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Seminars in Immunopathology
Published in: Seminars in Immunopathology 2/2011

01-03-2011 | Review

Special issues in the management and selection of the donor for lung transplantation

Authors: Priyumvada M. Naik, Luis F. Angel

Published in: Seminars in Immunopathology | Issue 2/2011

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Abstract

Lung transplantation is a viable treatment option for select patients with end-stage lung disease. Two issues hamper progress in transplantation: first, donor shortage is a major limitation to increasing the number of transplants performed. Secondly, recipient outcomes remain disappointing when compared with other solid organ transplant results. Outcomes are limited by primary graft dysfunction (PGD), the posttransplant acute lung injury that increases both short-and long-term mortality. Attempts to overcome donor shortage have included aggressively managing solid organ donors to increase the number of donor lungs suitable for transplantation. Yet, the quality of the lung donor is likely to be related to the probability of the recipient experiencing PGD. PGD is the culmination of a series of insults, hemodynamic, metabolic, and inflammatory, that begin with the brain dead donor and result in poor recipient outcomes. Understanding the mechanism of donor lung injury resulting from brain death and the possible treatment strategies for its inhibition could help to increase the number of usable lungs and decrease the rate of PGD in the recipient. Here we present a review of the key pathways which result in donor lung injury, and follow this with a brief review of recent biomarkers that are proving to be instrumental to our ability to predict truly unsuitable lungs, and our ability to predict and hopefully prevent or treat recipients with subsequent lung injury.
Literature
1.
2.
Veith FJ (1978) Lung transplantation. Surg Clin North Am 58(2):357–364PubMed
3.
Derom F et al (1971) Ten-month survival after lung homotransplantation in man. J Thorac Cardiovasc Surg 61(6):835–846PubMed
4.
Thabut G et al (2002) Primary graft failure following lung transplantation: predictive factors of mortality. Chest 121(6):1876–1882PubMedCrossRef
5.
Christie JD et al (2005) 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 24(10):1454–1459PubMedCrossRef
6.
Fiser SM et al (2002) Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome. Ann Thorac Surg 73(4):1041–1047, discussion 1047-8PubMedCrossRef
7.
Daud SA et al (2007) Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 175(5):507–513PubMedCrossRef
8.
Fisher AJ et al (1999) Enhanced pulmonary inflammation in organ donors following fatal non-traumatic brain injury. Lancet 353(9162):1412–1413PubMedCrossRef
9.
Avlonitis VS, JAK DJH (2005) The effect of time from donor brain death to retrieval on reperfusion injury after lung transplantation. J Heart Lung Transplant 24(2):S121CrossRef
10.
Gabbay E et al (1999) Maximizing the utilization of donor organs offered for lung transplantation. Am J Respir Crit Care Med 160(1):265–271PubMed
11.
Angel LF et al (2006) Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes. Am J Respir Crit Care Med 174(6):710–716PubMedCrossRef
12.
Annual report of the U.S. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients (2008): transplant data 1998–2007. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD; United Network for Organ Sharing, Richmond, VA
13.
Terasaki PI et al (1995) High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med 333(6):333–336PubMedCrossRef
14.
Pratschke J et al (2000) Accelerated rejection of renal allografts from brain-dead donors. Ann Surg 232(2):263–271PubMedCrossRef
15.
Wilhelm MJ et al (2000) Activation of the heart by donor brain death accelerates acute rejection after transplantation. Circulation 102(19):2426–2433PubMed
16.
Van der Hoeven JA et al (2001) Donor brain death reduces survival after transplantation in rat livers preserved for 20 h. Transplantation 72(10):1632–1636PubMedCrossRef
17.
Zweers N et al (2004) Donor brain death aggravates chronic rejection after lung transplantation in rats. Transplantation 78(9):1251–1258PubMedCrossRef
18.
Avlonitis VS et al (2003) Pulmonary transplantation: the role of brain death in donor lung injury. Transplantation 75(12):1928–1933PubMedCrossRef
19.
Avlonitis VS et al (2005) The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor. Am J Transplant 5(4 Pt 1):684–693PubMedCrossRef
20.
Smith M (2004) Physiologic changes during brain stem death—lessons for management of the organ donor. J Heart Lung Transplant 23(9 Suppl):S217–S222PubMedCrossRef
21.
Rosendale JD et al (2003) Aggressive pharmacologic donor management results in more transplanted organs. Transplantation 75(4):482–487PubMedCrossRef
22.
Chen EP et al (1996) Hormonal and hemodynamic changes in a validated animal model of brain death. Crit Care Med 24(8):1352–1359PubMedCrossRef
23.
Smith WS, Matthay MA (1997) Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema. Chest 111(5):1326–1333PubMedCrossRef
24.
25.
Wray NP, Nicotra MB (1978) Pathogenesis of neurogenic pulmonary edema. Am Rev Respir Dis 118(4):783–786PubMed
26.
Novitzky D et al (1987) Pathophysiology of pulmonary edema following experimental brain death in the chacma baboon. Ann Thorac Surg 43(3):288–294PubMedCrossRef
27.
28.
Shanahan W (1908) Acute pulmonary oedema as a complication of epileptic seizures. NY Med J 37:54
29.
Simmons RL et al (1969) Respiratory insufficiency in combat casualties. II. pulmonary edema following head injury. Ann Surg 170(1):39–44PubMedCrossRef
30.
Shohami E et al (1994) Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue. J Cereb Blood Flow Metab 14(4):615–619PubMedCrossRef
31.
Wang CX, Shuaib A (2002) Involvement of inflammatory cytokines in central nervous system injury. Prog Neurobiol 67(2):161–172PubMedCrossRef
32.
Skrabal CA et al (2005) Organ-specific regulation of pro-inflammatory molecules in heart, lung, and kidney following brain death. J Surg Res 123(1):118–125PubMedCrossRef
33.
Lentsch AB, Ward PA (2001) Regulation of experimental lung inflammation. Respir Physiol 128(1):17–22PubMedCrossRef
34.
Strieter RM, Kunkel SL (1994) Acute lung injury: the role of cytokines in the elicitation of neutrophils. J Investig Med 42(4):640–651PubMed
35.
Naik P et al (2008) Oxidative stress in lung allograft recipients with and without graft dysfunction. J Heart Lung Transplant 28(2):S283--S284
36.
Sutherland AJ et al (2007) The endothelin axis and gelatinase activity in alveolar macrophages after brain-stem death injury: a pilot study. J Heart Lung Transplant 26(10):1040–1047PubMedCrossRef
37.
Bobadilla JL et al (2008) Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am J Respir Crit Care Med 177(6):660–668PubMedCrossRef
38.
Iwata T et al (2008) Lung transplant ischemia reperfusion injury: metalloprotease inhibition down-regulates exposure of type V collagen, growth-related oncogene-induced neutrophil chemotaxis, and tumor necrosis factor-alpha expression. Transplantation 85(3):417–426PubMed
39.
Burlingham WJ et al (2007) IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 117(11):3498–3506PubMedCrossRef
40.
Donnelly SC et al (1993) Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet 341(8846):643–647PubMedCrossRef
41.
Fisher AJ et al (2001) Elevated levels of interleukin-8 in donor lungs is associated with early graft failure after lung transplantation. Am J Respir Crit Care Med 163(1):259–265PubMed
42.
De Perrot M et al (2002) Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am J Respir Crit Care Med 165(2):211–215PubMed
43.
Ramasamy R et al (2005) Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15(7):16R–28RPubMedCrossRef
44.
Schmidt AM et al (2001) The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 108(7):949–955PubMed
45.
Liliensiek B et al (2004) Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response. J Clin Invest 113(11):1641–1650PubMed
46.
Uchida T et al (2006) Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury. Am J Respir Crit Care Med 173(9):1008–1015PubMedCrossRef
47.
Calfee CS et al (2007) Plasma receptor for advanced glycation end-products predicts duration of ICU stay and mechanical ventilation in patients after lung transplantation. J Heart Lung Transplant 26(7):675–680PubMedCrossRef
48.
Christie JD et al (2009) Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction. Am J Respir Crit Care Med 180(10):1010–1015PubMedCrossRef
49.
Pelaez A et al (2010) Receptor for advanced glycation end products in donor lungs is associated with primary graft dysfunction after lung transplantation. Am J Transplant 10(4):900–907PubMedCrossRef
50.
Sternberg DI et al (2008) Blockade of receptor for advanced glycation end product attenuates pulmonary reperfusion injury in mice. J Thorac Cardiovasc Surg 136(6):1576–1585PubMedCrossRef
51.
Novitzky D et al (2006) Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation 82(11):1396–1401PubMedCrossRef
52.
Ueno T, Zhi-Li C, Itoh T (2000) Unique circulatory responses to exogenous catecholamines after brain death. Transplantation 70(3):436–440PubMedCrossRef
53.
van Der Hoeven JA et al (2000) Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat. Ann Surg 232(6):804–813CrossRef
54.
Keogh AM et al (1988) Pituitary function in brain-stem dead organ donors: a prospective survey. Transplant Proc 20(5):729–730PubMed
55.
Howlett TA et al (1989) Anterior and posterior pituitary function in brain-stem-dead donors. a possible role for hormonal replacement therapy. Transplantation 47(5):828–834PubMedCrossRef
56.
Yoshioka T et al (1986) Prolonged hemodynamic maintenance by the combined administration of vasopressin and epinephrine in brain death: a clinical study. Neurosurgery 18(5):565–567PubMedCrossRef
57.
Mukadam ME et al (2005) Does donor catecholamine administration affect early lung function after transplantation? J Thorac Cardiovasc Surg 130(3):926–927PubMedCrossRef
58.
Ware LB et al (2002) Selected contribution: mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung. J Appl Physiol 93(5):1869–1874PubMed
59.
van der Hoeven JA et al (2003) Relationship between duration of brain death and hemodynamic (in)stability on progressive dysfunction and increased immunologic activation of donor kidneys. Kidney Int 64(5):1874–1882PubMedCrossRef
60.
Auphan N et al (1995) Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 270(5234):286–290PubMedCrossRef
61.
Folkesson HG et al (2000) Dexamethasone and thyroid hormone pretreatment upregulate alveolar epithelial fluid clearance in adult rats. J Appl Physiol 88(2):416–424PubMed
62.
Follette DM, Rudich SM, Babcock WD (1998) Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death. J Heart Lung Transplant 17(4):423–429PubMed
63.
Goarin JP et al (1996) The effects of triiodothyronine on hemodynamic status and cardiac function in potential heart donors. Anesth Analg 83(1):41–47PubMed
64.
65.
Pierre AF et al (2002) Marginal donor lungs: a reassessment. J Thorac Cardiovasc Surg 123(3):421–427, discussion, 427-8PubMedCrossRef
66.
Spital A (2005) Conscription of cadaveric organs for transplantation: a stimulating idea whose time has not yet come. Cambridge Q Healthc Ethics 14:107–112
67.
Mozes MF et al (1991) Impediments to successful organ procurement in the “required request” era: an urban center experience. Transplant Proc 23(5):2545PubMed
68.
69.
Michielsen P (1996) Presumed consent to organ donation: 10 years’ experience in Belgium. J R Soc Med 89(12):663–666PubMed
70.
71.
Weill D (2002) Donor criteria in lung transplantation: an issue revisited. Chest 121(6):2029–2031PubMedCrossRef
72.
73.
Bonde PN et al (2006) Impact of donor lung organisms on post-lung transplant pneumonia. J Heart Lung Transplant 25(1):99–105PubMedCrossRef
74.
Weill D et al (2002) A positive donor gram stain does not predict outcome following lung transplantation. J Heart Lung Transplant 21(5):555–558PubMedCrossRef
75.
Ruiz I et al (2006) Donor-to-host transmission of bacterial and fungal infections in lung transplantation. Am J Transplant 6(1):178–182PubMedCrossRef
76.
Bhorade SM et al (2000) Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation. J Heart Lung Transplant 19(12):1199–1204PubMedCrossRef
77.
Dahlman S et al (2006) Expanding the donor pool: lung transplantation with donors 55 years and older. Transplant Proc 38(8):2691–2693PubMedCrossRef
78.
Fischer S et al (2005) Lung transplantation with lungs from donors fifty years of age and older. J Thorac Cardiovasc Surg 129(4):919–925PubMedCrossRef
79.
Lardinois D et al (2005) Extended donor lungs: eleven years experience in a consecutive series. Eur J Cardiothorac Surg 27(5):762–767PubMedCrossRef
80.
Aigner C et al (2005) Extended donor criteria for lung transplantation—a clinical reality. Eur J Cardiothorac Surg 27(5):757–761PubMedCrossRef
81.
Ware LB et al (2002) Assessment of lungs rejected for transplantation and implications for donor selection. Lancet 360(9333):619–620PubMedCrossRef
82.
Straznicka M et al (2002) Aggressive management of lung donors classified as unacceptable: excellent recipient survival one year after transplantation. J Thorac Cardiovasc Surg 124(2):250–258PubMedCrossRef
83.
Kirschbaum CE, Hudson S (2010) Increasing organ yield through a lung management protocol. Prog Transplant 20(1):28–32PubMed
Metadata
Title
Special issues in the management and selection of the donor for lung transplantation
Authors
Priyumvada M. Naik
Luis F. Angel
Publication date
01-03-2011
Publisher
Springer-Verlag
Published in
Seminars in Immunopathology / Issue 2/2011
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-011-0256-x

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