{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:29:40Z","timestamp":1789709380218,"version":"4.0.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The best described endotype of COPD is alpha-1 antitrypsin (AAT) deficiency, due to a genetic abnormality in the <jats:italic>SERPINA1<\/jats:italic> gene. Common deficient PI variants are the Z and S variants. Homozygotes for the Z allele (PI*ZZ individuals) carry the genotype most commonly associated with severe AAT deficiency (AATD), but a highly prevalent endotype is the heterozygous state (PI*MZ individuals). The effect of PI*MZ status on exacerbations and health care utilization is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Study design and methods<\/jats:title>\n            <jats:p>Cleveland electronic health record data was examined to compare healthcare utilization between PI*MZ and PI*MM individuals. Three outcomes were assessed: moderate COPD exacerbation (defined as short-term steroid prescription), any emergent care (defined as an express care, urgent care, or emergency department visit), and any hospitalization. Models were adjusted for age, sex, race, BMI, smoking status, comorbidity count, liver disease, zip code median income.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>4,148 individuals had the PI*MM genotype and 308 PI*MZ. PI*MZ was associated with increased risk for moderate COPD exacerbations (HR [95% CI]: 1.66 [1.27, 2.17]) and hospitalizations (HR [95% CI]: 1.44 [1.19, 1.75]) compared to PI*MM. The risk of hospitalization was higher among PI*MZ individuals with AAT levels\u2009&lt;\u200990\u00a0mg\/dL (HR [95% CI]: 1.59 [1.14, 2.23]) but not in those with AAT levels\u2009&gt;\u200990\u00a0mg\/dL, as compared to PI*MM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Interpretation<\/jats:title>\n            <jats:p>Given the high prevalence, PI*MZ represents a COPD phenotype that is associated with worse outcomes, inviting additional investigation to identify predictive biomarkers of worse disease and treatable traits. Future prospective studies to better characterize the longitudinal course and healthcare utilization among individuals with a PI*MZ genotype.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12931-025-03322-6","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T07:48:29Z","timestamp":1752220109000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Increased exacerbations and hospitalizations among PI*MZ compared to PI*MM individuals: an electronic health record analysis"],"prefix":"10.1186","volume":"26","author":[{"given":"Vickram","family":"Tejwani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Munoz","family":"Tremblay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Azzato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianne K.","family":"Baldomero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Wendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Attaway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Bowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umur","family":"Hatipoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Hutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Strange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor E.","family":"Ortega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Zein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James K.","family":"Stoller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"3322_CR1","unstructured":"Kochanek KD, Murphy SL, Xu J, Arias E. 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AKB reports receiving research grant support from the NIH National Institute of Environmental Health Sciences. JKS has served as a consultant regarding alpha-1antitrypsin deficiency to: Grifols, Vertex, Takeda, 23andMe, 4DMT, Korro, InhibRx; he previously served as a member of the Board of Directors of the Alpha-1 Foundation and serves on the Medical and Scientific Advisory Committee of the Alpha-1 Foundation. All other authors reported no relevant disclosures.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}},{"value":"Preliminary results of this work were presented at the American Thoracic Society Conference in May, 2023.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Prior presentation"}},{"value":"Institutional review board approval was obtained from the Cleveland Clinic IRB (IRB #22\u2013390) as minimal risk with waived consent.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Institutional review board information"}}],"article-number":"243"}}