Comparison of Hydrofluoroalkane-Beclomethasone Dipropionate Autohaler^TM with Budesonide Turbuhaler^TM in Asthma Control

Abstract

Background: Hydrofluoroalkane-beclomethasone dipropionate Autohaler^TM (HFA-BDP AH) is a breath-actuated chlorofluorocarbon (CFC)-free metered dose inhaler in which BDP is in a solution of HFA propellant. Budesonide Turbuhaler^TM (BUD TH) is a breath-dependent dry powder inhaler. Objectives: To test the hypothesis that half the daily dose of HFA-BDP AH would provide an equivalent control of asthma symptoms to the BUD TH. Methods: This was an 8-week open study in patients with symptomatic moderate-to-severe asthma, previously on BUD 500–1,000 µg day^–1, or an equivalent. After 5–14 days’ run-in, patients were randomized to HFA-BDP AH 800 µg day^–1 or BUD TH 1,600 µg day^–1. The intent-to-treat population consisted of 111 patients on HFA-BDP AH and 98 patients on BUD TH. Results: Mean change from baseline in PEF in the morning (AM PEF) at week 8 was 23.95 liters min^–1 for HFA-BDP AH and 24.46 liters min^–1 for BUD TH. A two-sided equivalence test using the 0.51 liter min^–1 difference gave 95% confidence intervals within a defined equivalence interval of (–∞, 25 liters min^–1) indicating that the mean change in AM PEF was equivalent for the two groups. There were no significant differences in the mean change from baseline in FEV₁ or β-agonist use. Patients using HFA-BDP AH had a significantly greater mean change from baseline in the percentage of days free from shortness of breath (p = 0.05), chest tightness (p = 0.02) and nights without sleep disturbance (p = 0.04) at week 3, and wheeze (p = 0.01), shortness of breath (p = 0.02), chest tightness (p < 0.01) and daily asthma symptoms (p = 0.03) at week 8. The incidence, type and severity of adverse events were similar in each group. At week 8, the mean change from baseline in corrected urine cortisol/creatinine ratio in a subgroup of patients was –0.36 for HFA-BDP and –4.88 for BUD TH (p < 0.01). Conclusions: HFA-BDP 800 µg day^–1 provided control of moderate-to-severe asthma with efficacy and safety at least similar to BUD TH 1,600 µg day^–1.

The functional benefit of anti-inflammatory aerosols in the lung periphery

“…6,7 Even when assuming that Table I. Data shown are averages 6 SEMs; significant changes from DPI-BUD: *P < .05; P < .01. the use of each device is optimal in study populations that are being compared, the equivalence factor for dosing between any 2 formulations will depend on the study parameter used.…”

“…4 Scintigraphy studies have demonstrated more than 50% lung deposition of HFA-BDP aerosols in healthy volunteers and in patients with asthma 3-5 with a preferential distribution toward peripheral air spaces. 5 Comparative clinical studies using spirometric indices have indicated that only half the HFA-BDP dose suffices to obtain similar or better therapeutic efficacy than the standard inhaled steroids [6][7][8][9][10][11][12] with no clinically relevant systemic side effects for daily HFA-BDP doses below 800 mg. 13 Several studies have attempted to assess the effect of HFA-BDP on small airway function. 6,10,[14][15][16][17] Improvements in end-expiratory flows were observed when HFA-BDP was added to the baseline steroid treatment of patients with poorly controlled asthma, 14 or when steroid-naive patients with asthma were given HFA-BDP.…”

Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma

“…One possibility could be that the increased and more peripheral lung deposition from Autohaler was not associated with a similar increase in clinical effect. This seems unlikely, since several studies in children and adults using other outcomes have found increased clinical effects from Autohaler, as compared with less effective delivery devices [25][26][27][28][29]. Another reason could be that BDP is not suitable for q.d.…”

The Usefulness of Inspiratory Flow Rate during Inhalation Corticosteroid Therapy in Asthma

“…However, they do require a sufficient peak inspiratory flow rate (PIF) to achieve an adequate concentration of small respirable particles of the drug to achieve optimal lung deposition [4,5,6]. In contrast, HFA-BDP provides a pressurized metered dose of a micro aerosol, which results in a smaller particle size than with conventional DPIs; thus, it is expected to deposit drug particles into the smaller airways of the lung over a wider range of PIFs [7,8,9,10]. …”

“…The handheld In-Check device (Clement Clarke, Harlow, UK) has recently become available for measuring the PIF and is reportedly useful in assessing whether children and adults should use a DPI [4,5,6,7,8,9,10,11]. It has also been reported that 12% of adult patients with asthma or chronic obstructive pulmonary disease are unable to generatethe optimal inspiratory flow required for DPI use [12].…”