Cystic fibrosis diagnosis
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Cystic fibrosis (CF) diagnosis is typically a multi-step process that may involve blood tests, genetic analyses, and assessments of sweat to identify the rare genetic disease. Due to the widespread adoption of newborn screening programs, most patients are increasingly being diagnosed in the first months of life, which can facilitate early CF treatment and better clinical outcomes.
Most testing for CF is focused on the mutations that cause the disorder, which affect the gene CFTR. This gene provides instructions for making a protein that helps to regulate the movement of chloride ions, more commonly known as salt molecules, in and out of cells. Chloride flow helps control the balance of water on tissue surfaces. As a result of a CFTR gene mutation, this protein does not work properly or is absent in people with CF, which leads to the production of thick, sticky mucus that builds up in the body’s organs and gives rise to disease symptoms.
Diagnostic tests for CF broadly look for signs of CFTR dysfunction.
Newborn screening
Newborn screening involves testing babies for CF (and other conditions, simultaneously) within the first few days after birth. Such screening can allow babies to be diagnosed before they start to experience notable disease symptoms, and facilitate the start of early treatment to manage the disease. Early cystic fibrosis treatment can minimize disease progression, ultimately leading to better outcomes for the child.
In the U.S., newborn screening for cystic fibrosis has been implemented in all states. It’s also done in many other countries worldwide, including Canada and Australia, and has been implemented in nations in Europe and South America.
Screening is typically carried out by taking a sample of blood, usually by pricking the baby’s heel; it may involve one or more specific diagnostic tests for CF.
Immunoreactive trypsinogen test
In all 50 U.S. states and the District of Columbia, the first-line assessment used to screen for potential cases of CF is the immunoreactive trypsinogen test, known as the IRT test.
IRT is a protein that’s made by the pancreas, and normally gets secreted from that organ into the intestines to help with digestion. In CF, thick mucus can build up in the pancreas, stopping it from releasing IRT to the small intestine. As a result, IRT builds up to high levels in the blood.
Detecting high levels of IRT in the blood can therefore indicate that a baby has CF — but high IRT levels also can occur due to other reasons, like an early or difficult birth. Most babies with a positive finding on the IRT test do not have CF, despite the screen positive result. As such, additional cystic fibrosis testing is required to confirm the diagnosis of CF after an initial high IRT test.
It’s also possible, though uncommon, for a baby with CF to have normal IRT levels at birth, resulting in a false negative result from screening. Consequently, additional CF testing may still be recommended after a negative IRT test if a patient shows symptoms indicative of the disease.
Genetic testing
Cystic fibrosis genetic testing involves analyzing the sequence of the CFTR gene to look for CF-causing mutations. In newborn screening, genetic tests are usually done after a positive IRT test to help confirm the diagnosis, which requires CFTR mutations in both gene copies. People generally inherit two copies of a gene — one from each biological parent. Genetic testing also can help to inform the risk of passing CF on to future generations.
Most CF genetic tests will specifically look for a few dozen of the most common CF-causing mutations. Positive results in such screenings mean there’s a 99% chance of being a CF carrier.
However, with more than 2,500 mutations in CFTR described to date, tests that only look for the most common alterations may miss rarer disease-causing mutations, resulting in false negative results. CF genetic tests have historically focused more on mutations that are common in people of European ancestry, so false negative results from genetic testing are more common in nonwhite populations.
Sweat test
The sweat test is considered the gold standard for diagnosing cystic fibrosis. This test involves measuring levels of chloride ions in a person’s sweat. In CF, dysfunction of the CFTR protein results in abnormally high levels of chloride in sweat. Among patients, chloride can crystallize into salt on the skin, with salty skin thus being one of the disease signs.
The CF sweat test is commonly used to confirm a diagnosis after a positive result from a newborn screening. However, the test is not performed on newborns because they don’t produce enough sweat to collect for the test — babies typically won’t start sweating enough to undergo this test until they’re about 2 weeks old.
The Cystic Fibrosis Foundation recommends babies who get a positive CF newborn screening result should get a sweat test by the age of 1 month at the latest. Testing can be done later, however, and the sweat test also may be performed on older children and adults who show signs of CF.
In some cases, babies who are positive for CF newborn screening by the IRT test may have results from the sweat test that fall in an intermediate range, higher than normal but not clearly elevated to disease levels. When a conclusive CF diagnosis cannot be established, it’s referred to as CFTR-related metabolic syndrome (CRMS) or a CF Screen Positive, Inconclusive Diagnosis (CFSPID).
Most babies with CRMS/CFSPID do not develop CF, though they may be at higher risk of certain health problems. Some infants with CRMS/CFSPID will go on to develop disease symptoms and be diagnosed with CF. It’s generally recommended that children with CRMS/CFSPID get regular medical monitoring so that early signs of cystic fibrosis can be detected.
Prenatal screening
Every person inherits two copies of the CFTR gene, one from each biological parent. CF is a recessive disorder, meaning that a person will only develop the disease if both of their copies of CFTR are mutated. A person with just one mutated gene copy will not develop CF, but can pass the mutated gene on to their children. Such individuals are called carriers.
Genetic testing may be conducted to determine whether two people who want to have biological children are CF carriers, especially if one or both have a family history of the disease. Knowing whether or not a person or that individual’s partner is a carrier for CF can be of importance in family planning.
If two carriers are expecting a baby, prenatal screening — which tests the DNA of the developing fetus — can determine if their child may have CF.
Prenatal screening can be done by either amniocentesis or chorionic villus sampling, known as CVS. Amniocentesis involves the removal of some of the amniotic fluid that surrounds the fetus, while CVS requires taking a sample of tissue from the placenta, a structure that provides oxygen and nutrients to the developing baby. Chorionic villus sampling can be done earlier in pregnancy, whereas amniocentesis is usually done between 15 and 20 weeks of pregnancy.
Nasal potential difference
The nasal potential difference, or NPD, is a test that measures the electrical potential difference — essentially, a small electrical charge — that occurs in the airway lining inside the nose. In CF, dysfunction or absence of the CFTR protein causes characteristic abnormalities in these small charges.
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, and the voltmeter records how these solutions change the electric potential difference.
The main advantages of NPD are that it’s minimally invasive, usually tolerated well, and provides a direct measurement of the disease-causing mechanisms of CF. Perhaps most importantly, it yields immediate results. In addition to serving as a tool for diagnosing CF, NPD also can be used to assess the effectiveness of different treatments.
However, there are some challenges and limitations to the use of NPD. The test requires a fair amount of expertise to perform and interpret correctly, and it may be may be unreliable in people with conditions like airway infections or nasal polyps. 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 and young children.
Other tests
Other tests may be involved in diagnosing and monitoring CF.
- Imaging tests, like X-rays, MRIs, or CT scans, can be used to detect and track damage to the lungs and other internal bodily structures.
- Lung function tests — such as forced expiratory volume (FEV), forced vital capacity (FVC), or lung clearance index (LCI) — may help track respiratory function.
- Cultures of sputum, the thick mucus coughed up from the lungs, can be used to detect infections.
- Analyses of stool samples may aid in assessing digestive health, particularly how well fat is being digested.
Cystic Fibrosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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FAQs about cystic fibrosis diagnosis
In the U.S., all newborns are screened for cystic fibrosis (CF) within the first few days after birth. Newborn screening for CF also has been implemented in many other countries around the world, but it is not available in every place.
It is possible to diagnose cystic fibrosis (CF) at any age. In the U.S. and many other countries, newborn screening programs for CF have been implemented, so most people with the disorder nowadays are diagnosed as infants.
In the U.S., the initial test used to screen newborns for cystic fibrosis (CF) is the immunoreactive trypsinogen (IRT) test. Having a positive result in genetic screening means there’s a 99% chance of being a CF carrier; however, false positives are common — nearly 9 in 10 babies who have a positive newborn screening are found to not actually have CF when testing is done to confirm the initial results. It also is possible to have a false negative result from CF newborn screening.
The mutations that cause cystic fibrosis (CF) are present from the moment that a fetus is conceived. It is possible to test the DNA from a developing fetus to look for CF-causing mutations and determine whether the child may have CF.
The sweat test for cystic fibrosis (CF), which measures the amount of chloride in a person’s sweat, is the gold standard for diagnosing the condition. Chloride is a salt (the “chloride” in “sodium chloride” or table salt), and CF is caused by CFTR gene mutations that affect how chloride moves in and out of cells. As a result, people with cystic fibrosis have abnormally high chloride levels in their sweat.
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