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Primary graft dysfunction: lessons learned about the first 72?h after lung transplantation.

ABSTRACT: In 2005, the International Society for Heart and Lung Transplantation published a standardized definition of primary graft dysfunction (PGD), facilitating new knowledge on this form of acute lung injury that occurs within 72?h of lung transplantation. PGD continues to be associated with significant morbidity and mortality. This article will summarize the current literature on the epidemiology of PGD, pathogenesis, risk factors, and preventive and treatment strategies.Since 2011, several manuscripts have been published that provide insight into the clinical risk factors and pathogenesis of PGD. In addition, several transplant centers have explored preventive and treatment strategies for PGD, including the use of extracorporeal strategies. More recently, results from several trials assessing the role of extracorporeal lung perfusion may allow for much-needed expansion of the donor pool, without raising PGD rates.This article will highlight the current state of the science regarding PGD, focusing on recent advances, and set a framework for future preventive and treatment strategies.

SUBMITTER: Porteous MK

PROVIDER: S-EPMC4624097 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other

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Primary graft dysfunction: lessons learned about the first 72 h after lung transplantation.

Porteous Mary K MK Diamond Joshua M JM Christie Jason D JD

Current opinion in organ transplantation 20151001 5

<h4>Purpose of review</h4>In 2005, the International Society for Heart and Lung Transplantation published a standardized definition of primary graft dysfunction (PGD), facilitating new knowledge on this form of acute lung injury that occurs within 72 h of lung transplantation. PGD continues to be associated with significant morbidity and mortality. This article will summarize the current literature on the epidemiology of PGD, pathogenesis, risk factors, and preventive and treatment strategies.<h ...[more]

PMID: 26262465

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Project description:BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear. We proposed that local complement activation would help identify those who develop PGD after LTx. We also aimed to identify which complement activation pathways are associated with PGD.METHODSWe performed a multicenter cohort study at the University of Pennsylvania and Washington University School of Medicine. Bronchoalveolar lavage (BAL) and plasma specimens were obtained from recipients within 24 hours after LTx. PGD was scored based on the consensus definition. Complement activation products and components of each arm of the complement cascade were measured using ELISA.RESULTSIn both cohorts, sC4d and sC5b-9 levels were increased in BAL of subjects with PGD compared with those without PGD. Subjects with PGD also had higher C1q, C2, C4, and C4b, compared with subjects without PGD, suggesting classical and lectin pathway involvement. Ba levels were higher in subjects with PGD, suggesting alternative pathway activation. Among lectin pathway-specific components, MBL and FCN-3 had a moderate-to-strong correlation with the terminal complement complex in the BAL but not in the plasma.CONCLUSIONComplement activation fragments are detected in the BAL within 24 hours after LTx. Components of all 3 pathways are locally increased in subjects with PGD. Our findings create a precedent for investigating complement-targeted therapeutics to mitigate PGD.FUNDINGThis research was supported by the NIH, American Lung Association, Children's Discovery Institute, Robert Wood Johnson Foundation, Cystic Fibrosis Foundation, Barnes-Jewish Hospital Foundation, Danish Heart Foundation, Danish Research Foundation of Independent Research, Svend Andersen Research Foundation, and Novo Nordisk Research Foundation.

Dataset Information

Primary graft dysfunction: lessons learned about the first 72?h after lung transplantation.

Publications

Primary graft dysfunction: lessons learned about the first 72 h after lung transplantation.

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