Unique effect of aspirin on local 15-oxo-eicosatetraenoic acid synthesis in asthma patients with aspirin hypersensitivity

IF 4.6 2区医学 Q2 ALLERGY Clinical and Translational Allergy Pub Date : 2024-12-25 DOI:10.1002/clt2.70004

Piotr Szatkowski, Anna Gielicz, Adam Stępień, Patryk Hartwich, Radosław Kacorzyk, Hanna Plutecka, Adam Ćmiel, Gabriela Trąd-Wójcik, Marek Sanak, Lucyna Mastalerz

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Abstract

Background

Nonsteroidal anti-inflammatory drugs–exacerbated respiratory disease (NSAIDs-ERD) is characterized by altered arachidonic acid (AA) metabolism. Aspirin hypersensitivity is diagnosed using aspirin challenge, while induced sputum is collected to perform cell counts and to identify local biomarkers in induced sputum supernatant (ISS). This study aimed to assess the levels of a newly identified eicosanoid, 15-oxo-eicosatetraenoic acid (15-oxo-ETE), in ISS at baseline and during aspirin-induced bronchospasm in patients with NSAIDs-ERD.

Methods

Oral aspirin challenge was performed in 27 patients with NSAIDs-ERD and in 17 patients with aspirin-tolerant asthma (ATA) serving as controls. Sputum was collected before and after aspirin challenge to determine eosinophil, neutrophil, macrophage, and lymphocyte counts as well as the concentration of AA metabolites via 15-lipoxygenase-1 (15-LOX-1) and 5-LOX pathways in ISS. Chromatography–tandem mass spectrometry was used to measure ISS levels of 15-oxo-ETE, 15-hydroxyeicosatetranoic acid (15-HETE), and leukotriene E₄ (LTE₄).

Results

At baseline, ISS levels of 15-oxo-ETE were higher in NSAIDs-ERD than in ATA (p = 0.04). In contrast, baseline 15-HETE levels in ISS were lower in patients with NSAIDs-ERD (p = 0.03). After aspirin challenge, 15-oxo-ETE levels decreased only in patients with NSAIDs-ERD (p = 0.001) who developed bronchospasm. In both study groups, there was a reduction in sputum macrophage count after aspirin challenge (p = 0.03 and p = 0.02, respectively) irrespective of bronchospasm.

Conclusions

Patients with NSAIDs-ERD are characterized by higher baseline 15-oxo-ETE levels in ISS than patients with ATA. Aspirin-induced bronchospasm inhibited the local generation of 15-oxo-ETE.

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阿司匹林对阿司匹林过敏哮喘患者局部15-氧-二十碳四烯酸合成的独特影响。

背景：非甾体抗炎药加重呼吸系统疾病（NSAIDs-ERD）以花生四烯酸（AA）代谢改变为特征。阿司匹林超敏反应是通过阿司匹林刺激来诊断的，同时收集诱导痰进行细胞计数，并在诱导痰上清（ISS）中识别局部生物标志物。本研究旨在评估一种新发现的类二十碳酸15-氧-二十碳四烯酸（15-氧- ete）在非甾体抗炎药- erd患者的ISS基线和阿司匹林诱导支气管痉挛期间的水平。方法：对27例非甾体抗炎药- erd患者和17例阿司匹林耐受性哮喘（ATA）患者进行口服阿司匹林治疗。通过15-脂氧合酶-1 （15-LOX-1）和5-LOX途径测定ISS患者服用阿司匹林前后的痰液中嗜酸性粒细胞、中性粒细胞、巨噬细胞和淋巴细胞的计数以及AA代谢物的浓度。采用色谱-串联质谱法测定15-氧- ete、15-羟基二碳四烷酸（15-HETE）和白三烯E4 （LTE4）的ISS水平。结果：基线时，NSAIDs-ERD患者15-oxo-ETE的ISS水平高于ATA患者（p = 0.04）。相比之下，NSAIDs-ERD患者ISS的基线15-HETE水平较低（p = 0.03）。服用阿司匹林后，只有发生支气管痉挛的非甾体抗炎药- erd患者15-oxo-ETE水平下降（p = 0.001）。在两个研究组中，与支气管痉挛无关，阿司匹林刺激后痰中巨噬细胞计数减少（分别为p = 0.03和p = 0.02）。结论：ISS患者nsaid - erd的基线15-oxo-ETE水平高于ATA患者。阿司匹林引起的支气管痉挛抑制15-oxo-ETE的局部生成。

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来源期刊

Clinical and Translational Allergy Immunology and Microbiology-Immunology

CiteScore

7.50

自引率

4.50%

发文量

117

审稿时长

12 weeks

期刊介绍： Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience. Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.