To determine if oral prednisolones given to acutely wheezing preschool-aged children alter respiratory outcomes.A total of 3247 children (aged 24–59 months) with acute wheezing episodes between August 2014 and September 2016 in 3 New Zealand emergency departments (EDs) were potentially eligible. A total of 493 were randomly assigned, and 477 patients were included in the intention-to-treat analysis (238 in the prednisolone group and 239 in the placebo group). Primary outcome data were available on 393 patients (82% overall; 195 (79%) in the prednisolone group and 198 (83%) in the placebo group). Children <24 months of age were purposely excluded, ensuring that those with bronchiolitis were not included.In this double-blind placebo-controlled trial, preschool-aged children with viral-induced wheeze who presented to the ED were randomly assigned to receive 3 days of prednisolone (2 mg/kg) or a placebo. The primary outcome measure was a change in the validated Preschool Respiratory Assessment Measure (PRAM) score 24 hours after the intervention. Secondary outcomes included PRAM score at 4 hours, admission rate, length of ED and inpatient stay, amount of albuterol given in 48 hours, additional treatment with open-label prednisolone, time to return to normal activity, and adverse events, including the need for intravenous (IV) medication, ICU admission, and representation to the ED or primary care provider within 7 days. Pediatric Respiratory Assessment Measure (PRAM) scores (ranging from 0–12) were calculated on the basis of suprasternal retractions, scalene retractions, wheezing, and oxygen saturation in room air. The study was designed as an equivalence trial and powered (power: 95%) to detect the minimal difference in PRAM scores that would disprove the null hypothesis that corticosteroids and placebo are equivalent treatments. In a pilot study (n = 137), researchers determined a SD of 2.3 for change in PRAM score at 24 hours was significant. Therefore, analysis was by intention to treat.Between groups, there was no difference in the primary outcome, the change in PRAM score at 24 hours (difference between means: −0.39; 95% confidence interval [CI]: −0.84 to 0.06, P = .09). The median PRAM score at 24 hours for both groups was 0, with only approximately one-third in either group showing mild disease (PRAM score 1–4) and few with PRAM scores >4 (2.0% and 3.6% in treatment and control groups, respectively). Change in PRAM score at 4 hours was significantly different in the treatment group (−0.67; 95% CI: −1.18 to −0.16; P = .01). No difference in length of ED stay was observed (−0.57; 95% CI: −1.15 to 0.02; P = .06), although admission to the hospital occurred more often in the placebo group (0.67; 95% CI: 0.45 to 1.01; P = .05) as well as additional corticosteroid (0.22; 95% CI: 0.06 to 0.79; P = .01) and IV medication use (0.27; 95% CI: 0.07 to 0.96; P = .03). No difference was observed in representation to the hospital or the primary care provider within 7 days (P = .33 and P = .22, respectively) or ICU admission (undefined P value because only 2 total children went to the ICU) as well as the amount of albuterol given in 48 hours (P = .27).Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool-aged children presenting with acute wheezing to the ED because most children improved after 24 hours regardless of initial treatment. Subgroup analyses revealed no evidence that the 24-hour treatment effect differed for albuterol responsive children, those with a positive Asthma Predictive Index, or more severe disease at presentation (higher PRAM score). However, those who received prednisolone had less respiratory distress 4 hours after medication administration and a reduced requirement for hospital admission, additional corticosteroid, or IV treatment. These findings suggest that early in-hospital administration of oral prednisolone to preschoolers with wheeze may prevent further deterioration and requirement for escalation of therapy. Additionally, considering the lack of significant difference at 24 hours, oral prednisolone may improve short-term respiratory outcomes for preschoolers presenting with wheeze. However, subsequent doses of oral prednisolone may provide no additional therapeutic benefit.With this robustly designed randomized controlled trial, we are reminded that wheezing preschoolers are a heterogeneous group with numerous factors contributing to a wheezy phenotype. We should consider that they should not be treated the same as older asthmatics, with regards to corticosteroids. With this study, the authors question oral steroid dosing dogma and demonstrate that oral prednisolone may improve short-term respiratory outcomes for wheezing preschoolers but subsequent doses of oral prednisolone may provide no additional therapeutic benefit. Further studies are needed in this population to understand the timing and dosing of corticosteroids.
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Apr 19, 2024
Yang Chou + 3
