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Background In asthmatic children, 60–80% of exacerbations are triggered by respiratory pathogens and represent an important burden of illness. The impact of pathogens on exacerbation severity and treatment response remains unclear. Our aim was to describe the prevalence of respiratory pathogens in children presenting to the emergency department (ED) and investigate the association between pathogens and (i) exacerbation severity on presentation and (ii) ED treatment failure. Methods We performed a secondary analysis of the DOORWAY study, a prospective multi-center cohort of children (1–17 years) presenting to the ED with moderate or severe asthma exacerbation. All received per protocol oral corticosteroids and bronchodilators. Nasopharyngeal (NPA) secretions were analyzed by RT-PCR for 30 different pathogens. Linear and logistic multivariate regression models were used to estimate absolute risks and risk differences (RD) with their 95% CI representing average marginal effects. Results Of 958 patients with NPA specimens, 591 (61.7%) were positive for ≥ 1 pathogens; human rhinovirus (HRV) was the most prevalent (29.4%). Non-HRV infection (RD -12.9%; 95% CI -19.5; -6.3), human metapneumovirus (RD -13.6%; 95% CI -23.0%; -4.3%) and parainfluenza virus (PIV) (RD -31.7%; 95% CI -44.5%; -18.9%) were negatively associated with severity; no association was found between severity and the presence of any pathogen, co-infection, or the specific viruses HRV-A, HRV-B, HRV-C, respiratory syncytial virus, influenza (INF), enterovirus serotype D68, adenovirus or coronavirus. The risk of treatment failure in the absence of a pathogen was 12.5% (95% CI 9.0%; 16.0%). The presence of any pathogen (RD 8.2%; 95% CI 3.3%; 13.1%) and non-HRV infection as a group (RD 13.1%; 95% CI 6.4%; 19.8%), and of INF and PIV specifically (RD 24.9%; 95% CI 4.7%; 45.1% and RD 34.1%; 95% CI 7.5%; 60.7%) were positively associated with treatment failure. Conclusion In this large cohort of children with moderate or severe exacerbation, no single respiratory pathogen was associated with higher severity on presentation. However, in addition to any pathogen and non-HVR infection, INF and PIV were specifically associated with higher treatment failure in the ED, supporting the need for influenza prevention, pathogen identification at presentation and exploration of pathogen-therapy interaction. Disclosures All authors: No reported disclosures.

Asthma Exacerbations and Risk of Emergency Department Management Failure: Burden and Impact of Various Respiratory Pathogens in a Pediatric Population