Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.
Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts.
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DOI：
10.1016/j.jaci.2017.09.044
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Brown SJ
中科院分区：
文献类型：
--
作者：
Paternoster L;Savenije OEM;Heron J;Evans DM;Vonk JM;Brunekreef B;Wijga AH;Henderson AJ;Koppelman GH;Brown SJ
特应性皮炎（AD）是一种流行疾病，其自然病程多变。纵向出生队列研究为根据疾病轨迹定义亚组提供了机会，这些亚组可能代表不同的遗传和环境发病机制。
我们试图研究特应性皮炎是否存在不同的纵向表型，并检验这些发现在两个独立队列中是否可重复。
在两项出生队列研究中检查了特应性皮炎的存在情况，这两项研究包括来自英国（ALSPAC）的9894名儿童和来自荷兰（PIAMA）的3652名儿童。特应性皮炎由父母报告典型的瘙痒和/或屈侧皮疹来定义。纵向潜在类别分析用于研究从出生到11至16岁的特应性皮炎模式。我们研究了与已知的特应性皮炎风险因素的关联，包括丝聚蛋白（FLG）无效突变、其他23个已确定的特应性皮炎遗传风险变异以及特应性合并症。
确定了六个潜在类别，代表特应性皮炎的亚表型，两个队列之间具有显著的一致性。最常见的类别是早发早缓解特应性皮炎，与男性性别相关。确定了两类持续性疾病（早发持续性和早发晚缓解）；这些与特应性皮炎遗传风险评分以及个人和父母的特应性疾病史密切相关。还确定了一类尚未被认识的中发缓解特应性皮炎，它与丝聚蛋白突变无关，但与哮喘密切相关。
在两个人群队列中一致确定了基于皮疹时间轨迹的六个类别。不同的风险因素特征和多样的预后表明了分层医学方法对特应性皮炎的潜在重要性。
Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms. We sought to investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in 2 independent cohorts. The presence of AD was examined in 2 birth cohort studies including 9894 children from the United Kingdom (ALSPAC) and 3652 from the Netherlands (PIAMA). AD was defined by parental report of a typical itchy and/or flexural rash. Longitudinal latent class analysis was used to investigate patterns of AD from birth to the age of 11 to 16 years. We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants, and atopic comorbidity. Six latent classes were identified, representing subphenotypes of AD, with remarkable consistency between the 2 cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male sex. Two classes of persistent disease were identified (early-onset-persistent and early-onset-late-resolving); these were most strongly associated with the AD-genetic risk score as well as personal and parental history of atopic disease. A yet unrecognized class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified. Six classes based on temporal trajectories of rash were consistently identified in 2 population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.
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