Methods: An untargeted profile of serum from asthmatics in Group 1 (AERD: n = 45, and aspirin tolerant asthma <ATA>: n = 44) and normal controls (n = 28) was developed using UHPLC/Q-ToF MS system. The metabolites which discriminate AERD from ATA were quantified in serum and urine. The serum metabolites were validated in Group 2 composing 50 AERD and 50 ATA patients.
Results: The clear discrimination of metabolome was found between AERD and ATA and 11 metabolites correlated with clinical phenotypes of AERD. The levels of LTE4 and LTE4/PGF2α ratio from both serum and urine were significantly higher in AERD than in ATA (P <0.05) in Group 1. Serum 15-HETE levels were significantly higher in AERD than in ATA (P=0.028) in Group 1 which were replicated in in Group 2 (AERD vs. ATA, P < 0.05, respectively). Serum LTE4/PGF2α ratio discriminated AERD from ATA with 71.6% sensitivity and 62.8% specificity (AUC = 0.732, P <0.001). The levels of urine LTE4 and PGF2α were significantly correlated with the fall of FEV1% after lysine-aspirin bronchoprovocation test in AERD (r=0.463, P=0.008, and r=0.610, P<0.001, respectively).
Conclusions: We identified useful serum biomarkers for AERD, LTE4 and LTE4/PGF2α ratio using UHPLC/Q-ToF MS based metabolomics, which were closely related with major pathogenic mechanisms of AERD.