Anti-neutrophil-elastase defenses of the lower respiratory tract in alpha 1-antitrypsin deficiency directly augmented with an aerosol of alpha 1-antitrypsin. Academic Article uri icon

Overview

MeSH

  • Aerosols
  • Animals
  • Humans
  • Permeability
  • Pulmonary Alveoli
  • Sheep

MeSH Major

  • Lung
  • Neutrophils
  • Pancreatic Elastase
  • alpha 1-Antitrypsin
  • alpha 1-Antitrypsin Deficiency

abstract

  • 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. Nonrandomized, before-and-after trial with a 7-day treatment period. Companion studies in animals to determine lung epithelial permeability to alpha 1-antitrypsin. Twelve patients with homozygous Z-type alpha 1-antitrypsin deficiency and mild to moderate emphysema. 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. 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. 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.

publication date

  • August 1, 1989

has subject area

  • Aerosols
  • Animals
  • Humans
  • Lung
  • Neutrophils
  • Pancreatic Elastase
  • Permeability
  • Pulmonary Alveoli
  • Sheep
  • alpha 1-Antitrypsin
  • alpha 1-Antitrypsin Deficiency

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 2787611

Additional Document Info

start page

  • 206

end page

  • 212

volume

  • 111

number

  • 3