How Is Cystic Fibrosis Diagnosed?
Cystic fibrosis (CF) is most often diagnosed in childhood, but older people and those with rare forms of the disease may not be diagnosed until well into adulthood. The tests used to diagnose someone with CF are:
- Newborn screening
- Sweat test
- Genetic tests
- Nasal potential difference test1-5
Prenatal tests for cystic fibrosis are run if CF is known to run in a family, or if an ultrasound during pregnancy reveals that the baby has a bowel obstruction (abnormal meconium or hyperechoic bowel). First, the mother will get a blood test to see if she carries one or two CFTR mutations. If the mother carries a CFTR mutation, the father’s blood will be tested. If both parents are found to carry a CFTR mutation, then amniocentesis will be done to test the baby for CF.2,4
Newborn screening for cystic fibrosis became standard in all 50 states in 2010.3 The exact test may vary by state, but basically, a drop of blood is taken from a heel prick and dried on filter paper. The droplet is then tested for the amount of immunoreactive trypsinogen (IRT).
A high level of IRT means that the baby may have partially blocked pancreatic ducts. If a high level of IRT is found, the next test will be a sweat test or a CFTR mutation analysis, which is a type of genetic testing.2
A sweat test measures the amount of salt in someone’s sweat. The official name for a sweat test is quantitative pilocarpine iontophoresis. It is considered the gold standard for diagnosing CF. This test should be conducted at a CF center accredited by the Cystic Fibrosis Foundation.4
There are two types of the sweat test: the Gibson-Cooke procedure and the Wescor Macroduct® Sweat Collection System. In both tests, an electrode is placed on the arm below the elbow or on the thigh, with a piece of filter paper or gauze between the electrode and skin. The paper collects sweat which is then weighed and analyzed for chloride concentration. This test is completely painless.4
Understanding sweat test results
|0-29 mmol/L||Normal – Cystic fibrosis not likely|
|60+ mmol/L||Indicates cystic fibrosis|
|0-39 mmol/L||Normal – Cystic fibrosis not likely|
|60+ mmol/L||Indicates cystic fibrosis|
Sweat tests may not be accurate in the first two days after birth. Premature babies may not generate enough sweat for an accurate test for two to three weeks after birth.4
For people whose test results are borderline, other factors may be used to diagnose cystic fibrosis, including family history, age, and the fact that certain CFTR mutations are known to create borderline or negative sweat test results. People with borderline results will need follow-up tests.2Malnutrition, thyroid issues, and other health conditions can cause a false positive sweat test.2
CFTR mutation analysis is a type of genetic (DNA) testing. This blood test looks to see if the baby has two copies of the mutated CFTR gene, which is the gene that causes cystic fibrosis. The first screening test looks for the 23 most common CF genetic mutations. If this test is inconclusive, another DNA test looks for the next 88 most common variations of CF. However, with 1,700 known CF mutations, genetic testing may still be inconclusive.
CFSPID, CRMS and CF-Related Disorders
A significant percentage of babies will show elevated levels of IRT but borderline sweat and inconclusive DNA test results. Known as Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID) in Europe and CFTR-Related Metabolic Syndrome (CRMS) in the U.S., these patients have their own treatment and monitoring guidelines.
Another small group of people test with a CFTR mutation and have borderline sweat test results, but do not seem to have cystic fibrosis. Most of these people are older children or adults who have a single symptom common to CF such as sinus or lung complications, chronic pancreatitis, or male infertility. To distinguish these cases from people who have full-blown CF, the name CFTR-Related Disorder was created.2
Nasal potential difference test
In rare cases, a nasal potential difference test is used for people who show some signs of having CF but have only one or no CFTR gene mutations. For this test, an electrode is placed on the lining inside the nose. Then, different salt solutions are run across the nose lining to measure salt transport in the nose cells.5
Since an impaired pancreatic function is found in 80% of people with CF, a common test, fecal elastase, is used to measure how well the pancreas is working. If a stool is tested and found to have too little or no elastase, pancreatic insufficiency may be diagnosed.6