Department of Paediatrics, Imperial College London, London, U.K.
National Heart and Lung Institute, Imperial College London, London, U.K.
Br J Dermatol. 2019 Dec;181(6):1272-1279. doi: 10.1111/bjd.17853. Epub 2019 Jun 26.
There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition.
To investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors.
We first reviewed the operational definitions of AD used in the literature. We then tested the impact of the choice of the most common definitions of 'cases' and 'controls' on AD prevalence estimates and associated risk factors (including filaggrin mutations) among children aged 5 years in two population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford. Model performance was measured by the percentage of children within an area of clinical indecision (defined as having a posterior probability of AD between 25% and 60%).
We identified 59 different definitions of AD across 45 reviewed studies. Of those, we chose four common 'case' definitions and two definitions of 'controls'. The prevalence estimates using different case definitions ranged between 22% and 33% in MAAS, and between 12% and 22% in Ashford. The area of clinical indecision ranged from 32% to 44% in MAAS and from 9% to 29% in Ashford. Depending on the case definition used, the associations with filaggrin mutations varied, with odds ratios (95% confidence intervals) ranging from 1·8 (1·1-2·9) to 2·2 (1·3-3·7) in MAAS and 1·7 (0·8-3·7) to 2·3 (1·2-4·5) in Ashford. Associations with filaggrin mutations also differed when using the same 'case' definition but different definitions of 'controls'.
Use of different definitions of AD results in substantial differences in prevalence estimates, the performance of prediction models and association with risk factors. What's already known about this topic? There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD) and no uniform clinical definition. This results in different definitions utilized in AD studies, raising concerns on the generalizability of the results and comparability across different studies. What does this study add? This study has shown that different definitions of 'cases' and 'controls' have major impacts upon prevalence estimates and associations with risk factors, including genetics, in two population-based birth cohorts. These findings suggest the importance of developing a consensus on AD definitions of both 'controls' and 'cases' to minimize biases in studies.
目前尚无能够明确诊断特应性皮炎（AD）的客观检测方法，也没有统一的临床定义。
本研究旨在探究 AD 的操作性定义在多大程度上会导致患病率估计值发生波动，以及与之相关的危险因素。
我们首先回顾了文献中 AD 的操作性定义。然后，我们在两个基于人群的出生队列（曼彻斯特哮喘和过敏研究[MAAS]和阿什福德哮喘）中，测试了选择最常见的“病例”和“对照”定义对 AD 患病率估计值和相关危险因素（包括丝聚蛋白突变）的影响。模型性能通过处于临床不确定区域（定义为 AD 的后验概率在 25%到 60%之间）的儿童比例来衡量。
我们在 45 项综述研究中确定了 59 种不同的 AD 定义。在这些定义中，我们选择了四个常见的“病例”定义和两个“对照”定义。使用不同病例定义的患病率估计值在 MAAS 中为 22%至 33%，在阿什福德为 12%至 22%。临床不确定区域在 MAAS 中为 32%至 44%，在阿什福德为 9%至 29%。根据使用的病例定义不同，与丝聚蛋白突变的关联也有所不同，优势比（95%置信区间）在 MAAS 中为 1.8（1.1-2.9）至 2.2（1.3-3.7），在阿什福德为 1.7（0.8-3.7）至 2.3（1.2-4.5）。当使用相同的“病例”定义但不同的“对照”定义时，与丝聚蛋白突变的关联也存在差异。
AD 不同定义的使用会导致患病率估计值、预测模型的性能以及与危险因素的关联产生显著差异。
关于这个主题已经知道些什么？目前尚无能够明确诊断特应性皮炎（AD）的客观检测方法，也没有统一的临床定义。这导致 AD 研究中使用了不同的定义，引起了人们对研究结果的可推广性和不同研究之间的可比性的关注。
这项研究增加了哪些新内容？本研究表明，在两个基于人群的出生队列中，“病例”和“对照”的不同定义对患病率估计值以及与遗传等危险因素的关联有重大影响。这些发现表明，制定 AD 病例和对照定义的共识对于减少研究中的偏倚非常重要。
