Late Breaking Abstract - Metabolomic endo-phenotypes based on eicosanoids of 15-lipooxygenase pathway in AERD

<bold>Background:</bold> Metabolism of arachidonic acid (AA) in aspirin-exacerbated respiratory disease (AERD) presented imbalance between the proinflammatory and anti-inflammatory eicosanoids. 15-hydroxy-eicosatetraenoic-acid (15-HETE) and 15-oxo-eicosatetraenoic acid (15-oxo-ETE) are included in AA pathway regulated by 15-lipoxygenases-1 (15-LOX-1). <bold>Objectives:</bold> To identify possible metabolomic clusters basing on the concentration of 15-HETE and 15-oxo-ETE in plasma and in urine with the hierarchical cluster analysis (HCA) in a cohort of patients with AERD. <bold>Methods:</bold> 78 patients with AERD were enrolled to the cluster analysis. 23 variables covering demographical, clinical, biochemical, and therapeutic data as well as plasma and urinary concentration of selected eicosanoids measured by high-performance liquid chromatography and tandem mass spectrometry, were considered in the HCA. <bold>Results:</bold> Two clusters (endo-phenotypes) were distinguished within the AERD cohort. Cluster 1 subjects were older (p=0.028) with higher body mass index (p=0.000), had severe and poor control asthma with lower FEV1 (p=0.016), also had higher concentration of plasma 15-HETE and plasma 15-oxo-ETE as well as lower concentration of urinary 15-oxo-ETE. There were not significant differences regarding blood eosinophil count (p=0.695), Lund-Mackay score on paranasal sinus computed tomography (p=0.879) and urinary leukotriene E4 concentration (p=0.556). <bold>Conclusions:</bold> A higher concentration of serum 15-oxo-ETE is associated with more severe asthma and worse disease control without affecting the course of chronic rhinosinusitis with nasal polyps in AERD patients. Our results support a more complex pathobiology of aspirin hypersensitivity.