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Lung size mismatch and primary graft dysfunction after bilateral lung transplantation.

ABSTRACT: Donor-to-recipient lung size matching at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC) ratio (donor pTLC/recipient pTLC). We aimed to determine whether the pTLC ratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT).We calculated the pTLC ratio for 812 adult BLTs from the Lung Transplant Outcomes Group between March 2002 to December 2010. Patients were stratified by pTLC ratio >1.0 ("oversized") and pTLC ratio ?1.0 ("undersized"). PGD was defined as any ISHLT Grade 3 PGD (PGD3) within 72 hours of reperfusion. We analyzed the association between risk factors and PGD using multivariable conditional logistic regression. As transplant diagnoses can influence the size-matching decisions and also modulate the risk for PGD, we performed pre-specified analyses by assessing the impact of lung size mismatch within diagnostic categories.In univariate analyses oversizing was associated with a 39% lower odds of PGD3 (OR 0.61, 95% CI, 0.45-0.85, p = 0.003). In a multivariate model accounting for center-effects and known PGD risks, oversizing remained independently associated with a decreased odds of PGD3 (OR 0.58, 95% CI 0.38 to 0.88, p = 0.01). The risk-adjusted point estimate was similar for the non-COPD diagnosis groups (OR 0.52, 95% CI 0.32 to 0.86, p = 0.01); however, there was no detected association within the COPD group (OR 0.72, 95% CI 0.29 to 1.78, p = 0.5).Oversized allografts are associated with a decreased risk of PGD3 after BLT; this effect appears most apparent in non-COPD patients.

SUBMITTER: Eberlein M

PROVIDER: S-EPMC4329253 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Lung size mismatch and primary graft dysfunction after bilateral lung transplantation.

Eberlein Michael M Reed Robert M RM Bolukbas Servet S Diamond Joshua M JM Wille Keith M KM Orens Jonathan B JB Brower Roy G RG Christie Jason D JD

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20140928 2

<h4>Background</h4>Donor-to-recipient lung size matching at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC) ratio (donor pTLC/recipient pTLC). We aimed to determine whether the pTLC ratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT).<h4>Methods</h4>We calculated the pTLC ratio for 812 adult BLTs from the Lung Transplant Outcomes Group between March 2002 to December 2010. Patients were stratified by pTLC ratio >1. ...[more]

PMID: 25447586

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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

Lung size mismatch and primary graft dysfunction after bilateral lung transplantation.

Publications

Lung size mismatch and primary graft dysfunction after bilateral lung transplantation.

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