Silica‐related diseases in the modern world

Abstract

Silicosis is an ancient and potentially fatal pneumoconiosis caused by exposure to respirable crystalline silica. Silicosis is historically a disease of miners; however, failure to recognize and control the risk associated with silica exposure in contemporary work practices such as sandblasting denim jeans and manufacturing of artificial stone benchtops has led to re‐emergence of silicosis around the world. This review outlines the mineralogy, epidemiology, clinical and radiological features of the various forms of silicosis and other silica‐associated diseases. Perspective is provided on the most recent studies shedding light on pathogenesis, including the central role of innate immune effector cells and subsequent inflammatory cascades in propagating pulmonary fibrosis and the extrapulmonary manifestations, which uniquely characterize this pneumoconiosis. Clinical conundrums in differential diagnosis, particularly between silicosis and sarcoidosis, are highlighted, as is the importance of obtaining a careful occupational history in the patient presenting with pulmonary infiltrates and/or fibrosis. While silicosis is a completely preventable disease, unfortunately workers around the world continue to be affected and experience progressive or even fatal disease. Although no treatments have been proven, opportunities to intervene to prevent progressive disease, founded in a thorough cellular and molecular understanding of the immunopathology of silicosis, are highlighted.

Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease

“…Silicosis is an occupational disease caused by the inhalation of dust containing crystalline silica particles, resulting in lung inflammation and leading to a progressive and irreversible lung fibrosis [67,68]. Choi and colleagues were the first to show that human bone marrow MSC-derived EVs were able to reduce the influx of inflammatory cells and collagen deposition in a murine silicosis pulmonary fibrosis model [50].…”

Silica‐related diseases in the modern world: A role for self‐DNA sensing in lung inflammatory diseases

“…Occupational silica dust exposure induces inflammatory and fibrotic lung disease such as silicosis, often considered as a disease of the past. However, a recent contribution in this journal highlights new causes of silicosis and reviews the clinical patterns of silicosis, which still represents a major concern of pneumoconiosis for man, lacking effective therapeutic treatment beside lung transplantation 1 …”

“…How silica particles cause inflammation and progressive fibrosis is still unresolved, and merits further investigation. The activation of several pathways has been established 1 . These include the activation of TNFα, alarmins, and NLRP3 inflammasome/IL‐1β axis following crystalline silica engulfment by alveolar macrophages, but also reactive oxygen species production and lysosomal damage, as important drivers of inflammation, as reviewed 1 …”

“…Indeed, self‐DNA release activating the cGAS/STING pathway is involved in several models of inflammatory lung diseases in mice such as exposure to cigarette smoke, 5 allergens 6 and ozone (unpublished), which depend on cGAS and/or STING expression. This may contribute to the additive joint effects of combined silica exposure and cigarette smoking on mortality 1 . Both cGAS and STING are druggable, and several small molecules which target these respective pathways are currently in pharmaceutical development.…”

Reply to correspondence: Silica‐related diseases in the modern world: A role for self‐DNA sensing in lung inflammatory

“…This principle applies just as well to newly emerging diseases such as COVID‐19, as it does to ancient conditions such as silicosis. In our review, we provided an overview of current understanding of silicosis epidemiology, risk factors, clinical presentation, radiologic features and pathogenesis and highlighted the central importance of inflammasome activation by macrophages which have phagocytosed reactive‐oxygen species producing silica particles 2 . Quesniaux and her colleagues highlight the increasing interest in the stimulator of interferon genes (STING) pathway and its role in inflammasome activation.…”