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DOI: 10.1055/s-0037-1617424
Acute Cellular Rejection: Is It Still Relevant?
Publikationsverlauf
Publikationsdatum:
26. März 2018 (online)
![](https://www.thieme-connect.de/media/srccm/201802/lookinside/thumbnails/10-1055-s-0037-1617424_01362-1.jpg)
Abstract
Despite significant progress in the field of transplant immunology, acute cellular rejection (ACR) remains a very frequent complication after lung transplantation (LTx), with almost 30% of LTx recipients experiencing at least one episode of treated ACR during the first year of follow-up. Most episodes respond to the first-line immunosuppressive treatment and are rarely a direct cause of death. However, the association of ACR with later adverse outcomes, such as chronic lung allograft dysfunction, bronchial stricture, and infectious complications associated with the intensification of immunosuppression, negatively impacts long-term survival. The burden imposed on patients and health-care resources is even higher in cases of refractory or recurrent ACR, which accelerates lung function decline. Although important laboratory and clinical research conducted over the last two decades has improved our understanding of the mechanisms underlying ACR, there are still many uncertainties about the risk factors for ACR, the optimal monitoring strategies, and the prediction of long-term outcomes. These knowledge gaps contribute to the large variability in clinical practice among LTx centers, which renders multicenter studies of ACR challenging. In this review, we summarize current evidence on the epidemiology, pathogenesis, and risk factors of ACR. We describe diagnostic and therapeutic approaches that are currently used in the clinical practice and also review promising diagnostic tools that are under investigation. Associations between ACR and other adverse outcomes of LTx are examined. Finally, within each topic of discussion, we highlight the main areas of controversy and opportunities for future research.
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References
- 1 Chambers DC, Yusen RD, Cherikh WS. , et al; International Society for Heart and Lung Transplantation. 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 Transplant 2017; 36 (10) 1047-1059
- 2 Goldfarb SB, Levvey BJ, Cherikh WS. , et al; International Society for Heart and Lung Transplantation. 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 Transplant 2017; 36 (10) 1070-1079
- 3 Bando K, Paradis IL, Komatsu K. , et al. Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation. J Thorac Cardiovasc Surg 1995; 109 (01) 49-57 , discussion 57–59
- 4 Krustrup D, Iversen M, Martinussen T, Andersen CB. Time elapsed after transplantation influences the relationship between the number of regulatory T cells in lung allograft biopsies and subsequent acute rejection episodes. Transpl Immunol 2014; 31 (01) 42-47
- 5 Mangi AA, Mason DP, Nowicki ER. , et al. Predictors of acute rejection after lung transplantation. Ann Thorac Surg 2011; 91 (06) 1754-1762
- 6 Schulman LL, Weinberg AD, McGregor C, Galantowicz ME, Suciu-Foca NM, Itescu S. Mismatches at the HLA-DR and HLA-B loci are risk factors for acute rejection after lung transplantation. Am J Respir Crit Care Med 1998; 157 (6 Pt 1): 1833-1837
- 7 Roberts DH, Wain JC, Chang Y, Ginns LC. Donor-recipient gender mismatch in lung transplantation: impact on obliterative bronchiolitis and survival. J Heart Lung Transplant 2004; 23 (11) 1252-1259
- 8 Hsiao HM, Scozzi D, Gauthier JM, Kreisel D. Mechanisms of graft rejection after lung transplantation. Curr Opin Organ Transplant 2017; 22 (01) 29-35
- 9 Moreau A, Varey E, Anegon I, Cuturi MC. Effector mechanisms of rejection. Cold Spring Harb Perspect Med 2013; 3 (11) 3
- 10 Li XC, Jevnikar AM. Transplant immunology. USA: Wiley; 2016
- 11 Handunnetthi L, Ramagopalan SV, Ebers GC, Knight JC. Regulation of major histocompatibility complex class II gene expression, genetic variation and disease. Genes Immun 2010; 11 (02) 99-112
- 12 Spierings E. Minor histocompatibility antigens: past, present, and future. Tissue Antigens 2014; 84 (04) 374-460
- 13 Snell GI, Holmes M, Levvey BJ. , et al. Lessons and insights from ABO-incompatible lung transplantation. Am J Transplant 2013; 13 (05) 1350-1353
- 14 Tsang JY, Chai JG, Lechler R. Antigen presentation by mouse CD4+ T cells involving acquired MHC class II:peptide complexes: another mechanism to limit clonal expansion?. Blood 2003; 101 (07) 2704-2710
- 15 Herrera OB, Golshayan D, Tibbott R. , et al. A novel pathway of alloantigen presentation by dendritic cells. J Immunol 2004; 173 (08) 4828-4837
- 16 Afzali B, Lombardi G, Lechler RI. Pathways of major histocompatibility complex allorecognition. Curr Opin Organ Transplant 2008; 13 (04) 438-444
- 17 Bharat A, Fields RC, Trulock EP, Patterson GA, Mohanakumar T. Induction of IL-10 suppressors in lung transplant patients by CD4+25+ regulatory T cells through CTLA-4 signaling. J Immunol 2006; 177 (08) 5631-5638
- 18 Braun RK, Molitor-Dart M, Wigfield C. , et al. Transfer of tolerance to collagen type V suppresses T-helper-cell-17 lymphocyte-mediated acute lung transplant rejection. Transplantation 2009; 88 (12) 1341-1348
- 19 Burlingham WJ, Love RB, Jankowska-Gan E. , et al. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 2007; 117 (11) 3498-3506
- 20 Csencsits KL, Bishop DK. Contrasting alloreactive CD4+ and CD8+ T cells: there's more to it than MHC restriction. Am J Transplant 2003; 3 (02) 107-115
- 21 VanBuskirk AM, Wakely ME, Orosz CG. Transfusion of polarized TH2-like cell populations into SCID mouse cardiac allograft recipients results in acute allograft rejection. Transplantation 1996; 62 (02) 229-238
- 22 Lemaître PH, Vokaer B, Charbonnier LM. , et al. Cyclosporine A drives a Th17- and Th2-mediated posttransplant obliterative airway disease. Am J Transplant 2013; 13 (03) 611-620
- 23 Bharat A, Fields RC, Steward N, Trulock EP, Patterson GA, Mohanakumar T. CD4+25+ regulatory T cells limit Th1-autoimmunity by inducing IL-10 producing T cells following human lung transplantation. Am J Transplant 2006; 6 (08) 1799-1808
- 24 Kingsley CI, Karim M, Bushell AR, Wood KJ. CD25+CD4+ regulatory T cells prevent graft rejection: CTLA-4- and IL-10-dependent immunoregulation of alloresponses. J Immunol 2002; 168 (03) 1080-1086
- 25 Shilling RA, Wilkes DS. Role of Th17 cells and IL-17 in lung transplant rejection. Semin Immunopathol 2011; 33 (02) 129-134
- 26 Kreisel D, Goldstein DR. Innate immunity and organ transplantation: focus on lung transplantation. Transpl Int 2013; 26 (01) 2-10
- 27 Khalifah AP, Hachem RR, Chakinala MM. , et al. Minimal acute rejection after lung transplantation: a risk for bronchiolitis obliterans syndrome. Am J Transplant 2005; 5 (08) 2022-2030
- 28 Chiang CY, Schneider HG, Lewey B, Mitchell L, Snell GI. Tacrolimus level variability is a novel measure associated with increased acute rejection in lung transplant recipients. JHLT 2013; 32: S170
- 29 Calabrese F, Lunardi F, Nannini N. , et al. Higher risk of acute cellular rejection in lung transplant recipients with cystic fibrosis. Ann Transplant 2015; 20: 769-776
- 30 Kshettry VR, Kroshus TJ, Savik K, Hertz MI, Bolman RM. Primary pulmonary hypertension as a risk factor for the development of obliterative bronchiolitis in lung allograft recipients. Chest 1996; 110 (03) 704-709
- 31 Ibrahim JE, Sweet SC, Flippin M. , et al. Rejection is reduced in thoracic organ recipients when transplanted in the first year of life. J Heart Lung Transplant 2002; 21 (03) 311-318
- 32 Christie JD, Edwards LB, Kucheryavaya AY. , et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report–2010. J Heart Lung Transplant 2010; 29 (10) 1104-1118
- 33 Gutierrez C, Al-Faifi S, Chaparro C. , et al. The effect of recipient's age on lung transplant outcome. Am J Transplant 2007; 7 (05) 1271-1277
- 34 Mahidhara R, Bastani S, Ross DJ. , et al. Lung transplantation in older patients?. J Thorac Cardiovasc Surg 2008; 135 (02) 412-420
- 35 Zheng HX, Zeevi A, McCurry K. , et al. The impact of pharmacogenomic factors on acute persistent rejection in adult lung transplant patients. Transpl Immunol 2005; 14 (01) 37-42
- 36 Yusen RD, Christie JD, Edwards LB. , et al; International Society for Heart and Lung Transplantation. 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 Transplant 2013; 32 (10) 965-978
- 37 Girnita DM, Burckart G, Zeevi A. Effect of cytokine and pharmacogenomic genetic polymorphisms in transplantation. Curr Opin Immunol 2008; 20 (05) 614-625
- 38 Abboudi H, Macphee IA. Individualized immunosuppression in transplant patients: potential role of pharmacogenetics. Pharm Genomics Pers Med 2012; 5: 63-72
- 39 Girnita DM, Webber SA, Zeevi A. Clinical impact of cytokine and growth factor genetic polymorphisms in thoracic organ transplantation. Clin Lab Med 2008; 28 (03) 423-440 , vi vi
- 40 Colobran R, Casamitjana N, Roman A. , et al. Copy number variation in the CCL4L gene is associated with susceptibility to acute rejection in lung transplantation. Genes Immun 2009; 10 (03) 254-259
- 41 Mu HJ, Xie P, Chen JY. , et al. Association of TNF-α, TGF-β1, IL-10, IL-6, and IFN-γ gene polymorphism with acute rejection and infection in lung transplant recipients. Clin Transplant 2014; 28 (09) 1016-1024
- 42 Zheng HX, Burckart GJ, McCurry K. , et al. Interleukin-10 production genotype protects against acute persistent rejection after lung transplantation. J Heart Lung Transplant 2004; 23 (05) 541-546
- 43 Palmer SM, Burch LH, Trindade AJ. , et al. Innate immunity influences long-term outcomes after human lung transplant. Am J Respir Crit Care Med 2005; 171 (07) 780-785
- 44 Palmer SM, Klimecki W, Yu L. , et al. Genetic regulation of rejection and survival following human lung transplantation by the innate immune receptor CD14. Am J Transplant 2007; 7 (03) 693-699
- 45 Zych B, García Sáez D, Sabashnikov A. , et al. Lung transplantation from donors outside standard acceptability criteria--are they really marginal?. Transpl Int 2014; 27 (11) 1183-1191
- 46 Snell GI, Levvey BJ, Paraskeva M. , et al. The influence of clinical donor factors on acute rejection among lung and kidney recipients from the same multi-organ donor. Ann Transplant 2013; 18: 358-367
- 47 Krutsinger D, Reed RM, Blevins A. , et al. Lung transplantation from donation after cardiocirculatory death: a systematic review and meta-analysis. J Heart Lung Transplant 2015; 34 (05) 675-684
- 48 Gammie JS, Pham SM, Colson YL. , et al. Influence of panel-reactive antibody on survival and rejection after lung transplantation. J Heart Lung Transplant 1997; 16 (04) 408-415
- 49 Peltz M, Edwards LB, Jessen ME, Torres F, Meyer DM. HLA mismatches influence lung transplant recipient survival, bronchiolitis obliterans and rejection: implications for donor lung allocation. J Heart Lung Transplant 2011; 30 (04) 426-434
- 50 Opelz G, Süsal C, Ruhenstroth A, Döhler B. Impact of HLA compatibility on lung transplant survival and evidence for an HLA restriction phenomenon: a collaborative transplant study report. Transplantation 2010; 90 (08) 912-917
- 51 Alvarez A, Moreno P, Illana J. , et al. Influence of donor-recipient gender mismatch on graft function and survival following lung transplantation. Interact Cardiovasc Thorac Surg 2013; 16 (04) 426-435
- 52 Pinderski LJ, Kirklin JK, McGiffin D. , et al. Multi-organ transplantation: is there a protective effect against acute and chronic rejection?. J Heart Lung Transplant 2005; 24 (11) 1828-1833
- 53 Hall DJ, Belli EV, Gregg JA. , et al. Two decades of lung retransplantation: a single-center experience. Ann Thorac Surg 2017; 103 (04) 1076-1083
- 54 Yusen RD, Edwards LB, Kucheryavaya AY. , et al; International Society for Heart and Lung Transplantation. The registry of the International Society for Heart and Lung Transplantation: thirty-first adult lung and heart-lung transplant report--2014; focus theme: retransplantation. J Heart Lung Transplant 2014; 33 (10) 1009-1024
- 55 Tikkanen JM, Cypel M, Machuca TN. , et al. Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation. J Heart Lung Transplant 2015; 34 (04) 547-556
- 56 Wallinder A, Riise GC, Ricksten SE, Silverborn M, Dellgren G. Transplantation after ex vivo lung perfusion: a midterm follow-up. J Heart Lung Transplant 2016; 35 (11) 1303-1310
- 57 Penninga L, Møller CH, Penninga EI, Iversen M, Gluud C, Steinbrüchel DA. Antibody induction therapy for lung transplant recipients. Cochrane Database Syst Rev 2013; (11) CD008927
- 58 Jaksch P, Ankersmit J, Scheed A. , et al. Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study. Am J Transplant 2014; 14 (08) 1839-1845
- 59 McCurry KR, 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 (02) 528-537
- 60 Whited LK, Latran MJ, Hashmi ZA. , et al. Evaluation of alemtuzumab versus basiliximab induction: a retrospective cohort study in lung transplant recipients. Transplantation 2015; 99 (10) 2190-2195
- 61 Shyu S, Dew MA, Pilewski JM. , et al. Five-year outcomes with alemtuzumab induction after lung transplantation. J Heart Lung Transplant 2011; 30 (07) 743-754
- 62 Guilinger RA, Paradis IL, Dauber JH. , 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
- 63 Penninga L, Penninga EI, Møller CH, Iversen M, Steinbrüchel DA, Gluud C. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients. Cochrane Database Syst Rev 2013; (05) CD008817
- 64 Speich R, Schneider S, Hofer M. , et al. Mycophenolate mofetil reduces alveolar inflammation, acute rejection and graft loss due to bronchiolitis obliterans syndrome after lung transplantation. Pulm Pharmacol Ther 2010; 23 (05) 445-449
- 65 Palmer SM, Baz MA, 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 (12) 1772-1776
- 66 Snell GI, Valentine VG, Vitulo P. , et al; RAD B159 Study Group. Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. Am J Transplant 2006; 6 (01) 169-177
- 67 Glanville AR, Aboyoun CL, Morton JM, Plit M, Malouf MA. Cyclosporine C2 target levels and acute cellular rejection after lung transplantation. J Heart Lung Transplant 2006; 25 (08) 928-934
- 68 Ruiz J, Herrero MJ, Bosó V. , et al. Impact of single nucleotide polymorphisms (SNPs) on immunosuppressive therapy in lung transplantation. Int J Mol Sci 2015; 16 (09) 20168-20182
- 69 Burckart GJ, Hutchinson IV, Zeevi A. Pharmacogenomics and lung transplantation: clinical implications. Pharmacogenomics J 2006; 6 (05) 301-310
- 70 Provenzani A, Santeusanio A, Mathis E. , et al. Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients. World J Gastroenterol 2013; 19 (48) 9156-9173
- 71 Johansson I, Mårtensson G, Nyström U, Nasic S, Andersson R. Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients. BMC Infect Dis 2013; 13: 582
- 72 Roux A, Mourin G, Fastenackels S. , et al. CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation. Clin Immunol 2013; 148 (01) 16-26
- 73 Manuel O, Kumar D, Moussa G. , et al. Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis. Transplantation 2009; 87 (05) 719-725
- 74 Paraskeva M, Bailey M, Levvey BJ. , et al. Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans syndrome. Am J Transplant 2011; 11 (10) 2190-2196
- 75 Soccal PM, Aubert JD, Bridevaux PO. , et al. Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients. Clin Infect Dis 2010; 51 (02) 163-170
- 76 Sayah DM, Koff JL, Leard LE, Hays SR, Golden JA, Singer JP. Rhinovirus and other respiratory viruses exert different effects on lung allograft function that are not mediated through acute rejection. Clin Transplant 2013; 27 (01) E64-E71
- 77 Kumar D, Husain S, Chen MH. , et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation 2010; 89 (08) 1028-1033
- 78 Lewandowska DW, Schreiber PW, Schuurmans MM. , et al. Metagenomic sequencing complements routine diagnostics in identifying viral pathogens in lung transplant recipients with unknown etiology of respiratory infection. PLoS One 2017; 12 (05) e0177340
- 79 Shields RK, Clancy CJ, Minces LR. , et al. Staphylococcus aureus infections in the early period after lung transplantation: epidemiology, risk factors, and outcomes. J Heart Lung Transplant 2012; 31 (11) 1199-1206
- 80 Yamamoto S, Nava RG, Zhu J. , et al. Cutting edge: pseudomonas aeruginosa abolishes established lung transplant tolerance by stimulating B7 expression on neutrophils. J Immunol 2012; 189 (09) 4221-4225
- 81 Moore CA, Pilewski JM, Venkataramanan R. , et al. Effect of aerosolized antipseudomonals on pseudomonas positivity and bronchiolitis obliterans syndrome after lung transplantation. Transpl Infect Dis 2017; 19 (03) 19
- 82 Glanville AR, Gencay M, Tamm M. , et al. Chlamydia pneumoniae infection after lung transplantation. J Heart Lung Transplant 2005; 24 (02) 131-136
- 83 Jamal AJ, Resende MR, Prochnow T. , et al. Simkania negevensis and acute cellular rejection in lung transplant recipients. Clin Transplant 2015; 29 (08) 705-711
- 84 Solé A, Morant P, Salavert M, Pemán J, Morales P. . Valencia Lung Transplant Group. Aspergillus infections in lung transplant recipients: risk factors and outcome. Clin Microbiol Infect 2005; 11 (05) 359-365
- 85 Becker J, Poroyko V, Bhorade S. The lung microbiome after lung transplantation. Expert Rev Respir Med 2014; 8 (02) 221-231
- 86 Benmerad M, Slama R, Botturi K. , et al; SysCLAD consortium. Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study. Eur Respir J 2017; 49 (01) 49
- 87 Ruttens D, Verleden SE, Bijnens EM. , et al. An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe. Eur Respir J 2017; 49 (01) 49
- 88 Verleden SE, Scheers H, Nawrot TS. , et al. Lymphocytic bronchiolitis after lung transplantation is associated with daily changes in air pollution. Am J Transplant 2012; 12 (07) 1831-1838
- 89 Hathorn KE, Chan WW, Lo WK. Role of gastroesophageal reflux disease in lung transplantation. World J Transplant 2017; 7 (02) 103-116
- 90 Hartwig MG, Appel JZ, Li B. , et al. Chronic aspiration of gastric fluid accelerates pulmonary allograft dysfunction in a rat model of lung transplantation. J Thorac Cardiovasc Surg 2006; 131 (01) 209-217
- 91 Meltzer AJ, Weiss MJ, Veillette GR. , et al. Repetitive gastric aspiration leads to augmented indirect allorecognition after lung transplantation in miniature swine. Transplantation 2008; 86 (12) 1824-1829
- 92 Fisichella PM, Davis CS, Lundberg PW. , et al. The protective role of laparoscopic antireflux surgery against aspiration of pepsin after lung transplantation. Surgery 2011; 150 (04) 598-606
- 93 Stovold R, Forrest IA, Corris PA. , et al. Pepsin, a biomarker of gastric aspiration in lung allografts: a putative association with rejection. Am J Respir Crit Care Med 2007; 175 (12) 1298-1303
- 94 Shah N, Force SD, Mitchell PO. , et al. Gastroesophageal reflux disease is associated with an increased rate of acute rejection in lung transplant allografts. Transplant Proc 2010; 42 (07) 2702-2706
- 95 Raviv Y, D'Ovidio F, Pierre A. , et al. Prevalence of gastroparesis before and after lung transplantation and its association with lung allograft outcomes. Clin Transplant 2012; 26 (01) 133-142
- 96 Girnita AL, McCurry KR, Iacono AT. , et al. HLA-specific antibodies are associated with high-grade and persistent-recurrent lung allograft acute rejection. J Heart Lung Transplant 2004; 23 (10) 1135-1141
- 97 Lobo LJ, Aris RM, Schmitz J, Neuringer IP. Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation. J Heart Lung Transplant 2013; 32 (01) 70-77
- 98 Lin-Wang HT, Cipullo R, Dinkhuysen JJ. , et al. Down regulation of protective genes is associated with cellular and antibody-mediated rejection. Clin Transplant 2017;31(10)
- 99 Gordon IO, Bhorade S, Vigneswaran WT, Garrity ER, Husain AN. SaLUTaRy: survey of lung transplant rejection. J Heart Lung Transplant 2012; 31 (09) 972-979
- 100 De Vito Dabbs A, Hoffman LA, Iacono AT, Zullo TG, McCurry KR, Dauber JH. Are symptom reports useful for differentiating between acute rejection and pulmonary infection after lung transplantation?. Heart Lung 2004; 33 (06) 372-380
- 101 Kundu S, Herman SJ, Larhs A. , et al. Correlation of chest radiographic findings with biopsy-proven acute lung rejection. J Thorac Imaging 1999; 14 (03) 178-184
- 102 Park CH, Paik HC, Haam SJ. , et al. HRCT features of acute rejection in patients with bilateral lung transplantation: the usefulness of lesion distribution. Transplant Proc 2014; 46 (05) 1511-1516
- 103 Bjørtuft O, Johansen B, Boe J, Foerster A, Holter E, Geiran O. Daily home spirometry facilitates early detection of rejection in single lung transplant recipients with emphysema. Eur Respir J 1993; 6 (05) 705-708
- 104 Otulana BA, Higenbottam T, Ferrari L, Scott J, Igboaka G, Wallwork J. The use of home spirometry in detecting acute lung rejection and infection following heart-lung transplantation. Chest 1990; 97 (02) 353-357
- 105 Van Muylem A, Mélot C, Antoine M, Knoop C, Estenne M. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax 1997; 52 (07) 643-647
- 106 Yousem SA, Berry GJ, Cagle PT. , 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
- 107 Stewart S, Fishbein MC, Snell GI. , et al. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant 2007; 26 (12) 1229-1242
- 108 Hwang DM, Yousem SA. Approach to a lung transplant biopsy. J Clin Pathol 2010; 63 (01) 38-46
- 109 Roden AC, Kern RM, Aubry MC. , et al. Transbronchial cryobiopsies in the evaluation of lung allografts: do the benefits outweigh the risks?. Arch Pathol Lab Med 2016; 140 (04) 303-311
- 110 Roden AC, Aisner DL, Allen TC. , et al. Diagnosis of acute cellular rejection and antibody-mediated rejection on lung transplant biopsies: a perspective from members of the Pulmonary Pathology Society. Arch Pathol Lab Med 2017; 141 (03) 437-444
- 111 Chakinala MM, Ritter J, Gage BF. , et al. Reliability for grading acute rejection and airway inflammation after lung transplantation. J Heart Lung Transplant 2005; 24 (06) 652-657
- 112 Stephenson A, Flint J, English J. , et al. Interpretation of transbronchial lung biopsies from lung transplant recipients: inter- and intraobserver agreement. Can Respir J 2005; 12 (02) 75-77
- 113 Geleff S, Draganovici D, Jaksch P, Segerer S. The role of chemokine receptors in acute lung allograft rejection. Eur Respir J 2010; 35 (01) 167-175
- 114 Jungraithmayr W, Draenert A, Marquardt K, Weder W. Ultrastructural changes in acute lung allograft rejection: novel insights from an animal study. J Heart Lung Transplant 2012; 31 (01) 94-100
- 115 Xu X, Golden JA, Dolganov G. , et al. Transcript signatures of lymphocytic bronchitis in lung allograft biopsy specimens. J Heart Lung Transplant 2005; 24 (08) 1055-1066
- 116 Lande JD, Patil J, Li N, Berryman TR, King RA, Hertz MI. Novel insights into lung transplant rejection by microarray analysis. Proc Am Thorac Soc 2007; 4 (01) 44-51
- 117 McWilliams TJ, Williams TJ, Whitford HM, Snell GI. Surveillance bronchoscopy in lung transplant recipients: risk versus benefit. J Heart Lung Transplant 2008; 27 (11) 1203-1209
- 118 Greenland JR, Jewell NP, Gottschall M. , et al. Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection. Am J Transplant 2014; 14 (04) 831-840
- 119 Tiroke AH, Bewig B, Haverich A. Bronchoalveolar lavage in lung transplantation. State of the art. Clin Transplant 1999; 13 (02) 131-157
- 120 Vanaudenaerde BM, Wuyts WA, Geudens N. , et al. Broncho-alveolar lavage fluid recovery correlates with airway neutrophilia in lung transplant patients. Respir Med 2008; 102 (03) 339-347
- 121 Patil J, Lande JD, Li N, Berryman TR, King RA, Hertz MI. Bronchoalveolar lavage cell gene expression in acute lung rejection: development of a diagnostic classifier. Transplantation 2008; 85 (02) 224-231
- 122 Reynaud-Gaubert M, Thomas P, Gregoire R. , et al. Clinical utility of bronchoalveolar lavage cell phenotype analyses in the postoperative monitoring of lung transplant recipients. Eur J Cardiothorac Surg 2002; 21 (01) 60-66
- 123 Slebos DJ, Postma DS, Koëter GH, Van Der Bij W, Boezen M, Kauffman HF. Bronchoalveolar lavage fluid characteristics in acute and chronic lung transplant rejection. J Heart Lung Transplant 2004; 23 (05) 532-540
- 124 Vanaudenaerde BM, Dupont LJ, Wuyts WA. , et al. The role of interleukin-17 during acute rejection after lung transplantation. Eur Respir J 2006; 27 (04) 779-787
- 125 Riise GC, Scherstén H, Nilsson F, Ryd W, Andersson BA. Activation of eosinophils and fibroblasts assessed by eosinophil cationic protein and hyaluronan in BAL. Association with acute rejection in lung transplant recipients. Chest 1996; 110 (01) 89-96
- 126 Tikkanen J, Lemström K, Halme M, Pakkala S, Taskinen E, Koskinen P. Cytological monitoring of peripheral blood, bronchoalveolar lavage fluid, and transbronchial biopsy specimens during acute rejection and cytomegalovirus infection in lung and heart–lung allograft recipients. Clin Transplant 2001; 15 (02) 77-88
- 127 Neujahr DC. Assessing the cells in the lung lavage: an untapped resource in lung transplant monitoring. Am J Transplant 2014; 14 (04) 748-749
- 128 Gregson AL, Hoji A, Saggar R. , et al. Bronchoalveolar immunologic profile of acute human lung transplant allograft rejection. Transplantation 2008; 85 (07) 1056-1059
- 129 Madsen CB, Nørgaard A, Iversen M, Ryder LP. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts. Transpl Immunol 2010; 24 (01) 26-32
- 130 San Segundo D, Brunet M, Ballesteros MA. , et al. Prospective study of biomarkers of immune response in lung transplant recipients. Transplant Proc 2012; 44 (09) 2666-2668
- 131 Meehan AC, Sullivan LC, Mifsud NA. , et al. Natural killer cell activation in the lung allograft early posttransplantation. Transplantation 2010; 89 (06) 756-763
- 132 Speck NE, Schuurmans MM, Murer C, Benden C, Huber LC. Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology. Respir Res 2016; 17 (01) 74
- 133 Speck NE, Schuurmans MM, Benden C, Robinson CA, Huber LC. Plasma and bronchoalveolar lavage samples in acute lung allograft rejection: the potential role of cytokines as diagnostic markers. Respir Res 2017; 18 (01) 151
- 134 White SR, Floreth T, Liao C, Bhorade SM. Association of soluble HLA-G with acute rejection episodes and early development of bronchiolitis obliterans in lung transplantation. PLoS One 2014; 9 (07) e103643
- 135 Sandmeier P, Speich R, Grebski E. , et al. Iron accumulation in lung allografts is associated with acute rejection but not with adverse outcome. Chest 2005; 128 (03) 1379-1384
- 136 Hodge G, Hodge S, Chambers DC, Reynolds PN, Holmes M. Increased expression of graft intraepithelial T-cell pro-inflammatory cytokines compared with native lung during episodes of acute rejection. J Heart Lung Transplant 2012; 31 (05) 538-544
- 137 Fisher AJ, Gabbay E, Small T, Doig S, Dark JH, Corris PA. Cross sectional study of exhaled nitric oxide levels following lung transplantation. Thorax 1998; 53 (06) 454-458
- 138 Silkoff PE, Caramori M, Tremblay L. , et al. Exhaled nitric oxide in human lung transplantation. A noninvasive marker of acute rejection. Am J Respir Crit Care Med 1998; 157 (6 Pt 1): 1822-1828
- 139 Studer SM, Orens JB, Rosas I. , et al. Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection. J Heart Lung Transplant 2001; 20 (11) 1158-1166
- 140 Dupont LJ, Dewandeleer Y, Vanaudenaerde BM, Van Raemdonck DE, Verleden GM. The pH of exhaled breath condensate of patients with allograft rejection after lung transplantation. Am J Transplant 2006; 6 (06) 1486-1492
- 141 Jones HA, Donovan T, Goddard MJ. , et al. Use of 18FDG-pet to discriminate between infection and rejection in lung transplant recipients. Transplantation 2004; 77 (09) 1462-1464
- 142 Chen DL, Wang X, Yamamoto S. , et al. Increased T cell glucose uptake reflects acute rejection in lung grafts. Am J Transplant 2013; 13 (10) 2540-2549
- 143 Shennib H, Lee AG, Serrick C, Giaid A. Altered nonspecific lymphocyte cytotoxicity in bronchoalveolar lavage of lung transplant recipients: can it be useful in monitoring rejection or infection?. Transplantation 1996; 62 (09) 1262-1267
- 144 Tikkanen J, Lemström K, Halme M, Pakkala S, Taskinen E, Koskinen P. Detailed analysis of cell profiles in peripheral blood, bronchoalveolar lavage fluid, and transbronchial biopsy specimens during acute rejection and CMV infection in lung and heart-lung allograft recipients. Transplant Proc 1999; 31 (1-2): 163-164
- 145 Trull A, Steel L, Cornelissen J. , et al. Association between blood eosinophil counts and acute cardiac and pulmonary allograft rejection. J Heart Lung Transplant 1998; 17 (05) 517-524
- 146 Sammons C, Doligalski CT. Utility of procalcitonin as a biomarker for rejection and differentiation of infectious complications in lung transplant recipients. Ann Pharmacother 2014; 48 (01) 116-122
- 147 De Vlaminck I, Martin L, Kertesz M. , et al. Noninvasive monitoring of infection and rejection after lung transplantation. Proc Natl Acad Sci U S A 2015; 112 (43) 13336-13341
- 148 Gielis EM, Ledeganck KJ, De Winter BY. , et al. Cell-Free DNA: an upcoming biomarker in transplantation. Am J Transplant 2015; 15 (10) 2541-2551
- 149 Zou J, Duffy B, Slade M. , et al. Rapid detection of donor cell free DNA in lung transplant recipients with rejections using donor-recipient HLA mismatch. Hum Immunol 2017; 78 (04) 342-349
- 150 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 Transplant 2008; 27 (09) 990-994
- 151 Husain S, Raza K, Pilewski JM. , et al. Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection. Transplantation 2009; 87 (12) 1852-1857
- 152 Shino MY, Weigt SS, Saggar R. , et al. Usefulness of immune monitoring in lung transplantation using adenosine triphosphate production in activated lymphocytes. J Heart Lung Transplant 2012; 31 (09) 996-1002
- 153 Baughman RP, Meyer KC, Nathanson I. , et al. Monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease and lung transplant recipients: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 142 (05) e1S-e111S
- 154 Fuehner T, Simon A, Dierich M. , et al. Indicators for steroid response in biopsy proven acute graft rejection after lung transplantation. Respir Med 2009; 103 (08) 1114-1121
- 155 Ensor CR, Rihtarchik LC, Morrell MR. , et al. Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation. Clin Transplant 2017; 31 (04) 31
- 156 Sarahrudi K, Carretta A, Wisser W. , et al. The value of switching from cyclosporine to tacrolimus in the treatment of refractory acute rejection and obliterative bronchiolitis after lung transplantation. Transpl Int 2002; 15 (01) 24-28
- 157 Vitulo P, Oggionni T, Cascina A. , et al. Efficacy of tacrolimus rescue therapy in refractory acute rejection after lung transplantation. J Heart Lung Transplant 2002; 21 (04) 435-439
- 158 Horning NR, Lynch JP, Sundaresan SR, Patterson GA, Trulock EP. Tacrolimus therapy for persistent or recurrent acute rejection after lung transplantation. J Heart Lung Transplant 1998; 17 (08) 761-767
- 159 Shennib H, Massard G, Reynaud M, Noirclerc M. Efficacy of OKT3 therapy for acute rejection in isolated lung transplantation. J Heart Lung Transplant 1994; 13 (03) 514-519
- 160 Reams BD, Musselwhite LW, Zaas DW. , et al. Alemtuzumab in the treatment of refractory acute rejection and bronchiolitis obliterans syndrome after human lung transplantation. Am J Transplant 2007; 7 (12) 2802-2808
- 161 Aigner C, Jaksch P, Mazhar S. , et al. Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging. Eur J Cardiothorac Surg 2004; 25 (02) 184-187
- 162 Keenan RJ, Iacono A, Dauber JH. , et al. Treatment of refractory acute allograft rejection with aerosolized cyclosporine in lung transplant recipients. J Thorac Cardiovasc Surg 1997; 113 (02) 335-340 , discussion 340–341
- 163 Cahill BC, O'Rourke MK, Strasburg KA. , et al. Methotrexate for lung transplant recipients with steroid-resistant acute rejection. J Heart Lung Transplant 1996; 15 (11) 1130-1137
- 164 Valentine VG, Robbins RC, Wehner JH, Patel HR, Berry GJ, Theodore J. Total lymphoid irradiation for refractory acute rejection in heart-lung and lung allografts. Chest 1996; 109 (05) 1184-1189
- 165 Isenring B, Robinson C, Buergi U. , et al. Lung transplant recipients on long-term extracorporeal photopheresis. Clin Transplant 2017;31(10)
- 166 Benden C, Speich R, Hofbauer GF. , et al. Extracorporeal photopheresis after lung transplantation: a 10-year single-center experience. Transplantation 2008; 86 (11) 1625-1627
- 167 Glanville AR, Aboyoun CL, Havryk A, Plit M, Rainer S, Malouf MA. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation. Am J Respir Crit Care Med 2008; 177 (09) 1033-1040
- 168 Girgis RE, Tu I, Berry GJ. , et al. Risk factors for the development of obliterative bronchiolitis after lung transplantation. J Heart Lung Transplant 1996; 15 (12) 1200-1208
- 169 Sharples LD, McNeil K, Stewart S, Wallwork J. Risk factors for bronchiolitis obliterans: a systematic review of recent publications. J Heart Lung Transplant 2002; 21 (02) 271-281
- 170 Burton CM, Iversen M, Carlsen J. , et al. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1. J Heart Lung Transplant 2009; 28 (09) 888-893
- 171 Verleden SE, Ruttens D, Vandermeulen E. , et al. Bronchiolitis obliterans syndrome and restrictive allograft syndrome: do risk factors differ?. Transplantation 2013; 95 (09) 1167-1172
- 172 Castleberry AW, Worni M, Kuchibhatla M. , et al. A comparative analysis of bronchial stricture after lung transplantation in recipients with and without early acute rejection. Ann Thorac Surg 2013; 96 (03) 1008-1017 , discussion 1017–1018
- 173 Koutsokera A, Royer PJ, Antonietti JP. , et al; SysCLAD Consortium. Development of a multivariate prediction model for early-onset bronchiolitis obliterans syndrome and restrictive allograft syndrome in lung transplantation. Front Med (Lausanne) 2017; 4: 109
- 174 Hachem RR, Khalifah AP, Chakinala MM. , et al. The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation 2005; 80 (10) 1406-1413
- 175 Hopkins PM, Aboyoun CL, Chhajed PN. , et al. Association of minimal rejection in lung transplant recipients with obliterative bronchiolitis. Am J Respir Crit Care Med 2004; 170 (09) 1022-1026
- 176 Shino MY, Weigt SS, Li N. , et al. The prognostic importance of bronchoalveolar lavage fluid CXCL9 during minimal acute rejection on the risk of chronic lung allograft dysfunction. Am J Transplant 2017; 21: 21
- 177 Davis WA, Finlen Copeland CA, Todd JL, Snyder LD, Martissa JA, Palmer SM. Spirometrically significant acute rejection increases the risk for BOS and death after lung transplantation. Am J Transplant 2012; 12 (03) 745-752
- 178 Bhorade SM, Chen H, Molinero L. , et al. Decreased percentage of CD4+FoxP3+ cells in bronchoalveolar lavage from lung transplant recipients correlates with development of bronchiolitis obliterans syndrome. Transplantation 2010; 90 (05) 540-546