CFTR genotype as a predictor of prognosis in cystic fibrosis

Chest. 2006 Nov;130(5):1441-7. doi: 10.1378/chest.130.5.1441.


Study rationale: Certain CFTR genotypes are associated with reduced mortality. The accuracy of using CFTR genotype as a predictor of survival and the mechanisms through which CFTR genotype influences survival are unknown.

Participants: All patients with cystic fibrosis (CF) enrolled in the US Cystic Fibrosis Foundation national registry between 1993 and 2002.

Design: We examined the prognostic value of CFTR genotype, grouped into "high-risk" and "low-risk" categories based on the effect of their CFTR genotype on phenotype and protein production.

Measurements and results: Clinical and genetic data were available from 15,651 patients with CF. Patients with a high-risk CFTR genotype had a greater than twofold increased risk of death compared to patients with a low-risk CFTR genotype (relative risk, 2.25; 95% confidence interval [CI], 1.77 to 2.84; p < 0.001). This association was partly explained by lung function, nutritional status, pancreatic insufficiency, and Pseudomonas aeruginosa colonization. Of the 1,672 patients who died, median age at death for the high-risk CFTR genotype was 24.2 years (interquartile range, 18.4 to 32.0 years) and for the low-risk CFTR genotype was 37.6 years (interquartile range, 28.8 to 47.9 years; p < 0.001). The positive predictive value of this classification method as a test to identify patients who died before or after their 30th birthday was 69% (95% CI, 67 to 72%) with a negative predictive value of 71% (95% CI, 60 to 80%).

Conclusions: Grouping patients into high-risk and low-risk CFTR genotype categories is associated with significant differences in survival and median age at death. These differences are not fully explained by lung function, nutritional measures, pancreatic insufficiency, or P aeruginosa colonization. Modest reassurance about the likelihood of a milder than average course can be provided for CF patients with a low-risk CFTR genotype, although it should be acknowledged that substantial phenotypic variability exists.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / mortality*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • Genotype
  • Humans
  • Lung / microbiology
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Pseudomonas aeruginosa / pathogenicity
  • Retrospective Studies
  • Risk Assessment
  • Survival Rate


  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator