Byung-Soon Choi

Serum Levels of Interleukin-8 and Tumor Necrosis Factor-alpha in Coal Workers' Pneumoconiosis: One-year Follow-up Study

Objectives Various cytokines induced by inhalation of coal dust may mediate inflammation and lead to tissue damage or fibrosis, such as coal workers pneumoconiosis (CWP). Methods To investigate the relevance of serum cytokines in CWP, the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as CWP biomarkers in 110 retired coal miners (22 controls and 88 CWP subjects) were related to cross sectional findings and 1-year progressive changes of the pneumoconiosis. Progressive changes of CWP were evaluated by paired comparison of chest radiographs. Analysis by a receiver operating characteristic curve assessed the biomarker potential of each cytokine. Results The mean serum IL-8 level was significantly higher in CWP compared to controls and IL-8 levels correlated with the degree of CWP. The median serum TNF-α level was significantly higher in subjects with progressive CWP compared to subjects without CWP progression. The area under the ROC curve for IL-8 (0.70) and TNF-α (0.72) for CWP identification and progression, respectively, indicated the biomarker potential of the two cytokines. Serum cutoff values of IL-8 and TNF-α were 11.63 pg/mL (sensitivity, 69%; specificity, 64%) and 4.52 pg/mL (sensitivity, 67%; specificity, 79%), respectively. Conclusion The results suggest that high levels of serum IL-8 are associated with the presence of CWP and those of serum TNF-α are associated with the progression of CWP.

Current Status of Pneumoconiosis Patients in Korea

This study identifies the number of pneumoconiosis patients after eliminating deceased patients between 2003 and 2008 as of January 1st and estimates it for the next five years. From 2003 to 2008, the pneumoconiosis patients were 16,929, 17,224, 17,366, 17,566, 17,542, and 17,546, respectively. The number of pneumoconiosis patients will have increased by 1,014 from 2008 to 18,560 in 2013 after applying the average change rates taken from 2003 to 2007. It takes 15-20 yr to develop coal workers pneumoconiosis (the main cause in Korea) and patients will continue to be diagnosed with pneumoconiosis for some years to come since it has only been 20 yr since the decline of the coal mining industry in Korea. In addition, pneumoconiosis patients are increasing in industries in which the risk of pneumoconiosis was relatively low shows the necessity to improve dust-exposed workplace environments.

Development of Standard Digital Images for Pneumoconiosis

We developed the standard digital images (SDIs) to be used in the classification and recognition of pneumoconiosis. From July 3, 2006 through August 31, 2007, 531 retired male workers exposed to inorganic dust were examined by digital (DR) and analog radiography (AR) on the same day, after being approved by our institutional review board and obtaining informed consent from all participants. All images were twice classified according to the International Labour Office (ILO) 2000 guidelines with reference to ILO standard analog radiographs (SARs) by four chest radiologists. After consensus reading on 349 digital images matched with the first selected analog images, 120 digital images were selected as the SDIs that considered the distribution of pneumoconiosis findings. Images with profusion category 0/1, 1, 2, and 3 were 12, 50, 40, and 15, respectively, and a large opacity were in 43 images (A = 20, B = 22, C = 1). Among pleural abnormality, costophrenic angle obliteration, pleural plaque and thickening were in 11 (9.2%), 31 (25.8%), and 9 (7.5%) images, respectively. Twenty-one of 29 symbols were present except cp, ef, ho, id, me, pa, ra, and rp. A set of 120 SDIs had more various pneumoconiosis findings than ILO SARs that were developed from adequate methods. It can be used as digital reference images for the recognition and classification 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.

Levels of Exhaled Breath Condensate pH and Fractional Exhaled Nitric Oxide in Retired Coal Miners

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 (FENO) , 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 FENO in the low percentage FEV1 (< 80%) was lower than that in the high percentage (80% ≤) (p = 0.023) . The mean concentration of FENO 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 FENO 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 FENO 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.

Blood Levels of IL-lβ, IL-6, IL-8, TNF-α, and MCP-1 in Pneumoconiosis Patients Exposed to Inorganic Dusts

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)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and monocyte chemoattractant 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-α (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-1β (rho = 0.218, p < 0.05), IL-8 (rho = 0.224, p < 0.05), TNF-α (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.