Background15‐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 E4 (LTE4) and assessed their diagnostic value to identify patients with N‐ERD.MethodsThe 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 LTE4 excretion were measured using high‐performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested.ResultsPlasma 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 LTE4‐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%.ConclusionsWe 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.

中文翻译：

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阿司匹林过敏诊断指数 (AHDI)：根据尿液 15-oxo-ETE 和 LTE4 排泄来诊断 N-ERD 的体外测试


背景15-氧代-二十碳四烯酸（15-氧代-ETE）是15-脂氧合酶-1（15-LOX-1）途径中花生四烯酸（AA）代谢的产物。患有非甾体类抗炎药加重的呼吸道疾病（N-ERD）患者的鼻息肉中 15-oxo-ETE 过量产生。在这项研究中，我们研究了 15-oxo-ETE 和白三烯 E4 (LTE4) 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。方法该研究包括 64 名 N-ERD 患者、59 名对阿司匹林耐受良好的哮喘患者（ ATA）和 51 名健康对照。哮喘患者的全面临床特征包括鼻旁窦的计算机断层扫描。使用高效液相色谱和串联质谱法测量血浆和尿液 15-oxo-ETE 水平以及尿液 LTE4 排泄量。测试了测量的重复性和精确度。结果血浆 15-oxo-ETE 水平在 N-ERD 中最高 (p < .001)。受试者操作特征（ROC）显示，15-oxo-ETE 对 N-ERD 辨别具有一定的敏感性（血浆中为 64.06%，尿液中为 88.24%），但特异性相当有限。变量建模允许构建基于尿液 LTE4-to-15-oxo-ETE 排泄的阿司匹林过敏诊断指数 (AHDI)，并校正性别和慢性鼻窦炎的 Lund-Mackay 评分。 AHDI 在区分哮喘患者 N-ERD 方面优于单一测量，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%。结论我们确认 15-oxo-ETE 是仅次于半胱氨酰白三烯的第二个测量方法N-ERD 的生物标志物。 基于这些类二十烷酸并校正性别和 Lund-Mackay 评分的指数与哮喘研究组患者的金标准口服阿司匹林激发试验具有相似的诊断价值。