Strategies for aerosol therapy of α 1-antitrypsin deficiency by the aerosol route Academic Article uri icon


MeSH Major

  • Braces
  • Exercise Therapy
  • Intervertebral Disc
  • Low Back Pain
  • Spinal Diseases


  • Alpha 1-antitrypsin (AAT) deficiency is a genetic disease in which low serum and lung levels of the antiprotease AAT cause a deficiency of the anti-elastase defensive screen of the lower respiratory tract such that neutrophil elastase is free to degrade the connective tissue of the lung, eventually resulting in emphysema. Intravenous AAT infusion therapy restores lung levels of AAT, but is inefficient, costly and a demanding form of therapy. As an alternative, we evaluated aerosol delivery of human plasma AAT (pAAT) and recombinant DNA-produced AAT (rAAT), as a means of providing anti-elastase protection to the lower respiratory tract. In vitro studies demonstrated that both pAAT and rAAT can be aerosolized into droplets suitable for alveolar deposition without loss of antiprotease activity. When administered by aerosol to individuals with AAT deficiency, pAAT and rAAT each significantly raised lung epithelial lining fluid levels of AAT and anti-neutrophil elastase capacity, with the likelihood that twice daily administration of 100 mg of either form would result in normalization of lung anti-elastase defenses at the alveolar surface. Studies in sheep further demonstrated that the aerosolized pAAT and rAAT were each able to pass through alveolar epithelium and gain access to the interstitial compartment of the lung, thus increasing anti-elastase defenses of the lung interstitium. Therapy was safe and well tolerated in all cases. Aerosol therapy with pAAT or rAAT is a safe, feasible, and likely a biochemically efficacious alternative to intravenous AAT augmentation therapy and merits further long-term studies for clinical therapy.

publication date

  • December 1990



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1007/BF02718179

Additional Document Info

start page

  • 565

end page

  • 78


  • 168


  • 1