Effects of fluticasone vs. fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma

Abstract

Aims: Inhaled corticosteroids alone or in combination with long acting beta2-agonists are indicated for use in mild persistent asthmatics. We set out to evaluate effects on airway hyperresponsiveness (AHR) and airway calibre using hydrofluoroalkane fluticasone/salmeterol (FP/SM) vs. double the dose of fluticasone alone (FP).

Methods: Fourteen mild persistent asthmatics completed a randomized double-blind crossover study with 1-week run-in and washout periods prior to treatments. Subjects received 3 weeks of FP 250 microg or FP 125 microg/SM 25 microg as 1 puff twice daily. Methacholine PD20 and lung function were measured after both baseline and treatment periods.

Results: There were no significant differences in baseline values prior to randomized treatments. Compared with pooled baseline, FP/SM and FP conferred improvements (P < 0.05) on methacholine PD20: 2.5 (95% confidence interval 1.7, 3.2) and 1.6 (0.8-2.3) doubling dose improvements, respectively; between FP/SM vs. FP there was a 0.9 (0.4, 1.4) doubling dose difference (P < 0.05). For forced expiratory volume in 1 s (FEV1), forced mid-expiratory flow (FEF25-75) and morning peak expiratory flow (PEF), FP/SM but not FP conferred improvements (P < 0.05) compared with pooled baseline, with FP/SM being greater than FP (P < 0.05): differences in FEV1 of 7.2% (3.8, 10.6) predicted, FEF25-75 of 11.2% (6.3, 16.1) predicted, and morning PEF of 17 L x min(-1)(1-32).

Conclusions: FP/SM conferred improvements on AHR and airway calibre, while twice the dose of FP improved only AHR in patients with mild asthma. The differential effects of FP/SM and FP suggest separate but complementary actions of the two moieties on airway inflammation and smooth muscle stabilization. This may explain the beneficial effects of combination inhalers on exacerbations.

Figure 1

Mean (SE) values as change from pooled baseline after fluticasone (FP) 250 BD (□) and FP 125/salmeterol (SM) 25 BD (). *Significant (P < 0.05) difference from pooled baseline. †Significant (P < 0.05) difference between FP 125/SM 25 BD vs. FP 250 BD. (a) Methacholine doubling dose shift. (b) Forced expiratory volume in 1 s (FEV₁) (% predicted). (c) FEF₂₅₋₇₅ (% pre-dicted). (d) Morning PEF (L min⁻¹).

Figure 2

Scatterplots illustrating individual changes and means (SE) from pooled baseline after fluticasone (FP) 250 BD or FP 125/salmeterol (SM) 25 BD for (a) methacholine doubling dose shift, and (b) forced expiratory volume in 1 s (% predicted).