Modulation of allergen-induced bronchoconstriction by fluticasone furoate and vilanterol alone or in combination.
BACKGROUND
This 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).


METHODS
Patients (n = 27) were randomized to FF (100 μg), VI (25 μg), FF/VI (100/25 μg), and placebo for 21 days (four periods). Allergen challenge was performed 1 h post-dose on day 21. AHR was assessed on day 22 using methacholine.


RESULTS
Allergen challenge caused an early change (0-2 h) in minimum forced expiratory volume in 1 s (FEV(1)) of -1.091 l (95% CI: -1.344; -0.837) following placebo therapy; changes were -0.955 l (-1.209; -0.702), -0.826 l (-1.070; -0.581), and -0.614 l (-0.858; -0.370) following VI, FF, or FF/VI therapy, respectively. Treatment differences were significant for all comparisons between therapies. Mean changes in 0-2 h %FEV(1) were as follows: -28.05 (placebo), -23.10 (VI), -22.33 (FF), and -16.10 (FF/VI). Following placebo, the late change (4-10 h) in weighted mean FEV(1) was -0.466 l (-0.589; -0.343) and -0.298 l (-0.415; -0.181) after VI, and was +0.018 l 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 4-10 h %FEV(1) were as follows: -21.08 (placebo), -14.30 (VI), -5.02 (FF), and -5.83 (FF/VI). AHR 24 h after allergen challenge was significantly reduced with FF/VI and FF vs placebo, and FF/VI was superior to either component.


CONCLUSIONS
Combined 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 24 h post-dose.
GlaxoSmithKline Respiratory and Immuno-Inflammation Medicines Development Centre, Stockley Park, UK.
A
A
Oliver
L
L
Bjermer
D
D
Quinn
P
P
Saggu
P
P
Thomas
K
K
Yarnall
J
J
Lötvall
D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000485:Allergens / Q000009:adverse effects / Q000276:immunology*; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology*; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000485:Allergens; D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; C550468:vilanterol; C523187:fluticasone furoate
allergen challenge; asthma; atopy; inhaled corticosteroid; long-acting beta2-agonist