Hrishikesh S Kulkarni1, Wida S Cherikh2, Daniel C Chambers3, Victoria C Garcia2, Ramsey R Hachem4, Daniel Kreisel5, Varun Puri5, Benjamin D Kozower5, Derek E Byers4, Chad A Witt4, Jennifer Alexander-Brett4, Patrick R Aguilar4, Laneshia K Tague4, Yuka Furuya4, G Alec Patterson5, Elbert P Trulock4, Roger D Yusen6. 1. Divisions of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Divisions of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2. United Network for Organ Sharing, Richmond, Virginia; International Society for Heart and Lung Transplantation, Dallas, Texas. 3. University of Queensland School of Medicine, The University of Queensland School of Medicine, Brisbane, Queensland, Australia; Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, Queensland, Australia. 4. Divisions of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 5. Divisions of Cardiothoracic Surgery, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 6. Divisions of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Divisions of General Medical Education, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. Electronic address: yusenr@wustl.edu.
Abstract
BACKGROUND: Lung transplant (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS). However, few long-term, multicenter, and precise estimates of BOS-free survival (a composite outcome of death or BOS) incidence exist. METHODS: This retrospective cohort study of primary LTx recipients (1994-2011) reported to the International Society of Heart and Lung Transplantation Thoracic Transplant Registry assessed outcomes through 2012. For the composite primary outcome of BOS-free survival, we used Kaplan-Meier survival and Cox proportional hazards regression, censoring for loss to follow-up, end of study, and re-LTx. Although standard Thoracic Transplant Registry analyses censor at the last consecutive annual complete BOS status report, our analyses allowed for partially missing BOS data. RESULTS: Due to BOS reporting standards, 99.1% of the cohort received LTx in North America. During 79,896 person-years of follow-up, single LTx (6,599 of 15,268 [43%]) and bilateral LTx (8,699 of 15,268 [57%]) recipients had a median BOS-free survival of 3.16 years (95% confidence interval [CI], 2.99-3.30 years) and 3.58 years (95% CI, 3.53-3.72 years), respectively. Almost 90% of the single and bilateral LTx recipients developed the composite outcome within 10 years of transplantation. Standard Registry analyses "overestimated" median BOS-free survival by 0.42 years and "underestimated" the median survival after BOS by about a half-year for both single and bilateral LTx (p < 0.05). CONCLUSIONS: Most LTx recipients die or develop BOS within 4 years, and very few remain alive and free from BOS at 10 years post-LTx. Less inclusive Thoracic Transplant Registry analytic methods tend to overestimate BOS-free survival. The Registry would benefit from improved international reporting of BOS and other chronic lung allograft dysfunction (CLAD) events.
BACKGROUND: Lung transplant (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS). However, few long-term, multicenter, and precise estimates of BOS-free survival (a composite outcome of death or BOS) incidence exist. METHODS: This retrospective cohort study of primary LTx recipients (1994-2011) reported to the International Society of Heart and Lung Transplantation Thoracic Transplant Registry assessed outcomes through 2012. For the composite primary outcome of BOS-free survival, we used Kaplan-Meier survival and Cox proportional hazards regression, censoring for loss to follow-up, end of study, and re-LTx. Although standard Thoracic Transplant Registry analyses censor at the last consecutive annual complete BOS status report, our analyses allowed for partially missing BOS data. RESULTS: Due to BOS reporting standards, 99.1% of the cohort received LTx in North America. During 79,896 person-years of follow-up, single LTx (6,599 of 15,268 [43%]) and bilateral LTx (8,699 of 15,268 [57%]) recipients had a median BOS-free survival of 3.16 years (95% confidence interval [CI], 2.99-3.30 years) and 3.58 years (95% CI, 3.53-3.72 years), respectively. Almost 90% of the single and bilateral LTx recipients developed the composite outcome within 10 years of transplantation. Standard Registry analyses "overestimated" median BOS-free survival by 0.42 years and "underestimated" the median survival after BOS by about a half-year for both single and bilateral LTx (p < 0.05). CONCLUSIONS: Most LTx recipients die or develop BOS within 4 years, and very few remain alive and free from BOS at 10 years post-LTx. Less inclusive Thoracic Transplant Registry analytic methods tend to overestimate BOS-free survival. The Registry would benefit from improved international reporting of BOS and other chronic lung allograft dysfunction (CLAD) events.
Authors: Marc Estenne; Janet R Maurer; Annette Boehler; James J Egan; Adaani Frost; Marshall Hertz; George B Mallory; Gregory I Snell; Samuel Yousem Journal: J Heart Lung Transplant Date: 2002-03 Impact factor: 10.247
Authors: G M Verleden; L J Dupont; M Delcroix; D Van Raemdonck; J Vanhaecke; T Lerut; M Demedts Journal: Eur Respir J Date: 2003-03 Impact factor: 16.671
Authors: D Hadjiliadis; C Chaparro; C Gutierrez; M P Steele; L G Singer; R D Davis; T K Waddell; M A Hutcheon; S M Palmer; S Keshavjee Journal: Am J Transplant Date: 2006-01 Impact factor: 8.086
Authors: Don Hayes; Benjamin T Kopp; Stephen E Kirkby; Susan D Reynolds; Heidi M Mansour; Joseph D Tobias; Dmitry Tumin Journal: Lung Date: 2016-06-08 Impact factor: 2.584
Authors: Sara A Hennessy; Tjasa Hranjec; Abbas Emaminia; Damien J Lapar; Benjamin D Kozower; Irving L Kron; David R Jones; Christine L Lau Journal: Ann Thorac Surg Date: 2011-10-31 Impact factor: 4.330
Authors: Gundeep S Dhillon; Vincent G Valentine; Joseph Levitt; Premal Patel; Meera R Gupta; Steven R Duncan; Leonardo Seoane; David Weill Journal: Clin Transplant Date: 2011-03-01 Impact factor: 2.863
Authors: Claus Neurohr; Patrick Huppmann; Dolores Thum; Werner Leuschner; Werner von Wulffen; Tobias Meis; Hanno Leuchte; Rainer Baumgartner; Gregor Zimmermann; Rudolf Hatz; Stephan Czerner; Lorenz Frey; Peter Ueberfuhr; Iris Bittmann; Juergen Behr Journal: Transpl Int Date: 2010-03-05 Impact factor: 3.782
Authors: Jan Paul Ouwens; Wim van der Bij; Thomas W van der Mark; Albert Geertsma; Do A Piers; Wim J de Boer; Gerard H Koëter Journal: J Heart Lung Transplant Date: 2004-01 Impact factor: 10.247
Authors: V G Valentine; R C Robbins; G J Berry; H R Patel; H Reichenspurner; B A Reitz; J Theodore Journal: J Heart Lung Transplant Date: 1996-04 Impact factor: 10.247
Authors: Oscar Okwudiri Onyema; Yizhan Guo; Bayan Mahgoub; Qing Wang; Amir Manafi; Zhongcheng Mei; Anirban Banerjee; Dongge Li; Mark H Stoler; Melissa T Zaidi; Adam G Schrum; Daniel Kreisel; Andrew E Gelman; Elizabeth A Jacobsen; Alexander Sasha Krupnick Journal: JCI Insight Date: 2019-06-06
Authors: Jamie L Todd; Megan L Neely; Heather Kopetskie; Michelle L Sever; Jerry Kirchner; Courtney W Frankel; Laurie D Snyder; Elizabeth N Pavlisko; Tereza Martinu; Wayne Tsuang; Michael Y Shino; Nikki Williams; Mark A Robien; Lianne G Singer; Marie Budev; Pali D Shah; John M Reynolds; Scott M Palmer; John A Belperio; S Sam Weigt Journal: Am J Respir Crit Care Med Date: 2020-08-15 Impact factor: 21.405
Authors: Nancy Y Greenland; Fred Deiter; Daniel R Calabrese; Steven R Hays; Jasleen Kukreja; Lorriana E Leard; Nicholas A Kolaitis; Jeffrey A Golden; Jonathan P Singer; John R Greenland Journal: Clin Transplant Date: 2022-03-12 Impact factor: 3.456
Authors: Daniel C Chambers; Andreas Zuckermann; Wida S Cherikh; Michael O Harhay; Don Hayes; Eileen Hsich; Kiran K Khush; Luciano Potena; Aparna Sadavarte; Tajinder P Singh; Josef Stehlik Journal: J Heart Lung Transplant Date: 2020-07-30 Impact factor: 10.247
Authors: Andrew M Courtwright; Anthony M Lamattina; Mai Takahashi; Anil J Trindade; Gary M Hunninghake; Ivan O Rosas; Suneet Agarwal; Benjamin A Raby; Hilary J Goldberg; Souheil El-Chemaly Journal: ERJ Open Res Date: 2020-06-15
Authors: Daniel T Dugger; Monica Fung; Steven R Hays; Jonathan P Singer; Mary E Kleinhenz; Lorriana E Leard; Jeffrey A Golden; Rupal J Shah; Joyce S Lee; Fred Deiter; Nancy Y Greenland; Kirk D Jones; Chaz R Langelier; John R Greenland Journal: Am J Transplant Date: 2020-09-22 Impact factor: 8.086
Authors: Hrishikesh S Kulkarni; Kevin Tsui; Suraj Sunder; Alex Ganninger; Laneshia K Tague; Chad A Witt; Derek E Byers; Elbert P Trulock; Ruben Nava; Varun Puri; Daniel Kreisel; Thalachallour Mohanakumar; Andrew E Gelman; Ramsey R Hachem Journal: Am J Transplant Date: 2019-12-24 Impact factor: 8.086