A comparison of 2 extrafine hydrofluoroalkane-134a–beclomethasone formulations on methacholine hyperresponsiveness

Small airways inflammation is a recognized pathologic component of asthma, and it is postulated that the observed airway-wall remodeling in small airways could be due to uncontrolled inflammation in airways that are not penetrated by conventional inhaled corticosteroids. Thus, extrafine particle formulations of inhaled corticosteroids are of clinical interest. To compare 2 extrafine solution hydrofluoroalkane-134a formulations of beclomethasone dipropionate (Beclate and Qvar). Fifteen asthmatic patients (mean ± SEM forced expiratory volume in 1 second [FEV 1], 2.62 ± 0.21 L; provocative concentration of methacholine causing a 20% decrease in FEV 1 [PC 20], 1.06 ± 0.58) were randomized to completion in a placebo-controlled, double-blind, crossover manner to receive Beclate or Qvar at doses of 100 or 400 μg/d for 2 weeks, with a 1-week washout period before each randomized treatment. Methacholine hyperresponsiveness was the primary outcome measure. The 2 formulations were equivalent in terms of predefined equivalence limits of ±1 doubling dilution for PC 20 at both doses: −0.25 (95% confidence interval [CI], −0.77 to 0.27) doubling dilution difference between the 100-μg doses and a 0.26 (95% CI, −0.29 to 0.82) doubling dilution difference between the 400-μg doses for the difference between Beclate and Qvar, respectively. Both formulations, at either dose, produced a statistically significant ( P < .05) reduction in mean exhaled nitric oxide levels: 400 μg/d of Beclate, 14.1 ppb (95% CI, 5.6 to 22.6 ppb); and 400 μg/d of Qvar, 14.2 ppb (95% CI, 6.0 to 22.4 ppb). The higher doses produced a statistically significant ( P < .05) reduction in early morning urinary cortisol-creatinine ratio (geometric mean fold suppression: Beclate, 1.48 [95% CI, 1.16 to 1.89]; and Qvar, 1.42 [95% CI, 1.12 to 1.79]). Both formulations significantly improved peak expiratory flow, FEV 1, and forced expiratory flow between 25% and 75% of forced vital capacity at the higher doses ( P < .05). Beclate and Qvar were equivalent for all primary and secondary outcome measures.