Augmentation therapy with human alpha-1-proteinase inhibitor reduces exacerbations in patient with bronchiectasis and alpha-1-antitrypsin deficiency

Abstract

Alpha-1-antitrypsin deficiency (AATD) is a rare cause of noncystic fibrosis (CF) bronchiectasis. The benefits of augmentation therapy in patients with chronic obstructive pulmonary disease (COPD) and pulmonary emphysema are well established. The role of augmentation therapy in AATD bronchiectasis in patients without pulmonary emphysema is not clear. We present the case of a 53-year-old woman (never smoker) who presented with increased susceptibility to infection, productive cough, and intermittent hemoptysis. Pulmonary function testing revealed restrictive impairment [VC 2,7 l (83% of pred.), FEV1 2,3 l (86% of pred.)]. A CT scan of the chest showed marked basal bronchiectasis with mucoid impaction, surrounding consolidation, and no emphysema. Despite frequent use of inhalation therapy, a satisfactory control of symptoms and exacerbations was not achieved. In the course of extended diagnostics regarding the genesis of bronchiectasis, a reduced alpha-1-antitrypsin (AAT) serum level was detected, and a genetic test revealed a homozygous Pi*ZZ genotype. We started augmentation therapy with AAT (Respreeza®, CLS Behring) at the dose of 60 mg/kg per week; the therapy was well tolerated by the patient, and she reported clinical improvement with a reduction in exacerbation frequency. AAT is a serine protease inhibitor and plays a major role in regulating inflammatory activities, in particular by inhibiting neutrophil elastase (NE). The present case illustrates the positive effect of augmentation therapy, including patients without airway obstruction. Among other causes, AATD should be considered as a possible cause of bronchiectasis, and the effects of augmentation therapy for this indication need to be prospectively studied.

Keywords: (AATD); AAT; Alpha-1-antitrypsin; Alpha-1-antitrypsin deficiency; Augmentation therapy; Bronchiectasis.