The objective of this research is to investigate the relationships between surfactant physico-chemical properties and the mechanical stress and fluid balances that exist during the opening of pulmonary airways that are either collapsed or occluded by fluid obstructions. These physico-chemical properties are postulated to be the key determinants of: 1) the pressure needed to open the airways; 2) the mechanical wall stresses induced during opening; 3) the volume of fluid that is retained within the airway after opening; 4) the uniformity of airway opening; and 5) the stability of the bronchial tree.
Four specific aims will investigate these hypotheses. To test the hypothesis that surfactant physico- chemical properties (strength, solubility and adsorption rate) dictate interfacial stresses, and to determine the forms of constitutive equations that describe this relationship, the pressures required to oscillate bubbles in simple and complex surfactant solutions will be compared with predictions from a computational model of an oscillating bubble. Next, clearance of capillary-tube model airways occluded with fluids containing model surfactants will be investigated. The relationships between the pressure, film lining thickness and surfactant physico-chemical properties will be used to estimate those surfactant properties that reduce the need for large driving pressures and stabilize the airway lining fluid. Flexible single and bifurcating airway models will be used to study the physico-chemical properties that affect both the magnitude of the transient pressure and the uniformity with which the bronchial tree can be opened. Finally, excised lung experiments will be used to evaluate the influence of surfactant properties on the pressures and stability characteristics of single and multiple collapsed airways. All studies will be conducted with single- and multiple- constituent model surfactants and exogenous surfactant substitutes. The proposed work will explain the fundamental force balances that exist in the pulmonary system during an infant's first breath. This work will predict exogenous surfactant physico- chemical properties that will minimize the mechanical stresses applied to airways during the opening of lungs that are afflicted with Respiratory Distress Syndrome (RDS).This work will also elucidate the force balances that occur during the reopening of collapsed or occluded airways common in disease states such as emphysema, asthma and cystic fibrosis, and may thus indicate new strategies for the treatment of these diseases.
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