BACKGROUND: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. METHODS: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathological, radiological, and epidemiologic data for all reported cases and workplaces was undertaken. RESULTS: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease (ILD) 4-13 years after first exposure (n=7) or PAP 1-2 years after first exposure (n=3). Common pulmonary histopathological features in these patients included intraalveolar exudate typical of alveolar proteinosis (n=9), cholesterol clefts and granulomas (n=10), and fibrosis (n=9). Two patients with ILD had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographical data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among co-workers. CONCLUSIONS: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.
Kristin J. Cummings, MD, MPH, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, MS 2800 47 Morgantown, WV 26505