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 b 2 -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 m g or FP 125 m g/SM 25 m g as 1 puff twice daily. Methacholine PD 20 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 PD 20 : 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 (FEV 1 ), forced mid-expiratory flow (FEF 25 -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 FEV 1 of 7.2% (3.8, 10.6) predicted, FEF 25 -75 of 11.2% (6.3, 16.1) predicted, and morning PEF of 17 L 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.

Modulation of GM-CSF release by enantiomers of β-agonists in human airway smooth muscle

“…48 It is thought that the success of this combination approach may be a result of a b 2 -adrenergic receptor agonist-mediated complimentary effect on the action of the corticosteroid. 49 Similar to other studies of racemic b 2 -adrenergic receptor agonists, our data demonstrate a potentially beneficial amplification of anti-inflammatory effects of the combination of steroid and the (R)-enantiomers. However, the suppression of this beneficial steroid effect by (S)-albuterol, for example, suggests that some combination therapies may be suboptimal because of opposing actions of the (S)-enantiomers obtained through administration of the racemate.…”

Levalbuterol versus albuterol

“…Furthermore, intracellular events consequent to β 2 -adrenoreceptor ligation can infl uence glucocorticoid receptor complex formation and upregulation of the cell-cycle inhibitor protein p21 -(Waf1/Cip1) , which in turn can diminish cell proliferation [35]. Such effects likely are responsible for the apparent anti-infl ammatory synergy between β 2 -adrenoreceptor agonists and corticosteroids [36] and may be among the mechanisms behind the success of current β 2 -adrenoreceptor agonist and steroid combination therapies in asthma [36,37].…”

Long-acting beta agonists in asthma therapy

“…In a recent study by Currie et al [4], the combination of fluticasone and salmeterol improved bronchial hyperresponsiveness (BHR) and airway caliber. Twice the dose of fluticasone alone improved only BHR in these patients with mild asthma.…”