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. 2025 Jan;13(1):95-104.e5.
doi: 10.1016/j.jaip.2024.09.020. Epub 2024 Oct 3.

Viral Determinants of Childhood Asthma Exacerbation Severity and Treatment Response

Nidhya Navanandan  1 , Nathan D Jackson  2 , Katharine L Hamlington  3 , Jamie L Everman  2 , Elmar Pruesse  2 , Elizabeth A Secor  2 , Zoe Stewart  2 , Katrina Diener  2 , Isabel Hardee  4 , Alec Edid  5 , Helio Sulbaran  5 , Rakesh D Mistry  6 , Todd A Florin  7 , Angela C Yoder  8 , Camille M Moore  9 , Stanley J Szefler  3 , Andrew H Liu  3 , Max A Seibold  10
Affiliations

Viral Determinants of Childhood Asthma Exacerbation Severity and Treatment Response

Nidhya Navanandan et al. J Allergy Clin Immunol Pract. 2025 Jan.

Abstract

Background: 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.

Objective: To assess viral infection characteristics of children experiencing ED asthma exacerbations and to test their associations with severity and treatment response.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: Asthma exacerbation; Children; Emergency department; Severity; Treatment response.

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Conflict of interest statement

Conflicts of Interest: Dr. Navanandan reported grants from the National Institutes of Health, Doris Duke Foundation, and Children’s Hospital Colorado Research Institute during the conduct of the study. Dr. Szefler reported consulting for Astra Zeneca, Eli Lilly, GlaxoSmithKline, Moderna, OM Pharma, Propeller Health, Regeneron and Sanofi and receiving research support from the National Institutes of Health National Heart, Lung and Blood Institute, Propeller Health, and the Colorado Department of Public Health and Environment (CDPHE) Cancer, Cardiovascular and Pulmonary Disease Program. Dr. Liu reported consulting for Phadia ThermoFisher Scientific, Labcorp, AstraZeneca, and OM Pharma, receiving research support from the National Institutes of Health, ResMed and OM Pharma, and receiving non-monetary research support from ResMed/Propeller Health and Revenio. Dr. Everman reported patents pending to National Jewish Health. Dr. Seibold reported consulting with Escient Pharmaceuticals Inc, receiving research support from the National Institutes of Health, and having patents pending to National Jewish Health. No other disclosures were reported.

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