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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.

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.

Background Silicosis and asbestosis, distinct forms of pneumoconiosis, manifest progressive interstitial fibrosis due to exposure to silica dust or asbestos fibers. This study aimed to identify potential biomarkers for diagnosing silicosis and asbestosis, while also evaluating disease severity and prognosis. We undertook an prospective observational study involving patients with silicosis or asbestosis. The correlation between baseline CC-chemokine ligand 18 (CCL18), CXC motif chemokine 13 (CXCL13), osteopontin (OPN), periostin, and fibulin-3 and clinical variables was analyzed. Diagnostic sensitivity was evaluated using receiver operating characteristic curves, and correlations between baseline biomarker levels and disease severity were analyzed. Multivariable Cox regression assessed the baseline concentrations’ strength in predicting all-cause mortality for silicosis and asbestosis. Of 231 silicosis and 163 asbestosis included in the study, 29 silicosis (12.6%) and 28 (17.2%) asbestosis died within the five years follow-up period. Elevated baseline concentrations of CCL18, CXCL13, and OPN were observed in 231 silicosis patients and 163 asbestosis patients compared to 118 HCs. Diagnostic accuracy for silicosis or asbestosis, in order, was CCL18, OPN, and CXCL13. Combining CCL18, OPN, and CXCL13 enhanced diagnostic accuracy. In silicosis patients, these concentrations were significantly associated with lung function values. However, these biomarkers were not the risk factor for all-cause mortality. CCL18, CXCL13, and OPN stand out as promising biomarkers for diagnosing silicosis and asbestosis. Meanwhile, CCL18, CXCL13, and OPN may be used for the evaluation of silicosis conditions.

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.

Silicosis is an irreversible, incurable and progressive occupational disease caused by prolonged exposure to crystalline-silica dust while working in the relevant industries. Conventionally diagnosis is done by chest radiology, often in an advanced stage as early symptoms often go unnoticed. Early detection and necessary intervention (secondary prevention) could be a realistic possible control strategy for controlling silicosis as no effective treatment is available to stop and/or reverse the pathological process. Additionally, these patients are also vulnerable to pulmonary tuberculosis, which often becomes difficult to treat and with uncertain treatment outcome. Considering India has a huge burden of silicosis and silico-tuberculosis, a rapid and inexpensive screening method was realized to be an urgent need for early detection of silicosis among silica dust exposed workers. Serum club cell protein 16 (CC16) is evidenced to be a useful proxy screening marker for early detection of silicosis as evidenced from the recent research work of ICMR-National Institute of Occupational Health (ICMR-NIOH), India. In this study a lateral-flow assay for semi-quantitative estimation of serum CC16 level was developed. The detection was performed using gold nanoparticles conjugated anti-CC16 monoclonal antibodies. A sum of 106 serum samples was tested to do the performance evaluation of the assay. A concentration of 6 ng/ml or less produced one band, 6.1–9 ng/ml produced two bands, while more than 9 ng/ml produced all the three bands at the test zone. The sensitivity of the assay was 100% while the specificity was 95%. This assay may be used as a sensitive tool for periodic screening of silica dust exposed vulnerable workers for early detection of silicosis in them.

Background Silicosis is an irreversible and progressive pulmonary fibrosis that results in prolonged inhalation of crystalline silica. Despite its significant impact, no specific blood biomarkers currently exist for the early diagnosis of this disease. This study aims to evaluate the levels of Krebs von den Lungen-6 (KL-6) in patients with early-stage silicosis and explore its potential as a diagnostic biomarker. Methods Blood samples were collected from 40 stage I silicosis patients, 57 dust-exposed workers (DEWs), and 70 healthy controls (HCs). The concentrations of KL-6, C-reactive protein (CRP), and angiotensin-converting enzyme (ACE) were measured using the automatic biochemical analyzer. Receiver operating characteristic (ROC) curve analysis was utilized to evaluate the diagnostic efficacy of KL-6, in combination with other biomarkers for the early stage of silicosis. The association between lung function and KL-6 levels in silicosis patients was evaluated using partial correlation analysis. Results Serum levels of KL-6, CRP, and ACE were remarkably elevated in stage I silicosis patients compared to HCs and DEWs. KL-6 demonstrated an adjusted area under the curve (AUC) of 0.770 for distinguishing stage I silicosis patients from HCs, with a sensitivity of 80.0% and a specificity of 70.0%. When comparing silicosis patients to DEWs, KL-6 alone achieved an adjusted AUC of 0.735, with sensitivity and specificity of 45.0% and 89.5%, correspondingly. The integration of KL-6, CRP, and ACE demonstrated the highest diagnostic efficacy among all tested combinations. Furthermore, serum KL-6 levels were negatively correlated with vital capacity (VC) in silicosis patients. Conclusions Serum KL-6 may serve as a potential biomarker for early silicosis diagnosis. Its diagnostic performance is significantly improved when combined with CRP ad ACE, offering a potential multi-biomarker approach for enhanced detection in the early stages of the disease. Further validation in larger and more diverse populations is needed to confirm its clinical utility.

PurposeThe degree of silicosis exposure is closely related to the progress of silicosis. At present, we use animal and human studies to explore whether silicon can be an important exposure marker in the development of silicosis.MethodsRats were randomly divided into 2 groups: (1) controls; and (2) silicosis. Rats in the silicosis group were killed at 4, 8, 12, 16, 24 h, 3, 7, 14, 21, and 28 days. Hematoxylin–eosin (HE) and immunohistochemistry (IHC) were performed to observe the histomorphology of lung tissue. The expression levels of CC16 and SP-D were detected using ELISA kits. In addition, we conducted a population study. Workers who have been selected to work in an iron mine for more than 1 year as research objects. The population was divided into four groups: silicosis exposure group (workers exposed to silica dust for more than 1 year in an iron mine were selected); patients group (silicosis patients); observation group (evidence of disease not meeting formal diagnostic criteria) and control group. Both the levels of trace silicon in the urine and blood of rats and human subjects were measured with ICP-MS.ResultsSerum levels of silicon were immediately increased in rats exposed to silicon dust. Similarly, our population study revealed that the silicon level in the silica exposure group and the observing group (exposed but no obvious symptoms) were significantly increased over that of the control group (P < 0.05). In subjects with extended exposure to silica, the serum and urine silicon level in exposed workers appeared to rapidly increase, reaching its peak in 1–5 years, followed by a gradual decline thereafter. Workers exposed to dust for less than 10 years were divided into subgroups by 2-year limit. The levels of serum silicon, urine silicon, TGF-β1, and TNF-α were significantly higher than that of control group.ConclusionChanges of the serum levels of silicon occurred earlier than the expression of cytokines such as TNF-α, TGF-β1, CC16, and SP-D. The level of silicon in workers rapidly increased after exposure to silica, and the change occurred before the expression of TGF-β1 and TNF-α. As a whole, the findings suggest that determining the level of silicon in vivo might be an effective exposure marker in the diagnosis and pathogenesis of silicosis.

Growth differentiation factor 15 (GDF-15) has been implicated in multiple biological functions. However, the role of GDF15 in silicosis remains unclear. In this study, the serum level of GDF-15 was investigated in 46 patients with silicosis by ELISA and results showed it was higher than that of control patients. The effects of exogenous GDF15 on mRNA and miRNA expression profiles of MRC5 cells were analyzed by RNA sequencing. GDF15 activated human embryonic lung fibroblast MRC5 cells with upregulation of col1a and α-SMA. GDF15 reduced miR-338 expression and increased STAT1 expression in MRC5 cells. The results of the luciferase reporter assay and bioinformatics analysis indicated that STAT1 was a direct target of miR-338. miR-338 mimics down-regulated col1a and α-SMA expression induced by GDF15 with STAT1 overexpression, whereas miR-338 inhibitor up-regulated col1a and α-SMA expression induced by GDF15 with STAT1 knockdown. Those results indicated GDF15 activated MRC5 cells through the miR-338/STAT1 pathway and GDF-15 may play an important role in silicosis.

Silicosis is a devastating disease caused by inhalation of silica dust that leads to inflammatory cascade and then scarring of the lung tissue. Increasing evidences indicate that soluble receptor for advanced glycation end products (sRAGE) is involved in inflammatory diseases. However, no data on the possible relationship between sRAGE and inflammation of silicosis are available. In this study, serum from subjects with silicosis (n=59) or from healthy controls (HC, n=14) was analyzed for the secretion of sRAGE, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and oxidized low-density lipoprotein (ox-LDL). The associations between sRAGE and cytokines and ox-LDL and lung function were assessed by Pearson’s correlation analyses. Mean levels of serum sRAGE were lower in silicosis than those in controls (p<0.05). The subjects who had a longer term of occupational exposure had higher levels of sRAGE (p<0.05). The secretion of TNF-α, IL-1β, IL-6, TGF-β1, and ox-LDL was significantly higher in the silicosis group than that in the HC group (p<0.05). Furthermore, the levels of sRAGE were negatively correlated with TNF-α, IL-6, IL-1β, and ox-LDL. There is no correlation between sRAGE and TGF-β1 and lung function. The optimal point of sRAGE for differentiating silicosis from healthy controls was 14250.02 pg/ml by ROC curve analysis. A decrease in serum sRAGE and its association with inflammatory response might suggest a role for sRAGE in the pathogenesis of silicosis.

Objective: To identify predictive factors of excess decline in forced expiratory volume in one second (FEVi) in patients with chronic silicosis. Methods: Forty-six male patients enrolled in 2004 were screened and received pulmonary function tests. Results: Among the 33 included patients, 12 were categorized as rapid decliners (reduction in FEV₁ > 60 mL/yr). The mean level of serum heme oxygenase-1 (HO-1), a marker of oxidative stress, was significantly lower in rapid decliners than in normal decliners (P = 0.002). Logistic regression analysis revealed that serum HO-1 was a factor affecting clinically important decline in FEV₁ (odds ratio = 0.52; 95% confidence interval, 0.31 to 0.88) independent of the effects of age, height, weight, smoking, exposure status, and C-reactive protein. Conclusions: Serum HO-1 may be a predictor of lung function decline in silicosis patients.