INTRODUCTION
Normothermic ex vivo lung perfusion (EVLP) has emerged as a promising technique to expand the donor pool by assessing and reconditioning donor lungs previously considered unsuitable for transplant [1]. The lung is highly susceptible to injury in the critical care environment, and in the hours or days leading up to the donor’s demise it may be exposed to the sequelae of brain-stem death together with infection, aspiration, barotrauma, fluid overload or multiple transfusions [2–4]. Because the extent of lung injury is difficult to assess at the time of organ procurement, donor acceptance criteria are therefore conservative and poor discriminators of injury and infection in the donor lung [5]. The increased use of extended-criteria donors may further elevate the risk of primary graft dysfunction (PGD) and other more severe postoperative complications [6–8].
The use of ex vivo reconditioned donor lungs is steadily growing and now accounts for about 20% of the activity in some established centres [9–11]. The decision to accept organs for transplant after EVLP has, however, been based on the same questionable physiological measures and organ appearance used during standard procurement. Reported discard rates of 10–60% of perfused lungs suggest that some donor lungs may be inappropriately used or declined for transplant after EVLP [1].
In donor lungs transplanted without exvivo evaluation, there is an established relationship between their inflammatory burden and early outcome [12–15]. However, this phenomenon has not been as extensively investigated during EVLP.
In this proof-of-concept study, we evaluated a panel of inflammatory mediators and tissue injury-associated proteins in both perfusate and bronchoalveolar lavage fluid (BALF) from human donor lungs undergoing clinical EVLP with intent for transplant. The panel was based on our own previous work and on available studies of biological markers in standard lung transplant and preclinical and clinical observations during EVLP. The aim was to assess the potential for specific protein markers in perfusate and BALF to distinguish which donor lungs, initially deemed unsuitable for immediate transplantation are most likely to successfully recondition during EVLP and thereby provide a basis for further investigations in a larger validation cohort.