-
International Journal of Environmental... May 2024The lifetime risk of silicosis associated with low-level occupational exposure to respirable crystalline silica remains unclear because most previous radiographic...
The lifetime risk of silicosis associated with low-level occupational exposure to respirable crystalline silica remains unclear because most previous radiographic studies included workers with varying exposure concentrations and durations. This study assessed the prevalence of silicosis after lengthy exposure to respirable crystalline silica at levels ≤ 0.10 mg/m. Vermont granite workers employed any time during 1979-1987 were traced and chest radiographs were obtained for 356 who were alive in 2017 and residing in Vermont. Work history, smoking habits and respiratory symptoms were obtained by interview, and exposure was estimated using a previously developed job-exposure matrix. Associations between radiographic findings, exposure, and respiratory symptoms were assessed by ANOVA, chi-square tests and binary regression. Fourteen workers (3.9%) had radiographic evidence of silicosis, and all had been employed ≥30 years. They were more likely to have been stone cutters or carvers and their average exposure concentrations and cumulative exposures to respirable crystalline silica were significantly higher than workers with similar durations of employment and no classifiable parenchymal abnormalities. This provides direct evidence that workers with long-term exposure to low-level respirable crystalline silica (≤0.10 mg/m) are at risk of developing silicosis.
Topics: Humans; Silicon Dioxide; Silicosis; Occupational Exposure; Male; Vermont; Middle Aged; Adult; Female; Follow-Up Studies; Air Pollutants, Occupational; Prevalence; Inhalation Exposure; Aged
PubMed: 38791822
DOI: 10.3390/ijerph21050608 -
Ecotoxicology and Environmental Safety Jul 2024Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative...
Oxidative stress and inflammation play a fundamental role in the beginning and advancement of silicosis. Hence, questing active phytocompounds (APCs) with anti-oxidative and anti-inflammatory properties such as diosgenin (DG) and emodin (ED) can be a therapeutic intervention targeting silica-induced pulmonary inflammation and fibrosis. Hydrophobicity and low bioavailability are the barriers that restrict the therapeutic efficacy of DG and ED against pulmonary defects. Encapsulating these APCs in polymeric nanoparticles can overcome this limitation. The present study has thus explored the anti-inflammatory and anti-fibrotic effects of polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) individually loaded with DG (DGn) or ED (EDn) and in combine DG+ED [(DG+ED)n] in respirable silica dust (RSD)-induced pulmonary fibrosis silicosis rat model. Our study found that individual and combined NPs revealed physiochemical characteristics appropriate for IV administration with sustained-drug release purposes. Physiological evaluations of RSD-induced silicosis rats suggested that no treatment could improve the body weight. Still, they reduced the lung coefficient by maintaining lung moisture. Only (DG+ED)n significantly cleared free lung silica. All interventions were found to attribute the increased per cent cell viability in BALF, reduce cytotoxicity via minimizing LDH levels, and balance the oxidant-antioxidant status in silicotic rats. The expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1, and TGF-β1) were efficiently down-regulated with NPs interventions compared to pure (DG+ED) treatment. All drug treatments significantly declined, the 8-HdG and HYP productions indicate that RSD-induced oxidative DNA damage and collagen deposition were successfully repaired. Moreover, histopathological investigations proposed that individual or combined drugs NPs interventions could decrease the fibrosis and alveolitis grades in RSD-induced silicosis rats. However, (DG+ED)n intervention significantly inhibited pulmonary fibrosis and alveolitis compared to pure (DG+ED) treatment. In conclusion, the RSD can induce oxidative stress and inflammation in rats, producing reactive oxygen species (ROS)-mediated cytotoxicity to pulmonary cells and leading to silicosis development. The IV administration of combined NP suppressed lung inflammation and collagen formation by maintaining oxidant-antioxidant status and effectively interrupting the fibrosis-silicosis progression. These results may be attributed to the improved bioavailability of DG and ED through their combined nano-encapsulation-mediated targeted drug delivery.
Topics: Animals; Diosgenin; Silicosis; Silicon Dioxide; Pulmonary Fibrosis; Rats; Emodin; Nanoparticles; Male; Dust; Oxidative Stress; Anti-Inflammatory Agents; Rats, Wistar; Lung; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 38788565
DOI: 10.1016/j.ecoenv.2024.116483 -
Indian Journal of Occupational and... 2024Silicosis is a progressive pneumoconiosis caused by inhalation of crystalline silica dust commonly seen in workers of construction sites, flour mills, and mining....
Silicosis is a progressive pneumoconiosis caused by inhalation of crystalline silica dust commonly seen in workers of construction sites, flour mills, and mining. Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus antigens commonly encountered in patients with asthma and cystic fibrosis. We report a case of 60-year-old flour mill worker presented with clinico-radiological features of silicosis; further evaluation was found to have an overlap of ABPA in view of severe atopic symptoms. We describe a rare duet of silicosis with ABPA overlap.
PubMed: 38783879
DOI: 10.4103/ijoem.ijoem_170_23 -
Frontiers in Immunology 2024TAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous...
INTRODUCTION
TAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous cellular turnover and generation of apoptotic cells. Some studies have identified failures in efferocytosis as a common driver of inflammation and tissue destruction in lung diseases. Our study is the first to characterize the function of the TAM receptors, Axl and MerTk, in the innate immune cell compartment, cytokine and chemokine production, as well as the alveolar macrophage (AM) phenotype in different settings in the airways and lung parenchyma.
METHODS
We employed MerTk and Axl defective mice to induce acute silicosis by a single exposure to crystalline silica particles (20 mg/50 μL). Although both mRNA levels of Axl and MerTk receptors were constitutively expressed by lung cells and isolated AMs, we found that MerTk was critical for maintaining lung homeostasis, whereas Axl played a role in the regulation of silica-induced inflammation. Our findings imply that MerTk and Axl differently modulated inflammatory tone via AM and neutrophil recruitment, phenotype and function by flow cytometry, and TGF-β and CXCL1 protein levels, respectively. Finally, Axl expression was upregulated in both MerTk and WT AMs, confirming its importance during inflammation.
CONCLUSION
This study provides strong evidence that MerTk and Axl are specialized to orchestrate apoptotic cell clearance across different circumstances and may have important implications for the understanding of pulmonary inflammatory disorders as well as for the development of new approaches to therapy.
Topics: Animals; Mice; Axl Receptor Tyrosine Kinase; c-Mer Tyrosine Kinase; Cytokines; Disease Models, Animal; Homeostasis; Lung; Macrophages, Alveolar; Mice, Inbred C57BL; Mice, Knockout; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Silicosis; Male
PubMed: 38774866
DOI: 10.3389/fimmu.2024.1380628 -
Scientific Reports May 2024Accurate and early detection of pneumoconiosis using chest X-rays (CXR) is important for preventing the progression of this incurable disease. It is also a challenging...
Accurate and early detection of pneumoconiosis using chest X-rays (CXR) is important for preventing the progression of this incurable disease. It is also a challenging task due to large variations in appearance, size and location of lesions in the lung regions as well as inter-class similarity and intra-class variance. Compared to traditional methods, Convolutional Neural Networks-based methods have shown improved results; however, these methods are still not applicable in clinical practice due to limited performance. In some cases, limited computing resources make it impractical to develop a model using whole CXR images. To address this problem, the lung fields are divided into six zones, each zone is classified separately and the zone classification results are then aggregated into an image classification score, based on state-of-the-art. In this study, we propose a dual lesion attention network (DLA-Net) for the classification of pneumoconiosis that can extract features from affected regions in a lung. This network consists of two main components: feature extraction and feature refinement. Feature extraction uses the pre-trained Xception model as the backbone to extract semantic information. To emphasise the lesion regions and improve the feature representation capability, the feature refinement component uses a DLA module that consists of two sub modules: channel attention (CA) and spatial attention (SA). The CA module focuses on the most important channels in the feature maps extracted by the backbone model, and the SA module highlights the spatial details of the affected regions. Thus, both attention modules combine to extract discriminative and rich contextual features to improve classification performance on pneumoconiosis. Experimental results show that the proposed DLA-Net outperforms state-of-the-art methods for pneumoconiosis classification.
Topics: Humans; Pneumoconiosis; Neural Networks, Computer; Radiography, Thoracic; Lung
PubMed: 38773153
DOI: 10.1038/s41598-024-61024-3 -
Cureus Apr 2024Pneumoconiosis is a form of interstitial lung disease (ILD) that commonly occurs secondary to occupational or environmental exposures. This is an emerging disease as...
Pneumoconiosis is a form of interstitial lung disease (ILD) that commonly occurs secondary to occupational or environmental exposures. This is an emerging disease as there are many potential forms of pathologic insults. Further adding to the complication is that clinical symptomatology secondary to pneumoconiosis can have long latent periods, as repetitive exposure over years leads to long-standing inflammation and subsequent irreversible damage. Exposure to asbestos, coal, silica, aluminum, talc, hay, and many more agents has the potential to cause pneumoconiosis. This case highlights a veteran, who made his career working with heavy metals such as chromium, beryllium, and titanium in the aerospace defense industry. This case discusses high-risk occupations, a workup for suspected pneumoconiosis, management, and the mechanism of lung injury underlying the three aforementioned pathologic agents. In each case of pneumoconiosis, a thorough history is essential, and diagnoses are made via the incorporation of the patient's historical risk factors, pulmonary function test (PFT) findings, and high-resolution chest computed tomography (HRCT).
PubMed: 38756299
DOI: 10.7759/cureus.58392 -
Association of smoking cessation with airflow obstruction in workers with silicosis: A cohort study.PloS One 2024Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease...
BACKGROUND
Studies in general population reported a positive association between tobacco smoking and airflow obstruction (AFO), a hallmark of chronic obstructive pulmonary disease (COPD). However, this attempt was less addressed in silica dust-exposed workers.
METHODS
This retrospective cohort study consisted of 4481 silicotic workers attending the Pneumoconiosis Clinic during 1981-2019. The lifelong work history and smoking habits of these workers were extracted from medical records. Spirometry was carried out at the diagnosis of silicosis (n = 4177) and reperformed after an average of 9.4 years of follow-up (n = 2648). AFO was defined as forced expiratory volume in one second (FEV1)/force vital capacity (FVC) less than lower limit of normal (LLN). The association of AFO with smoking status was determined using multivariate logistics regression, and the effect of smoking cessation on the development of AFO was evaluated Cox regression.
RESULTS
Smoking was significantly associated with AFO (current smokers: OR = 1.92, 95% CI 1.51-2.44; former smokers: OR = 2.09, 95% CI 1.65-2.66). The risk of AFO significantly increased in the first 3 years of quitting smoking (OR = 1.23, 95% CI 1.02-1.47) but decreased afterwards with increasing years of cessation. Smoking cessation reduced the risk of developing AFO no matter before or after the confirmation of silicosis (pre-silicosis cessation: HR = 0.58, 95% CI 0.46-0.74; post-silicosis cessation: HR = 0.62, 95% CI 0.48-0.79).
CONCLUSIONS
Smoking cessation significantly reduced the risk of AFO in the workers with silicosis, although the health benefit was not observed until 3 years of abstinence. These findings highlight the importance of early and long-term smoking cessation among silicotic or silica dust-exposed workers.
Topics: Humans; Silicosis; Male; Middle Aged; Smoking Cessation; Retrospective Studies; Adult; Pulmonary Disease, Chronic Obstructive; Female; Occupational Exposure; Forced Expiratory Volume; Smoking; Spirometry; Vital Capacity; Cohort Studies
PubMed: 38753732
DOI: 10.1371/journal.pone.0303743 -
Ecotoxicology and Environmental Safety Jun 2024Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO). Recent studies have found that a...
Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO-induced silicosis injury.
Topics: Animals; Humans; Male; Rats; Endothelial Cells; Lymphangiogenesis; MicroRNAs; Rats, Sprague-Dawley; Silicon Dioxide; Silicosis; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3
PubMed: 38728943
DOI: 10.1016/j.ecoenv.2024.116444 -
BMC Pulmonary Medicine May 2024Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases....
BACKGROUND
Simvastatin (Sim), a hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in prevention and treatment of cardiovascular diseases. Studies have suggested that Sim exerts anti-fibrotic effects by interfering fibroblast proliferation and collagen synthesis. This study was to determine whether Sim could alleviate silica-induced pulmonary fibrosis and explore the underlying mechanisms.
METHODS
The rat model of silicosis was established by the tracheal perfusion method and treated with Sim (5 or 10 mg/kg), AICAR (an AMPK agonist), and apocynin (a NOX inhibitor) for 28 days. Lung tissues were collected for further analyses including pathological histology, inflammatory response, oxidative stress, epithelial mesenchymal transformation (EMT), and the AMPK-NOX pathway.
RESULTS
Sim significantly reduced silica-induced pulmonary inflammation and fibrosis at 28 days after administration. Sim could reduce the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α and transforming growth factor-β1 in lung tissues. The expressions of hydroxyproline, α-SMA and vimentin were down-regulated, while E-cad was increased in Sim-treated rats. In addition, NOX4, p22pox, p40phox, p-p47phox/p47phox expressions and ROS levels were all increased, whereas p-AMPK/AMPK was decreased in silica-induced rats. Sim or AICAR treatment could notably reverse the decrease of AMPK activity and increase of NOX activity induced by silica. Apocynin treatment exhibited similar protective effects to Sim, including down-regulating of oxidative stress and inhibition of the EMT process and inflammatory reactions.
CONCLUSIONS
Sim attenuates silica-induced pulmonary inflammation and fibrosis by downregulating EMT and oxidative stress through the AMPK-NOX pathway.
Topics: Animals; Male; Rats; Acetophenones; Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Disease Models, Animal; Epithelial-Mesenchymal Transition; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung; NADPH Oxidase 4; NADPH Oxidases; Oxidative Stress; Pneumonia; Pulmonary Fibrosis; Ribonucleotides; Signal Transduction; Silicon Dioxide; Silicosis; Simvastatin; Transforming Growth Factor beta1
PubMed: 38720270
DOI: 10.1186/s12890-024-03014-9 -
Journal of Global Antimicrobial... May 2024Over 1 year, two KPC-producing and two non-KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the...
Over 1 year, two KPC-producing and two non-KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the first three strains as a clonal lineage, with carbapenem resistance changes due to a Tn2-like transposon on an IncR/IncFII plasmid. The fourth strain, carrying three plasmids, caused a lethal infection and represented a different lineage. All strains belonged to the ST11-SL47-OL101 type. This study highlights the Tn2-like transposon's role in carbapenemase gene spread and the importance of distinguishing between bacterial colonization and infection.
PubMed: 38719187
DOI: 10.1016/j.jgar.2024.04.011