BACKGROUND Local tissue eosinophilia and Th2-cytokines are characteristic features of seasonal allergic rhinitis. Airway-remodelling is a feature of asthma whereas evidence for remodelling in allergic rhinitis (AR) is conflicting. OBJECTIVE By use of a novel human repetitive nasal allergen challenge (RAC) model, we evaluated the relationship between allergic inflammation and features of remodelling in AR. METHODS Twelve patients with moderate-severe AR underwent 5-alternate day challenges with diluent which after 4-weeks were followed by 5-alternate day challenges with grass pollen extract. Nasal symptoms, Th1/Th2 cytokines in nasal secretion and serum were evaluated. Nasal biopsies were taken 24 hours after the 1st and 5th challenges with diluent and with allergen. Sixteen healthy controls underwent a single challenge with diluent and with allergen. Using immunohistochemistry, epithelial and sub-mucosal inflammatory cells, and remodelling markers were evaluated by computed image analysis. RESULTS There was an increase in early and late-phase symptoms after every allergen challenge compared to diluent (both p<0.05) with evidence of both clinical and immunological priming. Nasal tissue eosinophils and IL-5 in nasal secretion increased significantly after RAC compared to corresponding diluent challenges (p<0.01, p=0.01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r=0.79, p=0.007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r=0.69, p=0.06) in allergic rhinitis. No differences were observed after RAC with regards to epithelial integrity, reticular basement membrane thickness, glandular area, expression of markers of activation of airway-remodelling including α-SMA, HSP-47, extracellular matrix (MMP7, 9 and TIMP-1), angiogenesis and lymphangiogenesis for AR compared to healthy controls. CONCLUSION Novel repetitive nasal allergen challenge in participants with severe persistent seasonal allergic rhinitis resulted in tissue eosinophilia and increases in IL-5 but no structural changes. Our data support no link between robust Th2-inflammation and development of airway-remodelling in AR.

中文翻译：

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过敏性鼻炎中的重复性鼻过敏原挑战：引发和 Th2 型炎症，但没有重塑的证据

背景 局部组织嗜酸性粒细胞增多和 Th2 细胞因子是季节性变应性鼻炎的特征。气道重塑是哮喘的一个特征，而过敏性鼻炎 (AR) 重塑的证据是相互矛盾的。目的通过使用一种新的人类重复性鼻过敏原挑战 (RAC) 模型，我们评估了过敏性炎症与 AR 重塑特征之间的关系。方法 12 名中重度 AR 患者接受了 5 天的稀释剂攻击，4 周后，接下来是 5 天的草花粉提取物攻击。评估鼻部症状、鼻分泌物和血清中的Th1/Th2细胞因子。在第一次和第五次用稀释剂和过敏原攻击后 24 小时进行鼻活检。16 名健康对照者用稀释剂和过敏原进行了一次挑战。使用免疫组织化学，通过计算机图像分析评估上皮和黏膜下炎症细胞以及重塑标志物。结果 与稀释剂相比，每次过敏原激发后的早期和晚期症状均有所增加（均 p<0.05），有临床和免疫启动的证据。与相应的稀释剂挑战相比，RAC 后鼻腔分泌物中的鼻组织嗜酸性粒细胞和 IL-5 显着增加（分别为 p<0.01，p=0.01）。黏膜下肥大细胞与早期临床反应之间存在相关性（r=0.79，p=0.007），并且在过敏性鼻炎中，上皮嗜酸性粒细胞与鼻分泌物中 IL-5 浓度之间存在关联（r=0.69，p=0.06） . RAC 后在上皮完整性、网状基底膜厚度、腺体面积、气道重塑激活标志物的表达（包括 α-SMA、HSP-47、细胞外基质（MMP7、9 和 TIMP-1））方面没有观察到差异，与健康对照相比，AR 的血管生成和淋巴管生成。结论 在患有严重持续性季节性过敏性鼻炎的参与者中，新的重复性鼻过敏原挑战导致组织嗜酸性粒细胞增多和 IL-5 增加，但没有结构变化。我们的数据支持强大的 Th2 炎症与 AR 中气道重塑的发展之间没有联系。与健康对照相比，AR 的血管生成和淋巴管生成。结论 在患有严重持续性季节性过敏性鼻炎的参与者中，新的重复性鼻过敏原挑战导致组织嗜酸性粒细胞增多和 IL-5 增加，但没有结构变化。我们的数据支持强大的 Th2 炎症与 AR 中气道重塑的发展之间没有联系。与健康对照相比，AR 的血管生成和淋巴管生成。结论 在患有严重持续性季节性过敏性鼻炎的参与者中，新的重复性鼻过敏原挑战导致组织嗜酸性粒细胞增多和 IL-5 增加，但没有结构变化。我们的数据支持强大的 Th2 炎症与 AR 中气道重塑的发展之间没有联系。