儿童严重哮喘的分子表型
2010/07/06
背景：虽然对儿童严重哮喘的临床病因进行了详细描述，但是目前对下气道炎症反应的鉴别特征了解较少。
目的：采用线性判别分析（高维数据缩减的监督法）分析支气管肺泡灌洗液（BAL）和肺泡巨噬细胞（AM）裂解液中的细胞因子和趋化因子，以期在哮喘患儿中鉴别严重哮喘和中度哮喘。
方法：支气管镜检查时收集53名哮喘患儿（31例严重哮喘）和30名非吸烟成人的BAL。采用基于磁珠的多重分析检测23个细胞因子和趋化因子。线性判别分析BAL和AM裂解液中的上述因子，建立儿童严重哮喘的预测模型。
结果：虽然单变量分析显示，单个因子不能鉴别儿童严重哮喘和中度哮喘，线性判别分析基本能完全鉴别严重哮喘和中度哮喘。一些AM裂解物和BAL某些因子间存在显著相关性。在BAL中，IL-13和IL-6能鉴别哮喘患者和非哮喘对照者，而生长相关癌基因(CXCL1)、RANTES (CCL5)、IL-12、IFN-γ和IL-10能很好的鉴别严重哮喘和中度哮喘。在AM裂解物中，IL-6是最强的鉴别因子。
结论：严重哮喘患儿具有特征性气道分子表型，但没有明显的T(H)1或T(H)2倾向。改善严重哮喘患者分型方法有助于对难治性严重哮喘患儿采取靶向治疗。
（刘国梁 审校）
J Allergy Clin Immunol. 2010 Apr;125(4):851-857.e18.
The molecular phenotype of severe asthma in children.
Fitzpatrick AM, Higgins M, Holguin F, Brown LA, Teague WG; National Institutes of Health/National Heart, Lung, and Blood Institute’s Severe Asthma Research Program.
Emory University School of Medicine, Atlanta, Ga, USA. anne.fitzpatrick@emory.edu
Abstract
BACKGROUND: Although the clinical attributes of severe asthma in children have been well described, the differentiating features of the lower airway inflammatory response are less understood.
OBJECTIVES: We sought to discriminate severe from moderate asthma in children by applying linear discriminant analysis, a supervised method of high-dimensional data reduction, to cytokines and chemokines measured in the bronchoalveolar lavage (BAL) fluid and alveolar macrophage (AM) lysate.
METHODS: Bronchoalveolar lavage fluid was available from 53 children with asthma (severe asthma, n = 31) undergoing bronchoscopy for clinical indications and 30 nonsmoking adults. Twenty-three cytokines and chemokines were measured by using bead-based multiplex assays. Linear discriminant analyses of the BAL fluid and AM analytes were performed to develop predictive models of severe asthma in children.
RESULTS: Although univariate analysis of single analytes did not differentiate severe from moderate asthma in children, linear discriminant analyses allowed for near complete separation of the moderate and severe asthmatic groups. Significant correlations were also noted between several of the AM and BAL analytes measured. In the BAL fluid, IL-13 and IL-6 differentiated subjects with asthma from controls, whereas growth-related oncogene (CXCL1), RANTES (CCL5), IL-12, IFN-gamma, and IL-10 best characterized severe versus moderate asthma in children. In the AM lysate, IL-6 was the strongest discriminator of all the groups.
CONCLUSION: Severe asthma in children is characterized by a distinct airway molecular phenotype that does not have a clear T(H)1 or T(H)2 pattern. Improved classification of children with severe asthma may assist with the development of targeted therapeutics for this group of children who are difficult to treat.
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过敏性哮喘患者剧烈运动后血清及呼出气冷凝液中高敏C反应蛋白的变化
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小鼠早期病毒感染和过敏原暴露两者相互作用诱导哮喘表现型
