Metabolome subtyping of severe bronchiolitis in infancy and risk of childhood asthma.
J Allergy Clin Immunol
; 149(1): 102-112, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34119532
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Bronquiolite
/
Metaboloma
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article