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Integrated associations of nasopharyngeal and serum metabolome with bronchiolitis severity and asthma: A multicenter prospective cohort study
Author(s) -
Fujiogi Michimasa,
Camargo Carlos A.,
Raita Yoshihiko,
Zhu Zhaozhong,
Celedón Juan C.,
Mansbach Jonathan M.,
Spergel Jonathan M.,
Hasegawa Kohei
Publication year - 2021
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.13466
Subject(s) - medicine , bronchiolitis , asthma , metabolome , prospective cohort study , cohort , cohort study , carnitine , immunology , respiratory system , metabolite
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.