Acute local tolerability of acidic aqueous vehicles delivered via Respimat Soft Mist Inhaler in hyperreactive asthma patients.

BACKGROUND

Acidic inhalers can be associated with increased adverse reactions.

OBJECTIVES

This study aimed to determine the acute local tolerability of acidic aqueous placebo formulations delivered via Respimat Soft Mist Inhaler (SMI) and placebo chlorofluorocarbon metered dose inhaler (CFC-MDI).

METHODS

A single-dose (four inhalations), randomized, double-blind within Respimat SMI device, four-way crossover study in asthma patients with documented bronchial hyperresponsiveness was used. Patients received acidic placebo solutions [pH 2.7, 3.4 or 7.0 (neutral)], delivered via Respimat SMI or placebo CFC-MDI. The primary endpoint was the largest decrease in forced expiratory volume in 1 s (FEV(1)) from baseline to 0-30 min after dosing. Secondary endpoints included spirometry, paradoxical bronchoconstriction (defined as a fall in FEV(1) >or=15% below baseline within 30 min of dosing), cough episodes and adverse events.

RESULTS

Thirty-two patients were included in the per-protocol population (mean age 27 years, 62.5% males). The mean percentage decrease in FEV(1) was comparable between treatment groups: -1.6% (Respimat SMI pH 2.7), -1.8% (Respimat SMI pH 7.0), -1.9% (CFC-MDI), and -2.3% (Respimat SMI pH 3.4); no patient experienced paradoxical bronchoconstriction. The mean number of cough episodes was significantly lower in the Respimat SMI pH 2.7 group versus CFC-MDI (p = 0.0165). No patient used rescue medication. Only 3 patients experienced at least one adverse event.

CONCLUSIONS

The Respimat SMI pH 2.7 placebo solution does not induce adverse events in these patients. Compared with the CFC-MDI placebo suspension, Respimat SMI is a well-tolerated inhaled medication delivery system that can accommodate medication formulations with a wide range of pH solutions.