• Biomolecules & Therapeutics
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• v.32 no.6
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• pp.685-696
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• 2024

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion. For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD. At present, mechanisms involved in the genesis and development of COPD are poorly understood. Currently, there are no effective treatments for COPD. To develop better treatment strategies, it is necessary to study mechanisms of COPD using proper experimental models that can recapitulate distinctive features of human COPD. Therefore, this review will discuss representative established mouse models to investigate inflammatory processes and basic mechanisms of COPD. In addition, human COPD-mimicking human lung organoid models are introduced to help researchers overcome limits of mouse COPD models.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.215-220
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• 2006

Background : A spirometric reference equation was recently developed for the general population in Korea. The applicability of the new Korean equation to clinical practice was examined by comparing it with the Morris equation, which is one of the most popular reference equations used for interpreting the spirometric patterns and for grading the disease severity in Korea. Methods : Spirometry was performed on 926 men and 694 women, aged 20 years or older, in November 2004 at the Asan Medical Center, Seoul, Korea. The subjects' age, gender, height, weight, and spirometric values ($FEV_1$ [forced expiratory volume in one second], FVC [forced vital capacity], and $FEV_1/FVC$) were obtained. The spirometric patterns and disease severity were evaluated using both equations, and the results of the Korean equation were compared with the Morris equation. The spirometric patterns were defined as normal, restrictive, obstructive, and undetermined according to the level of $FEV_1/FVC$ and FVC. The disease severity was defined according to the level of $FEV_1$ level for subjects with an airflow limitation, and according to the FVC level for those subjects without an airflow limitation. Results : Spirometric patterns were differently interpreted in 22.5% (208/926) of the men and 24.8% (172/694) of the women after the application of the Korean equation compared with the Morris equation. Of the subjects with airflow limitation, disease severity was differently graded in 30.2% (114/378) of the men and 39.4% (37/94) of the women after the application of the Korean equation. Of the subjects without airflow limitation, disease severity was differently graded in 27.9% (153/548) of the men and 30.2% (181/600) of the women after the application of the Korean equation. Conclusion : Achange in the reference equation for spirometry could have an effect on the interpretation of spirometric patterns and on the grading of disease severity.

• Korean Journal of Radiology
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• v.21 no.9
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• pp.1104-1113
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• 2020

Objective: To assess the regional ventilation in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) using xenon-ventilation dual-energy CT (DECT), and to compare it to that in patients with COPD. Materials and Methods: Twenty-one patients with ACOS and 46 patients with COPD underwent xenon-ventilation DECT. The ventilation abnormalities were visually determined to be 1) peripheral wedge/diffuse defect, 2) diffuse heterogeneous defect, 3) lobar/segmental/subsegmental defect, and 4) no defect on xenon-ventilation maps. Emphysema index (EI), airway wall thickness (Pi10), and mean ventilation values in the whole lung, peripheral lung, and central lung areas were quantified and compared between the two groups using the Student's t test. Results: Most patients with ACOS showed the peripheral wedge/diffuse defect (n = 14, 66.7%), whereas patients with COPD commonly showed the diffuse heterogeneous defect and lobar/segmental/subsegmental defect (n = 21, 45.7% and n = 20, 43.5%, respectively). The prevalence of ventilation defect patterns showed significant intergroup differences (p < 0.001). The quantified ventilation values in the peripheral lung areas were significantly lower in patients with ACOS than in patients with COPD (p = 0.045). The quantified Pi10 was significantly higher in patients with ACOS than in patients with COPD (p = 0.041); however, EI was not significantly different between the two groups. Conclusion: The ventilation abnormalities on the visual and quantitative assessments of xenon-ventilation DECT differed between patients with ACOS and patients with COPD. Xenon-ventilation DECT may demonstrate the different physiologic changes of pulmonary ventilation in patients with ACOS and COPD.

• 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.87 no.2
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• pp.165-175
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• 2024

Background: The prevalence of small airway dysfunction (SAD) in patients with chronic obstructive pulmonary disease (COPD) across different ethnicities is poorly understood. This study aimed to estimate the prevalence of SAD in stable COPD patients. Methods: We conducted a cross-sectional study of 196 consecutive stable COPD patients. We measured pre- and post-bronchodilator (BD) lung function and respiratory impedance. The severity of COPD and lung function abnormalities was graded in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SAD was defined as either difference in whole-breath resistance at 5 and 19 Hz > upper limit of normal or respiratory system reactance at 5 Hz < lower limit of normal. Results: The cohort consisted of 95.9% men, with an average age of 66.3 years. The mean forced expiratory volume 1 second (FEV₁) % predicted was 56.4%. The median COPD assessment test (CAT) scores were 14. The prevalence of post-BD SAD across the GOLD grades 1 to 4 was 14.3%, 51.1%, 91%, and 100%, respectively. The post-BD SAD and expiratory flow limitation at tidal breath (EFL_T) were present in 62.8% (95% confidence interval [CI], 56.1 to 69.9) and 28.1% (95% CI, 21.9 to 34.2), respectively. COPD patients with SAD had higher CAT scores (15.5 vs. 12.8, p<0.01); poor lung function (FEV₁% predicted 46.6% vs. 72.8%, p<0.01); lower diffusion capacity for CO (4.8 mmol/min/kPa vs. 5.6 mmol/min/kPa, p<0.01); hyperinflation (ratio of residual volume to total lung capacity % predicted: 159.7% vs. 129%, p<0.01), and shorter 6-minute walk distance (367.5 m vs. 390 m, p=0.02). Conclusion: SAD is present across all severities of COPD. The prevalence of SAD increases with disease severity. SAD is associated with poor lung function and higher symptom burden. Severe SAD is indicated by the presence of EFL_T.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.126-135
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• 2018

Objectives: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and irreversible airflow. This study aimed to evaluate the effects of GHX02 in a COPD-induced mouse model. Methods: The COPD mouse model was established by exposure to cigarette smoke extract and lipopolysaccharide which were administered by intratracheal injection three times with a 7 day interval. GHX02 (100, 200, 400 mg/kg) and all other drugs were orally administrated for 14 days from Day 7 to Day 21. Results: GHX02 significantly decreased the neutrophil counts in bronchoalveolar lavage fluid (BALF) and the number of $CD4^+$, $CD8^+$, $CD69^+$, and $CD11b^+/GR1^+$ cells in BALF and lung cells. GHX02 also suppressed the secretion of tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-17A, macrophage inflammatory protein 2 (MIP2), and chemokine (C-X-C motif) ligand 1 (CXCL-1) in BALF and ameliorated the lung pathological changes. Conclusions: Thus, GHX02 effectively inhibited airway inflammation by inhibiting migration of inflammatory cells and expression of pro-inflammatory cytokines. Therefore, GHX02 may be a promising therapeutic agent for 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.

• CELLMED
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• v.14 no.2
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• pp.6.1-6.6
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• 2024

The prevalence of respiratory diseases is increasing due to social and environmental factors such as increased environmental pollution and air pollution, and among them, chronic obstructive pulmonary disease (COPD) in particular has a high mortality and morbidity rate worldwide. As a result, medical expenses are rapidly increasing, creating a social and economic burden. In response to this, there is a need to discuss ways to reduce the risk from diseases and manage them appropriately, and the most basic starting point in this process is how these chronic lung disease patients are treated in actual clinical settings and how to improve the quality of treatment. There is a need to look into whether there are effective drugs. Western treatment for chronic obstructive pulmonary disease is basically a disease in which the airway narrows, so bronchodilators are used to widen the bronchi, and corticosteroids and antibiotics are mainly used to relieve the inflammatory response in the lungs. However, since the mainly used Western medicine does not serve as a fundamental therapeutic drug and contains many side effects, there is a need for drugs that improve the quality of life of patients and are more effective in managing symptoms as symptomatic prescriptions. Therefore, Western and Oriental medicine treatments are needed. The purpose is to suggest better treatments through comparative analysis.

• Tuberculosis and Respiratory Diseases
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• v.79 no.2
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• pp.91-97
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• 2016

Background: Chronic obstructive pulmonary disease (COPD) is sometimes complicated with pneumonia, but little is known about the risk factors that promote the development of pneumonia in COPD. These risk factors were evaluated in the present study. Methods: The data of 324 patients with COPD from a prospective multi-center observational cohort with obstructive lung disease were evaluated retrospectively. To identify risk factors for the development of pneumonia in COPD, the clinical and radiological data at enrollment and the time to the first episode of pneumonia were analyzed by Cox proportional hazard analysis. Results: The median follow-up time was 1,099 days and 28 patients (8.6%) developed pneumonia. The Cox analysis showed that post-bronchodilator forced expiratory volume in one second ($FEV_1$, % of predicted) and the computed tomography (CT) emphysema extent (inspiratory V950) were independent risk factors for the development of pneumonia (post-bronchodilator $FEV_1$: hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.94-1.00; p=0.048 and inspiratory V950: HR, 1.04; 95% CI, 1.01-1.07; p=0.01). Conclusion: Emphysema severity measured by CT and post-bronchodilator $FEV_1$ are important risk factors for the development of pneumonia in COPD.

• Tuberculosis and Respiratory Diseases
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• v.85 no.3
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• pp.221-226
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• 2022

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation due to chronic airway inflammation and destruction of the alveolar structure from persistent exposure to oxidative stress. The body has various antioxidant mechanisms for efficiently coping with such oxidative stress. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) is a representative system. Dysregulation of the Nrf2-ARE pathway is responsible for the development and promotion of COPD. Furthermore, COPD severity is also closely related to this pathway. There has been a clinical impetus to use Nrf2 for diagnostic and therapeutic purposes. Therefore, in this work, we systematically reviewed the clinical significance of Nrf2 in COPD patients, and discuss the value of Nrf2 as a potential COPD biomarker.