Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/103341
Title: Alpha-1 proteinase inhibitors for the treatment of alpha-1 antitrypsin deficiency: safety, tolerability, and patient outcomes
Authors: Chotirmall, Sanjay Haresh
Al-Alawi, Mazen
McEnery, Thomas
McElvaney, Noel Gerard
Keywords: DRNTU::Science::Medicine::Pharmacy::Pharmaceutical technology
Issue Date: 2015
Source: Chotirmall, S. H., Al-Alawi, M., McEnery, T., & McElvaney, N. G. (2015). Alpha-1 proteinase inhibitors for the treatment of alpha-1 antitrypsin deficiency: safety, tolerability, and patient outcomes. Therapeutics and clinical risk management, 11, 143-151.
Series/Report no.: Therapeutics and clinical risk management
Abstract: Alpha-1 antitrypsin (AAT) deficiency remains an underrecognized genetic disease with predominantly pulmonary and hepatic manifestations. AAT is derived primarily from hepatocytes; however, macrophages and neutrophils are secondary sources. As the natural physiological inhibitor of several proteases, most importantly neutrophil elastase (NE), it plays a key role in maintaining pulmonary protease–antiprotease balance. In deficient states, unrestrained NE activity promotes damage to the lung matrix, causing structural defects and impairing host defenses. The commonest form of AAT deficiency results in a mutated Z AAT that is abnormally folded, polymerized, and aggregated in the liver. Consequently, systemic levels are lower, resulting in diminished pulmonary concentrations. Hepatic disease occurs due to liver aggregation of the protein, while lung destruction ensues from unopposed protease-mediated damage. In this review, we will discuss AAT deficiency, its clinical manifestations, and augmentation therapy. We will address the safety and tolerability profiles of AAT replacement in the context of patient outcomes and cost-effectiveness and outline future directions for work in this field.
URI: https://hdl.handle.net/10356/103341
http://hdl.handle.net/10220/25999
ISSN: 1178-203X
DOI: http://dx.doi.org/10.2147/TCRM.S51474
Rights: © 2015 Chotirmall et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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