This proposal is based on the hypothesis that the decline in airway responsiveness between infancy and adulthood is related to maturational changes in the balance of forces between the airways and the lung parenchyma. Understanding how coupling between the airways and the lung parenchyma and volume history affect airway responsiveness in the growing lung may provide insight into the mechanisms for the heightened airway responsiveness in asthma. If a weaker coupling between the airways and the lung parenchymal tissue causes hyperresponsiveness in infants, then this mechanism could persist as an underlying cause of airway hyperresponsiveness in children and adults with asthma.
The Specific Aims of this proposal are 1) characterize and quantify the changes in the structure and composition of the airways and the lung parenchyma during growth and maturation of the rabbit lung, 2) evaluate mechanisms for maturational differences in the pulmonary response to Mch induced bronchoconstriction under static conditions, 3) evaluate whether there are maturational differences in the effects of tidal volume and deep inspiration on airway closure and narrowing, and 4) determine whether the effect of volume history on airway responsiveness differs among human infants, older children, and adult subjects. The experiments are designed to evaluate the mechanisms for maturational differences in the pulmonary response to bronchoconstriction by investigating the mechanical interactions between the airways and the lung parenchyma which determine the static and the dynamic properties of the lung.
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