Skip to main content
SpringerLink
Log in

The Evolution of Lung Transplant Immunosuppression

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Advances in immunosuppression have been a key component to the ongoing success of lung transplantation. The demographics of patients receiving a lung transplant have evolved with older, more critically ill patients and those with previously contraindicated indications, now becoming recipients. Despite the lack of new classes of maintenance immunosuppression drugs becoming available, advances have been made in the prescribing of traditional immunosuppressive therapies. Developments in immunosuppressive regimens have seen changes in the route of administration, approaches to monitoring and combinations used. Long-term complications of immunosuppression, such as nephrotoxicity and malignancy can limit the success of lung transplantation, and strategies have evolved in recent years to minimise their long-term impact. Although survival outcomes have been steadily improving, chronic lung allograft dysfunction remains a barrier to long-term success. However, treatments for antibody-mediated rejection are emerging as a potential new therapeutic target to decrease the incidence of chronic lung allograft dysfunction. This article provides an update on the current status of immunosuppression after lung transplantation and reviews the evidence for immunosuppressive regimens and the implications for practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, et al. The registry of the international society for heart and lung transplantation: thirty-fourth adult lung and heart-lung transplantation report—2017; focus theme: allograft ischemic time. J Heart Lung Transpl. 2017;36(10):1047–59.

    Article  Google Scholar 

  2. Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Goldfarb SB, et al. The registry of the international society for heart and lung transplantation: thirty-second official adult lung and heart-lung transplantation report—2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34(10):1264–77.

    Article  PubMed  Google Scholar 

  3. Witt CA, Gaut JP, Yusen RD, Byers DE, Iuppa JA, Bennett Bain K, et al. Acute antibody-mediated rejection after lung transplantation. J Heart Lung Transpl. 2013;32(10):1034–40.

    Article  Google Scholar 

  4. Hachem RR. Acute rejection and antibody-mediated rejection in lung transplantation. Clin Chest Med. 2017;38(4):667–75.

    Article  PubMed  Google Scholar 

  5. Hachem RR. Humoral responses after lung transplantation. Curr Opin Organ Transpl. 2016;21(3):267–71.

    Article  CAS  Google Scholar 

  6. Valenzuela NM, Reed EF. Antibody-mediated rejection across solid organ transplants: manifestations, mechanisms, and therapies. J Clin Investig. 2017;127(7):2492–504.

    Article  PubMed  Google Scholar 

  7. Djamali A, Kaufman DB, Ellis TM, Zhong W, Matas A, Samaniego M. Diagnosis and management of antibody-mediated rejection: current status and novel approaches. Am J Transpl. 2014;14(2):255–71.

    Article  CAS  Google Scholar 

  8. Yusen RD, Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, et al. The registry of the international society for heart and lung transplantation: thirtieth adult lung and heart-lung transplant report—2013; focus theme: age. J Heart Lung Transpl. 2013;32(10):965–78.

    Article  Google Scholar 

  9. Hachem RR, Edwards LB, Yusen RD, Chakinala MM, Alexander Patterson G, Trulock EP. The impact of induction on survival after lung transplantation: an analysis of the International Society for Heart and Lung Transplantation Registry. Clin Transpl. 2008;22(5):603–8.

    Article  Google Scholar 

  10. Furuya Y, Jayarajan SN, Taghavi S, Cordova FC, Patel N, Shiose A, et al. The impact of alemtuzumab and basiliximab induction on patient survival and time to bronchiolitis obliterans syndrome in double lung transplantation recipients. Am J Transplant. 2016;16(8):2334–41.

    Article  PubMed  CAS  Google Scholar 

  11. Snell GI, Westall GP, Levvey BJ, Jaksch P, Keshavjee S, Hoopes CW, et al. A randomised, double-blind, placebo-controlled, multicenter study of rabbit ATG in the prophylaxis of acute rejection in lung transplantation. Am J Transpl. 2014;14(5):1191–8.

    Article  CAS  Google Scholar 

  12. Treede H, Glanville AR, Klepetko W, Aboyoun C, Vettorazzi E, Lama R, et al. Tacrolimus and cyclosporine have differential effects on the risk of development of bronchiolitis obliterans syndrome: results of a prospective, randomised international trial in lung transplantation. J Heart Lung Transpl. 2012;31(8):797–804.

    Article  Google Scholar 

  13. Keenan RJ, Konishi H, Kawai A, Paradis IL, Nunley DR, Iacono AT, et al. Clinical trial of tacrolimus versus cyclosporine in lung transplantation. Ann Thorac Surg. 1995;60(3):580–4 (discussion 4–5).

  14. Zuckermann A, Reichenspurner H, Birsan T, Treede H, Deviatko E, Reichart B, et al. Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a 2-center prospective randomised trial. J Thorac Cardiovasc Surg. 2003;125(4):891–900.

    Article  PubMed  CAS  Google Scholar 

  15. Treede H, Klepetko W, Reichenspurner H, Zuckermann A, Meiser B, Birsan T, et al. Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomised two-center trial comparing two different immunosuppressive protocols. J Heart Lung Transpl. 2001;20(5):511–7.

    Article  CAS  Google Scholar 

  16. Abecassis MM, Seifeldin R, Riordan ME. Patient outcomes and economics of once-daily tacrolimus in renal transplant patients: results of a modeling analysis. Transpl Proc. 2008;40(5):1443–5.

    Article  CAS  Google Scholar 

  17. Beckebaum S, Iacob S, Sweid D, Sotiropoulos GC, Saner F, Kaiser G, et al. Efficacy, safety, and immunosuppressant adherence in stable liver transplant patients converted from a twice-daily tacrolimus-based regimen to once-daily tacrolimus extended-release formulation. Transpl Int. 2011;24(7):666–75.

    Article  PubMed  CAS  Google Scholar 

  18. Doesch AO, Mueller S, Akyol C, Erbel C, Frankenstein L, Ruhparwar A, et al. Increased adherence eight months after switch from twice daily calcineurin inhibitor based treatment to once daily modified released tacrolimus in heart transplantation. Drug Des Devel Ther. 2013;7:1253–8.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kolonko A, Chudek J, Wiecek A. Improved kidney graft function after conversion from twice daily tacrolimus to a once daily prolonged-release formulation. Transpl Proc. 2011;43(8):2950–3.

    Article  CAS  Google Scholar 

  20. McCormack PL. Extended-release tacrolimus: a review of its use in de novo kidney transplantation. Drugs. 2014;74(17):2053–64.

    Article  PubMed  CAS  Google Scholar 

  21. Mendez A, Berastegui C, Lopez-Meseguer M, Monforte V, Bravo C, Blanco A, et al. Pharmacokinetic study of conversion from tacrolimus twice-daily to tacrolimus once-daily in stable lung transplantation. Transplantation. 2013;97(3):358–62.

    Google Scholar 

  22. Soto GAC, Ruiz-Antorán B, Laporta R, Sancho A, Lázaro MT, Herrera CP, et al. Dose increase needed in most cystic fibrosis lung transplantation patients when changing from twice- to once-daily tacrolimus oral administration. Eur J Clin Pharmacol. 2015;71(6):715–22.

    Article  PubMed  CAS  Google Scholar 

  23. Meltdose Baraldo M. Meltdose tacrolimus pharmacokinetics. Transpl Proc. 2016;48(2):420–3.

    Article  CAS  Google Scholar 

  24. Hirano Y, Sugimoto S, Mano T, Kurosaki T, Miyoshi K, Otani S, et al. Prolonged administration of twice-daily bolus intravenous tacrolimus in the early phase after lung transplantation. Ann Transpl. 2017;22:484–92.

    Article  Google Scholar 

  25. Doligalski CT, Liu EC, Sammons CM, Silverman A, Logan AT. Sublingual administration of tacrolimus: current trends and available evidence. Pharmacotherapy. 2014;34(11):1209–19.

    Article  PubMed  CAS  Google Scholar 

  26. Reams B, Palmer S. Sublingual tacrolimus for immunosuppression in lung transplantation: a potentially important therapeutic option in cystic fibrosis. Am J Respir Med. 2002;1(2):91–8.

    Article  PubMed  CAS  Google Scholar 

  27. Collin C, Boussaud V, Lefeuvre S, Amrein C, Glouzman AS, Havard L, et al. Sublingual tacrolimus as an alternative to intravenous route in patients with thoracic transplant: a retrospective study. Transpl Proc. 2010;42(10):4331–7.

    Article  CAS  Google Scholar 

  28. Nasiri-Toosi Z, Dashti-Khavidaki S, Nasiri-Toosi M, Khalili H, Jafarian A, Irajian H, et al. Clinical pharmacokinetics of oral versus sublingual administration of tacrolimus in adult liver transplant recipients. Exp Clin Transpl. 2012;10(6):586–91.

    Article  Google Scholar 

  29. Watkins KD, Boettger RF, Hanger KM, Leard LE, Golden JA, Hoopes CW, et al. Use of sublingual tacrolimus in lung transplant recipients. J Heart Lung Transpl. 2012;31(2):127–32.

    Article  Google Scholar 

  30. Tsapepas D, Saal S, Benkert S, Levine D, Delfin M, Cremers S, et al. Sublingual tacrolimus: a pharmacokinetic evaluation pilot study. Pharmacotherapy. 2013;33(1):31–7.

    Article  PubMed  CAS  Google Scholar 

  31. Stifft F, Vanmolkot F, Scheffers I, van Bortel L, Neef C, Christiaans M. Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol. 2014;78(5):996–1004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Vitulo P, Oggionni T, Cascina A, Arbustini E, D’Armini AM, Rinaldi M, et al. Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation. J Heart Lung Transpl. 2002;21(4):435–9.

    Article  Google Scholar 

  33. Cairn J, Yek T, Banner NR, Khaghani A, Hodson ME, Yacoub M. Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. J Heart Lung Transpl. 2003;22(1):50–7.

    Article  CAS  Google Scholar 

  34. Monchaud C, de Winter BC, Knoop C, Estenne M, Reynaud-Gaubert M, Pison C, et al. Population pharmacokinetic modelling and design of a Bayesian estimator for therapeutic drug monitoring of tacrolimus in lung transplantation. Clin Pharmacokinet. 2012;51(3):175–86.

    Article  PubMed  CAS  Google Scholar 

  35. Monchaud C, Marquet P. Pharmacokinetic optimization of immunosuppressive therapy in thoracic transplantation: part I. Clin Pharmacokinet. 2009;48(7):419–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Darley DR, Carlos L, Glanville AR. Trough blood concentrations are an accurate indicator of tacrolimus exposure early post lung transplantation. J Heart Lung Transpl. 2016;35(4):S238.

    Article  Google Scholar 

  37. de Winter BC, Monchaud C, Premaud A, Pison C, Kessler R, Reynaud-Gaubert M, et al. Bayesian estimation of mycophenolate mofetil in lung transplantation, using a population pharmacokinetic model developed in kidney and lung transplant recipients. Clin Pharmacokinet. 2012;51(1):29–39.

    Article  PubMed  Google Scholar 

  38. Monchaud C, Marquet P. Pharmacokinetic optimization of immunosuppressive therapy in thoracic transplantation: part II. Clin Pharmacokinet. 2009;48(8):489–516.

    Article  PubMed  CAS  Google Scholar 

  39. Gerbase MW, Fathi M, Spiliopoulos A, Rochat T, Nicod LP. Pharmacokinetics of mycophenolic acid associated with calcineurin inhibitors: long-term monitoring in stable lung recipients with and without cystic fibrosis. J Heart Lung Transpl. 2003;22(5):587–90.

    Article  Google Scholar 

  40. Stuckey L, Clark Ojo T, Park JM, Annesley T, Bartos C, Cibrik DM. Mycophenolic acid pharmacokinetics in lung transplant recipients with cystic fibrosis. Ther Drug Monit. 2014;36(2):148–51.

    Article  PubMed  CAS  Google Scholar 

  41. Kiang TK, Ensom MH. Therapeutic drug monitoring of mycophenolate in adult solid organ transplant patients: an update. Expert Opin Drug Metab Toxicol. 2016;12(5):545–53.

    Article  PubMed  CAS  Google Scholar 

  42. Kovarik JM, Snell GI, Valentine V, Aris R, Chan CK, Schmidli H, et al. Everolimus in pulmonary transplantation: pharmacokinetics and exposure-response relationships. J Heart Lung Transpl. 2006;25(4):440–6.

    Article  Google Scholar 

  43. Gullestad L, Eiskjaer H, Gustafsson F, Riise GC, Karason K, Dellgren G, et al. Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomised trial. Transpl Int. 2016;29(7):819–29.

    Article  PubMed  CAS  Google Scholar 

  44. Jacob S, Nair AB. A review on therapeutic drug monitoring of the mTOR class of immunosuppressants: everolimus and sirolimus. Drugs Ther Perspect. 2017;33(6):290–301.

    Article  Google Scholar 

  45. de Pablo A, Santos F, Sole A, Borro JM, Cifrian JM, Laporta R, et al. Recommendations on the use of everolimus in lung transplantation. Transpl Rev. 2013;27(1):9–16.

    Article  Google Scholar 

  46. Reichenspurner H. Overview of tacrolimus-based immunosuppression after heart or lung transplantation. J Heart Lung Transpl. 2005;24(2):119–30.

    Article  Google Scholar 

  47. Penninga L, Penninga EI, Moller CH, Iversen M, Steinbruchel DA, Gluud C. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients. Cochrane Database Syst Rev. 2013;5:CD008817.

  48. Fredericks EM, Dore-Stites D. Adherence to immunosuppressants: how can it be improved in adolescent organ transplant recipients? Curr Opin Organ Transpl. 2010;15(5):614–20.

    Article  Google Scholar 

  49. Pollock-Barziv SM, Finkelstein Y, Manlhiot C, Dipchand AI, Hebert D, Ng VL, et al. Variability in tacrolimus blood levels increases the risk of late rejection and graft loss after solid organ transplantation in older children. Pediatr Transpl. 2010;14(8):968–75.

    Article  Google Scholar 

  50. van Gelder T. Within-patient variability in immunosuppressive drug exposure as a predictor for poor outcome after transplantation. Kidney Int. 2014;85(6):1267–8.

    Article  PubMed  CAS  Google Scholar 

  51. Bucuvalas JC, Ryckman FC, Arya G, Andrew B, Lesko A, Cole CR, et al. A novel approach to managing variation: outpatient therapeutic monitoring of calcineurin inhibitor blood levels in liver transplant recipients. J Pediatr. 2005;146(6):744–50.

    Article  PubMed  CAS  Google Scholar 

  52. Hsiau M, Fernandez HE, Gjertson D, Ettenger RB, Tsai EW. Monitoring nonadherence and acute rejection with variation in blood immunosuppressant levels in pediatric renal transplantation. Transplantation. 2011;92(8):918–22.

    Article  PubMed  CAS  Google Scholar 

  53. Mittal N, Thompson JF, Kato T, Tzakis AG. Tacrolimus and diarrhea: pathogenesis of altered metabolism. Pediatr Transpl. 2001;5(2):75–9.

    Article  CAS  Google Scholar 

  54. Snell GI, Westall GP, Paraskeva MA. Immunosuppression and allograft rejection following lung transplantation: evidence to date. Drugs. 2013;73(16):1793–813.

    Article  PubMed  CAS  Google Scholar 

  55. Gallagher HM, Sarwar G, Tse T, Sladden TM, Hii E, Yerkovich ST, et al. Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival. J Heart Lung Transpl. 2015;34(11):1442–8.

    Article  Google Scholar 

  56. Arias M, Seron D, Herrero I, Rush DN, Wiebe C, Nickerson PW, et al. Subclinical antibody-mediated rejection. Transplantation. 2017;101(6S Suppl 1):S1–18.

  57. Mendez A, Monforte V, Berastegui C, Lopez-Meseguer M, Bravo C, Pou L, et al. High intra-individual variability of cyclosporine pharmacokinetics in lung transplant recipients without cystic fibrosis. Clin Transpl. 2014;28(6):743–8.

    Article  CAS  Google Scholar 

  58. Uber PA, Ross HJ, Zuckermann AO, Sweet SC, Corris PA, McNeil K, et al. Generic drug immunosuppression in thoracic transplantation: an ISHLT educational advisory. J Heart Lung Transpl. 2009;28(7):655–60.

    Article  Google Scholar 

  59. Christians U, Klawitter J, Clavijo CF. Bioequivalence testing of immunosuppressants: concepts and misconceptions. Kidney Int Suppl. 2010;115:S1–7.

    Article  CAS  Google Scholar 

  60. Abdulnour HA, Araya CE, Dharnidharka VR. Comparison of generic tacrolimus and Prograf drug levels in a pediatric kidney transplant program: brief communication. Pediatr Transpl. 2010;14(8):1007–11.

    Article  Google Scholar 

  61. del Mar Fernandez De Gatta M, Santos-Buelga D, Dominguez-Gil A, Garcia MJ. Immunosuppressive therapy for paediatric transplant patients: pharmacokinetic considerations. Clin Pharmacokinet. 2002;41(2):115–35.

  62. Molnar AO, Fergusson D, Tsampalieros AK, Bennett A, Fergusson N, Ramsay T, et al. Generic immunosuppression in solid organ transplantation: systematic review and meta-analysis. BMJ. 2015;350:h3163.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Shah RJ, Diamond JM. Update in chronic lung allograft dysfunction. Clin Chest Med. 2017;38(4):677–92.

    Article  PubMed  Google Scholar 

  64. Kim M, Townsend KR, Wood IG, Boukedes S, Guleria I, Gabardi S, et al. Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant candidates. Am J Respir Crit Care Med. 2014;189(10):1234–9.

    Article  PubMed  Google Scholar 

  65. Roux A, Bendib Le Lan I, Holifanjaniaina S, Thomas KA, Hamid AM, Picard C, et al. Antibody-mediated rejection in lung transplantation: clinical outcomes and donor-specific antibody characteristics. Am J Transpl. 2016;16(4):1216–28.

    Article  CAS  Google Scholar 

  66. Berry G, Burke M, Andersen C, Angelini A, Bruneval P, Calabrese F, et al. Pathology of pulmonary antibody-mediated rejection: 2012 update from the Pathology Council of the ISHLT. J Heart Lung Transpl. 2013;32(1):14–21.

    Article  Google Scholar 

  67. Jordan SC, Vo AA, Tyan D, Nast CC, Toyoda M. Current approaches to treatment of antibody-mediated rejection. Pediatr Transpl. 2005;9(3):408–15.

    Article  CAS  Google Scholar 

  68. Daoud AH, Betensley AD. Diagnosis and treatment of antibody mediated rejection in lung transplantation: a retrospective case series. Transpl Immunol. 2013;28(1):1–5.

    Article  PubMed  CAS  Google Scholar 

  69. Jordan SC, Lorant T, Choi J, Kjellman C, Winstedt L, Bengtsson M, et al. IgG endopeptidase in highly sensitised patients undergoing transplantation. N Engl J Med. 2017;377(5):442–53.

    Article  PubMed  CAS  Google Scholar 

  70. Baum C, Reichenspurner H, Deuse T. Bortezomib rescue therapy in a patient with recurrent antibody-mediated rejection after lung transplantation. J Heart Lung Transpl. 2013;32(12):1270–1.

    Article  Google Scholar 

  71. Woodle ES, Alloway RR, Girnita A. Proteasome inhibitor treatment of antibody-mediated allograft rejection. Curr Opin Organ Transpl. 2011;16(4):434–8.

    Article  CAS  Google Scholar 

  72. Neumann J, Tarrasconi H, Bortolotto A, Machuca T, Canabarro R, Sporleder H, et al. Acute humoral rejection in a lung recipient: reversion with bortezomib. Transplantation. 2010;89(1):125–6.

    Article  PubMed  Google Scholar 

  73. Hayes D, Nicholson KL, Baker PB. Bortezomib for antibody-mediated rejection in a young lung transplant recipient. Pediatr Transpl. 2016;20(1):178–9.

    Article  Google Scholar 

  74. Locke JE, Magro CM, Singer AL, Segev DL, Haas M, Hillel AT, et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transpl. 2009;9(1):231–5.

    Article  CAS  Google Scholar 

  75. Dawson KL, Parulekar A, Seethamraju H. Treatment of hyperacute antibody-mediated lung allograft rejection with eculizumab. J Heart Lung Transpl. 2012;31(12):1325–6.

    Article  Google Scholar 

  76. Miller Z, Ao L, Kim KB, Lee W. Inhibitors of the immunoproteasome: current status and future directions. Curr Pharm Des. 2013;19(22):4140–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Ensor CR, Yousem SA, Marrari M, Morrell MR, Mangiola M, Pilewski JM, et al. Proteasome inhibitor carfilzomib-based therapy for antibody-mediated rejection of the pulmonary allograft: use and short-term findings. Am J Transpl. 2017;17(5):1380–8.

    Article  CAS  Google Scholar 

  78. Benden C, Haughton M, Leonard S, Huber LC. Therapy options for chronic lung allograft dysfunction-bronchiolitis obliterans syndrome following first-line immunosuppressive strategies: a systematic review. J Heart Lung Transpl. 2017;36(9):921–33.

    Article  Google Scholar 

  79. Verleden SE, Sacreas A, Vos R, Vanaudenaerde BM, Verleden GM. Advances in understanding bronchiolitis obliterans after lung transplantation. Chest. 2016;150(1):219–25.

    Article  PubMed  Google Scholar 

  80. Pecoraro Y, Carillo C, Diso D, Mantovani S, Cimino G, De Giacomo T, et al. Efficacy of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation. Transpl Proc. 2017;49(4):695–8.

    Article  CAS  Google Scholar 

  81. Jain R, Hachem RR, Morrell MR, Trulock EP, Chakinala MM, Yusen RD, et al. Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transpl. 2010;29(5):531–7.

    Article  Google Scholar 

  82. Ruttens D, Verleden SE, Vandermeulen E, Bellon H, Vanaudenaerde BM, Somers J, et al. Prophylactic azithromycin therapy after lung transplantation: post hoc analysis of a randomised controlled trial. Am J Transpl. 2016;16(1):254–61.

    Article  CAS  Google Scholar 

  83. Vos R, Vanaudenaerde BM, Verleden SE, De Vleeschauwer SI, Willems-Widyastuti A, Van Raemdonck DE, et al. A randomised controlled trial of azithromycin to prevent chronic rejection after lung transplantation. Eur Respir J. 2011;37(1):164–72.

    Article  PubMed  CAS  Google Scholar 

  84. Corcoran TE, Niven R, Verret W, Dilly S, Johnson BA. Lung deposition and pharmacokinetics of nebulised cyclosporine in lung transplant patients. J Aerosol Med Pulm Drug Deliv. 2014;27(3):178–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Corcoran TE, Smaldone GC, Dauber JH, Smith DA, McCurry KR, Burckart GJ, et al. Preservation of post-transplant lung function with aerosol cyclosporin. Eur Respir J. 2004;23(3):378–83.

    Article  PubMed  CAS  Google Scholar 

  86. Burkart GJ, Smaldone GC, Eldon MA, Venkataramanan R, Dauber J, Zeevi A, et al. Lung deposition and pharmacokinetics of cyclosporine after aerosolization in lung transplant patients. Pharm Res. 2003;20(2):252–6.

    Article  PubMed  Google Scholar 

  87. Behr J, Zimmermann G, Baumgartner R, Leuchte H, Neurohr C, Brand P, et al. Lung deposition of a liposomal cyclosporine A inhalation solution in patients after lung transplantation. J Aerosol Med Pulm Drug Deliv. 2009;22(2):121–30.

    Article  PubMed  CAS  Google Scholar 

  88. Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, et al. A randomised trial of inhaled cyclosporine in lung-transplant recipients. NEJM. 2006;354(2):141–50.

    Article  PubMed  Google Scholar 

  89. Iacono AT, Keenan RJ, Duncan SR, Smaldone GC, Dauber JH, Paradis IL, et al. Aerosolised cyclosporine in lung recipients with refractory chronic rejection. Am J Respir Crit Care Med. 1996;153(4 Pt 1):1451–5.

    Article  PubMed  CAS  Google Scholar 

  90. Johnson BA, Zamora MR, Budev MM, Kotloff RM, Iacono A, Dilly SG, et al. 172 cyclosporine inhalation solution does not improve bronchiolitis obliterans syndrome-free survival following lung transplant: results from the CYCLIST trial. J Heart Lung Transpl. 2012;31(4):S66.

    Article  Google Scholar 

  91. Hayes D Jr, Zwischenberger JB, Mansour HM. Aerosolised tacrolimus: a case report in a lung transplant recipient. Transpl Proc. 2010;42(9):3876–9.

    Article  Google Scholar 

  92. Verleden GM, Verleden SE, Vos R, De Vleeschauwer SI, Dupont LJ, Van Raemdonck DE, et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a pilot study. Transpl Int. 2011;24(7):651–6.

    Article  PubMed  Google Scholar 

  93. Ruttens D, Verleden S, Vandermeulen E, Bellon H, Van Raemdonck D, Yserbyt J, et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a randomised controlled trial. J Heart Lung Transpl. 2016;35(4):S43–4.

    Article  Google Scholar 

  94. Pluchart H, Chanoine S, Beaumier L, Briault A, Quetant S, Pison C, et al. DI-087 Restrictive allograft syndrome in lung transplantation: nintedanib as a new therapeutic strategy? Eur J Hosp Pharm. 2017;24(Suppl 1):A152–A.

  95. Ihle F, von Wulffen W, Neurohr C. Pirfenidone: a potential therapy for progressive lung allograft dysfunction? J Heart Lung Transpl. 2013;32(5):574–5.

    Article  Google Scholar 

  96. von Suesskind-Schwendi M, Heigel E, Pfaehler S, Haneya A, Schmid C, Hirt SW, et al. Protective function of pirfenidone and everolimus on the development of chronic allograft rejection after experimental lung transplantation. Histol Histopathol. 2016;31(7):793–805.

    Google Scholar 

  97. Vos R, Verleden SE, Ruttens D, Vandermeulen E, Yserbyt J, Dupont LJ, et al. Pirfenidone: a potential new therapy for restrictive allograft syndrome? Am J Transpl. 2013;13(11):3035–40.

    Article  CAS  Google Scholar 

  98. Dusmet M, Maurer J, Winton T, Kesten S. Methotrexate can halt the progression of bronchiolitis obliterans syndrome in lung transplant recipients. J Heart Lung Transpl. 1996;15(9):948–54.

    CAS  Google Scholar 

  99. Sithamparanathan S, Thirugnanasothy L, Morley K, Fisher AJ, Lordan JL, Meachery G, et al. Methotrexate as a treatment strategy for bronchiolitis obliterans syndrome (BOS). J Heart Lung Transpl. 2015;34(4):S253.

    Article  Google Scholar 

  100. Date H, Lynch JP, Sundaresan S, Patterson GA, Trulock EP. The impact of cytolytic therapy on bronchiolitis obliterans syndrome. J Heart Lung Transpl. 1998;17(9):869–75.

    CAS  Google Scholar 

  101. Snell GI, Esmore DS, Williams TJ. Cytolytic therapy for the bronchiolitis obliterans syndrome complicating lung transplantation. Chest. 1996;109(4):874–8.

    Article  PubMed  CAS  Google Scholar 

  102. George E, Ivulich S, Paraskeva M, Levvey B, Snell G, Westall GP. Antithymocyte globulin therapy for chronic lung allograft dysfunction following lung transplantation. J Heart Lung Transpl. 2014;33(4):S312.

    Article  Google Scholar 

  103. Reams BD, Musselwhite LW, Zaas DW, Steele MP, Garantziotis S, Eu PC, et al. Alemtuzumab in the treatment of refractory acute rejection and bronchiolitis obliterans syndrome after human lung transplantation. Am J Transpl. 2007;7(12):2802–8.

    Article  CAS  Google Scholar 

  104. Rihtarchik LC, McDyer JF, Zeevi A, Pilewski JM, Crespo M, Johnson BA, et al. Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation at a single high-volume center. J Heart Lung Transpl. 2015;34(4):S242.

    Article  Google Scholar 

  105. Jaksch P, Scheed A, Keplinger M, Ernst MB, Dani T, Just U, et al. A prospective interventional study on the use of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transpl. 2012;31(9):950–7.

    Article  Google Scholar 

  106. Morrell MR, Despotis GJ, Lublin DM, Patterson GA, Trulock EP, Hachem RR. The efficacy of photopheresis for bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transpl. 2010;29(4):424–31.

    Article  Google Scholar 

  107. Greer M, Dierich M, De Wall C, Suhling H, Rademacher J, Welte T, et al. Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients. Am J Transpl. 2013;13(4):911–8.

    Article  CAS  Google Scholar 

  108. Fisher AJ, Rutherford RM, Bozzino J, Parry G, Dark JH, Corris PA. The safety and efficacy of total lymphoid irradiation in progressive bronchiolitis obliterans syndrome after lung transplantation. Am J Transpl. 2005;5(3):537–43.

    Article  Google Scholar 

  109. Verleden GM, Lievens Y, Dupont LJ, Van Raemdonck DE, De Vleeschauwer SI, Vos R, et al. Efficacy of total lymphoid irradiation in azithromycin nonresponsive chronic allograft rejection after lung transplantation. Transpl Proc. 2009;41(5):1816–20.

    Article  CAS  Google Scholar 

  110. Rafeeq MM, Murad HAS. Cystic fibrosis: current therapeutic targets and future approaches. J Transl Med. 2017;15:84.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Jordan CL, Noah TL, Henry MM. Therapeutic challenges posed by critical drug–drug interactions in cystic fibrosis. Pediatr Pulmonol. 2016;51(S44):S61–s70.

    Article  PubMed  Google Scholar 

  112. Donaldson SH, Pilewski JM, Griese M, Cooke J, Viswanathan L, Tullis E, et al. Tezacaftor/Ivacaftor in subjects with cystic fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med. 2018;197(2):214–24.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Garg V, Shen J, Li C, Argarwal S, Gebre A, Parkinson J, et al., editors. Drug-drug interaction profile of tezacaftor/ivacaftor in healthy adult subjects. In: 31st Annual North American Cystic Fibrosis Conference; 2017; Indianapolis, Indiana: Pediatric Pulmonology.

  114. Fitzgerald JL, Howes LG. Drug interactions of direct-acting oral anticoagulants. Drug Saf. 2016;39(9):841–5.

    Article  PubMed  CAS  Google Scholar 

  115. Voukalis C, Lip GY, Shantsila E. Drug-drug interactions of non-vitamin K oral anticoagulants. Expert Opin Drug Metab Toxicol. 2016;12(12):1445–61.

    Article  PubMed  CAS  Google Scholar 

  116. Vanhove T, Spriet I, Annaert P, Maertens J, Van Cleemput J, Vos R, et al. Effect of the direct oral anticoagulants rivaroxaban and apixaban on the disposition of calcineurin inhibitors in transplant recipients. Ther Drug Monit. 2017;39(1):77–82.

    Article  PubMed  CAS  Google Scholar 

  117. Shuster JE, LaRue SJ, Vader JM. Dabigatran may have more significant drug interactions with calcineurin inhibitors than oral anti-xa inhibitors. J Heart Lung Transpl. 2016;35(4):S417.

    Article  Google Scholar 

  118. Xue J, Wang L, Chen CM, Chen JY, Sun ZX. Acute kidney injury influences mortality in lung transplantation. Ren Fail. 2014;36(4):541–5.

    Article  PubMed  CAS  Google Scholar 

  119. Wehbe E, Duncan AE, Dar G, Budev M, Stephany B. Recovery from AKI and short- and long-term outcomes after lung transplantation. Clin J Am Soc Nephrol. 2013;8(1):19–25.

    Article  PubMed  CAS  Google Scholar 

  120. Jacques F, El-Hamamsy I, Fortier A, Maltais S, Perrault LP, Liberman M, et al. Acute renal failure following lung transplantation: risk factors, mortality, and long-term consequences. Eur J Cardiothorac Surg. 2012;41(1):193–9.

  121. Broekroelofs J, Navis GJ, Stegeman CA, van der Bij W, de Boer WJ, de Zeeuw D, et al. Long-term renal outcome after lung transplantation is predicted by the 1-month postoperative renal function loss. Transplantation. 2000;69(8):1624–8.

    Article  PubMed  CAS  Google Scholar 

  122. George TJ, Arnaoutakis GJ, Beaty CA, Pipeling MR, Merlo CA, Conte JV, et al. Acute kidney injury increases mortality after lung transplantation. Ann Thorac Surg. 2012;94(1):185–92.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Robinson PD, Shroff RC, Spencer H. Renal complications following lung and heart-lung transplantation. Pediatr Nephrol. 2013;28(3):375–86.

    Article  PubMed  Google Scholar 

  124. Clinckart F, Bulpa P, Jamart J, Eucher P, Delaunois L, Evrard P. Basiliximab as an alternative to antithymocyte globulin for early immunosuppression in lung transplantation. Transpl Proc. 2009;41(2):607–9.

    Article  CAS  Google Scholar 

  125. Shyu S, Dew MA, Pilewski JM, DeVito Dabbs AJ, Zaldonis DB, Studer SM, et al. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transpl. 2011;30(7):743–54.

    Article  Google Scholar 

  126. Swarup R, Allenspach LL, Nemeh HW, Stagner LD, Betensley AD. Timing of basiliximab induction and development of acute rejection in lung transplant patients. J Heart Lung Transpl. 2011;30(11):1228–35.

    Article  Google Scholar 

  127. Whitson BA, Lehman A, Wehr A, Hayes D Jr, Kirkby S, Pope-Harman A, et al. To induce or not to induce: a 21st century evaluation of lung transplant immunosuppression’s effect on survival. Clin Transpl. 2014;28(4):450–61.

    Article  CAS  Google Scholar 

  128. Schneer S, Kramer MR, Fox B, Rusanov V, Fruchter O, Rosengarten D, et al. Renal function preservation with the mTOR inhibitor, Everolimus, after lung transplant. Clin Transpl. 2014;28(6):662–8.

    Article  CAS  Google Scholar 

  129. Arora S, Gude E, Sigurdardottir V, Mortensen SA, Eiskjaer H, Riise G, et al. Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: the significance of baseline glomerular filtration rate. J Heart Lung Transpl. 2012;31(3):259–65.

    Article  Google Scholar 

  130. Gullestad L, Mortensen SA, Eiskjaer H, Riise GC, Mared L, Bjortuft O, et al. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomised trial. Transplantation. 2010;90(12):1581–9.

    Article  PubMed  CAS  Google Scholar 

  131. Stephany BR, Boumitri M, Budev M, Alao B, Poggio ED. Absence of proteinuria predicts improvement in renal function after conversion to sirolimus-based immunosuppressive regimens in lung transplant survivors with chronic kidney disease. J Heart Lung Transpl. 2009;28(6):564–71.

    Article  Google Scholar 

  132. Letavernier E, Legendre C. mToR inhibitors-induced proteinuria: mechanisms, significance, and management. Transpl Rev. 2008;22(2):125–30.

    Article  Google Scholar 

  133. Timofte I, Terrin M, Barr E, Sanchez P, Kim J, Reed R, et al. Belatacept for renal rescue in lung transplant patients. Transpl Int. 2016;29(4):453–63.

    Article  PubMed  CAS  Google Scholar 

  134. Ensor C, Winstead R, Johnson B, Morrell M, Kilaru S, Moore C, et al. Successful maintenance belatacept-based immunosuppression in lung transplantation recipients who failed calcineurin inhibitors. American Transplant Congress; Pittsburgh: American Journal of Transplant; 2016.

  135. Shigemura N, Sclabassi RJ, Bhama JK, Gries CJ, Crespo MM, Johnson B, et al. Early major neurologic complications after lung transplantation: incidence, risk factors, and outcome. Transplantation. 2013;95(6):866–71.

    Article  PubMed  Google Scholar 

  136. Pizzi M, Ng L. Neurologic complications of solid organ transplantation. Neurol Clin. 2017;35(4):809–23.

    Article  PubMed  Google Scholar 

  137. Mateen FJ, Dierkhising RA, Rabinstein AA, van de Beek D, Wijdicks EF. Neurological complications following adult lung transplantation. Am J Transpl. 2010;10(4):908–14.

    Article  CAS  Google Scholar 

  138. Moffatt-Bruce SD, Pesavento T, Von Viger J, Nunley D, Pope-Harman A, Martin S, et al. Successful management of immunosuppression in a patient with severe hyperammonemia after lung transplantation. J Heart Lung Transpl. 2008;27(7):801–3.

    Article  Google Scholar 

  139. Bharat A, Cunningham SA, Scott Budinger GR, Kreisel D, DeWet CJ, Gelman AE, et al. Disseminated Ureaplasma infection as a cause of fatal hyperammonemia in humans. Sci Transl Med. 2015;7(284):284re3.

  140. Wang X, Greenwood-Quaintance KE, Karau MJ, Block DR, Mandrekar JN, Cunningham SA, et al. Ureaplasma parvum causes hyperammonemia in a pharmacologically immunocompromised murine model. Eur J Clin Microbiol Infect Dis. 2017;36(3):517–22.

    Article  PubMed  CAS  Google Scholar 

  141. Lichtenstein GR, Yang YX, Nunes FA, Lewis JD, Tuchman M, Tino G, et al. Fatal hyperammonemia after orthotopic lung transplantation. Ann Intern Med. 2000;132(4):283–7.

    Article  PubMed  CAS  Google Scholar 

  142. Anwar S, Gupta D, Ashraf MA, Khalid SA, Rizvi SM, Miller BW, et al. Symptomatic hyperammonemia after lung transplantation: lessons learnt. Hemodial Int Symp Home Hemodial. 2014;18(1):185–91.

    Article  Google Scholar 

  143. Chen C, Bain KB, Iuppa JA, Yusen RD, Byers DE, Patterson GA, et al. Hyperammonemia syndrome after lung transplantation: a single center experience. Transplantation. 2016;100(3):678–84.

    Article  PubMed  CAS  Google Scholar 

  144. Nair N, Gongora E, Mehra MR. Long-term immunosuppression and malignancy in thoracic transplantation: where is the balance? J Heart Lung Transpl. 2014;33(5):461–7.

    Article  Google Scholar 

  145. Robbins HY, Arcasoy SM. Malignancies following lung transplantation. Clin Chest Med. 2011;32(2):343–55.

    Article  PubMed  Google Scholar 

  146. Fine NM, Kushwaha SS. Recent advances in mammalian target of rapamycin inhibitor use in heart and lung transplantation. Transplantation. 2016;100(12):2558–68.

    Article  PubMed  CAS  Google Scholar 

  147. Waldner M, Fantus D, Solari M, Thomson AW. New perspectives on mTOR inhibitors (rapamycin, rapalogs and TORKinibs) in transplantation. Br J Clin Pharmacol. 2016;82(5):1158–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  148. Vaysberg M, Balatoni CE, Nepomuceno RR, Krams SM, Martinez OM. Rapamycin inhibits proliferation of Epstein-Barr virus-positive B-cell lymphomas through modulation of cell-cycle protein expression. Transplantation. 2007;83(8):1114–21.

    Article  PubMed  CAS  Google Scholar 

  149. Goldfarb SB, Levvey BJ, Cherikh WS, Chambers DC, Khush K, Kucheryavaya AY, et al. Registry of the international society for heart and lung transplantation: twentieth pediatric lung and heart-lung transplantation report-2017; focus theme: allograft ischemic time. J Heart Lung Transpl. 2017;36(10):1070–9.

    Article  Google Scholar 

  150. Hayes D Jr, Glanville AR, McGiffin D, Tobias JD, Tumin D. Age-related survival disparity associated with lung transplantation in cystic fibrosis: an analysis of the registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transpl. 2016;35(9):1108–15.

    Article  Google Scholar 

  151. Goldfarb SB, Levvey BJ, Edwards LB, Dipchand AI, Kucheryavaya AY, Lund LH, et al. The registry of the international society for heart and lung transplantation: nineteenth pediatric lung and heart lung transplantation report-2016; focus theme: primary diagnostic indications for transplant. J Heart Lung Transpl. 2016;35(10):1196–205.

    Article  Google Scholar 

  152. Schmid FA, Benden C. Special considerations for the use of lung transplantation in pediatrics. Expert Rev Respir Med. 2016;10(6):655–62.

    Article  PubMed  CAS  Google Scholar 

  153. Malik S, Kassaï B, Cochat P. Overview of pediatric organ transplantation: current opinion and future perspectives on immunosuppression. Curr Opin Organ Transpl. 2015;20(5):527–35.

    Article  CAS  Google Scholar 

  154. Benden C. Specific aspects of children and adolescents undergoing lung transplantation. Curr Opin Organ Transpl. 2012;17(5):509–14.

    Article  Google Scholar 

  155. Benden C. Pediatric lung transplantation. J Thorac Dis. 2017;9(8):2675–83.

    Article  PubMed  PubMed Central  Google Scholar 

  156. Dew MA, Dabbs AD, Myaskovsky L, Shyu S, Shellmer DA, DiMartini AF, et al. Meta-analysis of medical regimen adherence outcomes in pediatric solid organ transplantation. Transplantation. 2009;88(5):736–46.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Hu L, Lingler JH, Sereika SM, Burke LE, Malchano DK, DeVito Dabbs A, et al. Nonadherence to the medical regimen after lung transplantation: a systematic review. Heart Lung. 2017;46(3):178–86.

    Article  PubMed  Google Scholar 

  158. Hayes D Jr, McCoy KS, Whitson BA, Mansour HM, Tobias JD. High-risk age window for mortality in children with cystic fibrosis after lung transplantation. Pediatr Transpl. 2015;19(2):206–10.

    Article  Google Scholar 

  159. Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, et al. Interventions for improving medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2017. https://doi.org/10.1002/14651858.CD012854.

    Article  Google Scholar 

  160. De Geest S, Dobbels F, Fluri C, Paris W, Troosters T. Adherence to the therapeutic regimen in heart, lung, and heart-lung transplant recipients. J Cardiovasc Nurs. 2005;20(5 Suppl):S88–98.

    Article  PubMed  Google Scholar 

  161. Dobbels F, De Bleser L, Berben L, Kristanto P, Dupont L, Nevens F, et al. Efficacy of a medication adherence enhancing intervention in transplantation: the MAESTRO-Tx trial. J Heart Lung Transpl. 2017;36(5):499–508.

    Article  Google Scholar 

  162. Vos R, Ruttens D, Verleden SE, Vandermeulen E, Bellon H, Vanaudenaerde BM, et al. Pregnancy after heart and lung transplantation. Best Pract Res Clin Obstetr Gynaecol. 2014;28(8):1146–62.

    Article  Google Scholar 

  163. Shaner J, Coscia LA, Constantinescu S, McGrory CH, Doria C, Moritz MJ, et al. Pregnancy after lung transplant. Prog Transpl. 2012;22(2):134–40.

    Article  Google Scholar 

  164. Mastrobattista JM, Gomez-Lobo V. Pregnancy after solid organ transplantation. Obstet Gynecol. 2008;112(4):919–32.

    Article  PubMed  Google Scholar 

  165. Casale JP, Doligalski CT. Pharmacologic considerations for solid organ transplant recipients who become pregnant. Pharmacotherapy. 2016;36(9):971–82.

    Article  PubMed  Google Scholar 

  166. Biswas Roy S, Alarcon D, Walia R, Chapple KM, Bremner RM, Smith MA. Is there an age limit to lung transplantation? Ann Thorac Surg. 2015;100(2):443–51.

    Article  PubMed  Google Scholar 

  167. Raman SM, Cahill BC. Lung transplantation in older adults: how old is too old? J Heart Lung Transpl. 2011;30(3):270–2.

    Article  Google Scholar 

  168. Vadnerkar A, Toyoda Y, Crespo M, Pilewski J, Mitsani D, Kwak EJ, et al. Age-specific complications among lung transplant recipients 60 years and older. J Heart Lung Transpl. 2011;30(3):273–81.

    Article  Google Scholar 

  169. Mahidhara R, Bastani S, Ross DJ, Saggar R, Lynch J 3rd, Schnickel GT, et al. Lung transplantation in older patients? J Thorac Cardiovasc Surg. 2008;135(2):412–20.

    Article  PubMed  Google Scholar 

  170. Bertani A, Grossi P, Vitulo P, D’Ancona G, Arcadipane A, Nanni Costa A, et al. Successful lung transplantation in an HIV- and HBV-positive patient with cystic fibrosis. Am J Transpl. 2009;9(9):2190–6.

    Article  CAS  Google Scholar 

  171. Morabito V, Grossi P, Lombardini L, Ricci A, Trapani S, Peritore D, et al. Solid organ transplantation in HIV + recipients: Italian experience. Transpl Proc. 2016;48(2):424–30.

    Article  CAS  Google Scholar 

  172. Tricot L, Teicher E, Peytavin G, Zucman D, Conti F, Calmus Y, et al. Safety and efficacy of raltegravir in HIV-infected transplant patients cotreated with immunosuppressive drugs. Am J Transpl. 2009;9(8):1946–52.

    Article  CAS  Google Scholar 

  173. Miro JM, Aguero F, Duclos-Vallee JC, Mueller NJ, Grossi P, Moreno A. Infections in solid organ transplant HIV-infected patients. Clin Microbiol Infect. 2014;20(Suppl 7):119–30.

    Article  PubMed  CAS  Google Scholar 

  174. Frassetto L, Floren L, Barin B, Browne M, Wolfe A, Roland M, et al. Changes in clearance, volume and bioavailability of immunosuppressants when given with HAART in HIV-1 infected liver and kidney transplant recipients. Biopharm Drug Dispos. 2013;34(8):442–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Han Z, Kane BM, Petty LA, Josephson MA, Sutor J, Pursell KJ. Cobicistat significantly increases tacrolimus serum concentrations in a renal transplant recipient with human immunodeficiency virus infection. Pharmacotherapy. 2016;36(6):e50–3.

    Article  PubMed  CAS  Google Scholar 

  176. Esposito I, Labarga P, Barreiro P, Fernandez-Montero JV, de Mendoza C, Benitez-Gutierrez L, et al. Dual antiviral therapy for HIV and hepatitis C—drug interactions and side effects. Expert Opin Drug Saf. 2015;14(9):1421–34.

    Article  PubMed  CAS  Google Scholar 

  177. Jimenez-Nacher I, Alvarez E, Morello J, Rodriguez-Novoa S, de Andres S, Soriano V. Approaches for understanding and predicting drug interactions in human immunodeficiency virus-infected patients. Expert Opin Drug Metab Toxicol. 2011;7(4):457–77.

  178. Kern RM, Seethamraju H, Blanc PD, Sinha N, Loebe M, Golden J, et al. The feasibility of lung transplantation in HIV-seropositive patients. Ann Am Thorac Soc. 2014;11(6):882–9.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Weill D, Benden C, Corris PA, Dark JH, Davis RD, Keshavjee S, et al. A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transpl. 2015;34(1):1–15.

    Article  Google Scholar 

  180. Doucette KE, Halloran K, Kapasi A, Lien D, Weinkauf JG. Outcomes of lung transplantation in recipients with hepatitis C virus infection. Am J Transpl. 2016;16(8):2445–52.

    Article  CAS  Google Scholar 

  181. D’Ambrosio R, Aghemo A, Rossetti V, Carrinola R, Colombo M. Sofosbuvir-based regimens for the treatment of hepatitis C virus in patients who underwent lung transplant: case series and review of the literature. Liver Int. 2016;36(11):1585–9.

    Article  PubMed  Google Scholar 

  182. Doucette K, Sumner S, Weinkauf J. Treatment of hepatitis C in a lung transplant recipient with sofosbuvir and daclatasvir. J Heart Lung Transpl. 2016;35(6):840–1.

    Article  Google Scholar 

  183. Koenig A, Stepanova M, Saab S, Ahmed A, Wong R, Younossi ZM. Long-term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the U.S. transplant registry. Alim Pharmacol Ther. 2016;44(3):271–8.

    Article  CAS  Google Scholar 

  184. Rai HS, Winder GS. Marijuana use and organ transplantation: a review and implications for clinical practice. Curr Psychiatry Rep. 2017;19(11):91.

    Article  PubMed  Google Scholar 

  185. Tetrault JM, Crothers K, Moore BA, Mehra R, Concato J, Fiellin DA. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med. 2007;167(3):221–8.

    Article  PubMed  PubMed Central  Google Scholar 

  186. Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46(1):86–95.

    Article  PubMed  CAS  Google Scholar 

  187. Sikma MA, van Maarseveen EM, van de Graaf EA, Kirkels JH, Verhaar MC, Donker DW, et al. Pharmacokinetics and toxicity of tacrolimus early after heart and lung transplantation. Am J Transpl. 2015;15(9):2301–13.

    Article  CAS  Google Scholar 

  188. Pea F, Pavan F, Furlanut M. Clinical relevance of pharmacokinetics and pharmacodynamics in cardiac critical care patients. Clin Pharmacokinet. 2008;47(7):449–62.

    Article  PubMed  CAS  Google Scholar 

  189. Lefaucheur C, Nochy D, Amrein C, Chevalier P, Guillemain R, Cherif M, et al. Renal histopathological lesions after lung transplantation in patients with cystic fibrosis. Am J Transpl. 2008;8(9):1901–10.

    Article  CAS  Google Scholar 

  190. Phapale PB, Kim SD, Lee HW, Lim M, Kale DD, Kim YL, et al. An integrative approach for identifying a metabolic phenotype predictive of individualised pharmacokinetics of tacrolimus. Clin Pharmacol Ther. 2010;87(4):426–36.

    Article  PubMed  CAS  Google Scholar 

  191. Gieser G, Harigaya H, Colangelo PM, Burckart G. Biomarkers in solid organ transplantation. Clin Pharmacol Ther. 2011;90(2):217–20.

    Article  PubMed  CAS  Google Scholar 

  192. Roedder S, Vitalone M, Khatri P, Sarwal MM. Biomarkers in solid organ transplantation: establishing personalised transplantation medicine. Genome Med. 2011;3(6):37.

    Article  PubMed  PubMed Central  Google Scholar 

  193. van Gelder T. Biomarkers in solid organ transplantation. Br J Clin Pharmacol. 2017;83(12):2602–4.

    Article  PubMed  Google Scholar 

  194. Capron A, Haufroid V, Wallemacq P. Intra-cellular immunosuppressive drugs monitoring: a step forward towards better therapeutic efficacy after organ transplantation? Pharmacol Res. 2016;111:610–8.

    Article  PubMed  CAS  Google Scholar 

  195. Gorzer I, Haloschan M, Jaksch P, Klepetko W, Puchhammer-Stockl E. Plasma DNA levels of Torque teno virus and immunosuppression after lung transplantation. J Heart Lung Transpl. 2014;33(3):320–3.

    Article  Google Scholar 

  196. Nordén R, Magnusson J, Lundin A, Tang K-W, Nilsson S, Lindh M, et al. Quantification of torque teno virus and epstein-barr virus is of limited value for predicting the net state of immunosuppression after lung transplantation. Open Forum Infect Dis. 2018;5(4):ofy050–ofy.

  197. Gorzer I, Jaksch P, Strassl R, Klepetko W, Puchhammer-Stockl E. Association between plasma Torque teno virus level and chronic lung allograft dysfunction after lung transplantation. J Heart Lung Transpl. 2017;36(3):366–8.

    Article  Google Scholar 

  198. Rodrigo E, Lopez-Hoyos M, Corral M, Fabrega E, Fernandez-Fresnedo G, San Segundo D, et al. ImmuKnow as a diagnostic tool for predicting infection and acute rejection in adult liver transplant recipients: a systematic review and meta-analysis. Liver Transpl. 2012;18(10):1245–53.

    Article  PubMed  Google Scholar 

  199. Bhorade SM, Janata K, Vigneswaran WT, Alex CG, Garrity ER. Cylex ImmuKnow assay levels are lower in lung transplant recipients with infection. J Heart Lung Transpl. 2008;27(9):990–4.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmacy Department, Alfred Hospital, Commercial Rd., Melbourne, 3008, Australia

    Steven Ivulich & Michael Dooley

  2. Lung Transplant Service, Alfred Hospital, Melbourne, 3008, Australia

    Glen Westall & Gregory Snell

Authors
  1. Steven Ivulich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Glen Westall
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Dooley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory Snell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven Ivulich.

Ethics declarations

Conflict of interest

Steven Ivulich has complied with the ethical standards and has no conflicts of interest. Michael Dooley has complied with the ethical standards and has no conflicts of interest. Glen Westall has complied with the ethical standards and has no conflicts of interest. Gregory Snell has complied with the ethical standards and has no conflicts of interest.

Funding

Steven Ivulich has received no funding that was used to assist with the preparation of the manuscript. Michael Dooley has received no funding that was used to assist with the preparation of the manuscript. Glen Westall has received no funding that was used to assist with the preparation of the manuscript. Gregory Snell has received no funding that was used to assist with the preparation of the manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ivulich, S., Westall, G., Dooley, M. et al. The Evolution of Lung Transplant Immunosuppression. Drugs 78, 965–982 (2018). https://doi.org/10.1007/s40265-018-0930-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-0930-6

Search

Navigation