Background Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by mutations in the SERPINA1 gene and associated with reduced levels of alpha-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 analyzed data from the European Alpha-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 and Bronchiectasis Severity Index (BSI) scores. Results 349 patients had bronchiectasis on CT scan, of whom 70.5% were Pi*ZZ, 18.6% PiSZ, 4.3% Pi*SS, and 6.6% rare variants. Lower lobe involvement was predominant across genotypes, while Pi*SS exhibited distinct upper lobe patterns and Pi*SZ showed more frequent middle lobe involvement. Rare genotypes and Pi*ZZ had worse lung function (FEV1(%): 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.
Mirizzi et al. (Thu,) studied this question.