Increased Moraxella and Streptococcus Species Abundance After Severe Bronchiolitis Is Associated With Recurrent Wheezing

This study evaluated the association between infant nasal microbiota at bronchiolitis-related hospitalization, as well as three later points, and risk of recurrent wheezing by age three or asthma by age four.

This multi-center study included 842 infants under the age of one who were hospitalized for viral bronchiolitis. Mean age at enrollment was 3.2 months.

Enrolled participants received nasopharyngeal swabs sent for 16s rRNA sequencing at four different time periods. Site researchers obtained initial nasopharyngeal swabs for sequencing and viral PCR testing within 24 hours of hospitalization for bronchiolitis. Caretakers were taught how to obtain samples prior to discharge. “Clearance” swabs were obtained three weeks post-hospitalization. “Summer” swabs were obtained in the months of June, July or August post-hospitalization. “Healthy” swabs were obtained one year after hospitalization during a randomly assigned season. A longitudinal analysis with joint modeling was done to characterize the relationship between microbiota abundance and recurrent wheezing.

Overall, 31% of enrolled patients had recurrent wheezing by the age of three. Patient characteristics associated with recurrent wheezing included older age at time of enrollment, maternal history of asthma, and RSV-negative bronchiolitis. At time of hospitalization, cross-sectional analyses of nasal swabs did not show a significant association between microbiota and risk of recurrent wheezing; however, significant associations were seen at subsequent time points. At the “clearance” time point, a 10% increase in the relative abundance of Moraxella (HR 1.75; 95% HDI 1.13–3.18) and Streptococcus (HR 2.84; 95% HDI 1.07–9.03) were associated with recurrent wheezing and asthma. In the summer posthospitalization, relative abundance of Streptococcus was also associated with recurrent wheezing (HR 1.76; 95% HDI 1.15–3.27). No associations were found with Haemophilus species.

Nasal microbiota at time of hospital admission for bronchiolitis was not associated with recurrent wheezing. However, changes in posthospitalization nasal microbiota, specifically increased relative abundance of Moraxella or Streptococcus three weeks posthospitalization and Streptococcus in the summer after hospitalization, were found to be associated with recurrent wheezing

This is the first study to show longitudinal associations with nasal microbiota and recurrent wheezing. While further confirmatory studies are required, it has identified a potential window for intervention to alter the nasal microbiome and decrease risk of recurrent wheezing and potentially asthma in children.