Indium lung disease

Abstract

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, 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 first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic 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 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 fibrosis 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 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.

Figure 1.

Case A: CT scans of the chest showing progression of disease over 5 years. A, In January 2001 at age 51 years, 3.5 months after leaving employment. In this area of the lung, the predominant finding is mild interlobular septal thickening. B, In July 2001 at age 51 years, 10 months after leaving employment. Increased septal thickening and the development of ground-glass opacities are seen. C, In February 2002 at age 52 years, 1.5 years after leaving employment and 6 months after whole-lung lavage. Fibrotic changes are now apparent, including subpleural septal thickening and traction bronchiectasis. D, In June 2005 at age 55 years, nearly 5 years after leaving employment. Early honeycombing changes are apparent posteriorly. E, In July 2006 at age 56 years, nearly 6 years after leaving employment. Further increases in septal thickening, traction bronchiectasis, and subpleural fibrosis have occurred.

Figure 2.

Case C: CT scans of the chest showing progression of disease over 3 years. A, In November 2007 at age 28 years, 4 months after leaving employment. The predominant findings are ground-glass opacities and interlobular septal thickening that in some areas give the appearance of crazy paving. B, In February 2009 at age 29 years, 1.5 years after leaving employment and 10 months after whole-lung lavage. Fibrosis is now apparent. C, In August 2010 at age 31 years, 3 years after leaving employment. Fibrosis has markedly increased. Prominent air spaces anteriorly may be a precursor to the emphysema seen in other cases.

Figure 3.

Spectrum of histopathologic features of indium lung disease (hematoxylin and eosin stains). A, Case B: intraalveolar exudate characteristic of alveolar proteinosis, with occasional cholesterol clefts (magnification × 200). B, Case D: innumerable cholesterol clefts (magnification × 200). C, Case G: intraalveolar exudate characteristic of alveolar proteinosis, cholesterol clefts, and fibrosis (magnification × 100). D, Case H: cholesterol clefts, associated multinucleated giant cells, interstitial fibrosis, and brown particles composed predominantly of indium (magnification × 200).