阿司匹林对阿司匹林超敏反应哮喘患者局部15-氧代-二十碳四烯酸合成的独特作用。

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

作者信息

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

机构信息

2nd Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.

Doctoral School of Medical and Health Sciences, Jagiellonian University, Krakow, Poland.

出版信息

Clin Transl Allergy. 2024 Dec;14(12):e70004. doi: 10.1002/clt2.70004.

DOI:10.1002/clt2.70004

PMID:39722441

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11669626/

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 E (LTE).

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.

摘要

背景

非甾体抗炎药加重的呼吸系统疾病（NSAIDs-ERD）的特征是花生四烯酸（AA）代谢改变。阿司匹林超敏反应通过阿司匹林激发试验诊断，同时收集诱导痰以进行细胞计数并鉴定诱导痰上清液（ISS）中的局部生物标志物。本研究旨在评估新鉴定的类二十烷酸15-氧代-二十碳四烯酸（15-oxo-ETE）在NSAIDs-ERD患者基线时以及阿司匹林诱导的支气管痉挛期间ISS中的水平。

方法

对27例NSAIDs-ERD患者和17例作为对照的阿司匹林耐受哮喘（ATA）患者进行口服阿司匹林激发试验。在阿司匹林激发试验前后收集痰液，以确定嗜酸性粒细胞、中性粒细胞、巨噬细胞和淋巴细胞计数，以及通过ISS中的15-脂氧合酶-1（15-LOX-1）和5-LOX途径的AA代谢物浓度。采用色谱-串联质谱法测量ISS中15-oxo-ETE、15-羟基二十碳四烯酸（15-HETE）和白三烯E（LTE）的水平。

结果

基线时，NSAIDs-ERD患者ISS中15-oxo-ETE水平高于ATA患者（p = 0.04）。相反，NSAIDs-ERD患者ISS中基线15-HETE水平较低（p = 0.03）。阿司匹林激发试验后，仅在发生支气管痉挛的NSAIDs-ERD患者中15-oxo-ETE水平降低（p = 0.001）。在两个研究组中，无论是否发生支气管痉挛，阿司匹林激发试验后痰巨噬细胞计数均减少（分别为p = 0.03和p = 0.02）。