Powrie 2007.

Methods	Design: a randomised, double‐blind, parallel‐group, placebo‐controlled study with one year treatment duration, conducted at a single‐centre, the London Chest Hospital (UK)
Participants	Population: 142 patients with COPD were randomised to tiotropium (69) and placebo (73) Baseline Characteristics: mean age 66 years, 41%‐ to 48% male, mean FEV1 1.3 L, mean FEV1 predicted 50%, 55 pack‐years smoking history Inclusion Criteria: patients aged ≥ 40 years with a diagnosis of COPD (FEV1 , 80% of the predicted value and FEV1/FVC , 70%) and a minimum 10‐ pack‐year smoking history Exclusion Criteria: patients with a history of asthma or atopy were excluded, as were those on long‐term oxygen therapy or with another clinically significant disease.
Interventions	1. 18 mcg tiotropium once daily 2. Placebo once daily Inhaler device: dry powder inhaler Co‐medication: anticholinergics other than the study drug were not permitted during the course of the study.
Outcomes	Primary: the concentration of interleukin (IL)‐6 in sputum Secondary: sputum IL‐8 and myeloperoxidase (MPO) levels, serum IL‐6 and C‐reactive protein (CRP) levels, sputum bacterial colonisation, FEV1 and exacerbation frequency
Notes	Funding: Boehringer Ingelheim Study number: Boehringer Ingelheim 205.270, ClinicalTrials.gov NCT00405236 Definitions: an exacerbation was defined as the presence, of > 2 days consecutively, of an increase in any two major symptoms (dyspnoea, sputum purulence and sputum volume) or in one major and one minor symptom (wheeze, sore throat, cough and symptoms of a common cold)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The randomisation list was generated by Boehringer Ingelheim using a validated system, which involved a pseudo‐random number generator so that the resulting treatment sequence was both reproducible and non‐predictable
Allocation concealment (selection bias)	Low risk	All investigational medication for each patient was identified by a unique medication number. Each eligible patient was assigned the lowest medication number available to the investigator at the time of randomisation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Boehringer Ingelheim was responsible for preparing and coding study medication in a blinded fashion (Boehringer Ingelheim study drug and control were indistinguishable). Patients, investigators and study personnel remained blinded with regard to the treatment assignments up to database lock
Blinding of outcome assessment (detection bias) All outcomes	Low risk	In all studies, a selection of standard respiratory endpoints like pulmonary function, SGRQ, TDI, treadmill, exacerbations, etc. were used. Outcome assessors remained blinded with regard to the treatment assignments up to database lock
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The withdrawal rates were high but relatively even (tiotropium 30.4%, placebo 28.8%)
Selective reporting (reporting bias)	Low risk	Results for all specified outcomes were reported