Dataset Information

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.

SUBMITTER: Cummings KJ

PROVIDER: S-EPMC3367484 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Publications

Indium lung disease.

Cummings Kristin J KJ Nakano Makiko M Omae Kazuyuki K Takeuchi Koichiro K Chonan Tatsuya T Xiao Yong-Long YL Harley Russell A RA Roggli Victor L VL Hebisawa Akira A Tallaksen Robert J RJ Trapnell Bruce C BC Day Gregory A GA Saito Rena R Stanton Marcia L ML Suarthana Eva E Kreiss Kathleen K

Chest 20111229 6

<h4>Background</h4>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.<h4>Methods</h4>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.<h4> ...[more]

PMID: 22207675

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Project description:RationaleOccupational exposure to indium compounds, including indium-tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood.ObjectivesTo determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities.MethodsAmong indium-tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models.Measurements and main resultsEighty-seven (93%) of 94 indium-tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures.ConclusionsIn indium-tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease.

Project description:We have recently shown that the toxicological potential of GaAs and InAs particulates in cells is size- and dissolution-dependent, tending to be more pronounced for nano- vs micron-sized particles. Whether the size-dependent dissolution and shedding of ionic III-V materials also apply to pulmonary exposure is unclear. While it has been demonstrated that micron-sized III-V particles, such as GaAs and InAs, are capable of inducing hazardous pulmonary effects in an occupational setting as well as in animal studies, the effect of submicron particles (e.g., the removal of asperities during processing of semiconductor wafers) is unclear. We used cytokine profiling to compare the pro-inflammatory effects of micron- and nanoscale GaAs and InAs particulates in cells as well as the murine lung 40 h and 21 days after oropharyngeal aspiration. Use of cytokine array technology in macrophage and epithelial cell cultures demonstrated a proportionally higher increase in the levels of matrix metalloproteinase inducer (EMMPRIN), macrophage migration inhibitory factor (MIF), and interleukin 1β (IL-1β) by nanosized (n) GaAs and n-InAs as well as As(III). n-GaAs and n-InAs also triggered higher neutrophil counts in the bronchoalveolar lavage fluid (BALF) of mice than micronscale particles 40 h post-aspiration, along with increased production of EMMPRIN and MIF. In contrast, in animals sacrificed 21 days after exposure, only n-InAs induced fibrotic lung changes as determined by increased lung collagen as well as increased levels of TGF-β1 and PDGF-AA in the BALF. A similar trend was seen for EMMPRIN and matrix metallopeptidase (MMP-9) levels in the BALF. Nano- and micron-GaAs had negligible subacute effects. Importantly, the difference between the 40 h and 21 days data appears to be biopersistence of n-InAs, as demonstrated by ICP-OES analysis of lung tissue. Interestingly, an ionic form of In, InCl3, also showed pro-fibrogenic effects due to the formation of insoluble In(OH)3 nanostructures. All considered, these data indicate that while nanoscale particles exhibit increased pro-inflammatory effects in the lung, most effects are transient, except for n-InAs and insoluble InCl3 species that are biopersistent and trigger pro-fibrotic effects. These results are of potential importance for the understanding the occupational health effects of III-V particulates.

Dataset Information

Indium lung disease.

Background

Methods

Results

Conclusions

Publications

Indium lung disease.

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