The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
Am J Respir Crit Care Med. 2010 Jun 1;181(11):1200-6. doi: 10.1164/rccm.200907-1101OC. Epub 2010 Feb 18.
The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy.
To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma.
In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity).
A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053, 4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% CI]: 29.3 [11.1-77.2] versus 12.4 [4.8-32.2] versus 11.6 [4.8-27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5-24.0], P < 0.001).
IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity.
IgE 反应模式（随时间或针对特定过敏原）可能反映出不同的特应性易感性，这些易感性与目前特应性的定义从根本上以不同的方式与哮喘的存在相关。
通过确定特定过敏原致敏的时间和类型，在复杂数据集内识别潜在结构，重新定义特应性表型，并将这些新表型与哮喘相关联。
在一个基于人群的出生队列中，在整个儿童期进行了多次皮肤和 IgE 检测，我们使用机器学习方法以无监督的方式将儿童聚类为多个特应性类别。然后，我们研究了这些类别与哮喘（症状、住院、肺功能和气道反应性）之间的关系。
五类别模型表明存在复杂的潜在结构，其中特应性易感性儿童聚类为四个不同的类别（多个早期[112/1053，10.6%]；多个晚期[171/1053，16.2%]；尘螨[47/1053，4.5%]；和非尘螨[100/1053，9.5%]），第五个类别描述了无潜在易感性的儿童（623/1053，59.2%）。与其他类别和传统定义的特应性相比，多个早期类别与哮喘的相关性要强得多（优势比[95%置信区间]：29.3[11.1-77.2]与 12.4[4.8-32.2]与 11.6[4.8-27.9]，多个早期类别与任何特应性年龄 8）。多个早期类别的儿童肺功能和气道反应性明显较差。Cox 回归分析显示，仅在多个早期类别的儿童中，3 岁后因喘息/哮喘住院的风险显著增加（HR 9.2[3.5-24.0]，P <0.001）。
IgE 抗体反应并不反映单一的特应性表型，而是反映出几种不同的特应性易感性，这些易感性在与哮喘的存在和严重程度的关系上存在差异。
