This proposal is for continuation of original research addressing the impact of acute infectious events during childhood on subsequent pulmonary health and those measures which could be applied to reduce long-term sequelae and resultant disability. This general goal is approached through a series of integrated, multidisciplinary projects which represent extensions of productive prior work as well as new proposals suggested by earlier findings and progress in the field. Broadly stated, the issues to be considered include: 1) assessment of the relative importance of selected factors which confound the outcome of natural intercurrent infections of the lungs; 2) analysis of patterns of injury and repair in specialized respiratory tract structures during the course of growth and development to identify steps in disease pathogenesis where intervention would be feasible; and 3) the exploration of novel diagnostic and therapeutic approaches in animals and natural human diseases to initiate practical applications of research progress. Studies on acute bronchiolitis (viral, bacterial, mycoplasmal) will continue as a central theme. Special attention will be given to the airways epithelium because of its principle involvement in many infectious processes and its importance in the muco-ciliary defense mechanism of the lungs. The work would be accomplished through clinical and epidemiological studies of children (normal and atopic individuals, subjects with cystic fibrosis), experiments with several animal models of the most common childhood respiratory infections, and use of in vitro models of differentiated respiratory cells and tissues. Together these approaches are designed to provide improved methods of diagnosis, treatment and prevention for the most common form of pulmonary disease in children.
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