Augmentation therapy in alpha-1 antitrypsin deficiency: advances and controversies

摘要

Alpha-1 antitrypsin (AAT) deficiency is a hereditary condition characterized by low levels of AAT in plasma and hence diffusion into tissues. One of the most relevant characteristics of the disease is the development of panacinar emphysema due to an imbalance between proteases and antiproteases in the presence of environmental triggers. Left untreated, severe obstructive lung disease may develop. Avoidance of environmental triggers such as cigarette smoking constitutes a critical component of AAT deficiency treatment. Intravenous augmentation therapy is the only specific therapy for the condition that has been approved by the US Food and Drug Administration (FDA). While this therapy likely slows the rate of progression of emphysema and may improve survival in selected individuals with severe AAT deficiency, the gold standard for proof of efficacy is lacking. Areas where controversy exists regarding the use of AAT augmentation therapy include: (1) indications for treatment, (2) selection of specific AAT augmentation therapy, (3) appropriate dose and interval of administration, (4) cost effectiveness, (5) frequency and mode of follow up of treated patients, (6) use of augmentation therapy after lung transplantation, (7) use of recombinant AAT supplementation, (8) alternative delivery routes, and (9) genetic therapy. In this review we describe the advances in treatment and try to address some of the current controversies in AAT deficiency management.