“Bronchiolitis is the most common reason for hospitalization in infancy, and respiratory viruses are detected in nasal samples in more than 90% of infants hospitalized with bronchiolitis,” Heidi Makrinioti, MD, PhD, MRCPCH, explains. “Therefore, detection of respiratory viruses is strongly associated with bronchiolitis incidence and severity. A plethora of studies have linked bronchiolitis hospitalization to preschool wheeze and asthma development. More specifically, respiratory syncytial virus (RSV)-induced and rhinovirus (RV)-induced bronchiolitis have been associated with increased risk for preschool wheeze and asthma development.”
However, there is no definitive evidence that shows whether there is a differential risk—eg, that RSV confers a higher or lower risk compared with RV—for chronic respiratory outcomes development, according to Dr. Makrinioti.
For a study published in Pediatric Allergy and Immunology, Dr. Makrinioti and colleagues conducted a systematic review and meta-analysis that examined the associations of RSV-induced and RV-induced bronchiolitis with preschool wheeze and childhood asthma. The researchers included 38 studies in their analysis, eight of which examined the association between infant bronchiolitis and recurrent wheeze and nine that included data on childhood asthma development.
Findings ‘Challenge the Current Dogma’ Regarding RSV Bronchiolitis
Results of the present study include “some important findings for clinicians involved in the care of infants with bronchiolitis,” Dr. Makrinioti says (Infographic).
“An expected finding was that infants hospitalized with RSV-induced bronchiolitis have higher odds of developing recurrent wheeze and asthma when compared with healthy infants,” she explains. “These odds reflect the association between bronchiolitis and recurrent wheeze and asthma when compared with a healthy population and do not consist of a measurement of effect of RSV exposure. When attempting to compare RSV and non-RSV exposures in the magnitude of recurrent wheeze and asthma development, there was no significant difference noted.”
Cumulative odds of developing recurrent wheeze and asthma after RSV bronchiolitis was not different than the odds of developing recurrent wheeze and asthma following non-RSV bronchiolitis, “implying that there are other exposures beyond RSV bronchiolitis that are associated with increased odds of chronic respiratory sequela development,” Dr. Makrinioti notes. “When performing a sub-analysis on a specific non-RSV-induced bronchiolitis exposures—an RV exposure—the odds were significantly higher for infants hospitalized with RV-induced bronchiolitis as compared with infants hospitalized with RSV-induced bronchiolitis.”
These results “challenge the current dogma around RSV bronchiolitis,” according to Dr. Makrinioti. “Although RSV bronchiolitis is indeed associated with increased severity, there is no evidence showing that it is significantly associated with recurrent wheeze and/or asthma development.”
Directions for Future Research: Biomarkers & Comparison of Respiratory Viruses
The current study should encourage clinicians “to ‘think outside the RSV exposure box’ when considering risk for recurrent wheeze and asthma development,” Dr. Makrinioti says. However, she acknowledges that the current research is based on a limited number of cohort studies that directly compared RSV-induced and RV-induced bronchiolitis exposures.
“Future studies will add to these comparisons,” she notes. “At that point, clinicians will be clearer about the benefits of utilizing a point-of-care respiratory virus test in guiding decision making for follow-up of these infants. It is also likely that, in addition to respiratory viral exposures, there are other confounders in this pathway (eg, allergic sensitization), and cohort studies exploring interactions between these exposures and recurrent wheeze and asthma development are eagerly anticipated.”
The variability in both clinical symptoms and treatment responses are significant barriers to timely diagnosis and effective treatment and follow-up.
“Bronchiolitis is the most common respiratory infection in infancy still managed with conservative methods, including oxygen supplementation and feeding support,” she says. “Point-of-care tests for RSV are inexpensive and can potentially provide good biomarkers for future asthma development. Existing evidence, though, even the evidence from our meta-analysis, cannot justify using RSV-negative tests to guide follow-up for asthma development.”
More studies that directly compare respiratory viral exposures in the magnitude of asthma development are needed.
“In addition, the interaction between exposures and host responses to exposures might mediate the causal pathway from bronchiolitis to asthma,” Dr. Makrinioti explains. “There are point-ofcare tests that detect more than respiratory virus biomarkers, including peripheral blood cells, cytokines, and microRNAs. Future research targeted in identifying new sensitive biomarkers or testing existing biomarkers, such as a combination of respiratory virus and cytokines biomarkers, in infants with bronchiolitis can possibly help identify infants with bronchiolitis at risk for recurrent wheeze and asthma development and contribute toward asthma prevention.”