Asbestos exposure and retention as determinants of airway disease and asbestos alveolitis.

To evaluate the relationships of asbestos exposure, retention, airway response, and the asbestos alveolitis, we exposed 2 groups of sheep every 2 wk for 3 yr to either 100 ml phosphate-buffered saline (PBS) or 100 mg UICC chrysotile fibers in 100 ml PBS. The sheep were evaluated periodically by pulmonary function tests (PFT), chest radiograph (CR), bronchoalveolar lavage (BAL), and transbronchial lung biopsy (TLB). At Month 24 of the study, all asbestos-exposed sheep had significant increases in lung resistance and upstream resistance. However, only 9 of the 16 asbestos-exposed sheep had significant changes in TLB, CR, Cst, and VC, which clearly separated them from the other 6 sheep in these parameters. The 2 groups, however, had similar air-flow limitation. At lung biopsy, all asbestos-exposed sheep had significant peribronchiolar fibrosis, with significant alveolitis only in the group of 9 sheep with radiographic and functional changes of early asbestosis. The 9 sheep also had significant changes in BAL cellularity and biochemical profile, which differentiated them from the other 6 asbestos-exposed sheep. Analysis of BAL fiber content at that point revealed that despite identical exposure, the group with interstitial lung disease had significantly more fiber retention (p less than 0.01). The data demonstrate that whereas asbestos airway disease appears to be primarily an exposure-dose-related response, the lung response appears to be more closely related to alveolar retention of the dust.