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THE MECHANISMS OF AIRWAY REMODELING IN BRONCHIAL ASTHMA.

支气管哮喘气道重塑的机制。

基本信息

批准号：
10670537
负责人：
KOIZUMI Tomonobu
金额：
$ 1.98万
依托单位：
SHINSHU UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

The inhalation of Ascaris suum twice a week for 8 weeks induced a marked accumulation in the airway of inflammatory cells, especially eosinophils, and goblet cell hyperplasia of epithelial cell in allergic sheep naturally sensitized by Ascaris. The eosinophil infiltration into the subepithelial mucosa and goblet cell hyperplasia were distributed from central airway to the small airway, and the changes were marked in the small airways. These changes are consistent with the changes observed in the patient with asthma developed to the airway remodeling. However, the apparent thickening of basement membrane, airway smooth muscle hyperplasia, and increase in submucosal glands observed in asthmatic airway remodeling were not observed in this animal model. To establish animal model of asthmatic airway remodeling, further examination may be needed. In clinical study, we measured the inflammatory cells, ECP, tryptase, and TGF-beta in induced sputum and exhaled nitric oxide (ENO) in patients wit … More h asthma, and examined the relationship with airway remodeling. The presence of airway remodeling was assessed by fixed airflow limitation and bronchial wall thickness (rt. B1) evaluated by using a chest HRCT. In asthmatics, the eosinophil numbers and the levels of ECP, TGF-beta were significantly higher than those in healthy subjects. Some asthmatics showed a higher tryptase level in sputum. However, there was no significant difference in these inflammatory cells and mediators between the asthmatics with and without airway remodeling, however, the level of TGF-beta in sputum had a tendency to increase in asthmatics with remodeling. The concentration and production of ENO dependent on the increase in airway pressure were significantly higher in asthmatics than those in healthy subjects. The ENO in asthmatics was significantly correlated positively with eosinophilia in sputum and negatively with FEVィイD21ィエD2. The concentration and production of ENO in asthmatics with airway remodeling were significantly lower than those in asthmatics without airway remodeling, whereas there was no significant difference in sputum eosinophilia between the two groups. It has been suggested that a sustaining eosinophilic airway inflammation may be associated with the development of airway remodeling. The eosinophilic inflammation evaluated induced sputum and the level of tryptase and TGF-beta in sputum may not be able to predict the presence of airway remodeling, however, the discrepancy of sputum eosinophilia and ENO production may be predicted the presence of airway remodeling. Less

每周2次连续8周吸入猪蛔虫，可引起致敏绵羊气道内炎性细胞，尤其是嗜酸性粒细胞的明显聚集，上皮细胞杯状细胞增生。嗜酸性粒细胞浸润和杯状细胞增生由中央气道向小气道分布，以小气道变化最明显。这些变化与在哮喘患者中观察到的气道重塑变化一致。然而，在该动物模型中未观察到哮喘气道重塑中观察到的明显基底膜增厚、气道平滑肌增生和粘膜下腺体增加。建立哮喘气道重塑动物模型尚需进一步研究。在临床研究中，我们检测了哮喘患者诱导痰和呼出气一氧化氮（ENO）中的炎性细胞、ECP、类胰蛋白酶和TGF-β。 ...更多信息 h哮喘，并检查与气道重塑的关系。通过使用胸部HRCT评估固定气流限制和支气管壁厚度（rt. B1）来评估气道重塑的存在。哮喘组嗜酸性粒细胞数、ECP、TGF-β水平均显著高于健康对照组。部分哮喘患者痰液中类胰蛋白酶水平较高。而气道重塑组与非气道重塑组的上述炎性细胞和介质无显著性差异，但气道重塑组痰液中TGF-β水平有升高的趋势。ENO的浓度和产量依赖于气道压力的增加，哮喘患者明显高于健康人。哮喘患者ENO与痰嗜酸粒细胞增多呈显著正相关，与FEV_（21）、FEV_（21）呈显著负相关。哮喘气道重塑组ENO浓度及产生量明显低于无气道重塑组，而痰液嗜酸性粒细胞计数两组间无显著性差异。研究表明，持续的嗜酸性粒细胞性气道炎症可能与气道重塑的发生有关。诱导痰中嗜酸性粒细胞炎症反应及痰中类胰蛋白酶和TGF-β的水平可能不能预测气道重塑的发生，但痰中嗜酸性粒细胞和ENO产生的差异可能预测气道重塑的发生。少