Richard C. Hubbard, MD; Mark L. Brantly, MD; Stephanie E. Sellers, BS; Marc E. Mitchell, MD; Ronald G. Crystal, MD
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 sheep 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 ΩM 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.
Richard C. Hubbard, Mark L. Brantly, Stephanie E. Sellers, Marc E. Mitchell, Ronald G. Crystal. Anti-Neutrophil-Elastase Defenses of the Lower Respiratory Tract in α1-Antitrypsin Deficiency Directly Augmented with an Aerosol of α1-Antitrypsin. Ann Intern Med. 1989;111:206–212. doi: 10.7326/0003-4819-111-3-206
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Published: Ann Intern Med. 1989;111(3):206-212.
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