Pathophysiology and classification of primary graft dysfunction after lung transplantation

Abstract

The term primary graft dysfunction (PGD) incorporates a continuum of disease severity from moderate to severe acute lung injury (ALI) within 72 h of lung transplantation. It represents the most significant obstacle to achieving good early post-transplant outcomes, but is also associated with increased incidence of bronchiolitis obliterans syndrome (BOS) subsequently. PGD is characterised histologically by diffuse alveolar damage, but is graded on clinical grounds with a combination of PaO2/FiO2 (P/F) and the presence of radiographic infiltrates, with 0 being absence of disease and 3 being severe PGD. The aetiology is multifactorial but commonly results from severe ischaemia-reperfusion injury (IRI), with tissue-resident macrophages largely responsible for stimulating a secondary 'wave' of neutrophils and lymphocytes that produce severe and widespread tissue damage. Donor history, recipient health and operative factors may all potentially contribute to the likelihood of PGD development. Work that aims to minimise the incidence of PGD in ongoing, with techniques such as ex vivo perfusion of donor lungs showing promise both in research and in clinical studies. This review will summarise the current clinical status of PGD before going on to discuss its pathophysiology, current therapies available and future directions for clinical management of PGD.

Keywords: Primary graft dysfunction (PGD); ex vivo lung perfusion (EVLP); inflammation; ischaemia-reperfusion injury (IRI); oedema.