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Background Silicosis, a disease characterized by fibrous changes in lung tissue due to prolonged silica dust inhalation, exhibits a complex pathogenesis that remains inadequately addressed by current interventions. Although osteoclast stimulatory transmembrane protein (OC-STAMP) is implicated in Silicosis progression, its regulatory mechanisms are not fully understood. In this study, we detected elevated OC-STAMP expression in Silicosis patients and found that treatment with OC-STAMP siRNA can alleviate the progression of Silicosis in mice, suggesting the potential of OC-STAMP as a diagnostic and therapeutic target for Silicosis. Methods First, rat models of Silicosis were developed at various stages. A suite of histological and molecular techniques, including Hematoxylin and eosin (HE), Masson, Prussian blue staining, and immunohistochemistry, along with real-time polymerase chain reaction (RT-PCR), were employed to assess the expression levels of OC-STAMP, as well as indicators of  ferroptosis and fibrosis.Second, MLE-12 cells were cultured in vitro to establish an OC-STAMP overexpression model, and the relationship between OC-STAMP and ferroptosis was evaluated using flow cytometry, and western blotting. Subsequently, to verify the role of OC-STAMP and ferroptosis in Silicosis progression, we administered OC-STAMP siRNA and Fer-1 to Silicosis mice respectively. Whole-body volumetric plethysmography (WBP) was utilized to assess the respiratory function of the mice, and Micro-CT was applied to detect the lung nodules in the mice. The levels of OC-STAMP, as well as indexes associated with ferroptosis and fibrosis, were assessed using Hematoxylin and eosin (HE), Masson, Sirius red staining, immunohistochemistry, and western blot analysis. The polarization of macrophages towards M1 and M2 phenotypes in lung tissues was analyzed by flow cytometry. Ultimately, the plasma expression of OC-STAMP in patients diagnosed with Silicosis was quantified using enzyme-linked immunosorbent assay (ELISA). Results In vivo experiments showed that OC-STAMP accelerates the fibrotic process of Silicosis, which may promote the epithelial-mesenchymal transformation by triggering ferroptosis of alveolar type II epithelial cells, and thus promote the progression of Silicosis. Furthermore, in vitro studies indicated that OC-STAMP overexpression causes ferroptosis in alveolar type II epithelial cells which contributes to fibrosis. Notably, treatment with siRNA in Silicosis mice confirmed that OC-STAMP inhibition effectively mitigates ferroptosis and retarded the progression of Silicosis fibrosis. Plasma of patients with Silicosis exhibited elevated OC-STAMP levels. Conclusions Overall, OC-STAMP induces ferroptosis and exacerbates fibrosis in Silicosis. OC-STAMP siRNA and Fer-1 mitigate abnormal collagen deposition and delay the progression of Silicosis. Collectively, these findings highlight the potential of OC-STAMP as a novel biomarker for diagnosing and treating Silicosis.

Silicosis is a fibrotic lung disease caused by inhalation of free crystalline silicon dioxide or silica. Occupational exposure to respirable crystalline silica dust particles occurs in many industries. Phagocytosis of crystalline silica in the lung causes lysosomal damage, activating the NALP3 inflammasome and triggering the inflammatory cascade with subsequent fibrosis. Impairment of lung function increases with disease progression, even after the patient is no longer exposed. Diagnosis of silicosis needs carefully documented records of occupational exposure and radiological features, with exclusion of other competing diagnoses. Mycobacterial diseases, airway obstruction, and lung cancer are associated with silica dust exposure. As yet, no curative treatment exists, but comprehensive management strategies help to improve quality of life and slow deterioration. Further efforts are needed for recognition and control of silica hazards, especially in developing countries.

ObjectivesHigh 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.MethodsSubjects 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.ResultsAmong 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.ConclusionScreening 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.

ObjectivesAutoimmune disorders are multifactorial but occupational exposures have long been implicated, including respirable crystalline silica (RCS). A modern epidemic of silicosis is emerging internationally, associated with dry processing of engineered stone with high (>90%) RCS content. We aimed to investigate the prevalence of clinical autoimmune disease and common autoantibodies in exposed workers.MethodsStone benchtop industry workers in Victoria, Australia were offered free screening for silicosis and related disorders. Symptoms or diagnoses of autoimmune disease were evaluated by questionnaire and blood tests taken for rheumatoid factor (RF), antinuclear antibodies (ANAs) and extractable nuclear antigens (ENAs).ResultsAmong 1238 workers (93.3% male) screened from 2019 to 2021, 0.9% were confirmed with autoimmune disease. Among those without clinical disease, 24.6% had detectable ANAs (93.5% male), 4.6% detectable ENAs and 2.6% were positive for RF. Silicosis was diagnosed in 253 workers (24.3% of those with diagnostic information available). Of those with ANA readings, 54 (6.6%) had ANA titre >1:320. The likelihood of positive autoantibodies increased with age; smoking; higher exposure to RCS and silicosis diagnosis.ConclusionThe proportion of workers with detectable ANAs or ENAs was considerably higher than the 5%–9% expected in the general population. Some of the antibodies detected (eg, Scl-70, CENPB) have high sensitivity and specificity for systemic sclerosis. Long-term follow-up will be needed to estimate incidence. Rheumatologists should explore occupational history in new cases of autoimmune disease. Screening for autoimmune disease is indicated in workers exposed to RCS as these individuals need specialised management and may be entitled to compensation.

BackgroundSilicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship.MethodsWeb of Science, Medline and Embase were searched on 24 February 2023. Studies of radiographic, autopsy or death certificate silicosis, with an estimated average follow-up of over 20 years since first employment, were included. Cumulative silicosis risk methods were compared. The relative risks (RR) of silicosis at increasing cumulative exposures were calculated and used to estimate the absolute risk reduction (ARR).ResultsEight eligible studies, including 10 cohorts, contributed 8792 cases of silicosis among 65 977 participants. Substantial differences in cumulative risk estimates between methodologies exist. Using the same method, we observed higher cumulative silicosis risks among mining compared with non-mining cohorts. A reduction from 4 to 2 mg/m³-years in cumulative RCS exposure corresponded to substantial risk reductions among miners (RR 0.23 (95% CI 0.18 to 0.29, I2=92.9%) with an ARR of 323 (95% CI 298 to 344) per 1000) and non-miners (RR 0.55 (95% CI 0.36 to 0.83, I2=77.0%) with an ARR of 23 (95% CI 9 to 33) per 1000).ConclusionDespite significant heterogeneity, our findings support a reduction in permissible exposure limits from 0.1 mg/m3 to 0.05 mg/m³, particularly among mining populations. Further research is needed among non-miners as only two studies were eligible.

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.

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. 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. 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). 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.

Silicosis is a global problem, and it has brought about great burdens to society and patients’ families. The etiology of silicosis is clear, preventable, and controllable, but the onset is hidden and the duration is long. Thus, it is difficult to diagnose it early and treat it effectively, leaving workers unaware of the consequences of dust exposure. As such, a lack of details in the work history and a slow progression of lung disease contribute to the deterioration of patients until silicosis has advanced to fibrosis. These issues are the key factors impeding the diagnosis and the treatment of silicosis. This article reviews the literature on the early identification, diagnosis, and treatment of silicosis as well as analyzes the difficulties in the diagnosis and the treatment of silicosis and discusses its direction of future development.

Macrophages play a key role in silicosis, and exosomes are potent mediators of intercellular communication. This suggests that macrophage‐derived exosomes have a potential contribution to the pathogenesis of silicosis. To investigate whether macrophage‐derived exosomes promote or inhibit lung fibrosis, in vitro, silica‐exposed macrophage‐derived exosomes (SiO2‐Exos) were collected and cocultured with fibroblasts. The expression of collagen I and α‐SMA was evaluated. Furthermore, the endoplasmic reticulum (ER) stress markers BIP, XBP1s and P‐eIF2α were assessed after treatment with or without the ER stress inhibitor 4‐PBA. In vivo, mice were pre‐treated with the exosome secretion inhibitor GW4869 prior to silica exposure. After sacrifice, lung tissues were histologically examined, and the expression of proinflammatory cytokines (TNF‐α, IL‐1β and IL‐6) in bronchoalveolar lavage fluid (BALF) was measured. The results showed that the expression of collagen I and α‐SMA was up‐regulated after treatment with SiO2‐Exos, accompanied by increased expression of BIP, XBP1s and P‐eIF2α. Pre‐treatment with 4‐PBA reversed this effect. More importantly, an in vivo study demonstrated that pre‐treatment with GW4869 decreased lung fibrosis and the expression of TNF‐α, IL‐1β and IL‐6 in BALF. These results suggested that SiO2‐Exos are profibrogenic and that the facilitating effect is dependent on ER stress.