Improved repeatability of nasal potential difference with a larger surface catheter.

Area of Science:

• Biomarker development
• Respiratory physiology
• Medical device innovation

Background:

• Nasal potential difference (NPD) is a biomarker for cystic fibrosis transmembrane conductance regulator (CFTR) function.
• Improving the repeatability of NPD measurements is crucial for enhancing its utility.
• Current NPD measurement methods may lack the necessary precision for robust biomarker application.

Purpose of the Study:

• To enhance the repeatability of nasal potential difference (NPD) measurements.
• To evaluate the impact of using a larger catheter surface area on NPD repeatability.
• To assess the effect of measuring NPD at a fixed location versus variable locations.

Main Methods:

• NPD was measured using a novel larger surface catheter (LSC) at fixed and maximal potential locations.
• Repeatability was assessed using LSC, a sidehole catheter (SHC), and an endhole catheter (EHC).
• Measurements were taken on two separate occasions to determine within-subject standard deviation (S(w)).

Main Results:

• The LSC at a fixed location (LSC-floor(5cm)) demonstrated the smallest within-subject standard deviation (S(w)) in controls (3.1 mV).
• Measuring NPD with the LSC at a fixed location significantly reduced the required sample size for clinical trials.
• In cystic fibrosis patients, S(w) values were consistently low across different measurement techniques.

Conclusions:

• Measuring NPD over a larger surface area at a fixed location significantly improves measurement repeatability.
• Enhanced repeatability of NPD measurements strengthens its power as a biomarker for CFTR function.
• This improved method has implications for more efficient clinical trials evaluating CFTR modulators.