Abstract
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.
Highlights
Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in U.S infants, and a major risk factor for asthma development
Of the infants enrolled into this longitudinal cohort, this study included 221 infants with respiratory syncytial virus (RSV) bronchiolitis who were randomly selected for the nasopharyngeal microbiome, transcriptome, and metabolome testing (Supplementary Fig. 1)
Virus, nasopharyngeal microbiome, transcriptome, and metabolome data from a multicentre prospective cohort study of 221 infants with RSV bronchiolitis, we identified four biologically distinct endotypes
Summary
Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in U.S infants, and a major risk factor for asthma development. 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. While bronchiolitis has been considered a single disease with similar mechanisms[2], emerging evidence suggests heterogeneity in clinical presentations[4] and chronic morbidities (e.g., subsequent risk of recurrent wheeze and asthma)[5,6]. Growing evidence suggests distinct upper airway microbiome[7,8], transcriptome[9], cytokine[10,11], and metabolome[12] profiles among infants with bronchiolitis. These findings have been solely derived from single-level (e.g., clinical or microbiome) data. Our still limited understanding of the heterogeneity of RSV bronchiolitis during infancy—an important period of lung development—has hindered efforts to develop endotype-specific
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