{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:46:14Z","timestamp":1760060774185,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biomedical Research Networking Center Consortium (CIBERES)"},{"name":"Instituto de Salud Carlos III"},{"name":"Ministry of Science and Innovation"},{"name":"Grifols SA (Barcelona, Spain)"},{"name":"Amadeu Monteiro research grant from the Alfa1 Espa\u00f1a Association"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M\/Plowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg\/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg\/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies.<\/jats:p>","DOI":"10.3390\/jcm14196789","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:05:13Z","timestamp":1758801913000},"page":"6789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Alpha1 Antitrypsin Deficiency-Associated Mutations in People with Cystic Fibrosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1703-1367","authenticated-orcid":false,"given":"Jose Luis","family":"Lopez-Campos","sequence":"first","affiliation":[{"name":"Unidad M\u00e9dico-Quir\u00fargica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/Universidad de Sevilla, 41013 Seville, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Garc\u00eda Tamayo","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dico-Quir\u00fargica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/Universidad de Sevilla, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9997-5048","authenticated-orcid":false,"given":"Maria Victoria","family":"Gir\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Departamento de Medicina y Dermatolog\u00eda, Universidad de M\u00e1laga, 29071 M\u00e1laga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA)-Plataforma Bionand, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Delgado-Pecell\u00edn","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Servicio de Pediatr\u00eda, Hospital Universitario Virgen del Roc\u00edo, 41013 Seville, Spain"},{"name":"Departamento de Farmacolog\u00eda, Pediatr\u00eda y Radiolog\u00eda, Universidad de Sevilla, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Olveira","sequence":"additional","affiliation":[{"name":"Departamento de Medicina y Dermatolog\u00eda, Universidad de M\u00e1laga, 29071 M\u00e1laga, Spain"},{"name":"UGC Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Regional Universitario de M\u00e1laga, IBIMA Plataforma BIONAND, 29009 M\u00e1laga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8174-0649","authenticated-orcid":false,"given":"Laura","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dico-Quir\u00fargica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/Universidad de Sevilla, 41013 Seville, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0777-5266","authenticated-orcid":false,"given":"Roc\u00edo","family":"Reinoso-Arija","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dico-Quir\u00fargica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/Universidad de Sevilla, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-7400","authenticated-orcid":false,"given":"Casilda","family":"Olveira","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Regional Universitario de M\u00e1laga, 29010 M\u00e1laga, Spain"},{"name":"Departamento de Medicina y Dermatolog\u00eda, Universidad de M\u00e1laga, 29071 M\u00e1laga, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA)-Plataforma Bionand, 29009 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2747-1921","authenticated-orcid":false,"given":"Esther","family":"Quintana-Gallego","sequence":"additional","affiliation":[{"name":"Unidad M\u00e9dico-Quir\u00fargica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Roc\u00edo\/Universidad de Sevilla, 41013 Seville, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.arbres.2023.02.004","article-title":"Variations in chronic obstructive pulmonary disease outpatient care in respiratory clinics: Results from the 2021 epoconsul audit","volume":"59","author":"Miravitlles","year":"2023","journal-title":"Arch. 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