Indium lung disease.
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.
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV. Electronic address: kcummings@cdc.gov.
Kristin J
KJ
Cummings
Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
Makiko
M
Nakano
Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.
Kazuyuki
K
Omae
Occupational Respiratory Disease Center, Toyama Rosai Hospital, Toyama, Japan.
Koichiro
K
Takeuchi
Department of Medicine, Nikko Memorial Hospital, Hitachi, Japan.
Tatsuya
T
Chonan
Department of Respiratory Medicine, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Yong-Long
YL
Xiao
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC.
Russell A
RA
Harley
Department of Pathology, Duke University Medical Center, Durham, NC.
Victor L
VL
Roggli
Department of Pathology, Tokyo National Hospital, Tokyo, Japan.
Akira
A
Hebisawa
Department of Radiology, West Virginia University School of Medicine, Morgantown, WV.
Robert J
RJ
Tallaksen
Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.
Bruce C
BC
Trapnell
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV.
Gregory A
GA
Day
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV.
Rena
R
Saito
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV.
Marcia L
ML
Stanton
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV; Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA.
Eva
E
Suarthana
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV.
Kathleen
K
Kreiss
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001999:Bronchoscopy; D003937:Diagnosis, Differential; D018450:Disease Progression; D006801:Humans; D007204:Indium / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced* / Q000175:diagnosis; D008297:Male; D009784:Occupational Diseases / Q000139:chemically induced* / Q000175:diagnosis; D016273:Occupational Exposure / Q000009:adverse effects*; D000073718:Pancreatitis-Associated Proteins; D012129:Respiratory Function Tests; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
D015415:Biomarkers; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D007204:Indium