SCOR Project 10 deals with clinical interventions directed at neonatal lung disease and injury, with a focus on infants having surfactant-deficiency or inactivation as a component of pathophysiology. A major emphasis is on the surfactant-deficient Respiratory Distress Syndrome (RDS) of premature infants, and on acute neonatal respiratory failure in term infants with pulmonary edema and potential surfactant inactivation (ARDS-related). The clinical interventions being studied also have direct significance for bronchopulmonary dysplasia (BPD), which is the chronic lung disorder of fibrosis, alveolar loss and reactive airway disease that often follows pulmonary disease requiring treatment with oxygen and mechanical ventilation in the newborn period. The project involves a series of randomized, controlled trials contained in the Specific Aims. In Aim 1, full term infants with severe respiratory pathology where surfactant inactivation may be important are assigned randomly to exogenous surfactant versus control groups to determine if surfactant is efficacious and safe in this kind of lung injury. In Aim 2, infants of less than 29 weeks gestation will receive prophylactic exogenous surfactant, but will be assigned randomly to receive it immediately following birth or after initial stabilization at 10-15 minutes, to address a critical current issue in surfactant therapy for RDS. In Aim 3, infants who have moderate RDS despite exogenous surfactant therapy will be randomly assigned to high frequency jet or conventional ventilation groups to determine if this mode of ventilation therapy will reduce barotrauma and the incidence and/or severity of BPD. In addition to these three clinical trials in Aims 1-3, another study anticipated for future years of the SCOR in Aim 4 will involve therapy using superoxide dismutase (SOD) along with surfactant as a multi-modal approach treating premature infants with RDS and lung injury secondary to hyperoxia and mechanical ventilation (pending animal studies with SOD in Project 5). Finally, Aim 5 studies will address the long term evaluation and surveillance of survival, rehospitilizations, health status, pulmonary sequelae, and school performance of those infants enrolled in our randomized clinical trials, as necessary for long-term outcome assessments.