Predicting Treatment Failure in Young Children With Moderate-to-Severe Wheezing in the Emergency Department

Asthma and wheezing-related illnesses are leading reasons for hospitalization of young children, but limited evidence exists to predict response to emergency department (ED) therapy. Prior research suggests that clinical history and nasopharyngeal (NP) viral or bacterial detection may be related to failure to respond to treatment. The objective of this secondary analysis was to determine demographic, clinical and microbiologic factors associated with failure to respond to standard asthma therapy for children age 18-59 months presenting to the ED with moderate-to-severe wheezing.

Children age 18-59 months were enrolled in a multicenter NHLBI PECARN funded clinical trial comparing azithromycin to placebo who presented to one of eight EDs with moderate-to-severe wheezing defined by a validated clinical score (initial PRAM > 4-12). All children were treated with high-dose albuterol, ipratropium and corticosteroids per standard protocol. Baseline factors included prior wheezing history, clinical assessment, and NP molecular testing. Primary outcome was failure to respond to initial ED treatment, defined as hospital admission, ED length of stay > 8 hours, or discharge with return visit for wheezing within 72 hours. Statistical methods included univariable comparisons and multivariable logistic regression examining factors associated with failure to respond.

We enrolled 840 children over a 3-year period and 626 had full data for multivariable analysis. Most children tested positive for a respiratory virus (86.3%) or bacteria (62.6%). Treatment failure occurred for 335 children due to ED/hospital stay longer than 8 hours and for 3 patients who returned within 72 hours of discharge. Factors associated with treatment failure included female sex, initial acute severity measured by PRAM score, infection with any respiratory virus, > 1 prior hospitalization for wheezing in the past year, and exposure to second-hand smoke. NP infection with bacteria, race/ethnicity and the study intervention of treatment with azithromycin were not associated with treatment failure.

Measures of acute and chronic severity of respiratory illness, second-hand smoke exposure, and infection with a respiratory virus, but not bacteria, were associated with increased odds of failure to respond to ED treatment in this prospective cohort of young children treated for acute wheezing.