Pathologic and immunologic alterations in early stages of beryllium disease. Re-examination of disease definition and natural history.

Beryllium lung disease is a chronic granulomatous disorder in which a beryllium-specific immune response plays a central role. By using a measure of cellular immune response to beryllium salts, bronchoalveolar lavage (BAL), and lung biopsy, we have identified 12 new cases of beryllium disease. Each of these individuals had pathologic changes on biopsy, lymphocytic alveolitis on BAL, and positive BAL lymphocyte transformation tests (LTT) in response to beryllium sulfate. This group of patients was remarkable for its paucity of clinical findings. At initial evaluation, seven had no respiratory symptoms, and four had normal physical examinations. Five had no increase in interstitial markings on chest radiograph. In eight cases, flow rates and lung volumes were normal. Diffusing capacity for carbon monoxide was low in only one case, and oxygen exchange during exercise was normal in six of nine subjects studied. In addition to the 12 cases, we evaluated eight beryllium-exposed workers who had other (nonberyllium) lung diseases; two of these eight demonstrated beryllium sensitization based on BAL LTT. We conclude that use of fiberoptic bronchoscopy with transbronchial biopsy and BAL facilitates diagnosis of beryllium workers who have histopathologic and immunologic alterations consistent with chronic beryllium disease. These findings may precede frank clinical illness and physiologic impairment, having important implications for our understanding of the natural history of beryllium disease.