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Occupational and Environmental Medicine Jun 2024Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations...
BACKGROUND
Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations between occupational exposure to respirable crystalline silica and the risk of idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis.
METHODS
The total Danish working population was followed 1977-2015. Annual individual exposure to respirable crystalline silica was estimated using a quantitative job exposure matrix. Cases were identified in the Danish National Patient Register. We conducted adjusted analyses of exposure-response relations between cumulative silica exposure and other exposure metrics and idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis.
RESULTS
Mean cumulative exposure was 125 µg/m-years among exposed workers. We observed increasing incidence rate ratios with increasing cumulative silica exposure for idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. For idiopathic interstitial pneumonias and pulmonary sarcoidosis, trends per 50 µg/m-years were 1.03 (95% CI 1.02 to 1.03) and 1.06 (95% CI 1.04 to 1.07), respectively. For silicosis, we observed the well-known exposure-response relation with a trend per 50 µg/m-years of 1.20 (95% CI 1.17 to 1.23).
CONCLUSION
This study suggests that silica inhalation may be related to pulmonary sarcoidosis and idiopathic interstitial pneumonias, though these findings may to some extent be explained by diagnostic misclassification. The observed exposure-response relations for silicosis at lower cumulative exposure levels than previously reported need to be corroborated in analyses that address the limitations of this study.
PubMed: 38902031
DOI: 10.1136/oemed-2023-108964 -
The European Respiratory Journal Jun 2024
Topics: Humans; Australia; Silicon Dioxide; Occupational Exposure; Silicosis
PubMed: 38901887
DOI: 10.1183/13993003.00138-2024 -
Chinese Medicine Jun 2024Extended contact with silica particles can lead to Silicosis, a chronic lung condition lacking established treatment protocols or clear mechanisms of development. The...
BACKGROUND
Extended contact with silica particles can lead to Silicosis, a chronic lung condition lacking established treatment protocols or clear mechanisms of development. The urgency for innovative treatments arises from the unavailability of effective treatment methodologies. The origin of silica-induced pulmonary fibrosis includes essential processes such as macrophage activation and the conversion of fibroblasts into myofibroblasts, with oxidative stress playing a pivotal role. Shionone (SHI), a triterpenoid extracted from the Aster tataricus plant, is recognized for its extensive health benefits. This study explores the capability of SHI to alleviate the effects of silica-induced lung fibrosis in mice.
METHODS
This investigation explored the impact of SHI on lung inflammation and fibrosis at different stages (early and late) triggered by silica in mice, focusing specifically on the initial and more developed phases. It comprised an analysis of isolated peritoneal macrophages and fibroblasts extracted from mice to elucidate SHI's therapeutic potential and its underlying mechanism. The methodology employed encompassed quantitative PCR, immunofluorescence, flow cytometry, and western blotting to examine macrophage activity and their transition into myofibroblasts. The activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by SHI was confirmed via immunofluorescence and western blot studies. SHI's antioxidative properties were evidenced by the measurement of reactive oxygen species (ROS) and mitochondrial ROS within both macrophages and fibroblasts, using 2', 7'-dichlorodihydrofluorescein diacetate and MitoSOX, respectively. The relevance of SHI was further underscored by applying ML385 and Nrf2 siRNA to gauge its effectiveness.
RESULTS
Starting SHI treatment early countered the harmful effects of lung inflammation and fibrosis caused by silica, while initiating SHI at a later phase decelerated the advancement of fibrosis. SHI's action was linked to the activation of the Nrf2 signaling pathway, a boost in antioxidant enzyme levels, and a decrease in oxidative stress and inflammation in macrophages affected by silica. Furthermore, SHI prevented the conversion of fibroblasts into myofibroblasts prompted by TGF-β, along with the resultant oxidative stress. The beneficial outcomes of SHI were negated when ML385 and Nrf2 siRNA were applied, highlighting the pivotal role of the Nrf2 pathway in SHI's efficacy.
CONCLUSION
SHI plays a significant role in stimulating the Nrf2 pathway, thereby defending against silica-induced oxidative stress and inflammatory reactions in macrophages, and inhibiting the conversion of fibroblasts to myofibroblasts due to TGF-β. This suggests that SHI is a viable option for treating lung inflammation and fibrosis in mice suffering from silicosis.
PubMed: 38898509
DOI: 10.1186/s13020-024-00947-5 -
International Journal of Molecular... May 2024Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few...
Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few reports have investigated leukocyte/lymphocyte subsets in ES-silicosis patients. The present study was designed to explore the proportions of the main lymphocyte subsets in ES-silicosis patients stratified into two groups, one with simple silicosis (SS) and the other with a more advanced state of the disease, defined as progressive massive fibrosis (PMF). The proportions of B (memory and plasmablasts) cells, T (helper, cytotoxic, regulatory) cells, and natural killer (NK) (regulatory and cytotoxic) cells were investigated by multiparameter flow cytometry in 91 ES-silicosis patients (53 SS patients and 38 PMF patients) and 22 healthy controls (HC). Although the total number of leukocytes did not differ between the groups studied, lymphopenia was observed in patients compared to healthy controls. Compared with those in healthy controls, the proportions of memory B cells, naïve helper T cells, and the CD4/CD8 T cells' ratio in the peripheral blood of patients with silicosis were significantly decreased, while the percentages of plasma cells, memory helper T cells, and regulatory T cells were significantly increased. For the NK cell subsets, no significant differences were found between the groups studied. These results revealed altered cellular immune processes in the peripheral blood of patients with ES-silicosis and provided further insight into silicosis pathogenesis.
Topics: Humans; Male; Silicosis; Middle Aged; Female; Silicon Dioxide; Adult; Killer Cells, Natural; Lymphocyte Subsets; Pneumonia; Aged; Case-Control Studies
PubMed: 38891910
DOI: 10.3390/ijms25115722 -
Archives of Public Health = Archives... Jun 2024Tuberculosis (TB) treatment is more challenging for patients with silicosis, as it complicates the diagnosis of both diseases and increases mortality risk. Silicosis, an...
Tuberculosis (TB) treatment is more challenging for patients with silicosis, as it complicates the diagnosis of both diseases and increases mortality risk. Silicosis, an incurable occupational disease, confounds the diagnosis of TB and vice versa, making it more difficult to accurately identify and treat either condition. Moreover, TB appears to accelerate the progression of silicosis. Exposure to silica dust, a common cause of silicosis, can also trigger latent TB to become active TB. This correspondence outlines a proposed framework for implementing collaborative TB-silicosis activities in India, aimed at improving early diagnosis and management for both diseases. An expert panel of medical professionals developed this framework through online consultations in October and November 2022. The panel's goal was to establish a consensus on integrating TB-silicosis activities, with a focus on early detection and proper management. The framework suggests testing all patients with silicosis for active TB and screening workers exposed to silica dust for latent TB infection. It also recommends that patients with TB who have a history of occupational exposure to silica dust should be tested for silicosis. Reliable diagnostic tools, such as chest X-rays, are emphasized, providing guidance on their use for both diseases. The proposed collaborative TB-silicosis framework offers a structured approach to identifying and managing these two diseases, contributing to the global goal of eliminating silicosis by 2030 and aligning with the World Health Organization's targets for reducing TB incidence and mortality. It recommends specific strategies for implementation, including testing, referral systems, and workplace-based interventions. The framework also underscores the need for coordinated efforts among stakeholders, including the ministries of health, labor, industry, and environment. This correspondence provides valuable insights into how India can successfully implement collaborative TB-silicosis activities, serving as a model for other regions with similar challenges.
PubMed: 38890764
DOI: 10.1186/s13690-024-01325-1 -
The Science of the Total Environment Jun 2024Silicosis, recognized as a severe global public health issue, is an irreversible pulmonary fibrosis caused by the long-term inhalation of silica particles. Given the...
Silicosis, recognized as a severe global public health issue, is an irreversible pulmonary fibrosis caused by the long-term inhalation of silica particles. Given the intricate pathogenesis of silicosis, there is no effective intervention measure, which poses a severe threat to public health. Our previous study reported that dysbiosis of lung microbiota is associated with the development of pulmonary fibrosis, potentially involving the lipopolysaccharides/toll-like receptor 4 pathway. Similarly, the process of pulmonary fibrosis is accompanied by alterations in metabolic pathways. This study employed a combined approach of 16S rDNA sequencing and metabolomic analysis to investigate further the role of lung microbiota in silicosis delving deeper into the potential pathogenesis of silicosis. Silica exposure can lead to dysbiosis of the lung microbiota and the occurrence of pulmonary fibrosis, which was alleviated by a combination antibiotic intervention. Additionally, significant metabolic disturbances were found in silicosis, involving 85 differential metabolites among the three groups, which are mainly focused on amino acid metabolic pathways. The changed lung metabolites showed a substantial correlation with lung microbiota. The relative abundance of Pseudomonas negatively correlated with L-Aspartic acid, L-Glutamic acid, and L-Threonine levels. These results indicate that dysbiosis in pulmonary microbiota exacerbates silica-induced fibrosis through impacts on amino acid metabolism, providing new insights into the potential mechanisms and interventions of silicosis.
PubMed: 38889818
DOI: 10.1016/j.scitotenv.2024.174028 -
Mediastinum (Hong Kong, China) 2024Endobronchial ultrasound (EBUS)-guided mediastinal cryobiopsy is a novel technique that increases the accuracy of diagnosing most pathologies that affect the... (Review)
Review
Endobronchial ultrasound (EBUS)-guided mediastinal cryobiopsy is a novel technique that increases the accuracy of diagnosing most pathologies that affect the mediastinum. Although EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is the first choice in the diagnosis of mediastinal pathology, mediastinal cryobiopsy offers a larger and higher quality biopsy with minimal artifacts and no crushing when compared to conventional cytological samples obtained through EBUS-TBNA. It is particularly valuable in pathologies where EBUS-TBNA has diagnostic limitations, such as lymphoproliferative diseases, benign granulomatous conditions like sarcoidosis and silicosis, some rare infectious processes, metastases from rare non-pulmonary tumors, and in advanced stages of non-small cell lung cancer (NSCLC) where immunohistochemistry and molecular analysis are essential for personalized treatment. Therefore, mediastinal cryobiopsy seems to play a crucial role in these challenging scenarios. However, there is ongoing debate in the field of interventional pulmonology regarding the best approach for obtaining a mediastinal cryobiopsy. Some interventional pulmonologists use a high-frequency needle knife to create an incision in the tracheobronchial wall adjacent to the mediastinal lesion before inserting the cryoprobe, while others use a needle to create a pathway to the target area. There are also variations in the use of endoscopic or ultrasound imaging for guidance. In this article, we aim to review the current literature on different methods of performing mediastinal cryobiopsy and share our own clinical experience and methodology in a systematic way for its implementation in a safe, fast, and effective way.
PubMed: 38881814
DOI: 10.21037/med-23-65 -
Redox Biology Jun 2024Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for...
Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.
PubMed: 38879894
DOI: 10.1016/j.redox.2024.103237 -
Scientific Reports Jun 2024The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for...
The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies.
Topics: Humans; India; Silicon Dioxide; Male; Latent Tuberculosis; Dust; Adult; Occupational Exposure; Cross-Sectional Studies; Silicosis; Female; Middle Aged; Prevalence
PubMed: 38879714
DOI: 10.1038/s41598-024-64837-4 -
Respiratory Research Jun 2024Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical...
BACKGROUND
Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear.
METHODS
To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions.
RESULTS
In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts.
CONCLUSION
In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.
Topics: Animals; Pulmonary Fibrosis; Alkaloids; Silicon Dioxide; Mice; Fibroblasts; Myofibroblasts; Cell Differentiation; Mice, Inbred C57BL; Silicosis; Male
PubMed: 38877465
DOI: 10.1186/s12931-024-02876-1