Written by Tatjana Djakovic, Staff Writer. Physicians use different diagnostic tests and criteria to diagnose individuals with cystic fibrosis.
Most commonly, cystic fibrosis is diagnosed when there are physical abnormalities characteristic of cystic fibrosis such as lowered respiratory function or digestive problems and evidence of abnormality in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. There are a few different diagnostic tests and criteria that physicians use to diagnose an individual with cystic fibrosis.
Newborn Screening Test
IRT-IRT (Immunoreactive Trypsinogen Test)
A heal prick test is administered to newborns in which a sample of blood is analyzed for elevated levels of a protein called trypsinogen. This protein is made by the pancreas which is involved with digestion, and is elevated in the bloodstream when there is stress placed on the pancreas. Since one of the organs affected by cystic fibrosis is pancreas this can be indicative of having the disorder. However, this is used only as a screening tool and needs to be confirmed by another method because pancreas can be stressed in other situation such as premature birth (1).
IRT-DNA
If the IRT test shows highly elevated trypsinogen levels in a newborn, a DNA analysis is performed in order to look for changes in the DNA sequence indicative of the disorder.. Currently, many places do a combined IRT and DNA analysis on the same sample of blood which provides quicker results and lessens the wait of anxious parents (1).
Sweat Chloride Test
The gold standard of diagnosis is the sweat chloride test. Cystic fibrosis is confirmed when the sweat chloride test is more than 60 mmol/L. The test has evolved since it was first described in 1959 by Gibson and Cooke. The procedure was performed by inducing a person to produce sweat by applying a current to a section of skin on the forearm using electrodes. The electrodes were then removed and a previously weighed filter paper was placed on the area that was treated with the current and covered with plastic wrap for 30 minutes. After 30 minutes, the moist filter paper was removed and reweighed on an analytical balance to determine the mass of the sweat. The sample was then sent to a lab to be analyzed for the chloride content using titration method (2).
Nasal Potential Difference Test
In case a sweat test is not clear, another method of confirming cystic fibrosis diagnosis is through a nasal potential difference test. The test is used to measure the voltage across the inner lining of the nose. Transport of ions such as chloride and sodium creates an electrical potential difference which can be measured by placing electrodes on the inner lining of the nose. After placement of electrodes, the nose is bathed in different solutions that are designed to change the flow of ions. The potential difference in normal patients and in those with cystic fibrosis will be different due to the defective CFTR channel (3).
In order to be diagnosed, an individual needs to have:
One or more physical features of cystic fibrosis and evidence of CFTR malfunction based on one of the following (4):
- Presence of two disease causing mutation (changes in DNA sequence) in CFTR
- Two abnormal sweat chloride values (>60 mmol/L)
- Nasal potential difference measurements characteristic of cystic fibrosis
References:
- Merelle, M. E., et al. “Newborn screening for cystic fibrosis.” the Cochrane library (2001).
- Mattar, Ana Claudia Veras, et al. “Sweat conductivity: An accurate diagnostic test for cystic fibrosis?.” Journal of Cystic Fibrosis 13.5 (2014): 528-533.
- Ng, Ronny Tah Yen, et al. “Nasal Potential Difference in Cystic Fibrosis considering Severe CFTR Mutations.” Disease Markers 2015 (2015).
- Moskowitz, Samuel M., James F. Chmiel, Darci L. Sternen, Edith Cheng, and Garry R. Cutting. “CFTR-related disorders.” (2008).
