• Tuberculosis and Respiratory Diseases
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• v.76 no.4
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• pp.169-174
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• 2014

Background: The Korean Obstructive Lung Disease (KOLD) Cohort Study is a prospective longitudinal study of patients with chronic obstructive pulmonary disease (COPD), asthma, or other unclassified obstructive lung diseases. It was designed to develop new classification models and biomarkers that predict clinically relevant outcomes for patients with obstructive lung diseases. Methods: Patients over 18 years old who have chronic respiratory symptoms and airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers in South Korea. After a baseline visit, the subjects were followed up every 3 months for various assessments. Results: From June 2005 to October 2013, a total of 477 subjects (433 [91%] males; 381 [80%] diagnosed with COPD) were enrolled. Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with COPD, and predictors of therapeutic responses and exacerbations as well as the factors related to pulmonary hypertension in COPD. In addition, several genotypes were associated with radiological phenotypes and therapeutic responses among Korean COPD patients. Conclusion: The KOLD Cohort Study is one of the leading long-term prospective longitudinal studies investigating heterogeneity of the COPD and is expected to provide new insights for pathogenesis and the long-term progression of COPD.

• Tuberculosis and Respiratory Diseases
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• v.87 no.4
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• pp.473-482
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• 2024

Background: Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroid (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases. Methods: We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability of treatment weighting (IPTW) to ensure a balanced analysis of covariates. Results: Of the 57,553 patients (mean age 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including nine among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI], 1.48 to 15.58). Higher risks were significant for patients ≥65 years (adjusted HR, 6.40; 95% CI, 1.28 to 31.94), females (adjusted HR, 10.91; 95% CI, 2.24 to 53.20), never-smokers (adjusted HR, 6.31; 95% CI, 1.49 to 26.64), systemic steroid users (adjusted HR, 50.19; 95% CI, 8.07 to 312.19), and those with higher comorbidity scores (adjusted HR, 6.64; 95% CI, 1.19 to 37.03). Conclusion: ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.

• Tuberculosis and Respiratory Diseases
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• v.80 no.4
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• pp.325-335
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• 2017

Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory response and airflow limitation. Acute exacerbation involves increased inflammatory burden leading to worsening respiratory symptoms, including dyspnea and sputum production. Some COPD patients have frequent exacerbations (two or more exacerbations per year). A substantial proportion of COPD patients may remain stable without exacerbation. Bacterial and viral infections are the most common causative factors that breach airway stability and lead to exacerbation. The increasing prevalence of exacerbation is associated with deteriorating lung function, hospitalization, and risk of death. In this review, we summarize the mechanisms of airway inflammation in COPD and discuss how bacterial or viral infection, temperature, air pollution, eosinophilic inflammation, and concomitant chronic diseases increase airway inflammation and the risk of exacerbation.

• IMMUNE NETWORK
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• v.19 no.1
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• pp.5.1-5.12
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• 2019

Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.510-515
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• 2006

Background : Although 17% of Korean adults over the age of 45 years have chronic obstructive pulmonary disease (COPD), there is only limited data on the cause of death in COPD patients in Korea. Therefore, this retrospective study was performed to examine the cause of death in COPD patients at a referral hospital in Korea. Methods : The medical records of 28 deceased patients diagnosed as COPD in Asan Medical Center from January to December 2003 were reviewed patients had died in Asan Medical Center and 16 patients had died outside the hospital. The Korean National Statistical Office confirmed 88 deceased patients out of 1,078 patients diagnosed as COPD in Asan Medical Center in 2003. After excluding those with tuberculous destroyed lung, bronchiectasis, and lung cancer, 28 COPD patients were evaluated. Results : The causes of death were pulmonary disease including pneumonia in 16 patients (57%), cardiac disease in 5 patients (18%), sudden death in 3 patients (11%), and other causes in 4 patients (14%). The cause of death was pulmonary disease in 83% (10 out of 12 patients) and 38% (6 out of 16 patients) of patients who died in Asan Medical Center and outside the center, respectively (P=0.05). The cause of death was pulmonary disease in 43% of patients with $FEV_1$ more than 50 % of the predicted value and in 55% of patients with $FEV_1$ less than 50 % of the predicted value (P=0.89). Conclusion : Pulmonary disease is the leading cause of death in COPD patients in Korea.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.786-796
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• 1999

Background: It has been anticipated that the amount and composition of mucin are changed in patients with chronic airway diseases. We evaluated whether RTO3(mAb against rat tracheal mucins) could quantify the amount of mucin from the airway in the patients with chronic airway diseases. Methods and results; 1) RTO3 was bound to high molecular weight of mucin based on Western blot in sputum and BALF from patients with chronic airway diseases. 2) The goblet cells and submucosal glands in main bronchus from human were observed by PAS stain. And immunohistochemical stain with RTO3 showed immunoreactivity on some goblet cells. 3) The amount of mucin was more increased in patients with chronic airway diseases compared to those in normal subjects. 4) In the exacerbation of asthmatics, mucin amounts were more increased than stable asthmatics. Conclusion: We suggested that secreted mucin in chronic airway diseases can be quantified by ELISA with RTO3.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.107-112
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• 2000

To investigate the alteration of airway mucin in airway disease patients, immunoassay procedures were employed using monoclonal antibodies HM02 and HM03 (Hybridoma, 18,457-463, 1999). Alteration of mucin release was determined by ELISA and the integrity of mucin was determined by Western blot. In ELISA, it was found that mucin release increased from pneumonia, chronic cough, bronchiectasis, eosinophilic pneumonia, lung cancer and bronchial asthma patients. In Western blot, the increase in immunoreactivity was observed in case of pneumonia, chronic cough, bronchiectasis and bronchial asthma. In bronchial asthma, there was no obvious degradation of mucin while in other diseases, varying degree of mucin degradation was observed. The data from the present study implicate that HMO2 and HM03 are suitable for the immunological analysis of mucin in airway disease patients. The role of increased mucin release and varying degree of mucin degradation on airway diseases should be further investigated in the future.

• Tuberculosis and Respiratory Diseases
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• v.78 no.1
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• pp.8-17
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• 2015

Background: AMP-activated protein kinase (AMPK) not only functions as an intracellular energy sensor and regulator, but is also a general sensor of oxidative stress. Furthermore, there is recent evidence that it participates in limiting acute inflammatory reactions, apoptosis and cellular senescence. Thus, it may oppose the development of chronic obstructive pulmonary disease. Methods: To investigate the role of AMPK in cigarette smoke-induced lung inflammation and emphysema we first compared cigarette smoking and polyinosinic-polycytidylic acid [poly(I:C)]-induced lung inflammation and emphysema in $AMPK{\alpha}1$-deficient ($AMPK{\alpha}1$-HT) mice and wild-type mice of the same genetic background. We then investigated the role of AMPK in the induction of interleukin-8 (IL-8) by cigarette smoke extract (CSE) in A549 cells. Results: Cigarette smoking and poly(I:C)-induced lung inflammation and emphysema were elevated in $AMPK{\alpha}1$-HT compared to wild-type mice. CSE increased AMPK activation in a CSE concentration- and time-dependent manner. 5-Aminoimidazole-4-carboxamide-1-${\beta}$-4-ribofuranoside (AICAR), an AMPK activator, decreased CSE-induced IL-8 production while Compound C, an AMPK inhibitor, increased it, as did pretreatment with an $AMPK{\alpha}1$-specific small interfering RNA. Conclusion: $AMPK{\alpha}1$-deficient mice have increased susceptibility to lung inflammation and emphysema when exposed to cigarette smoke, and AMPK appears to reduce lung inflammation and emphysema by lowering IL-8 production.

• Tuberculosis and Respiratory Diseases
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• v.63 no.6
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• pp.475-479
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• 2007

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.129-136
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• 2006

Background: To interpret lung function tests, it is necessary to determine the lower limits of normal (LLN) and to derive a consensus on the interpretative algorithm. '0.7 of LLN for the $FEV_1$/FVC' was suggested by the COPD International Guideline (GOLD) for defining obstructive disease. A consensus on a new interpretative algorithm was recently achieved by ATS/ERS in 2005. We evaluated the accuracy of '0.7 of LLN for the $FEV_1$/FVC' for diagnosing obstructive diseases, and we also determined the effect of the new algorithm on diagnosing ventilatory defects. Methods: We obtained the age, gender, height, weight, $FEV_1$, FVC, and $FEV_1$/FVC from 7362 subjects who underwent spirometry in 2005 at the Asan Medical Center, Korea. For diagnosing obstructive diseases, the accuracy of '0.7 of LLN for the $FEV_1$/FVC' was evaluated in reference to the $5^{th}$ percentile of the LLN. By applying the new algorithm, we determined how many more subjects should have lung volumes testing performed. Evaluation of 1611 patients who had lung volumes testing performed as well as spirometry during the period showed how many more subjects were diagnosed with obstructive diseases according to the new algorithm. Results: 1) The sensitivity of '0.7 of LLN for the $FEV_1$/FVC' for diagnosing obstructive diseases increased according to age, but the specificity was decreased according to age; the positive predictive value decreased, but the negative predictive value increased. 2) By applying the new algorithm, 34.5% (2540/7362) more subjects should have lung volumes testing performed. 3) By applying the new algorithm, 13% (205/1611) more subjects were diagnosed with obstructive diseases; these subjects corresponded to 30% (205/681) of the subjects who had been diagnosed with restrictive diseases by the old interpretative algorithm. Conclusion: The sensitivity and specificity of '0.7 of LLN for the $FEV_1$/FVC' for diagnosing obstructive diseases changes according to age. By applying the new interpretative algorithm, it was shown that more subjects should have lung volumes testing performed, and there was a higher probability of being diagnosed with obstructive diseases.