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Pulmonary alveolar proteinosis in indium-exposed workers.

Cummings-KJ; Donat-WE; Ettensohn-DB; Roggli-VL; Ingram-P; Burstein-JM; Pella-JA; Kreiss-K
Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A1742
Introduction: Indium is a relatively rare element that has been used for decades as a metal, in alloys, and for electronics applications. More recently, indium-tin oxide (ITO), a sintered material typically consisting of 90% indium oxide (In2O3) and 10% tin oxide (SnO2), has been used for the production of flat panel displays including liquid crystal displays. Methods: We reviewed documents available through a state workers' compensation system to identify indium-exposed workers with lung disease. Additional medical records were solicited from pulmonologists and occupational medicine physicians. We conducted literature reviews of indium toxicity and pulmonary alveolar proteinosis. Results: From 2000-2007, four male workers producing or recycling ITO at one facility developed radiographically-evident lung disease. The facility's ITO workforce consisted of approximately 15 people. Age of affected workers ranged from 28-51 years. Two of the workers presented with chest symptoms and were diagnosed with pulmonary alveolar proteinosis on the basis of lung tissue specimens showing granular, Periodic acid-Schiff (PAS)-positive intraalveolar material and cholesterol clefts; one of these cases was fatal. One worker with pulmonary alveolar proteinosis was tested for autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) and found to have an elevated level (52.9 mu/ml; normal <3 mu/ml). Both workers with pulmonary alveolar proteinosis had indium detected in lung tissue specimens. A third worker with chest symptoms had abnormalities on high resolution computed tomography (HRCT) scan of the chest, including diffuse 1 mm centrilobular nodules, areas of ground glass opacity, and extensive interlobular septal thickening. A fourth worker who was asymptomatic had HRCT showing mild diffuse prominence of interstitial markings. We found previous reports of exposure to indium resulting in pulmonary pathology, including animal studies showing alveolar proteinosis and two cases of interstitial lung disease in ITO-exposed workers in Japan. While most cases of adult pulmonary alveolar proteinosis are considered to be primary, cases have been reported in association with other occupational and environmental exposures. Conclusions: These cases suggest that inhalational exposure to ITO causes pulmonary alveolar proteinosis, as part of a spectrum of lung disease that includes interstitial lung disease. The detection of autoantibodies to GM-CSF in one of the cases of ITO-related pulmonary alveolar proteinosis indicates an autoimmune disease mechanism. Clinicians should be alert to the potential for pulmonary toxicity with ITO exposure, and effective control measures should be determined and implemented in workplaces where ITO is used.
Age-groups; Airborne-particles; Airway-obstruction; Biological-effects; Biological-monitoring; Breathing; Disease-incidence; Diseases; Dust-inhalation; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Lung; Lung-cells; Lung-disease; Lung-disorders; Lung-function; Lung-irritants; Metal-dusts; Metal-industry; Metal-industry-workers; Metallic-dusts; Metallic-poisons; Occupational-diseases; Occupational-exposure; Occupational-hazards; Occupational-health; Occupational-respiratory-disease; Particulate-dust; Pulmonary-congestion; Pulmonary-disorders; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Respirable-dust; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Risk-factors; Statistical-analysis; Toxic-effects; Toxins; Work-analysis; Work-areas; Work-environment; Worker-health; Work-operations; Work-performance; Workplace-studies; Work-practices; X-ray-analysis; X-ray-diagnosis
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American Journal of Respiratory and Critical Care Medicine