• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.93-104
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• 2004

Objectives : The aim was to identify the inhibitory effects of Liriopis Tuber on bleomycin-induced lung fibrosis by analysing the changes of imflammatory cell cytokines and SHI(Semiquantitative Histological Index), Materials and Methods : In this study fibrosis prone C57BL/6J mice were used. Control group was treated with blomycin(0.06mg/0.1 ml) by IT(intratracheal) instillation which is a popular method of inducing lung fibrosis and sample group took Liriopis Tuber water extract(38.0mg/10g body weight) orally for 14 days after IT instillation of blomycin. We measured the total and differential count of WBC, $IFN-{\gamma}$ & IL-4 in mice BALF and SHI(Semiquantitative Histological Index) from lung tissues of mice. BALF and lung tissues of mice were taken 14 days after IT instillation of blomycin. Results : In sample group total WBC count, proportion of neutrophil, SHI and IL-4 significantly(p<0.05) decreased, proportion of macrophage significantly(p<0.05) increased and proportion of lymphocyte, $IFN-{\gamma}$ did not decrease significantly. Conclusions : This study suggests that Liriopis Tuber has an inhibitory effects of pulmonary fibrosis by attenuation of inflammation and Th2 immune response. To determine whether this herbal medicine contribute to cure and prophylaxis of pulmonary fibrosis, further studies on the role of $IFN-{\gamma}$ relating to fibrosis are required.

• Tuberculosis and Respiratory Diseases
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• v.74 no.6
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• pp.264-268
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• 2013

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal pulmonary fibrotic disease. In general, the exaggerated activation of the coagulation cascade has been observed during initiation or maintenance of the fibrotic disease. In our recent study, immunohistochemical expression of protease-activated receptor-2 (PAR-2), which plays a key role in coagulation cascade, was observed in surgical specimen of IPF patients, and associated with poor clinical outcome. The aim of this study was to evaluate the overexpression of PAR-2 in inflammatory cells from peripheral blood and bronchoalveolar lavage fluid in IPF patients. Methods: From May 2011 to March 2012, IPF patients and controls were enrolled in Seoul National University Hospital. Peripheral blood and bronchoalveolar lavage fluid were collected for analysis of PAR-2 expression. Flow cytometry and reverse transcription polymerase chain reaction were used for PAR-2 receptor and mRNA assessment. Results: Twelve IPF patients and 14 controls were included in this study. Among them, flow cytometry analysis was conducted from 26 peripheral blood (patient group, 11; control group, 13) and 7 bronchoalveolar lavage fluid (patient group, 5; control group, 2). The expression of PAR-2 receptor was not different between patient and control groups (p=0.074). Among all 24 population, PAR-2 mRNA assessment was performed in 19 persons (patient group, 10; control group, 9). The mRNA expression of PAR-2 was not significant different (p=0.633). Conclusion: In IPF patients, PAR-2 receptor and mRNA expression were not different from control group.

• The Journal of Internal Korean Medicine
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• v.44 no.6
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• pp.1294-1317
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• 2023

Background: Post-COVID-19 pulmonary fibrosis (PCPF) is a common complication in severe COVID-19 cases, often associated with acute respiratory distress syndrome or mechanical ventilation. Patients with PCPF frequently experience a decline in their quality of life due to persistent COVID-19 sequelae, including cough and chest pain. However, there is currently no established standard treatment, and the efficacy of existing medications remains uncertain. Case Report: A 65-year-old female patient presenting with cough, dyspnea, chest pain, and fatigue due to PCPF received Korean medicine treatment for 25 days. Symptom evaluation utilized the modified Medical Research Council scale, the Leicester Cough Questionnaire, and the Numeral Rating Scale. Quality of life and functional status were assessed using the Post-COVID-19 Functional Status and the EuroQol 5-Dimensional 5-Level. The extent of pulmonary fibrosis was assessed by comparing chest computed tomography (chest CT) scans before and after hospitalization. Following treatment, the patient demonstrated clinically meaningful improvement in clinical symptoms, enhanced quality of life, and decreased fibrotic lesions on CT scans. Conclusion: This case report suggests that Korean medicine treatment may be effective in improving clinical symptoms, such as cough and dyspnea caused by PCPF, while also enhancing post-COVID-19 quality of life and ameliorating pulmonary fibrotic lesions.

• Journal of Radiation Protection and Research
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• v.42 no.4
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• pp.177-188
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• 2017

Background: Radiation-induced pneumonitis and pulmonary fibrosis are common dose-limiting complications in patients receiving radiotherapy for lung, breast, and lymphoid cancers. In this study, we investigated the characteristics of effective immune cells related to pneumonitis and fibrosis after irradiation. Materials and Methods: After anesthesia, the whole thorax of C57BL/6 mice was irradiated at 14 Gy. The lung tissue and bronchoalveolar lavage fluid were collected at defined time points post-irradiation for the determination of histological and immunohistochemical analysis and inflammatory cell population infiltrated into the lung. Results and Discussion: Whole thoracic irradiation increased the deposition of extracellular matrix (ECM), lung weight, and pleural effusions, which started to die from 4 months later. At 4 months after irradiation, the numbers of macrophages and lymphocytes as well as neutrophils were increased dramatically in the lung. Interestingly, the macrophages that were recruited into the lung after irradiation had an enlarged foamy morphology. In addition, the expressions of chemokines (CCL-2, CCL-3, CXCL-10) for the attraction of macrophages and T cells were higher in the lung of irradiated mice. The high expressions of these chemokines were sustained up to 6 months following irradiation. In thoracic irradiated mice, infiltrated macrophages into the lung had the high levels of Mac-3 antigens on their surface and upregulated the hallmarks of alternatively activated macrophages such as arginase-1 and CD206. Furthermore, the levels of IL-4 and IL-13 were higher in a BAL fluid of irradiated mice. Conclusion: All results show that thoracic irradiation induces to infiltrate various inflammation-related immune cells, especially alternatively activated macrophages, through enhancing the expression of chemokines, suggesting that alternatively activated macrophages are most likely important for leading to pulmonary fibrosis.

• Toxicological Research
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• v.20 no.1
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• pp.55-61
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• 2004

Respiratory effects in full time welders include bronchitis, airway irritation, lung function changes, and lung fibrosis. Welder's pneumoconiosis has been generally determined to be benign and not associated with respiratory symptoms based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Accordingly, to investigate pulmonary function changes during 60 days induced by welding-fume exposure, male Sprague-Dawley rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes with concentrations of 64.8$\pm$0.9 mg/$m^3$ (low dose) and 107.8 $\pm$ 2.6 mg/$m^3$ (high dose) total suspended particulates for 2 hr/day, 5 days/week in an inhalation chamber for 60 days. Pulmonary function was measured every week with whole body plethysmograph compensated (WBP Comp, SFT38116, Buxco Electronics, Sharon, CT). The rats exposed to the high dose of welding fumes exhibited statistically significant (p<0.05~0.01) body weight decrease as compared to the control whereas cell number increase of the bronchoalveolar lavage fluid (BALF) (total cell, macrophage, polymorphonuclear cell and lymphocyte) during the 60 days exposure period. And only tidal volume was significantly decreased in dosedependantly during 60 days of MMA-SS welding fume exposure. This pulmonary function change with inflammatory cell recruitment confirms the lung injury caused by the MMA-SS welding fume exposure.

• Tuberculosis and Respiratory Diseases
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• v.50 no.6
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• pp.704-709
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• 2001

Background : Spontaneous pneumopericardium is a very rare condition. Spontaneous pneumothorax and pneumomediastinum have been reported to be associated with an idiopathic pulmonary fibrosis (IPF). However, spontaneous pneumopericardium has not yet been reported in association with IPF. Here we report a case of spontaneous pneumomediastinum and pneumopericardium in a patient with acute exacerbation of IPF with a review of the relevant literature.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2021.05a
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• pp.144-146
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• 2021

Idiopathic pulmonary fibrosis (IPF) is one of the most dreadful lung diseases which effects the performance of the lung unpredictably. There is no any authentic natural history discovered yet pertaining to this disease and it has been very difficult for the physicians to diagnosis this disease. With the advent of Artificial intelligent and its related technologies this task has become a little bit easier. The aim of this paper is to develop and to explore the machine learning models for the prediction and diagnosis of this mysterious disease. For our study, we got IPF dataset from Haeundae Paik hospital consisting of 2425 patients. This dataset consists of 502 features. We applied different data preprocessing techniques for data cleaning while making the data fit for the machine learning implementation. After the preprocessing of the data, 18 features were selected for the experiment. In our experiment, we used different machine learning classifiers i.e., Multilayer perceptron (MLP), Support vector machine (SVM), and Random forest (RF). we compared the performance of each classifier. The experimental results showed that MLP outperformed all other compared models with 91.24% accuracy.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.102-117
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• 2019

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia, which presents with a progressive worsening dyspnea, and thus a poor outcome. The members of the Korean Academy of Tuberculosis and Respiratory Diseases as well as the participating members of the Korea Interstitial Lung Disease Study Group drafted this clinical practice guideline for IPF management. This guideline includes a wide range of topics, including the epidemiology, pathogenesis, risk factors, clinical features, diagnosis, treatment, prognosis, and acute exacerbation of IPF in Korea. Additionally, we suggested the PICO for the use of pirfenidone and nintendanib and for lung transplantation for the treatment of patients with IPF through a systemic literature review using experts' help in conducting a meta-analysis. We recommend this guideline to physicians, other health care professionals, and government personnel in Korea, to facilitate the treatment of patients with IPF.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.478-487
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• 2003

Background : There have been several studies showing that the angiotensin II and angiotensin converting enzyme(ACE) contributes to the apoptosis of alveolar epithelial cells in idiopathic interstitial pneumonia and the activation of fibroblasts during the process of pulmonary fibrosis. These results suggest that the pulmonary fibrosis can be inhibited by the angiotensin II receptor antagonist(AGIIRA). This study was performed to identify the therapeutic effect of AGIIRA in idiopathic pulmonary fibrosis(IPF). Method : Thirteen patients with IPF, who were diagnosed with an open lung biopsy(6 patients) and furfilling the ATS criteria(7 patients) between March 1999 and October 2001 at the Gachon medical center, were enrolled in this study. Of these patients, eight patients were treated with a regimen including AGIIRA(AT group), and five were treated without AGIIRA(NT group). The pulmonary function tests and dyspnea(ATS scale) were measured at diagnosis and 1 year after treatment. All the data was collected to analyze the therapeutic effect of AGIIRA on the patients with IPF. Results : The AT group contained 8 patients(M:F=4:4) and the NT group contained 5 patients(M:F=3:2). There was no significant difference in the serum angiotensin II level between the two groups($202.5{\pm}58.5$ vs $163.7{\pm}47.3pg/ml$, p>0.05). The AT group showed an upward trend in TLC(+3%), FVC(+4%), FEV1(+3%) and DLco(+2%) compared to the NT group(TLC(-14%), FVC(-3%), FEV1(-4%) except for DLco(+5%)). The dyspnea score in the AT group improved significantly but not in the NT group. Conclusion : These results suggest that the angiotensin II receptor antagonist may have an effect on stabilizing IPF.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.257-266
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• 2016

Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.