Asbestos-induced lung injury in the sheep model: the initial alveolitis

In order to study the cellular and biochemical changes in early asbestosis, three groups of sheep were repeatedly exposed to intratracheal instillations of either saline (controls), low doses of UICC chrysotile asbestos (LD), or high doses of the fibers (HD) until an alveolitis was observed in all HD sheep during the twelfth month of exposure. All sheep were studied bimonthly by transbronchial lung biopsy (LB), bronchoalveolar lavage (BAL), pulmonary function tests (PFT), and chest roentgenograms (CXR). While LBs of the HD sheep demonstrated large accumulations of monocyte-macrophages in the alveolar and interstitial spaces, those of controls and LD sheep did not. In BAL, there was no difference in total and differential cell counts between groups, but the BAL lymphocyte proliferative capacity was clearly depressed in all asbestos-exposed sheep. In the BAL supernatant, total proteins (mainly albumin, beta + gamma globulins) and lactate dehydrogenase were significantly elevated in the HD group only. This alveolitis was associated with a fall in vital capacity, lung compliance, diffusing capacity, and arterial PO2. Abnormalities on CXR appeared 3 months later. Thus, the cellular and biochemical features of early asbestosis are clearly distinct from those reported in idiopathic pulmonary fibrosis.