Characteristics of bronchiectasis in patients with different genotypes of severe α1-antitrypsin deficiency from the EARCO registry.

BACKGROUND

α-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by mutations in the SERPINA1 gene and associated with reduced levels of α-1 antitrypsin (AAT). It predisposes individuals to pulmonary diseases, including bronchiectasis, through protease-antiprotease imbalance and immune dysregulation. While the Pi*ZZ genotype has been extensively studied, the prevalence and characteristics of bronchiectasis in other genotypes remain unclear.

METHODS

This cross-sectional study analysed data from the European α-1 Research Collaboration (EARCO) registry, focusing on individuals with bronchiectasis on computed tomography (CT). Participants were stratified by AATD genotypes (Pi*ZZ, Pi*SZ, Pi*SS and rare variants) and data were compared. Disease severity was evaluated using FACED (forced expiratory volume in 1 s (FEV1), age, chronic colonisation, extension and dyspnoea) score and bronchiectasis severity index (BSI) scores.

RESULTS

349 patients had bronchiectasis on a CT scan, of whom 70.5% had Pi*ZZ, 18.6% had Pi*SZ, 4.3% had Pi*SS and 6.6% had rare variants. Lower lobe involvement was predominant across genotypes, whereas Pi*SS exhibited distinct upper lobe patterns and Pi*SZ showed more frequent middle lobe involvement. People with rare genotypes and Pi*ZZ had worse lung function (FEV1 % of 65.3% and 71.4%, respectively) and higher disease severity scores. Emphysema co-occurrence was most frequent in Pi*ZZ (60.6%). No significant differences were observed in sputum microbiology or systemic inflammatory markers, except for lower platelet counts in Pi*ZZ subjects.

CONCLUSION

Bronchiectasis in AATD is not limited to the Pi*ZZ genotype, with significant phenotypic variability across genotypes. Lower lobe involvement and mild disease predominate; however, severe forms are more frequent in rare genotypes and Pi*ZZ. These findings underscore the importance of systematic screening and genotype-specific management to improve patient outcomes.