RSS-Feed abonnieren
DOI: 10.1055/s-0041-1729859
Pushing the Envelope for Donor Lungs
![](https://www.thieme-connect.de/media/srccm/202103/lookinside/thumbnails/10-1055-s-0041-1729859_210304-1.jpg)
Abstract
The shortage of organ donors remains the major limiting factor in lung transplant, with the number of patients on the waiting list largely exceeding the number of available organ donors. Another issue is the low utilization rate seen in some types of donors. Therefore, novel strategies are continuously being explored to increase the donor pool. Advanced age, smoking history, positive serologies, and size mismatch are common criteria that decrease the rate of use when it comes to organ utilization. Questioning these limitations is one of the purposes of this review. Challenging these limitations by adapting novel donor management strategies could help to increase the rate of suitable lungs for transplantation while still maintaining good outcomes. A second goal is to present the latest advances in organ donation after controlled and uncontrolled cardiac death, and also on how to improve these lungs on ex vivo platforms for assessment and future specific therapies. Finally, pushing the limit of the donor envelope also means reviewing some of the recent improvements made in lung preservation itself, as well as upcoming experimental research fields. In summary, donor lung optimization refers to a global care strategy to increase the total numbers of available allografts, and preserve or improve organ quality without paying the price of early-, mid-, or long-term negative outcomes after transplantation.
Publikationsverlauf
Artikel online veröffentlicht:
24. Mai 2021
© 2021. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 De Meester J, Smits JMA, Persijn GG, Haverich A. Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience. J Heart Lung Transplant 2001; 20 (05) 518-524
- 2 Titman A, Rogers CA, Bonser RS, Banner NR, Sharples LD. Disease-specific survival benefit of lung transplantation in adults: a national cohort study. Am J Transplant 2009; 9 (07) 1640-1649
- 3 Van Raemdonck D, Neyrinck A, Verleden GM. et al. Lung donor selection and management. Proc Am Thorac Soc 2009; 6 (01) 28-38
- 4 Orens JB, Boehler A, de Perrot M. et al; Pulmonary Council, International Society for Heart and Lung Transplantation. A review of lung transplant donor acceptability criteria. J Heart Lung Transplant 2003; 22 (11) 1183-1200
- 5 Valapour M, Lehr CJ, Skeans MA. et al. OPTN/SRTR 2018 annual data report: lung. Am J Transplant 2020; 20 (suppl s1): 427-508
- 6 Choi AY, Jawitz OK, Raman V. et al. Predictors of older donor lung use: are we too good at saying no?. Ann Thorac Surg 2020; 110 (05) 1683-1690
- 7 Hayes Jr. D, Black SM, Tobias JD, Higgins RS, Whitson BA. Influence of donor and recipient age in lung transplantation. J Heart Lung Transplant 2015; 34 (01) 43-49
- 8 Hall DJ, Jeng EI, Gregg JA. et al. The impact of donor and recipient age: older lung transplant recipients do not require younger lungs. Ann Thorac Surg 2019; 107 (03) 868-876
- 9 Whited WM, Henley P, Schumer EM, Trivedi JR, van Berkel VH, Fox MP. Does donor age and double versus single lung transplant affect survival of young recipients?. Ann Thorac Surg 2018; 105 (01) 235-241
- 10 Divithotawela C, Cypel M, Martinu T. et al. Long-term outcomes of lung transplant with ex vivo lung perfusion. JAMA Surg 2019; 154 (12) 1143-1150
- 11 Bos S, Vos R, Van Raemdonck DE, Verleden GM. Survival in adult lung transplantation: where are we in 2020?. Curr Opin Organ Transplant 2020; 25 (03) 268-273
- 12 Bonser RS, Taylor R, Collett D, Thomas HL, Dark JH, Neuberger J. Cardiothoracic Advisory Group to NHS Blood and Transplant and the Association of Lung Transplant Physicians (UK). Effect of donor smoking on survival after lung transplantation: a cohort study of a prospective registry. Lancet 2012; 380 (9843): 747-755
- 13 Berman M, Goldsmith K, Jenkins D. et al. Comparison of outcomes from smoking and nonsmoking donors: thirteen-year experience. Ann Thorac Surg 2010; 90 (06) 1786-1792
- 14 Almenar M, Cerón J, Gómez MA, Peñalver JC, Jiménez MA, Padilla J. [Interleukin 8 concentrations in donor bronchoalveolar lavage: impact on primary graft failure in double lung transplant] (in Spanish). Arch Bronconeumol 2009; 45 (01) 12-15
- 15 Christie JD, Kotloff RM, Pochettino A. et al. Clinical risk factors for primary graft failure following lung transplantation. Chest 2003; 124 (04) 1232-1241
- 16 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
- 17 De Perrot M, Sekine Y, Fischer S. et al. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am J Respir Crit Care Med 2002; 165 (02) 211-215
- 18 Winhusen T, Theobald J, Kaelber DC, Lewis D. Regular cannabis use, with and without tobacco co-use, is associated with respiratory disease. Drug Alcohol Depend 2019; 204: 107557
- 19 Cypel M, Yeung JC, Liu M. et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 2011; 364 (15) 1431-1440
- 20 Van Raemdonck D, Keshavjee S, Levvey B. et al; International Society for Heart and Lung Transplantation. Donation after circulatory death in lung transplantation-five-year follow-up from ISHLT Registry. J Heart Lung Transplant 2019; 38 (12) 1235-1245
- 21 Aigner C, Winkler G, Jaksch P. et al. Extended donor criteria for lung transplantation--a clinical reality. Eur J Cardiothorac Surg 2005; 27 (05) 757-761
- 22 Okahara S, Levvey B, McDonald M. et al. Influence of the donor history of tobacco and marijuana smoking on early and intermediate lung transplant outcomes. J Heart Lung Transplant 2020; 39 (09) 962-969
- 23 Mehra MR, Jarcho JA, Cherikh W. et al. The drug-intoxication epidemic and solid-organ transplantation. N Engl J Med 2018; 378 (20) 1943-1945
- 24 Feld JJ, Jacobson IM, Hézode C. et al; ASTRAL-1 Investigators. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015; 373 (27) 2599-2607
- 25 Durand CM, Bowring MG, Thomas AG. et al. The drug overdose epidemic and deceased-donor transplantation in the United States a national registry study. Ann Intern Med 2018; 168 (10) 702-711
- 26 Afdhal N, Zeuzem S, Kwo P. et al; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med 2014; 370 (20) 1889-1898
- 27 Reese PP, Abt PL, Blumberg EA, Goldberg DS. Transplanting hepatitis C-positive kidneys. N Engl J Med 2015; 373 (04) 303-305
- 28 Khan B, Singer LG, Lilly LB. et al. Successful lung transplantation from hepatitis C positive donor to seronegative recipient. Am J Transplant 2017; 17 (04) 1129-1131
- 29 Woolley AE, Singh SK, Goldberg HJ. et al; DONATE HCV Trial Team. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med 2019; 380 (17) 1606-1617
- 30 Cypel M, Feld JJ, Galasso M. et al. Prevention of viral transmission during lung transplantation with hepatitis C-viraemic donors: an open-label, single-centre, pilot trial. Lancet Respir Med 2020; 8 (02) 192-201
- 31 Galasso M, Feld JJ, Watanabe Y. et al. Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion. Nat Commun 2019; 10 (01) 481
- 32 Cox ML, Mulvihill MS, Choi AY. et al. Implications of declining donor offers with increased risk of disease transmission on waiting list survival in lung transplantation. J Heart Lung Transplant 2019; 38 (03) 295-305
- 33 Bisson A, Bonnette P, el Kadi NB, Leroy M, Colchen A. Bilateral pulmonary lobe transplantation: left lower and right middle and lower lobes. Ann Thorac Surg 1994; 57 (01) 219-221
- 34 Eberlein M, Reed RM, Bolukbas S. et al; Lung Transplant Outcomes Group. Lung size mismatch and primary graft dysfunction after bilateral lung transplantation. J Heart Lung Transplant 2015; 34 (02) 233-240
- 35 Slama A, Ghanim B, Klikovits T. et al. Lobar lung transplantation--is it comparable with standard lung transplantation?. Transpl Int 2014; 27 (09) 909-916
- 36 Mitilian D, Sage E, Puyo P. et al; Foch Lung Transplant Group. Techniques and results of lobar lung transplantations. Eur J Cardiothorac Surg 2014; 45 (02) 365-369 , discussion 369–370
- 37 Inci I, Schuurmans MM, Kestenholz P. et al. Long-term outcomes of bilateral lobar lung transplantation. Eur J Cardiothorac Surg 2013; 43 (06) 1220-1225
- 38 Campo-Canaveral De La Cruz JL, Dunne B, Lemaitre P. et al. Deceased-donor lobar lung transplant: a successful strategy for small-sized recipients. J Thorac Cardiovasc Surg 2021; 161 (05) 1674-1685
- 39 Santos Silva J, Olland A, Massard G, Falcoz PE. Does lobar or size-reduced lung transplantation offer satisfactory early and late outcomes?. Interact Cardiovasc Thorac Surg 2020; 31 (01) 93-97
- 40 Domínguez-Gil B, Ascher N, Capron AM. et al. Expanding controlled donation after the circulatory determination of death: statement from an international collaborative. Intensive Care Med 2021; 47 (03) 265-281
- 41 Miñambres E, Cifrian JM, Alvarez C. et al. Excellent long-term outcome with lungs obtained from uncontrolled donation after circulatory death. J Heart Lung Transplant 2019; 19 (04) 1195-1201
- 42 Suberviola B, Mons R, Ballesteros MA. et al. Excellent long-term outcome with lungs obtained from uncontrolled donation after circulatory death. Am J Transplant 2019; 19 (04) 1195-1201
- 43 Healey A, Watanabe Y, Mills C. et al. Initial lung transplantation experience with uncontrolled donation after cardiac death in North America. Am J Transplant 2020; 20 (06) 1574-1581
- 44 Cypel M, Levvey B, Van Raemdonck D. et al; International Society for Heart and Lung Transplantation. International Society for Heart and Lung Transplantation donation after circulatory death registry report. J Heart Lung Transplant 2015; 34 (10) 1278-1282
- 45 Villavicencio MA, Axtell AL, Spencer PJ. et al. Lung transplantation from donation after circulatory death: united states and single-center experience. Ann Thorac Surg 2018; 106 (06) 1619-1627
- 46 Mooney JJ, Hedlin H, Mohabir PK. et al. Lung quality and utilization in controlled donation after circulatory determination of death within the United States. Am J Transplant 2016; 16 (04) 1207-1215
- 47 Downar J, Fowler RA, Halko R, Huyer LD, Hill AD, Gibson JL. Early experience with medical assistance in dying in Ontario, Canada: a cohort study. CMAJ 2020; 192 (08) E173-E181
- 48 Downar J, Shemie SD, Gillrie C. et al; for Canadian Blood Services, the Canadian Critical Care Society, the Canadian Society of Transplantation and the Canadian Association of Critical Care Nurses. Deceased organ and tissue donation after medical assistance in dying and other conscious and competent donors: guidance for policy. CMAJ 2019; 191 (22) E604-E613
- 49 Healey A, Cypel M, Pyle H. et al. Lung donation after medical assistance in dying at home. Am J Transplant 2021; 21 (01) 415-418
- 50 Carrel A, Lindbergh CA. The culture of whole organs. Science 1935; 81 (2112): 621-623
- 51 Hardesty RL, Griffith BP. Autoperfusion of the heart and lungs for preservation during distant procurement. J Thorac Cardiovasc Surg 1987; 93 (01) 11-18
- 52 Steen S, Sjöberg T, Pierre L, Liao Q, Eriksson L, Algotsson L. Transplantation of lungs from a non-heart-beating donor. Lancet 2001; 357 (9259): 825-829
- 53 Cypel M, Yeung JC, Hirayama S. et al. Technique for prolonged normothermic ex vivo lung perfusion. J Heart Lung Transplant 2008; 27 (12) 1319-1325
- 54 Aigner C, Slama A, Hötzenecker K. et al. Clinical ex vivo lung perfusion--pushing the limits. Am J Transplant 2012; 12 (07) 1839-1847
- 55 Sage E, Mussot S, Trebbia G. et al; Foch Lung Transplant Group. Lung transplantation from initially rejected donors after ex vivo lung reconditioning: the French experience. Eur J Cardiothorac Surg 2014; 46 (05) 794-799
- 56 Valenza F, Citerio G, Palleschi A. et al. Successful transplantation of lungs from an uncontrolled donor after circulatory death preserved in situ by alveolar recruitment maneuvers and assessed by ex vivo lung perfusion. Am J Transplant 2016; 16 (04) 1312-1318
- 57 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
- 58 Warnecke G, Moradiellos J, Tudorache I. et al. Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients. Lancet 2012; 380 (9856): 1851-1858
- 59 Zych B, Popov AF, Stavri G. et al. Early outcomes of bilateral sequential single lung transplantation after ex-vivo lung evaluation and reconditioning. J Heart Lung Transplant 2012; 31 (03) 274-281
- 60 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
- 61 Henriksen IS, Møller-Sørensen H, Møller CH. et al. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation. Dan Med J 2014; 61 (03) A4809
- 62 Zhang ZL, van Suylen V, van Zanden JE. et al. First experience with ex vivo lung perfusion for initially discarded donor lungs in the Netherlands: a single-centre study. Eur J Cardiothorac Surg 2019; 55 (05) 920-926
- 63 McMeekin N, Chrysos AE, Vale L, Fisher AJ. Incorporating ex-vivo lung perfusion into the UK adult lung transplant service: an economic evaluation and decision analytic model. BMC Health Serv Res 2019; 19 (01) 326
- 64 Southard JH, Belzer FO. Organ preservation. Annu Rev Med 1995; 46: 235-247
- 65 Sage AT, Richard-Greenblatt M, Zhong K. et al. Prediction of donor related lung injury in clinical lung transplantation using a validated ex vivo lung perfusion inflammation score. J Heart Lung Transplant 2021; (e-pub ahead of print). DOI: 10.1016/j.healun.2021.03.002.
- 66 Remund KF, Best M, Egan JJ. Infections relevant to lung transplantation. Proc Am Thorac Soc 2009; 6 (01) 94-100
- 67 Nakajima D, Cypel M, Bonato R. et al. Ex vivo perfusion treatment of infection in human donor lungs. Am J Transplant 2016; 16 (04) 1229-1237
- 68 Andreasson A, Karamanou DM, Perry JD. et al. The effect of ex vivo lung perfusion on microbial load in human donor lungs. J Heart Lung Transplant 2014; 33 (09) 910-916
- 69 Deppisch C, Herrmann G, Graepler-Mainka U. et al. Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study. Infection 2016; 44 (04) 513-520
- 70 Michaelsen VS, Ribeiro RVP, Ali A. et al. Safety of continuous 12-hour delivery of antimicrobial doses of inhaled nitric oxide during ex vivo lung perfusion. J Thorac Cardiovasc Surg 2020; (e-pub ahead of print). DOI: 10.1016/j.jtcvs.2020.11.150.
- 71 Mutlu GM, Dumasius V, Burhop J. et al. Upregulation of alveolar epithelial active Na+ transport is dependent on beta2-adrenergic receptor signaling. Circ Res 2004; 94 (08) 1091-1100
- 72 Lasnier JM, Wangensteen OD, Schmitz LS, Gross CR, Ingbar DH. Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury. J Appl Physiol (1985) 1996; 81 (04) 1723-1729
- 73 Frank JA, Briot R, Lee JW, Ishizaka A, Uchida T, Matthay MA. Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs. Am J Physiol Lung Cell Mol Physiol 2007; 293 (01) L52-L59
- 74 Machuca TN, Hsin MK, Ott HC. et al. Injury-specific ex vivo treatment of the donor lung: pulmonary thrombolysis followed by successful lung transplantation. Am J Respir Crit Care Med 2013; 188 (07) 878-880
- 75 Yeung JC, Wagnetz D, Cypel M. et al. Ex vivo adenoviral vector gene delivery results in decreased vector-associated inflammation pre- and post-lung transplantation in the pig. Mol Ther 2012; 20 (06) 1204-1211
- 76 Machuca TN, Cypel M, Bonato R. et al. Safety and efficacy of ex vivo donor lung adenoviral IL-10 gene therapy in a large animal lung transplant survival model. Hum Gene Ther 2017; 28 (09) 757-765
- 77 Machuca TN, Cypel M, Bonato R. et al. Safety and Efficacy of ex vivo donor lung adenoviral IL-10 gene therapy in a large animal lung transplant survival model. Hum Gene Ther 2017; 28 (09) 757-765
- 78 Jha D, Sachdeva S, Sulania A, Sachdeva R, Kaur G. Organ donation and transplantation: an updated overview. MAMC J Med Sci 2016; 2 (01) 18-27
- 79 Gonçalves GAR, Paiva RMA. Gene therapy: advances, challenges and perspectives. Einstein (Sao Paulo) 2017; 15 (03) 369-375
- 80 Loor G, Howard BT, Spratt JR. et al. Prolonged EVLP using OCS lung: cellular and acellular perfusates. Transplantation 2016
- 81 Takahashi M, Andrew Cheung HY, Watanabe T. et al; Extended Pig EVLP Research Group. Strategies to prolong homeostasis of ex vivo perfused lungs. J Thorac Cardiovasc Surg 2020; (e-pub ahead of print). DOI: 10.1016/j.jtcvs.2020.07.104.
- 82 Hozain AE, Tipograf Y, Pinezich MR. et al. Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine. J Thorac Cardiovasc Surg 2020; 159 (04) 1640-1653
- 83 Hozain AE, O'Neill JD, Pinezich MR. et al. Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs. Nat Med 2020; 26 (07) 1102-1113
- 84 Patterson GA, Cooper JD, Goldman B. et al. Technique of successful clinical double-lung transplantation. Ann Thorac Surg 1988; 45 (06) 626-633
- 85 Keshavjee SH, Yamazaki F, Cardoso PF, McRitchie DI, Patterson GA, Cooper JD. A method for safe twelve-hour pulmonary preservation. J Thorac Cardiovasc Surg 1989; 98 (04) 529-534
- 86 Keshavjee SH, Yamazaki F, Yokomise H. et al. The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation. J Thorac Cardiovasc Surg 1992; 103 (02) 314-325
- 87 Fischer S, Matte-Martyn A, De Perrot M. et al. Low-potassium dextran preservation solution improves lung function after human lung transplantation. J Thorac Cardiovasc Surg 2001; 121 (03) 594-596
- 88 Yeung JC, Krueger T, Yasufuku K. et al. Outcomes after transplantation of lungs preserved for more than 12 h: a retrospective study. Lancet Respir Med 2016; 2600 (16) 1-6
- 89 Hsin MKY, Iskender I, Nakajima D. et al. Extension of donor lung preservation with hypothermic storage after normothermic ex vivo lung perfusion. J Heart Lung Transplant 2016; 35 (01) 130-136
- 90 Date H, Lima O, Matsumura A, Tsuji H, d'Avignon DA, Cooper JD. In a canine model, lung preservation at 10 degrees C is superior to that at 4 degrees C. A comparison of two preservation temperatures on lung function and on adenosine triphosphate level measured by phosphorus 31-nuclear magnetic resonance. J Thorac Cardiovasc Surg 1992; 103 (04) 773-780
- 91 Wang LS, Yoshikawa K, Miyoshi S. et al. The effect of ischemic time and temperature on lung preservation in a simple ex vivo rabbit model used for functional assessment. J Thorac Cardiovasc Surg 1989; 98 (03) 333-342
- 92 Date H, Matsumura A, Manchester JK, Cooper JM, Lowry OH, Cooper JD. Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation. The maintenance of aerobic metabolism during lung preservation. J Thorac Cardiovasc Surg 1993; 105 (03) 492-501
- 93 Ali A, Gomes B, Wang A. et al. Revisiting an old concept in a new era: 36 hour lung preservation using 10°C static cold storage. J Heart Lung Transplant 2020; 39 (04) S147