The Emerging Role of Tiotropium for Patients with Asthma

OBJECTIVE: To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma. DATA SOURCES: A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics. STUDY SELECTION AND DATA EXTRACTION: Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not. DATA SYNTHESIS: Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting beta-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the beta(2)-adrenoreceptor (ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified. CONCLUSIONS: Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.