Jury Still Out on Using Oral Corticosteroids for Acute Wheeze in Toddlers

SEPTEMBER 04, 2018
Kenneth Bender, PharmD, MA
An analysis of controlled trials of the use of oral corticosteroids (OCS) for wheezing in toddlers reveals different results and conclusions across trials. These differences may reflect variations among the study populations and methodologies.

Elissa Abrams, MD, Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, Manitoba, Canada, and colleagues did not find consistent benefit of OCS in the studied toddler populations; however, the team suspects the study populations could have been better stratified to identify those more likely to respond to the treatment.

"The use of a toddler's atopic history as a means of stratification may help differentiate transient, viral infection associated wheezing (with less likelihood of response to OCS) from emerging persistent asthma," the investigators suggested.

For the study, Abrams and colleagues reviewed OCS trials on early childhood wheeze to examine whether their effectiveness may be different depending on the patient and family history, and the clinical presentation and the treatment settings, which ranged from home and outpatient environments to emergency departments (ED) or hospitals.

"The diagnostic conundrum is that while OCS use has been demonstrated to be effective in older children with an acute asthma exacerbation, there is a lack of demonstrated efficacy for its use in toddlers," Abrams explained to MD Magazine®.

Four randomized controlled trials of OCS treatment in this age group were identified. The trials were conducted between 1990 and 2018. In the most recent trial, 605 toddlers (aged 24 to 72 months) who presented to the ED with viral infection-associated wheeze were randomized to receive either prednisolone 1mg/kg/day for 3 days or placebo. Most of the toddlers had previous wheeze history, as well as a strong family history of asthma.

The results revealed that OCS was associated with significantly shorter length of stay than placebo (median 370 minutes vs 540 minutes). Furthermore, there were no serious adverse events reported during the study or in follow-up.

The other 3 studies—reported in 1995, 2003 and 2009, respectively—did not find statistically significant differences in efficacy measures between toddlers receiving OCS and placebo. In the 2009 study, Abrams and colleagues found that the cohort comprised more patients with transient, viral-induced wheeze than those with emerging persistent asthma.

The 2003 trial cohort was also principally made up of toddlers with viral bronchiolitis rather than emerging asthma. In addition, Abrams and colleagues note that there was poor compliance with the study protocol of prednisolone 20 mg daily for 5 days, with 68% of children who had a subsequent episode of viral infection-associated wheeze not receiving the trial medication or not completing the symptom diary.

Abrams and colleagues pointed out that in the 1995 study, there was no detailing of the atopic characteristics of patients, which could have resulted in recruiting fewer atopic toddlers who are more likely to develop persistent asthma. Furthermore, they noted that the treatment protocol of a one-time dose of prednisone would now be considered insufficient.

Despite the limitations in the reviewed studies, Abrams and colleagues concede that there is no consistent benefit of OCS demonstrated for wheeze in toddlers in home or outpatient settings, although there is some evidence of benefit in the hospital setting.

"In addition, while adverse events (with OCS) are rare, they can be significant, and must be weighed into the decision to use OCS in toddlers, in particular in the outpatient setting where their benefit has not been clearly demonstrated," Abrams told MD Magazine®.

The more favorable results in the ED and hospitalized setting, however, do support OCS use in that environment, according to Abrams. "OCS should still be considered in those toddlers at higher risk, such as those admitted to hospital, those toddlers who are otherwise allergic, or for those toddlers in the ED," she said.

The study, “Use of Oral Corticosteroids in the Wheezy Toddler,” was published in the Journal of Pediatrics.

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