The Toronto group performed the first clinical trial and currently has the largest clinical experience with EVLP – almost 200 clinical intent EVLP cases have been performed to date [47,48]. In 2012, the team reported their clinical experience with an initial 50 donor lungs that met criteria for EVLP and were subsequently transplanted. All lungs were sourced from DCD donors or initially unsuitable DBD donors, and EVLP duration was 4–6 h. During this time, bronchoscopies and radiographic images were performed at 1 and 3 h. During each hour, PaO2/FiO2, pulmonary artery pressure, lung compliance and peak airway pressure were assessed. Stable readings or improvements in these parameters, alongside a delta PaO2/FiO2 more than 350 mmHg, qualified these lungs for transplantation. PGD3, extracorporeal life support, bronchial complications, duration of mechanical ventilation, ICU and hospital LOS, as well as 30-day, 1-year and 3-year mortality rates were similar in the EVLP group compared with a control LTx group whose donor lungs were not treated with EVLP [47,48]. The Toronto group also published the functional outcomes and QOL of the first 63 patients receiving lungs treated with EVLP and compared these findings to those of 340 conventional donor lung recipients contemporarily transplanted. Five-year survival rates in the EVLP group were 71% vs. 57% in the control group (P > 0.05). Absence of chronic lung allograft dysfunction, highest forced expiratory volume in 1 s predicted, change in 6-min walk distance and the number of ACR episodes were similar between the two groups (P > 0.05). QOL was significantly improved in both groups compared with the time period before LTx. There were no differences in QOL improvement between EVLP and conventional lung groups [49▪▪]. These early- and mid-term results were confirmed worldwide in recent studies: PGD3, ICU and hospital LOS, 30-days and 1-year survival rates are not negatively affected by the use of EVLP [50–54]. Normothermic EVLP results in an increase of viable lungs in the donor pool by at least 20–30% [6,50,53].
An emerging clinical interest of EVLP is the assessment of lung allografts from DCD donors. cDCD donor lungs may experience relatively heightened injury and deterioration as a result of the withdrawal of life-sustaining therapies. The utilization rates of these lungs have traditionally been poor. Through assessment and treatment prior to transplant, EVLP could increase the safety and utilization of extended-criteria cDCD donor lungs. Specifically, EVLP provides the opportunity to thoroughly evaluate these lungs and confirm good lung function prior to initiating LTx. In 2015, the Toronto group reported their DCD LTx experience. First, they compared 55 cDCD LTx to 570 date-matched DBD LTx, and then compared 27 DCD LTx managed without EVLP (DCD-no EVLP group) to 28 DCD LTx associated with EVLP (DCD-EVLP group). There were no differences between DCD and DBD recipients in the duration of mechanical ventilation, ICU and hospital LOS, and 1-, 3- and 5-year survival rates. Compared with DCD-no EVLP, DCD-EVLP recipients had a shorter hospital LOS (23 [16–42] vs. 18 [14▪,22] days; P = 0.047). Although survival curves were comparable, the 3-year survival rate was notably higher in the DCD-EVLP than the DCD-no EVLP group (71% vs. 51%; P = 0.68) [55▪▪]. In a similar study, the Madrid group used EVLP in eight uDCD donor lungs, resulting in four bilateral LTx. Importantly, no recipients experienced PGD3 .
EVLP can be an ideal platform for delivering specific therapies to injured donor lungs. Injuries (including edema [57,58], inflammation [59,60], infection [60–62], aspiration [63,64], pulmonary embolism [65,66] and injury related to DCD-) and EVLP-specific treatments are listed in Table 4. Together, these preliminary results provide great promise for the continued development of injured donor lung rehabilitation and donor pool expansion strategies.
LTx using DCD donor lungs is now a clinical reality. Outcomes from the use of cDCD donor lungs are similar to those of DBD donor lungs. uDCD represents a significant potential additional lung allograft source. It is established that LTx from uCDC is feasible, but retrieval and assessment protocols should be optimized in order to decrease PGD incidence.
Living-donor LLTx is an emergent alternative strategy to expand the donor lung pool for critically ill children and small adult patients. Recipient outcomes are similar to those of cadaveric patients. Nevertheless, the specific issue related to the living donor makes the utilization of this technique a challenge.
Lung preservation and reconditioning using EVLP technology is now well established and outcomes are, at the very least, similar to that of cold static preservation. With the emergence of EVLP technology in the use of DCD lungs, clinicians can now better assess acutely injured lungs. Indeed, this technology represents an ex-vivo arsenal platform able to provide specific therapies for targeted injuries. It is hoped that better knowledge across all of these fields will soon enable clinicians to expand and use the full potential of the donor organ pool.
Papers of particular interest, published within the annual period of review, have been highlighted as:
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11▪▪. Krutsinger D, Reed RM, Blevins A, et al. Lung transplantation from donation after cardiocirculatory death: systematic review and meta-analysis. J Heart Lung Transplant 2014; 34:675–684.
This paper describes the only meta-analysis published studying the results of the lung transplantation from donation after cardiocirculatory death.
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This paper is related to a well designed unicenter study with long term follow-up comparing lung transplantation results from cardiocirculatory death donor vs. brain death donors.
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23▪▪. Date H, Sato M, Aoyama A, et al. Living-donor lobar lung transplantation provides similar survival to cadaveric lung transplantation even for very ill patients. Eur J Cardio Thorac Surg 2015; 47:967–972.
This paper describes the experience of the highest level center of living-donor lobar lung transplantation and compares results of lung transplantation using lobar lung living donors vs. cadaveric donors.
24. Chen F, Fujinaga T, Shoji T, et al. Short-term outcome in living donors for lung transplantation: the role of preoperative computer tomographic evaluations of fissures and vascular anatomy. Transplant Int 2012; 25:732–738.
25. Chen F, Oga T, Sakai H, et al. A prospective study analyzing one-year multidimensional outcomes in living lung transplant donors. Am J Transplant 2013; 13:3003–3009.
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This article describes the results of the cadaveric lobar lung transplantation with the largest cohort size published.
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44. De Perrot M, Imai Y, Volgyesi GA, et al. Effect of ventilator-induced lung injury on the development of reperfusion injury in a rat lung transplant model. J Thorac Cardiovasc Surg 2002; 124:1137–1144.
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46. Mulloy DP, Stone ML, Crosby IK, et al. Ex vivo rehabilitation of nonheart-beating donor lungs in preclinical porcine model: delayed perfusion results in superior lung function. J Thorac Cardiovasc Surg 2012; 144:1208–1215.
47. Cypel M, Yeung JC, Liu M, et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 2011; 364:1431–1440.
48. Cypel M, Yeung JC, Machuca T, et al. Experience with the first 50 ex vivo lung perfusions in clinical transplantation. J Thorac Cardiovasc Surg 2012; 144:1200–1206.
49▪▪. Tikkanen J, 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; 34:547–556.
This paper is published by the group with the highest level of clinical experience with ex-vivo lung perfusion. It is the only paper studying the long-term outcomes after lung transplantation using ex-vivo lung perfusion.
50. Valenza F, Rosso L, Coppola S, et al. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation. Transplant Int 2014; 27:553–561.
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52. Boffini M, Ricci D, Bonato R, et al. Incidence and severity of primary graft dysfunction after lung transplantation using rejected graft reconditioned with ex vivo lung perfusion. Eur J Cardiothorac Surg 2014; 46:789–793.
53. Henriksen IS, Moller-Sorensen H, Moller CH, et al. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation. Dan Med J 2014; 61:A4809.
54. Fildes JE, Archer LD, Blaikley J, et al. Clinical outcome of patients transplanted with marginal donor lungs via ex vivo lung perfusion compared to standard lung transplantation. Transplantation 2015; 99:1078–1083.
55▪▪. Machuca TN, Mercier O, Collaud S, et al. Lung transplantation with donation after circulatory determination of death donors and the impact of ex vivo lung perfusion. Am J Transplant 2015; 15:993–1002.
This paper is published by the group with the highest level of clinical experience with ex vivo lung perfusion. It is the only paper specifically describing the impact of the ex vivo lung perfusion after cardiocirculatory death donation.
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58. Valenza F, Rosso L, Coppola S, et al. Beta-adrenergic agonist infusion during extracorporeal lung perfusion: effects on glucose concentration in the perfusion fluid and on lung function. J Heart Lung Transplant 2012; 31:524–530.
59. Cypel M, Liu M, Rubacha M, et al. Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med 2009; 1:4ra9.
60. Lee JW, Fang X, Gupta N, et al. Allogenic human mesenchymal stem cells for treatment of E. coli
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66. 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; 188:878–880.
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