Molecular mechanisms of dust-induced lung disease: exploring the role of physicochemical composition and cellular pathways

Abstract

Respirable dust and fibres in occupational settings are major contributors to lung dysfunction, imposing a significant societal burden. Following the ban on asbestos in most countries, silica and coal mine dust have emerged as primary concerns due to their abundance and persistence in workplace dust. Exposure to dust containing these elements has been strongly linked to pulmonary fibrosis and lung cancer. Extensive research has explored the molecular mechanisms underlying respirable occupational dust-induced cytotoxicity and immune dysregulation. The toxic effects of respirable occupational dust and fibres are largely induced by oxidative stress, mitochondrial dysfunction, lysosomal damage, inflammasome activation and immune suppression. These exposures can trigger multiple cell death pathways, including ferroptosis, necrosis, and pyroptosis. While sharing common toxicological features, silica, coal dust, and asbestos exhibit distinct toxic effects on various pulmonary cell types involved in fibrosis and cancer progression. The immunological consequences of dust exposure are profound, as dust-induced activation of macrophages and neutrophils, together with natural killer (NK) cell dysfunction, sustains chronic inflammation and disrupts epithelial repair and fibroblast regulation, thereby promoting fibrosis and tumorigenesis. Although no curative treatments exist for pulmonary fibrosis, especially coal workers’ pneumoconiosis and silicosis, this review also discusses emerging therapeutic approaches, such as antifibrotic agents and immunotherapy, aimed at mitigating lung fibrosis and lung cancer. This review summarises recent findings on the toxicological mechanisms underlying respirable occupational dust- and fibre-induced lung diseases, with a focus on crystalline silica, and coal dust and asbestos, especially those bearing reduced iron minerals. By highlighting both cellular toxicity and immunological effects, as well as potential therapeutic strategies, this work provides insights into current trends, challenges, and future research directions in the study of respirable occupational dust- and fibre-induced lung diseases.