Chest
Original ResearchCFTR Genotype as a Predictor of Prognosis in Cystic Fibrosis
Section snippets
Materials and Methods
The study design is a retrospective cohort study using the Cystic Fibrosis Foundation patient registry,16, 17 measuring risk of death during an observation period from 1993 to 2002. The primary outcome of interest was all-cause mortality including patients who died after transplantation. Secondary outcome was all-cause mortality (excluding transplant-related deaths). All procedures were approved by the University of Washington Institutional Review Board.
Genotypes were classified into high-risk
Results
The patient population is outlined in Figure 1. There were a total of 30,396 patients included in the database, with 193,856 person-years at risk; 21,353 patients (70%) were genotyped. Of the genotyped patients, 15,651 patients had a CFTR genotype containing mutations with a known functional class. Of these, 14,525 patients (93%) had a high-risk CFTR genotype and 1,126 patients (7%) had a low-risk CFTR genotype. Median follow-up was 8.6 years for patients with a high-risk CFTR genotype vs 5.1
Discussion
The main findings of this study are that patients with CF can be classified into high-risk and low-risk genetic groups that have significant differences in survival and median age at death. These differences in survival are not fully explained by clinical measures of lung function, nutrition, and pancreatic insufficiency, suggesting that the CFTR genotype is an independent predictor of survival. In addition, using the CFTR genotype for risk stratification in CF may have some prognostic value,
ACKNOWLEDGMENT
We thank Bruce Marshall, Monica Brooks, Preston W. Campbell III, MD, and the Clinical Research Committee of the Cystic Fibrosis Foundation for access to the database. We also thank Wylie Burke MD, PhD, for her assistance in the preparation of this article.
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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).
The authors have no conflicts of interest to disclose.
Dr. McKone is supported by the Cystic Fibrosis Foundation and National Institutes of Health grant K23 HL/70849-01.