Biochemical Efficacy and Safety of a New Pooled Human Plasma α1-Antitrypsin, Respitin

Stoller, James K.; Rouhani, Farshid N.; Brantly, Mark; Shahin, Seta; Dweik, Raed A.; Stocks, James M.; Clausen, John A.; Campbell, Edward J.; Norton, Frank

doi:10.1378/chest.122.1.66

Cited by 75 publications

(52 citation statements)

References 15 publications

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“…Augmentation therapy recipients experienced on average fewer than two adverse events over 5 years of continuous therapy. Also, no instance of hepatitis, HIV, or prion disease transmission has been ascribed to intravenous augmentation therapy (167,174,175).…”

Section: Treatment Of Aatdmentioning

confidence: 99%

A Review of α₁-Antitrypsin Deficiency

Stoller

Aboussouan

2012

Am J Respir Crit Care Med

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388

330

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α(1)-Antitrypsin (AAT) deficiency is an underrecognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase). Among the approximately 120 variant alleles described to date, the Z allele is most commonly responsible for severe deficiency and disease. Z-type AAT molecules polymerize within the hepatocyte, precluding secretion into the blood and causing low serum AAT levels (∼ 3-7 μM with normal serum levels of 20-53 μM). A serum AAT level of 11 μM represents the protective threshold value below which the risk of emphysema is believed to increase. In addition to the usual treatments for emphysema, infusion of purified AAT from pooled human plasma-so-called "augmentation therapy"-represents a specific therapy for AAT deficiency and raises serum levels above the protective threshold. Although definitive evidence from randomized controlled trials of augmentation therapy is lacking and therapy is expensive, the available evidence suggests that this approach is safe and can slow the decline of lung function and emphysema progression. Promising novel therapies are under active investigation.

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Section: Treatment Of Aatdmentioning

confidence: 99%

A Review of α₁-Antitrypsin Deficiency

Stoller

Aboussouan

2012

Am J Respir Crit Care Med

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388

330

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“…In 2002, STOLLER et al [37] reported a randomised controlled trial in 26 AATD subjects to evaluate the bioequivalence of two commercially available preparations of pooled human plasma a 1 -AT. The study lasted 24 weeks, and urinary DES excretion was measured weekly by two methods simultaneously, the isotope-dilution HPLC method [15] and RIA [12].…”

Section: Urinary Des As a Surrogate End-point In Clinical Trials In Cmentioning

confidence: 99%

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

Luisetti¹,

Ma²,

Iadarola³

et al. 2008

Eur Respir J

116

110

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Desmosine (DES) and isodesmosine (IDES) are two unusual, tetrafunctional, pyridinium ring-containing amino acids involved in elastin cross-linking. Being amino acids unique to mature, cross-linked elastin, they are useful for discriminating peptides derived from elastin breakdown from precursor elastin peptides. According to these features, DES and IDES have been extensively discussed as potentially attractive indicators of elevated lung elastic fibre turnover and markers of the effectiveness of agents with the potential to reduce elastin breakdown. In the present manuscript, immunology-based and separation methods for the evaluation of DES and IDES are discussed, along with studies reporting increased levels of urine excretion in chronic obstructive pulmonary disease (COPD) patients with and without a 1 -antitrypsin deficiency. The results of the application of DES and IDES as surrogate end-points in early clinical trials in COPD are also reported. Finally, recent advances in detection techniques, including liquid chromatography tandem mass spectrometry and high-performance capillary electrophoresis with laser-induced fluorescence, are discussed. These techniques allow detection of DES and IDES at very low concentration in body fluids other than urine, such as plasma or sputum, and will help the understanding of whether DES and IDES are potentially useful in monitoring therapeutic intervention in COPD.

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“…Since these early studies of the first available preparation of pooled human plasma AAT prepared by pasteurization ( Prolastin 1 , Bayer, West Haven, CT), more recent studies have examined the biochemical profile of another pooled human plasma AAT preparation, which was purified using solvent-detergent and nanofiltration techniques ( Aralast 1 , Baxter, Westlake Village, CA) (70). The newer drug was evaluated in a 4-center randomized double-blind controlled trial in which 13 subjects received Aralast 1 or Prolastin 1 for 11 weekly infusions (of 60 mg/kg), after which an open-label follow-up with the new drug was conducted.…”

Section: Augmentation Therapymentioning

confidence: 99%

“…Overall, augmentation therapy recipients experienced on average fewer than 2 adverse events over 5 years of continuous therapy. Also, to date, no instance of hepatitis, HIV, or prion disease transmission has been ascribed to intravenous augmentation therapy (70,76). Table 5.…”

Section: Augmentation Therapymentioning

confidence: 99%

A Review of Alpha-1 Antitrypsin Deficiency

Ioachimescu

Stoller

2005

LCPD

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Alpha-1 antitrypsin (AAT) deficiency is a common but under-recognized disease. This hereditary disorder is characterized by low levels of AAT, and increased risks of panacinar emphysema at an early age, liver disease, vasculitis and panniculitis. Destruction of lung parenchyma and consequent emphysema result from an imbalance between different inflammatory proteases (in particular, leukocyte elastase), and the major natural antiprotease, AAT. To offer a review of key aspects of this important condition, we present the epidemiology, natural history, and pathogenesis of AAT deficiency and, in the context of recent data and the publication of an international standards document regarding the diagnosis and management of individuals with AAT deficiency, review current therapy of AAT deficiency.

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Biochemical Efficacy and Safety of a New Pooled Human Plasma α1-Antitrypsin, Respitin

Cited by 75 publications

References 15 publications

A Review of α₁-Antitrypsin Deficiency

A Review of α₁-Antitrypsin Deficiency

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

A Review of Alpha-1 Antitrypsin Deficiency

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Biochemical Efficacy and Safety of a New Pooled Human Plasma α1-Antitrypsin, Respitin

Cited by 75 publications

References 15 publications

A Review of α1-Antitrypsin Deficiency

A Review of α1-Antitrypsin Deficiency

Desmosine as a biomarker of elastin degradation in COPD: current status and future directions

A Review of Alpha-1 Antitrypsin Deficiency

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Product

Resources

About

A Review of α₁-Antitrypsin Deficiency

A Review of α₁-Antitrypsin Deficiency