Study Objective: To determine if aerosolization of purified human plasma α1-antitrypsin is an effective means for increasing lower respiratory anti-neutrophil-elastase defenses in α1-antitrypsin deficiency. Design: Nonrandomized, before-and-after trial with a 7-day treatment period. Companion studies in animals to determine lung epithelial permeability to α1-antitrypsin. Patients: Twelve patients with homozygous Z-type α1-antitrypsin deficiency and mild to moderate emphysema. Interventions: Aerosol administration of human plasma α1-antitrypsin, 100 mg every 12 hours for 7 days. Single, 100-mg aerosol dose to anesthetized shheep with indwelling thoracic lymph duct catheters for direct assessment of lung permeability. Measurements and Main Results: Treatment resulted in increased α1-antitrypsin levels in the lung epithelial lining fluid (0.28 ± 0.07 μM before therapy to 5.86 ± 1.03 μM after therapy) and increased anti-neutrophil-elastase capacity (0.78 ± 0.38 μM before therapy to 4.16 ± 0.95 μM after therapy). Aerosolized α1-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. Conclusion: Short-term aerosol administration of human plasma α1-antitrypsin to patients with α1-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 longterm evaluation as an alternative to other parenteral forms of administering therapeutic proteins.
ASJC Scopus subject areas
- Internal Medicine