This application proposes to continue multi-disciplinary studies of development, control and disorders of pulmonary alveolar stability. By alveolar stabilization we mean the integrated physicochemical and biological processes that develop and maintain alveolar architecture in the optimal state for pulmonary gas exchange. Disordered alveolar stability is the primary problem in respiratory distress syndrome of the newborn and contributes significantly to the pathophysiology of other common forms of lung disease including congenital respiratory distress syndrome and pneumonia. The objectives of this proposal are to examine some of the mechanisms involved in the stabilization of the alveolus during development and post-natal life, and in states of health and disease. The broad goals of the four inter-related projects proposed are: Structure and function of surfactant apoproteins. To study the role of the surfactant apoproteins in regulating surfactant homeostasis. Surface phenomena in lung function. To study mechanisms involved in the formation and modification of lung surfactant films. Effects of physical stimuli on lung development. To determine the effects of alterations in fetal lung growth on epithelial differentiation, lung fluid balance and the organization of alveolar cell cytoskeleton. Regulation of alveolar epithelial cell phenotype. To elucidate mechanisms responsible for the regulation of alveolar epithelial cell phenotypic expression, with a focus on the effects of mechanical forces. The overall purpose of these studies is to deepen our understanding of the processes underlying alveolar stability and to contribute to new concepts and treatments for lung diseases associated with disorders of alveolar stability or alveolar growth and maturation.
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