Features of asthma which provide meaningful insights for understanding the disease heterogeneity.
Features of asthma which provide meaningful insights for understanding the disease heterogeneity.
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DOI：
10.1111/cea.13014
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Custovic A
中科院分区：
文献类型：
--
作者：
Deliu M;Yavuz TS;Sperrin M;Belgrave D;Sahiner UM;Sackesen C;Kalayci O;Custovic A
数据驱动的方法，如分层聚类（HC）和主成分分析（PCA）已被用于识别哮喘亚型，但结果不一致。建立一个发现稳定且有临床意义的哮喘亚型的框架。我们在来自613名哮喘儿童的丰富数据集中使用45个临床变量（模型1）和PCA降维后（模型2）进行HC。然后，临床专家确定了一组哮喘特征/领域，这些特征/领域在两项分析中为聚类提供了信息。在模型3中，我们使用这些特征重新聚类数据，以确定这是否改善了发现过程。模型1和模型2中的簇稳定性较差。临床专家强调了四个哮喘特征/领域，它们区分了两种模型中的集群：发病年龄、过敏性致敏、严重程度和近期加重。在模型3中（HC使用这四个特征），集群稳定性大大提高。改变了聚类分配，提供了更多临床可解释的结果。在5簇模型中，我们将簇标记为："难治性哮喘"（n = 132）;"早发性轻度特应性"（n = 210）;"早发性轻度非特应性：（n = 153）;"晚发性"（n = 105）;和"易加重哮喘"（n = 13）。多项回归显示，"难治性哮喘"儿童的肺功能显著降低;血嗜酸性粒细胞增多是"难治性"、"早发性轻度特应性"和"晚发性哮喘"的显著特征。每个群组中均存在中度至重度哮喘儿童。一个综合的方法混合的数据与临床专家领域的知识，确定了四个功能，这可能是确定哮喘内源性的信息。这些发现表明，作为哮喘存在、严重程度或控制的关键决定因素的变量可能不是确定哮喘亚型的最有用的信息。我们的研究结果表明，急性发作倾向性哮喘可能是一种单独的哮喘内型，重度哮喘不是一个单一的实体，而是几种不同哮喘内型谱的极端。
Data‐driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5‐cluster model, we labelled the clusters as: “Difficult asthma” (n = 132); “Early‐onset mild atopic” (n = 210); “Early‐onset mild non‐atopic: (n = 153); “Late‐onset” (n = 105); and “Exacerbation‐prone asthma” (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with “Difficult asthma”; blood eosinophilia was a significant feature of “Difficult,” “Early‐onset mild atopic,” and “Late‐onset asthma.” Children with moderate‐to‐severe asthma were present in each cluster. An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation‐prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes.
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DOI：
10.1016/j.jaci.2016.11.003
发表时间：
2017-02
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Belgrave D;Henderson J;Simpson A;Buchan I;Bishop C;Custovic A
通讯作者：
Custovic A
影响因子：
24.3
作者：
Just, Jocelyne;Gouvis-Echraghi, Rahele;Annesi-Maesano, Isabella
通讯作者：
Annesi-Maesano, Isabella
影响因子：
14.2
作者：
Clemmer, George L.;Wu, Ann Chen;Weiss, Scott T.
通讯作者：
Weiss, Scott T.
影响因子：
12.4
作者：
Lazic, N.;Roberts, G.;Simpson, A.
通讯作者：
Simpson, A.
影响因子：
24.3
作者：
Miller, MR;Hankinson, J;Wanger, J
通讯作者：
Wanger, J