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


      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.


      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.


      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.


      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.



      (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)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Heart and Lung Transplantation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ramsey BW
        • Davies J
        • McElvaney NG
        • et al.
        A CFTR potentiator in patients with cystic fibrosis and the G551D mutation.
        N Engl J Med. 2011; 365: 1663-1672
        • Middleton PG
        • Mall MA
        • Drevinek P
        • et al.
        Elexacaftor-Tezacaftor-Ivacaftor for cystic fibrosis with a single Phe508del Allele.
        N Engl J Med. 2019; 381: 1809-1819
        • Heijerman HGM
        • McKone EF
        • Downey DG
        • et al.
        Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: A double-blind, randomised, phase 3 trial.
        Lancet. 2019; 394: 1940-1948
        • Thabut G
        • Christie JD
        • Mal H
        • et al.
        Survival benefit of lung transplant for cystic fibrosis since lung allocation score implementation.
        Am J Respir Crit Care Med. 2013; 187: 1335-1340
        • Liou TG
        • Adler FR
        • Cox DR
        • Cahill BC.
        Lung transplantation and survival in children with cystic fibrosis.
        N Engl J Med. 2007; 357: 2143-2152
        • Stephenson AL
        • Sykes J
        • Berthiaume Y
        • et al.
        Clinical and demographic factors associated with post-lung transplantation survival in individuals with cystic fibrosis.
        J Heart Lung Transplant. 2015; 34: 1139-1145
        • Hayes Jr, D
        • Glanville AR
        • McGiffin D
        • Tobias JD
        • Tumin D
        Age-related survival disparity associated with lung transplantation in cystic fibrosis: an analysis of the registry of the International Society for Heart and Lung Transplantation.
        J Heart Lung Transplant. 2016; 35: 1108-1115
        • Meachery G
        • De Soyza A
        • Nicholson A
        • et al.
        Outcomes of lung transplantation for cystic fibrosis in a large UK cohort.
        Thorax. 2008; 63: 725-731
        • Fanen P
        • Wohlhuter-Haddad A
        • Hinzpeter A.
        Genetics of cystic fibrosis: CFTR mutation classifications toward genotype-based CF therapies.
        Int J Biochem Cell Biol. 2014; 52: 94-102
        • McKone EF
        • Goss CH
        • Aitken ML.
        CFTR genotype as a predictor of prognosis in cystic fibrosis.
        Chest. 2006; 130: 1441-1447
        • Stephenson AL
        • Ramos KJ
        • Sykes J
        • et al.
        Bridging the survival gap in cystic fibrosis: an investigation of lung transplant outcomes in Canada and the United States.
        J Heart Lung Transplant. 2020; 40: 201-209
        • Ramos KJ
        • Sykes J
        • Stanojevic S
        • et al.
        Survival and lung transplant outcomes for individuals with advanced cystic fibrosis lung disease living in the United States and Canada: an analysis of National Registries.
        Chest. 2021; 160: 843-853
        • Jennerich AL
        • Pryor JB
        • Wai TYH
        • et al.
        Low body mass index as a barrier to lung transplant in cystic fibrosis.
        J Cyst Fibros. 2021; 21: 475-481
        • Pryor JB
        • Bradford MC
        • Jennerich AL
        • et al.
        Body mass index recovery following lung transplant for cystic fibrosis.
        Ann Am Thorac Soc. 2022; 19: 1130-1138
        • Knapp EA
        • Fink AK
        • Goss CH
        • et al.
        The Cystic Fibrosis Foundation Patient Registry. Design and methods of a National Observational Disease Registry.
        Ann Am Thorac Soc. 2016; 13: 1173-1179
        • Austin PC
        • Lee DS
        • Fine JP.
        Introduction to the analysis of survival data in the presence of competing risks.
        Circulation. 2016; 133: 601-609
        • Sethi J
        • Bugajski A
        • Patel KN
        • et al.
        Recipient age impacts long-term survival in adult subjects with cystic fibrosis after lung transplantation.
        Ann Am Thorac Soc. 2021; 18: 44-50
        • Lehr CJ
        • Blackstone EH
        • McCurry KR
        • Thuita L
        • Tsuang WM
        • Valapour M.
        Extremes of age decrease survival in adults after lung transplant.
        Chest. 2020; 157: 907-915
        • Lewis C
        • Blackman SM
        • Nelson A
        • et al.
        Diabetes-related mortality in adults with cystic fibrosis. Role of genotype and sex.
        Am J Respir Crit Care Med. 2015; 191: 194-200
        • Christie JD
        • Edwards LB
        • Kucheryavaya AY
        • et al.
        The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012.
        J Heart Lung Transplant. 2012; 31: 1073-1086
        • Hackman KL
        • Bailey MJ
        • Snell GI
        • Bach LA.
        Diabetes is a major risk factor for mortality after lung transplantation.
        Am J Transplant. 2014; 14: 438-445
        • Riou M
        • Renaud-Picard B
        • Munch M
        • et al.
        Organized management of diabetes mellitus in lung transplantation: study of glycemic control and patient survival in a single center.
        Transplant Proc. 2019; 51: 3375-3384
        • Hofer M
        • Schmid C
        • Benden C
        • et al.
        Diabetes mellitus and survival in cystic fibrosis patients after lung transplantation.
        J Cyst Fibros. 2012; 11: 131-136
        • Choi KJ
        • Cheng TZ
        • Honeybrook AL
        • et al.
        Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis.
        Int Forum Allergy Rhinol. 2018; 8: 389-393
        • Berkhout MC
        • van Rooden CJ
        • Rijntjes E
        • Fokkens WJ
        • el Bouazzaoui LH
        • Heijerman HG.
        Sinonasal manifestations of cystic fibrosis: A correlation between genotype and phenotype?.
        J Cyst Fibros. 2014; 13: 442-448
        • Ferril GR
        • Nick JA
        • Getz AE
        • et al.
        Comparison of radiographic and clinical characteristics of low-risk and high-risk cystic fibrosis genotypes.
        Int Forum Allergy Rhinol. 2014; 4: 915-920
        • Brook CD
        • Maxfield AZ
        • Ahmed H
        • Sedaghat AR
        • Holbrook EH
        • Gray ST.
        Factors influencing the need for endoscopic sinus surgery in adult patients with cystic fibrosis.
        Am J Rhinol Allergy. 2017; 31: 44-47
        • Augarten A
        • Paret G
        • Avneri I
        • et al.
        Systemic inflammatory mediators and cystic fibrosis genotype.
        Clin Exp Med. 2004; 4: 99-102
        • Kulkarni HS
        • Cherikh WS
        • Chambers DC
        • et al.
        Bronchiolitis obliterans syndrome-free survival after lung transplantation: An International Society for Heart and Lung Transplantation Thoracic Transplant Registry analysis.
        J Heart Lung Transplant. 2019; 38: 5-16
        • Raghavan D
        • Gao A
        • Ahn C
        • et al.
        Lung transplantation and gender effects on survival of recipients with cystic fibrosis.
        J Heart Lung Transplant. 2016; 35: 1487-1496
        • Merlo CA
        • Clark SC
        • Arnaoutakis GJ
        • et al.
        National healthcare delivery systems influence lung transplant outcomes for cystic fibrosis.
        Am J Transplant. 2015; 15: 1948-1957