Assessing accuracy of testing and diagnosis in cystic fibrosis

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• CFTR functional tests
• sweat test
• nasal potential difference
• intestinal current measurements

Article highlights

• Sweat chloride, nasal potential difference, and intestinal current measurements are the CFTR functional tests used to help with a diagnosis of CF, as outlined in the CF diagnostic guidelines.

• Each of the tests demonstrate high accuracy in identifying CF from non-CF individuals. This accuracy remains despite the biological and technical variation, which impact test results.

• Global adherence to standardized operating procedures for these tests is poor, and needs to be improved to increase test accuracy among the different CF centers.

• Individuals with CF-associated symptoms, and evidence for genetic and/or functional CFTR defects delineate a disease spectrum between those with CF and non-CF. In these cases, single functional test results may not be sufficiently accurate to identify the individual risk for CF/CFTR-related disease.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

M Barillaro received salary funding from the Canadian Institute of Health Research (PJY-175230).