儿童重症哮喘全身糖皮质激素的反应：表型和亚型特征
2016/11/09
摘要
背景：儿童严重哮喘是一种异质性疾病，与糖皮质激素治疗的可变反应相关。儿童皮质激素反应性评估的标准缺乏。
目的：本研究的目的是表征系统性糖皮质激素在重症哮喘患儿肌内注射治疗后的反应，以此确定肌肉注射反应的表型和分子预测因子。
方法：对56例重症哮喘儿童患者在基线和14天肌内注射曲安奈德后的生活质量、呼出的一氧化氮、血嗜酸性粒细胞、肺功能及炎性细胞因子及外周血单核细胞趋化因子mRNA基因的表达进行了评估。采用哮喘控制问卷将重症哮喘儿童分到糖皮质激素反应组。
结果：三组患有严重哮喘的儿童被确定：严重哮喘得到控制的儿童、曲安奈德注射后哮喘得到控制的儿童、哮喘没有得到控制的儿童。在基线时，这些群体的表型相似。注射之后，症状、肺功能、呼出气一氧化氮、血嗜酸性粒细胞等被发现组别之间不一致。临床表型预测在预测注射之后的反应中的应用是有限的，而与IL-2、IL-10和TNF信号通路相关的炎性细胞因子和趋化因子，即：AIMP1、CCR2、 IL10RB、和IL5的系统的mRNA的表达，可强烈区分那些未能通过曲安奈德管理来控制哮喘的孩子。
结论：重症哮喘患儿的系统性糖皮质激素的反应性是异质性的。可供选择的预测模型，包括分子亚型以及临床表型特征需要被用来确定哪一个孩子从临床中系统的糖皮质激素治疗中受益最大，即使有潜在的副作用。
关键词：儿童哮喘；糖皮质激素；基因表达；表型；难治性哮喘；严重哮喘
（杨冬 审校）
J Allergy Clin Immunol Pract. 2016 Sep 21. pii: S2213-2198(16)30376-2. doi: 10.1016/j.jaip.2016.08.001. [Epub ahead of print]
Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features.
Fitzpatrick AM1, Stephenson ST2, Brown MR2, Nguyen K2, Douglas S2, Brown LA3.
Author information
Abstract
BACKGROUND:Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking.
OBJECTIVE:This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response.
METHODS:Asthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups.
RESULTS:Three groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, AIMP1, CCR2, IL10RB, and IL5, strongly differentiated children who failed to achieve control with triamcinolone administration.
CONCLUSIONS:Systemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects.
Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
KEYWORDS:Childhood asthma; Corticosteroid; Gene expression; Phenotype; Refractory asthma; Severe asthma
J Allergy Clin Immunol Pract. 2016 Sep 21. pii: S2213-2198(16)30376-2. doi: 10.1016/j.jaip.2016.08.001. [Epub ahead of print]
