Assessing accuracy of testing and diagnosis in cystic fibrosis

Next to evaluating for defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, diagnostic guidelines for cystic fibrosis (CF) include CFTR function tests. The primarily used sweat test and genetics generally produce straightforward CF diagnoses. However, a widened CF disease spectrum and large number of CFTR gene variants with unknown or varying clinical consequences shift reliance on CFTR functional tests to assess for CF or CFTR-related disease. Recently, CFTR functional tests are used to record efficiency of CFTR modulator drugs.

This review provides background and accuracy of the currently used CFTR functional tests, including the sweat test, nasal potential difference (NPD), and intestinal current measurements (ICM). We summarize published evidence addressing technical and biological reasons for test variability and test result in relation to CF-associated symptoms.

The CFTR functional tests demonstrate high accuracy despite biological and technical variability. Data is scarce for ICM. Each test identifies CF from non-CF but show lower accuracy for individuals not fitting the classic CF diagnostic criteria. Adherence to standardized protocols is critical to improve test accuracy across different centers. Lastly, instead of relying on the single test results, diagnostic assessment should be based on integrating multiple functional and genetic test results.