The efficacy and safety of inhaled human α-1 antitrypsin in people with α-1 antitrypsin deficiency-related emphysema

Expert Rev Respir Med. 2015 Apr;9(2):143-51. doi: 10.1586/17476348.2015.1002472. Epub 2015 Jan 19.

Abstract

α-1 antitrypsin deficiency (AATD) is an autosomal co-dominant condition characterized by low circulating levels of α-1 antitrypsin (AAT), a serine protease inhibitor. Significant work has been carried out in the development of AAT augmentation therapy for AATD. While the majority of this activity has focused on intravenous (iv.) augmentation, evidence of a significant clinical benefit is still debated and iv. therapy is expensive, onerous and time consuming. Inhalation therapy offers the opportunity for easier and more efficient delivery of AAT directly to the lungs with some evidence of a reduction in local inflammatory and proteolytic activity, potentially offering an alternative therapeutic option to the iv. route. There are, however, theoretical obstacles to the potential efficacy of aerosol-delivered AAT and although there have been a number of short-term studies examining inhaled AAT and its effect on lung inflammation, there has only been one long-term study to date in AATD looking at clinical outcomes, which is as yet unpublished.

Keywords: aerosolized; augmentation; emphysema; inhaled; α-1 antitrypsin.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Animals
  • Enzyme Replacement Therapy* / adverse effects
  • Humans
  • Lung / drug effects*
  • Lung / enzymology
  • Lung / physiopathology
  • Pulmonary Emphysema / diagnosis
  • Pulmonary Emphysema / drug therapy*
  • Pulmonary Emphysema / enzymology
  • Pulmonary Emphysema / physiopathology
  • Treatment Outcome
  • alpha 1-Antitrypsin / administration & dosage*
  • alpha 1-Antitrypsin / adverse effects
  • alpha 1-Antitrypsin Deficiency / diagnosis
  • alpha 1-Antitrypsin Deficiency / drug therapy*
  • alpha 1-Antitrypsin Deficiency / enzymology
  • alpha 1-Antitrypsin Deficiency / physiopathology

Substances

  • Aerosols
  • SERPINA1 protein, human
  • alpha 1-Antitrypsin

Supplementary concepts

  • alpha-1-Antitrypsin Deficiency, Autosomal Recessive