Aspirin hypersensitivity diagnostic index (AHDI): In vitro test for diagnosing of N‐ERD based on urinary 15‐oxo‐ETE and LTE4 excretion

Abstract

AbstractBackground15‐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.