title: Improved repeatability of nasal potential difference with a larger surface catheter.
abstract: OBJECTIVE
  To increase the power of nasal potential difference (NPD) as a biomarker of CFTR function, improvement of its repeatability is needed. We evaluated the improvement in repeatability resulting from measuring NPD (1) over a larger surface area and (2) at a fixed location.
  
  
  METHODS
  To assess repeatability, NPD was measured on two occasions with a new method using a larger surface catheter at fixed locations on the nasal floor (LSC-floor(5cm) and LSC-floor(3cm)) or at the most negative basal potential (LSC-floor(max)); with a sidehole catheter on the nasal floor at 5 cm) from the nasal margin (SHC-floor(5cm)) or at the most negative potential (SHC-floor(max)); and with an endhole catheter below the inferior surface of the lower turbinate at the most negative potential (EHC-turb(max)).
  
  
  RESULTS
  The within-subject standard deviation (S(w)) for repeated measurements of the total chloride response in the controls was smallest with the LSC-floor at a fixed location (LSC-floor(5cm) 3.1 mV; 95% CI 2.3-4.6 mV) and highest with the SHC-floor (SHC-floor(max) 14.6 mV; 95% CI 10.9-22.2 mV) or the EHC-turbinate (EHC-turb(max) 12.5 mV; 95% CI 10.7-23.0 mV) at the most negative basal potential. Measuring with the LSC-floor at the maximal potential increased the Sw (LSC-floor(max) 8.8 mV, 95% CI 6.0-16.1 mV, p=0.009 vs LSC-floor(5cm)), while measuring with the SHC-floor at a fixed location slightly decreased the Sw (SHC-floor(5cm) 9.8 mV, 95% CI 8.9-20.6 mV, p=0.06 vs SHC-floor(max)). In patients with cystic fibrosis, the S(w) was comparable, between 2.2 mV and 4.3 mV. Sample size calculations for trials using NPD to assess changes in ion transport showed that the number of subjects to be included could be approximately halved measuring with the larger surface catheter at a fixed location vs SHC or EHC at fixed locations.
  
  
  CONCLUSIONS
  Measuring the NPD at a fixed location and over a larger surface resulted in increased repeatability and thereby also power as a biomarker of CFTR modulation.
authors.affiliation: CF Center, Department of Pediatrics, University Hospital of Leuven, Leuven, Belgium. Electronic address: Francois.vermeulen@uzleuven.be.
authors.forename: François
authors.initials: F
authors.lastname: Vermeulen
authors.affiliation: CF Center, Department of Pediatrics, University Hospital of Leuven, Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Proesmans
authors.affiliation: CF Center, Department of Pediatrics, University Hospital of Leuven, Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Boon
authors.affiliation: CF Center, Department of Pediatrics, University Hospital of Leuven, Leuven, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: De Boeck
mesh_terms: D057785:Catheters; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D003948:Diagnostic Techniques, Respiratory System / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D017136:Ion Transport; D008564:Membrane Potentials; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Biomarker; CFTR function; Surrogate endpoint