Alpha-1-antitrypsin replacement therapy: current status

Alpha-1-antitrypsin deficiency is a relatively common genetic disease that predisposes to the development of early-onset emphysema and, in some instances, liver disease. The use of alpha-1-antitrypsin replacement therapy in the treatment of alpha-1-antitrypsin deficiency related emphysema is much debated and the purpose of this review is to examine the results of recent studies. We will comment briefly on the pathogenesis and epidemiology of the disease together with new therapeutic approaches currently under intense research.

Several nonrandomized observational studies and one meta-analysis on the clinical effectiveness of alpha-1-antitrypsin replacement treatment showed a favourable result towards reducing forced expiratory volume in 1 s (FEV1) deterioration in alpha-1-antitrypsin-deficient individuals with moderate lung disease or accelerated FEV1 decline. Improved ways of monitoring disease progression, including computed tomography scanning and exacerbations, are being proposed as primary endpoints. Apart from one small randomized, placebo-controlled trial using computed tomography scanning, which showed a trend toward preservation of lung density on scanning with treatment, the literature lacks proof of effectiveness from large randomized trials.

There might be a possible, but so far unproven, role of alpha-1-antitrypsin augmentation therapy in reducing the progression of emphysema in subsets of patients with alpha-1-antitrypsin deficiency. Placebo-controlled, randomized clinical trials are required to draw firm conclusions. Recent advances in the understanding of the molecular pathology provide opportunities for development of new therapeutic targets for this genetic disorder.