This is an application for a Specialized Center of Research in Pediatric Pulmonary Diseases: Prevention and Treatment of Respiratory Distress in the Newborn. The center will explore factors controlling the synthesis and secretion of pulmonary surface active material in the lamb fetus and assess the effect of early administration of an exogenous surface active material on pulmonary, circulatory and neurological function and disease in newlyborn humans and lambs. The purposes of the proposal are: a) to carry out studies on the formation and release of pulmonary surfactant and the absorption of a synthetic surfactant; b) to elucidate factors which control fetal breathing movements and tracheal fluid production and how they change immediately before and after birth; c) to examine the relation between natural and synthetic pulmonary surfactant on fluid filtration into the lung and postnatal lung fluid clearance; d) to demonstrate the mechanism of closure of the ductus arteriosus particularly in relation to PGE2, asphyxia and administration of glucocorticoids and determine if ductal closure can be influenced by instillation of a synthetic surfactant; e) to assess the effect on the incidence of the respiratory distress syndrome and its complications of the instillation at birth of a synthetic surfactant into the lungs of infants with weight under 1350 g; f) to measure lung function and intellectual performance and assess neurological state at 1 and 3 years of age in children with birth weight under 1350 g who were treated with a synthetic surfactant and their controls; and g) to improve methods for the non-invasive measurement of cardiopulmonary function in infants and to use these methods to determine the importance of the chest wall in maintaining lung stability, to measure blood gases on the skin and to estimate the amount of flow through a patent ductus arteriosus.
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