Michimasa Fujiogi1, Carlos A Camargo1, Yoshihiko Raita1, Zhaozhong Zhu1, Juan C Celedón2, Jonathan M Mansbach3, Jonathan M Spergel4, Kohei Hasegawa1. 1. Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 2. Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA. 3. Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 4. Department of Pediatrics, Perelman School of Medicine and Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abstract
BACKGROUND: While infant bronchiolitis contributes to substantial acute (eg, severity) and chronic (eg, asthma development) morbidities, its pathobiology remains uncertain. We examined the integrated relationships of local (nasopharyngeal) and systemic (serum) responses with bronchiolitis morbidities. METHODS: In a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we applied a network analysis approach to identify distinct networks (modules)-clusters of densely interconnected metabolites-of the nasopharyngeal and serum metabolome. We examined their individual and integrated relationships with acute severity (defined by positive pressure ventilation [PPV] use) and asthma development by age 5 years. RESULTS: In 140 infants, we identified 285 nasopharyngeal and 639 serum metabolites. Network analysis revealed 7 nasopharyngeal and 8 serum modules. At the individual module level, nasopharyngeal-amino acid, tricarboxylic acid (TCA) cycle, and carnitine modules were associated with higher risk of PPV use (r > .20; P < .001), while serum-carnitine, amino acid, and glycerophosphorylcholine (GPC)/glycerophosphorylethanolamine (GPE) modules were associated with lower risk (all r < -.20; P < .05). The integrated analysis for PPV use revealed consistent findings-for example, nasopharyngeal-TCA (adjOR: 2.87, 95% CI: 1.68-12.2) and serum-GPC/GPE (adjOR: 0.54, 95% CI: 0.38-0.80) modules-and an additional module-serum-glucose-alanine cycle module (adjOR: 0.69, 95% CI: 0.56-0.86). With asthma risk, there were no individual associations, but there were integrated associations (eg, nasopharyngeal-carnitine module; adjOR: 1.48, 95% CI: 1.11-1.99). CONCLUSION: In infants with bronchiolitis, we found integrated relationships of local and systemic metabolome networks with acute and chronic morbidity. Our findings advance research into the complex interplay among respiratory viruses, local and systemic response, and disease pathobiology in infants with bronchiolitis.
BACKGROUND: While infant bronchiolitis contributes to substantial acute (eg, severity) and chronic (eg, asthma development) morbidities, its pathobiology remains uncertain. We examined the integrated relationships of local (nasopharyngeal) and systemic (serum) responses with bronchiolitis morbidities. METHODS: In a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we applied a network analysis approach to identify distinct networks (modules)-clusters of densely interconnected metabolites-of the nasopharyngeal and serum metabolome. We examined their individual and integrated relationships with acute severity (defined by positive pressure ventilation [PPV] use) and asthma development by age 5 years. RESULTS: In 140 infants, we identified 285 nasopharyngeal and 639 serum metabolites. Network analysis revealed 7 nasopharyngeal and 8 serum modules. At the individual module level, nasopharyngeal-amino acid, tricarboxylic acid (TCA) cycle, and carnitine modules were associated with higher risk of PPV use (r > .20; P < .001), while serum-carnitine, amino acid, and glycerophosphorylcholine (GPC)/glycerophosphorylethanolamine (GPE) modules were associated with lower risk (all r < -.20; P < .05). The integrated analysis for PPV use revealed consistent findings-for example, nasopharyngeal-TCA (adjOR: 2.87, 95% CI: 1.68-12.2) and serum-GPC/GPE (adjOR: 0.54, 95% CI: 0.38-0.80) modules-and an additional module-serum-glucose-alanine cycle module (adjOR: 0.69, 95% CI: 0.56-0.86). With asthma risk, there were no individual associations, but there were integrated associations (eg, nasopharyngeal-carnitine module; adjOR: 1.48, 95% CI: 1.11-1.99). CONCLUSION: In infants with bronchiolitis, we found integrated relationships of local and systemic metabolome networks with acute and chronic morbidity. Our findings advance research into the complex interplay among respiratory viruses, local and systemic response, and disease pathobiology in infants with bronchiolitis.
Authors: Carlos A Camargo; Tristram Ingham; Kristin Wickens; Ravi Thadhani; Karen M Silvers; Michael J Epton; G Ian Town; Philip K Pattemore; Janice A Espinola; Julian Crane Journal: Pediatrics Date: 2010-12-27 Impact factor: 7.124
Authors: Kohei Hasegawa; Claire E Hoptay; Brennan Harmon; Juan C Celedón; Jonathan M Mansbach; Pedro A Piedra; Robert J Freishtat; Carlos A Camargo Journal: Allergy Date: 2019-02-01 Impact factor: 13.146
Authors: Laura Toivonen; Carlos A Camargo; James E Gern; Yury A Bochkov; Jonathan M Mansbach; Pedro A Piedra; Kohei Hasegawa Journal: J Allergy Clin Immunol Date: 2019-01-14 Impact factor: 10.793
Authors: Rachel S Kelly; Bo L Chawes; Kevin Blighe; Yamini V Virkud; Damien C Croteau-Chonka; Michael J McGeachie; Clary B Clish; Kevin Bullock; Juan C Celedón; Scott T Weiss; Jessica A Lasky-Su Journal: Chest Date: 2018-06-13 Impact factor: 9.410
Authors: Yoshihiko Raita; Marcos Pérez-Losada; Robert J Freishtat; Andrea Hahn; Eduardo Castro-Nallar; Ignacio Ramos-Tapia; Nathaniel Stearrett; Yury A Bochkov; James E Gern; Jonathan M Mansbach; Zhaozhong Zhu; Carlos A Camargo; Kohei Hasegawa Journal: Eur Respir J Date: 2022-07-13 Impact factor: 33.795
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