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外周血嗜酸性粒细胞和其他非侵入性生物标志物可用于监测嗜酸性食管炎的治疗反应。

Peripheral blood eosinophils and other non-invasive biomarkers can monitor treatment response in eosinophilic oesophagitis.

机构信息

2nd Medical Department, Technische Universität München, Munich, Germany.

Center for Digestive Diseases Eppendorf, Hamburg, Germany.

出版信息

Aliment Pharmacol Ther. 2015 Nov;42(9):1122-30. doi: 10.1111/apt.13386. Epub 2015 Aug 27.

DOI:10.1111/apt.13386
PMID:26314389
Abstract

BACKGROUND

Monitoring of the treatment response in eosinophilic oesophagitis (EoE) requires structured endoscopical and histological examination of the oesophagus. Less invasive methods would be highly desirable.

AIM

To evaluate the utility of several EoE-associated blood and serum markers in order to non-invasively monitor the response to treatment with swallowed topical corticosteroids in adult EoE patients.

METHODS

In a randomised, controlled double-blind trial blood samples of EoE patients (n = 69) were collected at baseline and after 14 days of treatment with budesonide (n = 51) or placebo (n = 18) respectively. Absolute blood eosinophil count (AEC) as well as serum levels of CCL-17, CCL-18, CCL-26, eosinophil-cationic-protein (ECP) and mast cell tryptase (MCT) were determined and correlated with oesophageal eosinophil density and with symptom and endoscopy scores.

RESULTS

Histological remission, defined as mean number of <16 eos/mm(2) hpf at end-of-treatment, was achieved in 98% of the budesonide and 0% of the placebo recipients. AEC [380.2 vs. 214.7/mm(3) (P = 0.0001)], serum-CCL-17 [294.3 vs. 257.9 pg/mL (P = 0.0019)], -CCL-26 [26.7 vs. 16.2 pg/mL (P = 0.0058)], -ECP [45.5 ± 44.7 vs. 27.5 ± 25.0 μg/L (P = 0.0016)] and -MCT [5.3 ± 2.9 vs. 4.5 ± 2.6 μg/L (P = 0.0019)] significantly decreased under budesonide but not under placebo. AEC significantly correlated with oesophageal eosinophil density before (r = 0.28, P = 0.0236) and after (r = 0.42, P = 0.0004) budesonide treatment. In ROC-AUC analyses post-treatment values of AEC were significantly associated with histological remission (ROC-AUC 0.754; 95% CI: 0.617-0.891; P = 0.0003).

CONCLUSIONS

The budesonide-induced treatment response in EoE is mirrored by several blood and serum markers, and the absolute blood eosinophil count is the most valuable as it shows correlation with the oesophageal eosinophil density.

摘要

背景

监测嗜酸性食管炎(EoE)的治疗反应需要对食管进行结构化的内镜和组织学检查。如果能有一种非侵入性的方法,那将是非常理想的。

目的

评估几种与 EoE 相关的血液和血清标志物,以便非侵入性地监测成人 EoE 患者接受口服局部皮质类固醇治疗后的反应。

方法

在一项随机、对照、双盲试验中,分别在基线和接受布地奈德(n=51)或安慰剂(n=18)治疗 14 天后采集 EoE 患者(n=69)的血液样本。测定绝对血嗜酸性粒细胞计数(AEC)以及血清 CCL-17、CCL-18、CCL-26、嗜酸性粒细胞阳离子蛋白(ECP)和肥大细胞胰蛋白酶(MCT)水平,并与食管嗜酸性粒细胞密度以及症状和内镜评分相关。

结果

在接受布地奈德治疗的患者中,98%达到组织学缓解,定义为治疗结束时平均每高倍视野(hpf)<16 个嗜酸性粒细胞(P=0.0001),而接受安慰剂治疗的患者中无 1 例达到缓解。AEC[380.2 与 214.7/mm3(P=0.0001)]、血清 CCL-17[294.3 与 257.9 pg/mL(P=0.0019)]、CCL-26[26.7 与 16.2 pg/mL(P=0.0058)]、ECP[45.5±44.7 与 27.5±25.0 μg/L(P=0.0016)]和 MCT[5.3±2.9 与 4.5±2.6 μg/L(P=0.0019)]在布地奈德治疗后显著降低,但在安慰剂治疗后无显著降低。AEC 在布地奈德治疗前后均与食管嗜酸性粒细胞密度显著相关(治疗前 r=0.28,P=0.0236;治疗后 r=0.42,P=0.0004)。在 ROC-AUC 分析中,治疗后 AEC 值与组织学缓解显著相关(ROC-AUC 0.754;95%CI:0.617-0.891;P=0.0003)。

结论

EoE 患者接受布地奈德治疗后的反应与多种血液和血清标志物相关,绝对血嗜酸性粒细胞计数最有价值,因为它与食管嗜酸性粒细胞密度相关。

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