Alpha 1 antitrypsin deficiency: a rare multisystem disease, predominantly affecting the lung

Introduction: α-1-antitrypsin deficiency (AATD) is a rare hereditary disorder associated with early onset emphysema, chronic obstructive pulmonary disease, liver cirrhosis and panniculitis. The pathophysiology contributing to lung disease in patients with AATD involves the interplay of several complex molecular pathways. AAT is produced by hepatocytes and liver disease is most commonly associated with the Z allele which causes polymerization and accumulation of misfolded AAT proteins leading to inflammation and cirrhosis.

Areas covered: A literature search was conducted through Ovid to search Medline, Embase and the Cochrane Library. This article aims to review the clinical features of AATD and the latest evidence available on treatment will be discussed, including AAT replacement therapy, gene therapy and stem cells. Furthermore, ways in which current research could impact global practice as well as current problems faced by researchers will be discussed. This review article also includes a section about the future of AATD management.

Expert opinion: Recent randomized clinical trials have concluded that intravenous augmentation therapy slows progression of lung disease. However, more research is needed to identify the optimum regimen of AAT administration to stop disease progression as well as other effective treatment modalities that can be used in conjunction with or instead of augmentation therapy.