• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.944-955
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• 2000

Background : In patients with chronic obstructive pulmonary disease(COPD), several factors have been associated with a poor prognosis. These include old age, low $FEV_1$ low diffusing capacity, high alveolar-arterial oxygen pressure difference, and finally cor pulmonale. This study was done to investigate if the ECG signs suggesting cor pulmonale were independent prognostic factors in patients with COPD. Method : We analyzed ECG, pulmonary function data and arterial blood gas values in 61 patients who were admitted through the emergency department with an acute exacerbation of COPD. The ECG signs reflecting cor pulmonale were right strial overloading(RAO), right bundle branch block, right ventricular hypertrophy and low-voltage QRS. The 61 patients were divided into 2 groups ; group I with no ECG signs(n=36) and group II with one or more ECG signs(n=25) suggesting cor, pulmonale. Results : Poor, prognostic factors by univariate analysis were low $FEV_1$, $FEV_1$ % pred., VC % pred., DLco, DLco % pred., $PaO_2$ and $SaO_2$ high $PaCO_2$ presence of ECG signs reflecting cor pulmonale, presence of mental status change, use of mechanical ventilator, and long term use of glucocorticoid. A multivariate analysis indicated that age(risk ratio=1.13, 95% confidence interval 1.05-1.23), DLco % pred. (risk ratio=0,97. 95% confidence interval 0.94-0.99), $PaO_2$ (risk ratio=0.95, 95% confidence interval 0.90-0.99) and RAO(risk ratio=5.27, 95% confidence interval 1.40-19.85) were independent prognostic factors of survival. There was a significant difference in survival between the patients with and without RAO(p=0.038). The survival rates at 1, 2, and 5 years were 94.5%. 81.4%, and 50.0% in patients without RAO and 82.4%, 70.6%, and 27.5% in patients with RAO, respectively. Conclusion : These results suggest that the presence of ECG signs reflecting cor pulmonale is a predictor of survival and that RAO of these ECG signs is a significant independent predictor of survival in patients with COPD.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.88-97
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• 2003

Background : Although smoking is a major cause of chronic obstructive pulmonary disease (COPD), only 10-20% of cigarette smokers develop symptomatic COPD, which suggests the presence of genetic susceptibility. This genetic susceptibility to COPD might depend on variations in the activities of the enzyme that detoxify hazardous chemical products, such as microsomal epoxide hydrolase (mEPHX) and glutathione-S transferase M1 subunit (GSTM1) genes. Methods : The genotypes of 58 patients with COPD, and 79 age matched control subjects, were determined by a polymerase chain reaction, followed by restriction fragment length polymorphism (PCR-RFLP) for the mEPHX, and multiplex PCR for the GSTM1. Results : GSTM1 was deleted in 53.3% of the subjects. There was no difference in GSTM1 deletion rates between the COPD patients (32/58, 55.2%) and the control subjects (41/79, 51.9%). The combination patterns of two polymorphisms of mEPHX showed slow enzyme activity in 29(21.2%), normal in 73(53.3%) and fast in 32(23.4%). The COPD group (7/57, 12.3%) showed a significantly lower incidence of slow enzyme activity compared to the control subjects (22/77, 28.6%, p<0.05). However, when the COPD and control groups were compared with smokers only, there were no significant differences in the genotypes of GSTM1 and mEPHX. Conclusion : The genotypes of GSTM1 and mEPHX were not significant risk factors of COPD in this cohort of study.

• Tuberculosis and Respiratory Diseases
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• v.74 no.1
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• pp.7-14
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• 2013

Background: Fractional exhaled nitric oxide (FeNO) can be measured easily, rapidly, and noninvasively for the assessment of airway inflammation, particularly mediated by eosinophil, such as asthma. In bronchiectasis (BE), the pathogenesis has been known as chronic airway inflammation and infection with abnormal airway dilatation; however, there are little studies to evaluate the role of FeNO in BE. Methods: From March 2010 to February 2012, 47 patients with BE, diagnosed by high resolution computed tomography (HRCT), performed FeNO, compared with asthma and chronic obstructive pulmonary disease (COPD). All patients carried out a complete blood count including eosinophil count, chemistry, sputum examination, and spirometry, if indicated. A retrospective analysis was performed to elucidate the clinical role of FeNO in BE patients. Results: The mean FeNO levels in patients with BE was $18.8{\pm}1.5$ part per billion (ppb), compared to $48.0{\pm}6.4$ and $31.0{\pm}4.3$ in those with asthma and COPD, respectively (p<0.001). The FeNO levels tended to increase along with the disease severity scores by HRCT; however, it was statistically not significant. FeNO in BE with a co-infection of nontuberculous mycobacteria was the lowest at $17.0{\pm}3.5$ ppb among the study population. Conclusion: FeNO in BE was lower than other chronic inflammatory airway diseases, particularly compared with asthma. For clinical application of FeNO in BE, more large-scaled, prospective studies should be considered.

• Biomolecules & Therapeutics
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• v.28 no.3
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• pp.250-258
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• 2020

Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A₃ receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A₃ receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

• Biomedical Science Letters
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• v.15 no.4
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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).

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.25-30
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• 2005

Background : An insertion-deletion polymorphism of angiotensin converting enzyme (ACE) gene has been shown to be associated with enzyme activity levels of ACE. Reported results that have been mutually contradictory about asthmatic hypersensitiveness and occurrence according to ACE gene insertion (I)/deletion (D) polymorphism. Also, the involvement of the ACE genes as the genetic basis of bronchial asthma is currently controversy. We investigated whether there was any association between polymorphisms of the ACE genes and airway hyper-responsiveness in chronic obstructive pulmonary disease (COPD). Methods : A total of 100 patients with COPD were enrolled in this study. The ACE genotypes were determined in all subjects by polymerase chain reaction. Pulmonary function test including bronchodilator response (BDR), methacholine bronchial provocation test (MBPT) were done in those patients. Airway hyper-responsiveness include any findings of positive BDR or MBPT. Results : In COPD patients, the ACE genotype distribution did not differ significantly among groups of patients with severities of COPD, and with or without airway hyper-responsiveness. Conclusions : These results suggest that polymorphisms of the ACE gene may not be associated with airway hyper-responsiveness, development and severity of COPD.

• Tuberculosis and Respiratory Diseases
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• v.67 no.6
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• pp.536-544
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• 2009

Background: A combination of salmeterol and fluticasone propionate (SFC) and tiotropium bromide (TIO) is commonly prescribed for COPD patients but there is little data on their effectiveness, particularly in COPD patients with bronchial hyperresponsiveness. This study compared the spirometric improvement based on the change in $FEV_1$, $FEV_1$/FVC, and IC as well as the clinical outcomes of the therapeutic strategies with SFC and TIO versus the individual components in patients with severe COPD and bronchial hyperresponsiveness. Methods: This study examined the spirometric data and clinical outcomes of 214 patients with COPD and hyperresponsiveness, who were divided into three groups according to the therapeutic regimen (TIO only, SFC only, and a triple therapy regimen). Results: All regimen groups showed early improvement in the $FEV_1$ and IC (at 3- and 6 months after treatment). However, long-term beneficial effects were observed only in the SFC group (at 24 months after treatment). However, these beneficial effects decreased after a 36-month follow up. In all spirometric results, the 12-, 24-, and 36-months data showed a similar degree of improvement in the three groups. The triple therapy group showed higher St. George's Respiratory Questionnaire scores and lower acute exacerbations and hospitalization. Conclusion: SFC can be a more important component in the pharmacological treatment of severe COPD patients with hyperresponsiveness than TIO, particularly in the spirometric and clinical outcomes.

• Korean Journal of Medicinal Crop Science
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• v.19 no.5
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• pp.380-387
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• 2011

This study was carried out to investigate the inhibitory effect of Angelicae Dahuricae Radix (ADR) extract on chronic obstructive pulmonary disease (COPD) induced by cigarette smoke condensate (CSC) and lipopolysaccharide (LPS) in mice. COPD was induced by intratracheal instillation of LPS and CSC 5 times for 12 days; this increased airway hyperresoponsiveness (AHR) and inflammatory cells in bronchoalveolar lavage fluid (BALF). ADR extract was administered orally at a dose of 50 and 200 mg/kg. The concentration of imperatorin, a major component of ADR and therefore used as a measure of quality control, was $0.098%{\pm}0.018%$. Treatment of the mice with ADR extract (50 and 200 mg/kg) alleviated AHR and reduced inflammatory cell counts. Treatment with cyclosporin A (CSA; 10 mg/kg) also modulated AHR and reduced inflammatory cells effectively. Compared with CSA treatment, treatment with ADR (50 mg/kg) extract reduced neutrophil and $CD4^+/CD3^+$ cell counts by 22.67% and 44.92%, respectively. In addition, compared with CSA treatment, treatment ADR 200 mg/kg reduced neutrophils, $CD4^+/CD3^+$ cells and $CD8^+/CD3^+$ cells, by 32.10%, 83.17% and 82.11%, respectively. These results indicate that ADR extract may have an inhibitory effect on COPD induced by LPS and CSC in mice.

• Journal of Internet Computing and Services
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• v.22 no.1
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• pp.89-98
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• 2021

Community-acquired pneumonia (CAP) is a major risk factor of mortality in chronic obstructive pulmonary disease (COPD). Streptococcus pneumoniae (colloquially known as pneumococcus) is one of important pathogens of CAP in patients with COPD. Preventive interventions for pneumonia include pneumococcal and influenza vaccinations. A prospective, cohort study has been performed to investigate the protective effects of pneumococcal and influenza vaccinations on the severity of community-acquired pneumonia requring hospital admission in patients with COPD. Seven university-affiliated hospitals in Korea have participated in the study. The aim of this study was to construct an online registration system for the multi-institutional researchers that facilitates efficient collection and management of COPD patient data. This study has presented three basic strategies-accurate data input, convenient data completion, and real-time data management-to supplement the demerits of existing offline clinical study. The proposed online registration system has already been applied to a multi-institutional clinical study and was acknowledged for its high performance.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.114-114
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• 2002

Inhibitors of type IV phosphodiesterase (PDE IV) are currently being developed as new therapeutic agents for asthma, chronic obstructive pulmonary disease(COPD) and arthritis. Unfortunately, the anti-inflammatory effect of PDE IV inhibitors has been considered to be associated to some extent with vomiting as adverse effect. The first generation PDE IV inhibitor, rolipram, was known to induce emesis at clinical trials. (omitted)