Bronchial matrix and inflammation respond to inhaled steroids despite ongoing allergen exposure in asthma
Bronchial matrix and inflammation respond to inhaled steroids despite ongoing allergen exposure in asthma
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DOI：
10.1111/j.1365-2222.2005.02334.x
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发表时间：
2005-10-01
影响因子：
6.1
通讯作者：
Sterk, PJ
中科院分区：
文献类型：
--
作者：
de Kluijver, J;Schrumpf, JA;Sterk, PJ
背景气道黏膜的炎症和结构改变是哮喘的慢性特征。这些变化的机制及其调制类固醇prophylaxy.Objective我们推测，无症状的持续过敏原暴露可以驱动气道炎症以及细胞外基质（ECM）的变化，吸入性类固醇可以防止this.Methods因此，我们暴露轻度哮喘患者2周的重复低剂量过敏原，伴随吸入性类固醇或安慰剂治疗。对暴露前后的支气管活检进行染色和数字分析。结果低剂量过敏原暴露组支气管上皮细胞巨噬细胞数量明显增加，而对照组支气管上皮细胞巨噬细胞数量明显减少。尽管持续接触过敏原，吸入类固醇减少粘膜嗜酸性粒细胞，中性粒细胞和T淋巴细胞的数量。基线时，与正常对照组相比，哮喘患者支气管粘膜中蛋白聚糖（PGS）双糖链聚糖和核心蛋白聚糖的平均密度分别较高和较低。类固醇治疗，在过敏原暴露，增加了平均密度的PGS双糖蛋白聚糖和versican.Conclusions，我们得出结论，慢性过敏原暴露诱导支气管粘膜的炎症变化。尽管持续的过敏原暴露，类固醇治疗减少粘膜炎性细胞，同时改变PG密度。后一个观察结果强调了需要密切检查哮喘患者气道结构中类固醇诱导的变化。
Background Inflammatory and structural changes of the airway mucosa are chronic features of asthma. The mechanisms underlying these changes and their modulation by steroid prophylaxis have not been clarified.Objective We postulated that asymptomatic ongoing allergen exposure could drive airway inflammation as well as changes in the extracellular matrix (ECM), and that inhaled steroids could prevent this.Methods Therefore, we exposed patients with mild asthma to 2 weeks of repeated low-dose allergen, with concomitant inhaled steroid or placebo treatment. Bronchial biopsies, which were taken before and after this exposure, were stained and digitally analysed. The ECM proteins in asthmatics were also compared with a normal control group.Results Low-dose allergen exposure alone resulted in a significant increase of bronchial epithelial macrophages. Despite ongoing allergen exposure, inhaled steroids reduced the numbers of mucosal eosinophils, neutrophils and T lymphocytes. At baseline, the mean density of the proteoglycans (PGS) biglycan and decorin were, respectively, higher and lower in the bronchial mucosa of asthmatics as compared with normal controls. Steroid treatment, during allergen exposure, increased the mean density of the PGS biglycan and versican.Conclusions We conclude that chronic allergen exposure induces inflammatory changes in the bronchial mucosa. Despite ongoing allergen exposure, steroid treatment decreases mucosal inflammatory cells while altering PG density. The latter observation highlights the need to examine steroid-induced changes closely in the airway structure in patients with asthma.