Understanding the pathogenesis of occupational coal and silica dust-associated lung disease

Abstract

Workers in the mining and construction industries are at increased risk of respiratory and other diseases as a result of being exposed to harmful levels of airborne particulate matter (PM) for extended periods of time. While clear links have been established between PM exposure and the development of occupational lung disease, the mechanisms are still poorly understood. A greater understanding of how exposures to different levels and types of PM encountered in mining and construction workplaces affect pathophysiological processes in the airways and lungs and result in different forms of occupational lung disease is urgently required. Such information is needed to inform safe exposure limits and monitoring guidelines for different types of PM and development of biomarkers for earlier disease diagnosis. Suspended particles with a 50% cut-off aerodynamic diameter of 10 µm and 2.5 µm are considered biologically active owing to their ability to bypass the upper respiratory tract's defences and penetrate deep into the lung parenchyma, where they induce potentially irreversible damage, impair lung function and reduce the quality of life. Here we review the current understanding of occupational respiratory diseases, including coal worker pneumoconiosis and silicosis, and how PM exposure may affect pathophysiological responses in the airways and lungs. We also highlight the use of experimental models for better understanding these mechanisms of pathogenesis. We outline the urgency for revised dust control strategies, and the need for evidence-based identification of safe level exposures using clinical and experimental studies to better protect workers' health.

FIGURE 1

Pathogenesis of dust particulate matter (PM)-associated occupational lung diseases. Schematic shows the entry of particulate matter (PM₁₀ and below) through environmental/occupational exposure into lungs and development of subsequent respiratory complications, which include increased cellular influx (macrophages, neutrophils, T-lymphocytes and B-cells), alveolar destruction (emphysema) and structural changes (collagen and mucus deposition) leading to chronic bronchitis. PM_x: particles with a 50% cut-off aerodynamic diameter of x µm; CWP: coal worker's pneumoconiosis.

FIGURE 2

Mechanisms of dust particulate matter (PM) toxicity. Schematic representation depicting ambient airborne PM with various cellular mechanisms and triggering cascade reactions, i.e. cellular inflammation, reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, cytokine production and DNA damage, leading to cell death and scar tissue formation. Created with BioRender.com. IL: interleukin; NF-κB: nuclear factor-κB; TNF: tumour necrosis factor.

FIGURE 3

Pathogenesis of reactive crystalline silica (RCS). The illustration depicts the interaction of RCS with lung epithelial cells and subsequent activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway and production of pro-inflammatory cytokine interleukin (IL)-1β, free radicals and fibroblast-activating factor leading to fibrosis. Created with BioRender.com. ROS: reactive oxygen species; RNS: reactive nitrogen species; ASC: apoptosis-associated speck-like protein containing a caspase activation and recruitment domain; TNF: tumour necrosis factor; NF-κB: nuclear factor-κB.

FIGURE 4

Occupational exposure limits (OELs) of a) silica (quartz) and b) coal dust particulate matter (PM). The graphs show that the OEL or safe dust exposure limits of respirable and inhalable fractions of silica and coal dust PM vary significantly among different coal-producing countries. These limits are set primarily on particle size. TWA: time-weighted average; ACGIH: American Conference of Governmental Industrial Hygienists; NIOSH REL: National Institute for Occupational Safety and Health recommended exposure limit; OSHA PEL: Occupational Safety and Health Administration permissible exposure limit; TLV: threshold limit value; MSHA: Mine Safety and Health Administration.