Commentary

The anticholinergic agent ipratropium bromide is frontline treatment for patients with non-asthmatic COPD.¹ In most of these patients, ipratropium used alone is more effective as a bronchodilator than is an inhaled β-agonist used alone. (Combination therapy, however, is often more effective than either agent used alone.) Ipratropium bromide has a relatively short duration of action, requiring inhalation every 6 to 8 hours. In addition, ipratropium non-selectively inhibits all 3 of the known muscarinic receptors in the human airway (M₁, M₂, and M₃). This is of theoretical concern because the M₂ receptor normally acts as a feedback inhibitory receptor; blockade of the M₂ receptor results in increased acetylcholine release in the airway and could attenuate or reverse the bronchodilation achieved by blockade of the M₁ and M₃ receptors.² The clinical relevance of this issue is uncertain.

Tiotropium is a potent and long lasting muscarinic antagonist that has “kinetic selectivity” for M₁ and M₃ receptors over M₂ receptors.² A single dose of inhaled tiotropium produces bronchodilation for 24 hours in patients with COPD,³ and attenuates methacholine induced bronchoconstriction for 48 hours in patients with asthma.⁴ Once daily dosing for 4 weeks in stable patients with COPD provides sustained bronchodilation with an excellent safety profile.⁵

The study by van Noord et al provides important data, showing the superiority of tiotropium (18 μg once/d) over the usual dose of ipratropium (40 μg 4 times/d). Patients were permitted to use many of their own usual medications (including methylxanthines, inhaled steroids, and oral steroids up to 10 mg of prednisone/d) during the course of the trial, showing the effectiveness of tiotropium in a meaningful clinical context. Tiotropium, not yet approved for use in the United States, appears to have great potential in the long term maintenance treatment of COPD.