The authors note that patients with severe asthma may remain obstructed after up-titration of an inhaled corticosteroid and a long-acting beta-2-agonist, even with the recommended addition of another agent such as an antileukotriene or theophylline. “A potential alternative approach,” they say, “is the addition of a second bronchodilator with an alternative mode of action, the anticholinergic tiotropium bromide.”
Dr. Huib A. M. Kerstjens, at the University Medical Center Groningen, The Netherlands, and colleagues tested this approach in a trial involving 107 asthma patients with a post-bronchodilator FEV1 of 65% predicted despite maintenance treatment with at least a high-dose inhaled corticosteroid (ICS) plus a long-acting beta-2-agonist (LABA).
In a crossover design, the participants received tiotropium 5 mcg/d or 10 mcg/d or placebo in random order during three 8-week periods. The primary endpoint was the peak FEV1 at the end of each period. One hundred patients completed all periods of the study, according to the report.
Compared with placebo, both doses of tiotropium significantly improved peak FEV1 – by a difference of 139 mL on the 5-mcg dose and 170 mL on the 10-mcg dose (p=0.0001 for both). Furthermore, at-home PEF measurements were higher with both tiotropium treatments than during placebo administration, the investigators found.
Rates of adverse events were similar during all treatment periods, except that dry mouth was more frequent with 10-mcg tiotropium.
“In summary, adding tiotropium once daily as maintenance treatment through the Respimat inhaler in addition to at least high-dose ICSs combined with LABAs offers significant potential to improve airway patency in patients with severe persistent asthma who are still symptomatic and obstructed on maximal therapy,” Dr. Kerstjens and colleagues conclude.
J Allergy Clin Immunol 2011.