Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years

Background: A better understanding of bronchiolitis heterogeneity might help clarify its relationship with the development of recurrent wheezing and asthma. Objectives: We sought to identify severe bronchiolitis profiles using a clustering approach and to investigate for the first time their association with allergy/inflammatory biomarkers, nasopharyngeal microbiota, and development of recurrent wheezing by age 3 years. Methods: We analyzed data from a prospective, 17-center US cohort study of 921 infants (age < 1 year) hospitalized with bronchiolitis (2011-2014 winters) with posthospitalization follow-up. Severe bronchiolitis profiles at baseline (hospitalization) were determined by using latent class analysis based on clinical factors and viral etiology. Blood biomarkers and nasopharyngeal microbiota profiles were determined by using samples collected within 24 hours of hospitalization. Recurrent wheezing by age 3 years was defined based on parental report of breathing problem episodes after discharge. Results: Three severe bronchiolitis profiles were identified: profile A (15%), which was characterized by a history of breathing problems/eczema during infancy and non-respiratory syncytial virus (mostly rhinovirus) infection; profile B (49%), which has the largest probability of respiratory syncytial virus infection and resembled classic respiratory syncytial virus-induced bronchiolitis; and profile C (36%), which was composed of the most severely ill group. Profile A infants had higher eosinophil counts, higher cathelicidin levels, and increased proportions of Haemophilus-dominant or Moraxella-dominant microbiota profiles. Compared with profile B, we observed significantly increased risk of recurrent wheezing in children with profile A (hazard ratio, 2.64; 95% CI, 1.90-3.68) and, to a lesser extent, with profile C (hazard ratio, 1.51; 95% CI, 1.14-2.01). Conclusion: Although longer follow-up is needed, our results might help identify, among children hospitalized for bronchiolitis, subgroups with particularly increased risk of asthma.