Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in infancy and is primarily a consequence of premature birth, affecting approximately 30% of infants born at less than 28 weeks gestation. Surfactant dysfunction may play a primary or secondary role in the evolution of BPD, and thus exogenous surfactant may ameliorate this disruption in surfactant metabolism and function. Using stable isotope labeled precursors of surfactant phospholipid, our preliminary data suggest that surfactant turnover is faster in premature infants who still require mechanical ventilation at 1 month of age than at birth, and we suspect that this increased turnover is inadequate to maintain surfactant pool size. For the research component of this Career Development Award, we propose to use intratracheally administered stable isotope labeled DPPC and intravenously administered [1-13d]acetate and [1,2,3,4- 13C4]palmitate to address the hypothesis that late surfactant replacement therapy will augment the surfactant pool by increasing surfactant turnover and increasing recycling. Eligible infants < 28 weeks gestation who still require mechanical ventilation at 7 days of age will be randomized to receive a dose of exogenous surfactant at 7-10 days of life. The specific aims to be addressed are: Specific Aim I: To determine the effect of late surfactant therapy on surfactant turnover. Specific Aim II: To determine the effect of late surfactant therapy on surfactant recycling. Specific Aim III: To determine the effect of late surfactant therapy on absolute turnover rate. A companion clinical pilot trial in which we are participating will investigate the clinical outcomes of this population of patients receiving late replacement surfactant. These stable isotope studies in conjunction with the pilot trial offer a unique opportunity to investigate both the clinical and scientific questions regarding the potential role of late surfactant in managing evolving BPD in preterm infants. Public Health Relevance: Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in infancy and is primarily a consequence of premature birth, affecting approximately 30% of infants born at less than 28 weeks gestation. Surfactant dysfunction may play a primary or secondary role in the evolution of BPD, and thus exogenous surfactant may ameliorate this disruption in surfactant metabolism and function. Our proposed research utilizes stable isotope studies to investigate the potential role of late surfactant in managing evolving BPD in preterm infants. (End of Abstract) [unreadable] [unreadable] [unreadable]