Factors affecting lung clearance kinetics

Factors affecting the clearance of inhaled particles from the pulmonary region of the lung were investigated. Studies on the clearance of 239PuO2 and 57Co-FAP in rats showed that at low α-doses mechanical clearance of the two materials was similar. At higher doses (>5 Gy y-1) mechanical clearance of both was impaired. Instillation resulted in slightly faster lung clearance than inhalation, probably because of differences in deposition. 57Co3O4 was found to be a suitable material for measurement of both mechanical clearance and translocation. Mechanical clearance varied up to 80 times between rats, hamsters and guinea-pigs, whereas translocation varied by 4 times. Mechanical clearance was similar in rats of different ages, although translocation was faster in younger rats. The results support Cuddihy's hypotheses that; lung clearance occurs as competition between mechanical clearance and translocation; mechanical clearance is dependent on species, but independent of material; and translocation is dependent on the physical/chemical nature of the material. In vitro studies showed that pH was an important factor in determining particle dissolution. In a joint study similar pHs (4.5-4.6) were found in the lysosomes of guinea-pig, dog, baboon and rabbit alveolar macrophages. Hence pH could not account for the observed differences in translocation. Further studies are required to determine the reason for the interspecies differences in translocation. (author)