Pathology of arrested acinar development in postsurfactant bronchopulmonary dysplasia

Abstract

To define the pathology of bronchopulmonary dysplasia (BPD) in surfactant-treated patients (S-BPD), we reviewed 22 BPD patients (14 S-BPD and eight non-surfactant-treated [NS-BPD]) and 15 age-matched controls, the lungs from which had been processed after formalin inflation. These were studied for surfactant therapy, postconceptional age, crown-rump length, weight at autopsy, radial alveolar count (RAC), mean linear intercept (MLI), RAC/MLI ratio, and amount and extent of fibrosis. On trichrome staining, there was no alveolar septal fibrosis in the control group, whereas there was mild to moderate alveolar septal fibrosis in 5 of 14 S-BPD patients, of which three had fibrosis in most or all of the acini. In contrast, seven of eight NS-BPD had moderate to severe alveolar septal fibrosis in scattered acini throughout the lung. The patients were divided into two groups, with the first group having a postconceptional age at the time of death of up to 40 weeks' gestation. In group 1, the RAC in S-BPD (nine patients) was significantly lower than that of the controls (seven patients); mean, 4.14 and 5.13, respectively (P = .016), whereas the RAC in the NS-BPD (four patients) and the MLI in both S-BPD and NS-BPD were not statistically significantly different. In group 2, those with adjusted age greater than term, the mean RAC, a measure of acinar complexity, was 3.89 in the S-BPD (five patients) and 3.90 in the NS-BPD (four patients), whereas in the control group (eight patients), it was 5.79 (P = .0007). The mean MLI, a measure of alveolar size, was 0.21 and 0.17 in the S-BPD and NS-BPD groups, respectively, each of which was significantly greater than the mean value of 0.12 in the control group (P = .0003). The comparison of RAC/MLI ratios showed similar statistically significant differences. Based on these results, we conclude that (1) the amount of alveolar septal fibrosis is substantially less and tends to be more diffuse in S-BPD than in NS-BPD; (2) during the period after birth, there is a partial to complete arrest in acinar development (alveolar saccular and alveolar) of similar severity for S-BPD and NS-BPD; and (3) even though on histological examination there are minimal changes, RAC, MLI, and their ratio may be used to support the diagnosis of BPD and help in assessing the amount of lung damage that occurs in S-BPD.