Biomarkers for predicting response to aspirin therapy in aspirin-exacerbated respiratory disease

Abstract

Background: Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin-exacerbated respiratory disease (AERD). Objective: To assess clinical features as well as genetic, immune, cytological and biochemical biomarkers that might predict a positive response to high-dose aspirin therapy in AERD. Methods: We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52-week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high-dose aspirin were defined as patients with improvement in 5-item Asthma Control Questionnaire score, 22-item Sino-Nasal Outcome Test (SNOT-22) score and forced expiratory volume in 1 second at 52 weeks. Results: There were 28 responders (82%). Positive baseline predictors of response included female sex (p =.002), higher SNOT-22 score (p =.03), higher blood eosinophil count (p =.01), lower neutrophil percentage in induced sputum (p =.003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (p =.004) and lower expression of the proteoglycan 2 gene, PRG2 (p =.01). The best prediction model included Asthma Control Test and SNOT-22 scores, blood eosinophils and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. Conclusions and Clinical Relevance: Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression and low PRG2 expression may predict a positive response to long-term high-dose aspirin therapy in patients with AERD.