高迁移率族蛋白B1：中重度哮喘儿童吸入性糖皮质激素治疗反应的生物标志物。

High mobility group box 1: Biomarker of inhaled corticosteroid treatment response in children with moderate-severe asthma.

作者信息

Manti Sara, Leonardi Salvatore, Parisi Giuseppe F, De Vivo Dominique, Salpietro Annamaria, Spinuzza Antonietta, Arrigo Teresa, Salpietro Carmelo, Cuppari Caterina

出版信息

Allergy Asthma Proc. 2017 May 1;38(3):197-203. doi: 10.2500/aap.2017.38.4047.

DOI:10.2500/aap.2017.38.4047

PMID:28441990

Abstract

BACKGROUND

High mobility group box 1 (HMGB1) is abnormally expressed in serum and sputum of patients with allergic asthma.

OBJECTIVE

The aim of this study was to investigate the role of HMGB1 as guidance for treatment management of children with asthma.

METHODS

Thirty children with asthma and 44 healthy children were enrolled. The patients were classified according to Global Initiative for Asthma Guideline disease severity criteria. Sputum HMGB1 levels and lung function index (percentage forced expiratory volume in 1 second [FEV1%]) were recorded in the cohort study at baseline (T0) and after 3 (T3) and 6 (T6) months of inhaled corticosteroids (ICS) treatment.

RESULTS

Sputum HMGB1 levels were significantly higher in all the patients with asthma (p < 0.001). An inverse correlation between sputum HMGB1 levels and pulmonary function parameters was observed only in the children with moderate asthma (T0: FEV1%, r = -0.9891, p < 0.001; T3: FEV1%, r = -0.6763, p < 0.001; T6: FEV1%, r = -0.5419, p < 0.05) and in the children with severe asthma (T0: FEV1%, r = -0.8696, p < 0.001; T3: FEV1%, r = -0.6477, p < 0.05; T6: FEV1%, r = -0.8627, p < 0.001). After ICS treatment, a significant decrease of sputum HMGB1 levels was noted in moderate (T0 [93.44 ± 20.65 ng/mL] versus T3 [77.96 ± 1.81 ng/mL] versus T6 [67.75 ± 3.01 ng/mL]; p < 0.0001) and in the children with severe asthma (T0 [130.3 ± 7.48 ng/mL] versus T3 [156.9 ± 1.09 ng/mL] versus T6 [116.08 ± 4.77 ng/mL]; p < 0.0001) data are mean ± standard deviation, respectively. The area under the receiver operating characteristic curve, performed to define the diagnostic profile of sputum HMGB1 levels in identifying the children with asthma, was 0.713.

CONCLUSION

In addition to the findings that HMGB1 is a sensitive biomarker of allergic asthma in children, our data demonstrated a significant correlation between the decrease of HMGB1 levels and a successful treatment response.

摘要

背景

高迁移率族蛋白B1（HMGB1）在过敏性哮喘患者的血清和痰液中异常表达。

目的

本研究旨在探讨HMGB1在儿童哮喘治疗管理中的指导作用。

方法

纳入30例哮喘儿童和44例健康儿童。根据全球哮喘防治创议（GINA）疾病严重程度标准对患者进行分类。在队列研究中，记录基线时（T0）、吸入糖皮质激素（ICS）治疗3个月（T3）和6个月（T6）后痰液中HMGB1水平和肺功能指标（第1秒用力呼气容积百分比[FEV1%]）。

结果

所有哮喘患者痰液中HMGB1水平均显著升高（p<0.001）。仅在中度哮喘儿童（T0：FEV1%，r = -0.9891，p<0.001；T3：FEV1%，r = -0.6763，p<0.001；T6：FEV1%，r = -0.5419，p<0.05）和重度哮喘儿童（T0：FEV1%，r = -0.8696，p<0.001；T3：FEV1%，r = - \ 0.6477，p<0.05；T6：FEV1%，r = -0.8627，p<0.001）中观察到痰液中HMGB1水平与肺功能参数呈负相关。ICS治疗后，中度哮喘儿童（T0[93.44±20.65 ng/mL] vs T3[77.96±1.81 ng/mL] vs T6[67.75±3.01 ng/mL]；p<0.0001）和重度哮喘儿童（T0[130.3±7.48 ng/mL] vs T3[156.9±1.09 ng/mL] vs T6[116.08±4.77 ng/mL]；p<0.0001）痰液中HMGB1水平显著降低（数据分别为平均值±标准差）。为确定痰液中HMGB1水平在识别哮喘儿童中的诊断特征而绘制的受试者工作特征曲线下面积为0.713。