Jang Jae Hyuk, Woo Seong Dae, Lee Youngsoo, Kim Chang Keun, Shin Yoo Seob, Ye Young Min, Park Hae Sim
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
Asthma and Allergy Center, Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea.
Allergy Asthma Immunol Res. 2021 Mar;13(2):330-338. doi: 10.4168/aair.2021.13.2.330.
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 ( < 0.05 for both), while no changes were noted in FeNO/PON/TGF-β1 levels. FEV1% increased after 2 months of treatment ( < 0.05). A positive correlation was observed between TEC and EDN levels ( = 0.60, = 0.02). Significant negative correlations were noted between age and TEC/EDN levels ( = -0.57, = 0.02 and = -0.56, = 0.03, respectively). Baseline TEC was higher in the EDN-responder group (≥75% decrease) than in the non-responder group ( = 0.06) with a positive correlation between %reduction in EDN and TEC ( = 0.67, = 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 ( = 0.07 and = 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.
重度嗜酸性粒细胞性哮喘(SEA)患者频繁出现哮喘急性发作,其中嗜酸性粒细胞是气道炎症的主要效应细胞,抗白细胞介素(IL)-5成为控制SEA嗜酸性粒细胞炎症的有效治疗方式。本研究纳入了15例在韩国水原市阿朱大学医院接受抗IL-5(瑞利珠单抗,每月静脉注射100mg)治疗6个月的SEA患者。分析了包括全血嗜酸性粒细胞计数(TEC)、第一秒用力呼气容积百分比(FEV1%)、呼出一氧化氮分数(FeNO)水平以及嗜酸性粒细胞衍生神经毒素(EDN)、骨膜蛋白(PON)和转化生长因子-β1(TGF-β1)等血清生物标志物在内的临床参数。治疗1个月后EDN水平和TEC显著下降(两者均P<0.05),而FeNO/PON/TGF-β1水平无变化。治疗2个月后FEV1%升高(P<0.05)。观察到TEC与EDN水平呈正相关(r = 0.60,P = 0.02)。年龄与TEC/EDN水平呈显著负相关(分别为r = -0.57,P = 0.02和r = -0.56,P = 0.03)。EDN反应者组(下降≥75%)的基线TEC高于无反应者组(P = 0.06),EDN下降百分比与TEC呈正相关(r = 0.67,P = 0.01)。FEV1%无反应者组(增加<12%)的发病年龄比FEV1%反应者组年轻,哮喘病程更长(分别为P = 0.07和P = 0.007)。总之,血清EDN水平的变化可能是监测SEA患者抗IL-5治疗后嗜酸性粒细胞炎症的潜在生物标志物,其受发病年龄和哮喘病程的影响。