Lung injury associated with neonatal Respiratory Distress Syndrome and Bronchopulmonary Dysplasia requires understanding developmental responses of pulmonary proteolytic activity and defense mechanisms intrinsic to the newborn lung. Utilizing neonatal pulmonary effluent obtained by sequential tracheal aspiration, the aims of this proposal are to: 1. Determine sequentially, the levels of protease activity and protease inhibition in pulmonary effluent of human preterm infants and to relate these biochemical indices of lung injury to radiographic and ventilatory assessments to the severity of acute abd chronic lung disease, 2. Using homologous surface active materials derived from term human amniotic fluid, the proposed investigations seek to define whether surfactant supplementation in 20-30 preterm, infants per year with respiratory distress syndrome alters the clinical, radiological, cytologic, proteolytic activity, and protease inhibition activity in infants treated with surface active material supplemention in comparison to infants receiving conventional mechanical ventilatory support with oxygen supplementation using a multiple logistic regression model. In addition, these investigations will define whether or not evidence of immune complex formation results in infants receiving homologous surface active material using conglutinin assays, as well as, measurement of anti-surfactant antibody formation in the sera of treated infants throughout the first year of life in order to determine whether detectable immunologic reactivity occurs from tracheally instilled surface active material in developing preterm infants, 3. To determine whether active Alpha1 protease inhibitor levels, elastase levels, and alastase inhibitory capacities are altered in neonatal rabbits in graded exposure to varying concentrations of FiO2 previously established to result in lung injury, 4. Using neonatal and young New Zealand White rabbits, describe the effects of graded exposure of intratracheally instilled human derived surfactant on lung histology, presence of circulating antigen, and measures of pulmonary immunoreactivity.
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