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过敏和哮喘的早期起源 (ARIES):智利一项前瞻性产前出生队列研究的方案。

Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile.

机构信息

Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, 8th floor, 8330077, Santiago, Chile.

Department of Neonatology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.

出版信息

BMC Pediatr. 2020 Apr 15;20(1):164. doi: 10.1186/s12887-020-02077-x.

Abstract

BACKGROUND

Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring.

METHODS

We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma.

DISCUSSION

The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases.

TRIAL REGISTRATION

clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.

摘要

背景

越来越多的证据表明,特应性皮炎(AD)、食物过敏(FA)、过敏性鼻炎和哮喘在生命的前 1000 天(从受孕到 2 岁生日之间的时间)内基本确定。ARIES 出生队列旨在确定参与早期免疫反应的产前和围产期条件以及遗传和表观遗传因素,以及这些因素在后代过敏疾病和哮喘风险的后期确定中的作用。

方法

我们设计了一个由 250 个家庭组成的出生队列,这些家庭在产前招募(约 14 周)。我们将对三胞胎进行相关过敏/哮喘相关变异的基因分型,并在脐血中进行免疫表型和过敏生物标志物评估。在 1 岁和 2 岁时,我们将评估婴儿是否出现过敏致敏、AD、FA 以及包括哮喘预测指数在内的哮喘生物标志物。我们还将评估母体状况如何通过表观遗传修饰来改变免疫编程,然后描绘新生儿过敏/哮喘风险的表观遗传线索。接下来,我们将评估母体肠道、胎盘、母乳和婴儿肠道微生物组的组成/多样性及其与出生时免疫表型和生物标志物以及 1 岁和 2 岁时临床结局的关系。最后,我们计划评估环境暴露(围产期室外和室内污染、过敏原和内毒素)如何影响过敏致敏、AD、FA 的发生率以及哮喘的风险。

讨论

对 ARIES 出生队列的深入研究将为了解发展中国家过敏和哮喘发病率的上升提供关键信息,并有望提供有关如何预防和治疗这些疾病的线索。

试验注册

clinicaltrials.gov NCT04186949,于 2019 年 12 月 5 日回顾性注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1cc/7158062/8f2fa8dfe140/12887_2020_2077_Fig1_HTML.jpg

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