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

ABSTRACT

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.

KEYWORDS:

• Alpha 1 antitrypsin deficiency
• emphysema
• chronic obstructive pulmonary disease
• augmentation therapy
• treatment
• gene therapy

Article highlights

• More research is needed to identify the optimum treatment regimen of AAT augmentation therapy to stop disease progression.

• The advent of liver-directed therapy in the form of siRNA offers hope that combination treatment could address both lung and liver disease.

• Less expensive treatment options such as oral Neutrophil-Elastase inhibitors and recombinant AAT are key topics in current research.

• Personalized treatment regimens accounting for underlying pathogenic drivers are likely to be the future of management.

This box summarizes the key points contained in the article.

Declaration of interest

AM Turner has had, or currently receives, grants and/or money for consultancy work for CSL Behring and Grifols. She has also done consultancy work for other companies who intend to develop products for AATD, but for whom there is no direct conflict for the subject matter contained in this manuscript.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.