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 SK + 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 mu g/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. (c) 2009 Elsevier Ltd. All rights reserved.