PMID- 30723784
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2372-952X (Print)
IS  - 2372-952X (Electronic)
IS  - 2372-952X (Linking)
VI  - 5
IP  - 4
DP  - 2018 Sep 19
TI  - Alpha-1 Antitrypsin Substitution for Extrapulmonary Conditions in Alpha-1 
      Antitrypsin Deficient Patients.
PG  - 267-276
LID - 10.15326/jcopdf.5.4.2017.0161 [doi]
AB  - Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly 
      manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) 
      augmentation therapy aims to reduce the progression of emphysema, as achieved by 
      life-long weekly slow-drip infusions of plasma-derived affinity-purified human 
      AAT. However, not all AATD patients will receive this therapy, due to either lack 
      of medical coverage or low patient compliance. To circumvent these limitations, 
      attempts are being made to develop lung-directed therapies, including inhaled AAT 
      and locally-delivered AAT gene therapy. Lung transplantation is also an ultimate 
      therapy option. Although less common, AATD patients also present with disease 
      manifestations that extend beyond the lung, including vasculitis, diabetes and 
      panniculitis, and appear to experience longer and more frequent hospitalization 
      times and more frequent pneumonia bouts. In the past decade, new mechanism-based 
      clinical indications for AAT therapy have surfaced, depicting a safe, 
      anti-inflammatory, immunomodulatory and tissue-protective agent. Introduced to 
      non-AATD individuals, AAT appears to provide relief from steroid-refractory 
      graft-versus-host disease, from bacterial infections in cystic fibrosis and from 
      autoimmune diabetes; preclinical studies show benefit also in multiple sclerosis, 
      ulcerative colitis, rheumatoid arthritis, acute myocardial infarction and stroke, 
      as well as ischemia-reperfusion injury and aberrant wound healing processes. 
      While the current augmentation therapy is targeted towards treatment of 
      emphysema, it is suggested that AATD patients may benefit from AAT augmentation 
      therapy geared towards extrapulmonary pathologies as well. Thus, development of 
      mechanism-based, context-specific AAT augmentation therapy protocols is 
      encouraged. In the current review, we will discuss extrapulmonary manifestations 
      of AATD and the potential of AAT augmentation therapy for these conditions.
FAU - Baranovski, Boris M
AU  - Baranovski BM
AD  - Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Schuster, Ronen
AU  - Schuster R
AD  - Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Nisim, Omer
AU  - Nisim O
AD  - Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Brami, Ido
AU  - Brami I
AD  - Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Lior, Yotam
AU  - Lior Y
AD  - Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
FAU - Lewis, Eli C
AU  - Lewis EC
AD  - Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, 
      Ben-Gurion University of the Negev, Beer-Sheva, Israel.
LA  - eng
PT  - Journal Article
DEP - 20180919
PL  - United States
TA  - Chronic Obstr Pulm Dis
JT  - Chronic obstructive pulmonary diseases (Miami, Fla.)
JID - 101635411
PMC - PMC6361480
OTO - NOTNLM
OT  - autoimmunity
OT  - bone-marrow transplantation
OT  - cell survival
OT  - diabetes
OT  - immune system
OT  - inflammation
OT  - leukemia
OT  - organ transplantation
OT  - ulcerative colitis
OT  - wound healing
EDAT- 2019/02/07 06:00
MHDA- 2019/02/07 06:01
PMCR- 2018/09/19
CRDT- 2019/02/07 06:00
PHST- 2019/02/07 06:00 [entrez]
PHST- 2019/02/07 06:00 [pubmed]
PHST- 2019/02/07 06:01 [medline]
PHST- 2018/09/19 00:00 [pmc-release]
AID - 10.15326/jcopdf.5.4.2017.0161 [doi]
PST - epublish
SO  - Chronic Obstr Pulm Dis. 2018 Sep 19;5(4):267-276. doi: 
      10.15326/jcopdf.5.4.2017.0161.