Plasma 15-Hydroxyeicosatetraenoic Acid Predicts Treatment Outcomes in Aspirin-Exacerbated Respiratory Disease

Abstract

Aspirin desensitization followed by daily aspirin provides therapeutic benefits to patients with aspirin exacerbated respiratory disease (AERD). It is not well understood how eicosanoid levels change during aspirin treatment. We investigated associations between clinical outcomes of aspirin treatment and plasma eicosanoid levels in AERD patients. Thirty-nine AERD patients were offered aspirin treatment (650 mg twice daily) for four weeks. Respiratory parameters and plasma levels of multiple eicosanoids were recorded at baseline and after four weeks of aspirin therapy using the Asthma Control Test (ACT) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Respiratory function was evaluated using the forced expiratory volume in 1 second (FEV1) and nasal peak flow (NPF). After aspirin treatment, respiratory symptoms improved in sixteen patients, worsened in twelve patients, and did not change in four. Seven patients were unable to complete the desensitization protocol. Patients with symptom improvement had higher baseline plasma 15-hydroxyeicosatetraenoic acid (15-HETE) levels than patients with symptom worsening: 7006 (IQR 6056-8688) vs. 4800 (IQR 4238-5575) pg/ml, p=0.0005. Baseline 15-HETE plasma levels positively correlated with the change in ACT score (r=0.61, p=0.001) and in FEV1 after four weeks of aspirin treatment (r=0.49, p=0.01). It inversely correlated with RQLQ score (r=-0.58, p=0.002). Peripheral eosinophil counts after four weeks of aspirin treatment inversely correlated with the change in ACT score (r=-0.45, p=0.02) and change in FEV1 (r=-0.68, p=0.0001). In AERD patients, low baseline 15-HETE plasma levels and increased eosinophilia during aspirin treatment are associated with worsening of respiratory symptoms and function.