Add-on Effects of Tiotropium Over Formoterol in Exercise Tolerance on Chronic Obstructive Pulmonary Disease Patients

This will be a single center, randomized, double-blind study consisting of two 2-week treatment periods separated by a 5-7 days washout phase without long-acting bronchodilators. Eligible patients who complete the one week screening phase will be randomized to one of two treatment sequences: 1) Formoterol --> Formoterol + Tiotropium or 2) Formoterol + Tiotropium --> Formoterol. During the treatment periods, patients will be allowed to use a short-acting beta2-adrenergic+short-acting anticholinergic as rescue medication (salbutamol+ipratropium via MDI)

Inclusion criteria

• COPD patients aged ≥ 40 years with stable moderate-to-severe airflow obstruction (FEV1 < 70% and FEV1/FVC ≤ 70% of predicted normal value) post-bronchodilator
• presenting with a long history of smoking (> 20 pack-years) and chronic breathlessness (Baseline Dyspnoea Index total score < 9)

Exclusion criteria

• significant cardiovascular disease, hospitalization for COPD exacerbation or presence of a respiratory tract infection within 1 month of screening
• current or childhood asthma
• a history of allergic rhinitis or other atopic disease
• inability to interrupt usual bronchodilator medication
• use of oral steroids within a month before screening
• need for long-term oxygen therapy, arterial oxygen saturation < 85% at rest anemia, hypo- and hyperthyroidism, hyperadrenergic state
• uncontrolled insulin dependent diabetes mellitus, malignancy, or any disease or condition which limits exercise performance other than COPD
• change in inhaled corticosteroid or theophylline use within 1 month prior to screening