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Background: Identification of biomarkers associated with the diagnosis and prognosis of silicosis would be highly advantageous in the clinical setting. The aim of this study is to evaluate inflammatory and oxidative stress biomarkers in subjects exposed to silica., Methods: A cross-sectional study of crystal craftsmen currently (n = 34) or formerly (n = 35) exposed and a group of nonexposed subjects (n = 12) was performed. Personal respirable dust samples were collected. Plasma inflammatory mediators (bone morphogenetic protein- BMP2 and chemokines CXCL16, and CCL5), oxidative stress enzymes (thiobarbituric acid reactive substances [TBARs] and superoxide dismutase [SOD]), and nitrite (NO 2 - ) were analyzed in parallel with nitric oxide in exhaled breath (FeNO)., Results: Being currently or formerly exposed to silica was related to increased levels of CXCL16 and TBARs. Currently, exposed subjects showed decreased levels of SOD. Thirty-seven craftsmen with silicosis (26 formerly and 11 currently exposed) showed higher levels of CXCL16, which was positively associated with the radiological severity of silicosis. Compared with the nonexposed, subjects with silicosis had higher levels of TBARs and those with complicated silicosis had lower levels of SOD. In multivariate analysis, higher levels of CXCL16 were associated with exposure status and radiological severity of silicosis. Smoking was not a confounder. FeNO did not distinguish between the exposure status and the presence of silicosis., Conclusion: CXCL16 emerged as a potential biomarker that could distinguish both silica exposure and silicosis. TBARs were elevated in exposed individuals. However, their clinical applications demand further investigation in follow-up studies of representative samples., (© 2020 Wiley Periodicals, Inc.)

Background: Silica has been associated with end stage kidney disease and kidney dysfunction., Methods: Calculated glomerular filtration rate, history of kidney disease or chronic dialysis, elevated serum creatinine, and stages of chronic kidney disease among silicotics identified in Michigan's Silicosis Surveillance System from 1987 to 2009 were reviewed to determine the prevalence of kidney disease in confirmed cases of silicosis., Results: Twenty-four percent of 1,072 silicotics had a measure of kidney dysfunction (32.3% if diabetes or hypertension present vs. 20.2% if not). Sixty-nine percent of silicotics had Stage I or greater chronic kidney dysfunction versus 38.8% of the U.S. general population ≥60 years. No association was found between kidney function and measures of silica exposure., Conclusions: Individuals with silicosis have an increased prevalence of kidney disease. More work to define the pathological changes associated with silica exposure is needed to understand the cause of silica's adverse effect on the kidney., (© 2015 Wiley Periodicals, Inc.)

Aim: To study serum autoantibodies and immunoglobulin levels in cement workers., Methods: Blood samples for numerous antibodies were collected from 30 silicosis and 42 non-silicosis cement workers. Spirometry of the silicosis workers was also studied., Results: Serum IgA mean level showed a significant increase in the silicosis group compared to the non-silicosis group. Elevated titers of serum anti-smooth muscle antibodies (ASMA) and anti-glomerular basement membrane (anti-GBM) were detected only in the silicosis group. The duration of exposure showed a significant positive correlation with serum IgA, ASMA and anti-GBM, and a significant negative correlation with serum IgG. Serum anti-GBM showed a significant positive correlation with IgG while the inverse titer (1/titer) of anti-GBM showed highly significant positive correlations with serum IgA and ASMA. The percent predicted FVC was the ventilatory function most closely associated with immunological parameters in silicosis group., Conclusion: Serum IgA, ASMA, and anti-GBM are the principal immunologic parameters associated with silicosis., (© 2014 Wiley Periodicals, Inc.)

Objective: Cement masons are known to have significant silica exposure, and silica exposure and silicosis are thought to increase risk of autoimmune disease. Because the mechanisms remain obscure, with inconclusive reports of systemic immune effects following silica exposure, our goal was to identify potential early markers of silica-related immunologic and respiratory effects., Methods: We conducted a cross-sectional study of cement mason apprentices and electrician (control) apprentices. Demographics, dust exposure history, symptoms, spirometry, exhaled nitric oxide, and blood (for immunoglobulins, cytokines, cell counts, and surface markers) were obtained from 11 cement mason apprentices and a comparison group of 21 electrician apprentices., Results: Masons had significantly higher (P < 0.05) masonry dust exposure (42 versus 9 dust-hour-years), serum interleukin-1beta (IL-1beta; 12 versus 9 pg/ml), IL-2 (20 versus 8 pg/ml), IL-4 (193 versus 67 pg/ml), IL-10 (44 versus 21 pg/ml), and interferon-gamma (139 versus 65 pg/ml) compared with electricians. In contrast, masons had significantly lower percentages of CD25+ (12% versus 20%) and CD69+ (4% versus 9%) lymphocytes., Conclusion: Mason apprentices had higher levels of serum proinflammatory cytokines and lower percentages of CD25+ and CD69+ lymphocytes than did electrician apprentices. These preliminary findings suggest that mason apprentices may be at greater risk of a systemic proinflammatory state that is potentially linked to immune dysregulation. Although distinct limitations of this preliminary data are recognized, this is consistent with early biologic effects leading to increased incidence of autoimmune disease among silica-exposed workers. Prospective studies are needed to validate these initial findings and clarify the temporal sequence of observed relationships.

Background: Little is known about the crucial mediators involved in the inflammation and fibrogenesis in bagassosis. The aim of this study was to characterize the cellular and cytokine patterns in the airways of bagassosis and to compare these with silicosis subjects and controls., Methods: Bronchoalveolar lavage (BAL) was performed in 11 patients with bagassosis, 16 cases with silicosis, and 8 controls. Differential cell counts, total protein concentration, TNF-alpha, IL-1beta, IL-5, IL-6, and IL-8 were analyzed in the bronchoalveolar lavage fluid (BALF)., Results: Bagassosis was characterized with hypercellularity with neutrophilia in BALF; while the predominant cell in the BALF in silicosis was macrophage. Compared with control subjects, increased TNF-alpha, IL-1beta, IL-8, and IL-6 levels were found in the BALFs in both bagassosis and silicosis. Furthermore, IL-6 levels in the BALF of silicosis subjects were significantly higher than that seen in bagassosis. In contrast, bagassosis had higher level of IL-8 in BALF than that in silicosis. Relationship among these parameters were found between IL-8 levels and neutrophils, lymphocytes and IL-1 beta in bagassosis, macrophages and IL-1beta in silicosis. No significant differences of total protein concentrations and IL-5 in BALF were found between controls or bagassosis, and silicosis., Conclusions: The findings of this study suggest that neutrophils, TNF-alpha, IL-1beta, IL-8, and IL-6 are involved in the pathogenesis in bagassosis. The mechanisms underline the different cellular and cytokine profiles in bagassosis and silicosis warrant further investigation.

Objective: To determine the frequency and type of autoantibodies present in patients with systemic sclerosis (SSc) associated with an established environmental toxin., Methods: Clinical data and sera were available from 14 men with silica-associated SSc who had developed SSc after at least 2 years of exposure to silica at work. Controls included 27 men with silicosis without SSc. Autoantibodies were measured by immunodiffusion, immunoblotting, and functional inhibition of topoisomerase I (topo I)., Results: Nine of the 14 patients with silica-associated SSc had anti-topo I antibodies. All anti-topo I antibodies in the patients with silica-associated SSc and in 14 anti-topo I-positive patients with idiopathic SSc were directed at an active site of topo I, or at least sterically inhibited its function. One patient with silica-associated SSc had anticentromere antibodies. Unexpectedly, 2 patients with silicosis who had no symptoms of a connective tissue disease had autoantibodies to Ro/SS-A and La/SS-B autoantigens., Conclusion: Anti-topo I antibodies are the predominant autoantibodies present in silica-associated SSc. The generation of anti-topo I antibodies in genetically susceptible individuals may depend partly on the patient's sex and on the site of organ involvement, and may be triggered by silica particles acting as an immune adjuvant.