{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T11:30:09Z","timestamp":1789817409410,"version":"4.0.1"},"reference-count":41,"publisher":"European Respiratory Society (ERS)","issue":"5","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2023,6,20]]},"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alpha-1 antitrypsin deficiency (AATD) is an under-recognised genetic cause of chronic obstructive lung disease, and many fewer cases than estimated have been identified. Can a reported respiratory and hepatic disease history from a large AATD testing database be used to stratify a person's risk of severe AATD?<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed data extracted from the AATD National Detection Program. Demographics and medical history were evaluated to predict AATD PI*ZZ genotype. Logistic regression and integer programming models identified predictors and obtained risk scores. These were internally validated on a subset of the data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Out of 301\u2009343 subjects, 1529 (0.5%) had PI*ZZ genotype. Predictors of severe AATD were asthma, bronchitis, emphysema, allergies, bronchiectasis, family history of AATD, cirrhosis, hepatitis and history of abnormal liver function tests. The derived model establishes a subject's risk of severe AATD, and scores \u22650 had an estimated risk of 0.41%, sensitivity 84.62% and specificity 24.32%. A model simulating guideline recommendations had an estimated risk of 0.51% with a sensitivity of 37.98% and specificity 46.60%. By recommending screening for scores \u22650, we estimate that more subjects would be screened (75.7%<jats:italic>versus<\/jats:italic>53.4%) and detected (84.6%<jats:italic>versus<\/jats:italic>58.2%) compared to a guideline-simulated model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This medical history risk model is a useful predictive tool to detect subjects at greater risk of having severe AATD and improves sensitivity of detection. Scores &lt;0 are at lower risk and may need not be screened; testing is recommended for scores \u22650 and consistent with current guidelines.<\/jats:p><\/jats:sec>","DOI":"10.1183\/23120541.00302-2023","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T14:51:06Z","timestamp":1688655066000},"page":"00302-2023","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Development of a risk score to increase detection of severe alpha-1 antitrypsin deficiency"],"prefix":"10.1183","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0204-2573","authenticated-orcid":false,"given":"E. Leonard","family":"Riley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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