{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:44:54Z","timestamp":1792064694172,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100019210","name":"University Health Network Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019210","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Transplantation"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gastroesophageal reflux disease (GERD) is a known risk factor for chronic lung allograft dysfunction (CLAD), the main barrier to long\u2010term survival in lung transplant recipients (LTR). While proton pump inhibitors (PPI) are effective for symptomatic treatment of GERD, data are sparse on the prevalence of long\u2010term PPI use and association with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010center retrospective cohort of adult first\u2010time LTR between 1999 to 2018 who were alive and CLAD\u2010free at 1\u2010year post\u2010transplant. PPI exposure was defined as \u22658 continuous weeks in the first year, started within 6 months post\u2010transplant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>1308 LTR were included, with 1170 (89.4%) exposed to PPI. PPI use increased over time and remained above 90% from 2007 onwards. In multivariable analyses, LTR on PPI had similar time to CLAD and time to death\/retransplant compared to those not on PPI. Similarly, no differences in outcomes were observed between LTR on once\u2010daily and twice\u2010daily dosing, or after accounting for the number of reflux episodes on 24\u00a0h pH\u2010impedance monitoring. Positive bronchoalveolar lavage cultures and acute rejection over the first\u2010year post\u2010transplant was also comparable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Long\u2010term use of PPI became near\u2010universal without observable effect on clinical outcomes. While further research is needed, these findings question the routine use of PPI in LTR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ctr.70706","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:46:51Z","timestamp":1792061211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Term Proton Pump Inhibitors in Lung Transplant Recipients: Near\u2010Universal Use Without Clear Impact on Clinical Outcomes Over a 20\u2010Year Observational Study"],"prefix":"10.1111","volume":"40","author":[{"given":"Chen Yang Kevin","family":"Zhang","sequence":"first","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayoun","family":"Ramendra","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Aversa","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasheed","family":"Ghany","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Tikkanen","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Huszti","sequence":"additional","affiliation":[{"name":"Biostatistics Research Unit University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Yeung","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaf","family":"Keshavjee","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianne G.","family":"Singer","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Martinu","sequence":"additional","affiliation":[{"name":"Toronto Lung Transplant Program, Ajmera Transplant Centre University Health Network  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"issue":"5","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1378\/chest.124.5.1689","article-title":"Lung Transplantation Exacerbates Gastroesophageal Reflux Disease","volume":"124","author":"Young L. R.","year":"2003","journal-title":"Chest"},{"issue":"7","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1016\/j.transproceed.2010.05.155","article-title":"Gastroesophageal Reflux Disease Is Associated With an Increased Rate of Acute Rejection in Lung Transplant Allografts","volume":"42","author":"Shah N.","year":"2010","journal-title":"Transplantation Proceedings"},{"issue":"4","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1183\/09031936.00064807","article-title":"Gastro\u2010Oesophageal Reflux and Gastric Aspiration in Lung Transplant Patients With or Without Chronic Rejection","volume":"31","author":"Blondeau K.","year":"2008","journal-title":"European Respiratory Journal"},{"issue":"5","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.healun.2019.03.009","article-title":"Chronic Lung Allograft Dysfunction: Definition, Diagnostic Criteria, and Approaches to treatmentA Consensus Report From the Pulmonary Council of the ISHLT","volume":"38","author":"Verleden G. M.","year":"2019","journal-title":"Journal of Heart and Lung Transplantation"},{"issue":"1","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.14309\/ajg.0000000000001538","article-title":"ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease","volume":"117","author":"Katz P. O.","year":"2022","journal-title":"American Journal of Gastroenterology"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhlto.2025.100363","article-title":"Management of Microaspiration and Gastrointestinal Dysfunction After Lung Transplantation: A Narrative Review","volume":"10","author":"Hage R.","year":"2025","journal-title":"JHLT Open"},{"issue":"9","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.healun.2020.05.006","article-title":"Bronchoalveolar Bile Acid and Inflammatory Markers to Identify High\u2010Risk Lung Transplant Recipients With Reflux and Microaspiration","volume":"39","author":"Zhang C.","year":"2020","journal-title":"Journal of Heart and Lung Transplantation"},{"issue":"7","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","DOI":"10.1093\/dote\/doae020","article-title":"Concurrent Abnormal Non\u2010Acid Reflux Is Associated With Additional Chronic Rejection Risk in Lung Transplant Patients With Increased Acid Exposure","volume":"37","author":"Lo W.","year":"2024","journal-title":"Diseases of the Esophagus"},{"issue":"12","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1164\/rccm.201512-2316PP","article-title":"Idiopathic Pulmonary Fibrosis: Novel Concepts of Proton Pump Inhibitors as Antifibrotic Drugs","volume":"193","author":"Ghebre Y. T.","year":"2016","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"2","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s10620-017-4827-0","article-title":"Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation","volume":"63","author":"Lo W. K.","year":"2018","journal-title":"Digestive Diseases and Sciences"},{"issue":"3","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"00675","DOI":"10.1183\/23120541.00675-2024","article-title":"Chronic Lung Allograft Dysfunction After Lung Transplantation: Prevention, Diagnosis and Treatment in 44 European Centres","volume":"11","author":"Gottlieb J.","year":"2025","journal-title":"ERJ Open Research"},{"issue":"4","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1053\/j.gastro.2021.12.247","article-title":"AGA Clinical Practice Update on De\u2010Prescribing of Proton Pump Inhibitors: Expert Review","volume":"162","author":"Targownik L. E.","year":"2022","journal-title":"Gastroenterology"},{"issue":"6","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0128004","article-title":"Risk of Community\u2010Acquired Pneumonia With Outpatient Proton\u2010Pump Inhibitor Therapy: A Systematic Review and Meta\u2010Analysis","volume":"10","author":"Lambert A. A.","year":"2015","journal-title":"PLoS ONE"},{"issue":"1","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s12931-022-02131-5","article-title":"Utility of Bile Acids in Large Airway Bronchial Wash versus Bronchoalveolar Lavage as Biomarkers of Microaspiration in Lung Transplant Recipients: A Retrospective Cohort Study","volume":"23","author":"Zhang C.","year":"2022","journal-title":"Respiratory Research"},{"issue":"1","key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.ajt.2023.08.014","article-title":"Center Variability in the Prognostic Value of a Cumulative Acute Cellular Rejection \u201cA\u2010Score\u201d for Long\u2010Term Lung Transplant Outcomes","volume":"24","author":"Belousova N.","year":"2024","journal-title":"American Journal of Transplantation"},{"issue":"10","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.healun.2021.07.021","article-title":"The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty\u2010Eighth Adult Lung Transplantation Report \u20102021; Focus on Recipient Characteristics","volume":"40","author":"Chambers D. C.","year":"2021","journal-title":"Journal of Heart and Lung Transplantation"},{"issue":"2","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1136\/gutjnl-2023-330616","article-title":"Updates to the Modern Diagnosis of GERD: Lyon Consensus 2.0","volume":"73","author":"Gyawali C. 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