Mechanistically Identified Suitable Biomarkers of Exposure, Effect, and Susceptibility for Silicosis and Coal-Worker'S Pneumoconiosis: A Comprehensive Review

Abstract

Clinical detection of silicosis is currently dependent on radiological and lung function abnormalities, both late manifestations of disease. Markers of prediction and early detection of pneumoconiosis are imperative for the implementation of timely intervention strategies. Understanding the underlying mechanisms of the etiology of coal workers pneumoconiosis (CWP) and silicosis was essential in proposing numerous biomarkers that have been evaluated to assess effects following exposure to crystalline silica and/or coal mine dust. Human validation studies have substantiated some of these proposed biomarkers and argued in favor of their use as biomarkers for crystalline silica- and CWP-induced pneumoconiosis. A number of “ideal” biological markers of effect were identified, namely, Clara cell protein-16 (CC16) (serum), tumor necrosis factor-α (TNF-α) (monocyte release), interleukin-8 (IL-8) (monocyte release), reactive oxygen species (ROS) measurement by chemiluminescence (neutrophil release), 8-isoprostanes (serum), total antioxidant levels measured by total equivalent antioxidant capacity (TEAC), glutathione, glutathione peroxidase activity, glutathione S-transferase activity, and platelet-derived growth factor (PDGF) (serum). TNF-α polymorphism (blood cellular DNA) was identified as a biomarker of susceptibility. Further studies are planned to test the validity and feasibility of these biomarkers to detect either high exposure to crystalline silica and early silicosis or susceptibility to silicosis in gold miners in South Africa.

This research project was funded by the Safety in Mines Research Advisory Committee (SIMRAC) of the Mines Health and Safety Council. Guidance, stimulation, and intellectual support were provided by Prof. Mary Ross throughout the project. We wish to thank Lincoln Darwin, National Institute for Occupational Health, for valuable technical support throughout the project; Prof. Brendan Girdler-Brown, Head, Department of Community Health, School of Health Systems and Public Health, University of Pretoria; Dr. Belinda Dias, Occupational Medicine Practitioner, Environmental Control, Occupational Health, CSIR Miningtek; and Dr Michelle Wong, Principal Specialist and Head, Respiratory Unit, Chris Hani Baragwanath Hospital.