Another recent study demonstrated that the combination of ICSs and LABAs was noninferior to ICSs alone in preventing hospitalizations, intubations, and deaths.13 There are limited data on whether patients already on LABAs and ICSs should be continued on dual medications. Additionally, there is no clear method describing how to de-escalate therapy for those patients who are well controlled on ICSs and LABAs. A reasonable approach is to reduce doses of both medications and discontinue the LABA if tolerated.14,15 The US Food and Drug Administration has issued a black box warning that LABAs should not be used as a single controller medication because patients may be at increased risk of asthma-related deaths.16,17
What role for leukotriene receptor antagonists?
According to NHLBI guidelines, LTRAs can be considered as an alternative to ICSs when starting a control medication for mild persistent asthma.2 A recent meta-analysis, however, showed that there were increased rates of hospitalizations with LTRAs alone when compared to ICSs.18 The NHLBI guidelines also suggest that LTRAs can be used as adjunctive medication for those patients not well controlled on ICSs rather than increasing the ICS dose or adding a LABA.2
A 2011 clinical trial found no difference in quality of life measures between LTRAs and LABAs as adjunctive therapy at 2 months, but LABAs were more effective when patients were reassessed in 2 years.19 Similarly, the same study also found that adding LTRAs to low-dose ICSs rather than increasing the ICS dose was equivalent in the short term but not at 2 years.19
2 other adjunctive therapy options: Xanthines, cromolyn
Similar to LTRAs, xanthines can be considered as adjunctive therapy for children older than 5 years who are not well controlled on a low-dose ICS. Although xanthines decrease asthma symptoms when compared to placebo alone, they are not more effective than ICSs alone and should be considered only as adjunctive therapy.2,20 There have been few studies comparing xanthines to other adjunctive medications.21
Cromolyn is another adjunctive medication cited in the NHLBI guidelines for escalation of therapy.2 Although the medication has few adverse effects, its use is generally limited in the United States because data supporting its efficacy are lacking.
Omalizumab for allergy-related asthma exacerbations
Omalizumab, an anti-IgE antibody injected every 2 to 4 weeks, is available for children older than 6 years with moderate to severe asthma that is not responsive to ICSs and LABAs.22 The medication is effective in reducing allergy-related asthma exacerbations and hospitalizations, but data comparing it to other adjunctive medications are limited.22 Due to their significant systemic effects, the role of oral steroids as control medications is reserved for patients with severe asthma who are refractory to other medications. Children should be placed on oral steroids for the least amount of time required to achieve symptom control.
Acute exacerbation treatment: What to consider
Although there is no agreed-upon definition for an acute asthma exacerbation, the American Thoracic Society defines it as "an event characterized by a change from the patient’s previous status."23 All patients should be given an asthma action plan that clearly delineates the escalation of therapy in the event of an exacerbation, although only half of all patients report experiencing one.24 Symptom-based plans may prevent more acute care visits when compared to plans that use peak-flow measurements, although children on peak-flow plans may have fewer symptomatic days.25
Start with short-acting beta-agonists
The SABAs serve as the initial treatment of choice for management of asthma exacerbations. In young children (0-3 years), SABAs delivered by MDI with a spacer were more effective in reducing admission rates (11.3% vs 21.7%) when compared to SABAs delivered by nebulizers, resulting in a number needed to treat to prevent one admission of 10.26
In older children (3-18 years), SABAs delivered via spacer reduced ED length of stay, but did not significantly affect hospitalization rates. Additionally, SABAs administered with anticholinergics such as ipratropium bromide were more effective than SABAs alone in reducing admissions (16.9% vs 23.2%), particularly in older children with moderate to severe asthma, while also minimizing adverse effects.8,26
Corticosteroids: A mainstay in the ED
In addition to albuterol administration, corticosteroids remain the mainstay of ED management for asthma exacerbations. Administration of systemic steroids has been shown to reduce hospitalizations in children under 6 years, although, paradoxically, studies examining outpatient administration have demonstrated an increase in hospitalizations when compared to placebo.27
Dexamethasone and prednisone are the 2 most commonly used systemic steroids, and studies haven't indicated superiority of either.28,29 There is no difference in efficacy between oral and intravenous steroids.30 A recent clinical trial found a 2-day course of dexamethasone (0.6 mg/kg) had similar efficacy with fewer adverse effects when compared to a 5-day course of prednisone (1-2 mg/kg/day).28