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Therapy for α1-Antitrypsin Deficiency

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Abstract

α1-Antitrypsin (A1AT) deficiency is inherited as an autosomal codominant disorder characterised by reduced levels of A1AT in the serum. Low levels of A1AT in blood perfusing the lung cause low levels in the lung interstitium, making it susceptible to proteolytic damage from resident neutrophil elastase. A ‘protective threshold’ serum A1AT level of 11 μmol/L has been identified by epidemiological studies as a minimum value below which there is an increased risk of emphysema. Intravenous augmentation therapy for patients with severe deficiency of A1AT has been shown to have biochemical efficacy. Although the clinical efficacy of intravenous augmentation therapy has not been demonstrated in a randomised clinical trial, available studies suggest that augmentation therapy is associated with a slowed rate of decline of lung function and enhanced survival. The criteria for patient selection include: age >18 years, serum A1AT level ≤11 μmol/L, a high-risk phenotype (usually PI*ZZ), and documented fixed airflow obstruction (consistent with chronic obstructive pulmonary disease). Although intravenous augmentation is currently the only form of specific therapy approved in the US, active research in the fields of aerosol and gene therapy promise to offer new treatment prospects. In this article, we review the available literature on A1AT augmentation therapy and discuss our recommendations.

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Correspondence to James K. Stoller.

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Minai, O.A., Stoller, J.K. Therapy for α1-Antitrypsin Deficiency. BioDrugs 13, 135–147 (2000). https://doi.org/10.2165/00063030-200013020-00007

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