Changes in Type 2 Biomarkers After Anti-IL5 Treatment in Patients With Severe Eosinophilic Asthma

Abstract

Patients with severe eosinophilic asthma (SEA) suffer from frequent asthma exacerbations, where eosinophils are major effector cells in airway inflammation, and anti-interleukin (IL)-5 becomes an effective treatment modality to control eosinophilic inflammation of SEA. Fifteen patients with SEA who had been treated with anti-IL5 (reslizumab, 100 mg monthly intravenously) for 6 months at Ajou University Hospital (Suwon, Korea) were enrolled in this study. Clinical parameters, including total blood eosinophil count (TEC), FEV1%, fractional exhaled nitric oxide (FeNO) levels, and serum biomarkers such as eosinophil-derived neurotoxin (EDN), periostin (PON), and transforming growth factor-β1 (TGF-β1), were analyzed. EDN levels and TEC decreased significantly after 1 month of treatment (P < 0.05 for both), while no changes were noted in FeNO/PON/TGF-β1 levels. FEV1% increased after 2 months of treatment (P < 0.05). A positive correlation was observed between TEC and EDN levels (r = 0.60, P = 0.02). Significant negative correlations were noted between age and TEC/EDN levels (r = -0.57, P = 0.02 and r = -0.56, P = 0.03, respectively). Baseline TEC was higher in the EDN-responder group (≥75% decrease) than in the non-responder group (P = 0.06) with a positive correlation between %reduction in EDN and TEC (r = 0.67, P = 0.01). The onset age was younger and asthma duration was longer in the FEV1%-non-responder group (<12% increase) than in the FEV1%-responder group (P = 0.07 and P = 0.007, respectively). In conclusion, changes in the serum EDN level may be a potential biomarker for monitoring eosinophilic inflammation after anti-IL5 treatment in SEA, which is affected by onset age and asthma duration.

Keywords: Asthma; antibodies, monoclonal; asthma exacerbation; eosinophils; inflammation; interleukin-5.

Fig. 1. Changes in FEV1 (%pred value, A), FeNO (B), TECs (C), and EDN (D) levels during anti-IL5 treatment in patients with severe eosinophilic asthma. (A and B) show mean with standard error of mean. (C and D) show boxplot with median and interquartile by Tukey method.

FEV1, forced expiratory volume in 1 second; FeNO, fractional exhaled nitric oxide; TEC, total eosinophil count; EDN, eosinophil-derived neurotoxin; V, visit; NS, not significant. ^*P < 0.05, ^†P < 0.001.

Fig. 2. Comparison of responders and non-responders according to changes in EDN/FeNO/FEV1% levels.

EDN, eosinophil-derived neurotoxin; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second. ^*P < 0.05, ^†P < 0.01.