Oxidant-mediated lung disease in newborn infants

High concentrations of oxygen are administered with increased airway pressure to most preterm neonates with respiratory distress syndrome (RDS). Among 20% to 30% of survivors a form of chronic lung disease, bronchopulmonary dysplasia (BPD), develops. Its pathogenesis may include tissue damage caused by the superoxide anion (O2-) and other free oxygen radicals. Animal experiments and other data suggested a rationale for superoxide dismutase (SOD) administration in an effort to prevent or ameliorate BPD. Our preliminary studies in 19 prematures with RDS demonstrated its safety in human newborns and permitted measurement of its plasma levels. No adverse clinical findings occurred, and laboratory parameters were unchanged. Subcutaneous administration (0.25 mg/kg) of bovine SOD led to detectable levels at 1 1/2 h (mean 0.22 microgram/ml), with a slight rise to a higher peak at 2 1/2-4 h and a plateau over the remainder of the 12-h interval. Following doses 2-5, peak levels of 0.64 microgram/ml occurred at 4-8 h. With this background, a prospective double-blind controlled study of 45 neonates (mean gestational age, 29 weeks; birth weight, 1,100 g) showed a statistically significant reduction in prevalence of clinical and X-ray signs of BPD with fewer days of continuous positive airway pressure required. The safety and pharmacokinetics of bovine SOD were confirmed.