de Kluijver J, Schrumpf J A, Evertse C E, Sont J K, Roughley P J, Rabe K F, Hiemstra P S, Mauad T, Sterk P J
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Clin Exp Allergy. 2005 Oct;35(10):1361-9. doi: 10.1111/j.1365-2222.2005.02334.x.
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.
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.
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.
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.
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.
气道黏膜的炎症和结构变化是哮喘的慢性特征。这些变化的潜在机制以及类固醇预防对其的调节作用尚未阐明。
我们推测无症状的持续过敏原暴露可引发气道炎症以及细胞外基质（ECM）的变化，并且吸入类固醇可预防这种情况。
因此，我们让轻度哮喘患者暴露于2周的反复低剂量过敏原中，同时进行吸入类固醇或安慰剂治疗。在暴露前后采集支气管活检组织，进行染色并进行数字分析。还将哮喘患者的ECM蛋白与正常对照组进行比较。
仅低剂量过敏原暴露导致支气管上皮巨噬细胞显著增加。尽管持续暴露于过敏原，但吸入类固醇减少了黏膜嗜酸性粒细胞、中性粒细胞和T淋巴细胞的数量。在基线时，与正常对照组相比，哮喘患者支气管黏膜中蛋白聚糖（PGS）双糖链蛋白聚糖和核心蛋白聚糖的平均密度分别更高和更低。在过敏原暴露期间进行类固醇治疗，增加了PGS双糖链蛋白聚糖和多功能蛋白聚糖的平均密度。
我们得出结论，慢性过敏原暴露会诱导支气管黏膜发生炎症变化。尽管持续暴露于过敏原，但类固醇治疗可减少黏膜炎症细胞，同时改变PG密度。后一观察结果凸显了密切检查哮喘患者气道结构中类固醇诱导变化的必要性。
