美国国立卫生研究院/美国国家心脏,肺和血液研究所进行的严重哮喘研究项目，通过聚类分析，证实儿童严重哮
2011/03/28
摘要
背景：儿童哮喘是一种异质性疾病，具有多种表型。虽然非监督的聚类分析是鉴别哮喘表型的有用工具，但尚未在不同严重程度的持续哮喘的学龄期儿童中进行研究。
目的：本研究采用聚类分析，研究严重哮喘儿童的分布，以及这些聚类是怎样很好的顺应目前哮喘严重程度定义的。
方法：对严重哮喘研究项目注册的5个中心的161名儿童的12个连续和复合变量进行聚类分析。
结果：共鉴别出哮喘的4个聚类。聚类1的儿童(n = 48)肺功能相对正常，过敏症较少见。聚类2的儿童(n = 52)肺功能轻度降低，更多出现过敏症，症状和用药均增加。聚类3的儿童(n = 32)具有较多的共患病，支气管反应性增加，肺功能较低。聚类4的儿童(n = 29)肺功能最低，症状最明显，用药最频繁。聚类的预测因素为哮喘持续时间、哮喘控制用药种类和基线肺功能。严重哮喘患儿可出现在所有聚类中，无聚类与哮喘治疗指南的哮喘严重程度定义相对应。
结论：儿童严重哮喘具有较高的异质性。前期在成人中鉴别的独特表型聚类，在儿童中同样存在，但有重要差异。有必要进行纵向效度研究，在大型临床试验中探讨这些表型聚类的基线效度和预测效度。
（陈欣 审校）
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
Heterogeneity of severe asthma in childhood: Confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program.
Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H, Wenzel SE, Aujla S, Castro M, Bacharier LB, Gaston BM, Bleecker ER, Moore WC; for the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program.
Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga.
Abstract
BACKGROUND: Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to school-age children with persistent asthma across a wide range of severities.
OBJECTIVES: This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity.
METHODS: Cluster analysis was applied to 12 continuous and composite variables from 161 children at 5 centers enrolled in the Severe Asthma Research Program.
RESULTS: Four clusters of asthma were identified. Children in cluster 1 (n = 48) had relatively normal lung function and less atopy. Children in cluster 2 (n = 52) had slightly lower lung function, more atopy, and increased symptoms and medication use. Cluster 3 (n = 32) had greater comorbidity, increased bronchial responsiveness, and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the greatest symptoms and medication use. Predictors of cluster assignment were asthma duration, the number of asthma controller medications, and baseline lung function. Children with severe asthma were present in all clusters, and no cluster corresponded to definitions of asthma severity provided in asthma treatment guidelines.
CONCLUSION: Severe asthma in children is highly heterogeneous. Unique phenotypic clusters previously identified in adults can also be identified in children, but with important differences. Larger validation and longitudinal studies are needed to determine the baseline and predictive validity of these phenotypic clusters in the larger clinical setting.
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
背景：儿童哮喘是一种异质性疾病，具有多种表型。虽然非监督的聚类分析是鉴别哮喘表型的有用工具，但尚未在不同严重程度的持续哮喘的学龄期儿童中进行研究。
目的：本研究采用聚类分析，研究严重哮喘儿童的分布，以及这些聚类是怎样很好的顺应目前哮喘严重程度定义的。
方法：对严重哮喘研究项目注册的5个中心的161名儿童的12个连续和复合变量进行聚类分析。
结果：共鉴别出哮喘的4个聚类。聚类1的儿童(n = 48)肺功能相对正常，过敏症较少见。聚类2的儿童(n = 52)肺功能轻度降低，更多出现过敏症，症状和用药均增加。聚类3的儿童(n = 32)具有较多的共患病，支气管反应性增加，肺功能较低。聚类4的儿童(n = 29)肺功能最低，症状最明显，用药最频繁。聚类的预测因素为哮喘持续时间、哮喘控制用药种类和基线肺功能。严重哮喘患儿可出现在所有聚类中，无聚类与哮喘治疗指南的哮喘严重程度定义相对应。
结论：儿童严重哮喘具有较高的异质性。前期在成人中鉴别的独特表型聚类，在儿童中同样存在，但有重要差异。有必要进行纵向效度研究，在大型临床试验中探讨这些表型聚类的基线效度和预测效度。
（陈欣 审校）
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
Heterogeneity of severe asthma in childhood: Confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program.
Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H, Wenzel SE, Aujla S, Castro M, Bacharier LB, Gaston BM, Bleecker ER, Moore WC; for the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program.
Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga.
Abstract
BACKGROUND: Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to school-age children with persistent asthma across a wide range of severities.
OBJECTIVES: This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity.
METHODS: Cluster analysis was applied to 12 continuous and composite variables from 161 children at 5 centers enrolled in the Severe Asthma Research Program.
RESULTS: Four clusters of asthma were identified. Children in cluster 1 (n = 48) had relatively normal lung function and less atopy. Children in cluster 2 (n = 52) had slightly lower lung function, more atopy, and increased symptoms and medication use. Cluster 3 (n = 32) had greater comorbidity, increased bronchial responsiveness, and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the greatest symptoms and medication use. Predictors of cluster assignment were asthma duration, the number of asthma controller medications, and baseline lung function. Children with severe asthma were present in all clusters, and no cluster corresponded to definitions of asthma severity provided in asthma treatment guidelines.
CONCLUSION: Severe asthma in children is highly heterogeneous. Unique phenotypic clusters previously identified in adults can also be identified in children, but with important differences. Larger validation and longitudinal studies are needed to determine the baseline and predictive validity of these phenotypic clusters in the larger clinical setting.
J Allergy Clin Immunol. 2010 Dec 30. [Epub ahead of print]
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日本成人哮喘患病率的时间趋势：基于来自日本藤枝市1985、1999和2006年人群调查结果
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炼油厂污染物暴露儿童的哮喘症状、肺功能、氧化应激标志物和炎症
