Asthma Not Stopped by Boosting Inhaled Steroids in Children

Fran Lowry

March 06, 2018

ORLANDO — Clinicians commonly recommend that the dose of inhaled glucocorticoids be quintupled when patients start losing control of their asthma, but this strategy fails to prevent exacerbations in children, according to a new study.

Daniel Jackson

"We'd like to have options that would prevent exacerbations for children, so from this standpoint, we are disappointed that this isn't effective," said investigator Daniel Jackson, MD, from the University of Wisconsin School of Medicine and Public Health in Madison.

"But it is important to identify something that's being commonly done in standard practice as ineffective, so that moving forward, we are not doing something that isn't helpful," he said.

There was also a trend toward diminished linear growth related to the quintupled dose.

"It was a small effect, but it occurred with not a lot of exposure to the medication. If the children use the medication more frequently, the concern is that the effect could be greater," Jackson explained.

It is important to identify something that's being commonly done in standard practice as ineffective.

The practice of increasing the dose developed on the basis of anecdotal evidence and the general concept that reducing inflammation at the onset of an increase in symptoms would be helpful, he said.

"One of the reasons people felt it was effective is because, about 70% to 80% of the time, these episodes don't go on to exacerbation," he pointed out. This likely led "both parents and practitioners to believe it was effective."

The study was published online (N Engl J Med. Published online March 3, 2018) to coincide with its presentation here at the American Academy of Allergy, Asthma and Immunology and World Allergy Organization 2018 Joint Congress.

Jackson and his team assessed 254 children, 5 to 11 years of age, who had mild to moderate persistent asthma with at least one asthma exacerbation treated with systemic glucocorticoids in the previous year.

The children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (two inhalations of fluticasone propionate 44 μg per inhalation, twice daily). During the subsequent double-blind phase, half the children were randomized to a quintupled dose (two inhalations of fluticasone propionate 220 μg per inhalation, twice daily) for 7 days at the first sign of loss of asthma control — the so-called yellow zone — and the other half continued on the low dose.

The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids.

The number of children who experienced at least one severe asthma exacerbation that was treated with systemic glucocorticoids was not significantly different between the high-dose and low-dose groups (38 vs 30).

Table. Outcomes

Events per Year High-dose Group (n = 127) Low-Dose Group (n = 127) P Value
Number of exacerbations 0.48 0.37 .30
Number of visits to the emergency department or urgent care 0.64 0.47 .30
Mean growth, cm 5.43 5.65 .06

"Ultimately, it is important to recognize that low-dose inhaled steroids are still the recommended therapy for these children. Our results show that increasing the dose when children start to lose control has no benefit, but that doesn't mean that inhaled steroids aren't beneficial for treating children in general," Jackson said.

This study "clearly shows that there is no benefit, and even possibly harm in terms of height, which is something that parents are very concerned about," said Seong Ho Cho, MD, from University of South Florida Morsani College of Medicine in Tampa.

A Trend Toward Reduced Height

Seong Ho Cho

"The reduced height was not significant, but there was a trend, and the rate of exacerbations was higher with the high dose, so that is a signal," Cho told Medscape Medical News.

"This study puts to rest a practice that has been done with no real evidence. We now clearly know that it doesn't work. I think the results may be practice-changing," he said.

This randomized controlled trial clearly shows that "the short-term five-times dose increase in daily steroids in the setting of the yellow zone" has no significant impact on the need to be treated with oral steroids, does not delay when an attack starts, does not affect symptom scores, and does not reduce the use of rescue meds, said Matthew Greenhawt, MD, from Children's Hospital Colorado in Aurora.

Matthew Greenhawt

"Personally, I love the discussion of the fact that not many of such yellow-zone episodes actually progress to a full-blown asthma attack, and perhaps, with this perspective, it is easy to see how one could be misled into thinking that a cheap and readily available strategy, already in the patient's hands — to simply increase their daily steroid controller dose medicine — could work," he told Medscape Medical News.

"This is an incredibly insightful comment and one we should pay attention to, given that it provides a nice insight into why some may have observed such an effect in everyday practice," he added.

"More is not always better, but as noted here, symptom-driven episodes of increased inhaled steroids appear to have more side effects and more total steroid exposure, specifically detrimental effects on growth, without demonstrable clinical benefit," said Eric Macy, MD, from the Kaiser Permanente San Diego Medical Center.

"I have not tried quintupling inhaled steroids in the past with my patients," but, he added, "I mainly see adults."

"Several days of oral steroids still appear to be the best we can offer at this time for acute exacerbations in children, most of which are probably virally induced," Macy told Medscape Medical News.

This study was funded by the National Heart, Lung, and Blood Institute. Jackson reports financial relationships with Boehringer Ingelheim and Merck. Cho, Greenhawt, and Macy have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma and Immunology (AAAAI) and World Allergy Organization (WAO) 2018 Joint Congress: Abstract 2306. Presented March 3, 2018.

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