Serum YKL-40 in Workers at an Indium-Tin Oxide Production Facility

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• Personal Author:
  Cummings, Kristin J. ; Harvey, R. Reid ; Hawley BM ; Virji, M. Abbas
• Description:
  To the Editors: We read with great interest the study by Bonella et al., in which the authors evaluated the utility of serum YKL-40 as a biomarker for pulmonary alveolar proteinosis (PAP). They found that YKL-40 correlated with respiratory impairment and disease outcome. The study subjects had primary autoimmune PAP, characterized by elevated GM-CSF antibodies. Less commonly, secondary PAP can occur in association with immunosuppression, haematological disorders and occupational inhalation exposure to certain dusts or fumes. GM-CSF antibodies are generally within the normal range in cases of secondary PAP, although the role of GM-CSF antibodies in secondary PAP due to occupational dust exposure remains an area of active inquiry. Indium lung disease is a potentially fatal lung condition that is characterized by PAP, emphysema and/or fibrosis in workers exposed to indium-tin oxide (ITO) and/or other indium-containing compounds. We reported two cases of PAP in workers at a US ITO production facility in 2010, one of whom had elevated GM-CSF antibodies and the other was not tested. Xiao et al. reported a case of PAP in an indium-exposed worker who had GM-CSF antibodies within the normal range. In 2012, we evaluated the current workforce at the US ITO production facility where the PAP cases had occurred. In addition to symptoms and lung function, we assessed a number of biomarkers. No clinical cases of PAP or indium lung disease were identified in the 87 workers evaluated; however, plasma indium concentrations were associated with respiratory symptoms, decreased spirometric parameters and increased KL-6 and SP-D, which are biomarkers of interstitial lung disease. KL-6 and SP-D were elevated in 58% and 10% of workers, respectively. GM-CSF and LDH were not elevated in any of the workers tested. Interestingly, YKL-40 was elevated in 19% of workers, but was not correlated with plasma indium. We repeated the evaluation of current workers in 2014. Median YKL-40 from 2012 to 2014 evaluations was 57 ng/mL (mean: 80; range: 20-590 ng/mL). In light of the study by Bonella et al., we revisited our 2012 and 2014 data to evaluate relationships between YKL-40 and other biomarkers as well as lung function parameters in more detail. Although Bonella et al. found a positive correlation with LDH and an inverse correlation with diffusing capacity of the lung for carbon monoxide (DLCO), we found that YKL-40 did not correlate well with any biomarker or lung function parameter we tested. There was a weak correlation between YKL-40 and C-reactive protein (CRP). YKL-40 was higher in current or former smokers than never smokers (101 ng/mL vs 61 ng/mL; P = 0.01). We found no difference in YKL-40 by gender. Unlike in the study by Bonella et al., we did observe a significant positive correlation between YKL-40 and age. Our study population differed substantially from that of Bonella et al. We surveyed healthy workers potentially at risk for secondary PAP following occupational ITO exposure, whereas Bonella et al. surveyed patients with primary autoimmune PAP. However, the lack of significant associations between indium exposure and YKL-40, GM-CSF and LDH is noteworthy, and in contrast to the utility of KL-6 and SP-D in this worker population. [Description provided by NIOSH]
• Subjects:
  Antibodies Biomarkers Cells, Cultured Immune System Indium Lipids Lung Lung Diseases Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Surface-Active Agents

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• Keywords:
  Alveolar Cells Autoimmune Diseases Case Reports Cell Cultures Cell Culture Techniques Cytokines Employee Exposure Gene Expression Humans Immune Reaction Immune System Indium Compounds Lung-disorders Lung-function Proteins Pulmonary-function Pulmonary-system-disorders Respiratory-system-disorders Risk-factors Serology Surfactants Tin Oxides Tissue Disorders

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• ISSN:
  1323-7799
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  341-342
• Volume:
  23
• Issue:
  3
• NIOSHTIC Number:
  nn:20050760
• Citation:
  Respirology 2018 Mar; 23(3):341-342
• Contact Point Address:
  R. Reid Harvey, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, Mailstop H2800, Morgantown, WV 26505, USA
• Email:
  iez1@cdc.gov
• CAS Registry Number:
  Indium (CAS RN 7440-74-6) ; Indium tin oxide (In1.69Sn0.15O2.85) (CAS RN 71243-84-0)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  Respirology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7e131daea539503994da9d664216b7a75a95befdf560d7591df37097470ab1525e5451e4898ccdc82e13928321c68866a67f65ae3f05af014e1b4b74b199bbad
• Download URL:
  https://stacks.cdc.gov/view/cdc/210983/cdc_210983_DS1.pdf
• File Type:
  [PDF - 200.84 KB ]