PMID- 34172471
OWN - NLM
STAT- MEDLINE
DCOM- 20220406
LR  - 20220531
IS  - 1399-3003 (Electronic)
IS  - 0903-1936 (Linking)
VI  - 59
IP  - 2
DP  - 2022 Feb
TI  - Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective 
      threshold.
LID - 2101410 [pii]
LID - 10.1183/13993003.01410-2021 [doi]
AB  - 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 microM 
      (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 microM 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 microM threshold. Moreover, an abundance of recent clinical 
      data examining this threshold refutes the hypothesis. Conversely, the use of 
      11 microM 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 microM 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.
CI  - Copyright (c)The authors 2022. For reproduction rights and permissions contact 
      permissions@ersnet.org.
FAU - Franciosi, Alessandro N
AU  - Franciosi AN
AUID- ORCID: 0000-0002-4241-8718
AD  - Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, 
      Dublin, Ireland.
AD  - University of British Columbia, Vancouver, BC, Canada.
AD  - These authors share first authorship.
FAU - Fraughen, Daniel
AU  - Fraughen D
AD  - Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, 
      Dublin, Ireland.
AD  - Dept of Medicine, Beaumont Hospital, Dublin, Ireland.
AD  - These authors share first authorship.
FAU - Carroll, Tomas P
AU  - Carroll TP
AUID- ORCID: 0000-0002-0418-1641
AD  - Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, 
      Dublin, Ireland tcarroll@rcsi.ie.
AD  - Alpha-1 Foundation Ireland, Royal College of Surgeons in Ireland, Dublin, 
      Ireland.
FAU - McElvaney, Noel G
AU  - McElvaney NG
AD  - Irish Centre for Genetic Lung Disease, Royal College of Surgeons in Ireland, 
      Dublin, Ireland.
AD  - Dept of Medicine, Beaumont Hospital, Dublin, Ireland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220210
PL  - England
TA  - Eur Respir J
JT  - The European respiratory journal
JID - 8803460
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Genotype
MH  - Humans
MH  - *Pulmonary Disease, Chronic Obstructive/diagnosis
MH  - Risk Assessment
MH  - alpha 1-Antitrypsin/genetics
MH  - *alpha 1-Antitrypsin Deficiency/complications/diagnosis/genetics
COIS- 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.
EDAT- 2021/06/27 06:00
MHDA- 2022/04/07 06:00
CRDT- 2021/06/26 05:40
PHST- 2021/05/18 00:00 [received]
PHST- 2021/06/16 00:00 [accepted]
PHST- 2021/06/27 06:00 [pubmed]
PHST- 2022/04/07 06:00 [medline]
PHST- 2021/06/26 05:40 [entrez]
AID - 13993003.01410-2021 [pii]
AID - 10.1183/13993003.01410-2021 [doi]
PST - epublish
SO  - Eur Respir J. 2022 Feb 10;59(2):2101410. doi: 10.1183/13993003.01410-2021. Print 
      2022 Feb.