Randomised controlled trials (RCTs) that compared tiotropium with placebo, ipratropium bromide or long-acting beta2-agonists in patients with stable chronic obstructive pulmonary disease (COPD) were eligible for inclusion. Stable COPD was defined as no exacerbation one month prior to trial entry. Eligible trials had to have a follow-up of at least 12 weeks after randomisation. Concomitant medications were allowed including short-acting or long-acting beta2-agonists, and oral or inhalant glucocorticosteroids. Only reviews with a sensitive search strategy in several databases plus explicit criteria for inclusion and exclusion were eligible.
Outcomes comprised the number of exacerbations and the number of hospitalisations per patient year.
In the included trials, mean patient age ranged from 63.6 to 77.4 years; their baseline forced expiratory volume (FEV1) ranged from 36 to 51% predicted. Included patients had smoked at least 10 pack years and suffered from moderate to severe COPD. Most trials defined exacerbations as at least one or two new or increased respiratory symptoms (such as cough, wheeze, dyspnoea, chest congestion, shortness of breath or sputum production) that necessitate a change in treatment, although some trials a purely symptom-based definition not necessarily leading to change in treatment.
Papers were checked for eligibility by two reviewers; disagreements were resolved by consensus.