A nasal potential difference (NPD) test is a medical procedure that measures the electrical voltage across the lining of the nose, known as the nasal mucosa. This voltage is a natural result of the activity of the cells in this lining. The test provides a direct measurement of how these cells are functioning, giving insight into the health of the nasal epithelium.
The Purpose of Measuring Nasal Potential Difference
The NPD test is based on the principle of ion transport. Cells lining the nasal passages actively move charged particles called ions across their membranes through specific protein channels. Two primary ions in this process are positively charged sodium and negatively charged chloride. The regulated flow of these ions creates a measurable electrical voltage across the nasal lining.
This measurement is useful for evaluating the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, which acts as a channel for chloride ions. In cystic fibrosis (CF), the gene for the CFTR protein is mutated, leading to a defective or absent protein. Without functional CFTR channels, chloride cannot move properly out of the cells, and sodium transport into the cells increases. This disruption changes the electrical potential, allowing the NPD test to directly assess CFTR protein function.
The Nasal Potential Difference Procedure
The procedure involves placing a small, soft catheter into the nostril. A reference electrode is placed on the forearm, sometimes after a gentle skin abrasion, to serve as a baseline for the electrical measurement. The nasal catheter has a recording electrode to measure voltage and a channel for delivering a series of solutions onto the nasal lining.
During the test, which takes about an hour, different liquids are dripped onto the nasal mucosa in a specific sequence:
- A saline solution to establish a baseline voltage.
- A solution containing amiloride, which blocks sodium channels.
- A chloride-free solution.
- A substance like isoproterenol to stimulate functioning CFTR channels.
The process may cause a tickling sensation but is not considered painful.
Interpreting Test Results
The data from an NPD test is displayed on a graph, showing how the voltage across the nasal lining changes with each solution. In a person without cystic fibrosis, the baseline voltage is in a specific range. When the amiloride solution is introduced, there is a noticeable drop in voltage as sodium absorption is inhibited. The subsequent solutions cause the voltage to change again as chloride ions are secreted through CFTR channels.
In an individual with cystic fibrosis, the pattern is different. The initial baseline voltage is much more negative than normal due to excessive sodium absorption. Consequently, when amiloride is administered, the drop in voltage is significantly larger because there is more sodium transport to block. When the solutions designed to trigger chloride secretion are used, there is very little or no change in voltage, indicating the CFTR protein is not functioning correctly.
Role in Medical Diagnosis
The NPD test is a specialized diagnostic tool, not an initial screening test for cystic fibrosis, a role filled by newborn screening and the sweat chloride test. The NPD test is used when sweat test results are unclear or fall into an intermediate range. It can also be used for individuals who cannot produce enough sweat for a reliable test, which can occur in infants or adults.
Beyond CF, the NPD test can help diagnose other rare disorders that affect ion transport, such as Primary Ciliary Dyskinesia (PCD). The test also serves a function in medical research. It provides a direct way to measure the effectiveness of new treatments, like CFTR modulator therapies, by assessing if a drug restores ion transport in clinical trials.