway hyperresponsiveness and histo logic changes similar to those reported in bronchopulmonary dysplasia. Hype rresponsiveness may be ascribed to an increase in smooth muscle related to the release of yet undetermined mediators by inflammatory cells infiltratin g the airways. Lung immaturity definitely plays a role because similar alte rations are not observed in adult rats.