Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Pediatr Allergy Immunol. 2020 Oct;31(7):755-766. doi: 10.1111/pai.13296. Epub 2020 Jun 10.
Bronchiolitis is the leading cause of infant hospitalizations in the United States. Growing evidence supports the heterogeneity of bronchiolitis. However, little is known about the interrelationships between major respiratory viruses (and their species), host systemic metabolism, and disease pathobiology.
In an ongoing multicenter prospective cohort study, we profiled the serum metabolome in 113 infants (63 RSV-only, 21 RV-A, and 29 RV-C) hospitalized with bronchiolitis. We identified serum metabolites that are most discriminatory in the RSV-RV-A and RSV-RV-C comparisons using sparse partial least squares discriminant analysis. We then investigated the association between discriminatory metabolites with acute and chronic outcomes.
In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (P < 0.05). In the RSV-RV-A comparison, we identified 30 discriminatory metabolites, predominantly in lipid metabolism pathways (eg, sphingolipids and carnitines). In multivariable models, these metabolites were significantly associated with the risk of clinical outcomes (eg, tricosanoyl sphingomyelin, OR for recurrent wheezing at age of 3 years = 1.50; 95% CI: 1.05-2.15). In the RSV-RV-C comparison, the discriminatory metabolites were also primarily involved in lipid metabolism (eg, glycerophosphocholines [GPCs], 12,13-diHome). These metabolites were also significantly associated with the risk of outcomes (eg, 1-stearoyl-2-linoleoyl-GPC, OR for positive pressure ventilation use during hospitalization = 0.47; 95% CI: 0.28-0.78).
Respiratory viruses and their species had distinct serum metabolomic signatures that are associated with differential risks of acute and chronic morbidities of bronchiolitis. Our findings advance research into the complex interrelations between viruses, host systemic response, and bronchiolitis pathobiology.
毛细支气管炎是美国婴幼儿住院的主要原因。越来越多的证据支持毛细支气管炎的异质性。然而，对于主要呼吸道病毒（及其种属）、宿主全身代谢和疾病病理生物学之间的相互关系知之甚少。
在一项正在进行的多中心前瞻性队列研究中，我们对 113 例毛细支气管炎住院婴儿（63 例仅 RSV、21 例 RV-A 和 29 例 RV-C）的血清代谢组进行了分析。我们使用稀疏偏最小二乘判别分析确定了在 RSV-RV-A 和 RSV-RV-C 比较中最具判别力的血清代谢物。然后，我们研究了有判别力的代谢物与急性和慢性结局之间的关联。
在 113 例毛细支气管炎患儿中，我们测量了 639 种代谢物。两种比较中血清代谢组图谱均有差异（P ＜ 0.05）。在 RSV-RV-A 比较中，我们确定了 30 种有判别力的代谢物，主要涉及脂质代谢途径（如神经鞘脂和肉碱）。在多变量模型中，这些代谢物与临床结局的风险显著相关（例如，三癸酰基神经鞘氨醇，3 岁时反复喘息的 OR = 1.50；95%CI：1.05-2.15）。在 RSV-RV-C 比较中，有判别力的代谢物也主要涉及脂质代谢（如甘油磷酸胆碱 [GPC]，12,13-二氢）。这些代谢物也与结局的风险显著相关（例如，1-硬脂酰基-2-亚油酰基-GPC，住院期间需要正压通气的 OR = 0.47；95%CI：0.28-0.78）。
呼吸道病毒及其种属具有不同的血清代谢组学特征，与毛细支气管炎的急性和慢性发病率的差异风险相关。我们的研究结果推进了病毒、宿主全身反应和毛细支气管炎病理生物学之间复杂关系的研究。
