Modulation of allergen-induced bronchoconstriction by fluticasone furoate and vilanterol alone or in combination

BackgroundThis placebo-controlled study assessed the effects of the once-daily inhaled corticosteroid (ICS) fluticasone furoate (FF) and long-acting beta(2)-agonist (LABA) vilanterol (VI) on early and late asthmatic responses (EAR/LAR) and airway hyper-responsiveness (AHR). MethodsPatients (n=27) were randomized to FF (100g), VI (25g), FF/VI (100/25g), and placebo for 21days (four periods). Allergen challenge was performed 1h post-dose on day 21. AHR was assessed on day 22 using methacholine. ResultsAllergen challenge caused an early change (0-2h) in minimum forced expiratory volume in 1s (FEV1) of -1.091l (95% CI: -1.344; -0.837) following placebo therapy; changes were -0.955l (-1.209; -0.702), -0.826l (-1.070; -0.581), and -0.614l (-0.858; -0.370) following VI, FF, or FF/VI therapy, respectively. Treatment differences were significant for all comparisons between therapies. Mean changes in 0-2h%FEV1 were as follows: -28.05 (placebo), -23.10 (VI), -22.33 (FF), and -16.10 (FF/VI). Following placebo, the late change (4-10h) in weighted mean FEV1 was -0.466l (-0.589; -0.343) and -0.298l (-0.415; -0.181) after VI, and was +0.018l with both FF/VI (-0.089; 0.124) and FF (-0.089; 0.125). Treatment differences were significant for all comparisons between therapies except FF/VI vs FF. Mean changes in 4-10h%FEV1 were as follows: -21.08 (placebo), -14.30 (VI), -5.02 (FF), and -5.83 (FF/VI). AHR 24h after allergen challenge was significantly reduced with FF/VI and FF vs placebo, and FF/VI was superior to either component. ConclusionCombined treatment with FF/VI provides additive protection from the EAR relative to its components, significant protection over VI alone from the LAR, and confers sustained protection from hyper-responsiveness 24h post-dose. (Less)