Noneosinophilic asthma in children: relation with airway remodelling

Noneosinophilic asthma in children: relation with airway remodelling
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DOI:
10.1183/09031936.00168210
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发表时间:
2011-09-01
影响因子:
24.3
通讯作者:
Saetta, M.
Saetta, M.
中科院分区:
医学1区
文献类型:
--
作者:
Baraldo, S.;Turato, G.;Saetta, M.

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嗜酸性粒细胞性哮喘越来越被认为是一种重要的成人临床病理表型。然而,在儿童中很少对这种实体进行调查。特别是,目前尚不清楚非嗜酸性粒细胞哮喘患儿的气道重塑是否与嗜酸性粒细胞疾病患儿的气道重塑程度相同。我们分析了80名接受支气管镜检查的儿童的支气管活检,以寻找合适的临床适应症:21名非嗜酸性粒细胞哮喘患儿,34名嗜酸性粒细胞哮喘患儿和25名对照儿童。采用组织学和免疫组织化学方法量化气道重构特征——基底膜增厚、上皮细胞损失和血管生成;免疫激活特征——炎症浸润、白细胞介素(IL)-4、IL-5、转化生长因子(TGF)- β、TGF- β受体II型。非嗜酸性粒细胞性哮喘患儿气道重构的主要成分与嗜酸性粒细胞性疾病患儿一样。的确,与对照组儿童相比,非嗜酸性粒细胞和嗜酸性粒细胞哮喘儿童的基底膜增厚,上皮损失增加,血管数量增加。与对照组比较,两组哮喘患者IL-4、IL-5表达均升高,tgf - β受体ⅱ型表达均降低。本研究表明,哮喘儿童即使在没有明显嗜酸性粒细胞浸润的情况下也会发生典型的哮喘结构变化,这表明除了嗜酸性粒细胞炎症外,其他机制可能在生命早期促进气道重塑。
Noneosinophilic asthma is increasingly recognised as an important clinical-pathological phenotype in adults. However, this entity has scarcely been investigated in children. In particular, it is unknown whether airway remodelling would develop in children with non-eosinophilic asthma to the same degree as in children with eosinophilic disease.We analysed bronchial biopsies from 80 children undergoing bronchoscopy for appropriate clinical indications: 21 with noneosinophilic asthma, 34 with eosinophilic asthma and 25 control children. Features of airway remodelling - basement membrane thickening, epithelial loss and angiogenesis - and immune activation - inflammatory infiltrate, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-beta, TGF-beta receptor type II - were quantified by histology and immunohistochemistry.The main components of airway remodelling were present in children with noneosinophilic asthma just as in those with eosinophilic disease. Indeed, compared with control children, both noneosinophilic and eosinophilic asthmatic children had thickened basement membrane, increased epithelial loss and higher number of vessels. Moreover, in both groups of asthmatics, expression of IL-4 and IL-5 was increased, while that of TGF-beta receptor type II was reduced, compared with controls.This study demonstrates that structural changes typical of asthma develop in asthmatic children even in the absence of a prominent eosinophilic infiltrate, indicating that other mechanisms, besides eosinophilic inflammation, may promote airway remodelling early in life.