Mastalerz Lucyna, Trąd Gabriela, Szatkowski Piotr, Ćmiel Adam, Gielicz Anna, Kacorzyk Radosław, Plutecka Hanna, Szaleniec Joanna, Gawlewicz-Mroczka Agnieszka, Jakieła Bogdan, Sanak Marek
2nd Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
Doctoral School of Medical and Health Sciences, Jagiellonian University, Krakow, Poland.
Allergy. 2025 Feb;80(2):534-544. doi: 10.1111/all.16281. Epub 2024 Aug 23.
15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E (LTE) and assessed their diagnostic value to identify patients with N-ERD.
The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested.
Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%.
We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.
15-氧代二十碳四烯酸（15-oxo-ETE）是花生四烯酸（AA）在15-脂氧合酶-1（15-LOX-1）途径中代谢的产物。在非甾体抗炎药加重的呼吸道疾病（N-ERD）患者的鼻息肉中，15-氧代二十碳四烯酸产生过多。在本研究中，我们调查了15-氧代二十碳四烯酸和白三烯E（LTE）的全身生物合成，并评估了它们对识别N-ERD患者的诊断价值。
该研究纳入了64例N-ERD患者、59例对阿司匹林耐受良好的哮喘患者（ATA）和51例健康对照者。哮喘患者的详细临床特征包括鼻窦计算机断层扫描。使用高效液相色谱和串联质谱法测量血浆和尿液中15-氧代二十碳四烯酸水平以及尿液中LTE排泄量。测试了测量的重复性和精密度。
N-ERD患者的血浆15-氧代二十碳四烯酸水平最高（p <.001）。受试者工作特征（ROC）曲线显示，15-氧代二十碳四烯酸对N-ERD的鉴别具有一定的敏感性（血浆中为64.06%，尿液中为88.24%），而特异性相当有限。通过对变量进行建模，可以构建基于尿液LTE与15-氧代二十碳四烯酸排泄量（根据性别和慢性鼻-鼻窦炎的Lund-Mackay评分进行校正）的阿司匹林超敏诊断指数（AHDI）。在哮喘患者中，AHDI在鉴别N-ERD方面优于单次测量，ROC曲线下面积为0.889，敏感性为81.97%，特异性为87.23%，准确性为86.87%。
我们证实15-氧代二十碳四烯酸是仅次于半胱氨酰白三烯的N-ERD生物标志物。在研究的哮喘患者组中，基于这些类花生酸并根据性别和Lund-Mackay评分进行校正的指数与金标准口服阿司匹林激发试验具有相似的诊断价值。
