Preventing Asthma Exacerbations in Children: Does Increasing Inhaler Dose Help?

Author:
Jessica Tomaszewski, MD
Primary Care Pediatrics, Nemours Children’s Health System, Wilmington, Delaware

Citation:
Tomaszewski J. Preventing asthma exacerbations in children: Does increasing inhaler dose help?

Jackson DJ, Bacharier LB, Mauger DT, et al; National Heart, Lung, and Blood Institute AsthmaNet. Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. N Engl J Med. 2018;378(10):891-901. doi:10.1056/NEJMoa1710988.

Asthma exacerbations are common, particularly in school-aged children. Frequent flares can lead to complications such as progressive loss of lung function and worsening baseline asthma. The use of an inhaled glucocorticoid is effective for managing daily symptoms, but determining its role in managing an exacerbation has been challenging. Many clinicians increase the dose of the inhaled glucocorticoid at the start of exacerbation symptoms, but data about the safety and efficacy of this strategy have been limited.

Therefore, Dr Daniel J. Jackson and colleagues conducted a randomized, double-blind, parallel-group trial, called the Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS), to assess the effectiveness and safety of increasing maintenance glucocorticoids to 5 times the daily dose for 7 days in school-aged children with mild to moderate persistent asthma at the start of an exacerbation.

Their study included 254 children aged 5 to 11 years with mild to moderate persistent asthma from 17 trial sites. These participants all had had at least 1 asthma exacerbation requiring systemic glucocorticoids in the previous year.

After all of the children had been treated with 48 weeks of maintenance low-dose inhaled glucocorticoids, they were randomly assigned to either continue the baseline dose (low-dose group) or use a quintupled dose (high-dose group) for 7 days at the early signs of loss of asthma control (known as the “yellow zone”).

The primary outcome of the study was the rate of severe exacerbations requiring systemic glucocorticoids, which was analyzed via a generalized linear model. Systemic glucocorticoids were started after consultation with a trial physician.

The rate of severe asthma exacerbations treated with systemic glucocorticoids was not significantly different between the 2 treatment groups (0.48 exacerbations per year in the high-dose group vs 0.37 exacerbations per year in the low-dose group).

There were also no differences in the time to the first exacerbation, the rate of emergency department or urgent care visits, the rate of overall treatment failure, symptom scores, and albuterol use during yellow-zone episodes.

A difference was noted in linear growth between the high-dose group and the low-dose group (−0.23 cm per year). A dose-response relationship appeared to be present in children younger than 8 years in the high-dose group (0.12 cm per year lower growth per yellow-zone episode) compared with the low-dose group.

This study does not support increasing the dose of inhaled glucocorticoids for school-aged children with mild to moderate persistent asthma at the early signs of loss of asthma control, despite studies that may support this approach in adults and even preschool-aged children.¹ Some investigators suggest that this discrepancy stems from the idea that many yellow-zone episodes subside without the use of systemic glucocorticoids, a theory that would be challenging—and potentially harmful—to investigate. The authors also note that a decrease in linear growth is possible with the implementation of this increased-dose strategy. Further work needs to be done to identify better strategies to prevent asthma exacerbations.

Reference:

1. McKeever T, Mortimer K, Wilson A, et al. Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations. N Engl J Med. 2018;378:902-910. doi:10.1056/NEJMoa1714257.