Metabolome subtyping of severe bronchiolitis in infancy and risk of childhood asthma.
Metabolome subtyping of severe bronchiolitis in infancy and risk of childhood asthma.
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DOI：
10.1016/j.jaci.2021.05.036
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Hasegawa K
中科院分区：
文献类型：
--
作者：
Zhu Z;Camargo CA Jr;Raita Y;Fujiogi M;Liang L;Rhee EP;Woodruff PG;Hasegawa K
患有细支气管炎的婴儿患哮喘的风险增加。越来越多的证据表明细支气管炎是一种异质性疾病。根据代谢组学特征（代谢型），确定严重毛细支气管炎婴儿的生物学不同亚组，并检查其与哮喘发展的纵向关系。在一项针对因毛细支气管炎住院的婴儿（年龄<12个月）的多中心前瞻性队列研究中，在住院时对鼻咽气道代谢组进行了分析。使用聚类方法，我们确定了相互排斥的代谢型。我们还研究了它们与5岁时患哮喘风险的纵向关系。在918名因毛细支气管炎住院的婴儿（中位年龄，3个月）中，我们确定了5种不同的代谢型-以其鼻咽代谢组学特征为特征：A）甘油磷酸胆碱-高; B）氨基酸-高，多不饱和脂肪酸（PUFA）-低; C）氨基酸-高，甘油磷脂-低; D）甘油磷脂-高; E）混合。与代谢型A婴儿（临床上类似“典型”毛细支气管炎）相比，代谢型B婴儿发生哮喘的风险显著更高（23%对41%; OR调整后，2.22：95%CI，1.07-4.69）。途径分析显示代谢型B具有富集的氨基酸（例如，蛋氨酸、组氨酸、谷胱甘肽）和α-亚麻酸/亚油酸代谢途径（所有FDR<5<×10−14）。最后，转录组分析显示，代谢型B婴儿具有上调的干扰素-α和白细胞介素-6/Janus激酶/信号转导转录激活因子（IL-6/JAK/STAT 3）通路以及下调的脂肪酸代谢通路（FDR均<0.05）。在这项婴儿严重细支气管炎的多中心前瞻性队列研究中，代谢组学数据的聚类分析确定了生物学上不同的代谢型，包括一种以高炎性氨基酸和低PUFA为特征的代谢型，其发生哮喘的风险显著增加。在患有严重细支气管炎的婴儿中，鼻咽气道代谢组的聚类分析确定了生物学上不同的代谢型，包括一种特征为高炎性氨基酸和低PUFA的代谢型，其发生哮喘的风险增加。
Infants with bronchiolitis are at increased risk for developing asthma. Growing evidence suggests bronchiolitis is a heterogeneous condition. To identify biologically-distinct subgroups based on the metabolome signatures (metabotypes) in infants with severe bronchiolitis and to examine their longitudinal relationships with asthma development. In a multi-center prospective cohort study of infants (aged <12 months) hospitalized for bronchiolitis, the nasopharyngeal airway metabolome was profiled at hospitalization. Using a clustering approach, we identified mutually-exclusive metabotypes. We also examined their longitudinal association with the risk of developing asthma by age five years. Of 918 infants hospitalized for bronchiolitis (median age, 3 months), we identified 5 distinct metabotypes—characterized by their nasopharyngeal metabolome profile: A) glycerophosphocholine-high; B) amino acid-high, polyunsaturated fatty acid (PUFA)-low; C) amino acid-high, glycerophospholipid-low; D) glycerophospholipid-high; and E) mixed. Compared with metabotype A infants (who clinically resembled “classic” bronchiolitis), metabotype B infants had a significantly higher risk for developing asthma (23% vs. 41%; ORadjusted, 2.22: 95%CI, 1.07-4.69). The pathway analysis showed that metabotype B had enriched amino acid (e.g., methionine, histidine, glutathione) and α-linolenic/linoleic acid metabolism pathways (all FDR<5<×10−14). Finally, the transcriptome analysis revealed that metabotype B infants had up-regulated interferon-α and interleukin-6/Janus kinase/signal transducer activator of transcription (IL-6/JAK/STAT3) pathways and down-regulated fatty acid metabolism pathways (both FDR<0.05). In this multicenter prospective cohort study of infant severe bronchiolitis, the clustering analysis of metabolome data identified biologically-distinct metabotypes, including one characterized by high inflammatory amino acids and low PUFAs that is at significantly increased risk for developing asthma. Among infant with severe bronchiolitis, clustering analysis of the nasopharyngeal airway metabolome identified biologically distinct metabotypes, including one characterized by high inflammatory amino acids and low PUFAs that is at increased risk for developing asthma.
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影响因子：
14.9
作者：
Frolkis A;Knox C;Lim E;Jewison T;Law V;Hau DD;Liu P;Gautam B;Ly S;Guo AC;Xia J;Liang Y;Shrivastava S;Wishart DS
通讯作者：
Wishart DS
影响因子：
10
作者：
Dumas O;Mansbach JM;Jartti T;Hasegawa K;Sullivan AF;Piedra PA;Camargo CA Jr
通讯作者：
Camargo CA Jr
DOI：
10.1016/j.jaci.2018.08.043
发表时间：
2019-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Dumas O;Hasegawa K;Mansbach JM;Sullivan AF;Piedra PA;Camargo CA Jr
通讯作者：
Camargo CA Jr
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1183/13993003.00152-2016
发表时间：
2016-11
期刊：
The European respiratory journal
影响因子：
--
作者：
Hasegawa K;Mansbach JM;Ajami NJ;Espinola JA;Henke DM;Petrosino JF;Piedra PA;Shaw CA;Sullivan AF;Camargo CA Jr;the MARC-35 Investigators
通讯作者：
the MARC-35 Investigators