For patients with chronic obstructive pulmonary disease (COPD), many practitioners believe that anticholinergic agents have become the bronchodilator of choice. Not surprisingly, long-acting β-agonists (LABAs) in combination with inhaled glucocorticoids have become standard treatment for patients with asthma that is poorly controlled while receiving inhaled glucocorticoids alone. Although this treatment is effective in a majority of patients, many patients have poor asthma control despite taking LABAs combined with high doses of inhaled glucocorticoids. 

Tiotropium in asthma poorly controlled with standard combination therapy¹ reports the results of two large, replicate, multinational studies. They show that add-on therapy with the long-acting anticholinergic agent tiotropium (delivered by the Respimat inhaler) provided sustained bronchodilation and resulted in reduced asthma exacerbations in patients who were symptomatic and had persistent airflow limitation despite the use of LABAs and inhaled glucocorticoids (800μg to 1,600μg per day of budesonide or its equivalent). These results extend recent findings of Peters and colleagues² who found that in patients with mild-to-moderate asthma, the addition of tiotropium to monotherapy with inhaled glucocorticoids was as effective as adding salmeterol and more effective than doubling the dose of inhaled glucocorticoids. 

Although promising, the data have some limitations. Firstly, in patients with difficult-to-control asthma, more than 80% have poor adherence to controller therapy. In the studies by Kerstjens et al, adherence with trial medications was carefully checked, but such was not the case with the background treatment that each patient was receiving at the time of enrolment in the trials. Thus, relative under-treatment might have left room for additional bronchodilation by tiotropium. 

Secondly, the results cannot be generalised to all patients with uncontrolled asthma who are receiving inhaled glucocorticoids and LABAs, since this study selectively enrolled patients who had persistent airflow limitation. The inclusion criterion of a post-bronchodilator ratio of FEV1 to forced vital capacity (FVC) of less than 0.7 puts these asthma patients in the same category as non-smokers with COPD. It is conceivable that the beneficial effects of tiotropium are restricted to such non-smoking, COPD-look-alike patients with asthma, given the overwhelming evidence of the beneficial effects of tiotropium in COPD. 

Tiotropium that is delivered by the soft-mist inhaler Respimat has a high fine-particle fraction that probably has effects deep in the lung. Bronchodilation of small airways by these fine particles might lead to recruitment of lung volume and a reduction in air trapping, which is a prominent characteristic of patients with more severe forms of asthma. However, tiotropium Respimat may impose a substantial risk in patients with a history of cardiovascular events, in particular in those receiving frequent burst or chronic oral glucocorticoids. Therefore, the present study should be considered as a valuable, but intermediate, step towards safe application of long-acting anticholinergic agents in patients with asthma. 

References 

1. Kerstjens HAM, Engel M, Dahl R et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012; 367: 1198-1207
2. Peters SP, Kunselman SJ, Icitovic N et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med 2010; 363: 1715-1726