GRADS Alpha-1Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) - Alpha-1 Protocol

Study start date: May 1, 2013

Inclusion Criteria: Age between age 40 and 80 (inclusive) at Baseline Visit Alpha-1 Antitrypsin genotype PiZZ or PiMZ Able to tolerate and willing to undergo study procedures Signed informed consent Exclusion Criteria: History of comorbid condition severe enough to significantly increase risks based on investigator discretion Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia Partial pressure of oxygen in the blood (PaO2) on room air at rest <50 mmHg or saturation level of oxygen in hemoglobin(SaO2) on room air at rest <85% Post bronchodilator Forced Expiratory Volume in One Second (FEV1)<30% predicted Use of anticoagulation (patients on warfarin or clopidogrel will be excluded; patients on aspirin alone can be studied even with concurrent use) Dementia or other cognitive dysfunction which in the opinion of the investigator would prevent the participant from consenting to the study or completing study procedures Active pulmonary infection with tuberculosis History of pulmonary embolism in the past 2 years Non-COPD obstructive disease (various bronchiolitides, sarcoid, LAM, histiocytosis X) or parenchymal lung disease, pulmonary vascular disease, pleural disease, severe kyphoscoliosis, neuromuscular weakness, or other cardiovascular and pulmonary disease, that, in the opinion of the investigator, limit the interpretability of the pulmonary function measures Prior significant difficulties with pulmonary function testing Hypersensitivity to or intolerance of albuterol sulfate or ipratropium bromide or propellants or excipients of the inhalers Hypersensitivity to or intolerance of all drugs required for sedation during conscious sedation bronchoscopy. History of Lung volume reduction surgery, lung resection or bronchoscopic lung volume reduction in any form History of lung or other organ transplant History of large thoracic metal implants (e.g., Automatic Implantable Cardioverter Defibrillators (AICD) and/or pacemaker) that in the opinion of the investigator limit the interpretability of CT scans Currently taking >=10mg a day/20mg every other day of prednisone or equivalent systemic corticosteroid Currently taking any immunosuppressive agent excepting systemic corticosteroids History of lung cancer or any cancer that spread to multiple locations in the body Current illicit substance abuse, excluding marijuana Known HIV/AIDS infection History of or current exposure to chemotherapy or radiation treatments that, in the opinion of the investigator, limits the interpretability of the pulmonary function measures. Has a BMI > 40 kg/m2 at baseline exam Current or planned pregnancy within the study course. Currently institutionalized (e.g., prisons, long-term care facilities) Have a genotype of PiMZ and ever received intravenous or inhaled alpha-1 augmentation therapy (Alpha-1 Proteinase Inhibitor, A1PI) Conditional Exclusions Participants who present with an upper respiratory infection or pulmonary exacerbation, either solely participant-identified or that has been clinically treated, in the last six weeks can be rescreened for the study once the six-week window has passed. Participants who present with current use of acute antibiotics or steroids can be rescreened for the study ≥30 days after discontinuing acute antibiotics/steroids. This does not apply to participants who are on chronic prednisone therapy of <10 mg per day or <20 mg every other day. Participants who present with a myocardial infarction or eye, chest, or abdominal surgery within six weeks can be rescreened after the six week window has passed. Study coordinators should consult with the site principal investigator prior to rescreening these participants. Female participants who present <3 months after giving birth will be asked to reschedule their visit until three months have passed since the birth. Individuals who are PiZZ receiving alpha-1 augmentation therapy (Alpha-1 Proteinase Inhibitor, A1PI) must be off augmentation therapy for >6 months to qualify for stratified enrollment in the PiZZ group not receiving augmentation therapy.