• Toxicological Research
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• 제26권4호
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• pp.329-337
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• 2010

Inhaled inorganic dusts, such as coal, can cause inflammation and fibrosis in the lungs, known as pneumoconiosis. Diagnosis of pneumoconiosis depends on morphological changes by radiological findings and functional change by pulmonary function test (PFT). Unfortunately, current diagnostic findings are limited only to lung fibrosis, which is usually irreversibly progressive. Therefore, it is important that research on potential and prospective biomarkers for pneumoconiosis should be conducted prior to initiation of irreversible radiological or functional changes in the lungs. Analytical techniques using exhaled breath condensate (EBC) or exhaled gas are non-invasive methods for detection of various respiratory diseases. The objective of this study is to investigate the relationship between inflammatory biomarkers, such as EBC pH or fractional exhaled nitric oxide ($FE_{NO}$), and pneumoconiosis among 120 retired coal miners (41 controls and 79 pneumoconiosis patients). Levels of EBC pH and FENO did not show a statistically significant difference between the pneumoconiosis patient group and pneumoconiosis patients with small opacity classified by International Labor Organization (ILO) classification. The mean concentration of $FE_{NO}$ in the low percentage $FEV_1$ (< 80%) was lower than that in the high percentage (80% $\leq$) (p = 0.023). The mean concentration of $FE_{NO}$ in current smokers was lower than that in non smokers (never or past smokers) (p = 0.027). Although there was no statistical significance, the levels of $FE_{NO}$ in smokers tended to decrease, compared with non smokers, regardless of pneumoconiosis. In conclusion, there was no significant relationship between the level of EBC pH or $FE_{NO}$ and radiological findings or PFT. The effects between exhaled biomarkers and pneumoconiosis progression, such as decreasing PFT and exacerbation of radiological findings, should be monitored.

• Safety and Health at Work
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• 제5권2호
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• pp.91-96
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• 2014

Background: Chronic obstructive pulmonary disease (COPD) is an important cause of occupational mortality in miners exposed to coal mine dust. Although the inflammatory mediators involved in COPD have not been defined, many studies have shown that inflammatory mediators such as reactive oxygen and nitrogen species are involved in orchestrating the complex inflammatory process in COPD. Methods: To investigate the relevance of exhaled biomarkers of oxidative and nitrosative stress in participants with COPD, we determined the levels of hydrogen peroxide, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) in exhaled breath condensate (EBC) in 90 retired elderly coal miners (53 non-COPD and 37 COPD participants). Results: Mean levels of MDA (4.64 nMvs. 6.46 nM, p = 0.005) and 3-NT (3.51 nMvs. 5.50 nM, p = 0.039) in EBC were significantly higher in participants with COPD. The median level of MDA did show statistical difference among the COPD severities (p = 0.017), and the area under the receiver operating characteristic curve forMDA (0.67) for the diagnostic discrimination of COPD indicated the biomarker. The optimal cutoff values were 5.34 nM (64.9% sensitivity and 64.2% specificity) and 5.58 nM (62.2% sensitivity and 62.3% specificity) forMDA and 3-NT, respectively. The results suggest that high levels ofMDA and 3-NT in EBC are associated with COPD in retired elderly miners. Conclusion: These results showed that the elevated levels of EBC MDA and EBC 3-NT in individuals with COPD are biomarkers of oxidative or nitrosative stress.

• 한국산업보건학회지
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• 제29권3호
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• pp.404-413
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• 2019

Objectives: Chronic obstructive pulmonary disease(COPD) is an important cause of mortality in workers exposed to hazardous dust, such as crystalline silica or coal, and COPD is related to inflammation and oxidative stress in the lung. The aim of this study was to evaluate the association of oxidative stress and inflammation to COPD in retired workers exposed to mineral dust. Methods: The levels of malondialdehyde(MDA) in EBC as biomarkers for oxidative stress and C-reactive protein(CRP) and lactate dehydrogenase(LD) as biomarkers for inflammation were measured in 107 male subjects(63 pneumoconiosis and 42 COPD subjects). Results: Mean levels of EBC MDA(2.03 nmol/L vs. 4.65 nmol/L, p=0.010) and serum LD(170.3 U/L vs. 185.9 U/L, p=0.022) were significantly higher in subjects with COPD, but mean levels of serum CRP(p=0.469) did not show a statistical difference between the study groups. Level of EBC MDA was negatively correlated with ${%}FEV_1$ predicted(r=-0.279, p=0.004) and ${%}FEV_1/FVC$ ratio(r=-0.397, p<0.001). Conclusions: These results suggest that EBC is a useful biological matrix for investigation of respiratory oxidative stress. High levels of EBC MDA and serum LD are related to COPD in retired workers exposed to mineral dust.

• Toxicological Research
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• 제25권4호
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• pp.217-224
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• 2009

Inhaled inorganic dusts such as coal can cause inflammation and fibrosis in the lung called pneumoconiosis. Chronic inflammatory process in the lung is associated with various cytokines and reactive oxygen species (ROS) formation. Expression of some cytokines mediates inflammation and leads to tissue damage or fibrosis. The aim of the present study was to compare the levels of blood cytokines interleukin (IL)-$1\beta$, IL-6, IL-8, tumor necrosis factor (TNF)-$\alpha$ and monocyte chemoatlractant protein (MCP)-1 among 124 subjects (control 38 and pneumoconiosis patient 86) with category of chest x-ray according to International Labor Organization (ILO) classification. The levels of serum IL-8 (p= 0.003), TNF-$\alpha$ (p=0.026), and MCP-1 (p=0.010) of pneumoconiosis patients were higher than those of subjects with the control. The level of serum IL-8 in the severe group with the small opacity (ILO category II or III) was higher than that of the control (p=0.035). There was significant correlation between the profusion of radiological findings with small opacity and serum levels of IL-$1\beta$(rho=0.218, p<0.05), IL-8 (rho=0.224, p<0.05), TNF-$\alpha$ (rho=0.306, p<0.01), and MCP-1 (rho=0.213, p<0.01). The serum levels of IL-6 and IL-8, however, did not show significant difference between pneumoconiosis patients and the control. There was no significant correlation between serum levels of measured cytokines and other associated variables such as lung function, age, BMI, and exposure period of dusts. Future studies will be required to investigate the cytokine profile that is present in pneumoconiosis patient using lung specific specimens such as bronchoalveolar lavage fluid (BALF), exhaled breath condensate, and lung tissue.

• 대한의생명과학회지
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• 제15권4호
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• pp.309-317
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• 2009

Occupational exposure to inorganic dusts such as coal and silica has been identified as a chronic obstructive pulmonary disease (COPD) risk factor. This risk factor causes lung inflammation and protease-antiprotease imbalance. This abnormal inflammatory response of the lung induces parenchymal tissue destruction and leads to progressive airflow limitation that is characteristics of COPD. The aim of this study was to determine the relationship of proteases such as neutrophil elastase (NE) and matrix metalloproteinase (MMP)-9 and antiproteases such as alpha-1 antitrypsin (AAT) and tissue inhibitors of metalloproteinase (TIMP)-1 with lung function. The study population contained 223 retired workers exposed to inorganic dusts. We performed lung function test, including percent of forced expiratory volume in one second ($%FEV_1$) predicted and $%FEV_1$/forced vital capacity (FVC). We analyzed serum MMP-9, AAT, TIMP-1 and plasma NE concentrations by sandwich enzyme immunoassay. NE, AAT, and TIMP-1 concentrations in workers, who had $%FEV_1$<80% predicted, were higher than those of workers who had $%FEV_1{\geq}80%$ (P<0.05). Both AAT and TIMP-1 concentrations in workers with airflow limitation were higher than those of workers with normal airflow (P<0.05). $%FEV_1$ predicted showed significant negative correlation with AAT (r=-0.255, P<0.0l), TIMP-1 (r=-0.232, P<0.01), and NE (r=-0.196, P<0.01). $%FEV_1$/FVC predicted showed significant negative correlation with NE (r=-0.172, P<0.05). From the results of stepwise multiple regression analysis about $%FEV_1$ and $%FEV_1$/FVC, significant independents were NE (r=-0.135, P=0.001) and AAT (r=-0.100, P=0.013) in $%FEV_1$, and NE (r=-0.160, P=0.014) in $%FEV_1$/FVC. In the present study, there were significant correlations between airflow limitation and protease concentration and between airflow limitation and antiprotease concentration. Serum protease and antiprotease concentrations, however, may be affected by the biological and inflammatory responses. It is necessary to evaluate specimens more reflected the effects of proteases and antiproteases in the lung such as lung tissue, bronchoalveolar lavage fluid, and exhaled breath condensate (EBC).