Increasing daily inhaled glucocorticoid doses by 5-fold does not reduce asthma severity in children with mild to moderate asthma during exacerbating events, according to a study published in The New England Journal of Medicine.

Daniel J. Jackson, MD, of the Department of Pediatrics at the University of Wisconsin School of Medicine and Public Health in Madison, and associates conducted a randomized, double-blind, parallel cohort study to analyze the effects of dramatic dosage increases in pediatric patients with mild to moderate persistent asthma.

Eligible volunteers included children aged 5 to 11 years (N=254) who were clinically diagnosed with asthma and treated with glucocorticoids in the year preceding the study. The main outcome of the study was the rate of asthma severity during treatment.

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All participants used low-dose inhaled glucocorticoids (2 inhalations per day at 44 µg per inhalation) for 48 weeks.

Following treatment, the volunteers either continued their dosage regularly (control group; n=127) or increased their dosage 5-fold (220 µg twice daily) at early indications of uncontrolled asthma for 7 days. Uncontrolled cases that required additional treatment or medical attention were defined as “yellow zone” episodes.

The varying systemic glucocorticoid doses did not significantly affect asthma severity rates among participants of the entire cohort. Approximately 30% of children in the high-dose cohort—and nearly 24% in the control group—had at least one case of severe asthma with exacerbation rates of 0.48 and 0.37, respectively per year (relative rate, 1.3).

Secondary results, including time to initial episode of worsening, treatment failure rates, symptoms, and yellow-zone rescue albuterol use all insignificantly varied between both groups.

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“It is important to recognize that our findings are specific to school-age children with mild-to-moderate persistent asthma regularly treated with daily low-dose inhaled glucocorticoids (with good adherence),” reported the authors.

“Given that more exacerbations occurred in the high-dose group, we speculate that it is unlikely that a clinically significant beneficial effect of treatment with a quintupled dose would have been observed in this trial even if we had enrolled more participants.


Jackson DJ, Bacharier LB, Mauger DT, et al; for the National Heart, Lung, and Blood Institute AsthmaNet. Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. N Engl J Med. 2018;378:891-901.