Exploring predisposing factors and pathogenesis contributing to injuries of donor lungs

ABSTRACTIntroduction Lung transplantation (LTx) remains the only therapeutic strategy for patients with incurable lung diseases. However, its use has been severely limited by the narrow donor pool and potential concerns of inferior quality of donor lungs, which are more susceptible to external influence than other transplant organs. Multiple insults, including various causes of death and a series of perimortem events, may act together on donor lungs and eventually culminate in primary graft dysfunction (PGD) after transplantation as well as other poor short-term outcomes.Areas covered This review focuses on the predisposing factors contributing to injuries to the donor lungs, specifically focusing on the pathogenesis of these injuries and their impact on post-transplant outcomes. Additionally, various maneuvers to mitigate donor lung injuries have been proposed.Expert opinion The selection criteria for eligible donors vary and may be poor discriminators of lung injury. Not all transplanted lungs are in ideal condition. With the rapidly increasing waiting list for LTx, the trend of using marginal donors has become more apparent, underscoring the need to gain a deeper understanding of donor lung injuries and discover more donor resources.KEYWORDS: Donor selectionlung injurylung transplantationmarginal donor lungsorgan donation Article highlights The significant discrepancy between the increasing demand for LTx and a severe shortage of suitable donor lungs necessitates the use of marginal lungs. A conservative-to-extended transition has occurred in donor selection criteria.Identifying multiple predisposing factors and pathogenetic elements contributing to donor lung injuries is an essential step in procuring more potential donor lungs.Various predisposing factors associated with donor lung injuries are not entirely unrelated. The ultimate activation of the innate immune system and inflammatory cascade accounts for the shared mechanisms of lung injury.Ex vivo lung perfusion is emerging as a promising platform for optimizing donor lung quality and increasing lung graft pool.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer DisclosuresA reviewer has disclosed that they were a principal investigator in the Inspire trial. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.AbbreviationARDS, acute respiratory distress syndrome; BD, Brain death; CA, circulatory arrest; CMV, cytomegalovirus; COVID-19, Corona Virus Disease; CPB, Cardiopulmonary bypass; CSP, cold static preservation; DAMPs, damage-associated molecular patterns; DBD, donation after brain death; DCD, donation after circulatory death; ECD, extended criteria donor; ECLS, extracorporeal life support; ECMO, extracorporeal membrane oxygenation; EVLP, ex vivo lung perfusion; HAP, hospital-acquired pneumonia; HBV, hepatitis B; HCV, hepatitis C; HIV, human immunodeficiency virus; ICP, intracranial pressure; ICU, intensive care units; IFN-β, interferon-β; IR, ischemia-reperfusion; IRF-3, interferon regulatory factor-3; ISHLT, International Society for Heart and Lung Transplantation; LTx, lung transplantation; LPS, lipopolysaccharide; mPTP, mitochondrial permeability transition pore; MYD88, myeloid differentiation factor 88; NETs, neutrophil extracellular traps; NF-κB, nuclear factor κB; NLRP3, NOD-like receptor thermal protein domain associated protein 3; NPE, neurogenic pulmonary edema; OCS, Organ Care System; PAMPs, pathogen-associated molecular patterns; PCD, programmed cell death; PCR, polymerase chain reaction; PE, Pulmonary embolism; PGD, primary graft dysfunction; PRRs, pattern recognition receptors; SILI, patient-self-inflicted lung injury; RBC, red blood cell; ROS, reactive oxygen species; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SI-ALI, smoke inhalation-induced acute lung injury; TLRs, toll-like receptors; TRALI, transfusion-related acute lung injury; VAP, ventilator-associated pneumonia; VILI, ventilator-induced lung injury.Additional informationFundingThis work was supported by the National Natural Science Foundation of China (No. 82170107) (Z.M.W.), the Program of Shanghai Municipal Health Commission, China (No. 202140406) (Z.M.W.), and the Subject Leader Program of Shanghai Municipal Health Commission (No. 2022XD007) (Z.M.W.).