Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program
Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program
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DOI：
10.1164/rccm.200906-0896oc
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发表时间：
2010-02-15
影响因子：
24.7
通讯作者：
Bleecker, Eugene R.
中科院分区：
文献类型：
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作者：
Moore, Wendy C.;Meyers, Deborah A.;Bleecker, Eugene R.
严重哮喘研究计划队列包括已接受详细表型表征的持续性哮喘受试者。以前的单变量方法比较功能的轻度，中度和重度asthma.Objectives：To identify novel asthma phenotypes using an unsupervised hierarchical cluster analysis.Methods：通过消除冗余数据和分类变量转化为有序复合变量，将初始628个变量减少到34个核心变量。对726名受试者进行聚类分析。第1组受试者（n = 110）患有早发性特应性哮喘，肺功能正常，接受两种或更少的控制药物治疗（82%），医疗保健利用率最低。第2组（n = 321）包括早发性特应性哮喘受试者，肺功能保留，但药物需求增加（29%使用三种或三种以上药物）和医疗保健利用增加。第3组（n = 59）是一个独特的组，大多数为老年肥胖女性，患有迟发性非特应性哮喘，FEV1中度降低，频繁使用口服皮质类固醇来控制病情加重。受试者在集群4（n = 120）和5（n = 116）有严重的气流阻塞与支气管扩张剂的反应，但不同的能力，以达到正常的肺功能，哮喘发作的年龄，特应性状态，并使用口服corticosteroids.Conclusions：五个不同的临床表型哮喘已被确定使用无监督的分层聚类分析。所有聚类均包含符合美国胸科学会重度哮喘定义的受试者，该定义支持哮喘的临床异质性以及对哮喘疾病严重程度分类的新方法的需求。
Rationale The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma.Objectives: To identify novel asthma phenotypes using an unsupervised hierarchical cluster analysis.Methods: Reduction of the initial 628 variables to 34 core variables was achieved by elimination of redundant data and transformation of categorical variables into ranked ordinal composite variables. Cluster analysis was performed on 726 subjects.Measurements and Main Results: Five groups were identified. Subjects in Cluster 1 (n = 110) have early onset atopic asthma with normal lung function treated with two or fewer controller medications (82%) and minimal health care utilization. Cluster 2 (n = 321) consists of subjects with early-onset atopic asthma and preserved lung function but increased medication requirements (29% on three or more medications) and health care utilization. Cluster 3 (n = 59) is a unique group of mostly older obese women with late-onset non-atopic asthma, moderate reductions in FEV1, and frequent oral corticosteroid use to manage exacerbations. Subjects in Clusters 4 (n = 120) and 5 (n = 116) have severe airflow obstruction with bronchodilator responsiveness but differ in to their ability to attain normal lung function, age of asthma onset, atopic status, and use of oral corticosteroids.Conclusions: Five distinct clinical phenotypes of asthma have been identified using unsupervised hierarchical cluster analysis. All clusters contain subjects who meet the American Thoracic Society definition of severe asthma, which supports clinical heterogeneity in asthma and the need for new approaches for the classification of disease severity in asthma.