Metal-Induced Diffuse Lung Disease

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The number of metals that are associated with the development of diffuse parenchymal lung disease continues to expand. In addition to lung fibrosis, inhalation of metal particulates can induce a wide range of lung pathology, including reactive airways disease and cancer. This article focuses on diffuse parenchymal diseases resulting from the inhalation of beryllium and cobalt. More is known regarding the immunopathogenesis of beryllium-induced disease than is known for disease induced by any other metal. Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium exposure in the workplace and is characterized by the accumulation of beryllium-specific CD4+ T cells in the bronchoalveolar lavage. Genetic susceptibility markers associated with increased risk have been identified for both CBD and hard metal lung disease. The mechanism for the genetic susceptibility of CBD lies in the ability of certain human leukocyte antigen (HLA)-DP molecules to bind and present beryllium to pathogenic CD4+ T cells. Whether the same is true for hard metal lung disease is unknown. In contrast, no HLA allelic association has been identified in nickel allergic subjects. The study of metal-induced lung disease allows the investigation of the relationship between environmental exposure and genetic susceptibility. These studies will enhance our understanding of the immunopathogenesis of metal-induced disease and how exposure to these metals results in irreversible lung fibrosis.

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