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Journal of Internal Medicine Dec 2023Millions of workers are exposed to substances known to cause occupational interstitial lung diseases (ILDs), particularly in developing countries. However, the burden of... (Review)
Review
Millions of workers are exposed to substances known to cause occupational interstitial lung diseases (ILDs), particularly in developing countries. However, the burden of the disease is likely to be underestimated due to under-recognition, under-reporting or both. The diagnosis of occupational ILD requires a high level of suspicion and a thorough occupational history, as occupational and non-occupational ILDs may be clinically, functionally and radiologically indistinguishable, leading to delayed diagnosis and inappropriate management. A potential occupational aetiology should always be considered in the differential diagnosis of ILD, as removal from the workplace exposure, with or without treatment, is a key therapeutic intervention and may lead to significant improvement. In this article, we provide an overview of the 'traditional' inorganic dust-related ILDs but also address idiopathic pulmonary fibrosis and the immunologically mediated chronic beryllium disease, sarcoidosis and hypersensitivity pneumonitis, with emphasis on the importance of surveillance and prevention for reducing the burden of these conditions. To this end, health-care professionals should be specifically trained about the importance of occupational exposures as a potential cause of ILD.
Topics: Humans; Diagnosis, Differential; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Sarcoidosis
PubMed: 37535448
DOI: 10.1111/joim.13707 -
Journal of Hazardous Materials Jan 2024Macrophages are essential for the maintenance of endothelial cell function. However, the potential impact and mechanisms of crosstalk between macrophages and endothelial...
Macrophages are essential for the maintenance of endothelial cell function. However, the potential impact and mechanisms of crosstalk between macrophages and endothelial cells during silicosis progression remain unexplored. To fill this knowledge gap, a mouse model of silicosis was established. Single cell sequencing, spatial transcriptome sequencing, western blotting, immunofluorescence staining, tube-forming and wound healing assays were used to explore the effects of silicon dioxide on macrophage-endothelial interactions. To investigate the mechanism of macrophage-mediated fibrosis, MMP12 was specifically inactivated using siRNA and pharmacological approaches, and macrophages were depleted using disodium chlorophosphite liposomes. Compared to the normal saline group, the silica dust group showed altered macrophage-endothelial interactions. Matrix metalloproteinase family member MMP12 was identified as a key mediator of the altered function of macrophage-endothelial interactions after silica exposure, which was accompanied by pro-inflammatory macrophage activation and fibrotic progression. By using ablation strategies, macrophage-derived MMP12 was shown to mediate endothelial cell dysfunction by accumulating on the extracellular matrix. During the inflammatory phase of silicosis, MMP12 secreted by pro-inflammatory macrophages caused decreased endothelial cell viability, reduced migration, decreased trans-endothelial resistance and increased permeability; while during the fibrotic phase, macrophage-derived MMP12 sustained endothelial cell injury through accumulation on the extracellular matrix.
Topics: Animals; Mice; Matrix Metalloproteinase 12; Endothelial Cells; Fibrosis; Macrophages; Silicosis; Silicon Dioxide
PubMed: 37816293
DOI: 10.1016/j.jhazmat.2023.132733 -
Molecular Aspects of Medicine Aug 2023Fibrosis, or tissue scarring, develops as a pathological deviation from the physiological wound healing response and can occur in various organs such as the heart, lung,... (Review)
Review
Fibrosis, or tissue scarring, develops as a pathological deviation from the physiological wound healing response and can occur in various organs such as the heart, lung, liver, kidney, skin, and bone marrow. Organ fibrosis significantly contributes to global morbidity and mortality. A broad spectrum of etiologies can cause fibrosis, including acute and chronic ischemia, hypertension, chronic viral infection (e.g., viral hepatitis), environmental exposure (e.g., pneumoconiosis, alcohol, nutrition, smoking) and genetic diseases (e.g., cystic fibrosis, alpha-1-antitrypsin deficiency). Common mechanisms across organs and disease etiologies involve a sustained injury to parenchymal cells that triggers a wound healing response, which becomes deregulated in the disease process. A transformation of resting fibroblasts into myofibroblasts with excessive extracellular matrix production constitutes the hallmark of disease, however, multiple other cell types such as immune cells, predominantly monocytes/macrophages, endothelial cells, and parenchymal cells form a complex network of profibrotic cellular crosstalk. Across organs, leading mediators include growth factors like transforming growth factor-β and platelet-derived growth factor, cytokines like interleukin-10, interleukin-13, interleukin-17, and danger-associated molecular patterns. More recently, insights into fibrosis regression and resolution of chronic conditions have deepened our understanding of beneficial, protective effects of immune cells, soluble mediators and intracellular signaling. Further in-depth insights into the mechanisms of fibrogenesis can provide the rationale for therapeutic interventions and the development of targeted antifibrotic agents. This review gives insight into shared responses and cellular mechanisms across organs and etiologies, aiming to paint a comprehensive picture of fibrotic diseases in both experimental settings and in human pathology.
Topics: Humans; Endothelial Cells; Fibrosis; Myofibroblasts; Cytokines; Fibroblasts
PubMed: 37236017
DOI: 10.1016/j.mam.2023.101191 -
Surgical Pathology Clinics Jun 2024Although silicosis has been an established disease with a recognized cause for more than 100 years, many workers continue to be exposed to silica and new outbreaks of... (Review)
Review
Although silicosis has been an established disease with a recognized cause for more than 100 years, many workers continue to be exposed to silica and new outbreaks of disease continue to occur. This article describes some of the well-established and new exposures, including denim sandblasting, artificial stone cutting, and some forms of "coal worker's pneumoconiosis." The authors review the imaging and pathology of acute silicosis (silicoproteinosis), simple silicosis, and progressive massive fibrosis and summarize known and putative associations of silica exposure, including tuberculosis, lung cancer, connective tissue disease (especially systemic sclerosis), and vasculitis.
Topics: Silicosis; Humans; Occupational Exposure; Silicon Dioxide
PubMed: 38692804
DOI: 10.1016/j.path.2023.11.005 -
Nederlands Tijdschrift Voor Geneeskunde Jun 2023Silicosis is a potentially severe but preventable occupational lung disease caused by inhalation of silica particles. There is a wide application in the usage of silica...
BACKGROUND
Silicosis is a potentially severe but preventable occupational lung disease caused by inhalation of silica particles. There is a wide application in the usage of silica especially in lesser known industries. This disease has yet not been eradicated due to insufficient application of protective measures.
CASE DESCRIPTION
A 57-year-old patient presents to the pulmonary outpatient clinic with progressive dyspnea d'effort. The professional history states that he worked as a sandblaster 10 years ago. The accompanying protective measures were not properly followed by the patient at the time. The CT chest showed a nodular interstitial lung disease and silica particles were detected in the bronchial lavage conforming the diagnosis of silicosis.
CONCLUSION
Early detection of silicosis is essential to prevent further lung damage and silicosis associated complications. The occupational history and radiological diagnostics are essential to confirm the diagnosis. There is no specific treatment for silicosis. Therefore prevention is better than cure.
Topics: Male; Humans; Middle Aged; Silicosis; Lung; Silicon Dioxide; Occupational Diseases; Dyspnea; Occupational Exposure
PubMed: 37493338
DOI: No ID Found -
Medicina Clinica Aug 2023
Topics: Humans; Silicosis
PubMed: 37142514
DOI: 10.1016/j.medcli.2023.03.028 -
Journal of Hazardous Materials Jul 2023Environmental exposure to crystalline silica (CS) can lead to silicosis. Alveolar macrophages (AMs) play a crucial role in the pathogenesis of silicosis. Previously, we...
Environmental exposure to crystalline silica (CS) can lead to silicosis. Alveolar macrophages (AMs) play a crucial role in the pathogenesis of silicosis. Previously, we demonstrated that enhancing AMs mitophagy exerted protective effects on silicosis with a restrained inflammatory response. However, the exact molecular mechanisms are elusive. Pyroptosis and mitophagy are two different biological processes that determine cell fate. Exploring whether there were interactions or balances between these two processes in AMs would provide new insight into treating silicosis. Here we reported that crystalline silica induced pyroptosis in silicotic lungs and AMs with apparent mitochondria injury. Notably, we identified a reciprocal inhibitory effect between mitophagy and pyroptosis cascades in AMs. By enhancing or diminishing mitophagy, we demonstrated that PINK1-mediated mitophagy helped clear damaged mitochondria to negatively regulate CS-induced pyroptosis. While constraining pyroptosis cascades by NLRP3, Caspase1, and GSDMD inhibitors, respectively, displayed enhanced PINK1-dependent mitophagy with lessened CS-injured mitochondria. These observed effects were echoed in the mice with enhanced mitophagy. Therapeutically, we demonstrated abolishing GSDMD-dependent pyroptosis by disulfiram attenuated CS-induced silicosis. Collectively, our data demonstrated that macrophage pyroptosis interacting with mitophagy contributes to pulmonary fibrosis via modulating mitochondria homeostasis, which may provide potential therapeutic targets.
Topics: Mice; Animals; Pulmonary Fibrosis; Silicon Dioxide; Mitophagy; Pyroptosis; Macrophages; Silicosis; Protein Kinases; Mitochondria
PubMed: 37148789
DOI: 10.1016/j.jhazmat.2023.131562