Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema

Area of Science:

• Pulmonology
• Biochemistry
• Pharmacology

Background:

• Emphysema in alpha 1-antitrypsin deficiency is linked to protease activity on lung tissue.
• Investigating alpha 1-antitrypsin (AAT) replacement therapy is crucial for managing this genetic disorder.

Purpose of the Study:

• To assess the feasibility, safety, and biochemical efficacy of intermittent AAT infusions.
• To evaluate AAT's impact on serum and lung fluid biochemical markers in deficient patients.

Main Methods:

• Twenty-one patients received weekly infusions of 60 mg/kg active plasma-derived AAT for up to six months.
• Serum and lung epithelial lining fluid levels of AAT and anti-neutrophil elastase capacity were measured.

Main Results:

• Infusions significantly increased trough serum AAT levels (30 to 126 mg/dL) and anti-neutrophil elastase capacity (5.4 to 13.3 microM).
• Lung fluid AAT levels and anti-neutrophil elastase capacity also showed significant increases post-infusion (P < 0.0001).
• The therapy was safe, with only self-limited fever as a notable adverse reaction in 507 infusions.

Conclusions:

• Plasma-derived AAT infusions are safe and effectively reverse biochemical abnormalities in AAT deficiency.
• This replacement therapy, combined with smoking cessation, represents a logical long-term treatment strategy.