Nasal Potential Difference (NPD)

A test known as nasal potential difference, or NPD, is used as a diagnostic tool for cystic fibrosis (CF), a genetic disorder caused by mutations that lead to defects in the protein CFTR.

The NPD test was designed to measure an electrical potential difference — essentially, a small electrical charge — that occurs in the airway lining. It works by placing an electrode on the lining of the nose, which measures that electrical charge.

In CF, the CFTR protein normally works like a “gate” at the surface of cells, helping to regulate the flow of water and ions (salts) in and out of the cell.

Ions have a small amount of electrical charge — for example, sodium chloride (table salt) is composed of a positively charged sodium ion and a negatively charged chloride ion. In the airway lining, the movement of ions through protein channels like CFTR creates an electrical potential difference, or that small electrical charge.

In addition to serving as a tool for diagnosing CF, NPD also can be used to assess the effectiveness of different treatments.

How NPD is measured

NPD is measured using a device called a voltmeter, which is attached to electrodes to record the potential difference across the membrane of the nose.

After the electrodes are positioned, the lining of the nose is bathed with a series of solutions that contain different salts. This is designed to change the flow of ions across the nasal epithelium in predictable ways.

Because patients with CF have impaired CFTR channels, the potential across their nasal epithelium responds differently than normal to the administration of these different solutions, in characteristic ways indicative of the disease.

Advantages and limitations of NPD

The main advantages of NPD are that it’s minimally invasive, usually well-tolerated, provides a direct measurement of the disease-causing mechanisms of CF, and yields immediate results.

However, there are some challenges and limitations to the use of NPD. The test requires a fair amount of expertise to perform correctly, and there are many considerations with regard to the equipment and solutions used that need to be taken into account when interpreting results.

The test may not be reliable in certain conditions — for example, when there is an infection in the nose or airways. It also may be unreliable in people with polyps in the nose, or in smokers, or those who have had sinus surgery. NPD also may give false-negative results in people with rarer subtypes of atypical CF.

There also can be variability in NPD results, including facility-to-facility differences, or even between the right and left nostrils. Such variability may complicate the interpretation of the results.

Also, since the procedure involves putting electrodes in the nose, it requires cooperation from the person being tested; as such, NPD can be challenging to perform in infants.


Last updated: Sept. 22, 2021


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