Exploration study on serum metabolic profiles of Chinese male patients with artificial stone silicosis, silicosis, and coal worker's pneumoconiosis.

Long-term exposure to inhaled silica dust induces pneumoconiosis, which remains a heavy burden in developing countries. Modern industry provides new resources of occupational SiO2 leading to artificial stone silicosis especially in developed countries. This study aimed to characterize the serum metabolic profile of pneumoconiosis and artificial stone silicosis patients. Our case-control study recruited 46 pairs of pneumoconiosis patients and dust-exposed workers. Nontargeted metabolomics and lipidomics by ultra-high-performance liquid chromatography-tandem mass spectrometry platform were conducted to characterize serum metabolic profile in propensity score-matched (PSM) pilot study. 54 differential metabolites were screened, 24 of which showed good screening efficiency through receiver operating characteristics (ROC) in pilot study and validation study (both AUC > 0.75). 4 of the 24 metabolites can predict pneumoconiosis stages, which are 1,2-dioctanoylthiophosphatidylcholine, phosphatidylcholine(O-18:1/20:1), indole-3-acetamide and l-homoarginine. Kynurenine, N-tetradecanoylsphingosine 1-phosphate, 5-methoxytryptophol and phosphatidylethanolamine(22:6/18:1) displayed the potential as specific biomarkers for artificial stone silicosis. Taken together, our results confirmed that tryptophan metabolism is closely related to pneumoconiosis and may be related to disease progression. Hopefully, our results could supplement the biomarkers of pneumoconiosis and provide evidence for the discovery of artificial stone silicosis-specific biomarkers.

Associations of HMGB1 gene polymorphisms with risk of coal workers' pneumoconiosis susceptibility in Chinese Han population.

Background: High-mobility group box 1 (HMGB1) protein plays an important pathogenic role in various diseases such as pulmonary fibrosis. However, the relationship between variation of HMGB1 gene and susceptibility to coal worker's pneumoconiosis (CWP) remains unclear. The objective of the study was to determine the association between HMGB1 polymorphisms and CWP in Chinese Han population.Methods: The genotypes of HMGB1 gene rs1045411, rs2249825, rs1412125 and rs1360485 in 340 CWP patients and 312 healthy controls were determined and serum HMGB1 levels were detected.Results: Our finding showed that the HMGB1 rs1360485 G allele increased the risk of CWP in comparison with A allele (P = 0.005). HMGB1 rs1360485 GG genotype as well as AG+GG genotype increased the risk of CWP in comparison with AA genotype (P = 0.010, P = 0.025, respectively). Four haplotypes were identified and we found that the GCTA haplotype was associated with resistance to CWP (P = 0.005), while GCTG haplotype was associated with risk to CWP (P<0.001). Meanwhile, multifactor dimensionality reduction (MDR) analysis showed that the interaction between rs1360485 and exposure had the strongest, followed by rs2249825 and rs1412125. This study also found that the serum HMGB1 levels of the case group were significantly higher than that of the control group, and the serum HMGB1 levels of homozygous subjects with rs1360485 mutant were higher than that of the heterozygous wild type, respectively (P<0.001). Meanwhile, the levels of HMGB1 with GCTA haplotype was lower than with GCTG haplotype (P<0.001)Conclusion: Our findings indicated that HMGB1 gene rs1360485 polymorphism was associated with the susceptibility to CWP in Chinese Han population.

Extracellular Histones Promote Pulmonary Fibrosis in Patients With Coal Workers' Pneumoconiosis.

OBJECTIVE: This investigation assessed the profibrotic role that extracellular histones play in the pathogenesis of coal workers' pneumoconiosis (CWP). METHODS: The correlation of extracellular histones with small opacity profusion (SOP) and transforming growth factor-ß (TGF-ß) was analyzed. The stimulating effect of extracellular histones on pulmonary fibroblast was assessed in vitro. RESULTS: The levels of extracellular histones in plasma were positively correlated with SOP and TGF-ß in the coal miners investigated. Plasma collected from patients with CWP caused apparent lung fibroblast proliferation, while anti-H4 antibody antagonized the stimulating effect of the patient plasma by blocking histone H4. In vitro experiments showed that extracellular histones directly stimulated fibroblast proliferation. CONCLUSION: Consistent with our hypothesis, the concentrations of extracellular histones were indices of the severity of pulmonary fibrosis in simple CWP, and extracellular histones-targeted intervention could inhibit the proliferation of lung fibroblast.

[Analysis of the characteristics of lymphocyte subsets in peripheral blood among coal worker's pneumoconiosis patients].

Objective: To preliminary analysis of the characteristics of lymphocyte subsets in peripheral blood among 135 cases of coal worker's pneumoconiosis patients in Huainan mining area. Methods: The peripheral bloods of 135 cases of coal worker's pneumoconiosis patients and 112 cases of health examiners were collected. Flow cytometry was used to detect peripheral blood lymphocytes, T cell subsets and CD4(+)CD25(+) regulatory T cells. Results: Compared with the control group, CD64 index of granulocytes and lymphocytes was slightly higher. The total T cells (CD3(+)) increased in peripheral blood, CD4(+) expression was reduced and CD8(+) expression was increased in infection group, CD4(+)/CD8(+) ratio was inverted, the differences between the infection group and the control group were statistically significant (P<0.05) . There were significantly fewer NK (nature killer) and B cells, significantly more double negative T cells (DNT, CD3(+)CD4(-)CD8(-)) than the control group (P<0.05) . There was no statistically significant difference of CD4(+)CD25(+)CD127(+low)、CD4(+)CD25(+)CD127(+hi) and the ration of Treg/CD4(+)CD25(+)CD127(+hi) protein expression in peripheral blood in two groups (P>0.05) . Conclusion: The analysis of peripheral blood lymphocyte and subgroup is an ideal index to monitor the immune status of coal worker's pneumoconiosis patients. It has theoretical significance for studying the immune mechanism of pneumoconiosis and guiding clinical treatment.

Plasma LncRNA-ATB, a Potential Biomarker for Diagnosis of Patients with Coal Workers' Pneumoconiosis: A Case-Control Study.

LncRNA-ATB (lncRNA was activated by transforming growth factor-ß) has been reported to be involved in specific physiological and pathological processes in human diseases, and could serve as biomarkers for cancers. However, the role of lncRNA-ATB in coal workers' pneumoconiosis (CWP) is still unknown. This study aimed to investigate the association between lncRNA-ATB and CWP. Quantitative real-time polymerase chain reaction was performed to detect plasma lncRNA-ATB expression in 137 CWP patients, 72 healthy coal miners and 168 healthy controls. LncRNA-ATB was significantly upregulated in CWP (p < 0.05). Compared with the healthy controls and healthy coal miners, the odds ratios (ORs) (95% confidence interval (CI)) for CWP were 2.57 (1.52-4.33) and 2.17 (1.04-4.53), respectively. LncRNA-ATB was positively associated with transforming growth factor-ß1 (TGF-ß1) (r = 0.30, p = 0.003) and negative correlated with vital capacity (VC) (r = -0.18, p = 0.033) and forced vital capacity (FVC) (r = -0.18, p = 0.046) in CWP patients. Compared with healthy controls, the area under the curve (AUC) was 0.84, resulting in a 71.17% sensitivity and 88.14% specificity. When compared with healthy coal miners, the AUC was 0.83, the sensitivity and specificity were 70.07% and 86.36%, respectively. LncRNA-ATB expression is commonly increased in CWP and significantly correlates with the TGF-ß1 in CWP patients. Furthermore, elevated lncRNA-ATB was associated with CWP risk and may serve as a potential biomarker for CWP.

Differential gene expression associated with inflammation in peripheral blood cells of patients with pneumoconiosis.

OBJECTIVES: To study expression changes in inflammation-related genes in peripheral blood of patients with pneumoconiosis and to explore the possibility of these genes as pneumoconiosis biomarkers. METHODS: Peripheral blood samples of patients with pneumoconiosis patients and controls were collected, and total RNA of the blood cells were extracted and reverse transcribed to cDNA. Screenings of deferentially expressed genes associated with inflammation between patients with pneumoconiosis and controls were performed using real-time quantitative PCR array and the expressions of the three most upregulated genes were confirmed by real-time PCR. RESULTS: The expression of 11 genes was significantly altered in patients with pneumoconiosis compared with those of the control. Among these 11 genes, 8 genes were upregulated and 3 were downregulated. Preliminary results indicated that interleukin 6 (IL-6) mRNA expression in patients with pneumoconiosis was higher than that in controls (P=0.019). The level of IL6 mRNA expression in the patients was higher than that in non-smoking controls, but it was neither affected by type and stage of pneumoconiosis nor by time of contact with dust. CONCLUSIONS: IL6 was possibly involved in the development of pneumoconiosis.

Platelet Indices in Patients with Coal Workers' Pneumoconiosis.

PURPOSE: Coal workers' pneumoconiosis (CWP) is caused by an accumulation of coal particles in the lung parenchyma. Reactive oxygen species (ROS) play an important role in the pathogenesis of CWP. It is well documented that ROS stimulate platelet activation, adhesion, and aggregation. The aim of the present study was to investigate the relationship between platelet indices and CWP. METHODS: The demographic features, occupational and medical history, exposure time, and complete blood count of retired coal miners were retrospectively analysed. The control group comprised healthy subjects who had not worked underground. Chest radiographs were evaluated according to the CWP classification of the International Labour Office. RESULTS: The study population was divided into following groups: 50 controls, 97 without CWP, 142 simple pneumoconiosis (SP), 157 progressive massive fibrosis (PMF). The platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) were significantly higher in patients with CWP compared to those in patients without CWP and controls. The platelet count, MPV, and PCT were higher in patients with PMF compared to those in the SP group (p < 0.05). The results of multiple logistic regression analyses indicated that the platelet count, MPV, and PCT were independently associated with the development of CWP. CONCLUSIONS: Platelet indices may be considered as disease markers for pneumoconiosis in coal miners and as a useful indicator of the progression of pneumoconiosis.

Serum levels of IL-8 and ICAM-1 as biomarkers for progressive massive fibrosis in coal workers' pneumoconiosis.

Coal workers' pneumoconiosis (CWP) is characterized as a chronic inflammation of the lung associated with activation of macrophages and endothelial cells in the lung. The aim of the present study was to compare the levels of serum interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-α), and intercellular adhesion molecule-1 (ICAM-1) as biomarkers for progressive massive fibrosis (PMF) in 106 subjects (27 non-CWP and 79 CWP patients). The levels of serum IL-8 (P<0.001) and ICAM-1 (P=0.001) of subjects with PMF were higher than those of non-CWP subjects. The IL-8 levels of PMF subjects were also higher than those of simple CWP subjects (P=0.003). Among the subjects without PMF, IL-8 levels in the subjects with International Labour Organization (ILO) category II or III were higher than those in the subjects with ILO category 0 (P=0.006) and with category I (P=0.026). These results suggest that high serum levels of IL-8 and ICAM-1, which are important as neutrophil attractants and adhesion molecules, are associated with PMF.

COPD and levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes among coal workers: a case-control study.

This case-control study aimed to investigate whether the levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes were associated with the risk of chronic obstructive pulmonary disease (COPD) among coal workers. A total of 76 COPD cases and 48 age-matched healthy controls from a group of coal workers were included. The case group consisted of 35 COPD patients whose condition was complicated with coal workers' pneumoconiosis (CWP) and 41 COPD patients without CWP. Heat shock proteins (Hsps) in plasma and lymphocytes were detected by ELISA and flow cytometry, respectively. Multiple logistic regression models were applied to estimate the association between Hsp levels and COPD risk. Our results showed that plasma Hsp70 and lymphocyte Hsp27 levels were significantly higher and plasma Hsp27 levels were significantly lower in COPD cases than in controls (p < 0.01). No significant differences in lymphocyte Hsp70 levels were found between COPD cases and the matched subjects. Higher plasma Hsp70 levels (odds ratio (OR) = 13.8, 95 % confidence interval (CI) = 5.7-33.5) and lower plasma Hsp27 levels (OR = 4.6, 95 % CI = 2.0-10.5) were significantly associated with an increased risk of COPD after adjusting for confounders. Higher lymphocyte Hsp27 levels were only associated with an increased risk of COPD with CWP (OR = 6.6, 95 % CI = 2.0-22.1) but not with an increased risk of COPD without CWP (OR = 3.0, 95 % CI = 0.9-8.9). Additionally, there were strong joint effects of different Hsps on COPD risk. These results showed that higher levels of plasma Hsp70 and lower levels of plasma Hsp27 might be associated with an increased risk of COPD among coal workers. They may have the potential to serve as monitoring markers for COPD in coal workers.

[Regulatory effect of miR-149 on interleukin-6 expression in silica-induced pulmonary fibrosis].

OBJECTIVE: To investigate the regulatory effect of miR-149 on interleukin-6 (IL-6) expression in silica-induced pulmonary fibrosis. METHODS: A mouse model of pulmonary fibrosis was established using silica dust; the level of miR-149 in the lung tissues of mice with silica-induced pulmonary fibrosis was measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein expression of IL-6 was measured by immunohistochemistry and Western blot. Type II alveolar epithelial cells (A549) and bronchial epithelial cells (HBE) were exposed to silica dust to establish a model; the level of miR-149 was measured by qRT-PCR, while the protein expression of IL-6 was measured by Western blot. A549 cells were transfected with miR-149 mimics and inhibitor in vitro, and the cellular expression of IL-6 was measured by Western blot. Serum samples from patients with coal workers' pneumoconiosis were examined by double-antibody sandwich ELISA to measure the protein expression of IL-6. RESULTS: At three time points after silica treatment, the miR-149 expression in lung tissues was significantly down-regulated while an evident increase in IL-6 expression was observed in lung tissues (P < 0.01). Silica-stimulated epithelial cell (A549 and HBE) had up-regulated IL-6 expression and down-regulated miR-149 expression (P < 0.01). Increased levels of miR-149 attenuated IL-6 expression, whereas adverse results were found when miR-149 was inhibited. Compared with that in control group, serum level of IL-6 was significantly increased in patients with stage II and III coal workers' pneumoconiosis (P < 0.01). CONCLUSION: Down-regulation of miR-149 and up-regulation of IL-6 might be involved in the progression of silica-induced pulmonary fibrosis; miR-149 could negatively regulate IL-6 expression.

Serum levels of TGF-ß1 and MCP-1 as biomarkers for progressive coal workers' pneumoconiosis in retired coal workers: a three-year follow-up study.

Various cytokines activated by the inhalation of coal dust may mediate inflammation and lead to tissue damage. Objective of this study was to examine the relationships between coal workers' pneumoconiosis (CWP) progression over a 3 yr period and the serum levels of cytokines in 85 retired coal workers. To investigate the relevance of serum cytokines in CWP, serum levels of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta1 (TGF-ß1), and monocyte chemotactic protein-1 (MCP-1) as progressive CWP biomarkers were studied in relation to the progression of pneumoconiosis over a 3 yr period in 85 patients with CWP. CWP progression was evaluated through paired comparisons of chest radiographs. Median levels of TGF-ß1 and MCP-1 were significantly higher in subjects with progressive CWP than in those without CWP progression. The area under the ROC curve for TGF-ß1 (0.693) and MCP-1 (0.653) indicated that these cytokines could serve as biomarkers for the progression of CWP. Serum TGF-ß1 levels were related to the progression of CWP (ß=0.247, p=0.016). The results suggest that high serum levels of TGF-ß1 and MCP-1 are associated with the progression of CWP.

Genome-wide analysis of aberrantly expressed circulating miRNAs in patients with coal workers' pneumoconiosis.

Emerging evidence indicates that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, have important roles in multiple biological processes. To determine the potential contribution of miRNAs to coal workers' pneumoconiosis (CWP), we comprehensively surveyed and identified differentially expressed miRNA profiles in patients with CWP by small RNA sequencing and analysis. Mixed serum samples from the different stages of CWP and the control samples were subjected to deep sequencing by applying next-generation sequencing technology. Samples at different disease stages exhibited inconsistent miRNA expression profiles and differentially expressed miRNA profiles. Generally, these miRNAs were dynamically expressed across the different disease stages and showed various relative expression levels. Some miRNAs (such as miR-18a*, 149, 222 and 671-3p) were consistently up-regulated or down-regulated in the different stages of CWP samples. Most of the aberrantly expressed miRNAs showed a down-regulation trend. Differentially expressed miRNAs were also subjected to pairwise comparison between the different stages. Some miRNAs showed significant inconsistent expression trends across the three stages, although they were not significantly dysregulated based on the control sample. Furthermore, a series of special miRNAs organized into miRNA gene clusters and gene families were also surveyed for aberrant expression (such as mir-200 gene family and mir-222 gene cluster). According to experimentally validated target mRNAs of the aberrantly and abundantly expressed miRNAs, functional enrichment analysis suggests that these miRNAs play important roles in various biological processes, including lung tumorigenesis. In summary, we demonstrated that aberrantly expressed circulating miRNAs showed dynamic expression patterns across diseased samples, which suggests that these miRNAs may have critical roles in the occurrence and development of CWP. In addition, some significantly dysregulated miRNAs may be potential non-invasive diagnosis biomarkers based on further study.

[Value of oxygenic injury sensitive index in the screening of the early coal workers' pneumoconiosis].

OBJECTIVE: To study the significance of oxidative injury in the screening of coal workers' pneumoconiosis (CWP). METHODS: With the method of nitrate reductase, TBA, et al, the content of NO, MDA and other indexes of peroxidation in plasma lipid were detected in 112 patients suffering from coal workers' pneumoconiosis and 114 healthy coal workers as controls. RESULTS: There were statistical significant between two groups (P < 0.05) with the content or density of MDA, CuZn-SOD, GSH-Px, T-AOC, UA, NO and iNOS except CP. As screening index of pneumoconiosis, there were statistical significant in area under the curve (AUC) of MDA, T-AOC, NO and iNOS between the two groups by ROC. As screening index of pneumoconiosis, MDA, T-AOC, NO and iNOS can be selected as early screening index. Especially, T-AOC was the best index of four indexes (sensitivity is 70.5%, specificity is 68.1%). CONCLUSION: Joint screening of MDA, T-AOC and iNOS is better than single index or series of T-AOC and MDA to the screening of CWP.

Alterations of serum biomarkers associated with lung ventilation function impairment in coal workers: a cross-sectional study.

BACKGROUND: Previous studies have demonstrated that alterations in certain circulating biomarkers may be correlated with Coal workers' pneumoconiosis (CWP). This study investigated the relationship between changes of serum biomarkers and pulmonary function during the development of CWP. METHODS: Lung function parameters and specific serum indices were measured in 69 non-smoking coal workers, including 34 miners with CWP, 24 asymptomatic miners and 11 miners with minimal symptoms. The associations between changes in pulmonary function and serum indices were tested with Pearson's correlation coefficients. Multivariable analysis was used to estimate the predictive power of potential determinant variables for lung function. RESULTS: Compared to healthy miners, lung function (FVC, FEV1, FEF50, FEF75, FEF25-75 % of predicted values) was decreased in miners with CWP (p < 0.05). Increased serum matrix metalloproteinase-9 (MMP-9) was associated with decreased FVC% of predicted values in the asymptomatic miners (r = -0.503, p = 0.014). CONCLUSIONS: In coal mine workers, alterations of lung function parameters are associated with the development of CWP and with changes in circulating MMP-9, TIMP-9, IL-13 and IL-18R. These serum biomarkers may likely reflect the pathogenesis and progression of CWP in coal workers, and may provide for the importance of serum indicators in the early diagnosis of lung function injury in coal miners.

Possible effect of gene polymorphisms on the release of TNFα and IL1 cytokines in coal workers' pneumoconiosis.

It has been shown that coal dust exposure stimulates inflammatory response leading to increased release of cytokines from monocytes such as TNF-alpha and IL1. These released cytokines play the key role in the pathogenesis of pneumoconiosis including coal workers' pneumoconiosis. In this study, we investigated TNFA, IL1A, IL1B and IL1RA genes variations on basal, lipopolysaccharide and coal dust-induced cytokine release from blood monocytes of homozygous allele and minor variant allele carriers in Turkish coal workers and CWP patients. According to the genotyping results, TNFA -238 gene polymorphism was found as a risk factor in CWP development (OR=3.79) and to in vitro results; release of both TNF-alpha and IL1 cytokines from the monocytes in CWP patients was significantly increased compared to the healthy workers. Also, LPS and coal dust stimulated release of TNF-alpha, which was significantly higher in allele 2 carriers compared to subjects carrying allele 1 in both the groups. These data suggest that the coal dust-induced release of TNF-alpha from monocytes may be a useful biomarker of CWP.

Pulmonary lesions and serum levels of soluble Fas (sCD95) in former hard coal miners.

OBJECTIVE: Fas/APO-1 (CD95) and Fas Ligand (FasL) is a major mediator system that activates programmed cell death (apoptosis) and is most important for pulmonary cellular homeostasis. Another form of Fas, circulating soluble Fas (sCD95), produced by alternative mRNA splicing antagonizes the cell-surface Fas function. It was the aim of the study to test the hypothesis that the Fas/FasL system is implicated in the development of silica-induced pulmonary nodular lesions. MATERIAL AND METHODS: We investigated the serum levels of sCD95 in 55 former hard coal miners. Coal workers' pneumoconiosis (CWP) was assumed when the profusion of small round opacities according to the ILO 2000 classification system was 1/1 or greater. Analyses of sCD95 were performed by a sandwich ELISA. RESULTS: Radiologic CWP was found in 34 of the 55 individuals. The age of subjects with and without CWP was similar (73.5 (SD 7.2) years vs. 73.5 (7.1) years; P = 0.924). sCD95 could be quantified in all samples; significantly higher levels were observed in subjects with radiologic signs of CWP (914 (752-1251) pg/ml vs. 632 (509-804) pg/ml, P < 0.001). However, there was no relationship between sCD95 serum concentrations and the quantity of profusion according to ILO. CONCLUSIONS: The hypothesis of elevated sCD95 concentrations in CWP was corroborated. The usefulness of sCD95 for prevention and diagnosis of CWP and other forms of silica-induced fibrosis needs to be established by epidemiological studies.

[Changes of serum matrix metalloproteinases-9 and tissue inhibitors of metalloproteinases-9 in coal workers' pneumoconiosis].

OBJECTIVE: To explore the changes and significance of matrix metalloproteinases (MMP)-9 and tissue inhibitors of metalloproteinases (TIMP)-9 in serum of patients with coal workers' pneumoconiosis (CWP). METHODS: Serum MMP-9 and TIMP-9 were determined by sandwich ELISA in 188 cases of coal workers' pneumoconiosis (including 53 cases of coal pneumoconiosis, 67 cases of coal-silica pneumoconiosis and 68 cases of silicosis), 57 cases of 0+ miner (group 0+), 64 cases of healthy miner (dust exposed control) and 50 healthy people (healthy control) , and were further evaluated according to stage, complication, and the duration of exposure to dust in CWP group. RESULTS: The median of serum MMP-9 in coal pneumoconiosis, coal-silica pneumoconiosis and silicosis were 17.16, 15.14 and 17.50 ng/ml respectively. The levels of serum MMP-9 in silicosis and coal-silica pneumoconiosis were lower than that in dust exposed control and 0+ group (P < 0.05), and there were no differences among 3 groups of CWP. The levels of serum TIMP-9 in coal pneumoconiosis, coal-silica pneumoconiosis and silicosis were (330.00 +/- 108.42), (312.04 +/- 120.09) and (366.81 +/- 135.50) ng/ml respectively, and compared with dust exposed control and 0+ group, it increased in silicosis and coal pneumoconiosis significantly (P < 0.05). The levels of serum TIMP-9 in silicosis were higher significantly than that of coal-silica pneumoconiosis (P < 0.05). No significant difference was observed in the levels of serum MMP-9 and TIMP-9 in CWP according to CWP stage, complications and the duration of exposure to dust (P > 0.05). There was a positive correlation between age and the concentration of TIMP-9 in silicosis (r = 0.249, P < 0.05). A positive correlation was shown between the levels of serum MMP-9 and TIMP-9 only in dust exposed control (r = 0.294, P < 0.05). CONCLUSIONS: The levels of serum MMP-9 and TIMP-9 are associated with the harmful effect to miner resulted from dust. The apparent disturbance of MMP-9 and TIMP-9 might take part in the pathogenesis of CWP. Dynamic observation of its concentration in group 0+ and health miners might contribute to the prevention, early diagnosis and differential diagnosis of CWP.