• BMB Reports
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• v.54 no.10
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• pp.522-527
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• 2021

Lysine-specific demethylase 1 (LSD1) is an epigenetic regulator that modulates the chromatin status, contributing to gene activation or repression. The post-translational modification of LSD1 is critical for the regulation of many of its biological processes. Phosphorylation of serine 112 of LSD1 by protein kinase C alpha (PKCα) is crucial for regulating inflammation, but its physiological significance is not fully understood. This study aimed to investigate the role of Lsd1-S112A, a phosphorylation defective mutant, in the cigarette smoke extract/LPS-induced chronic obstructive pulmonary disease (COPD) model using Lsd1^SA/SA mice and to explore the potential mechanism underpinning the development of COPD. We found that Lsd1^SA/SA mice exhibited increased susceptibility to CSE/LPS-induced COPD, including high inflammatory cell influx into the bronchoalveolar lavage fluid and airspace enlargement. Additionally, the high gene expression associated with the inflammatory response and oxidative stress was observed in cells and mice containing Lsd1-S112A. Similar results were obtained from the mouse embryonic fibroblasts exposed to a PKCα inhibitor, Go6976. Thus, the lack of LSD1 phosphorylation exacerbates CSE/LPS-induced COPD by elevating inflammation and oxidative stress.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.241-247
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• 2016

Bronchodilators are the cornerstone of symptomatic chronic obstructive pulmonary disease (COPD) treatment. They are routinely recommended for symptom reduction, with a preference of long-acting over short-acting drugs. Bronchodilators are classified into two classes based on distinct modes of action, i.e., long-acting antimuscarinics (LAMA, once-daily and twice-daily), and long-acting ${\beta}2$-agonists (LABA, once-daily and twice-daily). In contrast to asthma management, evidence supports the efficacy of both classes of long-acting bronchodilators as monotherapy in preventing COPD exacerbations, with greater efficacy of LAMA drugs versus LABAs. Several novel LAMA/LABA fixed dose combination inhalers are currently approved for COPD maintenance treatment. These agents show superior symptom control to monotherapies, and some of these combinations have also demonstrated superior efficacy in exacerbation prevention versus monotherapies, or combinations of inhaled corticosteroids plus LABA. This review summarizes the current data on clinical effectiveness of bronchodilators alone or in combination to prevent exacerbations of COPD.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.207-213
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• 2016

Chronic obstructive pulmonary disease (COPD) encompasses several clinical syndromes, most notably emphysema and chronic bronchitis. Most of the current treatments fail to attenuate severity and progression of the disease, thereby requiring better mechanistic understandings of pathogenesis to develop disease-modifying therapeutics. A number of theories on COPD pathogenesis have been promulgated wherein an increase in protease burden from chronic inflammation, exaggerated production of reactive oxygen species and the resulting oxidant injury, or superfluous cell death responses caused by enhanced cellular injury/damage were proposed as the culprit. These hypotheses are not mutually exclusive and together likely represent the multifaceted biological processes involved in COPD pathogenesis. Recent studies demonstrate that mitochondria are involved in innate immune signaling that plays important roles in cigarette smoke-induced inflammasome activation, pulmonary inflammation and tissue remodeling responses. These responses are reviewed herein and synthesized into a view of COPD pathogenesis whereby mitochondria play a central role.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.85 no.2
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• pp.101-110
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• 2022

There is a considerable number of individuals who exhibit features of both asthma and chronic obstructive pulmonary disease (COPD), defined as asthma-COPD overlap (ACO). Many studies have reported that these patients have a greater burden of symptoms, including cough and dyspnea, and experience more exacerbations and hospitalizations than those with non-ACO COPD or asthma. Although diagnostic criteria for ACO have not yet been clearly established, their clinical significance remains to be determined. As interest in ACO grows, related studies have been conducted in South Korea as well. The present review summarizes ACO-related studies in South Korea to better understand Korean ACO patients and guide further research. Several cohort studies of asthma and COPD and population-based studies for ACO were reviewed and the key results from demographics, clinical features, lung function, biomarkers, treatment, and prognosis were summarized.

• Tuberculosis and Respiratory Diseases
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• v.86 no.3
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• pp.166-175
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• 2023

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. The lower airways contain a rich and diverse microbiome, which may play a significant regulatory role in both health and disease. In COPD, the microbiome becomes perturbed, causing dysbiosis. Increased representation of members in the Proteobacteria phylum and certain members in the Firmicutes phylum has been associated with increased risk of exacerbations and mortality. Therapies such as inhaled corticosteroids and azithromycin may modulate the airway microbiome or its metabolites in patients with COPD. This paper provides an up-to-date overview of the airway microbiome and its importance in the pathophysiology of COPD and as potential therapeutic target in the future.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.330-338
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• 2006

Background: The main factors associated with weight loss in patients with COPD are not well known. Since chronic inflammation and oxidative stress play a major pathogenic role in COPD, these factors may be responsible for the patients' weight loss. Therefore, this study measured the body mass index (BMI) in COPD patients and evaluated the variables, such as systemic inflammatory marker, oxidative stress and lung function, that correlate with the BMI. Method: The stable COPD patients (M:F=49:4, mean age=$68.25{\pm}6.32$) were divided into the lower (<18.5), normal (18.5-25) and higher (>25) BMI group. The severity of the airway obstruction was evaluated by measuring the $FEV_1$. The serum IL-6 and TNF-$\alpha$ levels were measured to determine the degree of systemic inflammation, and the carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ level was measured to determine the level of oxidative stress. Each value in the COPD patients and normal control was compared with the BMI. Results: 1) Serum 8-iso-prostaglandin $F_2{\alpha}$ in COPD patients was significantly higher ($456.08{\pm}574.12pg/ml$) than that in normal control ($264.74{\pm}143.15pg/ml$) (p<0.05). However, there were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein between the COPD patients and normal controls. 2). In the COPD patients, the $FEV_1$ of the lower BMI group was significantly lower ($0.93{\pm}0.25L$) than that of the normal BMI ($1.34{\pm}0.52L$) and higher BMI groups ($1.72{\pm}0.41L$) (p<0.05). The lower $FEV_1$ was significantly associated with a lower BMI in COPD patients (p=0.002, r=0.42). The BMI of very severe COPD patients was significantly lower ($19.8{\pm}2.57$) than that of the patients with moderate COPD ($22.6{\pm}3.14$) (p<0.05). 3). There were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ according to the BMI in the COPD patients. Conclusion: The severity of the airway obstruction, not the systemic inflammatory markers and oxidative stress, might be associated with the BMI in stable COPD patients. Further study will be needed to determine the factors associated with the decrease in the BMI of COPD patients.

• 월간산업보건
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• s.354
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• pp.39-51
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• 2017

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.14-22
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• 2005

• Tuberculosis and Respiratory Diseases
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• v.67 no.1
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• pp.1-7
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• 2009