Viral Determinants of Childhood Asthma Exacerbation Severity and Treatment Response

Abstract

Although respiratory viruses are common triggers of asthma exacerbations, the influence of viral infection characteristics on exacerbation presentation and treatment response in the pediatric emergency department (ED) is unclear. To assess viral infection characteristics of children experiencing ED asthma exacerbations and to test their associations with severity and treatment response. This is a prospective study of children, aged 4 to 18 years, who received standard ED asthma exacerbation treatment with inhaled bronchodilators and systemic corticosteroids. Nasal swabs collected for viral metagenomic analyses determined virus presence, load, and species. Outcomes included exacerbation severity (Pediatric Asthma Severity [PAS] score, clinician impression, and vital signs) and treatment response (discharge home without needing additional asthma therapies). Of 107 children, 47% had moderate/severe exacerbations by PAS and 64% demonstrated treatment response. Viral metagenomic analysis on nasal swabs from 73 children detected virus in 86%, with 10 different species identified, primarily rhinovirus A (RV-A), RV-C, and enterovirus D68. Exacerbations involving RV-A were milder (odds ratio [OR]= 0.25; 95% confidence interval [CI]= 0.07-0.83) and tended to be more responsive to treatment than non-RV-A infections, whereas exacerbations involving enterovirus D68 were more severe (OR= 8.3; 95% CI= 1.3-164.7) and had no treatment response association. Viral load was not associated with treatment response but exhibited a strong linear relationship with heart rate (rpartial= 0.48), respiratory rate (rpartial= 0.25), and oxygen saturation (rpartial= -0.25), indicative of severity. The majority of ED asthma exacerbations are triggered by respiratory viruses. Viral species are associated with severity and treatment response, suggesting that early pathogen detection could inform ED treatment decisions. Additional studies are needed to identify differences in pathobiology underlying exacerbations triggered by different viral species, and how to effectively treat these heterogeneous exacerbations.