Primary Graft Dysfunction in Lung Transplantation: A Review of Mechanisms and Future Applications

Abstract

Lung allograft recipients have worse survival than all other solid organ transplant recipients, largely because of primary graft dysfunction (PGD), a major form of acute lung injury affecting a third of lung recipients within the first 72 h after transplant. PGD is the clinical manifestation of ischemia–reperfusion injury and represents the predominate cause of early morbidity and mortality. Despite PGD’s impact on lung transplant outcomes, no targeted therapies are currently available; hence, care remains supportive and largely ineffective. This review focuses on molecular and innate immune mechanisms of ischemia–reperfusion injury leading to PGD. We also discuss novel research aimed at discovering biomarkers that could better predict PGD and potential targeted interventions that may improve outcomes in lung transplantation.

Impact of Pre-Transplant Left Ventricular Diastolic Pressure on Primary Graft Dysfunction after Lung Transplantation: A Narrative Review

“…Furthermore, the infiltration of neutrophils into the alveoli is a recognized pathological aspect of IRI in the transplanted lungs, potentially leading to an amplification of cytokine release [45,52]. Finally, proinflammatory cytokines involved in HF pathogenesis include TNF-α, IL-6, IL-8, IL-10, IL-1α, IL-1β, IL-2, TGF-β, and IFN-γ, paralleling those associated with IRI in PGD [53,54].…”

Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury

“…Lung transplantation (LTx) has emerged as a life-saving option for thousands of patients with end-stage lung disease (ESLD) [ 1 ]. While significant progress has been achieved in organ preservation, surgical techniques, and transplant rejection treatment in recent years, the persistent challenge of primary graft dysfunction (PGD) continues to impact post-LTx morbidity and mortality [ 2 , 3 ]. PGD typically presents within the first 72 h after LTx, and lung ischemia/reperfusion (I/R) injury is widely recognized as a primary trigger of PGD [ 4 ].…”

Mesenchymal Stromal Cell Therapy in Lung Transplantation

“…Almost 5000 lung transplants are reported annually in the International Society of Heart and Lung Transplantation Registry, and the results have improved over time [ 1 ]. However, the median survival of lung transplant recipients is limited to less than 7 years, and the main obstacles are primary graft dysfunction (PGD), acute rejection, chronic lung allograft dysfunction (CLAD), and side-effects of immunosuppressive drugs [ 2 , 3 , 4 , 5 ].…”