Toxic inhaled aerosols can initiate or aggravate pulmonary disease, and drugs for treatment of lung disease can be used effectively by inhalation. The research objectives of this study are to identify and to understand the determinants of inhaled particle deposition sites in the lungs as well as the sites of subsequent redistribution and clearance. In the past, morphometric methods have been developed to precisely localize the site of particle deposition in defined compartments of the respiratory tract. These techniques have been used to describe sites and define clearance pathways. Now, these methods will be applied to answer specific questions concerning the clearance and redistribution of particles in the respiratory tract. From previous studies with 0.9-mum particles, it is known that a significant fraction of inhaled particles are retained in the airways of the respiratory tract beyond 24 hours. This is contrary to popular belief. First, the validity of the traditional interpretation of the clearance curve will be tested. The results of these studies will be of great value, since these types of curves are the only method of measuring particle clearance in man at present. Second, a potential mechanism will be examined that may lead to delayed clearance of particles from the airways. Our hypothesis is that slow clearance from the airways is particle dependent. The hydrophobicity of the particle will determine if it either is quickly cleared or passes through the surfactant layer landing adjacent to airway epithelium and thus slowly cleared. Third, new technologies available in our laboratory, the Life Cell cryofixation and molecular distillation system and the Zeiss CEM902 electron microscope, will be applied to examine the relationship of the constituents of airway mucus and alveolar lining material to particle clearance. Using particles with different hydrophobicity and surface charge, the extent to which endogenous constituents coat inhaled particles in situ to facilitate mucocilliary action or phagocytosis will be examined. The new technologies coupled with new approaches to immunocytochemistry will provide direct visualization and new understanding of an important interaction which has never been studied directly. The information gained from these studies should help explain mechanisms of clearance from the airways, and the precise interactions of particles and lung surface lining materials.
