• Korean Journal of Radiology
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• v.21 no.7
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• pp.880-890
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• 2020

Objective: Patients with chronic obstructive pulmonary disease (COPD) are known to be at risk of osteoporosis. The purpose of this study was to evaluate the association between thoracic vertebral bone density measured on chest CT (D_Thorax) and clinical variables, including survival, in patients with COPD. Materials and Methods: A total of 322 patients with COPD were selected from the Korean Obstructive Lung Disease (KOLD) cohort. D_Thorax was measured by averaging the CT values of three consecutive vertebral bodies at the level of the left main coronary artery with a round region of interest as large as possible within the anterior column of each vertebral body using an in-house software. Associations between D_Thorax and clinical variables, including survival, pulmonary function test (PFT) results, and CT densitometry, were evaluated. Results: The median follow-up time was 7.3 years (range: 0.1-12.4 years). Fifty-six patients (17.4%) died. D_Thorax differed significantly between the different Global Initiative for Chronic Obstructive Lung Disease stages. D_Thorax correlated positively with body mass index (BMI), some PFT results, and the six-minute walk distance, and correlated negatively with the emphysema index (EI) (all p < 0.05). In the univariate Cox analysis, older age (hazard ratio [HR], 3.617; 95% confidence interval [CI], 2.119-6.173, p < 0.001), lower BMI (HR, 3.589; 95% CI, 2.122-6.071, p < 0.001), lower forced expiratory volume in one second (FEV₁) (HR, 2.975; 95% CI, 1.682-5.262, p < 0.001), lower diffusing capacity of the lung for carbon monoxide corrected with hemoglobin (DL_CO) (HR, 4.595; 95% CI, 2.665-7.924, p < 0.001), higher EI (HR, 3.722; 95% CI, 2.192-6.319, p < 0.001), presence of vertebral fractures (HR, 2.062; 95% CI, 1.154-3.683, p = 0.015), and lower D_Thorax (HR, 2.773; 95% CI, 1.620-4.746, p < 0.001) were significantly associated with all-cause mortality and lung-related mortality. In the multivariate Cox analysis, lower D_Thorax (HR, 1.957; 95% CI, 1.075-3.563, p = 0.028) along with older age, lower BMI, lower FEV₁, and lower DL_CO were independent predictors of all-cause mortality. Conclusion: The thoracic vertebral bone density measured on chest CT demonstrated significant associations with the patients' mortality and clinical variables of disease severity in the COPD patients included in KOLD cohort.

• 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.76 no.5
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• pp.226-232
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• 2014

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposures can influence COPD. The purpose of this study is to investigate the clinical characteristics of COPD according to the history of environmental exposure. Methods: The study population comprised of 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals within the Korean Obstructive Lung Disease Study Group. We classified environmental exposures according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life, exercise capacity, and computed tomography phenotypes. Results: Thirty-one subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure history to briquette, and 184 (53.3%) had exposure history to firewood. Patients with history of living near a factory had a significantly longer duration of sputum, while patients with exposure to firewood tended to have lower forced expiratory volume in one second, and patients with exposure to briquette tended to have lower six minute walk distance. Conclusion: COPD subjects with the history of living near factory had more frequent respiratory symptoms such as sputum. Our data suggest that environmental exposure may influence clinical phenotype of COPD.

• Tuberculosis and Respiratory Diseases
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• v.80 no.1
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• pp.11-20
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• 2017

Approximately one in four patients with chronic obstructive pulmonary disease (COPD) have asthmatic features consisting of wheezing, airway hyper-responsiveness or atopy. The Global initiative for Asthma/Globalinitiative for chronic Obstructive Lung Disease committee recently labelled these patients as having asthma-COPD overlap syndrome or ACOS. ACOS also encompasses patients with asthma, ${\geq}40$ years of age, who have been cigarette smokers (more than 5-10 pack years) or have had significant biomass exposure, and demonstrate persistent airflow limitation defined as a post-bronchodilator forced expiratory volume in 1 second ($FEV_1$)/forced vital capacity of <70%. Data over the past 30 years indicate that patients with ACOS have greater burden of symptoms including dyspnea and cough and show higher risk of COPD exacerbations and hospitalizations than those with pure COPD or pure asthma. Patients with ACOS also have increased risk of rapid $FEV_1$ decline and COPD mortality. Paradoxically, experimental evidence to support therapeutic decisions in ACOS patients is lacking because traditionally, patients with ACOS have been systematically excluded from therapeutic COPD and asthma trials to maintain homogeneity of the study population. In this study, we summarize the current understanding of ACOS, focusing on definitions, epidemiology and patient prognosis.

• Tuberculosis and Respiratory Diseases
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• v.71 no.4
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• pp.254-258
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• 2011

Background: Although the aging process and features of chronic obstructive pulmonary disease (COPD) have several similarities, the relationship between aging and COPD pathogenesis remains incompletely understood. The klotho gene was found to be related to premature aging and emphysematous changes in an animal model. We investigated whether klotho gene polymorphisms are related to COPD susceptibility and emphysema severity. Methods: A total of 219 COPD subjects from the Korean Obstructive Lung Disease Cohort and 305 control subjects were genotyped for two single nucleotide polymorphisms (SNPs) of the klotho gene associated with coronary artery disease. Logistic regression was performed to determine the association of these SNPs with COPD susceptibility and linear regression was performed to investigate their association with emphysema severity in COPD subjects. Results: The mean age of the COPD subjects was 66 years and their mean FEV1 was 1.46 L. There were no associations between either SNP or COPD susceptibility (p=0.6 and 0.2, respectively) and there were no associations with emphysema severity. Conclusion: Genetic polymorphisms of the klotho gene were not associated with COPD in a Korean population.

• Sleep Medicine and Psychophysiology
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• v.6 no.1
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• pp.19-25
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• 1999

Sleep alters both breathing pattern and the ventilatory responses to external stimuli. These changes during sleep permit the development or aggravation of sleep-related hypoxemia in patients with respiratory disease and contribute to the pathogenesis of apneas in patients with the sleep apnea syndrome. Fundamental effects of sleep on the ventilatory control system are 1) removal of wakefulness input to the upper airway leading to the increase in upper airway resistance, 2) loss of wakefulness drive to the respiratory pump, 3) compromise of protective respiratory reflexes, and 4) additional sleep-induced compromise of ventilatory control initiated by reduced functional residual capacity on supine position assumed in sleep, decreased $CO_2$ production during sleep, and increased cerebral blood flow in especially rapid eye movement(REM) sleep. These effects resulted in periodic breathing during unsteady non-rapid eye movement(NREM) sleep even in normal subjects, regular but low ventilation during steady NREM sleep, and irregular breathing during REM sleep. Sleep-induced breathing instabilities are divided due primarily to transient increase in upper airway resistance and those that involve overshoots and undershoots in neural feedback mechanisms regulating the timing and/or amplitude of respiratory output. Following ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include 1) hypocapnia, 2) inhibitory effect from lung stretch, 3) baroreceptor stimulation, 4) upper airway mechanoreceptor reflexes, 5) central depression by hypoxia, and 6) central system inertia. While the respiratory control system functions well during wakefulness, the control of breathing is commonly disrupted during sleep. These changes in respiratory control resulting in breathing instability during sleep are related with the pathophysiologic mechanisms of obstructive and/or central apnea, and have the therapeutic implications for nocturnal hypoventilation in patients with chronic obstructive pulmonary disease or alveolar hypoventilation syndrome.

• Journal of Korean Biological Nursing Science
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• v.19 no.1
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• pp.38-47
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• 2017

Purpose: This study was undertaken to examine the relationship between airflow obstruction and subjective health status reported by stable patients with chronic obstructive pulmonary disease (COPD) residing in the community. Methods: A cross-sectional descriptive study was conducted with 78 stable COPD patients aged 69.7 years old on average and selected by a convenient sampling from an outpatient department of pulmonology in tertiary hospitals. They completed a constructed questionnaire including general characteristics, smoking history, dyspnea by modified medical research council (mMRC) scale, and health status by COPD assessment test (CAT). Anthropometric measurements were performed for body mass index (BMI) and pulse oxymetry for $O_2$ saturation (Sat $O_2$). Medical records were reviewed to obtain disease-related characteristics including duration of the disease, cardiovascular comorbidity, and forced expiratory volume in 1 second ($FEV_1$). Data were analyzed using PASW statistics 20.0. Results: Mean $FEV_1%$ and CAT scores were 55.11% and 17.73, respectively. Those in the lower stage of mMRC showed significantly higher $FEV_1$ and lower CAT. $FEV_1$ and CAT showed significant negative correlations; age and BMI with $FEV_1$, and Sat $O_2$ with CAT. Conclusion: The findings suggest that the less airway obstruction was, the better health status was, and provide the support for using subjective measures in clinical practices for COPD patients.

• Tuberculosis and Respiratory Diseases
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• v.77 no.3
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• pp.116-123
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• 2014

Background: Mesenchymal stem cells (MSCs) obtained from bone marrow or adipose tissue can successfully repair emphysematous animal lungs, which is a characteristic of chronic obstructive pulmonary disease. Here, we describe the cellular distribution of MSCs that were intravenously injected into mice with elastase-induced emphysema. The distributions were also compared to the distributions in control mice without emphysema. Methods: We used fluorescence optical imaging with quantum dots (QDs) to track intravenously injected MSCs. In addition, we used a human Alu sequence-based real-time polymerase chain reaction method to assess the lungs, liver, kidney, and spleen in mice with elastase-induced emphysema and control mice at 1, 4, 24, 72, and 168 hours after MSCs injection. Results: The injected MSCs were detected with QD fluorescence at 1- and 4-hour postinjection, and the human Alu sequence was detected at 1-, 4- and 24-hour postinjection in control mice (lungs only). Injected MSCs remained more in mice with elastase-induced emphysema at 1, 4, and 24 hours after MSCs injection than the control lungs without emphysema. Conclusion: In conclusion, our results show that injected MSCs were observed at 1 and 4 hours post injection and more MSCs remain in lungs with emphysema.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.2
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• pp.157-163
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• 2020

Chronic inflammatory airway diseases, such as chronic rhinosinusitis, chronic obstructive pulmonary disease, and asthma, are associated with excessive mucus production. Hence, the regulation of mucus production is important for the treatment of upper and lower airway diseases. Eupatilin is a pharmacologically active ingredient obtained from Artemisia asiatica Nakai (Asteraceae) and exerts potent anti-inflammatory, anti-allergic, and anti-tumor activities. In the present study, we investigated the effect of eupatilin on phorbol 12-myristate 13-acetate (PMA)-induced MUC5AC and MUC5B expression in human airway epithelial cells. We found that eupatilin treatment significantly inhibited PMA-induced mucus secretion in PAS staining. In addition, qRT-PCR results showed that eupatilin dose-dependently decreased the mRNA expression of MUC5AC in human airway epithelial cells. Western blot and immunofluorescence assay also showed that PMA-induced protein expression of MUC5AC was inhibited by eupatilin treatment. Finally, we investigated MAPKs activity after stimulation with PMA using western blot analysis in human airway epithelial cells. The results showed that eupatilin downregulated the levels of phosphorylated p38, ERK, and JNK. In summary, the anti-inflammatory activities of eupatilin, characterized as the suppression of MUC5AC expression and secretion in human airway epithelial cells, were found to be associated with the inhibition of p38/ERK/JNK MAPKs signaling pathway of MUC5AC secretion.

• Journal of Microbiology and Biotechnology
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• v.33 no.5
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• pp.634-643
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• 2023

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is caused by repeated exposure to harmful matter, such as cigarette smoke. Although Lilium longiflorum Thunb (LLT) has anti-inflammatory effects, there is no report on the fermented LLT bulb extract regulating lung inflammation in COPD. Thus, we investigated the protective effect of LLT bulb extract fermented with Lactobacillus acidophilus 803 in COPD mouse models induced by cigarette smoke extract (CSE) and porcine pancreas elastase (PPE). Oral administration of the fermented product (LS803) suppressed the production of inflammatory mediators and the infiltration of immune cells involving neutrophils and macrophages, resulting in protective effects against lung damage. In addition, LS803 inhibited CSE- and LPS-induced IL-6 and IL-8 production in airway epithelial H292 cells as well as suppressed PMA-induced formation of neutrophil extracellular traps in HL-60 cells. In particular, LS803 significantly repressed the elevated IL-6 and MIP-2 production after CSE and LPS stimulation by suppressing the activity of the nuclear factor kappa-light-chain-enhancer of activated B (NFκB) in mouse peritoneal macrophages. Therefore, our results suggest that the fermented product LS803 is effective in preventing and alleviating lung inflammation.