PMID- 29996870
OWN - NLM
STAT- MEDLINE
DCOM- 20190318
LR  - 20190318
IS  - 1750-1172 (Electronic)
IS  - 1750-1172 (Linking)
VI  - 13
IP  - 1
DP  - 2018 Jul 11
TI  - Alpha-1 antitrypsin deficiency: outstanding questions and future directions.
PG  - 114
LID - 10.1186/s13023-018-0856-9 [doi]
LID - 114
AB  - BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition 
      that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, 
      significantly increasing the risk of serious lung and/or liver disease in 
      children and adults, in which some aspects remain unresolved. METHODS: In this 
      review, we summarise and update current knowledge on alpha-1 antitrypsin 
      deficiency in order to identify and discuss areas of controversy and formulate 
      questions that need further research. RESULTS: 1) AATD is a highly underdiagnosed 
      condition. Over 120,000 European individuals are estimated to have severe AATD 
      and more than 90% of them are underdiagnosed. CONCLUSIONS: 2) Several clinical 
      and etiological aspects of the disease are yet to be resolved. New strategies for 
      early detection and biomarkers for patient outcome prediction are needed to 
      reduce morbidity and mortality in these patients; 3) Augmentation therapy is the 
      only specific approved therapy that has shown clinical efficacy in delaying the 
      progression of emphysema. Regrettably, some countries reject registration and 
      reimbursement for this treatment because of the lack of larger randomised, 
      placebo-controlled trials. 4) Alternative strategies are currently being 
      investigated, including the use of gene therapy or induced pluripotent stem 
      cells, and non-augmentation strategies to prevent AAT polymerisation inside 
      hepatocytes.
FAU - Torres-Duran, Maria
AU  - Torres-Duran M
AD  - Pulmonary Department, Hospital Alvaro Cunqueiro EOXI, Vigo, Spain.
AD  - NeumoVigo I+i Research Group, IIS Galicia Sur, Vigo, Spain.
FAU - Lopez-Campos, Jose Luis
AU  - Lopez-Campos JL
AD  - Unidad Medico-Quirurgica de Enfermedades Respiratorias, Instituto de Biomedicina 
      de Sevilla (IBiS), Hospital Universitario Virgen del Rocio, Universidad de 
      Sevilla, Sevilla, Spain.
AD  - CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
FAU - Barrecheguren, Miriam
AU  - Barrecheguren M
AD  - CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
AD  - Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
FAU - Miravitlles, Marc
AU  - Miravitlles M
AD  - CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
AD  - Pneumology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
FAU - Martinez-Delgado, Beatriz
AU  - Martinez-Delgado B
AD  - Molecular Genetics Unit, Instituto de Investigacion de Enfermedades Raras (IIER), 
      Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
FAU - Castillo, Silvia
AU  - Castillo S
AD  - Fundacion Investigacion Hospital Clinico Valencia, Instituto de Investigacion 
      Sanitaria INCLIVA, c/Menendez y Pelayo, 4, 46010, Valencia, Spain.
AD  - School of Medicine, Department of Physiology, Research group on Rare Respiratory 
      Diseases (ERR), University of Valencia, Valencia, Spain.
FAU - Escribano, Amparo
AU  - Escribano A
AD  - Fundacion Investigacion Hospital Clinico Valencia, Instituto de Investigacion 
      Sanitaria INCLIVA, c/Menendez y Pelayo, 4, 46010, Valencia, Spain.
AD  - School of Medicine, Department of Paediatrics, Obstetrics and Gynaecology, 
      University of Valencia, Valencia, Spain.
AD  - School of Medicine, Department of Physiology, Research group on Rare Respiratory 
      Diseases (ERR), University of Valencia, Valencia, Spain.
FAU - Baloira, Adolfo
AU  - Baloira A
AD  - Pneumology Department, Complejo Hospitalario Universitario de Pontevedra, 
      Pontevedra, Spain.
FAU - Navarro-Garcia, Maria Mercedes
AU  - Navarro-Garcia MM
AD  - Fundacion Investigacion Hospital Clinico Valencia, Instituto de Investigacion 
      Sanitaria INCLIVA, c/Menendez y Pelayo, 4, 46010, Valencia, Spain.
AD  - School of Medicine, Department of Physiology, Research group on Rare Respiratory 
      Diseases (ERR), University of Valencia, Valencia, Spain.
FAU - Pellicer, Daniel
AU  - Pellicer D
AD  - Fundacion Investigacion Hospital Clinico Valencia, Instituto de Investigacion 
      Sanitaria INCLIVA, c/Menendez y Pelayo, 4, 46010, Valencia, Spain.
AD  - School of Medicine, Department of Physiology, Research group on Rare Respiratory 
      Diseases (ERR), University of Valencia, Valencia, Spain.
FAU - Banuls, Lucia
AU  - Banuls L
AD  - Fundacion Investigacion Hospital Clinico Valencia, Instituto de Investigacion 
      Sanitaria INCLIVA, c/Menendez y Pelayo, 4, 46010, Valencia, Spain.
AD  - School of Medicine, Department of Physiology, Research group on Rare Respiratory 
      Diseases (ERR), University of Valencia, Valencia, Spain.
FAU - Magallon, Maria
AU  - Magallon M
AD  - Fundacion Investigacion Hospital Clinico Valencia, Instituto de Investigacion 
      Sanitaria INCLIVA, c/Menendez y Pelayo, 4, 46010, Valencia, Spain.
AD  - School of Medicine, Department of Physiology, Research group on Rare Respiratory 
      Diseases (ERR), University of Valencia, Valencia, Spain.
FAU - Casas, Francisco
AU  - Casas F
AD  - Pneumology Department, Hospital Universitario San Cecilio, Granada, Spain.
FAU - Dasi, Francisco
AU  - Dasi F
AUID- ORCID: 0000-0003-2938-2965
AD  - Fundacion Investigacion Hospital Clinico Valencia, Instituto de Investigacion 
      Sanitaria INCLIVA, c/Menendez y Pelayo, 4, 46010, Valencia, Spain. 
      Francisco.Dasi@uv.es.
AD  - School of Medicine, Department of Physiology, Research group on Rare Respiratory 
      Diseases (ERR), University of Valencia, Valencia, Spain. Francisco.Dasi@uv.es.
LA  - eng
GR  - PI17/01250/Instituto de Salud Carlos III/International
GR  - 201/2013/Sociedad Espanola de Neumologia y Cirugia Toracica/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20180711
PL  - England
TA  - Orphanet J Rare Dis
JT  - Orphanet journal of rare diseases
JID - 101266602
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Animals
MH  - Fibrosis/metabolism/pathology
MH  - Humans
MH  - Panniculitis/metabolism/pathology
MH  - Pulmonary Disease, Chronic Obstructive/metabolism/pathology
MH  - Vasculitis/metabolism/pathology
MH  - alpha 1-Antitrypsin/*metabolism
MH  - alpha 1-Antitrypsin Deficiency/*metabolism/*pathology
PMC - PMC6042212
OTO - NOTNLM
OT  - Alpha-1 antitrypsin
OT  - Alpha-1 antitrypsin deficiency
OT  - Augmentation therapy
OT  - COPD
OT  - Cirrhosis
OT  - Panniculitis
OT  - Rare respiratory diseases
OT  - SERPINA1
OT  - Vasculitis
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Not applicable. CONSENT FOR 
      PUBLICATION: Not applicable. COMPETING INTERESTS: Drs. Maria Torres-Duran, Silvia 
      Castillo, Amparo Escribano, Maria Mercedes Navarro Garcia, Daniel Pellicer, Lucia 
      Banuls, Francisco Casas and Francisco Dasi report no disclosures. Dr. Jose Luis 
      Lopez-Campos reports personal fees and non-financial support from Grifols, during 
      the conduct of the study. Dr. Miriam Barrecheguren reports personal fees from 
      Menarini, personal fees from GlaxoSmithKline, personal fees from Gebro pharme, 
      personal fees from Novartis, personal fees from Grifols, outside the submitted 
      work. Dr. Miravitlles reports personal fees from Boehringer Ingelheim, 
      AstraZeneca, Chiesi, GlaxoSmithKline, Menarini, Teva, Grifols and Novartis, 
      personal fees from Bayer Schering, Boehringer Ingelheim, GlaxoSmithKline, Gebro 
      Pharma, CLS Behring, Cipla, MediImmune, Mereo Biopharma, Teva, Novartis and 
      Grifols, outside the submitted work. Dr. Martinez-Delgado reports grants from 
      Ministerio de Economia y Competitividad. ISCIII. (Spain), other from Registro 
      Espanol de pacientes con Deficit de alfa-1 antitripsina (REDAAT). Fundacion 
      Espanola de Pulmon, during the conduct of the study. Dr. Baloira reports personal 
      fees and non-financial support from GRIFOLS during the conduct of the study. 
      PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional 
      claims in published maps and institutional affiliations.
EDAT- 2018/07/13 06:00
MHDA- 2019/03/19 06:00
PMCR- 2018/07/11
CRDT- 2018/07/13 06:00
PHST- 2018/02/05 00:00 [received]
PHST- 2018/06/26 00:00 [accepted]
PHST- 2018/07/13 06:00 [entrez]
PHST- 2018/07/13 06:00 [pubmed]
PHST- 2019/03/19 06:00 [medline]
PHST- 2018/07/11 00:00 [pmc-release]
AID - 10.1186/s13023-018-0856-9 [pii]
AID - 856 [pii]
AID - 10.1186/s13023-018-0856-9 [doi]
PST - epublish
SO  - Orphanet J Rare Dis. 2018 Jul 11;13(1):114. doi: 10.1186/s13023-018-0856-9.