Risk Factors for Primary Graft Dysfunction in Patients with Cystic Fibrosis Receiving Lung Transplants

Abstract

Purpose The primary driver of poor outcomes in the early stages of lung transplantation is primary graft dysfunction (PGD). Patients with cystic fibrosis (CF) have unique physiology and demographics compared to other lung transplant recipients. Therefore, we sought to identify risk factors for PGD in the CF patient population undergoing lung transplantation. Methods We utilized clinical data on lung transplant recipients with CF and their donors from the Lung Transplant Outcomes Group cohort, a multi-center prospective cohort study of PGD pathogenesis. The primary outcome was grade 3 PGD within the first 72 hours after transplantation. Potential covariates were identified in univariate analysis and assessed for collinearity. Independent PGD risk factors were identified using multivariate logistic regression. A sensitivity analysis was performed using grade 3 PGD 48 to 72 hours after transplantation. Results We identified 195 patients with CF who received lung transplants between August 2014 and June 2018 across ten centers. Grade 3 PGD developed in 80 subjects (41%). Risk factors for PGD in CF patients based on the multivariable model were white donor race (odds ratio [OR]: 2.6, 95% confidence interval [CI]: 1.4-5.1), any positive panel reactive antibodies (PRA) (OR: 2.2, 95% CI: 1.0-4.7), recipient female gender (OR: 2.1, 95% CI: 1.1-3.9), intraoperative cardiopulmonary bypass use (OR: 2.2, 95% CI: 1.2-4.2), increasing lung allocation score (LAS) (OR: 1.2 per 10 point increase in LAS, 95% CI: 1.0-1.4), and ECMO (extracorporeal membrane oxygenation) bridge to transplant (OR: 2.7, 95% CI: 1.1-6.7). LAS and ECMO were assessed in separate models due to their collinearity. Mean pulmonary artery pressure at the time of transplant was included as a potential confounder. Similar findings were seen in a more severe phenotype of PGD that developed 48 to 72 hours after transplant. Conclusion The CF population is often considered to be at low risk of PGD, however we observed a relatively high rate of PGD in this study. Any positive PRA, female recipient gender, intraoperative bypass, increasing LAS, and ECMO are PGD risk factors that have been identified non-CF transplant populations. We validated these risk factors in recipients with CF. White donor race is a novel risk factor that has not been previously identified in lung transplant recipients with another primary diagnosis.