We describe a case of a 69-year-old Caucasian female patient, late diagnosis of AATD, with both severe bronchial hyperreactivity and numerous exacerbations due to the peculiar clinical history and the presence of a rare mutation; although not presenting forced expiratory volume in 1 second (FEV1) between 30 and 65%, the patient was treated with alpha-1 antitrypsin (AAT) augmentation therapy and achieved clinical and functional improvement. The gene discussed is SERPINA1; the disease is alpha 1-antitrypsin deficiency.