title: Anti-neutrophil-elastase defenses of the lower respiratory tract in alpha 1-antitrypsin deficiency directly augmented with an aerosol of alpha 1-antitrypsin.
abstract: OBJECTIVE
  To determine if aerosolization of purified human plasma alpha 1-antitrypsin is an effective means for increasing lower respiratory anti-neutrophil-elastase defenses in alpha 1-antitrypsin deficiency.
  
  
  METHODS
  Nonrandomized, before-and-after trial with a 7-day treatment period. Companion studies in animals to determine lung epithelial permeability to alpha 1-antitrypsin.
  
  
  METHODS
  Twelve patients with homozygous Z-type alpha 1-antitrypsin deficiency and mild to moderate emphysema.
  
  
  METHODS
  Aerosol administration of human plasma alpha 1-antitrypsin, 100 mg every 12 hours for 7 days. Single, 100-mg aerosol dose to anesthetized sheep with indwelling thoracic lymph duct catheters for direct assessment of lung permeability.
  
  
  RESULTS
  Treatment resulted in increased alpha 1-antitrypsin levels in the lung epithelial lining fluid (0.28 +/- 0.07 microM before therapy to 5.86 +/- 1.03 microM after therapy) and increased anti-neutrophil-elastase capacity (0.78 +/- 0.38 microM before therapy to 4.16 +/- 0.95 microM after therapy). Aerosolized alpha 1-antitrypsin diffused across the respiratory epithelium and entered lung interstitial lymph (in sheep) and reached the systemic circulation (in sheep and humans). No side effects were noted.
  
  
  CONCLUSIONS
  Short-term aerosol administration of human plasma alpha 1-antitrypsin to patients with alpha 1-antitrypsin deficiency is safe and feasible, resulting in a return to normal of anti-neutrophil-elastase defenses in the lower respiratory tract. The aerosol approach, therefore, merits serious long-term evaluation as an alternative to other parenteral forms of administering therapeutic proteins.
authors: National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors: R C
authors: RC
authors: Hubbard
authors: M L
authors: ML
authors: Brantly
authors: S E
authors: SE
authors: Sellers
authors: M E
authors: ME
authors: Mitchell
authors: R G
authors: RG
authors: Crystal
mesh_terms: D000336:Aerosols; D000818:Animals; D006801:Humans; D008168:Lung / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010539:Permeability; D011650:Pulmonary Alveoli / Q000378:metabolism; D012756:Sheep; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019896:alpha 1-Antitrypsin Deficiency
chemical_list: D000336:Aerosols; D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase