Beryllium causes progressive granulomatous interstitial lung disease, which is an ongoing problem in the nuclear, aerospace, telecommunications and computer industries. Persons with beryllium disease have cell-mediated immune responses to beryllium, detected by beryllium-specific blast transformation of lung lymphocytes obtained through bronchoalveolar lavage. Preliminary work suggests that this assay on lymphocytes taken from peripheral blood can identify cases of subclinical beryllium disease among a beryllium-exposed worker population. The purpose of this proposal is to determine whether the lymphocyte transformation test, currently required for diagnosis of beryllium disease, is useful for screening for beryllium disease and for beryllium-sensitized persons who may be at high risk of developing beryllium disease. This proposal will study the lymphocyte transformation test as a screening tool in a descriptive cross-sectional study of 750 beryllium-exposed and 100 stainless steel (control) machinists among the 5,500-person employment of Rockwell International's Rocky Flats plant. Subjects will be interviewed for symptoms, medical history, and work history, and will give a blood sample to test for lymphocyte transformation to beryllium salts. Beryllium- sensitized subjects identified by the test, as well as subjects with abnormal chest radiographs, will undergo clinical evaluation to diagnose whether they have beryllium disease. The clinical evaluation includes pulmonary function tests, bronchoalveolar lavage for lung lymphocyte transformation to beryllium, and transbronchial biopsy for a tissue diagnosis. In a nested case- control study, possible risk factors for beryllium sensitization and disease will be evaluated, including indices of cumulative beryllium exposure and exposure to beryllium fume, in contrast to dust from machining. A validated screening test for beryllium disease would be invaluable in identifying persons in whom removal from further beryllium exposure or treatment with steroid medications might lower risk of subsequent impairment from this chronic respiratory disease. The validity and reproducibility of the blood lymphocyte test will be established by the test's identification of subclinical beryllium disease cases and by retesting a random sample of study participants. The sensitivity of the test will be evaluated by diagnostic evaluation of persons with abnormal chest radiographs whose lymphocyte transformation tests are negative. The specificity of the test may require longitudinal study in the event that beryllium-sensitized persons are identified who do not currently have subclinical beryllium disease. This proposal is the critical step in development of a screening test for the prevention of beryllium disease among the 800,000 Americans who have had industrial exposure to beryllium.
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