TY - JOUR A1 - Eickmeier, Olaf A1 - Zißler, Ulrich M. A1 - Wittschorek, Julia A1 - Unger, Frederike A1 - Schmitt-Grohé, Sabina A1 - Schubert, Ralf A1 - Herrmann, Eva A1 - Zielen, Stefan T1 - Clinical relevance of Aspergillus fumigatus sensitization in cystic fibrosis T2 - Clinical & experimental allergy N2 - Rationale: The clinical relevance of sensitization to Aspergillus (A) fumigatus in cystic fibrosis (CF) is unclear. Some researchers propose that specific A fumigatus IgE is an innocent bystander, whereas others describe it as the major cause of TH‐2‐driven asthma‐like disease. Objectives: Lung function parameters in mild CF patients may be different in patients with and without A fumigatus sensitization. We aimed to ascertain whether allergen exposure to A fumigatus by bronchial allergen provocation (BAP) induces TH‐2 inflammation comparable to an asthma‐like disease. Methods: A total of 35 patients, aged 14.8 ± 8.5 years, and 20 healthy controls were investigated prospectively. The patients were divided into two groups: group 1 (n = 18): specific (s)IgE negative, and group 2 (n = 17): sIgE positive (≥0.7 KU/L) for A fumigatus. Lung function, exhaled NO, and induced sputum were analysed. All sensitized patients with an FEV1 > 75% (n = 13) underwent BAP with A fumigatus, and cell counts, and the expression of IL‐5, IL‐13, INF‐γ, and IL‐8 as well as transcription factors T‐bet, GATA‐3, and FoxP3, were measured. Results: Lung function parameters decreased significantly compared to controls, but not within the CF patient group. After BAP, 8 of 13 patients (61%) had a significant asthmatic response and increased eNO 24 hours later. In addition, marked TH‐2‐mediated inflammation involving eosinophils, IL‐5, IL‐13, and FoxP3 became apparent in induced sputum cells. Conclusion: Our study demonstrated the clinical relevance of A fumigatus for the majority of sensitized CF patients. A distinct IgE/TH‐2‐dominated inflammation was found in induced sputum after A fumigatus exposure. KW - Aspergillus fumigatus KW - basic mechanisms KW - bronchial allergen provocation KW - clinical immunology KW - cystic fibrosis KW - IgE Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56311 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-563110 VL - 50.2020 SP - 325 EP - 333 PB - Wiley-Blackwell CY - Oxford ER -