PMID- 33757485
OWN - NLM
STAT- MEDLINE
DCOM- 20211012
LR  - 20211012
IS  - 1471-2466 (Electronic)
IS  - 1471-2466 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Mar 23
TI  - Alpha-1 antitrypsin (AAT) augmentation therapy in individuals with the PI*MZ 
      genotype: a pro/con debate on a working hypothesis.
PG  - 99
LID - 10.1186/s12890-021-01466-x [doi]
LID - 99
AB  - Alpha-1 antitrypsin deficiency (AATD) is a significantly under-diagnosed genetic 
      condition caused by reduced levels and/or functionality of alpha-1 antitrypsin 
      (AAT), predisposing individuals to lung, liver or other systemic diseases. The 
      management of individuals with the PI*MZ genotype, characterized by mild or 
      moderate AAT deficiency, is less clear than of those with the most common severe 
      deficiency genotype (PI*ZZ). Recent genetic data suggest that the PI*MZ genotype 
      may be significantly more prevalent than currently thought. The only specific 
      treatment for lung disease associated with severe AATD is the intravenous 
      infusion of AAT augmentation therapy, which has been shown to slow disease 
      progression in PI*ZZ individuals. There is no specific evidence for the clinical 
      benefit of AAT therapy in PI*MZ individuals, and the risk of emphysema 
      development in this group remains controversial. As such, current guidelines do 
      not support the use of AAT augmentation in PI*MZ individuals. Here, we discuss 
      the limited data on the PI*MZ genotype and offer pro and con perspectives on 
      pursuing an AAT-specific therapeutic strategy in PI*MZ individuals with lung 
      disease. Ultimately, further research to demonstrate the safety, risk/benefit 
      balance and efficacy of AAT therapy in PI*MZ individuals is needed.
FAU - Barjaktarevic, Igor
AU  - Barjaktarevic I
AD  - Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine 
      at University of California Los Angeles, Los Angeles, CA, USA.
FAU - Miravitlles, Marc
AU  - Miravitlles M
AUID- ORCID: 0000-0002-9850-9520
AD  - Pneumology Department, Hospital Universitari Vall D'Hebron, Vall D'Hebron 
      Institut de Recerca (VHIR), Vall d'Hebron Hospital Campus, CIBER de Enfermedades 
      Respiratorias (CIBERES), Barcelona, Spain. marcm@separ.es.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210323
PL  - England
TA  - BMC Pulm Med
JT  - BMC pulmonary medicine
JID - 100968563
RN  - 0 (SERPINA1 protein, human)
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Genotype
MH  - Humans
MH  - Practice Guidelines as Topic
MH  - Pulmonary Disease, Chronic Obstructive/*etiology
MH  - alpha 1-Antitrypsin/genetics/*therapeutic use
MH  - alpha 1-Antitrypsin Deficiency/complications/*drug therapy/genetics
PMC - PMC7989144
OTO - NOTNLM
OT  - Alpha-1 antitrypsin deficiency
OT  - Chronic obstructive pulmonary disease
OT  - Genotype
OT  - PI*MZ
OT  - Pulmonary disease
COIS- IB has received consulting fees from Astra Zeneca, Boehringer Ingelheim, CSL 
      Behring, Grifols, Verona Pharma, GE Healthcare, Mylan, Theravance, GSK and has 
      received research grants from AMGEN, GE Healthcare, Theravance and Mylan. MM has 
      received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, 
      Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, 
      consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, 
      Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo 
      Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi 
      and Grifols and research grants from GlaxoSmithKline and Grifols.
EDAT- 2021/03/25 06:00
MHDA- 2021/10/13 06:00
PMCR- 2021/03/23
CRDT- 2021/03/24 05:42
PHST- 2020/07/04 00:00 [received]
PHST- 2021/03/15 00:00 [accepted]
PHST- 2021/03/24 05:42 [entrez]
PHST- 2021/03/25 06:00 [pubmed]
PHST- 2021/10/13 06:00 [medline]
PHST- 2021/03/23 00:00 [pmc-release]
AID - 10.1186/s12890-021-01466-x [pii]
AID - 1466 [pii]
AID - 10.1186/s12890-021-01466-x [doi]
PST - epublish
SO  - BMC Pulm Med. 2021 Mar 23;21(1):99. doi: 10.1186/s12890-021-01466-x.