Lung transplantation (LTx) is the ultimate therapy for patients suffering from end-stage lung diseases, prolonging survival and improving quality of life.1 However, this treatment remains limited due to the relative shortage of organ donors and acceptable pulmonary grafts (15–30%).2 Therefore, the number of patients waiting for lung transplantation still greatly exceeds the number of donor lungs available, resulting in a current wait list mortality up to 30%.3 Over the last decade several strategies were implemented in transplant centers worldwide to expand the available lung donor pool, including the use of lungs from extended-criteria donors, lobar transplantation, and an increase in the rate of donors after circulatory death (DCD).4 Most of these lung grafts, however, have an increased risk of lung injury that may lead to primary graft dysfunction (PGD) and long-term consequences for LTx recipients. These challenges have prompted clinicians and scientists to grasp the opportunity of the ex situ phase (between procurement and transplantation) for further evaluation and reconditioning of pulmonary grafts. To take advantage of this opportunity, however, it is necessary to preserve donor lungs under safe conditions. One strategy, termed ex vivo lung perfusion (EVLP), attempts to maintain donor lungs in a physiologic state prior to transplantation through ventilation and normothermic perfusion of the graft (Fig. 115-1).5 A major advantage of normothermic preservation, compared with cold storage, is that it maintains lung metabolism and function, resulting in prolonged assessment of the organ, active reconditioning and treatment, and hopefully in the future genetic therapy and immunomodulation. This chapter describes the technical aspects of EVLP, reviews the existing modules currently available, covers the different protocols, and focuses on four potential benefits: organ preservation, assessment, repair, and immunomodulation.
Donor lungs preserved and assessed on an ex vivo normothermic lung perfusion device (OCSTM, Transmedics, Andover, USA).
In 1935 Alexis Carrel and Charles Lindbergh originally postulated that normothermic ex vivo organ perfusion could maintain organs viable for several days.6 In 1970 Jirsch et al. described EVLP as a method to assess the quality of the pulmonary graft during storage using a canine model.7 However, clinical attempts at EVLP in those eras largely failed because of an inability to maintain the air/fluid barrier integrity within the lung, which led to the development of edema and increased pulmonary vascular resistance in the donor lung.8 In 2001, the concept of EVLP was clinically reintroduced by Steen et al. as a technique to evaluate lungs from an uncontrolled DCD prior to transplantation and as a platform to recondition an unacceptable lung from a donor after brain death (DBD).9,10 These unique case reports demonstrated that lungs could be transplanted successfully after a period of warm ischemia and ex vivo perfusion. This clinical breakthrough stimulated research groups worldwide ...