The role of tiotropium in the hospital management of exacerbation of chronic obstructive pulmonary disease.

According to current guidelines regarding the hospital management of exacerbations of chronic obstructive pulmonary disease (COPD), short-acting inhaled 2 agonists are generally the preferred bronchodilators (evidence grade A).1 In the absence of a prompt response to those drugs, addition of a short-acting anticholinergic bronchodilator is recommended, although the effectiveness of this combination in the hospital setting has not been firmly established, in contrast to the well-known additive effects of combined therapy in stable COPD.2,3 The role of methylxanthines when there is an inadequate response to shortacting bronchodilators also remains controversial. On the other hand, there is grade A evidence in support of the addition of oral or intravenous corticosteroids to other therapies.1,4 Despite the established efficacy of long-acting inhaled bronchodilators (the anticholinergic tiotropium, and the 2 agonists salmeterol and formoterol) in the management of stable COPD,5 little evidence exists concerning the efficacy of long-acting inhaled bronchodilators during an exacerbation. A recent 3-way crossover study evaluated the bronchodilator effects of a single-day treatment with either tiotropium, formoterol, or their combination in patients with mild-to-moderate COPD exacerbations managed at home.6 The duration of bronchodilation with tiotropium and formoterol was shorter than that in stable COPD. The difference in the time course of the effects of these agents in acute and stable COPD could be due to several factors, including (1) less effective respiratory delivery of the inhaled medication during an exacerbation, due to the associated increase in airways obstruction from increased inflammation, airway mucus, and bronchospasm, and (2) possibly greater functional antagonism by bronchoconstrictor mediators associated with the acute-on-chronic inflammation. Interestingly, while the bronchodilator effect of tiotropium and formoterol as single agents administered during an exacerbation did not extend as long as the 24hour and 12-hour durations, respectively, observed with these agents in stable COPD, the co-administration of the 2 classes of long-acting inhaled bronchodilator did result in an additive bronchodilator effect that was still evident at 24 hours. A clinical implication of the above-cited study is that the combination of 2 different long-acting inhaled bronchodilators might have benefits over each agent alone even during an exacerbation, although supplementation with a short-acting 2 agonist might still be required. The latter study therefore provides a useful extension to the acute setting of other information from studies with patients with stable COPD concerning the additive bronchodilation from combining long-acting inhaled anticholinergic and -adrenergic bronchodilators,7-10 including nebulized formoterol.11