Lack of paradoxical bronchoconstriction after administration of tiotropium via Respimat® Soft Mist™ Inhaler in COPD

Abstract

Bronchoconstriction has been reported in asthma and chronic obstructive pulmonary disease (COPD) patients after administration of some aqueous inhalation solutions. We investigated the incidence of this event during long-term clinical trials of tiotropium delivered via Respimat(®) Soft Mist™ Inhaler (SMI). We retrospectively analyzed pooled data from two identical Phase III clinical trials, in which 1990 patients with COPD received 48 weeks' treatment with once-daily tiotropium (5 or 10 μg) or placebo inhaled via Respimat(®) SMI. We recorded the incidence of bronchospasm and of a range of respiratory events that could suggest bronchoconstriction during the first 30 minutes after inhalation of study treatment on each of the eight test days. No patients reported bronchospasm. Six patients (0.3%) reported a combination of at least two events suggestive of bronchoconstriction, and 21 (1.1%) reported either rescue medication use or a respiratory adverse event. Asymptomatic falls in forced expiratory volume in one second (FEV(1)) of ≥15% were recorded on all test days, with no change in incidence over time, and affected 8.2% of those in the tiotropium groups and 14.5% of those on placebo. In COPD patients receiving long-term treatment with tiotropium 5 or 10 μg via Respimat(®) SMI, no bronchospasm was recorded, and the number of events possibly indicative of paradoxical bronchoconstriction was very low.

Trial registration: ClinicalTrials.gov NCT00168831 NCT00168844.

Keywords: COPD; bronchoconstriction; inhalation device; tiotropium.

Figure 1

Proportion of patients (%) with respiratory events suggestive of administration-related bronchoconstriction during the 30 minutes immediately after inhalation of study treatment on each test day. Events are shown by treatment for Categories B–D (no Category A events occurred), and patients are grouped according to the worst category of event experienced. The number of patients tested on each day fell as the study progressed (see Table 4). See text for definition of categories.