Integrated nasopharyngeal airway metagenome and asthma genetic risk endotyping of severe bronchiolitis in infancy and risk of childhood asthma
Abstract
Graphical abstract Overview of the study. MARC-35: 35th Multicenter Airway Research Collaboration; PRS: polygenic risk score; M. catarrhalis: Moraxella catarrhalis; RSV: respiratory syncytial virus; S. pneumoniae: Streptococcus pneumoniae; H. influenzae: Haemophilus influenzae; RV: rhinovirus. Background Infants with bronchiolitis are at increased risk of developing asthma. Growing evidence suggests bronchiolitis is a heterogeneous condition. However, little is known about its biologically distinct subgroups based on the integrated metagenome and asthma genetic risk signature and their longitudinal relationships with asthma development. Methods In a multicentre prospective cohort study of infants with severe bronchiolitis (i.e. bronchiolitis requiring hospitalisation), we profiled nasopharyngeal airway metagenome and virus at hospitalisation, and calculated the polygenic risk score of asthma. Using similarity network fusion clustering approach, we identified integrated metagenome–asthma genetic risk endotypes. In addition, we examined their longitudinal association with the risk of developing asthma by the age of 6 years. Results Out of 450 infants with bronchiolitis (median age 3 months), we identified five distinct endotypes, characterised by their nasopharyngeal metagenome, virus and asthma genetic risk profiles. Compared with endotype A infants (who clinically resembled “classic” bronchiolitis), endotype E infants (characterised by a high abundance of Haemophilus…
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