Aerosolized administration is the principal and in many cases the most appropriate route for administration of newly developed therapies for the lungs. Information on deposition and clearance mechanisms in the airspaces are critical in understanding and optimizing drug delivery to critical sites in the lungs. In the proposed study we will examine the role of exogenous surfactant as a therapy for hyperoxic injury in the adult lung. Newly developed tracers of deposition and clearance and morphometric techniques will he used to quantitatively examine aerosolized therapy at the resolution of single particles at all levels of lung airspaces. Deposition and clearance rates will be measured at critical deposition and injury sites. These will include large and small airway bifurcations, the first alveolus at the transition from airways to gas exchange space and more distal alveoli. The overall goal of the study is to obtain information on deposition and clearance processes throughout the lungs so that delivery and residence of aerosolized therapies at the desired site(s) may be optimized. In order to determine the interactions between aerosol therapy and lung injury we will examine the alterations in deposition, clearance and inflammatory cell responses following hyperoxic exposures with and without exogenous surfactant as an aerosol therapy.
