Download PDF
Semin Respir Crit Care Med 2006; 27(5): 470-479
DOI: 10.1055/s-2006-954605
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Evolving Immunosuppressive Regimens for Lung Transplant Recipients

Nuala J. Meyer1 , Sangeeta M. Bhorade1
  • 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, Illinois
Further Information

Publication History

Publication Date:
26 October 2006 (online)

    Permissions and Reprints

ABSTRACT

In organ transplantation, the key tenet remains the maintenance of graft function through the induction of allograft tolerance. Immunosuppression has been the mainstay of therapy to maintain graft function and induce tolerance. Immunosuppression for lung transplant and indeed all solid organ transplantation has greatly evolved in the past decade. Although calcineurin inhibitors, corticosteroids, and azathioprine remain the foundation of immunosuppression in lung transplantation, the arsenal of effective immunosuppression is ever expanding to include biological agents and newer drugs that are directed against increasingly specific targets of the immune cascade. This review examines the characteristics of both traditional and new pharmacological agents, describes a patient-centered approach to their use following lung transplantation, and discusses the controversies surrounding immunosuppression in the lung transplant recipient.

KEYWORDS

Immunosuppression - lung transplantation - calcineurin inhibitors - mammalian target of rapamycin - induction therapy

REFERENCES

  • 1 Levine S M. A survey of clinical practice of lung transplantation in North America.  Chest. 2004;  125 1224-1238
    CrossrefPubMedGoogle Scholar
  • 2 Rhen T, Cidlowski J A. Antiinflammatory action of glucocorticoids: new mechanisms for old drugs.  N Engl J Med. 2005;  353 1711-1723
    CrossrefPubMedGoogle Scholar
  • 3 Karin M. New twists in gene regulation by glucocorticoid receptor: is DNA binding dispensable?.  Cell. 1998;  93 487-490
    CrossrefPubMedGoogle Scholar
  • 4 Silverborn M, Jeppsson A, Martensson G, Nilsson F. New-onset cardiovascular risk factors in lung transplant recipients.  J Heart Lung Transplant. 2005;  24 1536-1543
    PubMedGoogle Scholar
  • 5 Elion G B. The purine path to chemotherapy.  Science. 1989;  244 41-47
    PubMedGoogle Scholar
  • 6 Poppe D, Tiede I, Fritz G et al.. Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins.  J Immunol. 2006;  176 640-651
    PubMedGoogle Scholar
  • 7 Tiede I, Fritz G, Strand S et al.. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4 + T lymphocytes.  J Clin Invest. 2003;  111 1133-1145
    CrossrefPubMedGoogle Scholar
  • 8 Palmer S M, Baz M A, Sanders L et al.. Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection.  Transplantation. 2001;  71 1772-1776
    CrossrefPubMedGoogle Scholar
  • 9 McNeil K, Glanville A R, Wahlers T et al.. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients.  Transplantation. 2006;  81 998-1003
    CrossrefPubMedGoogle Scholar
  • 10 Buell J F, Gross T G, Woodle E S. Malignancy after transplantation.  Transplantation. 2005;  80(Suppl 2) S254-S264
    CrossrefPubMedGoogle Scholar
  • 11 Kahan B D. Cyclosporine: a revolution in transplantation.  Transplant Proc. 1999;  31(1-2A) 14S-15S
    PubMedGoogle Scholar
  • 12 Ahsan N, Johnson C, Gonwa T et al.. Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.  Transplantation. 2001;  72 245-250
    PubMedGoogle Scholar
  • 13 Meier-Kriesche H U, Kaplan B. Cyclosporine microemulsion and tacrolimus are associated with decreased chronic allograft failure and improved long-term graft survival as compared with sandimmune.  Am J Transplant. 2002;  2 100-104
    CrossrefPubMedGoogle Scholar
  • 14 Keenan R J, Konishi H, Kawai A et al.. Clinical trial of tacrolimus versus cyclosporine in lung transplantation.  Ann Thorac Surg. 1995;  60 580-584 discussion 584-585
    CrossrefPubMedGoogle Scholar
  • 15 Zuckermann A, Reichenspurner H, Birsan T et al.. Cyclosporine A versus tacrolimus in combination with mycophenolate mofetil and steroids as primary immunosuppression after lung transplantation: one-year results of a two-center prospective randomized trial.  J Thorac Cardiovasc Surg. 2003;  125 891-900
    CrossrefPubMedGoogle Scholar
  • 16 Kesten S, Chaparro C, Scavuzzo M, Gutierrez C. Tacrolimus as rescue therapy for bronchiolitis obliterans syndrome.  J Heart Lung Transplant. 1997;  16 905-912
    PubMedGoogle Scholar
  • 17 Mentzer Jr R M, Jahania M S, Lasley R D. Tacrolimus as a rescue immunosuppressant after heart and lung transplantation. The US. Multicenter FK506 Study Group.  Transplantation. 1998;  65 109-113
    PubMedGoogle Scholar
  • 18 Lipson D A, Palevsky H I, Kotloff R M, Edelman J. Conversion to tacrolimus (FK506) from cyclosporine after orthotopic lung transplantation.  Transplant Proc. 1998;  30 1505-1507
    CrossrefPubMedGoogle Scholar
  • 19 Wiebe K, Harringer W, Franke U et al.. FK506 rescue therapy in lung transplantation.  Transplant Proc. 1998;  30 1508-1509
    CrossrefPubMedGoogle Scholar
  • 20 Sarahrudi K, Estenne M, Corris P et al.. International experience with conversion from cyclosporine to tacrolimus for acute and chronic lung allograft rejection.  J Thorac Cardiovasc Surg. 2004;  127 1126-1132
    CrossrefPubMedGoogle Scholar
  • 21 Keenan R J, Duncan A J, Yousem S A et al.. Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation.  Transplantation. 1992;  53 20-25
    PubMedGoogle Scholar
  • 22 Keenan R J, Iacono A, Dauber J H et al.. Treatment of refractory acute allograft rejection with aerosolized cyclosporine in lung transplant recipients.  J Thorac Cardiovasc Surg. 1997;  113 335-340 discussion 340-341
    CrossrefPubMedGoogle Scholar
  • 23 Iacono A T, Corcoran T E, Griffith B P et al.. Aerosol cyclosporin therapy in lung transplant recipients with bronchiolitis obliterans.  Eur Respir J. 2004;  23 384-390
    CrossrefPubMedGoogle Scholar
  • 24 Iacono A T, Johnson B A, Grgurich W F et al.. A randomized trial of inhaled cyclosporine in lung-transplant recipients.  N Engl J Med. 2006;  354 141-150
    CrossrefPubMedGoogle Scholar
  • 25 Halloran P F. Immunosuppressive drugs for kidney transplantation.  N Engl J Med. 2004;  351 2715-2729
    CrossrefPubMedGoogle Scholar
  • 26 Akhlaghi F, Gonzalez L, Trull A K. Association between cyclosporine concentrations at 2 hours post-dose and clinical outcomes in de novo lung transplant recipients.  J Heart Lung Transplant. 2005;  24 2120-2128
    PubMedGoogle Scholar
  • 27 Knoop C, Thiry P, Saint-Marcoux F, Rousseau A, Marquet P, Estenne M. Tacrolimus pharmacokinetics and dose monitoring after lung transplantation for cystic fibrosis and other conditions.  Am J Transplant. 2005;  5 1477-1482
    CrossrefPubMedGoogle Scholar
  • 28 Ragette R, Kamler M, Weinreich G, Teschler H, Jakob H. Tacrolimus pharmacokinetics in lung transplantation: new strategies for monitoring.  J Heart Lung Transplant. 2005;  24 1315-1319
    CrossrefPubMedGoogle Scholar
  • 29 Sehgal S N. Sirolimus: its discovery, biological properties, and mechanism of action.  Transplant Proc. 2003;  35(Suppl 3) 7S-14S
    CrossrefPubMedGoogle Scholar
  • 30 Brown E J, Albers M W, Shin T B et al.. A mammalian protein targeted by G1-arresting rapamycin-receptor complex.  Nature. 1994;  369 756-758
    CrossrefPubMedGoogle Scholar
  • 31 Dumont F J, Melino M R, Staruch M J, Koprak S L, Fischer P A, Sigal N H. The immunosuppressive macrolides FK-506 and rapamycin act as reciprocal antagonists in murine T cells.  J Immunol. 1990;  144 1418-1424
    PubMedGoogle Scholar
  • 32 Lai J H, Tan T H. CD28 signaling causes a sustained down-regulation of I kappa B alpha which can be prevented by the immunosuppressant rapamycin.  J Biol Chem. 1994;  269 30077-30080
    PubMedGoogle Scholar
  • 33 Flanagan W M, Crabtree G R. Rapamycin inhibits p34cdc2 expression and arrests T lymphocyte proliferation at the G1/S transition.  Ann NY Acad Sci. 1993;  696 31-37
    PubMedGoogle Scholar
  • 34 Kim H S, Raskova J, Degiannis D, Raska Jr K. Effects of cyclosporine and rapamycin on immunoglobulin production by preactivated human B cells.  Clin Exp Immunol. 1994;  96 508-512
    PubMedGoogle Scholar
  • 35 Marx S O, Jayaraman T, Go L O, Marks A R. Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells.  Circ Res. 1995;  76 412-417
    CrossrefPubMedGoogle Scholar
  • 36 Poon M, Marx S O, Gallo R, Badimon J J, Taubman M B, Marks A R. Rapamycin inhibits vascular smooth muscle cell migration.  J Clin Invest. 1996;  98 2277-2283
    CrossrefPubMedGoogle Scholar
  • 37 Marx S O, Marks A R. Bench to bedside: the development of rapamycin and its application to stent restenosis.  Circulation. 2001;  104 852-855
    PubMedGoogle Scholar
  • 38 Kahan B D. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group.  Lancet. 2000;  356 194-202
    CrossrefPubMedGoogle Scholar
  • 39 Kreis H, Cisterne J M, Land W et al.. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients.  Transplantation. 2000;  69 1252-1260
    PubMedGoogle Scholar
  • 40 Watson C J, Friend P J, Jamieson N V et al.. Sirolimus: a potent new immunosuppressant for liver transplantation.  Transplantation. 1999;  67 505-509
    PubMedGoogle Scholar
  • 41 King-Biggs M B, Dunitz J M, Park S J, Kay Savik S, Hertz M I. Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation.  Transplantation. 2003;  75 1437-1443
    CrossrefPubMedGoogle Scholar
  • 42 Groetzner J, Kur F, Spelsberg F et al.. Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression.  J Heart Lung Transplant. 2004;  23 632-638
    CrossrefPubMedGoogle Scholar
  • 43 Dean P G, Lund W J, Larson T S et al.. Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus.  Transplantation. 2004;  77 1555-1561
    CrossrefPubMedGoogle Scholar
  • 44 Kuppahally S, Al-Khaldi A, Weisshaar D et al.. Wound healing complications with de novo sirolimus versus mycophenolate mofetil-based regimen in cardiac transplant recipients.  Am J Transplant. 2006;  6(5 Pt 1) 986-992
    CrossrefPubMedGoogle Scholar
  • 45 Nair R V, Huang X, Shorthouse R et al.. Antiproliferative effect of rapamycin on growth factor-stimulated human adult lung fibroblasts in vitro may explain its superior efficacy for prevention and treatment of allograft obliterative airway disease in vivo.  Transplant Proc. 1997;  29 614-615
    CrossrefPubMedGoogle Scholar
  • 46 Fahrni J A, Berry G J, Morris R E, Rosen G D. Rapamycin inhibits development of obliterative airway disease in a murine heterotopic airway transplant model.  Transplantation. 1997;  63 533-537
    PubMedGoogle Scholar
  • 47 Cahill B C, Somerville K T, Crompton J A et al.. Early experience with sirolimus in lung transplant recipients with chronic allograft rejection.  J Heart Lung Transplant. 2003;  22 169-176
    CrossrefPubMedGoogle Scholar
  • 48 Snell G I, Levvey B J, Chin W et al.. Rescue therapy: a role for sirolimus in lung and heart transplant recipients.  Transplant Proc. 2001;  33 1084-1085
    CrossrefPubMedGoogle Scholar
  • 49 Ussetti P, Laporta R, de Pablo A, Carreno C, Segovia J, Pulpon L. Rapamycin in lung transplantation: preliminary results.  Transplant Proc. 2003;  35 1974-1977
    CrossrefPubMedGoogle Scholar
  • 50 Groetzner J, Wittwer T, Kaczmarek I et al.. Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation.  Transplantation. 2006;  81 355-360
    CrossrefPubMedGoogle Scholar
  • 51 Fritsche L, Budde K, Dragun D, Einecke G, Diekmann F, Neumayer H H. Testosterone concentrations and sirolimus in male renal transplant patients.  Am J Transplant. 2004;  4 130-131
    CrossrefPubMedGoogle Scholar
  • 52 Gonwa T, Mendez R, Yang H C, Weinstein S, Jensik S, Steinberg S. Randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: results at 6 months.  Transplantation. 2003;  75 1213-1220
    PubMedGoogle Scholar
  • 53 Pham P T, Pham P C, Danovitch G M et al.. Sirolimus-associated pulmonary toxicity.  Transplantation. 2004;  77 1215-1220
    PubMedGoogle Scholar
  • 54 Chhajed P N, Dickenmann M, Bubendorf L, Mayr M, Steiger J, Tamm M. Patterns of pulmonary complications associated with sirolimus.  Respiration. 2005;  73 367-379
    PubMedGoogle Scholar
  • 55 Champion L, Stern M, Israel-Biet D et al.. Brief communication: sirolimus-associated pneumonitis: 24 cases in renal transplant recipients.  Ann Intern Med. 2006;  144 505-509
    PubMedGoogle Scholar
  • 56 McWilliams T J, Levvey B J, Russell P A, Milne D G, Snell G I. Interstitial pneumonitis associated with sirolimus: a dilemma for lung transplantation.  J Heart Lung Transplant. 2003;  22 210-213
    CrossrefPubMedGoogle Scholar
  • 57 Rehm B, Keller F, Mayer J, Stracke S. Resolution of sirolimus-induced pneumonitis after conversion to everolimus.  Transplant Proc. 2006;  38 711-713
    CrossrefPubMedGoogle Scholar
  • 58 Eisen H J, Tuzcu E M, Dorent R et al.. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients.  N Engl J Med. 2003;  349 847-858
    PubMedGoogle Scholar
  • 59 Snell G I, Valentine V G, Vitulo P et al.. Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial.  Am J Transplant. 2006;  6 169-177
    CrossrefPubMedGoogle Scholar
  • 60 Valentine V G, Love R B, Snell G I, Vitulo P, Glanville A, Pirron U. Everolimus (RAD) shows superiority over azathioprine to inhibit the decline of pulmonary function in stable lung transplant recipients - 24-month results of a multicenter, randomized, double-blind study [abstract].  Am J Transplant. 2004;  79(Suppl 8) 403
    PubMedGoogle Scholar
  • 61 Trulock E P, Edwards L B, Taylor D O, Boucek M M, Keck B M, Hertz M I. Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult lung and heart-lung transplant report-2005.  J Heart Lung Transplant. 2005;  24 956-967
    CrossrefPubMedGoogle Scholar
  • 62 Cosimi A B, Cho S I, Delmonico F L, Kaplan M M, Rohrer R J, Jenkins R L. A randomized clinical trial comparing OKT3 and steroids for treatment of hepatic allograft rejection.  Transplantation. 1987;  43 91-95
    PubMedGoogle Scholar
  • 63 Cosimi A B, Colvin R B, Burton R C et al.. Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts.  N Engl J Med. 1981;  305 308-314
    PubMedGoogle Scholar
  • 64 Trofe J, Stratta R J, Egidi M F et al.. Thymoglobulin for induction or rejection therapy in pancreas allograft recipients: a single centre experience.  Clin Transplant. 2002;  16(Suppl 7) 34-44
    CrossrefPubMedGoogle Scholar
  • 65 Renlund D G, O'Connell J B, Gilbert E M et al.. A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation: decreased rejection and less corticosteroid use with OKT3.  Transplantation. 1989;  47 599-605
    PubMedGoogle Scholar
  • 66 Hibberd P L, Snydman D R. Cytomegalovirus infection in organ transplant recipients.  Infect Dis Clin North Am. 1995;  9 863-877
    PubMedGoogle Scholar
  • 67 Swinnen L J, Costanzo-Nordin M R, Fisher S G et al.. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients.  N Engl J Med. 1990;  323 1723-1728
    CrossrefPubMedGoogle Scholar
  • 68 Duvoux C, Pageaux G P, Vanlemmens C et al.. Risk factors for lymphoproliferative disorders after liver transplantation in adults: an analysis of 480 patients.  Transplantation. 2002;  74 1103-1109
    CrossrefPubMedGoogle Scholar
  • 69 Palmer S M, Miralles A P, Lawrence C M, Gaynor J W, Davis R D, Tapson V F. Rabbit antithymocyte globulin decreases acute rejection after lung transplantation: results of a randomized, prospective study.  Chest. 1999;  116 127-133
    CrossrefPubMedGoogle Scholar
  • 70 Wiebe K, Harringer W, Wahlers T et al.. ATG induction therapy and the incidence of bronchiolitis obliterans after lung transplantation: does it make a difference?.  Transplant Proc. 1998;  30 1517-1518
    CrossrefPubMedGoogle Scholar
  • 71 Gaber A O, First M R, Tesi R J et al.. Results of the double-blind, randomized, multicenter, phase III clinical trial of thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.  Transplantation. 1998;  66 29-37
    PubMedGoogle Scholar
  • 72 Merion R M, Howell T, Bromberg J S. Partial T-cell activation and anergy induction by polyclonal antithymocyte globulin.  Transplantation. 1998;  65 1481-1489
    PubMedGoogle Scholar
  • 73 Basiliximab approved for use in renal transplant patients.  Am J Health Syst Pharm. 1998;  55 1444-1445
    PubMedGoogle Scholar
  • 74 Beniaminovitz A, Itescu S, Lietz K et al.. Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody.  N Engl J Med. 2000;  342 613-619
    CrossrefPubMedGoogle Scholar
  • 75 Garrity Jr E R, Villanueva J, Bhorade S M, Husain A N, Vigneswaran W T. Low rate of acute lung allograft rejection after the use of daclizumab, an interleukin 2 receptor antibody.  Transplantation. 2001;  71 773-777
    PubMedGoogle Scholar
  • 76 Gerbase M W, de Perrot M, Spiliopoulos A, Nicod L P. Selective monoclonal versus polyclonal antibodies for induction of immunosuppression in lung recipients.  Clin Pharmacol Ther. 2002;  72 103
    CrossrefPubMedGoogle Scholar
  • 77 Hachem R R, Chakinala M M, Yusen R D et al.. A comparison of basiliximab and anti-thymocyte globulin as induction agents after lung transplantation.  J Heart Lung Transplant. 2005;  24 1320-1326
    CrossrefPubMedGoogle Scholar
  • 78 Burton C M, Andersen C B, Jensen A S et al.. The incidence of acute cellular rejection after lung transplantation: a comparative study of anti-thymocyte globulin and daclizumab.  J Heart Lung Transplant. 2006;  25 638-647
    CrossrefPubMedGoogle Scholar
  • 79 Brock M V, Borja M C, Ferber L et al.. Induction therapy in lung transplantation: a prospective, controlled clinical trial comparing OKT3, anti-thymocyte globulin, and daclizumab.  J Heart Lung Transplant. 2001;  20 1282-1290
    CrossrefPubMedGoogle Scholar
  • 80 Bhorade S M, Jordan A, Villanueva J et al.. Comparison of three tacrolimus-based immunosuppressive regimens in lung transplantation.  Am J Transplant. 2003;  3 1570-1575
    CrossrefPubMedGoogle Scholar
  • 81 Flynn J M, Byrd J C. Campath-1H monoclonal antibody therapy.  Curr Opin Oncol. 2000;  12 574-581
    CrossrefPubMedGoogle Scholar
  • 82 Morris P J, Russell N K. Alemtuzumab (Campath-1H): a systematic review in organ transplantation.  Transplantation. 2006;  81 1361-1367
    CrossrefPubMedGoogle Scholar
  • 83 McCurry K R, Iacono A, Zeevi A et al.. Early outcomes in human lung transplantation with thymoglobulin or Campath-1H for recipient pretreatment followed by posttransplant tacrolimus near-monotherapy.  J Thorac Cardiovasc Surg. 2005;  130 528-537
    CrossrefPubMedGoogle Scholar
  • 84 Starzl T E, Zinkernagel R M. Antigen localization and migration in immunity and tolerance.  N Engl J Med. 1998;  339 1905-1913
    PubMedGoogle Scholar
  • 85 Trulock E P. Management of lung transplant rejection.  Chest. 1993;  103 1566-1576
    PubMedGoogle Scholar
  • 86 Yousem S A, Berry G J, Cagle P T et al.. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group.  J Heart Lung Transplant. 1996;  15(1 Pt 1) 1-15
    PubMedGoogle Scholar
  • 87 Guilinger R A, Paradis I L, Dauber J H et al.. The importance of bronchoscopy with transbronchial biopsy and bronchoalveolar lavage in the management of lung transplant recipients.  Am J Respir Crit Care Med. 1995;  152(6 Pt 1) 2037-2043
    PubMedGoogle Scholar
  • 88 Diamond D A, Michalski J M, Lynch J P, Trulock III E P. Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation.  Int J Radiat Oncol Biol Phys. 1998;  41 795-800
    CrossrefPubMedGoogle Scholar
  • 89 Andreu G, Achkar A, Couetil J P et al.. Extracorporeal photochemotherapy treatment for acute lung rejection episode.  J Heart Lung Transplant. 1995;  14 793-796
    PubMedGoogle Scholar
  • 90 Wise B V, King K E, Rook A H, Mogayzel Jr P J. Extracorporeal photopheresis in the treatment of persistent rejection in a pediatric lung transplant recipient.  Prog Transplant. 2003;  13 61-64
    PubMedGoogle Scholar
  • 91 Reams B D, Davis R D, Curl J, Palmer S M. Treatment of refractory acute rejection in a lung transplant recipient with Campath 1H.  Transplantation. 2002;  74 903-904
    CrossrefPubMedGoogle Scholar
  • 92 Suzuki H, Shimomura A, Ikeda K, Furukawa M, Oshima T, Takasaka T. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells.  Laryngoscope. 1997;  107(12 Pt 1) 1661-1666
    PubMedGoogle Scholar
  • 93 Ianaro A, Ialenti A, Maffia P et al.. Anti-inflammatory activity of macrolide antibiotics.  J Pharmacol Exp Ther. 2000;  292 156-163
    PubMedGoogle Scholar
  • 94 Elssner A, Jaumann F, Dobmann S et al.. Elevated levels of interleukin-8 and transforming growth factor-beta in bronchoalveolar lavage fluid from patients with bronchiolitis obliterans syndrome: proinflammatory role of bronchial epithelial cells. Munich Lung Transplant Group.  Transplantation. 2000;  70 362-367
    PubMedGoogle Scholar
  • 95 DiGiovine B, Lynch III J P, Martinez F J et al.. Bronchoalveolar lavage neutrophilia is associated with obliterative bronchiolitis after lung transplantation: role of IL-8.  J Immunol. 1996;  157 4194-4202
    PubMedGoogle Scholar
  • 96 Gerhardt S G, McDyer J F, Girgis R E, Conte J V, Yang S C, Orens J B. Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study.  Am J Respir Crit Care Med. 2003;  168 121-125
    CrossrefPubMedGoogle Scholar
  • 97 Yates B, Murphy D M, Forrest I A et al.. Azithromycin reverses airflow obstruction in established bronchiolitis obliterans syndrome.  Am J Respir Crit Care Med. 2005;  172 772-775
    CrossrefPubMedGoogle Scholar
  • 98 Verleden G M, Dupont L J. Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation.  Transplantation. 2004;  77 1465-1467
    CrossrefPubMedGoogle Scholar
  • 99 Kobashigawa J A. Statins in solid organ transplantation: is there an immunosuppressive effect?.  Am J Transplant. 2004;  4 1013-1018
    CrossrefPubMedGoogle Scholar
  • 100 Johnson B A, Iacono A T, Zeevi A, McCurry K R, Duncan S R. Statin use is associated with improved function and survival of lung allografts.  Am J Respir Crit Care Med. 2003;  167 1271-1278
    CrossrefPubMedGoogle Scholar
  • 101 Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator.  Nat Med. 2000;  6 1399-1402
    CrossrefPubMedGoogle Scholar
  • 102 Palmer S M, Miralles A P, Howell D N, Brazer S R, Tapson V F, Davis R D. Gastroesophageal reflux as a reversible cause of allograft dysfunction after lung transplantation.  Chest. 2000;  118 1214-1217
    CrossrefPubMedGoogle Scholar
  • 103 Hadjiliadis D, Duane Davis R, Steele M P et al.. Gastroesophageal reflux disease in lung transplant recipients.  Clin Transplant. 2003;  17 363-368
    CrossrefPubMedGoogle Scholar
  • 104 Davis Jr R D, Lau C L, Eubanks S et al.. Improved lung allograft function after fundoplication in patients with gastroesophageal reflux disease undergoing lung transplantation.  J Thorac Cardiovasc Surg. 2003;  125 533-542
    CrossrefPubMedGoogle Scholar
  • 105 Cantu III E, Appel III J Z, Hartwig M G et al.. J. Maxwell Chamberlain Memorial Paper. Early fundoplication prevents chronic allograft dysfunction in patients with gastroesophageal reflux disease.  Ann Thorac Surg. 2004;  78 1142-1151 discussion 1151
    CrossrefPubMedGoogle Scholar
  • 106 Massicot-Fisher J, Noel P, Madsen J C. Recommendations of the National Heart, Lung and Blood Institute Heart and Lung Tolerance Working Group.  Transplantation. 2001;  72 1467-1470
    PubMedGoogle Scholar
  • 107 Li S, Louis IV L B, Kawaharada N, Yousem S A, Pham S M. Intrathymic inoculation of donor bone marrow induces long-term acceptance of lung allografts.  Ann Thorac Surg. 2003;  75 257-263 discussion 263
    CrossrefPubMedGoogle Scholar

Sangeeta M BhoradeM.D. 

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago

5841 S. Maryland Ave., MC 0999, Chicago, IL 60637

Email: sbhorade@medicine.bsd.uchicago.edu

      >