1.Effect of Diarylpentanoid Analogues on LipopolysaccharideInduced Interleukin-6 and Interleukin-8 Gene Expression in Airway Inflammation
Malaysian Journal of Medicine and Health Sciences 2019;15(SP2):10-17
Introduction: Airway inflammation is the pathological hallmark of chronic inflammatory airway diseases, especially asthma and chronic obstructive pulmonary disease (COPD). Airway epithelium plays an indispensable role in these diseases by secreting inflammatory mediators and cytokines in response to foreign substances, such as lipopolysaccharide (LPS). Previous studies have shown that diarylpentanoid analogues, especially 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD) and 2-benzoyl-6-(3,4-dihydroxybenzylidene)cyclohexen-1-ol (BDHBC), significantly inhibited nitric oxide (NO) production; suggesting their anti-inflammatory property. However, the therapeutic potential of DHHPD and BDHBC in airway inflammation has not been explored. Thus, this study aims to investigate their effects on interleukin (IL)-6 and IL-8 gene expression in LPS-induced Calu-3 cells, a cellular model of human airway epithelium. Methods: MTT cytotoxicity assay was carried out to identify non-cytotoxic concentrations of DHHPD and BDHBC on Calu-3 cells. RT-PCR was done to determine IL-6 and IL-8 gene expression levels. Results: DHHPD and BDHBC were not cytotoxic on Calu-3 cells up to 200µM. Four non-cytotoxic concentrations were chosen – 6.25, 12.5, 25 and 50µM to determine the effect of both compounds on gene expression. All four concentrations of DHHPD and BDHBC significantly inhibited LPS-induced mRNA expression of IL-6 while all concentrations of BDHBC, except 6.25µM, significantly reduced IL-8 mRNA expression. Similar finding was obtained for DHHPD, except that at 50µM, there was no inhibition of IL-8 mRNA expression. Conclusion: Diarylpentanoid analogues, DHHPD and BDHBC, are proven to be effective in suppressing LPS-induced IL-6 and IL-8 gene expression. However, further studies are required to confirm their inhibitory effects on the production of pro-inflammatory cytokines.
Airway inflammation
2.Clinical and Pathophysiological Characteristics of Severe Asthma.
Korean Journal of Medicine 2012;83(4):424-429
Severe asthma is characterized by poor asthma control and frequent exacerbation despite high degree of medication. Severe asthma leads to not only increased morbidity and mortality but high socioeconomic burden. To date, several research networks have been organized to understand the clinical and pathophysiological characteristics of severe asthma. These groups organized multicenter registries and collected both clinical and biological information. The results of these groups revealed that severe asthma is a very heterogeneous entity, which could not be defined based on a single feature. Various phenotypes of asthma has been identified based on clinical, inflammatory and immune responses. To understand severe asthma more drastically in consideration of many phenotypes, cluster analysis and endotyping severe asthma have been tried. Although uncontrolled inflammation and airway remodeling underlies the development of severe asthma, much is not known about its pathomechanisms. This review discusses the current understanding of the clinical and pathogenic mechanisms of severe asthma based on the recent publications.
Airway Remodeling
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Asthma
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Inflammation
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Phenotype
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Registries
3.Role of Matrix Metalloproteinase-9 in Asthma.
Pediatric Allergy and Respiratory Disease 2006;16(1):12-22
Variable airway obstruction, increased bronchial hyperresponsiveness, allergic inflammatory reaction and airway remodeling are main characteristics of asthma. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases(TIMPs) do play important roles to pathogenesis and pathology of asthma via influence on the function and migration of inflammatory cells as well as extracellular matrix(ECM) deposition and degradation. MMP-9 is the predominant MMP in asthma and chronic obstructive pulmonary disease(COPD), and its expression is enhanced when asthma patients have spontaneous exacerbations or in response to local instillation of allergen in the airway. As acute inflammation of asthma resolves, MMP-9 levels return to normal. TIMPs bind MMPs in a 1:1 fashion. Thus, an increase in the molar ratio of MMP/TIMP can favor tissue injury, while the reverse ratio could be associated with increased fibrosis. Glucocorticosteroids could downregulate MMPs and enhance TIMPs. Even though it is clear that stimulated allergic inflammation in airway is associated with increased expression of MMPs, whether specific inhibitors of MMPs could reduce airway structural changes and facilitate orderly healing in asthma is still unknown.
Airway Obstruction
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Airway Remodeling
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Asthma*
;
Fibrosis
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Humans
;
Inflammation
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Matrix Metalloproteinase 9*
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Matrix Metalloproteinases
;
Molar
;
Pathology
4.Pathogenesis and pathophysiology of COPD.
Korean Journal of Medicine 2009;77(4):383-400
Chronic obstructive pulmonary disease (COPD) is a slowly progressed disease characterized by chronic irreversible airway obstruction with increased airway resistance and loss of elastic recoil by lung parenchymal destruction. COPD is a leading cause of morbidity and mortality worldwide. COPD is defined as a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Pathological changes characteristic of COPD are found in the proximal airways, peripheral airways, lung parenchyma, and pulmonary vasculature, showing chronic inflammation, and structural changes resulting from repeated injury and repair mostly caused by inhaled cigarette smoke. This pathological changes lead to airway trapping and progressive airway limitation.
Airway Obstruction
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Airway Resistance
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Humans
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Inflammation
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Lung
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Pulmonary Disease, Chronic Obstructive
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Smoke
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Tobacco Products
5.Evolution of Asthma Concept and Effect of Current Asthma Management Guidelines.
Sohei MAKINO ; Hironori SAGARA
Allergy, Asthma & Immunology Research 2010;2(3):172-176
Concept of asthma has changed from symptom-complex or airway hypersensitivity to airway inflammation and airway remodeling. Based on this concept asthma management guidelines (JGL) has been developed in Japan. Death from asthma has decreased drastically since the publication of the guidelines, although it is still high in elderly population. Further works are expected for "zero-death" from asthma and for tighter control of airway inflammation and resultant airway remodeling.
Aged
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Airway Remodeling
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Asthma
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Humans
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Hypersensitivity
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Inflammation
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Japan
;
Publications
6.Airway inflammation and small airway wall remodeling in neutrophilic asthma.
Xiao Yan GAI ; Chun CHANG ; Juan WANG ; Ying LIANG ; Mei Jiao LI ; Yong Chang SUN ; Bei HE ; Wan Zhen YAO
Journal of Peking University(Health Sciences) 2018;50(4):645-650
OBJECTIVE:
To investigate the distribution of airway inflammation phenotype in patients with bronchial asthma (asthma), and to analyze clinical characteristics, inflammatory cytokines, pulmonary small vessels remodeling and small airway wall remodeling in patients with neutrophilic asthma.
METHODS:
Sixty-three patients with asthma were enrolled from January 2015 to December 2015 in Peking University Third Hospital. Clinical data including gender, age, body mass index (BMI), pulmonary function tests (PFTs), asthma control test (ACT) were recorded. All the patients underwent sputum induction. The cellular composition of the sputum was evaluatedand the concentration of active MMP-9 in the sputum tested. Blood routine tests were done and the concentration of IgE, periostin, and TGF-beta1 levels were measured in serum by enzyme-linked immunosorbent assay (ELISA). Small airway wall remodeling was measured in computed tomography (CT) scans, as the luminal diameter, luminal area, wall thickness and wall area % adjusted by body surface area (BSA) at the end of the 6th generation airway, in which the inner diameter was less than 2 mm. Small vascular alterations were measured by cross-sectional area (CSA), and the total vessel CSA < 5 mm2 was calculated using imaging software.
RESULTS:
The distributions of airway inflammatory phenotypes of the asthmatic patients were as follows: neutrophilic asthma (34.9%, 22/63), eosinophilic asthma (34.9%, 22/63), mixed granulocytic asthma (23.8%, 15/63), and paucigranulocytic asthma (6.3%, 4/63). The neutrophilic subtype patients had a significantly higher active MMP-9 level in sputum compared with the eosinophilic phenotypepatuents, as 179.1 (74.3, 395.5) vs. 50.5 (9.7, 225.8), P<0.05. Sputum neutrophil count was negatively correlated with FEV1%pred (r=-0.304,P<0.05), and positively correlated with active MMP-9 level in sputum (r=-0.304, P<0.05), and positive correlation trend with airway wall thickness (r=0.533, P=0.06). There was a significantly negative correlation of active MMP-9 level in sputum with FEV1%pred (r=-0.281, P<0.05), in positive correlation with small airway wall area (%)(r=0.612, P<0.05), and inpositive correlation trend with airway wall thickness (r=0.612, P=0.06). Neutrophils count in peripheral blood was positively correlated with neutrophil counts in sputum.
CONCLUSION
Neutrophil count in airway is related to lung function in asthmatic patients. Neutrophils may accelerate small airway wall remodeling through the release of active MMP-9. Neutrophil count in peripheral blood is related to neutrophils count in sputum, which may be used as a substitute for evaluating inflammatory phenotype.
Airway Remodeling
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Asthma/physiopathology*
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Eosinophils
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Humans
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Inflammation
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Sputum
7.Bronchial Structural Changes in Childhood Asthma.
Yong Seung SHIN ; Bok Yang PYUN
Pediatric Allergy and Respiratory Disease 1998;8(2):190-197
PURPOSE: While asthma has been considered to be a completely reversible obstructive airway disease, many asthmatics have evidences of residual airway obstruction. Therefore, with the recent attention to the cells participating in inflammation, the definition of asthma was modified based on pathophysiologic observations including the inflammation of the airways. Airway inflammation, demonstrable in most of the asthmatics, is already present in the airways of patients with very mild asthma and is increased with the severity of the disease. It also has been associated with the development of airway hyperresponsiveness. However, the mechanisms by which the airway inflammation leads to airway hyperresponsiveness may result from various factors including the evidences of airway remodeling. These findings indicate that asthma is a disease with important airway remodeling which may leads to permanent tissue destruction. High-resolution computed tomography (HRCT) provides a high degree of anatomic details and can indirectly confirm airways remodeling in asthmatics, such as bronchial thickening, mucoid impaction, bronchial dilatation and bronchiectasis. METHODS: Twenty children with asymptomatic chronic moderate to severe asthma, who have visited pediatric allergy clinic in Soonchunhyang University, were performed HRCT to find out the airway changes in comparison with the asthma severity and the duration of asthma history. RESULTS: High resolution computed tomography revealed various findings, such as bronchial wall thickening, mosaic perfusion, atelectasis and bronchiectasis. The results indicate no positive correlation with the asthma severity and the duration of asthma history. CONCLUSION: Therefore, early intervention for diagnosis and treatment of asthma is very important to prevent the permenant chronic airway obstruction and airway remodeling in childhood asthma.
Airway Obstruction
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Airway Remodeling
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Asthma*
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Bronchiectasis
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Child
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Diagnosis
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Dilatation
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Early Intervention (Education)
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Humans
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Hypersensitivity
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Inflammation
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Perfusion
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Pulmonary Atelectasis
8.Effects of CpG-oligodeoxynucleotides in Chronic Inflammation and Remodeling of Airway in a Murine Model of Bronchial Asthma.
So Hyang SONG ; Chi Hong KIM ; Dong Hwa HAN ; Seung Joon KIM ; Hwa Sik MOON ; Jeong Sup SONG ; Sung Hak PARK
Tuberculosis and Respiratory Diseases 2004;57(6):543-552
BACKGROUND: Airway remodeling of the asthmatic airway, the result of persistent inflammation in the bronchial wall, is associated with irreversible airway obstruction and the severity of asthma. Previous reports had represented that adminitering CpG-oligodeoxynucleotides (CpG-ODN) before sensitization or challenge by allergens inhibits the development of eosinophilic airway inflammation in a murine model of asthma, but the effects of CpG-ODNs on chronic inflammation and airway remodeling had not been characterized. To investigate the influence of CpG-ODNs on chronic inflammation and remodeling of the airway, we performed studies using a murine model of chronic allergen-induced asthma. METHODS: Balb/C mice were sensitized to ovalbumin(OVA) and subsequently exposed to nebulized OVA by means of inhalation twice weekly for 7 weeks. CpG-ODNs(30 microgram) was administered intraperitoneally at sensitization. After final inhalation, mice were evaluated for airway hyperresponsiveness, chronic airway inflammation and remodeling. RESULTS: The mice exposed to chronic and recurrent airway challenge with OVA had persistent airway hyperresponsiveness, chronic inflammation and airway remodeling. Mice treated with CpG-ODNs exhibited decreased bronchial hyperresponsiveness, OVA-specific IgE, chronic inflammation and evidence of airway remodeling, including goblet cell hyperplasia and subepithelial fibrosis. CONCLUSION: CpG-ODNs was thought to prevent chronic inflammation and remodeling changes in a murine model of chronic asthma.
Airway Obstruction
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Airway Remodeling
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Allergens
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Animals
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Asthma*
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Eosinophils
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Fibrosis
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Goblet Cells
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Hyperplasia
;
Immunoglobulin E
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Inflammation*
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Inhalation
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Mice
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Ovum
9.Airway Management of a Patient with Esophago-tracheal Perforation by Endotracheal Tube: A case report.
Mi Young KWON ; Hee Yeong KIM ; Su Jin KANG ; In Cheol CHOI
Korean Journal of Anesthesiology 2006;51(5):627-631
Although uncommon and rarely reported, tracheo-esophageal perforation during traumatic intubation is life threatening and associated with a high mortality rate. It may result in severe airway complications such as a pneumothorax, pneumomediastium, pneumonia, and mediastinitis. The mortality rate of esophageal perforation has been reported to range from 6 to 34%, and up to 56% if the diagnosis is delayed by more than 12 hours after the event. In our case, the patient had been intubated for 3 weeks with an esophago-tracheal perforation. The perforation was not found by the physician because he had no signs of esophageal perforation, the tip of endotracheal tube was well in the trachea and balloon of the tube was sufficient to prevent air leakage. After the failure of extubation for three times, the diagnosis was carried out by gastrofibroscopy, bronchoscopy and chest 3-dimensional computed tomography. His tracheal and esophageal walls were injured with severe inflammation. Therefore, primary repair could not be done and only a tracheostomy was performed.
Airway Management*
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Bronchoscopy
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Diagnosis
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Esophageal Perforation
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Humans
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Inflammation
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Intubation
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Mediastinitis
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Mortality
;
Pneumonia
;
Pneumothorax
;
Thorax
;
Trachea
;
Tracheostomy
10.Airway remodelling of severe bronchial asthma patients according to disease duration.
Mi Seung SHIN ; Jung Hyun CHANG ; Hye Young CHOI ; Yoon Hae CHANG ; Sung Sook PARK ; Young Joo CHO
Journal of Asthma, Allergy and Clinical Immunology 1998;18(4):701-709
BACKGROUND: Bronchial asthma is classically defined as a reversible obstruction and hypsrresponsiveness of the airway attributed to an inflammatory process. However, some individuals with asthma show an irreversible component of airflow obstruction. It may be associated with structural changes in the airway resulting from severe or long standing air- way inflammation and remodelling. OBJECTIVE: The study was undertaken to compare the clinical characteristics of patient and airway remodelling as shown in bronchial wall thickness in HRCT according to the duration of asthma. MATERIALS AND METHODS: A retrospective clinical study was done on 119 patients with bronchial asthma, who had been admitted to Ewha Womans University Mokdong Hospital. Patients were divided to three groups according to disease duration and, clinical characteristics, pulmonary function test and HRCT were done. RESULTS: Basal FEV, and FVC was significantly lower in patient with longer duration. (p<0. 05) However pulmonary function was improved regardless of disease duration after 2 weeks steroid and bronchodilator therapy, and there was no significant difference in level changes according to the disease duration. The inner diameter of the bronchi and thickness of the bronchial wall at segmental and subsegmental bronchi increased significantly in patient with longer duration of asthma(p<0.05). Conclusion: These findings showed that airway remodelling was more extensive in patients with longer duration of disease resulting in decreased pulmonary function. These facts suggested that early anti-inflammatory therapy would be helpful for prevention of airway remodelling.
Airway Remodeling*
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Asthma*
;
Bronchi
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Female
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Humans
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Inflammation
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Respiratory Function Tests
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Retrospective Studies