Indium Lung Disease

Abstract

Indium is a relatively rare element that has had limited use for decades as a metal, in alloys, and for electronics applications. During the past 15 years, global demand for indium has increased several-fold, driven by the novel use of indium-tin oxide (ITO) thin fi lms in the production of fl at-panel displays (such as liquid crystal displays [LCDs]), touch screens, and other electronic devices. 1,2 ITO is a sintered ceramic material typically consisting of 90% indium oxide (In 2 O 3 ) and 10% tin oxide (SnO 2 ). Exposures to indium metal and indium compounds (including indium hydroxide [In(OH) 3 ], indium oxide, and ITO) may occur during ITO production, ITO use for the creation of thin fi lms, and reclamation. The bulk of the ITO industry is located in Japan, with some activity in the United States, China, Taiwan, and South Korea. 3 As of May 2010, 10 clinical cases of lung disease in indium workers from three countries (Japan, United States, and China) had been reported. 2 Seven cases were described as interstitial lung disease (ILD) characterized by pulmonary fi brosis with or without emphysema. Three cases were described as pulmonary alveolar proteinosis (PAP). Individually, these 10 case reports left unclear why some workers developed ILD and others developed PAP, and the relationship, if any, between these distinct pulmonary disease processes.Background: Reports of pulmonary fi brosis, 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, histopathologic, radiologic, 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 4-13 years after fi rst exposure (n 5 7) or PAP 1-2 years after fi rst exposure (n 5 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n 5 9), cholesterol clefts and granulomas (n 5 10), and fi brosis (n 5 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fi brosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fi brosis, 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 fi brosis and emphysema, and, in som...

Cytotoxicity and Characterization of Particles Collected From an Indium–Tin Oxide Production Facility

“…If pulmonary macrophages are injured and cannot perform their normal functions, phagocytosis of pathogens is reduced, leading to increased risk of infections. Furthermore, it is hypothesized that indium lung toxicity results in the accumulation of alveolar surfactant proteins due to macrophage dysfunction (Cummings et al, 2012). This is seen in pulmonary alveolar proteinosis, which is one of the main lung diseases seen in workers from the ITO industry (Cummings et al, 2010(Cummings et al, , 2012.…”

“…Furthermore, it is hypothesized that indium lung toxicity results in the accumulation of alveolar surfactant proteins due to macrophage dysfunction (Cummings et al, 2012). This is seen in pulmonary alveolar proteinosis, which is one of the main lung diseases seen in workers from the ITO industry (Cummings et al, 2010(Cummings et al, , 2012. In addition to the consequences of cell death, it is possible that prior to a loss in viability, release of cytokines, and initiation of an inflammatory response might further damage the epithelium and propagate the disease.…”

“…The resulting diseases were identified as pulmonary alveolar proteinosis (within 6-14 mo of hire) and fibrotic interstitial lung disease with and without emphysema (within 2-14 yr of hire), based on a comprehensive clinical and epidemiologic analysis of 10 reported cases, including 2 from an ITO production facility in the United States (Cummings et al, 2012). Our study utilizes indium compounds collected from this facility at various stages in the ITO production process, from the starting materials to waste generated during the indium reclamation process (Figure 1).…”

Particle-induced Pulmonary Alveolar Proteinosis and Subsequent Inflammation and Fibrosis: A Toxicologic and Pathologic Review

“…Three cases of PAP from indium compounds have been described in the literature (Cummings et al 2010(Cummings et al , 2012Xiao et al 2010). In all 3 cases, PAP occurred within 1-2 yr after initial exposure.…”

“…The radiographic data, using different methods, showed that in 2 patients with PAP a subsequent fibrosis developed. The authors suggested that this disease may begin with PAP and progress to include fibrosis (Cummings et al 2012).…”