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Alpha 1 antitrypsin to treat lung disease in alpha 1 antitrypsin deficiency: recent developments and clinical implications

Authors Chapman KR, Chorostowska-Wynimko J, Koczulla AR, Ferrarotti I, McElvaney NG

Received 18 August 2017

Accepted for publication 12 November 2017

Published 31 January 2018 Volume 2018:13 Pages 419—432


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Charles Downs

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

Kenneth R Chapman,1 Joanna Chorostowska-Wynimko,2 A Rembert Koczulla,3 Ilaria Ferrarotti,4 Noel G McElvaney5

1Department of Medicine, University of Toronto, Toronto, ON, Canada; 2Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland; 3Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University, Marburg, Germany; 4Center for Diagnosis of Inherited Alpha-1 Antitrypsin Deficiency, Department of Internal Medicine and Therapeutics, Pneumology Unit, University of Pavia, Pavia, Italy; 5Department of Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland

Abstract: Alpha 1 antitrypsin deficiency is a hereditary condition characterized by low alpha 1 proteinase inhibitor (also known as alpha 1 antitrypsin [AAT]) serum levels. Reduced levels of AAT allow abnormal degradation of lung tissue, which may ultimately lead to the development of early-onset emphysema. Intravenous infusion of AAT is the only therapeutic option that can be used to maintain levels above the protective threshold. Based on its biochemical efficacy, AAT replacement therapy was approved by the US Food and Drug administration in 1987. However, there remained considerable interest in selecting appropriate outcome measures that could confirm clinical efficacy in a randomized controlled trial setting. Using computed tomography as the primary measure of decline in lung density, the capacity for intravenously administered AAT replacement therapy to slow and modify the course of disease progression was demonstrated for the first time in the Randomized, Placebo-controlled Trial of Augmentation Therapy in Alpha-1 Proteinase Inhibitor Deficiency (RAPID) trial. Following these results, an expert review forum was held at the European Respiratory Society to discuss the findings of the RAPID trial program and how they may change the landscape of alpha 1 antitrypsin emphysema treatment. This review summarizes the results of the RAPID program and the implications for clinical considerations with respect to diagnosis, treatment and management of emphysema due to alpha 1 antitrypsin deficiency.

Keywords: alpha 1 antitrypsin deficiency, computed tomography, emphysema, efficacy

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