A Biomathematical Model of Particle Clearance and Retention in the Lungs of Coal Miners: I. Model Development

摘要: To understand better the factors influencing relationships among airborne particle exposure, lung burden, and fibrotic disease, we developed a biologically based kinetic model to predict long-term retention of particles in lungs coal miners. This includes alveolar, interstitial, hilar lymph node compartments. The 131 miners this study had worked Beckley, West Virginia, area died during 1960s. data used develop include exposure respirable mine dust by intensity duration within each job, burdens at autopsy, pathological classification smoking history. Initial parameter estimates for were on both human animal deposition clearance biological physical these processes. Parameter estimation fit determined using least squares. Results show that end-of-life substantially higher than expected from first-order kinetics, yet lower overloading alveolar predicted rodent studies. best-fitting most parsimonious processes alveolar-macrophage-mediated transfer interstitium. These results are consistent with patterns observed previously primates. findings indicate models extrapolated humans, without adjustment differences retention, would be inadequate predicting humans. Also, predicts greater retained occupational current data. is useful risk assessment particle-induced diseases, estimating equivalent internal doses rodents humans exposures.