摘要
背景：肥胖相关的并发症包括内脏脂肪、代谢异常，营养缺乏和免疫紊乱相互依存，但与儿童哮喘有独立相关性。
目的：通过量化肥胖相关并发症对症状和肺功能的影响，对儿童肥胖相关哮喘进行基因分型。
方法：采用相似网络融合和中介分析进行多组学分析，通过人体测量、代谢、营养和Th细胞转录组和DNA甲基组数据集的不同组合，量化预测肥胖哮喘表型。
结果：两组（n=28和26）在人体测量（颈围和臂围、腰臀比（WHR）和BMI z评分）、代谢、营养和Th细胞转录组方面表现不同，DNA甲基组足迹预测了7个不同数据集组合中5个或更多的肺功能指数。代谢指标减弱了颈部、腰臀比和BMI z评分与FEV1/FVC比率和ERV的相关性，颈部、中臂和BMI z评分与FRC的相关性，腰臀比与IC的相关性。营养水平减弱了颈部、上肢中围和BMI z评分与FRC的相关性，以及WHR与FEV1/FVC比率、ERV和IC的相关性。Th细胞转录组减弱了所有四种人体测量指标与FEV1/FVC比率的相关性，以及WHR与ERV和IC的相关性。DNA甲基组减弱了所有四种人体测量指标与FEV1/FVC比率和ERV的相关性，以及WHR与IC的相关性。
结论：人体测量、代谢、营养和免疫干扰对肥胖哮喘表型有独立但相互依存的贡献，WHR的作用最为一致，突出了躯干肥胖在儿童肥胖相关哮喘内型中的作用。
Endotyping pediatric obesity-related asthma: contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes, to pulmonary function
David Thompson, Lisa G Wood, Evan J Williams, Rebecca F McLoughlin, Deepa Rastogi
Abstract
Background：Obesity-related complications including visceral fat, metabolic abnormalities, nutrient deficiencies, and immune perturbations are interdependent but have been individually associated with childhood asthma.
Objective：To endotype childhood obesity-related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function.
Methods：Multi-omics analysis using Similarity Network Fusion followed by mediation analysis were performed to quantify prediction of obese asthma phenotype by different combinations of anthropometric, metabolic, nutrient, and Th cell transcriptome and DNA methylome datasets.
Results：Two clusters (n=28 and 26) distinct in their anthropometric (neck and midarm circumference, waist to hip ratio (WHR) and BMI z-score), metabolic, nutrient, and Th cell transcriptome and DNA methylome footprint predicted 5 or more pulmonary function indices across 7 different dataset combinations. Metabolic measures attenuated the association of neck, WHR and BMI z-score with FEV1/FVC ratio and ERV, of neck, midarm, and BMI z-score with FRC, but only of WHR with IC. Nutrient levels attenuated the association of neck, midarm circumference, and BMI z-score with FRC, and of WHR with FEV1/FVC ratio, ERV and IC. Th cell transcriptome attenuated the association of all four anthropometric measures with FEV1/FVC ratio, but only of WHR with ERV and IC. The DNA methylome attenuated the association of all four anthropometric measures with FEV1/FVC ratio and ERV, but only of WHR with IC.
Conclusion：Anthropometric, metabolic, nutrient, and immune perturbations have individual but interdependent contributions to obese asthma phenotype, with the most consistent effect of WHR, highlighting the role of truncal adiposity in endotyping childhood obesity-related asthma.
背景：肥胖相关的并发症包括内脏脂肪、代谢异常，营养缺乏和免疫紊乱相互依存，但与儿童哮喘有独立相关性。
目的：通过量化肥胖相关并发症对症状和肺功能的影响，对儿童肥胖相关哮喘进行基因分型。
方法：采用相似网络融合和中介分析进行多组学分析，通过人体测量、代谢、营养和Th细胞转录组和DNA甲基组数据集的不同组合，量化预测肥胖哮喘表型。
结果：两组（n=28和26）在人体测量（颈围和臂围、腰臀比（WHR）和BMI z评分）、代谢、营养和Th细胞转录组方面表现不同，DNA甲基组足迹预测了7个不同数据集组合中5个或更多的肺功能指数。代谢指标减弱了颈部、腰臀比和BMI z评分与FEV1/FVC比率和ERV的相关性，颈部、中臂和BMI z评分与FRC的相关性，腰臀比与IC的相关性。营养水平减弱了颈部、上肢中围和BMI z评分与FRC的相关性，以及WHR与FEV1/FVC比率、ERV和IC的相关性。Th细胞转录组减弱了所有四种人体测量指标与FEV1/FVC比率的相关性，以及WHR与ERV和IC的相关性。DNA甲基组减弱了所有四种人体测量指标与FEV1/FVC比率和ERV的相关性，以及WHR与IC的相关性。
结论：人体测量、代谢、营养和免疫干扰对肥胖哮喘表型有独立但相互依存的贡献，WHR的作用最为一致，突出了躯干肥胖在儿童肥胖相关哮喘内型中的作用。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol.2022 May 30;S0091-6749(22)00753-9. doi: 10.1016/j.jaci.2022.04.033.)
(J Allergy Clin Immunol.2022 May 30;S0091-6749(22)00753-9. doi: 10.1016/j.jaci.2022.04.033.)
Endotyping pediatric obesity-related asthma: contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes, to pulmonary function
David Thompson, Lisa G Wood, Evan J Williams, Rebecca F McLoughlin, Deepa Rastogi
Abstract
Background：Obesity-related complications including visceral fat, metabolic abnormalities, nutrient deficiencies, and immune perturbations are interdependent but have been individually associated with childhood asthma.
Objective：To endotype childhood obesity-related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function.
Methods：Multi-omics analysis using Similarity Network Fusion followed by mediation analysis were performed to quantify prediction of obese asthma phenotype by different combinations of anthropometric, metabolic, nutrient, and Th cell transcriptome and DNA methylome datasets.
Results：Two clusters (n=28 and 26) distinct in their anthropometric (neck and midarm circumference, waist to hip ratio (WHR) and BMI z-score), metabolic, nutrient, and Th cell transcriptome and DNA methylome footprint predicted 5 or more pulmonary function indices across 7 different dataset combinations. Metabolic measures attenuated the association of neck, WHR and BMI z-score with FEV1/FVC ratio and ERV, of neck, midarm, and BMI z-score with FRC, but only of WHR with IC. Nutrient levels attenuated the association of neck, midarm circumference, and BMI z-score with FRC, and of WHR with FEV1/FVC ratio, ERV and IC. Th cell transcriptome attenuated the association of all four anthropometric measures with FEV1/FVC ratio, but only of WHR with ERV and IC. The DNA methylome attenuated the association of all four anthropometric measures with FEV1/FVC ratio and ERV, but only of WHR with IC.
Conclusion：Anthropometric, metabolic, nutrient, and immune perturbations have individual but interdependent contributions to obese asthma phenotype, with the most consistent effect of WHR, highlighting the role of truncal adiposity in endotyping childhood obesity-related asthma.
上一篇：
没有了
下一篇：
没有了
