Effect of salmeterol/fluticasone propionate combination on airway hyper-responsiveness in patients with well-controlled asthma

Abstract

The hypothesis that regular treatment aimed at achieving and maintaining asthma control is accompanied by reduced airway hyper-responsiveness (AHR) was investigated. Adult patients (PC(20) methacholine <8 mg/ml, FEV(1)% predicted >or=70%) received salmeterol/fluticasone propionate combination 50/250 microg bd (SFC250) for a 12-week run-in; those achieving well-controlled (WC) asthma were randomised to SFC250 (n = 88) or SFC50/500 microg bd (SFC500) (n = 90) for 24 weeks. AHR (PC(20) methacholine), asthma control, lung function, symptoms, exacerbations and safety were assessed. During the 12 week run-in (SFC250), a greater than 1 doubling dose increase in PC(20) was observed. During randomised treatment, the increase in AHR was similar, and less than 1 doubling dose, for both groups (adjusted geometric mean PC(20) (mg/mL) at 24 weeks: SFC250: 2.796, SFC500: 2.802; p = 0.992). Compared with SFC250, patients receiving SFC500 had a more rapid improvement in AHR (adjusted mean ratio to baseline respectively at week 4: 1.193 vs. 1.386; week 12: 1.395 vs. 1.672; p = non-significant for both) and showed a greater response to treatment in patients with a low baseline PC(20). Patients maintaining WC asthma were 72 (84%) and 64 (74%) in the SFC250 and SFC500 groups respectively. Both doses of SFC were well tolerated; only four exacerbations were reported, all in the SFC500 group. Regular treatment with SFC resulted in continuous improvement in AHR with maintenance of asthma control in the majority of patients. SFC500 showed a trend for a more rapid improvement in AHR and resulted in greater improvements in patients with a lower baseline PC(20).