PMID- 36965591
OWN - NLM
STAT- MEDLINE
DCOM- 20230427
LR  - 20230427
IS  - 1532-3064 (Electronic)
IS  - 0954-6111 (Linking)
VI  - 211
DP  - 2023 May
TI  - Small airways disease in patients with alpha-1 antitrypsin deficiency.
PG  - 107222
LID - S0954-6111(23)00110-5 [pii]
LID - 10.1016/j.rmed.2023.107222 [doi]
AB  - Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder, characterized by 
      panacinar emphysema mainly in the lower lobes, and predisposes to chronic 
      obstructive pulmonary disease (COPD) at a younger age, especially in patients 
      with concomitant cigarette smoking. Alpha-1 antitrypsin (a1-AT) is a serine 
      protease inhibitor that mainly blocks neutrophil elastase and maintains 
      protease/antiprotease balance in the lung and AATD is caused by mutations in the 
      SERPINA1 gene that encodes a1-AT protein. PiZZ is the most common genotype 
      associated with severe AATD, leading to reduced circulating levels of a1-AT. 
      Besides its antiprotease function, a1-AT has anti-inflammatory and antioxidative 
      effects and AATD results in defective innate immunity. Protease/antiprotease 
      imbalance affects not only the lung parenchyma but also the small airways and 
      recent studies have shown that AATD is associated with small airway dysfunction. 
      Alterations in small airways structure with peripheral ventilation 
      inhomogeneities may precede emphysema formation, providing a unique opportunity 
      to detect early disease. The aim of the present review is to summarize the 
      current evidence for the contribution of small airways disease in AATD-associated 
      lung disease.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Toumpanakis, Dimitrios
AU  - Toumpanakis D
AD  - National Heart and Lung Institute, Imperial College London, London, United 
      Kingdom; General State Hospital for Thoracic Diseases of Athens "Sotiria", 
      Greece. Electronic address: d.toumpanakis@imperial.ac.uk.
FAU - Usmani, Omar S
AU  - Usmani OS
AD  - National Heart and Lung Institute, Imperial College London, London, United 
      Kingdom.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230323
PL  - England
TA  - Respir Med
JT  - Respiratory medicine
JID - 8908438
RN  - 0 (alpha 1-Antitrypsin)
RN  - 0 (Protease Inhibitors)
RN  - 0 (SERPINA1 protein, human)
SB  - IM
MH  - Humans
MH  - alpha 1-Antitrypsin/genetics
MH  - *alpha 1-Antitrypsin Deficiency/complications/genetics/diagnosis
MH  - Lung
MH  - Protease Inhibitors
MH  - *Pulmonary Disease, Chronic Obstructive
MH  - *Pulmonary Emphysema/etiology
OTO - NOTNLM
OT  - Alpha-1 antitrypsin
OT  - COPD
OT  - Emphysema
OT  - Small airways
COIS- Declaration of competing interest DT has received honoraria for presentations 
      from Menarini, Chiesi and ELPEN pharmaceutical company. OSU reports grants and 
      personal fees from Astra Zeneca, Boehringer Ingelheim, Chiesi, Glaxosmithkline, 
      personal fees from Cipla, Covis, Deva, Kamada, Kyorin, Napp, Novartis, Orion, 
      Menarini, Mereobiopharma, Mundipharma, Trudell Medical, UCB, Sandoz, Takeda, 
      grants from Edmond outside the submitted work.
EDAT- 2023/03/26 06:00
MHDA- 2023/04/25 10:19
CRDT- 2023/03/25 20:28
PHST- 2023/02/07 00:00 [received]
PHST- 2023/03/21 00:00 [revised]
PHST- 2023/03/22 00:00 [accepted]
PHST- 2023/04/25 10:19 [medline]
PHST- 2023/03/26 06:00 [pubmed]
PHST- 2023/03/25 20:28 [entrez]
AID - S0954-6111(23)00110-5 [pii]
AID - 10.1016/j.rmed.2023.107222 [doi]
PST - ppublish
SO  - Respir Med. 2023 May;211:107222. doi: 10.1016/j.rmed.2023.107222. Epub 2023 Mar 
      23.