Reference: Lancet Respir Med 2018 Feb;6(2):97-106 (Level 2 [mid-level] evidence)
Wheeze is a common symptom experienced in childhood, affecting approximately 1 in 3 children by the age of three (Pediatr Pulmonol 2007). In early childhood, virus-related respiratory illnesses are the most common cause of acute wheeze (Pediatr Allergy Immunol 2007). Immune responses to viral organisms may promote reactions in the epithelium of airways that lead to wheezing. Treatments aimed at alleviating wheeze in children vary based on the cause, frequency of episodes, and severity, and include short acting beta agonists, inhaled hypertonic saline, inhaled corticosteroids, oral corticosteroids, antibiotics, and magnesium sulfate. Prior research on the efficacy of oral corticosteroid use in children with virus-associated wheeze has been inconclusive due to limited trial power and the inability to distinguish wheeze related to viral illness from bronchiolitis (J Pediatr 2003, Pediatr Infect Dis J 2006, NEJM 2009, NEJM 2009). The study being reviewed adds to the available evidence.
A double-blind, randomized non-inferiority trial compared the efficacy of oral prednisolone to placebo in 624 preschool children (24-72 months old) who presented to the ER with suspected virus-associated wheeze. Eligible patients included 605 children in the modified intention-to-treat analysis (300 in placebo group and 305 in prednisolone group). Children presenting to the ER with wheeze and viral-like upper respiratory symptoms were randomly selected to receive oral prednisolone 1mg/kg or placebo daily for three days. Exclusion criteria included other possible causes of wheeze, oxygen saturation less than 92%, sepsis, previous asthma exacerbation requiring ICU admission, or oral corticosteroid use in the last 14 days. Initial analysis evaluated whether placebo was non-inferior to oral prednisolone and was followed by post-hoc sensitivity analyses. Primary outcome was length of stay in the hospital until the patient was ready for discharge. Secondary outcomes were related to variables within the first 7 days after hospital discharge, which included hospital re-attendance, readmission, salbutamol treatments during hospitalization and after discharge, and residual symptoms and therapies at discharge and 3 months after hospital discharge, including recurrence of wheeze, drugs regularly administered for wheeze, and number of medical attendances for wheeze.
The initial non-inferiority analysis of primary outcomes found oral prednisolone to be non-inferior to placebo, with length of stay significantly increased in the placebo group (9 hours) compared to oral prednisolone group (6.2 hours, p = 0.039). In the post-hoc superiority analyses, there was not a significant difference comparing prednisolone to placebo in the 391 children that had to stay over 4 hours but less than 7 hours (64% compared to 65%), but the effect of prednisolone became significant in analyses comparing lengthier hospital stays. The proportion of children having to stay over 7 hours (309 total children) was 46% in prednisolone group compared to 57% of the placebo group (p = 0.017, NNT 9). Twenty-five percent of the prednisolone group had to stay over 12 hours compared to 38% of the placebo group (p = 0.002, NNT 8). For both > 7-hour and > 12-hour stays, there were significant differences favoring oral prednisolone over placebo in subgroup analyses of children with previous history of asthma vs. no asthma history, children who received inhaled salbutamol prior to presenting to the ER vs. no salbutamol, and children with severe wheeze but not moderate wheeze. Length of stay exceeding 12 hours was significantly reduced in the prednisolone group regardless of the result of the viral antigen. There were no significant differences reported for secondary outcomes.
This study provides support for the use of oral corticosteroids in children 2-6 years old with wheeze presumed to be related to viral upper respiratory illness. Oral prednisolone reduced the length of stay in these patients. However, a major limitation of this study was subgroup analyses showing reduced length of hospital stay in patients with a history of asthma only, which is consistent with improved length of stay after inhaled salbutamol treatment. Oral corticosteroids may be particularly useful in those already diagnosed with asthma, with more severe wheeze and if inhaled bronchodilators are used alongside oral corticosteroids. Nonetheless, the evidence presented does not support oral prednisolone use outside of this context.
For more information, see the Corticosteroids for wheezing in children topic in DynaMed.
KIMBERLY FORDHAM, MD
is a third year family medicine resident at Memorial Health University Medical Center in Savannah, GA. She is originally from Minneapolis, MN. She completed her undergraduate training at the University of St. Thomas in St. Paul, MN. Prior to medical school, she spent four year in clinical medical research at the University of Minnesota. She matriculated to Ross University School of Medicine where she graduated with high honors prior to matching in the Family Medicine Residency Program in Savannah. She is interested in women’s health, minority/underserved health, and lifestyle medicine.
Faculty contributions by Marvin H. Sineath, Jr., MD.