Lung disease in never-smokers with severe α-antitrypsin deficiency: the EARCO registry
Premuda, Chiara Aljama, Cristina Granados, Galo Ferrarotti, Ilaria Corsico, Angelo Guido Turner, Alice M Torres-Duran, María Tanash, Hanan Rodríguez-García, Carlota Jensen, Jens-Ulrik Stæhr
Premuda, Chiara
Aljama, Cristina
Granados, Galo
Ferrarotti, Ilaria
Corsico, Angelo Guido
Turner, Alice M
Torres-Duran, María
Tanash, Hanan
Rodríguez-García, Carlota
Jensen, Jens-Ulrik Stæhr
Affiliation
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; University of Milan; Vall d'Hebron Barcelona Hospital Campus; IRCCS Policlinico San Matteo Foundation; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Hospital Álvaro Cunqueiro; Skåne University Hospital; Lund University; Complejo Hospitalario Clínico-Universitario de Santiago; Herlev and Gentofte Hospital; University of Copenhagen; University of Barcelona
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Publication date
2025-11-03
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Abstract
Background: Although the role of smoking as a risk factor for emphysema in α1-antitrypsin deficiency (AATD) is well known, never-smokers with severe AATD may also develop lung disease, ranging from mild asymptomatic disease to severe emphysema.
Methods: We performed a cross-sectional and observational study to analyse the characteristics of the population of never-smoker severe AATD (genotype) individuals of the international EARCO Registry.
Results: 914 PI*ZZ individuals were analysed, of whom 472 (51.7%) were active or former smokers and 442 (48.3%) were never-smokers. Never-smokers were older (p<0.001), more frequently females (58.8% versus 43.9%; p<0.001) and had better forced expiratory volume in 1 s (FEV1) (81.3±26.5% versus 48.4±23% predicted; p<0.001). Lung disease was more frequent in smokers compared to never-smokers (98.5% versus 75%; p<0.001), but bronchiectasis was more frequent in never-smokers (28.6% versus 17.7%; p<0.001). A total of 319 (34.9%) patients were receiving augmentation therapy, of whom 235 (49.9%) were former smokers and 84 (19.2%) never-smokers. Among never-smokers, 320 (72.7%) were index cases, were older (61.8±11.2 versus 55.3±10.9 years; p<0.001) and had lower FEV1 (77.2±27.5% versus 92.7±19.3% predicted; p<0.001) compared to non-index cases, but there were no differences in sex distribution. Of the 84 never-smokers on augmentation, 11 (9.4%) were non-index cases.
Conclusions: Among PI*ZZ never-smokers lung disease remains prevalent, even if milder. Nonetheless, some never-smokers develop severe lung impairment requiring augmentation therapy. Non-index cases are healthier with a higher quality of life. Among never-smokers, lower body mass index, male sex, comorbidities and pulmonary exacerbations are associated with fixed airflow obstruction.
Citation
Premuda C, Aljama C, Granados G, Ferrarotti I, Corsico AG, Turner AM, Torres-Duran M, Tanash H, Rodríguez-García C, Jensen JS, Mantero M, Blasi F, Miravitlles M, Barrecheguren M, Esquinas C. Lung disease in never-smokers with severe α1-antitrypsin deficiency: the EARCO Registry. ERJ Open Res. 2025 Nov 3;11(6):01279-2024. doi: 10.1183/23120541.01279-2024.
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Article