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Alpha-1 Antitrypsin Deficiency Associated COPD. Alpha-1 antitrypsin deficiency (AATD) was the first genetic risk factor for chronic obstructive pulmonary disease (COPD) described. In the more than 50 years since its description, the disease continues to provide insights into more common forms of COPD. Although AATD is caused by a single genetic variant, the clinical manifestations of disease include panacinar emphysema, airway hyperresponsiveness, and bronchiectasis. With improved molecular understanding of the mechanisms of disease pathogenesis and progression, new therapies in addition to intravenous augmentation therapy are on the horizon.