A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome

Abstract

Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review on the clinical, physiological, radiological, histological and cellular level of PGD. PGD is graded based on hypoxemia and chest X-ray (CXR) infiltrates. High-grade PGD is associated with inferior outcome after LTx. Lung edema is the main characteristic of PGD and alters pulmonary compliance, gas exchange and circulation. A conventional CXR provides a rough estimate of lung edema, while a chest computed tomography (CT) results in a more in-depth analysis. Macroscopically, interstitial and alveolar edema can be distinguished below the visceral lung surface. On the histological level, PGD correlates to a pattern of diffuse alveolar damage (DAD). At the cellular level, ischemia-reperfusion injury (IRI) is the main trigger for the disruption of the endothelial-epithelial alveolar barrier and inflammatory cascade. The multilevel approach integrating all PGD-related aspects results in a better understanding of acute lung failure after LTx, providing novel insights for future therapies.

S100A8/A9 as a prognostic biomarker in lung transplantation

“…The present study also showed that PGD grade was a prognostic marker, as previously reported. 26,27 Although S100A8/A9 was also a prognos-tic marker, there was no significant correlation between S100A8/A9 and PGD grade. In addition, a high S100A8/A9 level was an independent prognostic factor according to the multivariable analysis.…”

Effect of intraoperative support mode on circulating inflammatory biomarkers after lung transplantation surgery

“…The pathogenesis of PGD is characterized by ischemiareperfusion that leads to inflammatory activation, endothelial cell dysfunction, pulmonary edema, and hypoxia. 14 This can result in substantial short-term morbidity, as well as long-term graft complications. 15,22,23 Inflammatory mediators detected in the blood of patients after LTx have been associated with PGD.…”

“…7 The pathogenesis of PGD includes activation of the innate immune system, as evidenced by increased circulating plasma levels of inflammatory chemokines and cytokines. [11][12][13][14] This inflammatory activation is also involved in acute and chronic rejection. 15 Thus, identifying potentially modifiable events that activate the immune response at the time of reperfusion is of substantial importance to the transplant community.…”

“…The pathogenesis of PGD includes activation of the innate immune system, as evidenced by increased circulating plasma levels of inflammatory chemokines and cytokines 11–14 . This inflammatory activation is also involved in acute and chronic rejection 15 .…”

Advances in Lung Transplantation

“…The theme of PGD is assessed by an up-to-date review from the Leuven group; clinical, physiological, radiological and histological aspects are discussed, since a better understanding of acute lung failure after LTx can provide novel insights for future therapies [ 12 ].…”