50 VE-Cadherin Is Associated with Primary Graft Dysfunction in Lung Transplant Recipients

Abstract

Purpose: Primary Graft Dysfunction (PGD) after lung transplantation is the result of ischemia-reperfusion (I-R) injury. Abnormal activation of innate immunity, in response to I-R injury, mediated by Toll-like receptors and interleukin-1 induced long pentraxin-3 (PTX3) release leading to complement activation may play a role in PGD pathogenesis. We hypothesized that elevated PTX3 levels are associated with PGD. Methods and Materials: We performed a case control study of lung transplant recipients with Idiopathic Pulmonary Fibrosis (IPF) or Chronic Obstructive Pulmonary Disease (COPD) from the multicenter, prospective Lung Transplant Outcomes Group cohort. PTX3 levels were measured pre-transplant, and 6 and 24 hours post reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. Multivariable logistic regression was used to evaluate for effect modification and confounding. Results: Of the 119 subjects evaluated, there were 40 cases and 79 nonPGD controls. Twenty-four cases (40%) and 47 controls (59%) had IPF. Pre-transplant PTX3 levels were significantly higher in IPF (2.15ng/ml) than COPD (0.81ng/ml), p 0.01. Overall, the odds of developing PGD per standard deviation increase in PTX3 level at 6 hours was 1.2 (p 0.5) and at 24 hours was 1.4 (p 0.07). Pre-transplant diagnosis was an effect modifier of the relationship between PTX3 level and PGD; among patients with IPF, PTX3 levels at 6 and 24 hours were associated with PGD (OR 3.9, p 0.02 at 6hrs; OR 2.4, p 0.008 at 24hrs), with no apparent association in COPD patients (interaction p 0.03). The relationship between PTX3 level and PGD in IPF subjects was not attenuated by intraoperative pulmonary artery systolic pressure, surgical type, or cardiopulmonary bypass use. Conclusions: Elevated PTX3 levels were associated with the development of PGD after lung transplantation in IPF patients. Pre-transplant levels were also elevated in IPF patients compared with COPD patients. Elucidating differences in innate immune activation in IPF compared to COPD in lung transplant recipients is an area of future study.