Department of Allergy, Pulmonology, and Cystic Fibrosis, Children's Hospital, Goethe-University, Frankfurt, Germany.
Respir Res. 2012 Sep 19;13(1):78. doi: 10.1186/1465-9921-13-78.
Both standard and low-dose allergen provocations are an established tool in asthma research to improve our understanding of the pathophysiological mechanism of allergic asthma. However, clinical symptoms are less likely to be induced. Therefore, we designed a protocol for repetitive high-dose bronchial allergen challenges to generate clinical symptoms and airway inflammation.
A total of 27 patients aged 18 to 40 years with positive skin-prick tests and mild asthma underwent repetitive high-dose allergen challenges with household dust mites for four consecutive days. Pulmonary function and exhaled NO were measured at every visit. Induced sputum was analysed before and after the allergen challenges for cell counts, ECP, IL-5, INF-γ, IL-8, and the transcription factor Foxp3.
We found a significant decrease in pulmonary function, an increased use of salbutamol and the development of a late asthmatic response and bronchial hyperresponsiveness, as well as a significant induction of eNO, eosinophils, and Th-2 cytokines. Repeated provocation was feasible in the majority of patients. Two subjects had severe adverse events requiring prednisolone to cope with nocturnal asthma symptoms.
Repeated high-dose bronchial allergen challenges resulted in severe asthma symptoms and marked Th-2-mediated allergic airway inflammation. The high-dose challenge model is suitable only in an attenuated form in diseased volunteers for proof-of-concept studies and in clinical settings to reduce the risk of severe asthma exacerbations.
ClinicalTrials.govNCT00677209.
标准剂量和低剂量过敏原激发都是哮喘研究中一种既定的工具，旨在增进我们对变应性哮喘病理生理机制的理解。然而，激发后引发临床症状的可能性较低。因此，我们设计了一个方案，进行重复的高剂量支气管过敏原激发，以产生临床症状和气道炎症。
共有 27 名年龄在 18 至 40 岁之间、皮肤点刺试验阳性且患有轻度哮喘的患者接受了为期 4 天的重复高剂量尘螨过敏原激发。每次就诊时均测量肺功能和呼出气一氧化氮（eNO）。在过敏原激发前后进行诱导痰分析，以检测细胞计数、ECP、IL-5、INF-γ、IL-8 和转录因子 Foxp3。
我们发现肺功能显著下降，沙丁胺醇的使用增加，出现迟发性哮喘反应和支气管高反应性，以及 eNO、嗜酸性粒细胞和 Th2 细胞因子显著诱导。大多数患者的重复激发是可行的。有 2 名患者发生严重不良事件，需要使用泼尼松龙来应对夜间哮喘症状。
重复的高剂量支气管过敏原激发可导致严重的哮喘症状和明显的 Th2 介导的过敏性气道炎症。高剂量激发模型仅适合在患病志愿者中以减轻形式进行概念验证研究，以及在临床环境中使用，以降低严重哮喘恶化的风险。
ClinicalTrials.govNCT00677209。
