{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T02:14:13Z","timestamp":1770516853931,"version":"3.49.0"},"reference-count":46,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T00:00:00Z","timestamp":1511740800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL125583"],"award-info":[{"award-number":["R01HL125583"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL130512"],"award-info":[{"award-number":["R01HL130512"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01HL105339"],"award-info":[{"award-number":["P01HL105339"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Severe alpha-1 antitrypsin (AAT) deficiency is one of the most common serious genetic diseases in adults of European descent. Individuals with AAT deficiency have a greatly increased risk for emphysema and liver disease. Other manifestations include bronchiectasis, necrotizing panniculitis and granulomatosis with polyangiitis. Despite the frequency and potential severity, AAT deficiency remains under-recognized, and there is often a delay in diagnosis. This review will focus on three recent updates that should serve to encourage testing and diagnosis of AAT deficiency: first, the publication of a randomized clinical trial demonstrating the efficacy of intravenous augmentation therapy in slowing the progression of emphysema in AAT deficiency; second, the mounting evidence showing an increased risk of lung disease in heterozygous PI MZ genotype carriers; last, the recent publication of a clinical practice guideline, outlining diagnosis and management. Though it has been recognized for more than fifty years, AAT deficiency exemplifies the modern paradigm of precision medicine, with a diagnostic test that identifies a genetic subtype of a heterogeneous disease, leading to a targeted treatment.<\/ns4:p>","DOI":"10.12688\/f1000research.12399.1","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T04:25:06Z","timestamp":1511756706000},"page":"2049","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Diagnosing alpha-1 antitrypsin deficiency: the first step in precision medicine"],"prefix":"10.12688","volume":"6","author":[{"given":"Craig P.","family":"Hersh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2017,11,27]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1316-21","DOI":"10.1056\/NEJM197606102942404","article-title":"Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants.","volume":"294","author":"T Sveger","year":"1976","journal-title":"N Engl J Med."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"961-6","DOI":"10.1164\/ajrccm\/140.4.961","article-title":"Alpha-1-antitrypsin deficiency. 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Research, University of Birmingham, Birmingham, UK, 27 Nov 2017, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/6-2049\/v1#referee-response-28281","order":2,"name":"referee-response-28281","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by U.S. National Institutes of Health grants R01HL125583, R01HL130512, and P01HL105339. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}