Lung function decline is delayed but not decreased in patients with cystic fibrosis and the R117H gene mutation

Jeffrey S Wagener; Stefanie J Millar; Nicole Mayer-Hamblett; Gregory S Sawicki; Edward F McKone; Christopher H Goss; Michael W Konstan; Wayne J Morgan; David J Pasta; Richard B Moss

doi:10.1016/j.jcf.2017.10.003

Lung function decline is delayed but not decreased in patients with cystic fibrosis and the R117H gene mutation

J Cyst Fibros. 2018 Jul;17(4):503-510. doi: 10.1016/j.jcf.2017.10.003. Epub 2017 Oct 31.

Affiliations

¹ Department of Pediatrics, University of Colorado, Aurora, CO, USA. Electronic address: [email protected].
² ICON Clinical Research, San Francisco, CA, USA.
³ US CFF Patient Registry Committee, Bethesda, MD, USA; Department of Pediatrics and Biostatistics, University of Washington, Seattle, WA, USA.
⁴ US CFF Patient Registry Committee, Bethesda, MD, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁵ Thoracic Medicine, St. Vincent's University Hospital, Dublin, Ireland.
⁶ US CFF Patient Registry Committee, Bethesda, MD, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
⁷ Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
⁸ US CFF Patient Registry Committee, Bethesda, MD, USA; Department of Pediatrics, University of Arizona, Tucson, AZ, USA.
⁹ Department of Pediatrics, Stanford University, Palo Alto, CA, USA.

Abstract

Background: Patients with cystic fibrosis (CF) experience variable lung disease phenotypes. The R117H mutation is often associated with preserved lung function. Our objective was to compare the rate of lung function decline in patients with the R117H mutation and patients homozygous for the F508del mutation.

Methods: Rate of decline in percentage-of-predicted FEV₁ (ppFEV₁) was analyzed using the 2006-2010 US CF Foundation Patient Registry.

Results: 4-year rate of decline was slower in 156 R117H patients compared with 6251 F508del patients (-0.61 vs -2.03 ppFEV₁/year, P<0.001). Rates of decline in children were slower in R117H vs F508del patients (6-12-year-olds: +0.73 vs -1.91 ppFEV₁/year, P<0.001 and 13-17-year-olds: -1.55 vs -2.66 ppFEV₁/year, P=0.046), whereas rates in adults were not significantly different (18-24-year-olds: -1.52 vs -2.12, P=0.26 and ≥25-year-olds: -1.17 vs -1.40, P=0.33).

Conclusions: These findings are consistent with a delayed onset, but ultimately similar progression, of lung disease in R117H compared with homozygous F508del patients.

Keywords: Cystic fibrosis; F508del; Lung function; Lung function decline; R117H.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Age Factors
Age of Onset
Airway Obstruction* / diagnosis
Airway Obstruction* / epidemiology
Airway Obstruction* / etiology
Child
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Cystic Fibrosis* / diagnosis
Cystic Fibrosis* / epidemiology
Cystic Fibrosis* / genetics
Disease Progression
Female
Homozygote
Humans
Lung / physiopathology*
Male
Mutation
Registries / statistics & numerical data
Respiratory Function Tests* / methods
Respiratory Function Tests* / statistics & numerical data
United States / epidemiology

Substances

Cystic Fibrosis Transmembrane Conductance Regulator

Grants and funding

P30 DK089507/DK/NIDDK NIH HHS/United States