This research involves the study of airway growth from two perspectives: 1) a quantitative morphometric analysis of how a variety of events during periods of rapid airway growth influence airway geometry at maturity, and 2) physiologic studies to elucidate how the same events influence subsequent airway function. The extent to which mechanical stretch applied to the airways early in infancy influences airway growth will be studied by measurements of the anatomic and physiologic consequences of two maneuvers designed to decrease these forces (pleural plombage to decrease lung volume, and administration of B-aminoproprionitrile to decrease lung recoil). In addition, the influence of airway injury early in life on subsequent airway growth will be determined from anatomic and physiologic measurements on mature animals exposed in infancy to levels of nitrogen dioxide sufficient to induce extensive airway inflammation. Morphometric studies will be based on analysis of 3-dimensionl silicon-rubber bronchial casts. The analytical techniques used allow precise comparisons between experimental animals of the relationship of airway size to lung volume, airway size to body size, and central airway size to peripheral airway size. Physiologic studies will include measurements of lung recoil, pulmonary resistance, maximal expiratory flows, and density dependence of maximal flows obtained from anesthetized animals using an integrated-flow plethysmograph with appropriate frequency response characteristics. These studies will provide basic data concerning airway growth and will help elucidate how events during infancy and childhood may be involved in the pathogenesis of the chronic obstructive airway diseases. They will have general physiologic significance in allowing direct correlations between measurement of airway geometry and airway function in individual experimental animals. These studies may also be useful in defining manipulations of growth which can be used to develop animals with specific abnormalities of airway geometry which could be useful in future physiologic studies.
