Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective threshold.

Autor:	Franciosi AN; Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Dublin, Ireland.; University of British Columbia, Vancouver, BC, Canada.; These authors share first authorship., Fraughen D; Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Dublin, Ireland.; Dept of Medicine, Beaumont Hospital, Dublin, Ireland.; These authors share first authorship., Carroll TP; Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Dublin, Ireland tcarroll@rcsi.ie.; Alpha-1 Foundation Ireland, Royal College of Surgeons in Ireland, Dublin, Ireland., McElvaney NG; Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, Dublin, Ireland.; Dept of Medicine, Beaumont Hospital, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2022 Feb 10; Vol. 59 (2). Date of Electronic Publication: 2022 Feb 10 (Print Publication: 2022).
DOI:	10.1183/13993003.01410-2021
Abstrakt:	Alpha-1 antitrypsin deficiency (AATD) is the only readily identifiable monogenic cause of COPD. To date the only condition-specific treatment for AATD-associated COPD is weekly administration of intravenous plasma-purified human alpha-1 antitrypsin (IV-AAT). Uncertainties regarding which AATD genotypes should benefit from IV-AAT persist. IV-AAT is costly and involves weekly administration of a plasma product. Much of the risk stratification has been centred around the long-accepted hypothesis of a "putative protective threshold" of 11 µM (0.57 g·L -1 ) AAT in serum. This hypothesis has become central to the paradigm of AATD care, although its derivation and accuracy for defining risk of disease remain unclear.We reviewed the literature and examined the association between the 11 µM threshold and clinical outcomes to provide context and insight into the issues surrounding this topic.We found no data demonstrating an increased risk of COPD dependent on the 11 µM threshold. Moreover, an abundance of recent clinical data examining this threshold refutes the hypothesis. Conversely, the use of 11 µM as a treatment target in appropriate ZZ individuals is supported by clinical evidence, although more refined dosing regimens are being explored.Continued use of the 11 µM threshold as a determinant of clinical risk is questionable, perpetuates inappropriate AAT-augmentation practices, may drive increased healthcare expenditure and should not be used as an indicator for commencing treatment.Genotype represents a more proven indicator of risk, with ZZ and rare ZZ-equivalent genotypes independently associated with COPD. New and better risk assessment models are needed to provide individuals diagnosed with AATD with reliable risk estimation and optimised treatment goals. Competing Interests: Conflict of interest: A.N. Franciosi reports grants from Michael Smith Foundation for Health Research (Research Trainee Award 2020), outside the submitted work. Conflict of interest: D. Fraughen has nothing to disclose. Conflict of interest: T.P. Carroll has nothing to disclose. Conflict of interest: N.G. McElvaney reports grants from Grifols, personal fees for advisory board work from CSL Behring, Takeda and Vertex, outside the submitted work. (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)
Databáze:	MEDLINE
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