Lung disease in never-smokers with severe α1-antitrypsin deficiency : the EARCO Registry
(2025) In ERJ open research 11(6).- 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)... (More)
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.
(Less)
- author
- organization
- publishing date
- 2025-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- ERJ open research
- volume
- 11
- issue
- 6
- article number
- 01279-2024
- publisher
- European Respiratory Society
- external identifiers
-
- scopus:105022304757
- pmid:41189584
- ISSN
- 2312-0541
- DOI
- 10.1183/23120541.01279-2024
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The authors 2025.
- id
- d3f35a4c-7a0f-4649-bcb0-09da4cae106c
- date added to LUP
- 2026-01-22 15:15:32
- date last changed
- 2026-01-23 11:18:02
@article{d3f35a4c-7a0f-4649-bcb0-09da4cae106c,
abstract = {{<p>Background Although the role of smoking as a risk factor for emphysema in α<sub>1</sub>-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 (FEV<sub>1</sub>) (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 FEV<sub>1</sub> (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.</p>}},
author = {{Premuda, Chiara and Aljama, Cristina and Granados, Galo and Ferrarotti, Ilaria and Corsico, Angelo Guido and Turner, Alice M. and Torres-Duran, María and Tanash, Hanan and Rodríguez-García, Carlota and Jensen, Jens Ulrik Stæhr and Mantero, Marco and Blasi, Francesco and Miravitlles, Marc and Barrecheguren, Miriam and Esquinas, Cristina}},
issn = {{2312-0541}},
language = {{eng}},
number = {{6}},
publisher = {{European Respiratory Society}},
series = {{ERJ open research}},
title = {{Lung disease in never-smokers with severe α<sub>1</sub>-antitrypsin deficiency : the EARCO Registry}},
url = {{http://dx.doi.org/10.1183/23120541.01279-2024}},
doi = {{10.1183/23120541.01279-2024}},
volume = {{11}},
year = {{2025}},
}