• Tuberculosis and Respiratory Diseases
• /
• v.57 no.6
• /
• pp.567-572
• /
• 2004

Background : The effect of PEEP(ed note: Define PEEP.) on the lung volume in patients with auto-PEEP during mechanical ventilation is not even. In patients with an expiratory limitation such as COPD, a PEEP of 85% from an auto-PEEP can be used with minimal increase in the lung volume. However, the application of PEEP to patients without an expiratory flow limitation can result in progressive lung. This study was carried out to evaluate the different PEEP effects on the lung volume according to the different pulmonary diseases. Methods : Sixteen patients who presented with auto-PEEP during mechanical ventilation were enrolled in this study. These patients were divided into 3 groups: asthma, COPD and tuberculosis sequela (patients with severe cicatrical fibrosis as a result of previous tuberculosis and compensatory emphysema). A PEEP of 25, 50, 75 and 100% of the auto-PEEP was applied, and the lung volume increments were estimated using the trapped lung volume. Results : In the asthma group, the trapped lung volume was not increased at a PEEP of 25 and 50% of the auto-PEEP. This group showed a significant lung volume increment from a 75% PEEP. In the COPD group, the lung volume was increased only at 100% PEEP. In the tuberculosis sequela group, the lung volume was increased progressively from low PEEP levels. However, a significant increment of the lung volume was noted only at 100% PEEP. Conclusion : The effects of the applied PEEP on the lung volume were different depending on the underlying lung pathology. The level of the applied PEEP >50% of the auto-PEEP might increase the trapped lung volume in patients with asthma.

• Tuberculosis and Respiratory Diseases
• /
• v.58 no.3
• /
• pp.267-276
• /
• 2005

Background : The transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) plays a key role in lung fibrosis. However, the molecular mechanisms involved in $TGF-{\beta}1$-induced lung fibrosis are unclear. $TGF-{\beta}1$ is the key inducer of myofibroblast transdifferentiation via de novo synthesis of ${\alpha}-smooth$ muscle actin (${\alpha}-SMA$). Since $TGF-{\beta}1$ signals through reactive oxygen species (ROS) and ROS have been shown to induce accumulation of extracellular matrix (ECM) in various tissues, this study examined if ROS play a role in $TGF-{\beta}1$-induced fibronectin secretion and ${\alpha}-SMA$ expression in human lung fibroblasts, MRC-5 cells. Methods : Growth arrested and synchronized MRC-5 cells were stimulated with $TGF-{\beta}1$ (0.2-10 ng/ml) in the presence or absence of N-acetylcysteine (NAC) or diphenyleneiodonium (DPI) for up to 96 hours. Dichlorofluorescein (DCF)-sensitive cellular ROS were measured by FACScan and secreted fibronectin and cellular ${\alpha}-SMA$ by Western blot analysis. Results : $TGF-{\beta}1$ increased the level of fibronectin secretion and ${\alpha}-SMA$ expression in MRC-5 cells in a dosedependent manner. Both NAC (20 and 30 mM) and DPI (1 and $5{\mu}M$) significantly inhibited $TGF-{\beta}1$-induced fibronectin and ${\alpha}-SMA$ upregulation. The $TGF-{\beta}1$-induced cellular ROS level was also significantly reduced by NAC and DPI. Conclusions : The results suggest that NADPH oxidase-dependent ROS play an important role in $TGF-{\beta}1$-induced fibronectin secretion and ${\alpha}-SMA$ expression in MRC-5 cells, which leads to myofibroblast transdifferentiation and progressive lung fibrosis.

• Tuberculosis and Respiratory Diseases
• /
• v.51 no.4
• /
• pp.303-314
• /
• 2001

Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

• Journal of the Korean Society of Radiology
• /
• v.82 no.3
• /
• pp.562-574
• /
• 2021

MRI has the advantages of having excellent soft-tissue contrast and providing functional information without any harmful ionizing radiation. Although previous technical limitations restricted the use of chest MRI, recent technological advances and expansion of insurance coverage are increasing the demand for chest MRI. Recognizing the need for guidelines on appropriate use of chest MRI in Korean clinical settings, the Korean Society of Radiology has composed a development committee, working committee, and advisory committee to develop Korean chest MRI justification guidelines. Five key questions were selected and recommendations have been made with the evidence-based clinical imaging guideline adaptation methodology. Recommendations are as follows. Chest MRI can be considered in the following circumstances: for patients with incidentally found anterior mediastinal masses to exclude non-neoplastic conditions, for pneumoconiosis patients with lung masses to differentiate progressive massive fibrosis from lung cancer, and when invasion of the chest wall, vertebrae, diaphragm, or major vessels by malignant pleural mesothelioma or non-small cell lung cancer is suspected. Chest MRI without contrast enhancement or with minimal dose low-risk contrast media can be considered for pregnant women with suspected pulmonary embolism. Lastly, chest MRI is recommended for patients with pancoast tumors planned for radical surgery.

• Tuberculosis and Respiratory Diseases
• /
• v.61 no.4
• /
• pp.366-373
• /
• 2006

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.3
• /
• pp.241-250
• /
• 2002

Background : Coal-worker's pneumoconiosis(CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in the alveolar spaces. CWP is usually divided into two stage : simple pneumoconiosis(SP) where there are a limited number of fibrotic lesions remain limited, with radiological opacities smaller than 1cm and progressive massive fibrosis(PMF), which is characterized by the development of a perifocal extensive fibrotic response of the lung and severe alterations in pulmonary function. In this study, the lymphocyte compartment and cytokine were evaluated by measuring the serum levels in the control, SP and PMF groups. Materials and Methods : The coal workers selected for this study were employees(patients?) of the Tae-Baek and Dong-Hae hospital. All were men, 45-76 years old and the mean duration of their exposure to coal dust was 23.2 years in the lymphocyte compartment and 24.3 years in the cytokine checked group. According to X-ray examination results, the patients were classified into either one of the SP, PMF categories. The normal controls examined were 26-70 years old men. The serum cytokine levels were estimated by using an end point enzyme immunoassay technique. Results : T lymphocyte, helper and suppressor T cells were highly related to pneumoconiosis in this study. A statistically significant decrease in the number of suppressor T lymphocytes was observed in the simple pneumoconiosis patients and at the same time, there was an increase in the lymphocyte index. Howevere, there was no statistically difference in the serum cytokines levels among the SP, PMF and control groups. Conclusion : T lymphocyte, helper T, and suppressor T cells may be highly related to the development of CWP compared to the control group particularly in the early stage of pneumoconiosis. The changes observed in the immunological system in patients with pneumoconiosis may lie at the bottom of the pathogenesis of fibrosis. Further study is needed to evaluate the lymphocyte compartment as a marker for pneumoconiosis development in the early stage.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.3
• /
• pp.222-230
• /
• 1994

Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.5
• /
• pp.601-613
• /
• 2000

Background : Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrous disease of the lung of unknown etiology. Recently it has been classified into several distinct entities on the basis of pathologic and clinical characteristics, ie : usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), acute interstitial pneumonia (AIP), bronchiolitis obliterans with organizing pneumonia (BOOP), and nonspecific interstitial pneumonia (NSIP). IPF is now applied only for UIP, which has the worst prognosis. The previous reports of 3-5 year median survival appears to be overoptimistic because other types with better prognosis like NSIP or BOOP might have been included. Therefore, this study was performed to determine the clinical course and the prognostic factors of UIP as diagnosed by surgical lung biopsy. Methods : The subjects were 72 UIP patients (age $58.2{\pm}11.6$ years, M : F=45 : 27, median follow up period : 18.1 months (0.7-103.6) diagnosed by surgical lung biopsy at the Asan Medical Center (68 patients) and the Paik Hospital in Seoul (4 patients). Clinical scores (level of dyspnea : 1-20 points), radiologic score (honeycombing : HC score 0-5 points, ground glass : GG score 0-5 points), and physiologic scores (FVC : 1-12 points, $FEV_1$ : 0-3 points, TLC : 0-10 points, $D_{LCO)$ : 0-5 points, $AaDO_2$ : 0-10 points) were summed into a total CRP score. Results : 1) The one year survival rate was 78.3%, while the rate for three year survival was 58.1%, and the median survival period was 42.5months. 2) Short term (1 year) prognosis : The patients who died within one year of diagnosis (14 patients) had the higher initial total CRP score ($28.6{\pm}8.3$ vs. $16.6{\pm}9.7$) than those who lived longer than one year (46 patients). The difference in the total CRP score was attributed to the symptom score ($8.4{\pm}2.1$ vs. $5.7{\pm}3.9$) and the physiologic score ($15.7{\pm}7.1$ vs. $6.7{\pm}5.7$) including FVC, $D_{LCO)$ and $AaDO_2$. 3) Long-term (3year) prognosis : The total CRP score ($12.2{\pm}6.7$ vs. $28.7{\pm}7.9$ : including symptom score, FVC, $D_{LCO)$ and $AaDO_2$) at the time of diagnosis were also different for the long-term survivors and those who lived less than 3 years. 4) Cox regression analysis showed $D_{LCO)$ (${\geq}$60%) (Hazard ratio : 4.56, 95% CI : 2.30-16.04) was the independent prognostic factors of UIP (P<0.05). Conclusion : These results suggest that $D_{LCO)$ at the time of diagnosis seem to be a prognostic markers of biopsy-proven UIP.