Nonspecific refractoriness to adenylyl cyclase stimulation in alveolar macrophages from infants with recurrent bronchiolitis

Abstract

Epidemiologic studies suggest an association between recurrent bronchiolitis in children younger than 3 years of age and diagnosis of asthma later in life. Bronchoalveolar lavages from 20 infants with recurrent wheezing and 18 nonwheezy control subjects were analyzed to determine whether alveolar macrophages of wheezy infants present abnormalities similar to those described in adults with asthma. Alveolar macrophages from both groups responded in vitro, in a concentration-dependent manner, to prostaglandin E 2, salbutamol, and forskolin, drugs that increase cyclic adenosine monophosphate levels. However, alveolar macrophages from infants with recurrent wheezing accumulated less cyclic adenosine monophosphate than those from control subjects in response to all three stimulations. These results are in agreement with the reduced cyclic adenosine monophosphate response to different agonists demonstrated in leukocytes from patients with asthma, and suggest that this refractoriness could be one of the precipitating events in the development of asthma observed in a large proportion of infants who have had bronchiolitis.