Abstract
Based primarily on extrapolation from adult studies, current pediatric asthma guidelines advise the addition of long-acting beta(2)-agonists for children symptomatic on low/moderate-dose inhaled corticosteroids before increasing the corticosteroid dose. This study was designed to compare the effect of combination salmeterol/fluticasone propionate (SFC) with doubling the dose of fluticasone propionate (FP) on specific airway resistance (sR(aw)) in moderate/severe persistent asthmatic children. A double-blind, randomized, controlled study was performed; children with asthma (4-11 years old; sR(aw) > 1.3 kPa.s) were randomized after a 2-week run-in (FP, 100 mu g, b.i.d.) to either SFC (50 mu g/100 mu g b.i.d.) or FP (200 mu g b.i.d.) via Diskus (GlaxoSmithKline, Stockley Park, U.K.) for 6 weeks. Lung function (sR(aw)-plethysmography and forced expiratory volume in 1 second [FEV1]) was measured before run-in, at randomization, after 3 weeks, at the end of 6-week treatment, and after 48-hour washout. Symptom scores and rescue medication use were recorded throughout. Thirty-five children entered run-in and 24 were randomized (mean age, 7.3 +/- 2.2 years; 50% boys). All children showed an improvement in sR(aw). After adjusting for age, gender, and baseline sR(aw), children receiving SFC had a significantly greater improvement in sR(aw) compared with those receiving FP (adjusted means ratio [95% confidence interval (CI)], 0.81 [0.68-0.97]; p = 0.021). There was a significant interaction between treatment and gender (sR(aw), adjusted geometric mean [95% CI]kPa.s, SFC versus FP: boys, 1.25 [1.10-1.41] [n = 7] versus 1.87 [1.61-2.17] [n = 5]; girls, 1.29 [1.10-1.52] [n = 5] versus 1.29 [1.13-1.47] [n = 7]; p = 0.008). There were no differences in FEV1, symptoms, or rescue medication use between the groups. Addition of salmeterol provides greater improvement in sR(aw) than doubling the dose of FP in children with moderate/severe persistent asthma.