DEVELOPMENT AND APPLICATION OF A MODEL FOR ESTIMATING ALVEOLAR AND INTERSTITIAL DUST LEVELS *

Abstract

A generalized compartmental model of dust deposition and transport in the alveolar area of mammalian lungs has been developed. It is similar to earlier models but has three modifications: (1) the pulmonary area is divided into two compartments, alveolar and interstitial, with dust movement into the interstitium by penetration through the alveolar membrane; (2) dust in the interstitium is either mobile or fixed by sequestration; and (3) the rates of dust movement (the model parameters) are assumed to change in response to toxic effects of the dust. Because the rate ‘constants’ are variable, the differential equations describing the model were solved by numerical integration. Estimates of the model parameters were obtained from an extensive analysis of published human and animal data. These analyses showed that different parameters were needed for the fibrosis model for cigarette smokers and non-smokers, but did not provide enough data to quantitatively deal with the effects of smoking. The application of the model was tested for occupational pneumoconioses, which is characterized by the retention of respirable dust within the interstitial area of the lungs, and by the formation of fibrotic tissue (observable in chest radiographs) around the dust deposits. Formation of fibrosis was modelled as a non-linear process that depends on the level of interstitial dust, and has a maximum rate of fibrosis formation. The model was used to estimate interstitial dust and fibrosis levels of 171 silicon carbide production workers, which were compared to evidence of fibrosis in chest radiographs. A significant correlation ( r =0.62) was found between estimated fibrosis and profusion of opacities on the radiographs. The model predicted that cigarette smokers would have more pulmonary dust and fibrosis than non-smokers with equivalent exposures, which is contrary to epidemiological findings. Differences in dust deposition patterns and mechanisms of dust effects are proposed to explain the observed differences between smokers and non-smokers.