Pathophysiology of Alpha-1 Antitrypsin Lung Disease

Methods Mol Biol. 2017:1639:9-19. doi: 10.1007/978-1-4939-7163-3_2.

Abstract

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.

Keywords: Alpha-1 antitrypsin; Alpha-1 antitrypsin deficiency; Chronic obstructive pulmonary disease (COPD); Emphysema; Neutrophil Elastase.

Publication types

  • Review

MeSH terms

  • Humans
  • Lung Diseases / diagnosis
  • Lung Diseases / epidemiology
  • Lung Diseases / physiopathology*
  • Lung Diseases / therapy
  • alpha 1-Antitrypsin Deficiency / diagnosis
  • alpha 1-Antitrypsin Deficiency / epidemiology
  • alpha 1-Antitrypsin Deficiency / physiopathology*
  • alpha 1-Antitrypsin Deficiency / therapy