In children with persistent asthma, does adding a long-acting beta agonist (LABA) to existing treatment with an inhaled corticosteroid decrease exacerbations and admissions, or improve measurable lung function?
In children with persistent asthma who are already taking inhaled corticosteroids, the addition of a LABA does not lower the rate of exacerbations requiring oral steroids, rescue medication, or hospitalizations, but it improves measurable lung function. (Strength of Recommendation = A, based on consistent and good quality patient-oriented evidence). When the addition of LABAs is compared with doubling the current inhaled corticosteroid dose, there is no evidence of decreased rate of exacerbations or hospitalizations to definitively guide treatment. There appeared to be a deleterious effect on growth with doubling the dose of inhaled corticosteroids in trials lasting 52 weeks.
In the United States, 6 million children have a diagnosis of asthma, corresponding to a prevalence of 8.5 percent.1 In Great Britain, LABAs are accepted as first choice step-up therapy versus increasing the dose of inhaled corticosteroids for uncontrolled asthma in children as young as five years.2 As of 2007 in the United States, the National Heart, Lung, and Blood Institute (NHLBI) consensus guidelines give no preferred choice between increase in the corticosteroid dose or addition of an LABA when a child's asthma is not controlled.3 Furthermore, questions exist about the inhibitory growth effects of corticosteroids and the tachyphylaxis of beta agonists.
This Cochrane review included 25 trials with a total of 5,572 children who had a mean age of 10 years. Some of the participants' asthma was controlled on current medication, and some had a pretrial forced expiratory volume in one second (FEV1) greater than 80 percent, but most participants' asthma was not controlled. The Cochrane review divided the corticosteroid-only treatment groups (which were compared with LABA plus corticosteroid treatment) into two intervention types—treatment with the current corticosteroid dose or an increased corticosteroid dose. The meta-analysis included the LABAs salmeterol (Serevent) and formoterol (Foradil).
The first intervention type compared children who remained on their current dose of inhaled corticosteroids with children who had an LABA added to their current dose of inhaled corticosteroid. The trials showed no statistically significant difference between groups regarding rates of hospital admissions or exacerbations requiring oral corticosteroids as an outpatient. Lung function, which was measured by FEV1 or peak flow, demonstrated a statistically significant improvement in all studies with the addition of LABAs to inhaled corticosteroids compared with inhaled corticosteroid use alone in studies measuring that outcome, but the clinical significance of this is not clear. In studies with durations up to 24 weeks, there were no incidents of tachyphylaxis in children taking LABAs.
The second portion of the Cochrane review considered two interventions: children given twice their current dose of inhaled corticosteroids and children who had an LABA added to their current dose of inhaled corticosteroid. There was no statistically significant change in rates of hospitalizations or outpatient exacerbations requiring oral steroids. In the children who had an LABA added to an inhaled corticosteroid, lung function improved by peak flow measurement, but not in trials where FEV1 was used to measure lung function. Growth also was studied in two trials with durations of 52 weeks. Over a one-year period, children in whom the corticosteroid dose was doubled grew a mean of 1.2 cm less than those in whom LABA was added; the authors suggested that this may support the addition of a LABA instead of doubling the current corticosteroid regimen. There was insufficient evidence regarding nocturnal symptoms or use of rescue medication.
Physicians who treat children with persistent asthma must consider the safety profile of chronic medications as well as the benefits. Adding LABAs does not appear to improve patient-oriented outcomes, but it increases physiologic endpoints and may avoid the small loss of growth associated with higher corticosteroid doses. Other medications, such as leukotriene inhibitors and cromolyn, remain non-preferred alternatives to inhaled corticosteroids for persistent asthma treatment, per the NHLBI asthma guidelines.3 In addition, increasing the dose of inhaled corticosteroids may be an option. In this review, the longest study duration was 52 weeks. Previous trials on growth effects that had a duration longer than one year have demonstrated less of an inhibitory effect on growth after the first year, and potential catch-up growth when the inhaled corticosteroid was stopped.4 Therefore, the best treatment option for a child whose asthma is uncontrolled on the initial inhaled corticosteroid dose is still decided among the physician, patient, and parent.