Persistent eosinophilic inflammation in adult asthmatics with high serum and urine levels of leukotriene E4

Abstract

Background: Cysteinyl leukotrienes (CysLTs) are key mediators for bronchoconstriction, eosinophil recruitment and mucus production in the airways of asthmatic patients. To better understand the role of CysLTs in different asthma phenotypes, we compared the levels of arachidonic acid metabolites in relation to asthma control status and phenotypes in adult asthmatics on regular anti-asthma medications. Methods: A total of 137 adult asthmatics (47 with aspirin-exacerbated respiratory disease [AERD] and 90 asthmatics with aspirin-tolerant asthma [ATA]) and 20 healthy controls were enrolled. Arachidonic acid metabolites in serum and urine were analyzed using LC-MS/MS methods, and clinical data, including asthma control status, exhaled NO (FeNO) and lung function tests, were collected. Results: Urine LTE4 levels were significantly higher in AERD patients on inhaled corticosteroid-long-acting β2-agonist plus leukotriene receptor antagonist (LTRA) treatment than in ATA patients (P=0.001). No differences were found in the serum or urine levels of 15-HETE, TXB2, or PGF2α. High serum LTE4 levels were associated with lower FEV1% and uncontrolled status in AERD patients (P=0.006 and P=0.002, respectively), but not in ATA patients. Multivariate analysis demonstrated that blood eosinophil counts, FeNO levels and aspirin hypersensitivity were significant factors affecting urine LTE4 levels. Conclusion: Despite LTRA treatment in AERD, the LTE4 levels remained high and showed close associations with blood eosinophilia, high FeNO levels and impaired disease control. Our real-world evidence indicates that control of asthma is not fully achieved by blocking the CysLT pathway with LTRA. Thus, introduction of treatment modalities targeting eosinophilia could be a better option for patients with high CysLTs.