Michimasa Fujiogi1, Carlos A Camargo1, Yoshihiko Raita1, Yury A Bochkov2, James E Gern2,3, Jonathan M Mansbach4, Pedro A Piedra5, Kohei Hasegawa1. 1. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 2. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 3. Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 4. Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 5. Departments of Molecular Virology and Microbiology and Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (Ppermutation < 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). CONCLUSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: In 113 infants with bronchiolitis, we measured 639 metabolites. Serum metabolomic profiles differed in both comparisons (Ppermutation < 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). CONCLUSION: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.
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Authors: Peter Liptak; Eva Baranovicova; Robert Rosolanka; Katarina Simekova; Anna Bobcakova; Robert Vysehradsky; Martin Duricek; Zuzana Dankova; Andrea Kapinova; Dana Dvorska; Erika Halasova; Peter Banovcin Journal: Metabolites Date: 2022-07-13
Authors: Michimasa Fujiogi; Yoshihiko Raita; Marcos Pérez-Losada; Robert J Freishtat; Juan C Celedón; Jonathan M Mansbach; Pedro A Piedra; Zhaozhong Zhu; Carlos A Camargo; Kohei Hasegawa Journal: Nat Commun Date: 2022-08-30 Impact factor: 17.694