Metabolome subtyping of severe bronchiolitis in infancy and risk of childhood asthma - 05/01/22
, Carlos A. Camargo, MD, DrPH a, Yoshihiko Raita, MD, MPH, MMSc a, Michimasa Fujiogi, MD a, Liming Liang, PhD b, c, Eugene P. Rhee, MD d, Prescott G. Woodruff, MD, MPH e, Kohei Hasegawa, MD, MPH aAbstract |
Background |
Infants with bronchiolitis are at increased risk for developing asthma. Growing evidence suggests bronchiolitis is a heterogeneous condition.
Objectives |
We sought to identify biologically distinct subgroups based on the metabolome signatures (metabotypes) in infants with severe bronchiolitis and to examine the longitudinal relationships of metabotypes with asthma development.
Methods |
In a multicenter prospective cohort study of infants (age, <12 months) hospitalized for bronchiolitis, the nasopharyngeal airway metabolome was profiled at hospitalization. Using a clustering approach, this study identified mutually exclusive metabotypes. This study also examined their longitudinal association with the risk of developing asthma by 5 years of age.
Results |
Of 918 infants hospitalized for bronchiolitis (median age, 3 months), this study identified 5 distinct metabotypes—characterized by their nasopharyngeal metabolome profile: A, glycerophosphocholine-high; B, amino acid–high, polyunsaturated fatty acid–low; C, amino acid–high, glycerophospholipid-low; D, glycerophospholipid-high; and E, mixed. Compared with infants with metabotype A (who clinically resembled “classic” bronchiolitis), infants with metabotype B had a significantly higher risk for developing asthma (23% vs 41%; adjusted odds ratio, 2.22; 95% CI, 1.07-4.69). The pathway analysis showed that metabotype B had enriched amino acid (eg, methionine, histidine, glutathione) and α-linolenic/linoleic acid metabolism pathways (false discovery rate, <5 × 10−14 for all). Finally, the transcriptome analysis revealed that infants with metabotype B had upregulated IFN-α and IL-6/JAK/STAT3 pathways and downregulated fatty acid metabolism pathways (false discovery rate, <0.05 for both).
Conclusions |
In this multicenter prospective cohort study of infants with severe bronchiolitis, the clustering analysis of metabolome data identified biologically distinct metabotypes, including a metabotype characterized by high inflammatory amino acids and low polyunsaturated fatty acids that is at significantly increased risk for developing asthma.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Severe bronchiolitis, heterogeneity, subtype, asthma, metabolome, inflammatory amino acids, polyunsaturated fatty acids, transcriptome
Abbreviations used : FDR, GP, HODE, HRadj, OR, PUFA
Plan
| This study was supported by the National Institutes of Health (grants K01 AI-153558, U01 AI-087881, R01 AI-114552, R01 AI-127507, R01 AI-134940, R01 AI-137091, R01 AI-148338, and UG3/UH3 OD-023253). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding organizations were not involved in the collection, management, or analysis of the data; preparation or approval of the manuscript; or decision to submit the manuscript for publication. |
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| Disclosure of potential conflict of interest: Z. Zhu reports grants from National Institutes of Health during the conduct of the study. C. A. Camargo reports grants from National Institutes of Health during the conduct of the study. P. G. Woodruff reports personal fees from Sanofi, Regeneron, Astra Zeneca, Glenmark Pharma, Theravance, NGM Pharma, and GSK, outside the submitted work. K. Hasegawa reports grants from National Institutes of Health during the conduct of the study; and grants from Novartis, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 149 - N° 1
P. 102-112 - janvier 2022 Retour au numéro
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