Background: Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease. People who smoke are more seriously affected and have a greater risk of dying from the disease.
Objectives: To review the benefits and harms of augmentation therapy with alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency and lung disease.
Search strategy: PubMed, the Cochrane Trials Register and ClinicalTrials.gov (7 January 2010), and the Cochrane Cystic Fibrosis & Genetic Disorders Group's Trials Register (13 March 2009).
Selection criteria: Randomised trials of augmentation therapy with alpha-1 antitrypsin compared with placebo or no treatment.
Data collection and analysis: The two authors independently selected trials, extracted outcome data and assessed the risk of bias.
Main results: Two trials were included (total 140 patients) that ran for two to three years. All patients were ex- or never-smokers and had genetic variants that carried a very high risk of developing chronic obstructive pulmonary disease. Mortality data were not reported. There was no information on harms in the first trial; in the second trial, serious adverse events were reported to have occurred in 10 patients in the active group and in 18 patients in the placebo group. Annual number of exacerbations and quality of life were similar in the two groups; none of the trials reported on average number of lung infections or hospital admissions. Forced expiratory volume in one second deteriorated a little more in the active group than in the placebo group (difference was -20 ml per year; 95% confidence interval -41 to 1; p = 0.06). For carbon monoxide diffusion, the difference was -0.06 mmol/min/kPa per year (95% confidence interval -0.17 to 0.05; p = 0.31). Lung density measured by CT scan deteriorated a little less in the active group than in the placebo group (difference 1.14 g/l; 95% confidence interval 0.14 to 2.14; p = 0.03) over the total course of the trials.
Authors' conclusions: Augmentation therapy with alpha-1 antitrypsin cannot be recommended, in view of the lack of evidence of clinical benefit and the cost of treatment.