Additional effects of pranlukast in salmeterol/fluticasone combination therapy for the asthmatic distal airway in a randomized crossover study.

Background: Salmeterol/fluticasone combination (SFC) therapy is used to control inflammation in the distal airway of patients with well-controlled asthma, but the efficacy of this approach is unclear.

Objectives: The goal of the study was to evaluate the effect of pranlukast, a leukotriene receptor antagonist (LTRA), on distal airway inflammation and pulmonary resistance in patients with asthma that was well-controlled using SFC therapy alone.

Methods: The subjects were 32 patients with well-controlled asthma (age 61.1+/-17.8 years old, Step 3 in the GINA guidelines, Asthma Control Test score 23.2+/-1.8 points) based on use of SFC therapy alone for more than 3 months. These subjects were randomly assigned to groups receiving SFC alone or SFC+LTRA (pranlukast 450 mg daily) and then switched to the opposite group after 4 weeks in a crossover manner. Eosinophilic inflammation in induced sputum samples was assessed after each treatment period. Sputum was induced by inhalation of 10% hypertonic saline for 15 min. Impulse oscillometry parameters (R5, R20, X5 and AX) and spirometry were examined during each period. The Asthma-related Quality of Life Questionnaire (AQLQ) was also administered in each period.

Results: The ECP levels in late-phase sputum were significantly higher than those in early-phase sputum with SFC therapy alone (178.3+/-166.0 vs. 65.5+/-68.9 microg/l, p<0.001), whereas these values did not differ significantly with SFC+LTRA treatment (70.9+/-95.1 vs. 54.6+/-65.7, p=0.554). ECP levels in late-phase sputum with SFC therapy were also significantly higher than those with SFC+LTRA (p=0.045). The values of R5, R20, R5-R20 (kPa/(L/s)), and AX (kPa/L) all significantly improved during with SFC+LTRA treatment compared with SFC alone (median (25-75 percentile)): 0.350 (0.283-0.440) vs. 0.340 (0.280-0.378), p=0.036; 0.280 (0.233-0.365) vs. 0.270 (0.240-0.318), p=0.019; 0.050 (0.030-0.110) vs. 0.500 (0.030-0.073), p=0.032; and 0.570 (0.308-1.045) vs. 0.410 (0.263-0.820), p=0.014; respectively. Pulmonary function indexes did not differ significantly between the two treatments, but the symptom and activity limitation domains of the AQLQ were significantly improved by SFC+LTRA treatment.

Conclusion: This study suggests that the combination of SFC and LTRA may give better control of residual eosinophilic inflammation in the distal airway compared with SFC therapy alone.