Effect of a Higher Dose of Alpha-1 Antitrypsin Augmentation Therapy on Lung Inflammation in Subjects With Alpha-1 Antitrypsin Deficiency.

Study start date: July 1, 2012

Inclusion Criteria: Males or Females aged between 18 and 75 years. Diagnosis of AATD, based on documentation of "at-risk" genotypes such as Pi ZZ, SZ or Znull OR documentation of a pre-therapy AAT level < 11 µM. Evidence of COPD (emphysema or airflow obstruction) with FEV1 < 80% Receiving standard dose of augmentation therapy (with any commercial formulation) for at least 1 month at the dose of 60 mg/kg/week. At least ONE of the following criteria of disease severity: 2 or more acute exacerbations or 1 hospitalization due to respiratory symptoms in the past 12 months. Definition of exacerbations: the use of antibiotics and a course of steroids to treat a flare of pulmonary symptoms, regardless if the subject required emergency room care or hospital admission. The diagnosis of the acute exacerbation will be obtained by direct history obtained from the patient and confirmed by the PI. Attempts should be made to have documentation from the patient's treating physicians, although not required for study entry. St. George Respiratory Questionnaire (SGRQ) total score ≥ 60. Chronic bronchitis: daily or almost daily sputum expectoration at least 3 months of the year for at least 2 consecutive years. The diagnosis of chronic bronchitis will be obtained by direct history obtained from the patient and confirmed by the PI. Attempts should be made to have documentation from the patient's treating physicians, although not required for study entry. Documented FEV1 decline of at least ≥ 60 ml/year for 2 consecutive years while receiving augmentation therapy Exclusion Criteria: - Patients unsuitable to have a bronchoscopy due to poor clinical condition as judged by the PI. In general we will exclude subjects with hypoxemia, coagulopathy or FEV1 below 40% predicted. Note: Subjects with FEV1 values below 40% predicted may be included and reassessed after optimization of therapy. Final determination to include the patient if deemed suitable for the procedure will be determined by the PI before first planned bronchoscopy (regardless of FEV1 value). Patients participating in other clinical trials. Use of chronic antibiotics or oral steroids Continues to smoke Inability to sign informed consent Pregnancy or willing to become pregnant Known IgA deficiency (we will include only patients already receiving augmentation therapy so it will be unlikely to encounter this exclusion criteria)