Asbestos-related diseases are a major public health problem in the United States. An estimated 14 million individuals have been exposed to asbestos during their working lives. Asbestos has been causally linked to interstitial lung disease, pleural fibrosis, lung cancer, mesothelioma and cancers of the gastrointestinal tract, larynx and possibly kidney. Preliminary studies suggest that altered immunoregulation may play a role in the pathogenesis of asbestos-related diseases. Preliminary findings of increased OKT4+/OKT8+ ratio in peripheral blood of patients with pleural plaques or asbestosis of the lung and increased OKT8+ in lung tissue of patients with idiopathic pulmonary fibrosis suggest compartmental shifts of circulating T8 bearing lymphocytes into tissue. Preliminary findings of decreased natural killer activity in peripheral blood of subjects with asbestos exposure suggest decreased immune surveillance which may be related to carcinogenicity of asbestos.
The aim of this prospective exposure control study is to evaluate further the prevalence of abnormalities of the cellular immune system in asbestos workers and to relate those abnormalities to extent of asbestos exposure and to the presence of asbestos-related diseases. Subjects with low and moderate to high asbestos exposure and normal controls will be evaluated. The investigation will characterize lymphocytes and macrophages by virtue of their reactivity with monoclonal antibodies and by measurements of cell function. With respect to lymphocytes, in vitro natural killer activity will be assessed as will immunoglubin production. With respect to macrophages, assessment of phagocytosis, fibronectin and secretion of soluble mediators will be performed in lung lavage fluid. As an index of asbestos exposure, ferruginous body and asbestos fiber counts will be performed on lung lavage fluid. Fibers will be characterized by elemental analysis and scanning electron microscopy to elucidate fiber type and composition. Serial changes in the immune findings will be correlated with extent of exposure and with clinical manifestations and progression of disease. Statistical methods to be used are one-way analysis of variance, contingency table analysis, multiple linear regression, and longitudinal multivariate analysis. This study will test the validity of measurements of immunity as an index of severity of clinical disease and extent of asbestos exposure.
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