Recent advances in α-1-antitrypsin deficiency-related lung disease

Expert Rev Respir Med. 2013 Jun;7(3):213-29; quiz 230. doi: 10.1586/ers.13.20.


α-1-antitrypsin deficiency (A1ATD) is an under-recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease. There is considerable heterogeneity in the phenotypic expression of lung disease in A1ATD and the pathophysiology is complex, involving the interaction of multiple pathways. Other genetic factors that may contribute to emphysema risk in A1AT-deficient individuals are beginning to be identified. Methods of monitoring disease progression have evolved, including the use of computed tomography densitometry and biomarkers of disease activity. Progress in the development of novel treatment strategies continues, including the hope for a potential cure through the use of gene therapies. In this article, the authors review the recent advances in this field and outline potential future directions of research in A1ATD.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Disease Progression
  • Enzyme Replacement Therapy
  • Genetic Predisposition to Disease
  • Genetic Therapy
  • Humans
  • Phenotype
  • Protein Conformation
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / enzymology
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / therapy
  • Pulmonary Emphysema / diagnosis
  • Pulmonary Emphysema / enzymology
  • Pulmonary Emphysema / epidemiology
  • Pulmonary Emphysema / genetics*
  • Pulmonary Emphysema / therapy
  • Respiratory System Agents / therapeutic use
  • Structure-Activity Relationship
  • Treatment Outcome
  • alpha 1-Antitrypsin / chemistry
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin / metabolism
  • alpha 1-Antitrypsin / therapeutic use
  • alpha 1-Antitrypsin Deficiency / diagnosis
  • alpha 1-Antitrypsin Deficiency / enzymology
  • alpha 1-Antitrypsin Deficiency / epidemiology
  • alpha 1-Antitrypsin Deficiency / genetics*
  • alpha 1-Antitrypsin Deficiency / therapy


  • Biomarkers
  • Respiratory System Agents
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin

Supplementary concepts

  • Pulmonary Disease, Chronic Obstructive, Severe Early-Onset