Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts
Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts
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DOI：
10.1016/j.jaci.2016.08.046
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发表时间：
2017-06-01
影响因子：
14.2
通讯作者：
Frey, Urs
中科院分区：
文献类型：
--
作者：
Hose, Alexander J.;Depner, Martin;Frey, Urs
背景：儿童期起病哮喘的表型具有不同的发展轨迹和功能特征。对于特应性，儿童期表型的定义不太明确。
目的：我们试图利用潜在类别分析（LCA），综合特应性的3个维度：过敏原特异性、时间进程和特异性IgE（sIgE）水平，来定义生命最初6年的特应性致敏表型。
方法：在多中心过敏研究（MAS）的680名儿童和农村环境中预防过敏研究（PASTURE）出生队列的766名儿童中，通过LCA定义表型，并与季节性、常年性和食物致敏的经典非分离性定义在特应性疾病和肺功能方面进行比较。在PASTURE队列中测量细胞因子水平。
结果：LCA主要根据致敏类型和多重性（食物与吸入物）、过敏原组合以及sIgE水平进行分类。潜在类别与特应性疾病表现相关，其敏感性和特异性高于经典定义。LCA在两个队列中均一致检测到一组具有严重特应性的儿童，其特征为季节性sIgE水平高，且极易患哮喘、花粉热、湿疹以及肺功能受损，甚至在未确诊哮喘的儿童中也是如此。严重特应性与IL - 5/IFN - γ比值升高有关。对致敏儿童进行的路径分析显示，在严重特应性的所有特征中，只有生命早期过度的sIgE产生影响哮喘风险。
结论：LCA揭示了一组良性、有症状和严重的特应性表型。严重表型作为一种潜在状况出现，伴有免疫反应失衡的迹象。它通过过度的sIgE产生决定了高哮喘风险，并直接影响肺功能受损。
Background: Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear.Objective: We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE).Methods: Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort.Results: The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-gamma ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk.Conclusions: LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.