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Semin Respir Crit Care Med 2018; 39(02): 148-154
DOI: 10.1055/s-0037-1615797
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Primary Graft Dysfunction (PGD) Following Lung Transplantation

Rupal J. Shah
1   Division of Pulmonary, Allergy, and Critical Care, University of California, San Francisco, California
,
Joshua M. Diamond
2   Division of Pulmonary, Allergy, and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
› Author Affiliations Funding National Heart, Lung, and Blood Institute (Grant K23 HL121406 to JMD).
Further Information

Publication History

Publication Date:
28 March 2018 (online)

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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.

Keywords

primary graft dysfunction - lung transplantation
 

  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 3 Christie JD, Bavaria JE, Palevsky HI. , et al. Primary graft failure following lung transplantation. Chest 1998; 114 (01) 51-60
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 8 Sleiman C, Mal H, Fournier M. , et al. Pulmonary reimplantation response in single-lung transplantation. Eur Respir J 1995; 8 (01) 5-9
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 11 Christie JD, Bavaria JE, Palevsky HI. , et al. Primary graft failure following lung transplantation. Chest 1998; 114 (01) 51-60
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 14 Pereszlenyi Jr A, Harustiak S, Klepetko W. Extracorporeal membrane oxygenation in lung transplantation. Bratislavske Lekarske Listy 2002; 103 (01) 34-35
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 16 Zenati M, Yousem SA, Dowling RD, Stein KL, Griffith BP. Primary graft failure following pulmonary transplantation. Transplantation 1990; 50 (01) 165-167
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 19 Kundu S, Herman SJ, Winton TL. Reperfusion edema after lung transplantation: radiographic manifestations. Radiology 1998; 206 (01) 75-80
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 40 Manara AR, Murphy PG, O'Callaghan G. Donation after circulatory death. Br J Anaesth 2012; 108 (Suppl. 01) i108-i121
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 72 Smith PJ, Rivelli S, Waters A. , et al. Neurocognitive changes after lung transplantation. Ann Am Thorac Soc 2014; 11 (10) 1520-1527
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar