Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency

Irina Petrache1, Joud Hajjar1, Michael Campos21Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; 2Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Miller School of Medicine, University of Miami, Florida, USA Abstract: Alpha-1-a...

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Autores principales:	Irina Petrache, Joud Hajjar, Michael Campos
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2009
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8716671a62674c23988e2a9f97cd9609
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spelling	oai:doaj.org-article:8716671a62674c23988e2a9f97cd96092021-12-02T00:10:08ZSafety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency1177-54751177-5491https://doaj.org/article/8716671a62674c23988e2a9f97cd96092009-05-01T00:00:00Zhttp://www.dovepress.com/safety-and-efficacy-of-alpha-1-antitrypsin-augmentation-therapy-in-the-a3088https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Irina Petrache1, Joud Hajjar1, Michael Campos21Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; 2Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Miller School of Medicine, University of Miami, Florida, USA Abstract: Alpha-1-antitrypsin deficiency (AATD), also known as alpha1-proteinase inhibitor deficiency, is an autosomal co-dominant condition. The genotypes associated with AATD include null, deficient, and dysfunctional alpha-1-antitrypsin (A1AT) variants, which result in low levels of circulating functional A1AT, unbalanced protease activity, and an increased risk of developing lung emphysema, the leading cause of morbidity in these patients. Furthermore, the most common abnormal genotype, Pi*ZZ may also cause trapping of abnormally folded protein polymers in hepatocytes causing liver dysfunction. A major focus of therapy for patients with lung disease due to AATD is to correct the A1AT deficiency state by augmenting serum levels with intravenous infusions of human plasma-derived A1AT. This strategy has been associated with effective elevations of A1AT levels and function in serum and lung epithelial fluid and observational studies suggest that it may lead to attenuation in lung function decline, particularly in patients with moderate impairment of lung function. In addition, an observational study suggests that augmentation therapy is associated with a reduction of mortality in subjects with AATD and moderate to severe lung impairment. More recent randomized placebo-controlled studies utilizing computer scan densitometry suggest that this therapy attenuates lung tissue loss. Augmentation therapy has a relative paucity of side effects, but it is highly expensive. Therefore, this therapy is recommended for patients with AATD who have a high-risk A1AT genotype with plasma A1AT below protective levels (11 &micro;M) and evidence of obstructive lung disease. In this article, we review the published evidence of A1AT augmentation therapy efficacy, side effects, and safety profile.Keywords: alpha-1 antitrypsin, COPD, intravenous augmentation therapy Irina PetracheJoud HajjarMichael CamposDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2009, Iss default, Pp 193-204 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Irina Petrache Joud Hajjar Michael Campos Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency
description	Irina Petrache1, Joud Hajjar1, Michael Campos21Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; 2Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Miller School of Medicine, University of Miami, Florida, USA Abstract: Alpha-1-antitrypsin deficiency (AATD), also known as alpha1-proteinase inhibitor deficiency, is an autosomal co-dominant condition. The genotypes associated with AATD include null, deficient, and dysfunctional alpha-1-antitrypsin (A1AT) variants, which result in low levels of circulating functional A1AT, unbalanced protease activity, and an increased risk of developing lung emphysema, the leading cause of morbidity in these patients. Furthermore, the most common abnormal genotype, Pi*ZZ may also cause trapping of abnormally folded protein polymers in hepatocytes causing liver dysfunction. A major focus of therapy for patients with lung disease due to AATD is to correct the A1AT deficiency state by augmenting serum levels with intravenous infusions of human plasma-derived A1AT. This strategy has been associated with effective elevations of A1AT levels and function in serum and lung epithelial fluid and observational studies suggest that it may lead to attenuation in lung function decline, particularly in patients with moderate impairment of lung function. In addition, an observational study suggests that augmentation therapy is associated with a reduction of mortality in subjects with AATD and moderate to severe lung impairment. More recent randomized placebo-controlled studies utilizing computer scan densitometry suggest that this therapy attenuates lung tissue loss. Augmentation therapy has a relative paucity of side effects, but it is highly expensive. Therefore, this therapy is recommended for patients with AATD who have a high-risk A1AT genotype with plasma A1AT below protective levels (11 &micro;M) and evidence of obstructive lung disease. In this article, we review the published evidence of A1AT augmentation therapy efficacy, side effects, and safety profile.Keywords: alpha-1 antitrypsin, COPD, intravenous augmentation therapy
format	article
author	Irina Petrache Joud Hajjar Michael Campos
author_facet	Irina Petrache Joud Hajjar Michael Campos
author_sort	Irina Petrache
title	Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency
title_short	Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency
title_full	Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency
title_fullStr	Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency
title_full_unstemmed	Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency
title_sort	safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency
publisher	Dove Medical Press
publishDate	2009
url	https://doaj.org/article/8716671a62674c23988e2a9f97cd9609
work_keys_str_mv	AT irinapetrache safetyandefficacyofalpha1antitrypsinaugmentationtherapyinthetreatmentofpatientswithalpha1antitrypsindeficiency AT joudhajjar safetyandefficacyofalpha1antitrypsinaugmentationtherapyinthetreatmentofpatientswithalpha1antitrypsindeficiency AT michaelcampos safetyandefficacyofalpha1antitrypsinaugmentationtherapyinthetreatmentofpatientswithalpha1antitrypsindeficiency
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Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency

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