RSS-Feed abonnieren
DOI: 10.1055/s-0037-1615797
Primary Graft Dysfunction (PGD) Following Lung Transplantation
Funding National Heart, Lung, and Blood Institute (Grant K23 HL121406 to JMD).Publikationsverlauf
Publikationsdatum:
28. März 2018 (online)
![](https://www.thieme-connect.de/media/srccm/201802/lookinside/thumbnails/10-1055-s-0037-1615797_01358-1.jpg)
Abstract
Primary graft dysfunction (PGD) is a form of acute lung injury that results from ischemia reperfusion injury (IRI) and is the major cause of early posttransplant morbidity and mortality. Patients who survive PGD have decreased quality of life, an increased risk of chronic lung allograft dysfunction, specifically bronchiolitis obliterans syndrome, and a significantly increased risk of death. In 2017, the International Society for Heart and Lung Transplantation released updated consensus statements on the PGD definition, most up-to-date PGD risk factors, mechanisms of PGD development, and the state-of-the-art for PGD therapeutics. Risk factor identification has led to the development of PGD predictive algorithms, although their clinical utility remains limited. Ongoing areas of controversy and discussion include further refinements to the PGD grading scheme to account for technologic advances such as extracorporeal membrane oxygenation and the increased utilization of high flow nasal cannula, the use of PGD as an outcome measure in clinical trials of ex vivo lung perfusion, enhancement of predictive algorithms incorporating biochemical risk factors, and the need for development of therapies targeted at improving PGD outcomes.
-
References
- 1 Bharat A, Kuo E, Steward N. , et al. Immunological link between primary graft dysfunction and chronic lung allograft rejection. Ann Thorac Surg 2008; 86 (01) 189-195 , discussion 196–197
- 2 Bharat A, Narayanan K, Street T. , et al. Early posttransplant inflammation promotes the development of alloimmunity and chronic human lung allograft rejection. Transplantation 2007; 83 (02) 150-158 eng
- 3 Christie JD, Bavaria JE, Palevsky HI. , et al. Primary graft failure following lung transplantation. Chest 1998; 114 (01) 51-60
- 4 Christie JD, Kotloff RM, Ahya VN. , et al. The effect of primary graft dysfunction on survival after lung transplantation. Am J Respir Crit Care Med 2005; 171 (11) 1312-1316 eng
- 5 Christie JD, Kotloff RM, Pochettino A. , et al. Clinical risk factors for primary graft failure following lung transplantation. Chest 2003; 124 (04) 1232-1241
- 6 Daud SA, Yusen RD, Meyers BF. , et al. Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2007; 175 (05) 507-513
- 7 Haydock DA, Trulock EP, Kaiser LR, Knight SR, Pasque MK, Cooper JD. ; Washington University Lung Transplant Group. Management of dysfunction in the transplanted lung: experience with 7 clinical cases. Ann Thorac Surg 1992; 53 (04) 635-641
- 8 Sleiman C, Mal H, Fournier M. , et al. Pulmonary reimplantation response in single-lung transplantation. Eur Respir J 1995; 8 (01) 5-9
- 9 Fisher AJ, Wardle J, Dark JH, Corris PA. Non-immune acute graft injury after lung transplantation and the risk of subsequent bronchiolitis obliterans syndrome (BOS). J Heart Lung Transplant 2002; 21 (11) 1206-1212
- 10 Meyers BF, de la Morena M, Sweet SC. , et al. Primary graft dysfunction and other selected complications of lung transplantation: a single-center experience of 983 patients. J Thorac Cardiovasc Surg 2005; 129 (06) 1421-1429
- 11 Christie JD, Bavaria JE, Palevsky HI. , et al. Primary graft failure following lung transplantation. Chest 1998; 114 (01) 51-60
- 12 Glassman LR, Keenan RJ, Fabrizio MC. , et al. Extracorporeal membrane oxygenation as an adjunct treatment for primary graft failure in adult lung transplant recipients. J Thorac Cardiovasc Surg 1995; 110 (03) 723-726 , discussion 726–727
- 13 Oto T, Rosenfeldt F, Rowland M. , et al. Extracorporeal membrane oxygenation after lung transplantation: evolving technique improves outcomes. Ann Thorac Surg 2004; 78 (04) 1230-1235
- 14 Pereszlenyi Jr A, Harustiak S, Klepetko W. Extracorporeal membrane oxygenation in lung transplantation. Bratislavske Lekarske Listy 2002; 103 (01) 34-35
- 15 Colombat M, Castier Y, Leseche G. , et al. Early expression of adhesion molecules after lung transplantation: evidence for a role of aggregated P-selectin-positive platelets in human primary graft failure. J Heart Lung Transplant 2004; 23 (09) 1087-1092
- 16 Zenati M, Yousem SA, Dowling RD, Stein KL, Griffith BP. Primary graft failure following pulmonary transplantation. Transplantation 1990; 50 (01) 165-167
- 17 Anderson DC, Glazer HS, Semenkovich JW. , et al. Lung transplant edema: chest radiography after lung transplantation--the first 10 days. Radiology 1995; 195 (01) 275-281
- 18 Badesch DB, Zamora MR, Jones S, Campbell DW, Fullerton DA. Independent ventilation and ECMO for severe unilateral pulmonary edema after SLT for primary pulmonary hypertension. Chest 1995; 107 (06) 1766-1770
- 19 Kundu S, Herman SJ, Winton TL. Reperfusion edema after lung transplantation: radiographic manifestations. Radiology 1998; 206 (01) 75-80
- 20 Marom EM, Choi YW, Palmer SM, DeLong DM, Stuart MD, McAdams HP. Reperfusion edema after lung transplantation: effect of daclizumab. Radiology 2001; 221 (02) 508-514
- 21 Massard G, Rigolot JC, Hentz JG. , et al. Hemodilution is an effective treatment for reperfusion edema after lung transplantation. Thorac Cardiovasc Surg 1995; 43 (05) 293-295
- 22 Ware LB, Golden JA, Finkbeiner WE, Matthay MA. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation. Am J Respir Crit Care Med 1999; 159 (03) 980-988
- 23 Rabanal J, Mons R, Zurbano F, Ruiz I, Alcíbar J, Ortega J. Reimplantation edema in the transplanted lung. Reperfusion-ischemia or hydrostatic edema?. Rev Esp Anestesiol Reanim 2001; 48 (03) 146-150
- 24 Thabut G, Brugière O, Lesèche G. , et al. Preventive effect of inhaled nitric oxide and pentoxifylline on ischemia/reperfusion injury after lung transplantation. Transplantation 2001; 71 (09) 1295-1300
- 25 Belperio JA, Keane MP, Burdick MD. , et al. CXCR2/CXCR2 ligand biology during lung transplant ischemia-reperfusion injury. J Immunol 2005; 175 (10) 6931-6939
- 26 Mathur A, Baz M, Staples ED. , et al. Cytokine profile after lung transplantation: correlation with allograft injury. Ann Thorac Surg 2006; 81 (05) 1844-1849 , discussion 1849–1850
- 27 Fisher AJ, Donnelly SC, Hirani N. , et al. Elevated levels of interleukin-8 in donor lungs is associated with early graft failure after lung transplantation. Am J Respir Crit Care Med 2001; 163 (01) 259-265
- 28 Thabut G, Vinatier I, Brugière O. , et al. Influence of preservation solution on early graft failure in clinical lung transplantation. Am J Respir Crit Care Med 2001; 164 (07) 1204-1208
- 29 Khan SU, Salloum J, O'Donovan PB. , et al. Acute pulmonary edema after lung transplantation: the pulmonary reimplantation response. Chest 1999; 116 (01) 187-194
- 30 Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D. ; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2005; 24 (10) 1454-1459
- 31 Oto T, Griffiths AP, Levvey BJ, Pilcher DV, Williams TJ, Snell GI. Definitions of primary graft dysfunction after lung transplantation: differences between bilateral and single lung transplantation. J Thorac Cardiovasc Surg 2006; 132 (01) 140-147
- 32 Ranieri VM, Rubenfeld GD, Thompson BT. , et al; ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012; 307 (23) 2526-2533
- 33 Snell GI, Yusen RD, Weill D. , et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction, part I: definition and grading-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2017; 36 (10) 1097-1103
- 34 Cantu E, Diamond JM, Suzuki Y. , et al; Lung Transplant Outcomes Group. Quantitative evidence for revising the definition of primary graft dysfunction after lung transplant. Am J Respir Crit Care Med 2017
- 35 Boffini M, Ricci D, Bonato R. , et al. Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion. Eur J Cardiothorac Surg 2014; 46 (05) 789-793
- 36 Slama A, Schillab L, Barta M. , et al. Standard donor lung procurement with normothermic ex vivo lung perfusion: a prospective randomized clinical trial. J Heart Lung Transplant 2017; 36 (07) 744-753
- 37 Diamond JM, Arcasoy S, Kennedy CC. , et al. Report of the International Society for Heart and Lung Transplantation Working Group on Primary Lung Graft Dysfunction, part II: epidemiology, risk factors, and outcomes-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2017; 36 (10) 1104-1113
- 38 Kuntz CL, Hadjiliadis D, Ahya VN. , et al. Risk factors for early primary graft dysfunction after lung transplantation: a registry study. Clin Transplant 2009; 23 (06) 819-830
- 39 Levvey BJ, Harkess M, Hopkins P. , et al. Excellent clinical outcomes from a national donation-after-determination-of-cardiac-death lung transplant collaborative. Am J Transplant 2012; 12 (09) 2406-2413
- 40 Manara AR, Murphy PG, O'Callaghan G. Donation after circulatory death. Br J Anaesth 2012; 108 (Suppl. 01) i108-i121
- 41 Whitson BA, Nath DS, Johnson AC. , et al. Risk factors for primary graft dysfunction after lung transplantation. J Thorac Cardiovasc Surg 2006; 131 (01) 73-80
- 42 Diamond JM, Lee JC, Kawut SM. , et al; Lung Transplant Outcomes Group. Clinical risk factors for primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2013; 187 (05) 527-534
- 43 Oto T, Griffiths AP, Levvey B. , et al. A donor history of smoking affects early but not late outcome in lung transplantation. Transplantation 2004; 78 (04) 599-606
- 44 Lowery EM, Kuhlmann EA, Mahoney EL, Dilling DF, Kliethermes SA, Kovacs EJ. Heavy alcohol use in lung donors increases the risk for primary graft dysfunction. Alcohol Clin Exp Res 2014; 38 (11) 2853-2861
- 45 Pelaez A, Mitchell PO, Shah NS. , et al. The role of donor chronic alcohol abuse in the development of primary graft dysfunction in lung transplant recipients. Am J Med Sci 2015; 349 (02) 117-123
- 46 Liu Y, Liu Y, Su L, Jiang SJ. Recipient-related clinical risk factors for primary graft dysfunction after lung transplantation: a systematic review and meta-analysis. PLoS One 2014; 9 (03) e92773
- 47 Porteous MK, Ky B, Kirkpatrick JN. , et al. Diastolic dysfunction increases the risk of primary graft dysfunction after lung transplant. Am J Respir Crit Care Med 2016; 193 (12) 1392-1400
- 48 Lederer DJ, Kawut SM, Wickersham N. , et al; Lung Transplant Outcomes Group. Obesity and primary graft dysfunction after lung transplantation: the Lung Transplant Outcomes Group Obesity Study. Am J Respir Crit Care Med 2011; 184 (09) 1055-1061
- 49 Shigemura N, Bhama J, Gries CJ. , et al. Lung transplantation in patients with prior cardiothoracic surgical procedures. Am J Transplant 2012; 12 (05) 1249-1255
- 50 Aeba R, Griffith BP, Kormos RL. , et al. Effect of cardiopulmonary bypass on early graft dysfunction in clinical lung transplantation. Ann Thorac Surg 1994; 57 (03) 715-722
- 51 Force SD, Miller DL, Pelaez A. , et al. Outcomes of delayed chest closure after bilateral lung transplantation. Ann Thorac Surg 2006; 81 (06) 2020-2024 , discussion 2024–2025
- 52 Shigemura N, Orhan Y, Bhama JK. , et al. Delayed chest closure after lung transplantation: techniques, outcomes, and strategies. J Heart Lung Transplant 2014; 33 (07) 741-748
- 53 Porteous MK, Lee JC, Lederer DJ. , et al; Lung Transplant Outcomes Group. Clinical risk factors and prognostic model for primary graft dysfunction after lung transplantation in patients with pulmonary hypertension. Ann Am Thorac Soc 2017; 14 (10) 1514-1522
- 54 Gelman AE, Fisher AJ, Huang HJ. , et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: mechanisms: a 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2017; 36 (10) 1114-1120
- 55 Cantu E, Suzuki Y, Diamond JM. , et al; Lung Transplant Outcomes Group. Protein quantitative trait loci analysis identifies genetic variation in the innate immune regulator TOLLIP in post-lung transplant primary graft dysfunction risk. Am J Transplant 2016; 16 (03) 833-840
- 56 Christie JD, Shah CV, Kawut SM. , et al; Lung Transplant Outcomes Group. Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction. Am J Respir Crit Care Med 2009; 180 (10) 1010-1015
- 57 Diamond JM, Cantu E, Porteous MK. , et al; Clinical Trials in Organ Transplantation (CTOT)-03 Investigators. Peripheral blood gene expression changes associated with primary graft dysfunction after lung transplantation. Am J Transplant 2017; 17 (07) 1770-1777
- 58 Sayah DM, Mallavia B, Liu F. , et al; Lung Transplant Outcomes Group Investigators. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2015; 191 (04) 455-463
- 59 Weber DJ, Gracon AS, Ripsch MS. , et al. The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation. Sci Transl Med 2014; 6 (252) 252ra124
- 60 Belhaj A, Boven C, Dewachter L, Ruiz Patino M, Sokolow Y, Rondelet B. Influence of donor lung surfactant-A and -B protein expression on the development of primary graft dysfunction after lung transplantation: a pilot study. Ann Transplant 2017; 22: 361-369
- 61 Hashimoto K, Cypel M, Juvet S. , et al. Higher M30 and high mobility group box 1 protein levels in ex vivo lung perfusate are associated with primary graft dysfunction after human lung transplantation. J Heart Lung Transplant 2017; S1053-2498(17)31870-3
- 62 Hashimoto K, Cypel M, Kim H. , et al. Soluble adhesion molecules during ex vivo lung perfusion are associated with posttransplant primary graft dysfunction. Am J Transplant 2017; 17 (05) 1396-1404
- 63 Machuca TN, Cypel M, Zhao Y. , et al. The role of the endothelin-1 pathway as a biomarker for donor lung assessment in clinical ex vivo lung perfusion. J Heart Lung Transplant 2015; 34 (06) 849-857
- 64 Cantu E, Shah RJ, Lin W. , et al; Lung Transplant Outcomes Group Investigators. Oxidant stress regulatory genetic variation in recipients and donors contributes to risk of primary graft dysfunction after lung transplantation. J Thorac Cardiovasc Surg 2015; 149 (02) 596-602
- 65 Christie JD, Bellamy S, Ware LB. , et al. Construct validity of the definition of primary graft dysfunction after lung transplantation. J Heart Lung Transplant 2010; 29 (11) 1231-1239
- 66 Shah RJ, Diamond JM, Cantu E. , et al. Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. Chest 2013; 144 (02) 616-622
- 67 Huang HJ, Yusen RD, Meyers BF. , et al. Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome. Am J Transplant 2008; 8 (11) 2454-2462
- 68 Whitson BA, Prekker ME, Herrington CS. , et al. Primary graft dysfunction and long-term pulmonary function after lung transplantation. J Heart Lung Transplant 2007; 26 (10) 1004-1011
- 69 Yusen RD, Edwards LB, Dipchand AI. , et al; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart-Lung Transplant Report-2016; Focus Theme: primary diagnostic indications for transplant. J Heart Lung Transplant 2016; 35 (10) 1170-1184
- 70 Christie JD, Sager JS, Kimmel SE. , et al. Impact of primary graft failure on outcomes following lung transplantation. Chest 2005; 127 (01) 161-165
- 71 Smith PJ, Blumenthal JA, Hoffman BM. , et al. Reduced cerebral perfusion pressure during lung transplant surgery is associated with risk, duration, and severity of postoperative delirium. Ann Am Thorac Soc 2016; 13 (02) 180-187
- 72 Smith PJ, Rivelli S, Waters A. , et al. Neurocognitive changes after lung transplantation. Ann Am Thorac Soc 2014; 11 (10) 1520-1527
- 73 Pottecher J, Roche AC, Dégot T. , et al; Groupe de Transplantation Pulmonaire des Hôpitaux Universitaires de Strasbourg. Increased extravascular lung water and plasma biomarkers of acute lung injury precede oxygenation impairment in primary graft dysfunction after lung transplantation. Transplantation 2017; 101 (01) 112-121
- 74 Shah RJ, Diamond JM, Cantu E. , et al. Objective estimates improve risk stratification for primary graft dysfunction after lung transplantation. Am J Transplant 2015; 15 (08) 2188-2196
- 75 Hashimoto K, Besla R, Zamel R. , et al. Circulating cell death biomarkers may predict survival in human lung transplantation. Am J Respir Crit Care Med 2016; 194 (01) 97-105
- 76 Wigfield CH, Lindsey JD, Steffens TG, Edwards NM, Love RB. Early institution of extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation improves outcome. J Heart Lung Transplant 2007; 26 (04) 331-338
- 77 Fischer S, Bohn D, Rycus P. , et al. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: analysis of the Extracorporeal Life Support Organization (ELSO) registry. J Heart Lung Transplant 2007; 26 (05) 472-477
- 78 Bermudez CA, Adusumilli PS, McCurry KR. , et al. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival. Ann Thorac Surg 2009; 87 (03) 854-860
- 79 Kawut SM, Lederer DJ, Keshavjee S. , et al. Outcomes after lung retransplantation in the modern era. Am J Respir Crit Care Med 2008; 177 (01) 114-120