Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Institute for Medical Information Processing, Biometry, and Epidemiology, Pettenkofer School of Public Health, LMU Munich, Munich, Germany.
Allergy. 2023 Mar;78(3):836-850. doi: 10.1111/all.15511. Epub 2022 Sep 19.
Allergic diseases often develop jointly during early childhood but differ in timing of onset, remission, and progression. Their disease course over time is often difficult to predict and determinants are not well understood.
We aimed to identify trajectories of allergic diseases up to adolescence and to investigate their association with early-life and genetic determinants and clinical characteristics.
Longitudinal k-means clustering was used to derive trajectories of allergic diseases (asthma, atopic dermatitis, and rhinitis) in two German birth cohorts (GINIplus/LISA). Associations with early-life determinants, polygenic risk scores, food and aeroallergen sensitization, and lung function were estimated by multinomial models. The results were replicated in the independent Swedish BAMSE cohort.
Seven allergic disease trajectories were identified: "Intermittently allergic," "rhinitis," "early-resolving dermatitis," "mid-persisting dermatitis," "multimorbid," "persisting dermatitis plus rhinitis," and "early-transient asthma." Family history of allergies was more prevalent in all allergic disease trajectories compared the non-allergic controls with stronger effect sizes for clusters comprising more than one allergic disease (e.g., RRR = 5.0, 95% CI = [3.1-8.0] in the multimorbid versus 1.8 [1.4-2.4] in the mild intermittently allergic cluster). Specific polygenic risk scores for single allergic diseases were significantly associated with their relevant trajectories. The derived trajectories and their association with genetic effects and clinical characteristics showed similar results in BAMSE.
Seven robust allergic clusters were identified and showed associations with early life and genetic factors as well as clinical characteristics.
过敏性疾病常在儿童早期同时发生，但发病时间、缓解时间和进展情况存在差异。其随时间的疾病进程往往难以预测，发病机制也尚未完全阐明。
本研究旨在确定青少年时期过敏性疾病的发展轨迹，并探讨其与生命早期和遗传决定因素以及临床特征的相关性。
采用纵向 K-均值聚类方法对两个德国出生队列（GINIplus/LISA）中的过敏性疾病（哮喘、特应性皮炎和鼻炎）进行轨迹分析。采用多项模型评估与生命早期决定因素、多基因风险评分、食物和空气过敏原致敏以及肺功能的相关性。研究结果在独立的瑞典 BAMSE 队列中进行了复制。
共确定了 7 种过敏性疾病轨迹：“间歇性过敏”、“鼻炎”、“早期缓解性皮炎”、“中期持续性皮炎”、“多种疾病共存”、“持续性皮炎合并鼻炎”和“早期短暂性哮喘”。与非过敏性对照组相比，所有过敏性疾病轨迹的过敏家族史更为常见，且包含多种过敏性疾病的聚类具有更强的效应大小（例如，在多种疾病共存的聚类中，RRR=5.0，95%CI[3.1-8.0]，而在轻度间歇性过敏的聚类中，RRR=1.8，95%CI[1.4-2.4]）。特定的单一致敏性疾病的多基因风险评分与相应的轨迹显著相关。在 BAMSE 中，得出的轨迹及其与遗传效应和临床特征的相关性也表现出相似的结果。
本研究确定了 7 种稳健的过敏性聚类，并发现其与生命早期和遗传因素以及临床特征存在相关性。
