Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.
Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.
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DOI：
10.1111/bjd.19885
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Langan SM
中科院分区：
文献类型：
--
作者：
Mulick AR;Mansfield KE;Silverwood RJ;Budu-Aggrey A;Roberts A;Custovic A;Pearce N;Irvine AD;Smeeth L;Abuabara K;Langan SM
特应性皮炎（AD）在儿童时期的疾病活动度和严重程度差异很大。早期基于疾病发展轨迹识别亚型的尝试是在不考虑严重程度的情况下对一段时间内特应性皮炎的存在情况进行评估。
从症状严重程度和发展轨迹识别儿童特应性皮炎亚型，并确定其与遗传风险因素、合并症以及人口统计学和环境变量的关联。
我们将雅芳亲子纵向研究出生队列中儿童的数据分为开发集和验证集。为了识别亚型，我们对开发集中14岁以下的特应性皮炎症状报告进行了潜在类别分析。我们在相互调整的多重填补（遗传因素：未调整，完整病例）多项回归分析中，将识别出的亚型对非遗传变量进行回归分析。我们在验证集中重复分析，并报告得到确认的结果。
11866名儿童参与了分析。我们识别出一个未患病/罕见类别（占儿童的66%）和四种特应性皮炎亚型：重度 - 频繁型（4%）；中度 - 频繁型（7%）；中度 - 递减型（11%）；轻度 - 间歇型（12%）。前两种亚型内的症状模式似乎比后两种更具同质性。丝聚蛋白缺失突变（FLG）、特应性皮炎多基因风险评分（PRS）、女性、父母患特应性皮炎以及合并哮喘与某些或所有亚型的较高风险相关；FLG、特应性皮炎 - 多基因风险评分以及哮喘的相关性沿着按严重程度和发作频率递增排列的亚型梯度更强；FLG和特应性皮炎 - 多基因风险评分进一步将某些表型相互区分开来。
考虑严重程度和特应性皮炎的发展轨迹可得出四种定义明确且可识别的亚型。亚型之间以及亚型内部风险因素的差异关联是新颖的，需要进一步研究。
Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity. To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14. We regressed identified subtypes on non-genetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete-case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results. 11,866 children contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%); Moderate-Frequent (7%); Moderate-Declining (11%); and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin null mutations (FLG), an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other. Considering severity and AD trajectories leads to four well-defined and recognisable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.
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影响因子：
14.2
作者：
Hose, Alexander J.;Depner, Martin;Frey, Urs
通讯作者：
Frey, Urs
DOI：
10.1016/j.jaci.2017.09.044
发表时间：
2018-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Paternoster L;Savenije OEM;Heron J;Evans DM;Vonk JM;Brunekreef B;Wijga AH;Henderson AJ;Koppelman GH;Brown SJ
通讯作者：
Brown SJ
影响因子：
12.4
作者：
Bousquet, J.;Anto, J. M.;von Hertzen, L.
通讯作者：
von Hertzen, L.
影响因子：
10.3
作者：
McNally, NJ;Williams, HC;Strachan, DP
通讯作者：
Strachan, DP
影响因子：
2.4
作者：
Abuabara K;Margolis DJ;Langan SM
通讯作者：
Langan SM