Characteristics of bronchiectasis in patients with different genotypes of severe α-antitrypsin deficiency from the EARCO registry
Mandurino Mirizzi, Francesca Aljama, Cristina Santus, Pierachille Mantero, Marco Omcikus, Maja Torres-Duran, María Turner, Alice M Tanash, Hanan Rodríguez-García, Carlota Jensen, Jens-Ulrik Stæhr
Mandurino Mirizzi, Francesca
Aljama, Cristina
Santus, Pierachille
Mantero, Marco
Omcikus, Maja
Torres-Duran, María
Turner, Alice M
Tanash, Hanan
Rodríguez-García, Carlota
Jensen, Jens-Ulrik Stæhr
Abstract
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.
MIDER Authors
Affiliations
Università degli Studi di Milano; ASST Fatebenefratelli-Sacco; Hospital Universitari Vall d'Hebron; Health Care Provider of the European Reference Network on Rare Respiratory Diseases; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; University of Milan; University of Belgrade; University Clinical Center of Serbia; Hospital Álvaro Cunqueiro; Instituto de Salud Carlos III; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Skåne University Hospital; Lund University; Complejo Hospitalario Clínico-Universitario de Santiago; Herlev and Gentofte Hospital; University of Copenhagen; University of Pavia; IRCCS Policlinico San Matteo Foundation; Hospital Universitario Virgen del Rocío; Universidad de Sevilla; University Health Network Toronto; University of Toronto; University Hospital Zurich; Hospital da Senhora da Oliveira; Charles University; Hospital Universitario Nuestra Señora de La Candelaria; University of Barcelona
Date
2026-02-09
Type
Article
Collections
Citation
Mandurino Mirizzi F, Aljama C, Santus P, Mantero M, Omcikus M, Torres-Duran M, Turner AM, Tanash H, Rodríguez-García C, Jensen JS, Corsico AG, López-Campos JL, Chapman KR, Clarenbach C, Guimaraes C, Bartošovská E, Hernández-Pérez JM, Miravitlles M, Esquinas C, Barrecheguren M. Characteristics of bronchiectasis in patients with different genotypes of severe α1-antitrypsin deficiency from the EARCO registry. ERJ Open Res. 2026 Feb 9;12(1):00491-2025. doi: 10.1183/23120541.00491-2025.