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基于前瞻性出生队列的多种族儿童早期代谢组学特征及食物过敏和哮喘风险研究

2024/04/24

   摘要
   背景:关于食物过敏(FA)和哮喘的代谢组学研究日益增多,但这些研究主要因横断面设计、样本量小及仅在欧洲人群中进行受限。
   目的:本研究旨在识别多种族前瞻性出生队列(即波士顿出生队列)中FA和/或哮喘儿童特有代谢产物。
   方法:本研究采用儿童早期采集的静脉血浆(N=811)进行基于质谱的非靶向代谢组学分析。FA诊断依据为与食物摄入后的急性超敏反应一致的临床症状,且食物特异性IgE>0.35 kU/L。哮喘基于临床医生诊断。本研究采用广义估计方程分析FA和哮喘的代谢组学相关性,并对潜在的混杂因素进行调整。
   结果:在出生后11.8±5.2年的中位随访中,78名儿童出现FA,171名儿童出现哮喘。雄激素和孕烯醇酮类固醇与较低的FA风险显著相关,尤其是对鸡蛋过敏。N,N,N-三甲基-5-氨基戊酸酯(OR=0.65,95%CI=0.48-0.87)和1-油酰基-2-花生四烯酸-sn-甘油-3-磷酸肌醇(OR=0.77,95%CI0.66-0.90)与FA风险呈负相关。乳清酸核苷(OR=4.73,95%CI=2.2-10.2)和4-胆固醇-3-酮(OR=0.52,95%CI=0.35-0.77)是与哮喘风险相关的前两种代谢产物,但与FA无关。相比之下,既患FA又患哮喘的儿童表现出与FA一致的代谢组学变化,包括脂质和类固醇水平的变化。
   结论:本研究发现,在该美国多种族前瞻性出生队列中,儿童早期血浆代谢产物存在与罹患FA或哮喘或两者皆患风险相关的特异或共同的代谢产物变化。上述发现亟待进一步验证。
 
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2024 Mar 26:S0091-6749(24)00295-1.)

 
 
Metabolomic Profiles during Early Childhood and Risk of Food Allergies and Asthma in Multi-ethnic Children from a Prospective Birth Cohort.
 
Hong X, Nadeau K, Wang G, Larman B, Smith KN, Pearson C, Ji H, Frischmeyer-Guerrerio P, Liang L, Hu FB, Wang X.
 
Abstract
BACKGROUND:There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations.
OBJECTIVE:To identify metabolites which are unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort (the Boston Birth Cohort).
METHODS:Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (N=811). FA was diagnosed based on clinical symptoms consistent with an acute hypersensitivity reaction upon food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined based on physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders.
RESULTS:During a median follow-up of 11.8±5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (OR=0.65, 95%CI=0.48-0.87) and 1-Oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR=0.77, 95%CI=0.66-0.90) were inversely associated with FA risk. Orotidine (OR=4.73, 95%CI=2.2-10.2) and 4-cholesten-3-one (OR=0.52, 95%CI=0.35-0.77) were the top two metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids.
CONCLUSION: In this U.S. multi-ethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA, asthma, or both. These findings await further validation.



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