No Abstract available.
Airway Remodeling*

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 ; Asthma ; Inflammation ; Phenotype ; Registries

Airway Remodeling ; Asthma ; pathology ; physiopathology ; Child ; Humans

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 ; Airway Remodeling ; Asthma ; Humans ; Hypersensitivity ; Inflammation ; Japan ; Publications

BACKGROUND: Airway remodeling is characterized by an increase in the airway wall thickness. We aimed to compare the airway wall thickness among asthmatic subjects with different severity and to examine its relation to pulmonary function and airway hyperresponsiveness. METHODS: Thirty-seven adult asthmatics were assigned to mild (MA, n=17), moderate (MoA, n=11), and severe (SA, n=9) groups according to the Global Initiative for Asthma classification. Patients with more than 10 pack-years of smoking history were excluded. We measured the airway wall thickness (T) and internal diameter (d) using high-resolution computed tomography, and then calculated the external diameter (D). The T/D ratio was compared between the groups and correlations between the T/D ratio and pulmonary function (methacholine PC20) were assessed. RESULTS: The mean T/D ratio was significantly higher in the MoA and the SA groups than in the MA group for the total airways (0.278+/-0.014, 0.281+/-0 .019 vs. 0.228+/-0.013; p=0.022, p=0.021, respectively). The mean T/D ratio was also higher in the SA group than the MA group for the small airways (0.313+/-0.018 vs. 0.253+/-0.013; p=0.009). However, there were no significant differences for the large airways. The mean T/D ratio negatively correlated with FEV1 (L) and FEV1 (% of predicted) in total airways (r=-0.519, p=0.001; r=-0.396, p=0.015), small airways (r=-0.567, p<0.001; r=-0.450, p=0.008) and large airways (r=-0.395, p=0.015; r=-0.351, p=0.033). The methacholine PC20 was not related to the T/D ratio. CONCLUSIONS: This study suggests that patients with moderate to severe asthma have greater airway remodeling than those with mild asthma, and the degree of airway wall thickening correlates to the severity of airflow obstruction.
Adult ; Airway Remodeling* ; Asthma* ; Classification ; Humans ; Methacholine Chloride ; Smoke ; Smoking

Airway Remodeling ; Asthma ; physiopathology ; Bronchial Hyperreactivity ; etiology ; Bronchitis ; physiopathology ; Humans

No abstract available.
Airway Remodeling ; Angiogenesis Inducing Agents ; Rhinitis ; Rhinitis, Allergic, Perennial

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 ; Asthma/physiopathology* ; Eosinophils ; Humans ; Inflammation ; Sputum

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 ; Airway Remodeling ; Asthma* ; Fibrosis ; Humans ; Inflammation ; Matrix Metalloproteinase 9* ; Matrix Metalloproteinases ; Molar ; Pathology

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 ; Airway Remodeling ; Allergens ; Animals ; Asthma* ; Eosinophils ; Fibrosis ; Goblet Cells ; Hyperplasia ; Immunoglobulin E ; Inflammation* ; Inhalation ; Mice ; Ovum