PURPOSE OF THE STUDY.
To determine if the addition of a long-acting bronchodilator is noninferior to doubling the dose of inhaled corticosteroids in children whose asthma is not controlled with use of low-to-moderate doses of inhaled corticosteroids alone.
Children aged 6 to 16 years who were using fluticasone propionate (100 μg twice daily) to treat their asthma were enrolled in this study (N = 257). A 4-week run-in period was used to monitor these children. Those who were still symptomatic despite regular use of fluticasone propionate were included in the randomization of study groups (n = 158). The study was conducted at multiple pediatric medical centers throughout Europe.
Symptomatic children were randomly assigned to 1 of 2 treatment groups: fluticasone propionate (200 μg twice per day) or salmeterol/fluticasone propionate (50/100 μg twice per day), used for a 26-week treatment period. Lung-function measurements were recorded at the start of the run-in period, at time of randomization, and at all visits during the treatment period. The provocative dose of methacholine that causes a 20% decrease (PD20) in the forced expiratory volume in 1 second (FEV1) and exhaled nitric-oxide levels were measured at the start and end of the treatment period. The number of symptom-free days and asthma exacerbations were logged at each clinic visit. Exacerbations were classified as mild, moderate, or severe on the basis of the medical interventions needed.
There was no significant difference between the treatment groups in the percentage of symptom-free days. Each treatment group had an increase in symptom-free days by ∼25% while on treatment compared to baseline (P < .001). Furthermore, no significant difference was seen in the percentage of days in which rescue salbutamol was used; both groups had a gradual decline in use of the salbutamol. A combined ranked assessment of all exacerbations among the treatment groups revealed no statistically significant difference between the 2 groups. Lung-function parameters did not differ between groups other than a slightly greater effect on maximal expiratory flow seen in the salmeterol/fluticasone group during the first week of treatment. The 2 groups did not differ in statural growth or number of adverse events.
The results of this study indicate that the combination of a long-acting bronchodilator with inhaled corticosteroid has equal efficacy in controlling symptoms and preserving lung function when compared with doubling the dose of inhaled corticosteroids in children who were symptomatic on a moderate dose of inhaled corticosteroids. Therefore, combination of a long-acting bronchodilator is likely an appropriate alternative in step-up therapy.
This study provides us with an adequate alternative step 3 treatment option. The results of this study are in line with those of previous work. Further study is now needed to evaluate whether there might be specific asthma phenotypes that respond more favorably to 1 treatment option versus another. The fear of increased severe asthma exacerbations and asthma-related deaths associated with use of long-acting β2 agonists in children is still present. Further data from large numbers of children are needed to make a more definite conclusion about this possible risk.
- Copyright © 2011 by the American Academy of Pediatrics