CF is caused by abnormalities in salt transport that result from a defective CFTR protein, which is a chloride channel that regulates the salt content in the fluid that covers cell surfaces within the nose and lungs. Transport of ions such as sodium and chloride creates an electrical potential difference across the airway lining. This potential difference can be measured by placing an electrode on the lining of the nose. After the electrode is positioned, the lining of the nose is bathed in a series of solutions that contain different salts. These solutions are designed to change the flow of ions across the epithelium in predictable ways, thus changing the potential difference in predictable ways. These solutions contain (1) a Ringer’s saline solution (a special salt solution used to obtain the baseline NPD), (2) amiloride which blocks sodium channels, (3) a chloride-free solution and (4) isoproterenol, which stimulates CFTR. The solutions are always administered in the same order during the NPD testing.
Because patients with CF either don’t make CFTR chloride channels or have mutated forms of CFTR, the potential across their nasal epithelium responds differentially to the administration of the various solutions. Three specific features of the NPD test distinguish patients with CF:
- A more negative baseline potential difference.
- A larger inhibition of NPD after addition of amiloride.
- Little or no change in NPD after addition of the chloride-free and isoproterenol solutions.
NPD testing is not commercially available. Because the test is technically very difficult to perform, only a few CF centers around the country perform it, primarily as a research tool. Clinical features of the individual patient as well as sweat test and mutation analysis results must be taken into consideration when using the NPD to diagnose CF.