生命早期的胆红素代谢与学龄前期的呼吸健康:对两个独立出生队列的综合分析。

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Med Pub Date : 2024-08-13 DOI:10.1016/j.medj.2024.07.021
Min Kim, Nicklas Brustad, Anders U Eliasen, Mina Ali, Tingting Wang, Morten A Rasmussen, Madeleine Ernst, David Hougaard, Augusto A Litonjua, Craig E Wheelock, Rachel S Kelly, Yulu Chen, Nicole Prince, Paul A Townsend, Jakob Stokholm, Scott T Weiss, Klaus Bønnelykke, Jessica Lasky-Su, Bo Chawes
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引用次数: 0

摘要

背景:胆红素具有抗氧化特性,正常范围内的胆红素水平升高与成人肺功能改善和哮喘风险降低有关,但针对幼儿的研究却很少。在此,我们在两个独立的出生队列中调查了生命早期胆红素与学龄前呼吸健康终点之间的关系:方法:在 COPSAC2010(哥本哈根儿童哮喘前瞻性研究,2010 年)和 VDAART(维生素 D 减少产前哮喘试验)队列中,分别对 0.5 岁、1.5 岁和 6 岁时的胆红素代谢物以及 1 岁、3 岁和 6 岁时的胆红素代谢物进行了评估。通过元分析总结了各队列中胆红素代谢物水平与哮喘、感染、肺功能和 6 岁前过敏致敏之间的关系。研究还探讨了与编码胆红素代谢酶的葡萄糖醛酸转移酶家族 1 成员 A1(UGT1A)基因型之间的相互作用,并整合了代谢组学数据以研究其潜在机制:结果:1.5-3 岁时胆红素(Z,Z)的增加与过敏致敏风险的增加有关(调整后相对风险 [aRR] = 1.85 [1.20-2.85],p = 0.005),6 岁胆红素(Z,Z)也显示出与 6 岁过敏致敏相关的趋势(αRR = 1.31 [0.97-1.77],p = 0.08),6 岁胆红素(Z,Z)xUGT1A 基因型显示出显著的交互作用。此外,1.5-3 岁时胆红素(E,E)、胆红素(Z,Z)和胆红素的增加与 6 岁时较低的用力呼气量有关(αRR 范围 = 0.81-0.91,p 0.05)。网络分析显示胆红素代谢与酰基肉碱之间存在明显的相关性。胆红素代谢物与哮喘和感染风险之间没有关联:结论:生命早期的胆红素代谢可能对儿童呼吸系统健康有影响,尤其是对具有特定 UGT1A 基因型的儿童:灵北基金会(资助编号 R16-A1694)、卫生部(资助编号 903516)、丹麦战略研究委员会(资助编号 0603-00280B)和首都地区研究基金会为 COPSAC 研究中心提供了核心支持。该项目获得了欧洲研究理事会(ERC)在欧盟地平线 2020 研究与创新计划下提供的资助(资助协议编号 946228)。维生素 D 产前减少哮喘试验(VDDART,ClinicalTrials.gov 识别码:NCT00920621)得到了美国国立卫生研究院(NHLBI)的 U01HL091528 号基金和美国国家转化科学促进中心(NCATS)的 U54TR001012 号基金的支持。VDAART的代谢组学工作得到了美国国家心肺血液研究所(NHLBI)R01HL123915和R01HL141826基金的支持。S.T.W.得到了美国国家心肺和血液研究所 R01HL091528、美国国家卫生研究院主任办公室 UG3OD023268 和美国国家心肺和血液研究所 P01HL132825 的资助。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bilirubin metabolism in early life and respiratory health during preschool age: A combined analysis of two independent birth cohorts.

Background: Bilirubin has antioxidant properties, and elevated levels within the normal range have been associated with improved lung function and decreased risk of asthma in adults, but studies of young children are scarce. Here, we investigate associations between bilirubin in early life and respiratory health endpoints during preschool age in two independent birth cohorts.

Methods: Bilirubin metabolites were assessed at ages 0.5, 1.5, and 6 years in COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) and ages 1, 3, and 6 years in the VDAART (The Vitamin D Antenatal Asthma Reduction Trial) cohort. Meta-analyses were done to summarize the relationship between levels of bilirubin metabolites and asthma, infections, lung function, and allergic sensitization until age 6 across the cohorts. Interaction with the glucuronosyltransferase family 1 member A1 (UGT1A) genotype encoding for an enzyme in the bilirubin metabolism was explored, and metabolomics data were integrated to study underlying mechanisms.

Findings: Increasing bilirubin (Z,Z) at ages 1.5-3 years was associated with an increased risk of allergic sensitization (adjusted relative risk [aRR] = 1.85 [1.20-2.85], p = 0.005), and age 6 bilirubin (Z,Z) also showed a trend of association with allergic sensitization at age 6 (aRR = 1.31 [0.97-1.77], p = 0.08), which showed significant interaction for the age 6 bilirubin (Z,Z)xUGT1A genotype. Further, increasing bilirubin (E,E), bilirubin (Z,Z), and biliverdin at ages 1.5-3 years was associated with a lower forced expiratory volume at age 6 (aRR range = 0.81-0.91, p < 0.049) but without a significant interaction with the UGT1A genotype (p interactions > 0.05). Network analysis showed a significant correlation between bilirubin metabolism and acyl carnitines. There were no associations between bilirubin metabolites and the risk of asthma and infections.

Conclusions: Bilirubin metabolism in early life may play a role in childhood respiratory health, particularly in children with specific UGT1A genotypes.

Funding: The Lundbeck Foundation (Grant no R16-A1694), The Ministry of Health (Grant no 903516), Danish Council for Strategic Research (Grant no 0603-00280B), and The Capital Region Research Foundation have provided core support to the COPSAC research center. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 946228). The Vitamin D Antenatal Asthma Reduction Trial (VDDART, ClinicalTrials.gov identifier: NCT00920621) was supported by grant U01HL091528 from NHLBI, U54TR001012 from the National Centers for Advancing Translational Sciences (NCATS). Metabolomics work by VDAART was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL123915 and R01HL141826. S.T.W. was supported by R01HL091528 from the NHLBI, UG3OD023268 from Office of The Director, National Institute of Health, and P01HL132825 from the NHLBI.

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来源期刊
Med
Med MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
17.70
自引率
0.60%
发文量
102
期刊介绍: Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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