Therapeutics: Alpha-1 Antitrypsin Augmentation Therapy

2017 ◽  
pp. 249-262 ◽  
Author(s):  
Michael Campos ◽  
Jorge Lascano
Keyword(s):  
Augmentation Therapy ◽  
Alpha 1 Antitrypsin

scholarly journals Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know

2021 ◽  
Vol 12_suppl ◽  
pp. 204062232110101
Author(s):  
Igor Barjaktarevic ◽  
Michael Campos
Keyword(s):  
Lung Disease ◽  
Treatment Guidelines ◽  
Management Program ◽  
Lifestyle Changes ◽  
Chronic Obstructive ◽  
Augmentation Therapy ◽  
Lung Function Decline ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Management of lung disease in patients with alpha-1 antitrypsin deficiency (AATD) includes both non-pharmacological and pharmacological approaches. Lifestyle changes with avoidance of environmental pollutants, including tobacco smoke, improving exercise levels and nutritional status, all encompassed under a disease management program, are crucial pillars of AATD management. Non-pharmacological therapies follow conventional treatment guidelines for chronic obstructive pulmonary disease. Specific pharmacological treatment consists of administering exogenous alpha-1 antitrypsin (AAT) protein intravenously (augmentation therapy). This intervention raises AAT levels in serum and lung epithelial lining fluid, increases anti-elastase capacity, and decreases several inflammatory mediators in the lung. Radiologically, augmentation therapy reduces lung density loss over time, thus delaying disease progression. The effect of augmentation therapy on other lung-related outcomes, such as exacerbation frequency/length, quality of life, lung function decline, and mortality, are less clear and questions regarding dose optimization or route of administration are still debatable. This review discusses the rationale and available evidence for these interventions in AATD.

scholarly journals Anti-Proteases and Alpha-1 Antitrypsin Augmentation Therapy

2018 ◽  
Vol 63 (6) ◽  
pp. 690-698 ◽  
Author(s):  
Charlie Strange
Keyword(s):  
Augmentation Therapy ◽  
Alpha 1 Antitrypsin

Effect of intravenous alpha-1-antitrypsin augmentation therapy on proteinase-3-generated AaVal541 in deficient patients

2021 ◽  
Author(s):  
Iris G. M. Schouten ◽  
Abraham C. Van Der Linden ◽  
Pieter S. Hiemstra ◽  
Richard A. Mumford ◽  
Jan Stolk
Keyword(s):  
Proteinase 3 ◽  
Augmentation Therapy ◽  
Alpha 1 Antitrypsin

scholarly journals The impact of alpha-1 antitrypsin augmentation therapy on neutrophil-driven respiratory disease in deficient individuals

2018 ◽  
Vol Volume 11 ◽  
pp. 123-134 ◽  
Author(s):  
Danielle Dunlea ◽  
Laura Fee ◽  
Thomas McEnery ◽  
Noel G. McElvaney ◽  
Emer Reeves
Keyword(s):  
Respiratory Disease ◽  
Augmentation Therapy ◽  
Alpha 1 Antitrypsin ◽  
The Impact

scholarly journals Activation of complement component 3 is associated with airways disease and pulmonary emphysema in alpha-1 antitrypsin deficiency

Thorax ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 321-330 ◽  
Author(s):  
Michael E O'Brien ◽  
Laura Fee ◽  
Niall Browne ◽  
Tomás P Carroll ◽  
Paula Meleady ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Pulmonary Emphysema ◽  
Therapeutic Efficacy ◽  
Size Exclusion ◽  
Complement C3 ◽  
Breakdown Product ◽  
Healthy Controls ◽  
Augmentation Therapy ◽  
Alpha 1 Antitrypsin

IntroductionAlpha-1 antitrypsin (AAT) deficiency (AATD) is associated with early onset emphysema. The aim of this study was to investigate whether AAT binding to plasma constituents could regulate their activation, and in AATD, exploit this binding event to better understand the condition and uncover novel biomarkers of therapeutic efficacy.MethodsTo isolate AAT linker proteins, plasma samples were separated by size exclusion chromatography, followed by co-immunoprecipitation. AAT binding proteins were identified by mass spectrometry. Complement turnover and activation was determined by ELISA measurement of C3, C3a and C3d levels in plasma of healthy controls (n=15), AATD (n=51), non-AATD patients with obstructive airway disease (n=10) and AATD patients post AAT augmentation therapy (n=5).ResultsDirect binding of complement C3 to AAT was identified in vivo and in vitro. Compared with healthy controls, a breakdown product of C3, C3d, was increased in AATD (0.04 µg/mL vs 1.96 µg/mL, p=0.0002), with a significant correlation between radiographic pulmonary emphysema and plasma levels of C3d (R2=0.37, p=0.001). In vivo, AAT augmentation therapy significantly reduced plasma levels of C3d in comparison to patients not receiving AAT therapy (0.15 µg/mL vs 2.18 µg/mL, respectively, p=0.001).DiscussionResults highlight the immune-modulatory impact of AAT on the complement system, involving an important potential role for complement activation in disease pathogenesis in AATD. The association between plasma C3d levels and pulmonary disease severity, that decrease in response to AAT augmentation therapy, supports the exploration of C3d as a candidate biomarker of therapeutic efficacy in AATD.

Augmentation therapy of alpha-1 antitrypsin deficiency associated emphysema

2015 ◽  
Vol 32 (4) ◽  
pp. 435-446 ◽  
Author(s):  
J. Traclet ◽  
P. Delaval ◽  
P. Terrioux ◽  
J.-F. Mornex
Keyword(s):  
Augmentation Therapy ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin
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