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

Abstract

BackgroundNonsteroidal 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.MethodsOral 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).ResultsAt 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.ConclusionsPatients 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.