Published online: November 15, 2019
Bronchiolitis is an acute respiratory infection and the leading cause of hospitalization for US infants, accounting for ~130,000 hospitalizations annually. This large group of infants is 3-4 times more likely than healthy infants to develop long-term respiratory morbidity, including recurrent wheezing and childhood asthma. Most research examining the association between severe bronchiolitis (which requires hospitalization) and recurrent wheezing has focused on the viruses that cause bronchiolitis (such as respiratory syncytial virus). However, viruses infect infant airways colonized with bacteria, which composes part of the airway microbiome. Of relevance to human health, these bacteria have genes and make functional products that have been shown to influence multiple conditions, such as obesity and diabetes. Based on previous research, the authors were interested in 3 specific bacteria that may be related to wheezing and asthma: Moraxella, Haemophilus, and Streptococcus.
In an original article recently published in The Journal of Allergy and Clinical Immunology (JACI), Mansbach and colleagues analyzed data from the 35th Multicenter Airway Research Collaboration (MARC-35) cohort study. Over 3 consecutive winter seasons (i.e., November to April) from 2011-2014, site teams at 17 hospitals in 14 U.S. states enrolled infants (age less than 1 year) who were hospitalized for bronchiolitis. Within 24 hours of hospitalization, site teams collected clinical data and nasal samples. During the hospitalization, site teams taught parents how to collect nasal swabs, which they collected at 3 time points after hospitalization: 1) 3 weeks after the date of hospitalization; 2) the summer following hospitalization when the children were healthy; and 3) the year following hospitalization when the children were healthy.
The study team tested samples collected during the hospitalization for 17 different respiratory viruses. They also tested nasal swabs from hospitalization and the 3 later time points to generate microbiome data. Based on biannual parent phone interviews, the primary outcome was recurrent wheezing by age 3 years. Since wheezing may be transient, the study team extended this outcome to children who had recurrent wheezing by age 3 years and also had asthma at age 4 years. Both cross-sectional and longitudinal statistical methods were used to analyze these data.
Of 921 infants in the long-term MARC-35 cohort, there were 842 infants (91%) with a total of 2,086 nasal swabs who met quality control requirements. These 842 infants had a median age at hospitalization of 3 months and 80% had no history of wheezing. At age 3 years, there was 88% follow-up and 265 (31%) infants had developed recurrent wheezing. In both cross sectional and longitudinal analyses, Haemophilus was not associated with the outcomes. By contrast, higher Moraxella and Streptococcus abundance in the weeks and months after hospitalization was associated with an increased risk of recurrent wheezing. Specifically, the authors found that every 10% increase in the abundance of Moraxella in the weeks after hospitalization was significantly associated with a 38% increase in the risk of developing recurrent wheezing by age 3 years, even after controlling for 16 other factors that may confound this association. In addition, every 10% increase in Streptococcus abundance in the weeks after hospitalization or the summer after hospitalization were both significantly associated with a 76% increase in the risk of developing recurrent wheezing by age 3 years. Supportive of the recurrent wheezing results, the authors also found that children with higher Moraxella and Streptococcus abundance 3 weeks after hospitalization had an increased risk of recurrent wheezing accompanied by age 4 year asthma.
In summary, the authors found in a large, prospective, multicenter cohort of U.S. infants hospitalized with bronchiolitis that increased abundance of nasal Moraxella or Streptococcus in the weeks and months following hospitalization was related to recurrent wheezing by age 3 years. These results not only confirmed that Moraxella and Streptococcus are “higher risk” bacteria, but also identified that the weeks after hospitalization may provide a potential window of opportunity for clinicians to influence the chronic respiratory outcomes for this high-risk group of children. Currently, there is no proven preventive intervention for the long-term respiratory morbidity that often follows severe bronchiolitis. These findings provide a starting point to begin investigations of new approaches to the management of severe bronchiolitis (such as altering the airway microbiome) and possibly preventing the onset of childhood asthma.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.