Inhaled Steroids in Childhood Asthma: Does Dose Matter?

Can a Higher Inhaled Steroid Dose Halt Asthma Episodes?

An uncertainty in the management of children with poorly controlled asthma is whether increasing the inhaled glucocorticoid dose when asthma symptoms first begin to worsen can help to prevent asthma exacerbations.

A recent study^[1] explored this strategy. The randomized, double-blind, parallel-group trial enrolled children at 17 sites in the United States. Study children were aged 5-11 years, had mild or moderate persistent asthma, and had experienced at least one asthma exacerbation for which they received systemic glucocorticoids in the year before enrollment. All of the study children exhibited reasonable control of their asthma before enrollment on the basis of standardized measures.

During a 4-week run-in period, study children were switched to the same low-dose inhaled corticosteroid. They were trained in the use of a daily electronic diary for symptom documentation, and completed an asthma control test. For the remainder of the study, an additional 48 weeks, the children were randomly assigned in a 1:1 ratio to either continue the routine dose (88 µg daily) or change to a high dose (440 µg daily) of fluticasone for 7 days each time they experienced asthma symptoms that moved them into the "yellow zone" of their treatment plan.

The main outcome of interest was the frequency of severe asthma exacerbations that required systemic glucocorticoids. The study also evaluated secondary outcomes, such as time to first asthma exacerbation, unscheduled emergency department or urgent care visits, hospitalizations, total glucocorticoid exposure, and growth.

Study Findings

Each study group had 127 children. The trial was completed by 94 children in the high-dose group and 98 children in the low-dose group. Adherence among the study children was assessed to be 98%. The average age of children at enrollment was 8 years, and 64.2% were boys. There was a reasonable race and ethnic distribution, and 38.2% of the children were exposed to tobacco smoke.

Each group experienced two episodes of yellow-zone symptoms for each year of the trial. There was no significant difference between children in the low- or high-dose group in the number of annual exacerbations that required systemic steroids.

Of interest, the mean number of annual episodes was slightly higher in the high-dose group than the low-dose group (0.48 episode vs 0.37 episode, respectively). Other outcomes were also slightly worse in the high-dose group, including emergency department visits or hospitalizations, but these differences were not statistically significant. Children aged 5-7 years in the high-dose group experienced reduced linear growth (of about 0.23 cm) compared with those in the low-dose group.

The investigators concluded that among children aged 5-11 years whose asthma was treated with daily inhaled glucocorticoid therapy, increasing the dose of inhaled glucocorticoids at the first loss of asthma control did not reduce severe exacerbations but did result in a higher total glucocorticoid dose and possibly reduced linear growth.

Viewpoint

These data are no doubt disappointing to clinicians, patients, and parents. More than 80% of the yellow-zone episodes exhibited by study children did not progress to requiring systemic steroids. Therefore, although it might appear that the early strategy of increasing the child's inhaled steroid dose was effective, the reality may be that 4 out of 5 asthma episodes would not have progressed to the point of requiring systemic steroids anyway.

The investigators and the author of an accompanying editorial^[2] mention that existing data in patients not already using a daily controller support using one at the start of an asthma exacerbation to reduce the severity of the episode. This study certainly does not lend additional support for that strategy.

In the same issue of the New England Journal of Medicine,^[3] an adult and adolescent pragmatic (open-label) trial is reported, in which the severity of asthma exacerbations was reduced with quadrupling the inhaled steroid dose. However, the open-label, nonmasked nature of that trial limits its ability to provide a definitive answer.

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