Struß Nadja, Badorrek Philipp, Schwarz Katharina, Windt Horst, Straff Wolfgang, Höflich Conny, Hohlfeld Jens M
Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany.
German Environment Agency (UBA), Environmental Medicine and Health Effects Assessment, Berlin, Germany.
Int Arch Allergy Immunol. 2025 May 6:1-10. doi: 10.1159/000545509.
To determine threshold concentrations of pollen inducing symptoms in seasonal allergic rhinitis patients has been a challenge for decades. Allergen challenge chambers (ACC) allow a controlled, reproducible experimental design to address this problem. Hitherto, ACCs were only run with high pollen concentrations.
The Fraunhofer ACC was technically modified to deploy very low pollen concentrations. Then, adults with birch pollen-induced allergic rhinitis were challenged with varying birch pollen concentrations using a patient-blinded, sham challenge-controlled, part-randomized, titrate-to-effect clinical study setting. Mean increase in Total Nasal Symptom Score (TNSS) ≥0.55 compared to sham challenge was regarded as minimal clinically important difference (MCID). Further endpoints were nasal secretion weight, exhaled nitric oxide (FeNO), and inflammatory cells from nasal lavage.
Fifteen participants with mild to moderate allergic rhinitis participated in the experimental study part (mean age 45 years [22-64]; 7 females). Mean TNSS was: 1.08 at 0 pollen/m3; 1.05 at 10 pollen/m3; 1.2 at 50 pollen/m3; 1.74 at 100 pollen/m3; 1.61 at 200 pollen/m3; 2.79 at 1,000 pollen/m3. MCID of TNSS was observed at 100, 200, and 1,000 pollen/m3. More than half of the study population showed a lack of response at 10, 50, and 200 pollen/m3. Nasal secretion increased slightly with concentration. No clinically meaningful results could be derived from FeNO and inflammatory cells.
The applied technical modification of the Fraunhofer ACC produced stable, low pollen concentrations. Based on mean TNSS data, the threshold concentration for inducing symptoms with birch pollen was 50-100 pollen/m3.
数十年来，确定季节性变应性鼻炎患者出现症状的花粉阈值浓度一直是一项挑战。变应原激发试验舱（ACC）允许采用可控、可重复的实验设计来解决这一问题。迄今为止，ACC仅在高花粉浓度下运行。
对弗劳恩霍夫ACC进行技术改造，以设置极低的花粉浓度。然后，在一项患者盲法、假激发对照、部分随机、剂量递增至有效效应的临床研究中，用不同浓度的桦树花粉对桦树花粉诱发的变应性鼻炎成年患者进行激发试验。与假激发相比，总鼻症状评分（TNSS）平均增加≥0.55被视为最小临床重要差异（MCID）。其他终点指标包括鼻分泌物重量、呼出一氧化氮（FeNO）以及鼻灌洗中的炎性细胞。
15名轻至中度变应性鼻炎参与者参加了实验研究部分（平均年龄45岁[22 - 64岁]；7名女性）。平均TNSS为：花粉浓度0粒/m³时为1.08；10粒/m³时为1.05；50粒/m³时为1.2；100粒/m³时为1.74；200粒/m³时为1.61；1000粒/m³时为2.79。在花粉浓度100、200和1000粒/m³时观察到TNSS的MCID。超过一半的研究人群在花粉浓度10、50和200粒/m³时无反应。鼻分泌物随浓度略有增加。FeNO和炎性细胞未得出具有临床意义的结果。
对弗劳恩霍夫ACC进行的技术改造产生了稳定的低花粉浓度。基于平均TNSS数据，桦树花粉诱发症状的阈值浓度为50 - 100粒/m³。
