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Anti-neutrophil-elastase defenses of the lower respiratory tract in alpha 1-antitrypsin deficiency directly augmented with an aerosol of alpha 1-antitrypsin.
- Source :
-
Annals of Internal Medicine . 8/1/89, Vol. 111 Issue 3, p206-212. 7p. - Publication Year :
- 1989
-
Abstract
- <bold>Study Objective: </bold>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.<bold>Design: </bold>Nonrandomized, before-and-after trial with a 7-day treatment period. Companion studies in animals to determine lung epithelial permeability to alpha 1-antitrypsin.<bold>Patients: </bold>Twelve patients with homozygous Z-type alpha 1-antitrypsin deficiency and mild to moderate emphysema.<bold>Interventions: </bold>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.<bold>Measurements and Main Results: </bold>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.<bold>Conclusion: </bold>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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00034819
- Volume :
- 111
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Annals of Internal Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 6948081
- Full Text :
- https://doi.org/10.7326/0003-4819-111-3-206