Purpose of the Study
In studies involving adults, the addition of salmeterol to moderate doses of inhaled corticosteroids (ICS) led to better control of asthma symptoms, increased peak flow, and decreased diurnal variation in peak flow values. This study sought to compare the effects of 1 year of treatment with a moderate dose of an inhaled steroid, the same dose of the steroid with added salmeterol, and a doubling dose of an inhaled steroid in children with moderate asthma.
There were 177 children enrolled in the study. The children were 6 to 16 years old and all had moderate to severe asthma. The initial forced expiratory volume in 1 second (FEV1) was between 55% to 90% of predicted and increased at least 10% after the use of inhaled albuterol. All participants also had a positive methacholine challenge, stable asthma, and were on 200 to 800 μg of an ICS for at least 3 months before study entry.
The study was double-blinded and randomized. After a 6-week run-in period, there were 54 weeks of active treatment and a follow-up observation 2 weeks later. All patients were given beclomethasone dipropionate (BDP) 200 μg twice a day. Patients were randomized to receive either salmeterol 50 mcg, BDP 200 μg, or a placebo twice a day. At each clinic visit the children had their height and weight checked. Pulmonary functions were monitored at each visit. Compliance was checked by counting the number of blisters remaining on the medication cards. Diaries were kept with records of symptoms, rescue medication use, and peak flow values.
The baseline characteristics of all three treatment groups were similar with regard to sex, age, height, duration of asthma, allergic status, ICS use, and initial FEV1. Compliance was slightly better in the BDP + salmeterol group—94% of doses were taken. At the end of the 54-week treatment period, there was no significant difference found between the treatment groups for the FEV1. There was still no difference found when the results were analyzed according to presenting dose of ICS, duration of use, baseline FEV1, methacholine sensitivity, and symptom scores. When airway responsiveness to methacholine was evaluated, it was found that all treatment groups had improved; however, the type of treatment made no difference. All treatment groups had improved peak flow values, but there was a more significant change observed in the BDP + salmeterol group during the first few months of the study. There was no difference between the treatment groups in day to day peak flow variability. Symptom control was better in all but there was no difference between the treatment groups. Growth was significantly slower in the BDP-800 μg/day group at 3.6 cm over the study period (BDP 400 group-4.5 cm and BDP + salmeterol group-5.1 cm).
The addition of salmeterol to BDP or the doubling of the BDP dose in children with moderate asthma resulted in no difference in airway caliber, airway responsiveness, symptom scores, or exacerbation rates of asthma when compared with BDP 200 μg bid alone in children over the year of the study. The authors also conclude that rigorous monitoring and frequent visits help with medication compliance and subsequent improvement in disease activity. They also warn of the need to balance the antiinflammatory effect of higher doses of ICS against the effects on growth in children.
The adult literature would have us believe that salmeterol may offer significant improvement in children who have moderate asthma. This study has shown that salmeterol does not offer any significant degree of improvement and more importantly it also shows that increased ICS doses also do not provide any significant differences either. Could it be that in this type of asthma clinical outcomes are optimized not so much by the doses and mixtures of therapies, but more by monitoring, frequent evaluations, and making sure that the children adhere to the treatment program?