New Insights into Pathomechanisms and Treatment Possibilities for Lung Silicosis

Abstract

Inhalation of silica particles is an environmental and occupational cause of silicosis, a type of pneumoconiosis. Development of the lung silicosis is a unique process in which the vicious cycle of ingestion of inhaled silica particles by alveolar macrophages and their release triggers inflammation, generation of nodular lesions, and irreversible fibrosis. The pathophysiology of silicosis is complex, and interactions between the pathomechanisms have not been completely understood. However, elucidation of silica-induced inflammation cascades and inflammation-fibrosis relations has uncovered several novel possibilities of therapeutic targeting. This article reviews new information on the pathophysiology of silicosis and points out several promising treatment approaches targeting silicosis-related pathways.

Tuberculosis and Silicosis Burden in Artisanal and Small-Scale Gold Miners in a Large Occupational Health Outreach Programme in Zimbabwe

“…Inhaled silica dust is ingested by alveolar macrophages, which produce cytokines which stimulate fibroblasts to proliferate and produce increased amounts of collagen, resulting in lung fibrosis. However, the pathological changes in silica-injured lungs are complex and not completely understood [ 21 ]. In the early stages of silicosis, a chest radiograph shows isolated opacities against a normal lung parenchyma that can progress over years to a reticulonodular infiltrate.…”

Early Identification, Accurate Diagnosis, and Treatment of Silicosis

“…It is well documented that the inhalation of silica particles is an environmental and occupational cause of silicosis, a type of pneumoconiosis [ 5 ]. The diverse physiochemical properties, including size, morphology, polymorphism, porosity, and surface, determine the toxicity of the silica particles.…”

“…The diverse physiochemical properties, including size, morphology, polymorphism, porosity, and surface, determine the toxicity of the silica particles. Silica particles are defined as “respirable” when they are less than 5 μ m in diameter, which is small enough to reach the distal airways and alveoli [ 5 ]. Furthermore, crystalline silica particles are the leading cause of occupational respiratory disease and are generally considered more toxic than amorphous silica particles [ 3 ].…”

“…Other potential drugs have been reported to inhibit silica-induced pulmonary inflammation and fibrosis in silicotic models such as anticytokines (anakinra, anti-IL-17 antibody, and anti-IL-9 antibody), antioxidants (N-acetylcysteine, corticosteroids, and dexamethasone), agents influencing the autophagic-lysosome system (imipramine, dioscin, and rapamycin), agents increasing cAMP levels, and microRNAs [ 5 ]. Mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) possess immunoregulatory and reparative abilities, which modulate innate and adaptive immunity and have shown great therapeutic potential in silicosis [ 54 ].…”

COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends

“…Activation of P2X7 receptor enhances chemokine and cytokine release such as IL‐6, IL-8, TNF‐α, CCL2, CCL3 and pro‐fibrotic factors for example TGF‐β. In P2X7 deficient mice model of silica‐induced lung fibrosis or models of bleomycin, reduced inflammation was observed [169] , [170] , [171] . Thus, it suggests that P2X7 receptor deletion or antagonists might be of benefit for less severe COVID‐19 patients.…”