Effect of Double Dose of Alpha 1-antitrypsin Augmentation Therapy on Lung Inflammation.

This is a pilot study to test the effect of double dose augmentation therapy with Zemaira (CSL Behring) on lung inflammation, compared with standard doses of 60 mg/kg/week. Our hypothesis is that some patients with AATD receiving augmentation therapy at the standard dose of 60 mg/kg/week continue to have a significant lung inflammation that may lead to detrimental clinical consequences. This inflammation can be further reduced with higher AAT dosing. The study will enroll 20 subjects with AATD and COPD already receiving augmentation therapy with any brand at standard doses for at least a month. For inclusion and exclusion criteria see below. Protocol: The study will take place over approximately 12 weeks: a month receiving Zemaira at standard dose (60 mg/kg/week), a month at double dose (120 mg/kg/week) and a month at standard dose (60 mg/kg/week). The infusions at standard doses will be done at home and infusions with higher doses will be provided at the study site. the study involves scheduled blood draws for clinical labs and serum for research samples. At the end of each phase a bronchoscopy will be performed (3 in total) to obtain research samples (lung lavage, brushings and endobronchial biopsies). The first bronchoscopy after receiving 4 weeks of standard augmentation therapy will assess the "residual" inflammation that may be present despite augmentation therapy. The second bronchoscopy after double dose augmentation therapy phase will be to assess changes (decreases) in inflammatory markers. The third bronchoscopy after resuming standard dosing is to assess if inflammation returned to baseline levels (required for proof of concept). There will be approximately 9 visits to the study clinic. This study does not include placebo (no active drug) treatment. Besides blood draws and bronchoscopy, the study will include questionnaires and lung function testing.