Mirici 2004.

Methods	Randomised, double dummy, parallel group trial. Power analysis: not reported
Participants	Location: Erzum, Turkey 48 participants were randomised Baseline characteristics: comparable except for pH. Participants in the nebuliser group had a significantly lower pH than the pMDI group. Setting: hospital COPD definition: 1995 ATS guidelines, known FEV1/ FVC < 70% and maximum FEV1 < 80% Definition of the exacerbation: one of the following: increased dyspnoea, increased production and purulence, leading to a change of treatment Exclusion criteria: presence of other conditions such as cystic fibrosis, asthma, severe bronchiectasia, pneumonia, severe hypertension, and severe exacerbation requiring invasive or noninvasive mechanical ventilation. Patients who were not using the pMDI/spacer with the appropriate technique were also not included the study.
Interventions	Participants were randomised to pMDI/spacer group receiving 100 µg salbutamol and 20 µg ipratropium (4 times 4 puffs) and placebo nebuliser or the nebuliser group receiving 2.5 mg salbutamol and 500 µg ipratropium 4 times a day and placebo pMDI/spacer Beta2 ‐agonist: salbutamol Anticholinergic: ipratropium pMDI: not reported Spacer: yes, type not reported Nebuliser: not reported Dosage ratio spacer/nebuliser: 1:6.25 Co‐interventions: oral steroids, theophylline, antibiotics and supplementary oxygen Medication adherence rates: not reported
Outcomes	Cost effectiveness, FEV1 (not reported), PEF, PaO2, PaCO2, SaO2, pH Time points: baseline, 30 min, 24 h, 48 h and 10 d
Notes	Source of funding not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation protocol described a computer‐generated list of random numbers
Allocation concealment (selection bias)	Low risk	Quotation: "randomization was performed using unmarked, ordered, sealed envelopes"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Comment: fully blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Comment: blinded
Incomplete outcome data (attrition bias) All outcomes	High risk	Quotation: "PEFR measurements were used in the analysis, because FEV1 measurements after hospitalisation were not available for all patients."
Selective reporting (reporting bias)	High risk	Quotation: "PEFR measurements were used in the analysis, because FEV1 measurements after hospitalization were not available for all patients." FVC was not reported although baseline measurements were performed
Other bias	Unclear risk	The groups were relatively small (21 vs 22 participants) Comment: small and power calculation was not provided, leaving room for a type II error