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Use of miniradiographs to detect silicosis. Comparison of radiological with autopsy findings.

Radiological and routine autopsy findings from 241 South African gold miners were compared, using pathology as the "gold standard." Previous annual screening miniradiographs were read independently by two readers, using the International Labor Office (ILO) grading system, without reference to personal identifiers. Individual and consensus silicosis grades were recorded for each subject. When pathological and radiological silicosis were defined as any abnormal grade, the sensitivity and specificity of the radiological diagnosis was 67.5% and 80%, with positive and negative predictive values of 63% and 83%. Most undetected autopsy silicosis was early-grade. Using higher pathological and radiological grades to define silicosis (5 nodules or more and ILO grades 1/1 and above), sensitivity and specificity increased to 71% and 96%, and positive and negative predictive values increased to 76% and 95%, respectively. Use of a consensus grade made little difference to results from individual readers. For each radiological definition, sensitivity was considerably higher than, but specificity was similar to, that found in a previous study of South African gold miners which used the same pathology source and standard sized films. The difference between these two study findings, and unexpected demonstration of higher sensitivity from miniradiographs, suggests that further research is required into factors affecting radiological interpretation before silicosis grading can be considered to be adequately standardized.

Adult↗

[Dysregulation of Fas and related molecules in silicosis patients].

Silicosis patients not only suffer from respiratory disorders but also from autoimmune diseases. To clarify the mechanisms involved in the occurrence of the dysregulation of autoimmunity found in silicosis patients, we have been focusing on investigation of the Fas and Fas-related molecules in the Fas-mediated apoptotic pathway, since Fas is one of the most important molecules regulating autoimmunity in mainly T cells. Our findings showed that silicosis patients exhibited elevated serum soluble Fas levels, increased relative expression of soluble Fas and DcR 3 genes in peripheral blood mononuclear cells, other highly detectable variant messages of Fas transcripts, relatively decreased expression of several physiological inhibitors (Sentrin, I-Fline, ICAD/DFF45, and survivin), and dominancy of lower membrane Fas expressers in lymphocytes when compared with healthy volunteers. These parameters also constitute immunological factors with serum immunogulobulin G and the titer of anti-nuclear autoantibodies. In addition, anti-caspase 8 autoantibody and anti-Fas autoantibody were also detected in the serum from silicosis patients, and a functional assay showed that anti-Fas antibody stimulated Fas-mediated apoptosis. Taken together, we hypothesize that there are two subpopulations of silicosis lymphocytes. One is a long-term survival fraction including a self-recognizing fraction showing lower membrane Fas and inhibition of Fas/Fas ligand bindings in the extracellular region. The other is a fraction exhibiting apoptosis caused by silica/silicates, recruiting from bone marrow, showing higher membrane Fas and sensitive to anti-Fas autoantibody. Further investigations should be performed to confirm the effects of silica/silicates on the human immune system.

Apoptosis↗

Increased activity of serum angiotensin-converting enzyme in progressive silicosis.

The serum activity of angiotensin-converting enzyme (ACE, EC 3.4.15.1) in 135 male silicosis patients was analyzed. Twenty-eight of the patients had referents matched for silica dust exposure and age but without roentgenographic signs of silicosis. A reference group not exposed to silica dust comprised 34 lumberjacks. The serum mean activity of ACE was higher in silicosis patients (46.6 +/- 12.1 units/L) than in the referents exposed to silica (38.5 +/- 8.1 units/L) or in the lumberjacks (36.6 +/- 9.7 units/L). There was an association between the serum ACE level and the roentgenographic severity of fibrosis. A retrospective side-by-side assessment of roentgenographic progression was made in 49 silicosis patients. The ACE was higher in the 18 patients with progression (50.5 +/- 16.4 units/L) than in those with no progression (41.5 +/- 9.5 units/L). According to the multivariate regression analysis, progression of fibrosis explained the elevation of ACE better than profusion. The results confirm that the serum ACE activity is elevated in silicosis and suggest that the elevation is associated with progression of the disease.

Bronchitis↗

Silicosis among gold miners: exposure--response analyses and risk assessment.

OBJECTIVES: This study sought to estimate the risk of silicosis by cumulative exposure-years in a cohort of miners exposed to silica, as well as the lifetime risk of silicosis under the current Occupational Safety and Health Administration (OSHA) standard (0.09 mg/m3). METHODS: In a cohort study of 3330 gold miners who worked at least 1 year underground from 1940 to 1965 (average 9 years) and were exposed to a median silica level of 0.05 mg/m3 (0.15 mg/m3 for those hired before 1930), 170 cases of silicosis were determined from either death certificates or two cross-sectional radiographic surveys. RESULTS: The risk of silicosis was less than 1% with a cumulative exposure under 0.5 mg/m3-years, increasing to 68% to 84% for the highest cumulative exposure category of more than 4 mg/m3-years. Cumulative exposure was the best predictor of disease, followed by duration of exposure and average exposure. After adjustment for competing risks of death, a 45-year exposure under the current OSHA standard would lead to a lifetime risk of silicosis of 35% to 47%. CONCLUSIONS: Almost 2 million US workers are currently exposed to silica. Our results add to a small but increasing body of literature that suggests that the current OSHA silica exposure level is unacceptably high.

Adult↗

Potential Involvement of the IL-6/STAT3/MMP12 Signaling Axis in DMSO-Mediated Anti-Fibrotic Effects in Experimental Silicosis.

This study aims to investigate the anti-inflammatory and anti-fibrotic effects of dimethyl sulfoxide (DMSO) in a mouse model of silicosis, thereby exploring its potential therapeutic value. A mouse model of silicosis was established by intranasal instillation, and DMSO treatment was administered via intraperitoneal injection. The experiment was conducted over a period of 1 month. Lung tissues were collected from all mice; a subset was subjected to transcriptomic analysis, and differentially expressed genes were identified using the limma package. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were conducted using ClusterProfiler to investigate gene functions and associated pathways. The remaining samples were subjected to histopathological assessment by hematoxylin and eosin staining (HE) and Masson's trichrome staining, while Western blot analysis was performed to validate transcriptomic results. This study suggests that DMSO may alleviate the fibrotic process in silicosis by modulating the IL-6/STAT3-MMP12 signaling axis. In the silica-induced silicosis mouse model, DMSO attenuated disease-associated weight loss and reduced collagen deposition. Transcriptomic analysis indicated that DMSO suppressed the activity of multiple fibrosis-related pathways and identified 51 key genes, including MMP12, which was significantly downregulated. Western blot analysis further confirmed reduced MMP12 expression, accompanied by markedly decreased levels of IL-6 and p-STAT3, suggesting the IL-6/STAT3 pathway may play a crucial role in regulating MMP12 expression. DMSO may attenuate inflammatory responses and pulmonary fibrosis in silicosis by inhibiting activation of the IL-6/STAT3 signaling pathway, thereby reducing MMP12 expression.

Animals↗

Evaluation of cases with silicosis using the parameters related to Fas-mediated apoptosis.

To establish a new clinical index for immunological abnormalities occurring in silicosis, several clinical parameters related to Fas-mediated apoptosis; i.e., membrane Fas expression on peripheral blood lymphocytes (mFas), serum soluble Fas levels (sFas), serum soluble Fas ligand levels (sFasL), and soluble/membrane Fas mRNA expression ratios (s/mFas ExR) in peripheral blood mononuclear cells (PBMC) were investigated. Fifty-eight silicosis patients with no clinical symptoms of autoimmune diseases were the subjects of this study. Factor analysis was performed using 12 clinical parameters including four parameters related to Fas-mediated apoptosis. Two common factors were identified. Factor 1 which consisted of the following parameters; duration of exposure, symptomatic dyspnea, PO2, PCO2, and A-aDO2, should be designated as the respiratory factor for cases with silicosis. The parameters of factor 2 were serum IgG, sFas with high factor loading, titer of ANA, sFasL, and s/mFas ExR. These parameters of factor 2 are indicative of the immunological disorders occurring in silicosis cases. Some cases exhibited abnormalities in parameters of factor 2 but not factor 1. The factor analysis clearly demonstrated that the parameters related to Fas-mediated apoptosis should be the most beneficial for predicting the pre-clinical status of complicated autoimmune diseases in silicosis.

Aged↗

Relationship between silicosis and lung function.

In an examination of the relationship between silicosis and lung function, relevant studies of silica-exposed workers were reviewed. Smoking, dust exposure, and emphysema are three important factors that can confound the association between silicosis and lung function. Despite the importance of smoking in relation to lung function, some studies did not control for smoking, or smoking was controlled inadequately. The data suggest a weak association between lung function (mainly obstruction) and dust exposure, although some studies had crude measures of exposure. In general, the lung function of those with radiographic silicosis in category 1 was indistinguishable from those in category 0. Those in category 2 had small reductions in lung function relative to those with category 0 and little difference in the prevalence of emphysema. There were slightly greater decrements in lung function with category 3 and more significant reductions with progressive massive fibrosis. Emphysema was related to higher categories of silicosis, as well as to smoking. Silica exposure was often inadequately controlled in studies examining silicosis and lung function. A few studies suggested that emphysema is an independent risk factor associated with significant reductions in lung function.

Confounding Factors, Epidemiologic↗

[Dynamic analysis of incidence of silicosis in uranium miners].

OBJECTIVE: To understand the laws and characteristics of incidence of silicosis and to evaluate the effectiveness of prevention and treatment measures for it in uranium miners. METHODS: An epidemiological study was carried out in three uranium mines and two geological prospecting teams for uranium mines. RESULTS: Exposure to dust in all patients with silicosis initiated in 1950s to 1960s. Dust concentration and detection rate of silicosis have been decreasing, the length of employment in uranium mines and age at occurrence of the disease, interval between lower and upper stages of the disease, its duration and age at their death all have showed an increasing trend since the founding of the mines and geological prospecting teams more than thirty years ago. Those with delayed occurrence of the disease accounting for 20.31% of the total cases. The length of employment in the cases exposed to uranium dust averaged 7.47 years, and the age at occurrence averaged 36.74 years, less than in those exposed to mixed non-uranium dust. CONCLUSION: Effectiveness of comprehensive prevention and treatment measures for silicosis in uranium mines is significant. The average length of employment and age of the occurrence of the silicosis in those exposed only to uranium dust showed and younger.

Adult↗

[Two cases of silicosis exhibiting MPO-ANCA associated disorder].

We reported two cases of silicosis exhibiting MPO-ANCA associated disorder. Case 1 was a 69 year-old man with silicosis and chronic interstitial pneumonia. He was admitted because of fever, dry cough, left chest pain, dyspnea and body weight loss. He was diagnosed as acute exacerbation of interstitial pneumonia, pericarditis and gastrointestinal bleeding. Case 2 was a 67 year-old man with silicosis. He repeated attack of fever, hoarseness, dysphagia and headache. The cell counts of cerebrospinal fluid increased and the thickness of cerebellar tent and left dura mater was observed in the brain MRI. Therefore, he was diagnosed as pachymeningitis and neuropathy of cranial nerves. Both cases were complicated by silicosis and the laboratory findings showed high serum levels of P-ANCA, ANA and rheumatoid factor and inflammatory responses, indicating they were suspected vasculitis. The two cases were treated by steroid and immunosuppressive therapy and had good clinical response. Silicosis may affect multiple organ involvement associated with P-ANCA.

Aged↗

Characteristics of workers attending the pneumoconiosis clinic for silicosis assessment in Hong Kong: retrospective study.

OBJECTIVE: To describe and analyse the baseline characteristics of workers attending the pneumoconiosis clinic for assessment of silicosis. DESIGN: Retrospective cross-sectional study. SETTING: Outpatient clinic. PATIENTS: One thousand and fifty-six patients with silica dust exposure attending the pneumoconiosis clinic for compensation assessment. MAIN OUTCOME MEASURES: Baseline demographic characteristics, lung function parameters, and radiographic findings. RESULTS: Six hundred and forty-eight patients were diagnosed with silicosis, of which 10 were female. Excluding the data on female patients, the mean duration of dust exposure was 24.2 years. The majority of patients were involved in caisson work and stone splitting. Most newly diagnosed patients had simple silicosis. Less than a quarter (24.8%) had progressive massive fibrosis. Lung function parameters at diagnosis were within the normal range. Pulmonary tuberculosis remained an important co-existing disease. CONCLUSION: The major cause of silicosis in Hong Kong is chronic silica dust exposure in the construction industry. Simple silicosis predominated at diagnosis, with normal lung function parameters seen in the majority of patients.

Adult↗

[Mycobacterium tuberculosis L forms in patients with pulmonary silicotuberculosis and silicosis].

OBJECTIVE: To evaluate significance of Mycobacterium tuberculosis L forms in pathogenesis of silicotuberculosis and silicosis. METHODS: Sputum culture for Mycobacterium tuberculosis and its L forms was conducted from both silicotuberculosis and silicosis groups, and the results were compared. RESULTS: Among 60 silicotuberculosis patients, 6 (10%) were sputum Mycobacterium tuberculosis culture positive, of which 5 (83%) were Mycobacterium tuberculosis L forms culture positive; 28 were sputum Mycobacterium tuberculosis L forms culture positive (positive rates in the patients with silicosis stage I, stage II, stage III were 33%, 67%, 100% respectively), with a positive rate of 47%, and a significant difference was found comparing with the frequency of detecting Mycobacterium tuberculosis (P < 0.01). All of the 30 cases with silicosis were Mycobacterium tuberculosis culture negative, however, 3 of them were sputum Mycobacterium tuberculosis L forms culture positive, accounting for 10 percent. CONCLUSIONS: Sputum culture for Mycobacterium tuberculosis L forms is a convenient and rapid way to improve the detection rate of Mycobacterium tuberculosis, with a positive value in early diagnosis of silicotuberculosis by reducing misdiagnosis and underdiagnosis of this disease. Detection rate of Mycobacterium tuberculosis L forms significantly increases with deterioration of silicosis.

Aged↗

[Pulmonary clearance of 99mTC-DTPA aerosol in patients with silicosis].

99mTc-DTPA clearance was studied in 11 healthy nonsmokers, 20 patients with simple or complicated silicosis (5 of simple, 15 of complicated). The results indicated that both the patients with simple silicosis (T1/2 32.8 +/- 14.4min) and complicated silicosis (T1/2 26.6 +/- 8.5min) showed faster clearance of inhaled 99mTc-DTPA than observed in healthy nonsmokers (77.9 +/- 11.7min, p < 0.01). Regional clearance apico-basal difference was found in patients with silicosis. This study presents evidence of increased pulmonary epithelial permeability and regional distribution of pulmonary epithelial permeability in silicosis.

Adult↗

[A case of lung silicosis associated with plasmocytoma: the diagnosis and certification difficulties].

Silicosis is a chronic, progressing disease of the respiratory system. The aim of this paper was to describe a case of silicosis coexisting with not typical plasmocytoma. Silicosis was diagnosed in a 62-year old woman, after an 8-year employment as a grinder. The patient has suffered from progressing weakness, fatigue, and dyspnea for 2 years. The increased leucocytosis (18-20,000) and moderate lymphocytosis were found in laboratory tests. The patient was admitted to the hospital in a very serious condition, with fever and progressing insufficiency of the respiratory and circulatory systems. Following computed tomography (CT), tumorous silicosis was diagnosed in the Department of Internal and Occupational Diseases. After three months, the increased level of the whole number of serum proteins (until 90 g/l) was found for the first time together with few places of osteolysis in the x-ray cranium picture. The plasmocytoma infiltrations were found in the post-mortem lung examination. The described case seems to be interesting in view of a possible induction of monoclonal gammopathy by silicosis.

Diagnosis, Differential↗

[Apoptosis and caspase-3 in the model of rat silicosis].

OBJECTIVE: To explore the changes of apoptosis of cells in the lung tissue of rats with silica instillation and to its significance in silicosis, and to clarify the role of caspase-3 in the apoptosis progress. METHODS: Forty-eight rats were randomly divided into saline control groups and silica instillation groups, and the silicosis model was established in rats. Flow cytometry was used for detecting the rate of apoptosis at various stages. Immunohistochemistry for the expression of cleaved caspase-3. RESULTS: The model of rat silicosis was established successfully. The apoptosis rate in the experimental group was significantly higher than that in the control group, and was increased with time. Caspase-3 was mainly expressed in alveolar epithelium cells, pulmonary macrophages and infiltrated inflammation cells. The expression of caspase-3 in the experimental group was stronger than that in the control group, but its expression intensity was not related to the cell apoptosis (r = 0.215, P > 0.05). CONCLUSION: The apoptosis of the lung cells plays an important role during rat silicosis genesis. Caspase-3 plays an important role in regulating cell apoptosis during rat silicosis genesis.

Animals↗

Risk assessment of silicosis and lung cancer among construction workers exposed to respirable quartz.

OBJECTIVES: The aim of this study was to assess the magnitude of the silicosis and cancer risk among construction workers. METHODS: In 1998, 1335 of 4173 invited construction workers with expected high cumulative exposure to quartz were studied for early signs of silicosis. In 2002 the study was repeated for 96 persons. Exposure measurements were performed among 34 construction workers. Silicosis risk was assessed by converting study results to the whole group of construction workers and by risk analysis based on exposure data combined with documented exposure response relations. Excess risk for cancer was also calculated from available exposure measures. RESULTS: The initial study among construction workers revealed a prevalence of 0.8% of workers with rounded opacities on chest X-rays. The follow-up showed a much higher percentage (12%) of persons with rounded opacities on X-rays. The results were confirmed by high-resolution computed tomography. It was estimated that roughly 9% of the population initially studied (N = 1335) would have been observed with rounded opacities at follow-up. On the basis of the exposure data, a lifetime risk of silicosis above 5% is expected for workers exposed to levels above the occupational exposure limits. An excess lifetime risk for lung cancer is expected when workers are exposed to quartz levels above the occupational exposure limit. Due to the scarcity of exposure data, an estimation of the size of the group at risk is not yet possible. CONCLUSIONS: All available data indicate that construction workers exposed to quartz levels above occupational exposure limits are clearly at elevated risk of silicosis and other respiratory diseases.

Adult↗

[The effect of smoking on immunological parameters in silicosis].

The paper reports on the smoking influence on some immunologic parameters in a group of patients with micronodular silicosis. 3 groups of subjects were studied: I--group with micronodular silicosis, smokers with cigarette index 300; II--group with micronodular silicosis, nonsmokers; III--control group. The following immunologic parameters were determined: 1. Test of blastic transformation of LT at PHA and PHA+IL-1 TTB; 2. Inhibition of leukocyte migration--indirect test; 3. Phagocytosis test of sheep erythrocytes. The results obtained show, in the patients with silicosis, suppression of the ability of blastic transformation, of lymphokines release and non-efficient phagocytosis. Improvement of the lymphocyte function by adding IL-1 suggests a deficiency of this monokine in inducing modified immune response in these patients. Smoking depresses more obviously cellular mediated immune response, induced by silicosis.

Cell Migration Inhibition↗

Humoral immunologic dysfunction in silicosis.

Immunoglobulins may play an important role in the evolution of silicosis, and their determination may serve as a helpful criterion in the diagnosis of silicosis. Serum immunoglobulin levels were studied in slate pencil workers (130) exposed to high concentrations of silica dusts and non-exposed controls (50). Significantly higher levels of immunoglobulins were observed in the silica exposed individuals. A rising trend in the serum IgG from a mean of 1373 mg/dl in control group to 2193.68 mg/dl in exposed group (conglomerate) and IgM from 140.51 mg/dl in control to 201.19 mg/dl in exposed group (conglomerate silicosis) was observed with increase in the duration of dust exposure. Highest mean levels of IgG (2193.60 mg/dl) and IgM (201.19 mg/dl) were observed in the workers having conglomerate silicosis. The results indicate that though, the levels of immunoglobulins were raised in subjects exposed to silica, this parameter may be of limited value for determining progressive of silicosis.

Biomarkers↗

[N-procollagen(III)peptide and lysosomal beta-galactosidase in progressive scleroderma and silicosis].

The concentration of type III collagen aminopropeptide and the activity of lysosomal beta-galactosidase were determined in the serum of patients with progressive sclerosis (PS), silicosis and PS associated with silicosis. In PS-patients, the serum levels of both parameters were significantly increased with a high correlation to the stage of the disease and to each other. In patients with silicosis normal serum concentrations of both parameters were found, whereas in all patients suffering from silicosis and PS significantly elevated serum levels were detectable, independent of the stage of PS. Both parameters can also be used as markers of therapy (e.g. with D-penicillamine) and as early indicators for the development of PS in patients with silicosis.

Adult↗