Immunosuppression for Lung Transplantation: Current and Future

Overview

Journal Curr Transplant Rep

Date 2019 Feb 12

PMID 30740294

Citations 7

Authors

Satish Chandrashekaran

Stacy A Crow Pharm

Sadia Z Shah

Chris J Arendt Pharm

Cassie C Kennedy

Affiliations

Soon will be listed here.

Abstract

Purpose Of The Review: The number of lung transplantations performed worldwide continues to increase. There is a growing need in these patients for more effective immunosuppressive medications with less toxicity.

Recent Findings: This review article summarizes the recent studies and developments in lung transplant immunosuppression. Novel immunosuppressive medications and strategies used in other solid organ transplantations are being trialed in lung transplantation. This includes the use of co-stimulation blockers like belatacept and mTOR inhibitors like everolimus. Calcineurin sparing regimens have been described in an attempt to minimize nephrotoxicity. Assays to measure the bioactivity of immunosuppressive medications to determine the global immune competence, such as Immuknow assay and Gamma interferon response are gaining traction.

Summary: Immunosuppression in lung transplant is evolving with the development of newer drugs and promising strategies to optimize immunosuppression. Further studies with multicenter randomized trials are required to increase the strength of the evidence.

Citing Articles

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Current perspective of immunomodulators for lung transplant.

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Epidemiology and Prognosis of Invasive Fungal Disease in Chinese Lung Transplant Recipients.

Ju C, Lian Q, Xu X, Cao Q, Lan C, Chen R Front Med (Lausanne). 2021; 8:718747.

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References

Zuckermann A, Klepetko W, Birsan T, Taghavi S, Artemiou O, Wisser W . Comparison between mycophenolate mofetil- and azathioprine-based immunosuppressions in clinical lung transplantation. J Heart Lung Transplant. 1999; 18(5):432-40. DOI: 10.1016/s1053-2498(99)00004-2. View

Wiesner R, Rabkin J, Klintmalm G, McDiarmid S, Langnas A, Punch J . A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. Liver Transpl. 2001; 7(5):442-50. DOI: 10.1053/jlts.2001.23356. View

King-Biggs M, Dunitz J, Park S, Kay Savik S, Hertz M . Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation. Transplantation. 2003; 75(9):1437-43. DOI: 10.1097/01.TP.0000064083.02120.2C. View

HARDY J, Webb W, Dalton Jr M, WALKER Jr G . LUNG HOMOTRANSPLANTATION IN MAN. JAMA. 1963; 186:1065-74. DOI: 10.1001/jama.1963.63710120001010. View

Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G . Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005; 353(8):770-81. DOI: 10.1056/NEJMoa050085. View

Iacono A, Johnson B, Grgurich W, Youssef J, Corcoran T, Seiler D . A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006; 354(2):141-50. DOI: 10.1056/NEJMoa043204. View

Snell G, Valentine V, Vitulo P, Glanville A, McGiffin D, Loyd J . Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. Am J Transplant. 2006; 6(1):169-77. DOI: 10.1111/j.1600-6143.2005.01134.x. View

Burckart G, Hutchinson I, Zeevi A . Pharmacogenomics and lung transplantation: clinical implications. Pharmacogenomics J. 2006; 6(5):301-10. DOI: 10.1038/sj.tpj.6500376. View

McNeil K, Glanville A, Wahlers T, Knoop C, Speich R, Mamelok R . Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation. 2006; 81(7):998-1003. DOI: 10.1097/01.tp.0000202755.33883.61. View

10.

Kowalski R, Post D, Mannon R, Sebastian A, Wright H, Sigle G . Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay. Transplantation. 2006; 82(5):663-8. DOI: 10.1097/01.tp.0000234837.02126.70. View

11.

Hachem R, Edwards L, Yusen R, Chakinala M, Patterson G, Trulock E . The impact of induction on survival after lung transplantation: an analysis of the International Society for Heart and Lung Transplantation Registry. Clin Transplant. 2008; 22(5):603-8. DOI: 10.1111/j.1399-0012.2008.00831.x. View

12.

Husain S, Raza K, Pilewski J, Zaldonis D, Crespo M, Toyoda Y . Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection. Transplantation. 2009; 87(12):1852-7. DOI: 10.1097/TP.0b013e3181a75ad2. View

13.

Groves S, Galazka M, Johnson B, Corcoran T, Verceles A, Britt E . Inhaled cyclosporine and pulmonary function in lung transplant recipients. J Aerosol Med Pulm Drug Deliv. 2009; 23(1):31-9. PMC: 3145164. DOI: 10.1089/jamp.2009.0748. View

14.

Vincenti F, Charpentier B, Vanrenterghem Y, Rostaing L, Bresnahan B, Darji P . A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010; 10(3):535-46. DOI: 10.1111/j.1600-6143.2009.03005.x. View

15.

Bhorade S, Ahya V, Baz M, Valentine V, Arcasoy S, Love R . Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. Am J Respir Crit Care Med. 2010; 183(3):379-87. DOI: 10.1164/rccm.201005-0775OC. View

16.

Vincenti F, Larsen C, Alberu J, Bresnahan B, Garcia V, Kothari J . Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients. Am J Transplant. 2011; 12(1):210-7. DOI: 10.1111/j.1600-6143.2011.03785.x. View

17.

Shino M, Samuel Weigt S, Saggar R, Elashoff D, DerHovanessian A, Gregson A . Usefulness of immune monitoring in lung transplantation using adenosine triphosphate production in activated lymphocytes. J Heart Lung Transplant. 2012; 31(9):996-1002. PMC: 4204735. DOI: 10.1016/j.healun.2012.05.012. View

18.

Dawson K, Parulekar A, Seethamraju H . Treatment of hyperacute antibody-mediated lung allograft rejection with eculizumab. J Heart Lung Transplant. 2012; 31(12):1325-6. DOI: 10.1016/j.healun.2012.09.016. View

19.

Ho E, Wong G, Craig J, Chapman J . Once-daily extended-release versus twice-daily standard-release tacrolimus in kidney transplant recipients: a systematic review. Transplantation. 2013; 95(9):1120-8. DOI: 10.1097/TP.0b013e318284c15b. View

20.

Penninga L, Penninga E, Moller C, Iversen M, Steinbruchel D, Gluud C . Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients. Cochrane Database Syst Rev. 2013; (5):CD008817. DOI: 10.1002/14651858.CD008817.pub2. View