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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Survival difference between high-risk and low-risk CFTR genotypes after lung transplant

      Background

      While cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with clinical outcomes in cystic fibrosis patients, it is unknown if genotype impacts lung transplant outcomes. We sought to compare lung transplant survival and time to bronchiolitis obliterans syndrome (BOS) between high-risk, low-risk, and not yet classified CFTR genotypes.

      Methods

      We used merged data from the Organ Procurement and Transplantation Network (2005-2017) and United States Cystic Fibrosis Foundation Patient Registry (2005-2016). Cox Proportional Hazards models compared graft failure after lung transplant and time to BOS among high-risk, low-risk, and not yet classified risk CFTR genotype classes.

      Results

      Among 1,830 cystic fibrosis lung transplant recipients, median survival for those with low-risk, high-risk, and not yet classified genotype was 9.83, 6.25, and 5.75 years, respectively. Adjusted Cox models showed recipients with a low-risk genotype had 39% lower risk of death or re-transplant compared to those with high-risk genotype (adjusted HR 0.61, 95% CI = 0.40, 0.91). A subset of 1,585 lung transplant recipients were included in the BOS subgroup analysis. Adjusted analyses showed no significant difference of developing BOS among high-risk, low-risk, or not yet classified genotypes.

      Conclusions

      Lung transplant recipients with low-risk CFTR genotype have better survival after transplant compared to recipients with high-risk or not yet classified genotypes. Given these differences, future studies evaluating the mechanism by which CFTR genotype affects post-transplant survival could identify potential targets for intervention.

      Keywords

      Abbreviations:

      (CFTR) (cystic fibrosis transmembrane conductance receptor), (CLAD) (chronic lung allograft dysfunction), (CF) (cystic fibrosis), (FEV1) (forced expiratory volume in one second), (BMI) (body mass index), (OPTN) (Organ Procurement and Transplantation Network), (CFFPR) (Cystic Fibrosis Foundation Patient Registry), (BOS) (bronchiolitis obliterans syndrome), (LAS) (lung allocation score), (ECMO) (extracorporeal membrane oxygenation), (ICU) (intensive care unit), (CMV) (cytomegalovirus)
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