BACKGROUND: Club Cell Secretory Protein (CCSP) G38A polymorphism has recently been involved in lung epithelial susceptibility to external injuries. Lung transplantation (LT) is currently limited by ischemia-reperfusion injury leading to primary graft dysfunction (PGD). We thus hypothesized that donor CCSP G38A polymorphism might impact the risk of PGD after LT. METHODS: We focused on LT included in the French multicentric Cohort in Lung Transplantation (COLT), performed between January 2009 and December 2014, and associated with preoperative blood samples from the donor and the recipient. Characteristics of the donors, recipients, procedures, early and late outcomes were prospectively recorded in COLT. The CCSP serum concentration and CCSP gene G38A polymorphism were retrospectively determined in a blind manner. Their association with grade 3 PGD was studied in univariate and multivariate analysis. RESULTS: The study group included 104 LT donors and recipients, 84 with grade 0 to 2 PGD and 20 with grade 3 PGD. Preoperative CCSP serum concentration was significantly higher in the donors (median, 22.54 ng/mL; interquartile range, 9.6-43.9) than in the recipients (median, 7.03 ng/mL; interquartile range, 0.89-19.2; P \\textless 0.001) but none impacted the risk of grade 3 PGD (P = 0.93 and P = 0.69, respectively). Donor CCSP G38A polymorphism was associated with a decreased risk of grade 3 PGD in univariate (AG + AA 3/21 = 14.2% vs GG 10/26 = 38.4%, P = 0.044) and multivariate analysis (odds ratio associated with AG + AA, 0.22; 95% confidence interval, 0.041-0.88; P = 0.045), but recipient CCSP G38A polymorphism was not. CONCLUSIONS: Donor CCSP G38A polymorphism is associated with a decreased risk of severe PGD after LT in the COLT study. These findings should be confirmed in the frame of a prospective study.