Augmentation Therapy of Bronchiectasis Due to AATD – Case Report

Introduction 

Alpha-1-antitrypsin is a serine protease inhibitor and plays an important role in regulating inflammatory processes, particularly inhibiting neutrophil elastase. AAT deficiency is a genetic disease caused by a mutation in the SERPINA1 gene. AATD typically manifests as emphysema and airway obstruction, and can also develop into liver cirrhosis. The benefit of administering AAT to patients with chronic obstructive pulmonary disease (COPD) and pulmonary emphysema is well known. The role of augmentation therapy in patients with AATD and bronchiectasis without pulmonary emphysema is still unclear. The following practical case from German colleagues illustrates the positive effect of this treatment in a patient without airway obstruction. 

Case Description

A 53-year-old woman (lifelong non-smoker) was examined for productive cough with intermittent hemoptysis. She reported respiratory infections 3–4 times a year, denying dyspnea at rest or exertion. Apart from hypothyroidism and varicose veins, she was healthy. Auscultation revealed pronounced crackles, mainly over the left lung. 

Functional lung examination revealed restrictive impairment with low vital capacity (VC; 2.7 l = 83% of predicted value), one-second vital capacity (FEV₁; 2.3 l = 86% of predicted value) and FEV₁/FVX ratio at 85% of predicted value. Chest CT showed pronounced predominantly basal bilateral bronchiectasis with bronchial wall thickening and mucoid impactions without the presence of emphysema. Despite frequent application of inhalation therapy, satisfactory control of symptoms and exacerbations was not achieved. Extended diagnostics revealed reduced serum AAT level (30 mg/dl). Genetic testing showed homozygous Pi*ZZ genotype. 

After approval by insurance, augmentation therapy with AAT at a dose of 60 mg/kg weekly was initiated in this off-label indication. After initiation, serum AAT levels normalized and lung function stabilized, significantly reducing the frequency of exacerbations and improving the patient's clinical condition. The therapy was well tolerated and after several months, the patient was able to switch to home self-administration of AAT.  

Discussion and Conclusion

The only treatment specific for AATD is augmentation therapy using human AAT, which represents a safe and well-tolerated modality. Current data regarding the association between bronchiectasis and AATD are contradictory, and there is no evidence of causality of AATD. However, it is possible to assume that the lack of AAT, and thus the lack of its anti-inflammatory effects, may lead to inflammation in the bronchial wall and subsequently to bronchiectasis, especially in patients with Pi*ZZ genotype, who have a higher risk of bacterial infections. The pro-inflammatory effect of AATD may induce the development of bronchiectasis in 3 ways – through interaction of AAT with pro-inflammatory cytokines, through increased neutrophil elastase activity, and through AAT polymers.

Since AATD can be considered a cause of bronchiectasis, detailed evaluation of the effects of augmentation therapy in this indication is offered. There are no studies to date that have demonstrated clinical improvement or slowed progression of bronchiectasis in patients with AATD undergoing augmentation therapy. Genetic screening (identification of homozygous Pi*ZZ genotype in patients with bronchiectasis without emphysema) is needed to identify such cases, but this is not included in the recommended procedures of the European Respiratory Society (ERS) or the British Thoracic Society (BTS). 

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Source: Buck E., Presotto M., Brock J. et al. Augmentation therapy with human alpha-1-proteinase inhibitor reduces exacerbations in patient with bronchiectasis and alpha-1-antitrypsin deficiency. Respir Med Case Rep 2022; 39: 101740. doi: 10.1016/j.rmcr.2022.101740.