Association of complete blood count parameters with the risk of incident pulmonary heart disease in pneumoconiosis: a retrospective cohort study.

BACKGROUND: Pneumoconiosis mostly combines pulmonary and cardiovascular diseases, among which pulmonary heart disease (PHD) is of major concern due to its significant impact on the survival of pneumoconiosis patients. White cell count (WCC), red cell distribution width (RDW) and platelet parameters are thought to affect inflammatory responses and may be predictors of various cardiovascular diseases. However, very few studies have focused on PHD. OBJECTIVES: To examine the relationship between baseline complete blood count parameters (WCC, RDW, platelet parameters) and the risk of incident PHD in pneumoconiosis patients. DESIGN: A retrospective cohort study. SETTING: This was a single-centre, retrospective cohort study that used data from an Occupational Disease Hospital, Chengdu, Sichuan. PARTICIPANTS: A total of 946 pneumoconiosis patients from January 2012 to November 2021 were included in the study. Female patients and patients who had PHD, coronary heart disease, hypertensive heart disease, cardiomyopathy, heart failure, oncological disease, multiple organ dysfunction, AIDS at baseline and follow-up time of less than 6 months were also excluded. OUTCOME MEASURES: We identified PHD according to the patient's discharge diagnosis. We constructed Cox proportional hazard regression models to assess the HR of incident PHD in pneumoconiosis, as well as 95% CIs. RESULTS: In the multiple Cox proportional hazard regression analysis, platelet count (PLT) and plateletcrit (PCT) above the median at baseline were associated with an increased risk of PHD in pneumoconiosis with adjusted HR of 1.52 (95% CI 1.09 to 2.12) and 1.42 (95% CI 1.02 to 1.99), respectively. CONCLUSION: Higher baseline PLT and PCT are associated with a higher risk of PHD in pneumoconiosis.

Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals.

Workers processing nephrite, antigorite, or talc may be exposed to paragenetic asbestos minerals. An effective screening method for pneumoconiosis in workers exposed to asbestos-contaminated minerals is still lacking. The objective of this study was to assess the diagnostic accuracy of serum and urinary biomarkers for pneumoconiosis in workers exposed to asbestos-contaminated minerals. We conducted a case-control study in a cohort of stone craft workers in Hualien, where asbestos, nephrite, antigorite, and talc are produced. A total of 140 subjects were screened between March 2013 and July 2014. All subjects received a questionnaire survey and a health examination that included a physical examination; chest X-ray; and tests for standard pulmonary function, fractional exhaled nitric oxide, serum soluble mesothelin-related peptide (SMRP), fibulin-3, carcinoembryonic antigen (CEA), and urinary 8-Oxo-2'-deoxyguanosine (8-OHdG)/creatinine. After excluding subjects with uraemia and chronic obstructive pulmonary disease (COPD), we included 48 subjects with pneumoconiosis and 90 control subjects without pneumoconiosis for analysis. In terms of occupational history, 43/48 (90%) case subjects and 68% (61/90) of the control subjects had processed asbestos-contaminated minerals, including nephrite, antigorite, and talc. The case group had decreased pulmonary function in forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow between 25% and 75% of the FVC. The levels of SMRP, fibulin-3, urinary 8-OHdG/creatinine, and CEA were higher in the case group than in the control group. Subjects exposed to nephrite had significantly higher SMRP levels (0.84 ± 0.52 nM) than subjects exposed to other types of minerals (0.60 ± 0.30 nM). A dose-response relationship was observed between the SMRP level and the severity of pneumoconiosis. Machine learning algorithms, including variables of sex, age, SMRP, fibulin-3, CEA, and 8-OHdG/creatinine, can predict pneumoconiosis with high accuracy. The areas under the receiver operating characteristic curves ranged from 0.7 to 1.0. We suggest that SMRP and fibulin-3 could be used as biomarkers of pneumoconiosis in workers exposed to asbestos-contaminated minerals.

[The clinical study on the correlation of lysophosphatidic acid and vascular endotheli growth factor and endothelin in serum of pneumoconiosis].

Objective: To explore the role of lysophosphatidic acid, vascular endothelial growth facor and endothelin in the pathogenesis of pulmonary fibrosis in coal workers'pneumoconiosis patients, the relationship of lysophosphatidic acid, VEGF and ET in serum was studied. Methods: Sixty two pneumoconiosis patients were selected as cases group, which included 23 cases of stage Ⅰ, 25 cases of stageⅡand 14 cases of stageⅢ. Twenty workers were selected as dust exposure group who exposed to coal dust for more than 2 years and had not been diagnosed as pneumoconiosis. Ten healthy people who had no occupational dust exposure were simultaneously selected as the control group. The serum levels of LPA, VEGF and ET were measured by ELISA. Results: The serum levels of VEGF and ET in coal dust exposed group and pneumoconiosis group were much higher than in the control group. The differences were statistically significant among the three groups (P<0.01) . The serum levels of LPA increased in the dust exposed group, stage Ⅰand stage Ⅱgroup. The serum levels of LPA correlated positively with the levels of VEGF and ET (P<0.05) . Conclusions: The serum levels of LPA, VEGF and ET had evident correlation with the pulmonary fibrosis caused by coal dust, which indicate that LPA, VEGF and ET may play a pivotal role in the process of pulmonary fibrosis. The study will throw light on both pathogenesis and early intervention for pneumoconiosis.

Selenium and exposure to fibrogenic mineral dust: a mini-review.

Individuals exposed to fibrogenic mineral dust may exhibit an impaired antioxidant system and produce high levels of reactive oxygen and nitrogen species through immune cells, contributing to the perturbation of immune cell function, inflammation, fibrosis and lung cancer. The lung diseases which are caused by inhalation of fibrogenic mineral dust, known as pneumoconioses, develop progressively and irreversibly over decades. At the moment there is no known cure. The trace element selenium has potent antioxidant and anti-inflammatory properties mediated mainly through selenoproteins. Research has demonstrated that selenium has the ability to protect against cardiovascular diseases; to kill cancer cells in vitro and reduce cancer incidence; and to immunomodulate various cellular signaling pathways. For these reasons, selenium has been proposed as a promising therapeutic agent in oxidative stress associated pathology that in theory would be beneficial for the prevention or treatment of pneumoconioses such as silicosis, asbestosis, and coal worker's pneumoconiosis. However, studies regarding selenium and occupational lung diseases are rare. The purpose of this study is to conduct a mini-review regarding the relationship between selenium and exposure to fibrogenic mineral dust with emphasis on epidemiological studies. We carried out a systematic literature search of English published studies on selenium and exposure to fibrogenic mineral dust. We found four epidemiological studies. Reviewed studies show that selenium is lower in individuals exposed to fibrogenic mineral dust. However, three out of the four reviewed studies could not confirm cause-and-effect relationships between low selenium status and exposure to fibrogenic mineral dust. This mini-review underscores the need for large follow-up and mechanistic studies for selenium to further elucidate its therapeutic effects.

[The expression of vascular endothelial growth factor antibody in serum of coal workers with pneumoconiosis].

OBJECTIVE: To determine the role of serum VEGF-Ab in pneumoconiosis of coal workers. METHODS: Four groups of participants were recruited for this study, including 230 with early stage (less serious than stage one) changes in relation to pneumoconiosis, 328 with confirmed coal worker pneumoconiosis, 309 workers exposed to coal dust, and 393 healthy people. All participants completed a questionnaire, and have their peripheral venous blood sample taken. Serum VEGF-Ab was detected by ELISA. RESULTS: Compared with healthy controls and those with early stage changes, the participants with pneumoconiosis and those exposed to coal dust had higher levels of serum VEGF-Ab (P < 0.05). The level of serum VEGF-Ab increased with the progression of stages of pneumoconiosis but without statistical significance (P > 0.05). In those with early stage pneumoconiosis, higher levels of serum VEGF-Ab were found in their 20 yr. - and 40 yr. - compared with those in their 60 yr. - (P < 0.05). By contrast, in those with confirmed pneumoconiosis and the healthy controls, lower levels of serum VEGF-Ab were found in their 20 yr. - and 40 yr. - compared with those in their 60 yr. - (P < 0.05). In those with early stage or first-stage pneumoconiosis, longer than 25 years work experience was associated with higher levels of serum VEGF-Ahb (P < 0.05). In those with confirmed pneumoconiosis, coal mining workers had a higher level of serum VEGF-Ab than their colleagues involving in assistance tasks (P < 0.05). In those exposed to coal dust, tunnelling workers had a higher level of serum VEGF-Ab than their coal mining colleagues (P < 0.05). CONCLUSION: Serum VEGF-Ab is associated with the occurrence and development of coal worker pneumoconiosis. The level of serum VEGF-Ab increases with age and length of exposure to dust.

[Expression of serum cytokines in patients with pneumoconiosis by antibody chip].

OBJECTIVE: To investigate the changes in expression of serum cytokines in patients with pneumoconiosis using cytokine antibody chips (CACs). METHODS: The CAC technology was applied to measure the serum levels of 60 cytokines in 12 patients with pneumoconiosis and 3 normal controls. RESULTS: In the patients with pneumoconiosis, the highly expressed serum cytokines included interleukin (IL)-1α, IL-1ß, IL-2, ILs 4-16, macrophage colony-stimulating factor, interferon-γ, tumor necrosis factor (TNF)-α, TNF-ß, human bone morphogenetic protein-6, fibroblast growth factor-7, neurotrophin-3, and stem cell factor, and the lowly expressed serum cytokines included recombinant human I-309, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, MCP-4, macrophage inflammatory protein (MIP)-1-δ, and MIP-3-α. CONCLUSION: Patients with pneumoconiosis have changes in the expression of most serum cytokines.

Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation.

Titanium dioxide nanoparticles (TNP) are nanomaterials which have various applications including photocatalysts, cosmetics, and pharmaceuticals because of their high stability, anticorrosiveness, and photocatalytic properties. Induction of cytokines and potential chronic inflammation were investigated in mice treated with TNP (5 mg/kg, 20 mg/kg, and 50 mg/kg) by a single intratracheal instillation. Pro-inflammatory cytokines such as IL-1, TNF-a, and IL-6 were significantly induced in a dose-dependent manner at day 1 after instillation. The levels of Th1-type cytokines (IL-12 and IFN-gamma) and Th2-type cytokines (IL4, IL-5 and IL-10) were also elevated dose-dependently at day 1 and the inflammatory responses were sustained until the remainder of experimental period for 14 days. By the induction of Th2-type cytokines, the increased B cell distributions both in spleen and in blood, and increased IgE production in BAL fluid and serum were observed. In lung tissue, increase of inflammatory proteins (MIP and MCP) and granuloma formation were observed. Furthermore, the expressions of genes related with antigen presentation (H2-T23, H2-T17, H2-K1, and H2-Eb1) and genes related with the induction of chemotaxis of immune cells (Ccl7, Ccl3, Cxcl1, Ccl4, Ccl2) were markedly increased using microarray analysis. From these data, it could be suggested that TNP possibly cause chronic inflammatory diseases through Th2-mediated pathway in mice.

[Levels and clinic significance of serum soluble Fas and soluble Fas ligand in coal workers' pneumoconiosis].

OBJECTIVE: To investigate the changes of levels and clinic significance of serum soluble Fas (sFas) and soluble FasL (sFasL) in coal workers' pneumonoconiosis. METHODS: Serum levels of sFas and sFasL were determined in 52 patients with silicosis, 57 coal workers' pneumonoconiosis, 46 healthy underground coal workers' (the underground control group) and 40 healthy volunteers working on the ground (the ground control group) with a sandwich ELISA. RESULTS: Compared to the underground control and the ground control group, the serum levels of sFas and sFasL in the patients with silicosis and the coal workers' pneumonoconiosis were significantly higher (P < 0.01). Serum levels of sFas and sFasL in the underground control group were significantly higher than those in the ground control group (P < 0.01); Serum sFas levels in coal workers' pneumonoconiosis was significantly higher than those in the patients with silicosis (P < 0.01). Although the serum sFasL levels was also increased, there was no significant difference (P > 0.05). In the patients with silicosis and the coal workers' pneumonoconiosis patients, the serum sFas levels in Phase I patients combined with emphysema and simple Phase II + III patients were significantly higher than those in simple Phase I patients (P < 0.01). There was no significant difference in the serum sFasL levels among various groups with different parameters of pneumonoconiosis. In the patients with silicosis and the coal workers' pneumonoconiosis, serum levels of sFas and sFasL were not significantly altered among different duration of exposure to dusts. There was no correlation between serum levels of sFas and sFasL in the patients with silicosis while there was a slightly positive correlation between sFas and sFasL levels in the coal workers' pneumonoconiosis (r = 0.479, P < 0.05). CONCLUSION: In the patients with silicosis and the coal workers' pneumonoconiosis, the serum levels of sFas and sFasL are abnormal and associated with the development of the pneumonoconiosis. The changes of serum sFas levels may indicate the development and progression of the pneumonoconiosis. The detection of the serum sFas level may be used in the differential diagnosis for the silicosis and the coal worker's pneumonoconiosis.

Antioxidant response at early stages and low grades of simple coal worker's pneumoconiosis diagnosed by high resolution computed tomography.

In miners exposed to coal dusts, coal worker's pneumoconiosis (CWP) can occur. The purpose of the present study is to better understand the relations between coal dust exposure and activities of blood plasma antioxidant enzymes, namely, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and lipid peroxidation end product malondialdehyde (MDA) concentration in coal workers with early and low grade simple CWP diagnosed by high resolution computed tomography (HRCT). Forty-three coal workers who had profusions of 0/1-2/2 according to ILO 1980 chest X-ray (CXR) classification, 43 coal workers without CWP (control group 1) and 44 healthy subjects (control group 2) who were randomly selected from the population register or recruited from the hospital staff were enrolled. Coal workers were reevaluated by HRCT (Hosoda-Shida classification) due to its higher sensitivity than standard CXR. Then, blood plasma SOD and GSH-Px activities and MDA plasma levels were measured. CWP was found positive in 46 of 89 coal workers by HRCT evaluation. Profusion 0 (P0, CWP not present), profusion 1 (P1, early CWP) and profusion 2 (P2, low grade CWP) were found in 43, 23 and 19 of patients found to have CWP by HRCT, respectively. We had no worker with profusion 3 (P3). Complicated CWP was shown in four of 46 patients and thesecases were excluded as the study was restricted to early and low-grade pneumoconiosis. In respect to the plasma levels of MDA and plasma activities of SOD and GSH-Px, statistically significant differences were found between CWP cases and control groups (p < 0.01, p < 0.01, p < 0.001 respectively). Statistical differences were also obtained for the plasma activities of SOD and GSH-Px and levels of MDA in relation to HRCT profusions (p < 0.05). In conclusion, these findings suggest an oxidative stress due to increased free radicals and reactive oxygen metabolite production in early stages and low grades of simple CWP diagnosed by HRCT.

Differences in cellular and inflammatory cytokine profiles in the bronchoalveolar lavage fluid in bagassosis and silicosis.

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.

[Potential effect of tumor necrosis factor-alpha and its receptor II gene polymorphisms on the pathogenesis of coal worker's pneumoconiosis].

OBJECTIVE: To approach the effect of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor receptor II (TNFRII) gene polymorphisms on genetic susceptibility of coal worker's pneumoconiosis and their relationship with pulmonary fibrosis. METHODS: Two hundred and thirty-four cases of coal worker's pneumoconiosis (CWP) and four hundred and forty coal mine workers (controls) were selected, and the cases of CWP were divided into three subgroups based on the various stages of I, II and III. 3 ml peripheral vein blood was drawn from every subject. Using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) techniques, TNF-alpha and TNFRII gene polymorphisms were analyzed. RESULTS: In both group matching and 1:1 paired matching, there was no significant difference between CWP workers and controls in distribution frequencies of G/A + A/A (TNF-alpha -308) and T/G + G/G (TNFRII 196) genotypes. The distribution frequency of G/A + A/A genotype in CWP with stage III (20.00%) was higher than those in control (10.91%), and CWP cases with stage I (10.34%) and II (7.50%) respectively. The risk of CWP with stage III in those with G/A + A/A genotype was 2-fold higher than with G/G genotype (OR = 3.00, 95% CI: 0.35 approximately 25.84) for 1:1 paired matching. CONCLUSIONS: TNF-alpha and TNFRII gene polymorphisms does not play an important role in susceptibility to CWP of Han race. TNF-alpha gene promoter polymorphisms might be related with the degree of severe pulmonary fibrosis in CWP.

The presence of promatrix metalloproteinase-3 and its relation with different categories of coal workers' pneumoconiosis.

Extracellular matrix formation (ECM) and remodeling are critical events related to the pathogenesis of pulmonary fibrosis. Matrix metalloproteinases play an essential role in degrading and remodeling the ECM. In this study, we tried to show the presence and correlation of promatrix metalloproteinase-3 (proMMP-3) (the inactive form of metalloproteinase-3) levels in coal workers' pneumoconiosis (CWP) with different categories. The study population consisted of 44 coal miners with CWP (pos CWP). Coal miners without CWP (neg CWP, n = 24) and non-underground personnel (controls, n = 17) were taken as controls. All coal miners were stable and had no systemic infection or disease. Standard posterio-anterior chest radiographs and pulmonary function tests were performed to exclude any diseases other than CWP. Serum proMMP-3 was analysed using the sandwich enzyme-linked immunosorbent assay according to the manufacturer's instructions (The Binding Site, Birmingham, UK). Mean proMMP-3 values of the all three groups were compared and a significant statistical difference obtained (p < 0.001). In addition, a statistically significant difference was found between categories of the disease and proMMP-3 values (p < 0.05). The effects of age, exposure duration and cigarette smoking on proMMP-3 values in coal miners with CWP were investigated. There were no correlations between age, smoking and proMMP-3 values. However, a positive correlation was found between exposure duration and proMMP-3 values (r = 0.447, p = 0.008). In conclusion, proMMP-3 (prostromelysin 1) may play an essential role in degrading and remodeling the ECM in workers with pneumoconiosis. ProMMP-3 may also reflect the stage of pneumoconiosis disease.

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and their soluble receptors in coal workers' pneumoconiosis.

The aim of this study was to investigate whether systemic tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors (p55, p75), interleukin 6 (IL-6), and soluble IL-6 receptor could be markers of biological activities of coal workers' pneumoconiosis (CWP). The study population was composed of 182 Chinese retired coal miners who had similar dust exposure histories. Among them, 71 were cases with CWP and 111 were controls. Chest radiographs were classified according to International Labour Organization Criteria (ILO, 1980). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Serum concentrations of TNF-alpha, TNF-alpha receptors (p55, p75), IL-6, and IL-6 receptor were measured by ELISA techniques. Mean serum levels of p55, p75 and IL-6 were significantly higher in cases than in controls (P < or = 0.01 for each comparison by crude analyses). Results from logistic regression models, adjusted for age, dust exposure variables, and smoking habits, found similar associations between soluble p55 and p75 levels and the presence of CWP. Linear regression analysis revealed that CWP radiographic stage (by ILO criteria) was significantly correlated with the individual serum concentrations of p55, p75 and IL-6. Serum concentrations of all measured cytokines were notcorrelated to age, dust exposure, or smoking, but there were correlations between soluble p75 and p55 levels, and between p75 and IL-6 levels. The results of this study suggest that serum levels of TNF receptors and IL-6 are associated with the fibrotic process of CWP and serum cytokine levels may be correlated with the severity of CWP.

Functional variables associated with the clinical grade of dyspnoea in coal miners with pneumoconiosis and mild bronchial obstruction.

OBJECTIVES: Dyspnoea is a common symptom in coal miners with pneumoconiosis. Among others, gas exchange disturbances due to airway obstruction or mismatch between ventilation and perfusion may be underlying mechanisms. The validation of dyspnoea by the degree of airway obstruction is controversial, because the extent of airway obstruction often does not correlate with the clinical grade of breathlessness. METHODS: The association was investigated between breathlessness (self reported, on a six point scale) and indices of submaximal spiroergometry in 66 coal workers with radiographically confirmed pneumoconiosis (International Labour Organisation (ILO) grade of profusion > or =1/0, mean (SD) age 64 (5.5) years, mean (SD) forced expired volume in 1 second (FEV(1)) 77.5 (22.9) % predicted). RESULTS: The clinical degree of breathlessness was independently associated with minute ventilation/oxygen consumption (VE/VO(2)) ratio (beta 0.423, 95% confidence interval (95% CI) 0.18 to 0.67, p=0.001) and smoking (beta 0.318, 95% CI 0.21 to 1.79, p=0.014) in a multiple linear regression analysis. The VE/VO(2) ratio (beta 0.556, 95% CI 0.20 to 0.90, p=0.003) was also the best predictor of breathlessness when only coal miners with airway obstruction (FEV(1) < 80% predicted) were analyzed. CONCLUSION: The VE/VO(2) ratio as a measurement of mismatch between ventilation and perfusion predicted the clinical grade of breathlessness better than measurements of bronchial obstruction at rest in coal workers with pneumoconiosis.

Quantitative detection of tumor M2-pyruvate kinase in plasma of patients with lung cancer in comparison to other lung diseases.

Lung cancer is one of the predominant causes of cancer death. The aim of this project is the development of a screening method in persons with high risk for developing lung cancer, based on the measurement of Tumor M2-pyruvate kinase (Tumor M2-PK). Tumor M2-PK is quantitatively detectable in ethylenediaminetetraacetic acid-plasma with a sensitive enzyme-linked immunosorbent assay. So far, 60 patients with newly diagnosed lung cancer were included. These were compared to 24 patients with acute inflammatory lung diseases, 56 patients with pneumoconiosis, 22 patients with obstructive airway diseases, and 28 healthy persons. Tumor patients and some individuals suffering from severe inflammatory lung diseases had significantly higher Tumor M2-PK concentrations in ethylenediaminetetraacetic acid-plasma than all the other groups. The histologic tumor type had no influence on the plasma levels of Tumor M2-PK. Tumor M2-PK concentrations correlate strongly with the tumor stage, showing significantly increasing concentrations with progressive tumor stages. The present data indicate that Tumor M2-PK could be a valuable tumor marker for the detection of lung cancer.

Potential biomarker of coal workers' pneumoconiosis.

It is well known that various cytokines and growth factors secreted from macrophages/monocytes play the key role in the pathogenesis of pneumoconiosis. These can act as biosensors for the prediction of pneumoconiosis. To evaluate which cytokines can be used as sensitive biomarkers in pneumoconiosis, we measured tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and platelet-derived growth factor-AA (PDGF-AA) in supernatant of monocytes with or without coal dust (5 mg/ml) and serum in 42 coal miners with pneumoconiosis and ten healthy control. The coal-stimulated release of TNF-alpha and IL-8 from blood monocytes was significant increased in pneumoconiosis patients compared with controls. The level of TNF-alpha and IL-8 in blood serum was higher in subjects with pneumoconiosis than in controls.

Relations between occupational exposure to coal mine dusts, erythrocyte catalase and Cu++/Zn++ superoxide dismutase activities, and the severity of coal workers' pneumoconiosis.

OBJECTIVES: To better understand the relations between occupational exposure, blood antioxidant enzyme activities, total plasma antioxidant concentration, and the severity of coal workers' pneumoconiosis (CWP). METHODS: Blood samples were obtained from miners without CWP exposed to low dust concentrations for > or = 4 years at the time of the study (n = 105), or exposed to high dust concentrations for > or = 14 years at the time of the study (n = 58), and from retired miners with CWP (n = 19). Miners without CWP were classified into three subgroups according to their estimated cumulative exposure to dust. Chest x ray films were obtained for each miner. Miners were classified in five subgroups according to their International Labour Organisation (ILO) profusion grades. Univariate tests were completed by multiple linear regression analyses. RESULTS: The estimated cumulative exposure to dust was strongly positively related to erythrocyte catalase activity and strongly negatively related to Cu++/Zn++ SOD activity only in miners exposed to high dust concentrations for > or = 14 years at the time of the study (F tests p = 0.006 and p = 0.004 respectively). Moreover, catalase activity was strongly related to the severity of CWP expressed as five subgroups of ILO profusion grades (F test p = 0.003); the greatest difference in the mean values was found between the group of 1/1 to 1/2 ILO profusion grades and the group of 2/1 to 3/3 ILO profusion grades. CONCLUSION: These results are in good agreement with the hypothesis that production of reactive oxygen species may be an important event in the exposure to coal mine dusts and the severity of CWP. Erythrocyte catalase and Cu++/Zn++ SOD activities are more closely related to recent exposure to high dust concentrations than to cumulative exposure, and could be considered as biological markers of exposure rather than as markers of early adverse biological effect.

Polymorphisms in the promoter of the tumor necrosis factor-alpha gene in coal miners.

Tumor necrosis factor-alpha (TNF) is recognized as a central mediator of mineral dust-induced lung fibrosis, and genetic polymorphisms of the TNF promoter have been reported to influence levels of TNF production. To assess whether polymorphisms within the TNF promoter gene are associated with susceptibility to coal workers' pneumoconiosis (CWP), the DNA of 78 coal miners was typed for G-to-A transitions at positions -238 and -308. Our results show that frequency of A-308 genotype (T2) is significantly overpresented in coal miners with CWP (50%), as compared with miners without CWP (25%) and controls (29%). After correction for cumulative dust exposure and smoking, the A-308 transition genotype is still associated with the presence of CWP (OR = 3.0, 95% CI = 1.0-9.0). Both A-238 and A-308 transition genotypes were related to TNF release from endotoxin-stimulated blood monocytes; only the A-238 transition and not the A-308 transition was associated to coal dust-induced TNF release. In summary, this study shows that the A-308 transition is related to CWP, but this relation is not paralleled by a different TNF release in this genotype. A larger number of patients coupled to frequent TNF release are required to evaluate genotype screening to estimate individual health risks for effects of coal mine dust exposure.

Characterization of a soluble form of neutral endopeptidase-24.11 (EC 3.4.24.11) in human serum: enhancement of its activity in serum of underground miners exposed to coal dust particles.

A previous epidemiological study has reported the elevation of a serum metalloendopeptidase activity for underground coalminers exposed to chronic inhalation of coal mine dust particles. In this work, we have unambiguously characterized this activity as neutral endopeptidase (EC 3.4.24.11) using five different criteria. The apparent molecular weight of 100,000 g mol-1 calculated for the serum peptidase using Western blots or direct binding of the neutral endopeptidase 24.11 inhibitor [125I]-RB104 to the enzyme in acrylamide gels, suggests that the soluble form of this ectoenzyme is not generated by a post-translational cleavage of the membrane-bound form, as is the case for the closely related ectoenzyme, angiotensin-converting enzyme. The circulating endopeptidase very likely results from a shedding process. The increase in serum neutral endopeptidase 24.11 activity of underground miners compared with surface miners (5.7-fold), P < 0.01) is not correlated with systemic inflammation parameters, but seems to reflect the chronic pulmonary inflammatory state induced by coalmine dust exposure, and so may be a marker of lung injury.

Pulmonary disability in former Appalachian coal miners.

A prospective case-control study was undertaken to assess respiratory disability in 133 former coal miners who were claimants for "black lung" benefits. Consecutive assignment was made to either case or control group based on their chest radiograph having shown coal workers' pneumoconiosis or no coal workers' pneumoconiosis. A respiratory occupational survey was completed with physical examination that placed special emphasis on the cardiorespiratory systems. Subjects underwent pulmonary function testing while 92 of these also received arterial blood gases to assess respiratory disability and pulmonary insufficiency. Arterial blood gases were superior to spirometry in assessment of pulmonary insufficiency/disability. Smoking interacts with coal workers' pneumoconiosis to cause pulmonary insufficiency. The most frequent spirometric pattern was obstructive. Disability was caused by occupational injuries and comorbidities, both of which occurred with greater frequency in miners with coal workers' pneumoconiosis than in controls. Pulmonary insufficiency appears to be a better discriminator than respiratory disability in coal miners, suggesting that arterial blood gases replace spirometry in their evaluation. Greater emphasis on smoking intervention among coal miners should be given.