PMID- 28752442
OWN - NLM
STAT- MEDLINE
DCOM- 20180416
LR  - 20200306
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 1639
DP  - 2017
TI  - Pathophysiology of Alpha-1 Antitrypsin Lung Disease.
PG  - 9-19
LID - 10.1007/978-1-4939-7163-3_2 [doi]
AB  - Alpha-1 antitrypsin deficiency (AATD) is an inherited disorder characterized by 
      low serum levels of alpha-1 antitrypsin (AAT). Loss of AAT disrupts the 
      protease-antiprotease balance in the lungs, allowing proteases, specifically 
      neutrophil elastase, to act uninhibited and destroy lung matrix and alveolar 
      structures. Destruction of these lung structures classically leads to an 
      increased risk of developing emphysema and chronic obstructive pulmonary disease 
      (COPD), especially in individuals with a smoking history. It is estimated that 
      3.4 million people worldwide have AATD. However, AATD is considered to be 
      significantly underdiagnosed and underrecognized by clinicians. Contributing 
      factors to the diagnostic delay of approximately 5.6 years are: inadequate 
      awareness by healthcare providers, failure to implement recommendations from the 
      American Thoracic Society/European Respiratory Society, and the belief that AATD 
      testing is not warranted. Diagnosis can be attained using qualitative or 
      quantitative laboratory testing. The only FDA approved treatment for AATD is 
      augmentation therapy, although classically symptoms have been treated similarly 
      to those of COPD. Future goals of AATD treatment are to use gene therapy using 
      vector systems to produce therapeutic levels of AAT in the lungs without causing 
      a systemic inflammatory response.
FAU - Kalfopoulos, Michael
AU  - Kalfopoulos M
AD  - Division of Pulmonary Medicine, Department of Pediatrics, University of 
      Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA, 01655, USA.
AD  - Department of Gene Therapy, University of Massachusetts Medical School, 55 Lake 
      Ave. North, Worcester, MA, 01655, USA.
FAU - Wetmore, Kaitlyn
AU  - Wetmore K
AD  - Division of Pulmonary Medicine, Department of Pediatrics, University of 
      Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA, 01655, USA.
AD  - Department of Gene Therapy, University of Massachusetts Medical School, 55 Lake 
      Ave. North, Worcester, MA, 01655, USA.
FAU - ElMallah, Mai K
AU  - ElMallah MK
AD  - Division of Pulmonary Medicine, Department of Pediatrics, University of 
      Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA, 01655, USA. 
      mai.elmallah@umassmemorial.org.
AD  - Department of Gene Therapy, University of Massachusetts Medical School, 55 Lake 
      Ave. North, Worcester, MA, 01655, USA. mai.elmallah@umassmemorial.org.
LA  - eng
GR  - R21 NS098131/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
SB  - IM
MH  - Humans
MH  - Lung Diseases/diagnosis/epidemiology/*physiopathology/therapy
MH  - alpha 1-Antitrypsin Deficiency/diagnosis/epidemiology/*physiopathology/therapy
OTO - NOTNLM
OT  - Alpha-1 antitrypsin
OT  - Alpha-1 antitrypsin deficiency
OT  - Chronic obstructive pulmonary disease (COPD)
OT  - Emphysema
OT  - Neutrophil Elastase
EDAT- 2017/07/29 06:00
MHDA- 2018/04/17 06:00
CRDT- 2017/07/29 06:00
PHST- 2017/07/29 06:00 [entrez]
PHST- 2017/07/29 06:00 [pubmed]
PHST- 2018/04/17 06:00 [medline]
AID - 10.1007/978-1-4939-7163-3_2 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2017;1639:9-19. doi: 10.1007/978-1-4939-7163-3_2.