Dirksen 1999.

Methods	Double‐blind, placebo‐controlled
Participants	58 ex‐smokers from Denmark and The Netherlands with alpha‐1 antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV1 between 30% and 80% of predicted)
Interventions	Treated for at least 3 years Treatment: 4‐weekly infusions of alpha‐1 antitrypsin 250 mg/kg Placebo: 4‐weekly infusions of albumin 625 mg/kg
Outcomes	Primary: FEV1 Secondary: carbon monoxide diffusion, participant‐administered serial spirometry (PASS) at home, FVC, VC, lung density with CT scan
Notes	Trial supported by The Danish State Serum Institute, Laboratoire Français du Fractionnement et des Biotechnologies, The National Danish Research Council for Public Health, The Danish Lung Foundation and The Netherlands Asthma Foundation
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Patients were stratified by age, level of FEV1, and nationality and randomized by the minimization method". Randomisation procedure not described
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Described as double‐blind and placebo controlled. No information on method
Incomplete outcome data (attrition bias) All outcomes	High risk	Data and group assignment not available for 2 participants who dropped out
Selective reporting (reporting bias)	Low risk	The table of baseline values did not give data for the 2 randomised groups, but from the 2 countries that were included in the trial
Other bias	High risk	No information about possible conflicts of interest, but according to other publications, the first author had financial conflicts of interest