Alpha-1 Antitrypsin Therapy in Cystic Fibrosis and the Lung Disease Associated with Alpha-1 Antitrypsin Deficiency

Ann Am Thorac Soc. 2016 Apr;13 Suppl 2:S191-6. doi: 10.1513/AnnalsATS.201504-245KV.

Abstract

Cystic fibrosis and alpha-1 antitrypsin (AAT) deficiency are two of the commonest lethal hereditary lung diseases affecting white individuals. Although having quite different phenotypic extrapulmonary presentations, the lung disease associated with these conditions is exemplified by a neutrophil-dominated inflammation in which neutrophil elastase plays a major role. In AAT deficiency the diminution of the anti-neutrophil elastase protection, due to diminished AAT levels in the lung, predisposes the lung to an unopposed neutrophil elastase attack, whereas, in cystic fibrosis, the levels of AAT and other antiproteases are normal, but the neutrophil elastase burden is so large that it overwhelms the normal anti-neutrophil elastase protection. With this as background, it seems logical to augment the anti-neutrophil elastase defenses of the lung in both conditions using exogenous AAT. The type of AAT, the route of administration, and the physiologic, radiologic, and clinical readouts for this type of therapy are discussed, along with the similarities and differences between the two conditions and their responses to AAT therapy.

Keywords: alpha-1 antitrypsin deficiency; augmentation therapy; cystic fibrosis; inflammation; neutrophil elastase.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation
  • Administration, Intravenous
  • Cystic Fibrosis / drug therapy*
  • Humans
  • Leukocyte Elastase
  • Serine Proteinase Inhibitors / therapeutic use*
  • alpha 1-Antitrypsin / therapeutic use*
  • alpha 1-Antitrypsin Deficiency / drug therapy*

Substances

  • Serine Proteinase Inhibitors
  • alpha 1-Antitrypsin
  • Leukocyte Elastase