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This is an observational study investigating the epigenetic regulation of the immune system in people with alpha-1 antitrypsin deficiency (AATD). It enrolled people aged 18-85 with a diagnosis of AATD (PiZZ or PiMZ) confirmed by blood levels and genetic testing. It was conducted as a non-phase study and has been completed.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria: AATD * Age between the ages of 18 and 85 * Have a diagnosis of AATD PiZZ or PiMZ established by AAT blood levels and Pi genotyping * Are not and have not been on AAT augmentation therapy for the past 6 months * Able to tolerate and willing to undergo study procedures * Provide signed informed consent. Exclusion Criteria: AATD 1. History of comorbid condition severe enough to significantly increase risks based on investigator discretion 2. Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia 3. Partial Pressure of Oxygen (PaO2) on room air at rest \<50 mmHg or Oxygen saturation (SaO2) on room air at rest \<85% 4. Post bronchodilator Forced expiratory volume in one second (FEV1)\<30% predicted 5. Use of anticoagulation (patients on warfarin or clopidogrel will be excluded; patients on aspirin alone can be studied even with concurrent use) 6. 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 7. Active pulmonary infection with tuberculosis 8. History of pulmonary embolism in the past 2 years 9. Non-Chronic Obstructive Pulmonary Disease (COPD) obstructive disease (various bronchiolitides, sarcoid, lymphangioleiomyomatosis (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 10. Prior significant difficulties with pulmonary function testing 11. Hypersensitivity to or intolerance of albuterol sulfate or ipratropium bromide or propellants or excipients of the inhalers 12. Hypersensitivity to or intolerance of all drugs required for sedation during conscious sedation bronchoscopy. 13. History of Lung volume reduction surgery, lung resection or bronchoscopic lung volume reduction in any form 14. History of lung or other organ transplant 15. History of large thoracic metal implants (e.g., Implantable cardioverter-defibrillator (AICD) and/or pacemaker) that in the opinion of the investigator limit the interpretability of CT scans 16. Currently taking \>=10mg a day/20mg every other day of prednisone or equivalent systemic corticosteroid 17. Currently taking any immunosuppressive agent excepting systemic corticosteroids 18. History of lung cancer or any cancer that spread to multiple locations in the body 19. Current illicit substance abuse, excluding marijuana 20. Known HIV/AIDS infection 21. 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. 22. Has a BMI \> 40 kg/m2 at baseline exam 23. Current or planned pregnancy within the study course. 24. Currently institutionalized (e.g., prisons, long-term care facilities) 25. Have a genotype of PiMZ and ever received intravenous or inhaled alpha-1 augmentation therapy (Alpha-1 Proteinase Inhibitor, A1PI) Conditional Exclusions 1. 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. 2. 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. 3. 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. 4. Female participants who present \<3 months after giving birth will be asked to reschedule their visit until three months have passed since the birth. 5. 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.