Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma

Nat Commun. 2021 Jun 14;12(1):3601. doi: 10.1038/s41467-021-23859-6.


Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinicalclassicmicrobiomeM. nonliquefaciensinflammationIFN-intermediate, B) clinicalatopicmicrobiomeS. pneumoniae/M. catarrhalisinflammationIFN-high, C) clinicalseveremicrobiomemixedinflammationIFN-low, and D) clinicalnon-atopicmicrobiomeM.catarrhalisinflammationIL-6. Particularly, compared with endotype A infants, endotype B infants-who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection, S. pneumoniae/M. catarrhalis codominance, and high IFN-α and -γ response-had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08-21.9; P = 0.002). Our findings provide an evidence base for the early identification of high-risk children during a critical period of airway development.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / complications*
  • Asthma / epidemiology
  • Asthma / virology*
  • Bronchiolitis, Viral / complications*
  • Bronchiolitis, Viral / virology*
  • Female
  • Gene Expression
  • Genetic Predisposition to Disease
  • Hospitalization
  • Humans
  • Infant
  • Male
  • Metabolome
  • Microbiota
  • Prospective Studies
  • Respiratory Syncytial Virus Infections / complications*
  • Respiratory Syncytial Virus Infections / epidemiology
  • Respiratory Syncytial Virus Infections / virology*
  • Respiratory Syncytial Virus, Human / genetics
  • Respiratory System
  • Rhinovirus
  • Risk Factors
  • Transcriptome
  • United States / epidemiology