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Occupational and Environmental Medicine Aug 2023High silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to...
OBJECTIVES
High silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to determine the prevalence of and risk factors for silicosis among a large cohort of screened SBI workers, and determine the reliability of respiratory function testing (RFT) and chest x-ray (CXR) as screening tests in this industry.
METHODS
Subjects were recruited from a health screening programme available to all SBI workers in Victoria, Australia. Workers undertook primary screening, including an International Labour Office (ILO) classified CXR, and subject to prespecified criteria, also underwent secondary screening including high-resolution CT (HRCT) chest and respiratory physician assessment.
RESULTS
Among 544 SBI workers screened, 95% worked with artificial stone and 86.2% were exposed to dry processing of stone. Seventy-six per cent (414) required secondary screening, among whom 117 (28.2%) were diagnosed with silicosis (median age at diagnosis 42.1 years (IQR 34.8-49.7)), and all were male. In secondary screening, silicosis was associated with longer SBI career duration (12 vs 8 years), older age, lower body mass index and smoking. In those with silicosis, forced vital capacity was below the lower limit of normal in only 14% and diffusion capacity for carbon monoxide in 13%. Thirty-six (39.6%) of those with simple silicosis on chest HRCT had an ILO category 0 CXR.
CONCLUSION
Screening this large cohort of SBI workers identified exposure to dry processing of stone was common and the prevalence of silicosis was high. Compared with HRCT chest, CXR and RFTs had limited value in screening this high-risk population.
Topics: Humans; Male; Adult; Middle Aged; Female; Prevalence; Reproducibility of Results; Silicosis; Silicon Dioxide; Risk Factors; Victoria; Occupational Exposure
PubMed: 37328266
DOI: 10.1136/oemed-2023-108892 -
The Journal of Gene Medicine Aug 2023The overwhelming majority of subjects in the current silicosis mRNA and microRNA (miRNA) expression profile are of human blood, lung cells or a rat model, which puts...
BACKGROUND
The overwhelming majority of subjects in the current silicosis mRNA and microRNA (miRNA) expression profile are of human blood, lung cells or a rat model, which puts limits on the understanding of silicosis pathogenesis and therapy. To address the limitations, our investigation was focused on differentially expressed mRNA and miRNA profiles in lung tissue from silicosis patients to explore potential biomarker for early detection of silicosis.
METHODS
A transcriptome study was conducted based on lung tissue from 15 silicosis patients and eight normal people, and blood samples from 404 silicosis patients and 177 normal people. Three early stage silicosis, five advanced silicosis and four normal lung tissues were randomly selected for microarray processing and analyze. The differentially expressed mRNAs were further used to conduct Gene Ontology and pathway analyses. Series test of cluster was performed to explore possible changes in differentially expressed mRNA and miRNA expression patterns during the process of silicosis. The blood samples and remaining lung tissues were used in a quantitative real-time PCR (RT-qPCR) (RT-qPCR).
RESULTS
In total, 1417 and 241 differentially expressed mRNAs and miRNAs were identified between lung tissue from silicosis patients and normal people (p < 0.05). However, there was no significant difference in most mRNA or miRNA expression between early stage and advanced stage silicosis lung tissues. RT-qPCR validation results in lung tissues showed expression of four mRNAs (HIF1A, SOCS3, GNAI3 and PTEN) and seven miRNAs was significantly down-regulated compared to those of control group. Nevertheless, PTEN and GNAI3 expression was significantly up-regulated (p < 0.001) in blood samples. The bisulfite sequencing PCR demonstrated that PTEN had significantly decreased the methylation rate in blood samples of silicosis patients.
CONCLUSIONS
PTEN might be a potential biomarker for silicosis as a result of low methylation in the blood.
Topics: Humans; Rats; Animals; RNA, Messenger; Lung; MicroRNAs; Silicosis; Biomarkers; Real-Time Polymerase Chain Reaction; Gene Expression Profiling
PubMed: 37403412
DOI: 10.1002/jgm.3518 -
The Journal of the Association of... Oct 2023: Patients with silicosis are at increased risk of pneumothorax. However, the true incidence of pneumothorax in these patients is yet unknown. Our objective was to study...
: Patients with silicosis are at increased risk of pneumothorax. However, the true incidence of pneumothorax in these patients is yet unknown. Our objective was to study the proportion of secondary spontaneous pneumothorax (SSP) in patients with silicosis who present with acute respiratory deterioration. We also analyzed the risk factors, clinical course, actual management, and treatment outcomes of pneumothorax in patients with silicosis. : It was a hospital-based descriptive cross-sectional study. A total of hundred silicosis patients presenting with any acute worsening respiratory symptoms (dyspnea, cough, and chest pain) warranting admission were enrolled. A detailed history, clinical examination, and radiological investigations were done in all cases. : A total of 100 patients were included in this study. The mean age of subjects was 51.6 years. Breathlessness was the most common presenting symptom followed by chest pain. A total of 43 (43%) patients had pneumothorax at presentation. Right-sided pneumothorax was seen in 26 (26%) cases, left-sided in 11 (11%) cases, and six patients (6%) had bilateral pneumothorax. No significant correlation of smoking with pneumothorax was observed in the present study. Around 42% of patients had pulmonary tuberculosis which was microbiologically confirmed. : The present study emphasizes that all patients of silicosis who present with acute worsening shortness of breath and or chest pain need to be evaluated for pneumothorax. : Bairwa M, Sharma A, Luniwal M. Secondary Spontaneous Pneumothorax in Patients with Silicosis. J Assoc Physicians India 2023;71(10):64-66.
Topics: Humans; Silicosis; Pneumothorax; Middle Aged; Cross-Sectional Studies; Male; Female; Adult; Risk Factors; Aged; Chest Pain; Dyspnea; Tuberculosis, Pulmonary
PubMed: 38716526
DOI: 10.59556/japi.71.0348 -
Toxicological Sciences : An Official... Aug 2023Silicosis is a global occupational pulmonary disease due to the accumulation of silica dust in the lung. Lacking effective clinical drugs makes the treatment of this...
Silicosis is a global occupational pulmonary disease due to the accumulation of silica dust in the lung. Lacking effective clinical drugs makes the treatment of this disease quite challenging in clinics largely because the pathogenic mechanisms remain obscure. Interleukin 33 (IL33), a pleiotropic cytokine, could promote wound healing and tissue repair via the receptor ST2. However, the mechanisms governing the involvement of IL33 in silicosis progression remain to be further explored. Here, we demonstrated that the IL33 levels in the lung sections were significantly overexpressed after bleomycin and silica treatment. Chromatin immunoprecipitation assay, knockdown, and reverse experiments were performed in lung fibroblasts to prove gene interaction following exogenous IL33 treatment or cocultured with silica-treated lung epithelial cells. Mechanistically, we illustrated that silica-stimulated lung epithelial cells secreted IL33 and further promoted the activation, proliferation, and migration of pulmonary fibroblasts by activating the ERK/AP-1/NPM1 signaling pathway in vitro. And more, treatment with NPM1 siRNA-loaded liposomes markedly protected mice from silica-induced pulmonary fibrosis in vivo. In conclusion, the involvement of NPM1 in the progression of silicosis is regulated by the IL33/ERK/AP-1 signaling axis, which is the potential therapeutic target candidate in developing novel antifibrotic strategies for pulmonary fibrosis.
Topics: Animals; Mice; Fibroblasts; Fibrosis; Interleukin-33; Lung; Myofibroblasts; Nuclear Proteins; Pulmonary Fibrosis; Signal Transduction; Silicon Dioxide; Silicosis; Transcription Factor AP-1
PubMed: 37399107
DOI: 10.1093/toxsci/kfad061 -
Ecotoxicology and Environmental Safety Oct 2023The role and mechanisms of integrated stress response inhibitor (ISRIB) on silicosis are still not well defined. In the present study, the effects of ISRIB on cellular...
The role and mechanisms of integrated stress response inhibitor (ISRIB) on silicosis are still not well defined. In the present study, the effects of ISRIB on cellular senescence and pulmonary fibrosis in silicosis were evaluated by RNA sequencing, micro-computed tomography, pulmonary function assessment, histological examination, and Western blot analysis. The results showed that ISRIB significantly reduced the degree of pulmonary fibrosis in mice with silicosis and reduced the expression of type I collagen, fibronectin, α-smooth muscle actin, and transforming growth factor-β1. Both in vivo and in vitro results showed that ISRIB reversed the expression of senescence-related factors β-galactosidase, phosphor-ataxia telangiectasia mutated, phosphor-ataxia telangiectasia and Rad3-related protein, p-p53, p21, p16, and plasminogen activator inhibitor type 1. The aforementioned results were consistent with the sequencing results. These findings implied that ISRIB might reduce the degree of pulmonary fibrosis in mice with silicosis by inhibiting the cellular senescence of alveolar epithelial cell type II.
Topics: Animals; Mice; Pulmonary Fibrosis; Silicon Dioxide; Ataxia Telangiectasia; X-Ray Microtomography; Silicosis; Alveolar Epithelial Cells
PubMed: 37647802
DOI: 10.1016/j.ecoenv.2023.115410 -
Cureus Jan 2024This systematic review examines the transformative impact of artificial intelligence (AI) in managing lung disorders through a comprehensive analysis of articles... (Review)
Review
This systematic review examines the transformative impact of artificial intelligence (AI) in managing lung disorders through a comprehensive analysis of articles spanning 2014 to 2023. Evaluating AI's multifaceted roles in radiological imaging, disease burden prediction, detection, diagnosis, and molecular mechanisms, this review presents a critical synthesis of key insights from select articles. The findings underscore AI's significant strides in bolstering diagnostic accuracy, interpreting radiological imaging, predicting disease burdens, and deepening the understanding of tuberculosis (TB), chronic obstructive pulmonary disease (COPD), silicosis, pneumoconiosis, and lung fibrosis. The synthesis positions AI as a revolutionary tool within the healthcare system, offering vital implications for healthcare workers, policymakers, and researchers in comprehending and leveraging AI's pivotal role in lung disease management.
PubMed: 38313926
DOI: 10.7759/cureus.51581 -
Particle and Fibre Toxicology Jul 2023Chronic exposure to silica can lead to silicosis, one of the most serious occupational lung diseases worldwide, for which there is a lack of effective therapeutic drugs...
Chronic exposure to silica can lead to silicosis, one of the most serious occupational lung diseases worldwide, for which there is a lack of effective therapeutic drugs and tools. Epithelial mesenchymal transition plays an important role in several diseases; however, data on the specific mechanisms in silicosis models are scarce. We elucidated the pathogenesis of pulmonary fibrosis via single-cell transcriptome sequencing and constructed an experimental silicosis mouse model to explore the specific molecular mechanisms affecting epithelial mesenchymal transition at the single-cell level. Notably, as silicosis progressed, glycoprotein non-metastatic melanoma protein B (GPNMB) exerted a sustained amplification effect on alveolar type II epithelial cells, inducing epithelial-to-mesenchymal transition by accelerating cell proliferation and migration and increasing mesenchymal markers, ultimately leading to persistent pulmonary pathological changes. GPNMB participates in the epithelial-mesenchymal transition in distant lung epithelial cells by releasing extracellular vesicles to accelerate silicosis. These vesicles are involved in abnormal changes in the composition of the extracellular matrix and collagen structure. Our results suggest that GPNMB is a potential target for fibrosis prevention.
Topics: Mice; Animals; Transcriptome; Silicosis; Lung; Pulmonary Fibrosis; Silicon Dioxide; Epithelial Cells; Transcription Factors; Epithelial-Mesenchymal Transition
PubMed: 37468937
DOI: 10.1186/s12989-023-00543-9 -
Journal of Controlled Release :... Dec 2023Silicosis is a serious silica-induced respiratory disease for which there is currently no effective treatment. Irreversible pulmonary fibrosis caused by persistent...
Silicosis is a serious silica-induced respiratory disease for which there is currently no effective treatment. Irreversible pulmonary fibrosis caused by persistent inflammation is the main feature of silicosis. As an underlying mechanism, acetylation regulated by histone deacetylases (HDACs) are believed to be closely associated with persistent inflammation and pulmonary fibrosis. However, details of the mechanisms associated with the regulation of acetylated modification in silicosis have yet to be sufficiently established. Furthermore, studies on the efficient delivery of DNA to lung tissues by nebulized inhalation for the treatment of silicosis are limited. In this study, we established a mouse model of silicosis successfully. Differentially expressed genes (DEGs) between the lung tissues of silicosis and control mice were identified based on transcriptomic analysis, and HDAC10 was the only DEG among the HDACs. Acetylomic and combined acetylomic/proteomic analysis were performed and found that the differentially expressed acetylated proteins have diverse biological functions, among which 12 proteins were identified as the main targets of HDAC10. Subsequently, HDAC10 expression levels were confirmed to increase following nebulized inhalation of linear poly(β-amino ester) (LPAE)-HDAC10 nanocomplexes. The levels of oxidative stress, the phosphorylation of IKKβ, IκBα and p65, as well as inflammation were inhibited by HDAC10. Pulmonary fibrosis, and lung function in silicosis showed significant improvements in response to the upregulation of HDAC10. Similar results were obtained for the silica-treated macrophages in vitro. In conclusion, HDAC10 was identified as the main mediator of acetylation in silicosis. Nebulized inhalation of LPAE-HDAC10 nanocomplexes was confirmed to be a promising treatment option for silicosis. The ROS/NF-κB pathway was identified as an essential signaling pathway through which HDAC10 attenuates oxidative stress, inflammation, and pulmonary fibrosis in silicosis. This study provides a new theoretical basis for the treatment of silicosis.
Topics: Animals; Mice; Acetylation; Histone Deacetylases; Inflammation; NF-kappa B; Proteomics; Pulmonary Fibrosis; Reactive Oxygen Species; Silicon Dioxide; Silicosis
PubMed: 37848136
DOI: 10.1016/j.jconrel.2023.10.018 -
Journal of Occupational Medicine and... Jul 2023The contribution of bronchoalveolar lavage fluid (BALF) microbiota and mycobiota to silicosis has recently been noticed. However, many confounding factors can influence...
BACKGROUND
The contribution of bronchoalveolar lavage fluid (BALF) microbiota and mycobiota to silicosis has recently been noticed. However, many confounding factors can influence the accuracy of BALF microbiota and mycobiota studies, resulting in inconsistencies in the published results. In this cross-sectional study, we systematically investigated the effects of "sampling in different rounds of BALF" on its microbiota and mycobiota. We further explored the relationship between silicosis fatigue and the microbiota and mycobiota.
METHODS
After obtaining approval from the ethics board, we collected 100 BALF samples from 10 patients with silicosis. Demographic data, clinical information, and blood test results were also collected from each patient. The characteristics of the microbiota and mycobiota were defined using next-generation sequencing. However, no non-silicosis referent group was examined, which was a major limitation of this study.
RESULTS
Our analysis indicated that subsampling from different rounds of BALF did not affect the alpha- and beta-diversities of microbial and fungal communities when the centrifuged BALF sediment was sufficient for DNA extraction. In contrast, fatigue status significantly influenced the beta-diversity of microbes and fungi (Principal Coordinates Analysis, P = 0.001; P = 0.002). The abundance of Vibrio alone could distinguish silicosis patients with fatigue from those without fatigue (area under the curve = 0.938, 95% confidence interval [CI] 0.870-1.000). Significant correlations were found between Vibrio and haemoglobin levels (P < 0.001, ρ = -0.64).
CONCLUSIONS
Sampling in different rounds of BALF showed minimal effect on BALF microbial and fungal diversities; the first round of BALF collection was recommended for microbial and fungal analyses for convenience. In addition, Vibrio may be a potential biomarker for silicosis fatigue screening.
PubMed: 37430310
DOI: 10.1186/s12995-023-00377-3