Light microscopic and ultrastructural study of the adverse effects of oxygen therapy on the neonate lung.

Alterations of lung tissues were evaluated in 74 infants with respiratory distress who received respirator therapy and high concentrations of oxygen for varying durations. Infant survival ranged from 3 hours to 135 days. Sequential pathologic changes were revealed to be an exudative reaction superimposed upon the early stages of typical hyaline membrane disease. This merged with and was eventually replaced by a reparative fibroproliferative response that was most pronounced in those infants who survived for the longest period of time. This response appeared causally related to the development of pulmonary complications of interstitial fibrosis, emphysema, obliterative bronchiolitis and cystic bronchiolectasis. Correlative ultrastructural studies disclosed generalized capillary endothelial damage in early stages of oxygen therapy, interstitial edema and alteration of alveolar cells attributed to the toxic effects of oxygen. Proliferation of type 2 alveolar cells with incorporation of hyaline membranes into septal walls was a notable feature of the reparative reaction and appeared significant in the subsequent development of interstitial fibrosis.