婴儿期症状轨迹对 BILD 和 PASTURE 队列中后续喘息和哮喘的预测:动态网络分析

IF 23.8 1区 医学 Q1 MEDICAL INFORMATICS Lancet Digital Health Pub Date : 2024-09-25 DOI:10.1016/S2589-7500(24)00147-X
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引用次数: 0

摘要

背景早期生活中的宿主和环境风险因素与喘息症状随着时间的推移而加重有关;但是,这些因素的单独作用相对较小。我们假设,这些因素与婴儿呼吸系统发育过程中的动态相互作用是导致后续喘息和哮喘的主要因素。方法在这项动态网络分析中,我们使用了来自巴塞尔-伯尔尼婴儿肺发育(BILD)队列(1999 年 1 月 1 日至 2012 年 12 月 31 日期间在瑞士招募的 435 名 0-4 周大的新生儿)的足月健康婴儿的数据,并复制了农村环境中的抗过敏保护研究(PASTURE)队列(2002 年 1 月 1 日至 2006 年 10 月 31 日期间在德国、瑞士、奥地利、法国和芬兰招募的 498 名 0-12 个月大的婴儿)的研究结果。本次研究的 BILD 排除标准为早产(37 周)、重大出生缺陷、新生儿围产期疾病和随访时间不完整。PASTURE 的排除标准是:女性小于 18 岁、多胎妊娠、孩子的兄弟姐妹已被纳入研究、家庭打算搬离研究地区、家庭没有电话连接。结果分组为嗣后喘息、哮喘和健康。第一项结果定义为 2 岁至 6 岁期间曾经喘息。从第 2 周到第 52 周(BILD)和第 8 周到第 52 周(PASTURE),逐周计算决定因素与累积症状评分 (CSS) 的相关性。决定因素与 CSS 之间复杂的动态相互作用通过动态的宿主-环境相关网络进行评估,并通过简单的描述符进行量化:轨迹函数 G(t)。对来自 BILD 的 335 名婴儿和来自 PASTURE 的 437 名婴儿 2-6 岁时的喘息结果进行了比较,并对 783 名合并队列婴儿 6 岁时的哮喘结果进行了分析。对各组婴儿的每周症状进行了追踪,结果显示,随着时间的推移,症状呈非线性增加。通过逻辑回归分类,G(t)可区分健康组和喘息或哮喘组(曲线下面积>0-97,p<0-0001;敏感性分析证实 CSS 与喘息有显著关联 [BILD p=0-0002 和 PASTURE p=0-068]),G(t)还能区分养殖和非养殖暴露组(p<0-0001)。然而,在群体水平上,动态宿主-环境相关网络特性(G(t))在识别随后出现喘息和哮喘的婴儿群体方面表现出卓越的鉴别能力。这项研究的结果与2018年柳叶刀哮喘委员会的研究结果一致,后者强调了发育过程中风险因素之间动态相互作用的重要性,而不是风险因素本身的重要性。资金来源瑞士国家科学基金会、Kühne基金会、EFRAIM研究欧盟研究基金、FORALLVENT研究欧盟研究基金和莱布尼兹奖。
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Symptom trajectories in infancy for the prediction of subsequent wheeze and asthma in the BILD and PASTURE cohorts: a dynamic network analysis

Background

Host and environment early-life risk factors are associated with progression of wheezing symptoms over time; however, their individual contribution is relatively small. We hypothesised that the dynamic interactions of these factors with an infant's developing respiratory system are the dominant factor for subsequent wheeze and asthma.

Methods

In this dynamic network analysis we used data from term healthy infants from the Basel-Bern Infant Lung Development (BILD) cohort (435 neonates aged 0–4 weeks recruited in Switzerland between Jan 1, 1999, and Dec 31, 2012) and replicated the findings in the Protection Against Allergy Study in Rural Environments (PASTURE) cohort (498 infants aged 0–12 months recruited in Germany, Switzerland, Austria, France, and Finland between Jan 1, 2002, and Oct 31, 2006). BILD exclusion criteria for the current study were prematurity (<37 weeks), major birth defects, perinatal disease of the neonate, and incomplete follow-up period. PASTURE exclusion criteria were women younger than 18 years, a multiple pregnancy, the sibling of a child was already included in the study, the family intended to move away from the area where the study was conducted, and the family had no telephone connection. Outcome groups were subsequent wheeze, asthma, and healthy. The first outcome was defined as ever wheezed between the age of 2 years and 6 years. Week-by-week correlations of the determining factors with cumulative symptom scores (CSS) were calculated from weeks 2 to 52 (BILD) and weeks 8 to 52 (PASTURE). The complex dynamic interaction between the determining factors and the CSS was assessed via dynamic host–environment correlation network, quantified by a simple descriptor: trajectory function G(t). Wheeze outcomes at age 2–6 years were compared in 335 infants from BILD and 437 infants from PASTURE, and asthma outcomes were analysed at age 6 years in a merged cohort of 783 infants.

Findings

CSS was significantly different for wheeze and asthma outcomes and became increasingly important during infancy in direct comparison with all determining factors. Weekly symptoms were tracked for groups of infants, showing a non-linear increase with time. Using logistic regression classification, G(t) distinguished between the healthy group and wheeze or asthma groups (area under the curve>0·97, p<0·0001; sensitivity analysis confirmed significant CSS association with wheeze [BILD p=0·0002 and PASTURE p=0·068]) and G(t) was also able to distinguish between the farming and non-farming exposure groups (p<0·0001).

Interpretation

Similarly to other risk factors, CSS had weak sensitivity and specificity to identify risks at the individual level. At group level however, the dynamic host–environment correlation network properties (G(t)) showed excellent discriminative ability for identifying groups of infants with subsequent wheeze and asthma. Results from this study are consistent with the 2018 Lancet Commission on asthma, which emphasised the importance of dynamic interactions between risk factors during development and not the risk factors per se.

Funding

The Swiss National Science Foundation, the Kühne Foundation, the EFRAIM study EU research grant, the FORALLVENT study EU research grant, and the Leibniz Prize.
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来源期刊
CiteScore
41.20
自引率
1.60%
发文量
232
审稿时长
13 weeks
期刊介绍: The Lancet Digital Health publishes important, innovative, and practice-changing research on any topic connected with digital technology in clinical medicine, public health, and global health. The journal’s open access content crosses subject boundaries, building bridges between health professionals and researchers.By bringing together the most important advances in this multidisciplinary field,The Lancet Digital Health is the most prominent publishing venue in digital health. We publish a range of content types including Articles,Review, Comment, and Correspondence, contributing to promoting digital technologies in health practice worldwide.
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