Morphologic features and function of the airways in early asbestosis in the sheep model.

Previous studies of asbestos exposure in humans and small animals have suggested that air flow limitation associated with small airway disease may be an early manifestation of asbestosis, but the subject is still controversial. In this report, we present the airway morphologic aspects and function of our sheep model of the disease. Three groups of 6 sheep were exposed to repeated intratracheal injections of either saline (control group), 2 mg of UICC Canadian chrysotile asbestos in saline (low exposure group), or 128 mg of the same fibers (high exposure group). At the end of the twelfth month of exposure, an alveolitis had developed in the high exposure group only. Detailed pulmonary function tests were followed within 48 by lung biopsies according to methods described, to which were added air-helium flow-volume curves. Lung biopsies in control and low exposure groups did not demonstrate significant morphologic changes, whereas all biopsies in the high exposure group showed alveolitis characterized by an alveolar and interstitial accumulation of macrophages and mononuclear cells without interstitial fibrosis. On all biopsies, over half of the airways were altered by a similar peribronchiolar process, which at times compressed the peripheral airways. Functionally there was no significant difference between low exposure and control groups. However, compared with the control group, the high exposure group had significantly lower vital capacity (2.0 +/- 0.1 versus 2.9 + 0.1 L, p less than 0.01), lower static lung compliance (91 + 13 versus 132 + 9 ml/cmH2O, p less than 0.05), higher isoflow volume (2.15 + 0.08 versus 1.4 + 0.1 L, p less than 0.01), and higher upstream resistance below the isoflow volume (3.3 + 0.2 versus 1.3 + 0.3 cmH2O L/s, p less than 0.02). These data demonstrate that in the early asbestos-induced peribronchiolar alveolitis of the sheep, which restricts lung volumes, there is a concomitant small airway disease that significantly limits air flow.