ALPHA(1)-PROTEINASE INHIBITOR THERAPY FOR THE PREVENTION OF CHRONIC LUNG-DISEASE OF PREMATURITY - A RANDOMIZED, CONTROLLED TRIAL

Background. An imbalance between increased neutrophil elastase and a d ecreased antiprotease shield has been suggested as a factor contributi ng to the development of chronic lung disease (CLD). We hypothesized t hat administration of alpha(1)-proteinase inhibitor (A1PI), also known as alpha(1)-antitrypsin, to premature neonates would prevent CLD. Des ign. A randomized, placebo-controlled, prospective study of A1PI suppl ementation was performed. Neonates <24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory d istress syndrome (RDS) were eligible. Intravenous A1PI (60 mg/kg) or p lacebo was infused on days 0, 4, 7, and 14. Primary outcome was CLD in survivors, defined as the need for supplemental oxygen on day 28. Res ults. A total of 106 patients were recruited. There were no significan t differences between groups in birth weight or incidence of RDS. The incidence of CLD in survivors was lower in the treated group, but the difference did not reach statistical significance (relative risk [RR], 0.79; confidence interval [CI], 0.60-1.02). This beneficial trend per sisted at 36 weeks corrected gestational age (RR, 0.48; CI, 0.23-1.00) . The incidence of pulmonary hemorrhage was lower in the treated group (RR, 0.22; CI, 0.05-0.98). Other complications were not significantly different between groups. Conclusions. In this, the first trial of a protease inhibitor for the prevention of CLD in premature infants, the infusions were well-tolerated. A1PI therapy may impede the developmen t of CLD and appears to reduce the incidence of pulmonary hemorrhage i n some neonates horn prematurely.