The progression of morphologic changes in bronchopulmonary dysplasia.

Review of published reports shows confusion regarding the pathologic sequelae of neonatal respiratory distress. To examine this problem the authors studied histologic slides of lung from 46 patients so diagnosed listed in the autopsy files of The Johns Hopkins Hospital. Two distinct morphologic patterns emerged. In 26 patients (Group 1) there were varying sized areas of interstitial fibrosis with associated distortion of air spaces. The process was nonspecific and closely resembled the interstitial fibrosis of varying etiologies found in adults. This lesion appears to correspond to most descriptions of bronchopulmonary dysplasia. A second process predominated in 10 patients (Group 3). There were normal conducting bronchi, marked uniform enlargement of distal air spaces, and little or no interstitial fibrosis. In 10 patients (Group 2) both lesions coexisted. To gain further insight into the morphology of these disorders, the authors reconstructed serial histologic sections of lung from three infants of varying sizes with normal lungs and infants of varying ages with bronchopulmonary dysplasia. The results confirmed the observations made on routine histologic sections by showing interstitial fibrosis in the early stages of bronchopulmonary dysplasia and a reduced number of very large terminal air spaces without interstitial fibrosis in the late stages. There were no obvious differences in the clinical courses of infants with the different morphologic stages; but Group 1 patients averaged 39 days of age, Group 2 lived 142 days, and Group 3 survived 277 days. It seems probable that early bronchopulmonary dysplasia is simply the healing of alveolar wall injury of whatever cause, most commonly hyaline membrane disease of the newborn; and that in the later phases of repair, with continuing growth, there is a thinning of airway walls, but a failure of alveolar development. Recognition of these two pathologically different patterns is important for further studies of the pathogenesis of bronchopulmonary dysplasia.