{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:06:36Z","timestamp":1793862396525,"version":"4.6.1"},"reference-count":24,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016387","name":"Grifols","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100016387","id-type":"DOI","asserted-by":"publisher"}]},{"name":"pH Pharma","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kamada","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2025,3,29]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Although the role of smoking as a risk factor for emphysema in \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      -antitrypsin deficiency (AATD) is well known, never-smokers with severe AATD may also develop lung disease, ranging from mild asymptomatic disease to severe emphysema.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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&lt;0.001), more frequently females (58.8%\n                      <jats:italic>versus<\/jats:italic>\n                      43.9%; p&lt;0.001) and had better forced expiratory volume in 1\u2005s (FEV\n                      <jats:sub>1<\/jats:sub>\n                      ) (81.3\u00b126.5%\n                      <jats:italic>versus<\/jats:italic>\n                      48.4\u00b123% predicted; p&lt;0.001). Lung disease was more frequent in smokers compared to never-smokers (98.5%\n                      <jats:italic>versus<\/jats:italic>\n                      75%; p&lt;0.001), but bronchiectasis was more frequent in never-smokers (28.6%\n                      <jats:italic>versus<\/jats:italic>\n                      17.7%; p&lt;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\u00b111.2\n                      <jats:italic>versus<\/jats:italic>\n                      55.3\u00b110.9\u2005years; p&lt;0.001) and had lower FEV\n                      <jats:sub>1<\/jats:sub>\n                      (77.2\u00b127.5%\n                      <jats:italic>versus<\/jats:italic>\n                      92.7\u00b119.3% predicted; p&lt;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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.01279-2024","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T07:50:26Z","timestamp":1745481026000},"page":"01279-2024","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Lung disease in never-smokers with severe \u03b1\n                    <sub>1<\/sub>\n                    -antitrypsin deficiency: the EARCO Registry"],"prefix":"10.1183","volume":"11","author":[{"given":"Chiara","family":"Premuda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Aljama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1902-1835","authenticated-orcid":false,"given":"Galo","family":"Granados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4892-4192","authenticated-orcid":false,"given":"Ilaria","family":"Ferrarotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Guido","family":"Corsico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5947-3254","authenticated-orcid":false,"given":"Alice 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