Non-rhinoviruses Linked to Asthma Treatment Failure

Caroline Quach, MD, MSc

Following evidence that emergency department asthma treatment can be less effective in patients with virus infections, researchers have now identified those viruses that contribute to asthma treatment failure, but not to uniquely severe symptoms.

Researchers found that respiratory syncytial virus (RSV), influenza, and parainfluenza virus (PIV) increased the absolute risk of asthma treatment failure by 8% to 34%.

A follow-up analysis of the Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY) study conducted in 5 pediatric emergency departments in Canada has determined that while rhinovirus, the cause of the common cold, is the most prevalent, it is these non-rhinovirus pathogens that are associated with an increased absolute risk of treatment failure. Corresponding to the initial DOORWAY study findings across viral infections, however, none of the pathogens identified in the current analysis were associated with a higher severity of baseline symptoms.

"We were happy to see that children infected with rhinovirus responded as well to asthma treatment as others," principle investigator Caroline Quach, MD, MSc, Associate Professor, Department of Pediatric, Division of Infectious Diseases, Faculty of Medicine, McGill University, Montreal, Canada, told MD Magazine®.

"However, those infected with influenza, parainfluenza, and RSV (respiratory syncytial virus) had more risk of failing therapy," she added.

Quach and colleagues identified 958 children for the current study, from 1012 participants in the original DOORWAY study who had presented to an emergency department (ED) with exacerbation of asthma symptoms. Symptom severity was scored on the validated 12-point Pediatric Respiratory Asthma Measure (PRAM).

Of the 958 participants, 924 were included in full analysis, with 156 (16.9%, 95% Confidence Interval [CI] = 14.5-19.3%) failing to respond to the ED treatment. Treatment failure was defined as either requiring hospital admission, treatment in the ED lasting 8 hours or more after corticosteroid administration, or a return to the ED within 72 hours of discharge leading to hospital admission or prolonged ED stay.

Each participant provided a nasopharyngeal aspirate or swab specimen within 1 hour of study inclusion. Of 958 specimens tested, 591 (61.7%) were positive for ≥1 pathogen, with co-infection present in 81 specimens (8.5%). RSV and coronavirus were the most frequent co-pathogens (n = 13). Rhinoviruses were the most prevalent (n = 282; 29.4%), with rhinovirus C the most frequent species (n = 174; 18.2%). RSV had similar high prevalence (n = 171; 17.9%), while M pneumoniae was identified in only 2 patients.

One-third of the participants presented to the ED with severe exacerbation, as measured with PRAM, but there was no positive association between the presence of any pathogen and severe or moderate rating. Interestingly, there was actually a lower adjusted risk of severe exacerbation in the presence of a non-rhinovirus, human metapneumovirus (hMPV), or parainfluenza virus compared with no pathogen.

The presence of any pathogen was associated with an increased risk of treatment failure compared to no pathogen. Infection with a rhinovirus was not associated with high risk of failure, but non-rhinoviruses were associated with 25.4% absolute risk of treatment failure (CI: 19.8-31.0%), representing a 13.1% (CI:6.4-19.8%) adjusted risk difference than with no pathogen present.

Quach and colleagues indicate that the increased treatment failure risk in the presence of syncytial virus, influenza, and parainfluenza supports the need to prevent influenza in asthmatic children. Further, they suggest that development of expedited pathogen identification processes is warranted, and that asthma treatment intensification could be a consideration for patients infected with the pathogens which have been implicated in treatment failure.

The report, Respiratory Viruses and Treatment Failure in Children with Asthma Exacerbation, was published in Pediatrics.