Oral corticosteroids helped reduce wheeze severity and length of hospital stay in children experiencing acute preschool wheeze, a pooled analysis of patient-level randomized trial data showed.

The medication reduced wheezing severity score (WSS) after 4 hours to a greater degree than did placebo (mean difference -0.31 on a 12-point scale, P=0.011). This, however, was not maintained after 12 hours (-0.02 difference, P=0.68), reported Bohee Lee, PhD, of the University of Edinburgh in Scotland, and coauthors.

Patients treated with corticosteroids also spent 3.18 fewer hours in the hospital compared with placebo recipients (P=0.0021), according to the meta-analysis published in Lancet Respiratory Medicine.

Despite widespread use for treating acute wheeze associated with viral infection in patients ages 12-71 months, dubbed “preschool wheeze,” discordant results in clinical trials have led guidelines to suggest a cautious approach to treatment, typically only when hospitalization is necessary. Thus, oral corticosteroids are prescribed for acute preschool wheeze in the emergency department for anywhere from 12% to 81% of cases.

The impact at 4 hours is meaningful, even though it didn’t last longer term, Heidi Makrinioti, MD, PhD, of Harvard Medical School in Boston, argued in an invited editorial, calling it a “crucial period for decisions regarding admission to observational units.”

However, she and the researchers emphasized the subgroup findings: The benefits appeared largely reserved for those with a prior history of wheezing or asthma and those with at least moderate wheezing.

Improvement in WSS at 4 hours was significant in those with baseline moderate-to-severe wheeze but not in those with mild wheeze, although the interaction was not statistically significant (mean difference -0.38 vs -0.07, P=0.28 for interaction). That interaction was significant for reduction in hospital length of stay (-3.38 hour difference for the moderate-to-severe group, P<0.001 for interaction).

For those with a history of wheezing or asthma versus no prior episodes, the 4.54-hour reduction in length of hospital stay between groups was also significant (P=0.0007 for interaction).

“The use of oral corticosteroids in low-risk preschool children and those with mild acute wheeze could be deferred,” the study authors wrote. “Global guidelines could align to recommend the early use of oral corticosteroids in preschool children with a history of previous wheeze or asthma, particularly in those showing moderate-to-severe wheeze.”

Makrinioti, however, said that “although the findings are insufficient to warrant changes to current guidelines, they serve as a valuable guide for future studies in two specific areas: exploring the effectiveness of oral corticosteroids in preschool children with mild acute wheeze episodes and identifying biomarkers predictive of responses to oral corticosteroid treatment.”

The meta-analysis included individual participant data on a total of 1,728 pediatric patients ages 12 to 71 months across seven trials. Of those patients, 49.4% received oral corticosteroids as their treatment, while 50.6% received placebo. Patient populations were similar, with 36.2% of the intervention treatment and 33.4% of the placebo population being female.

Researchers screened trials published from January 1994 to June 2020 across eight different databases. An array of patient demographic information including age, sex, potential asthma history, wheeze, eczema, hay fever, the presence of pets in the family home, and food allergy status were also collected.

Administration of oral corticosteroids in emergency departments was associated with a greater reduction in hospital length of stay (-3.28 hours, 95% CI -4.30 to -2.26) than their administration in inpatient settings (-2.50 hours, 95% CI -30.71 to 25.71).

Additionally, emergency department administration was associated with greater reduction in need for additional steroids (OR 0.53, 95% CI 0.30-0.95) than when administered in an inpatient setting (OR 0.82, 95% CI 0.28-2.40).

Factors such as patient age, male sex, allergies, and history of parental allergies or asthma did not affect the impact of corticosteroids on preschool wheeze.

Adverse events were infrequent overall. However, using an oral corticosteroid was associated with an increased risk of vomiting (OR 2.27, 95% CI 0.87-5.88). Other common adverse events that were associated with use of an oral corticosteroid included diarrhea, agitation, stomach ache or upset, and nausea.

Prednisolone was the sole corticosteroid used throughout the studies. “This distinction is crucial when considering the interpretation of adverse effects, as oral dexamethasone is increasingly favored for its better tolerance (e.g., lower risk of vomiting),” said Makrinioti.

Other limitations to the study included the varied definitions for “chronic wheeze” throughout the studies included, lack of WSS records in some of the included studies, and variation in methods in confirming participant allergies and in level of details for the records analyzed.

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