Clinical question: Are such alternatives as tiotropium bromide, a long-acting anticholinergic agent, effective in improving symptoms and lung function in those patients who are inadequately controlled on a low-dose inhaled glucocorticoid?
Background: Many asthmatics remain uncontrolled on low doses of inhaled glucocorticoid therapy. Treatment options include increasing the dose or adding a long-acting beta-agonist (LABA). Safety concerns, however, have emerged recently regarding LABA use. It is unclear whether the use of alternatives, such as anticholinergics, is beneficial in managing symptoms.
Study design: Double-blind, three-way crossover trial.
Setting: Multicenter study.
Synopsis: Researchers studied a total of 210 patients with uncontrolled asthma. Three treatments were used with low-dose inhaled glucocorticoids (beclomethasone) as a baseline: adding tiotropium, doubling the dose of inhaled glucocorticoids, or adding an LABA (salmeterol). Patients were treated in all three groups, each lasting 14 weeks with a two-week washout period between treatments (when only the baseline medication was used). The primary outcome measure was the morning peak expiratory flow (PEF).
When compared to doubling the inhaled glucocorticoid dose, patients receiving tiotropium had a higher morning PEF (25.8 liters, 95% CI 14.4-37.1, P<0.001). Tiotropium use also showed statistically significant improvement in the evening PEF, pre-bronchodilator FEV1, proportion of asthma control days, and scores for daily symptoms.
Tiotropium was found to be noninferior to salmeterol, including no difference in morning PEF. Other measurements were similar, except that pre-bronchodilator FEV1 favored tiotropium (0.11 liter increase, 95% CI 0.04-0.18, P=0.003). Because treatments did not last for more than 14 weeks, long-term safety issues and exacerbation rates could not be determined.
Bottom line: When added to a low-dose inhaled glucocorticoid, tiotropium improves asthma symptoms and lung function compared with doubling the corticosteroid dose and is noninferior when compared to a LABA.
Citation: Peters SP, Kunselman SJ, Icitovic N, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med. 2010;363(18):1715-1726.
Reviewed for TH eWire by Elizabeth Schulwolf, MD, MA, Sean Greenhalgh, MD, Aziz Ansari, DO, FHM, Nathan Derhammer, MD, FAAP, Paula Marfia, MD, Elizabeth Wantuch, MD, MS, Division of Hospital Medicine, Loyola University, Chicago.
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