Serum and Nasal Lavage Fluid Eosinophil-Derived Neurotoxin Levels in Clinically Defined Asthma Phenotypes

Abstract

Background: As a surrogate for eosinophilic activation, eosinophil-derived neurotoxin (EDN) is a potential clinical biomarker. However, EDN levels and discriminatory ability in different asthma phenotypes are unknown. We quantified serum and nasal lavage fluid (NLF) EDN levels and assessed the potential to differentiate clinically defined asthma phenotypes in an adult-representative sample. Methods: A total of 1499 serum and 386 NLF samples from individuals with current asthma obtained from the West Sweden Asthma Study were analyzed for EDN. Eosinophilic asthma was defined as blood eosinophil count of ≥ 300 cells/mm3, T2-high asthma was defined as blood eosinophil count of ≥ 300 cells/mm3 or fractional exhaled nitric oxide (FeNO) levels of ≥ 25 ppb. Other asthma phenotypes were defined based on presence of atopy, chronic rhinosinusitis (CRS), nasal polyposis, and obesity. Results: Subjects with eosinophilic asthma had higher serum and NLF EDN levels than those with non-eosinophilic asthma. In ROC analyses, serum EDN provided excellent discrimination between eosinophilic and non-eosinophilic asthma (area under curve [AUC] = 0.84, 95% CI = 0.82–0.86); the corresponding AUC for NLF EDN was 0.67 (95% CI = 0.62–0.73). Serum and NLF EDN were higher in atopic asthma, T2-high asthma, and asthma with nasal polyposis compared to their counterparts, but not in asthma with CRS. The highest absolute values of serum and NLF EDN were observed in the high eosinophil + FeNO group, followed by the high-eosinophil-only and high-FeNO-only groups. Conclusion: Both serum and NLF EDN were higher in those with eosinophilic compared to non-eosinophilic asthma. However, only serum EDN appears to distinguish eosinophilic asthma in ROC analyses.