CF gene mutation. The most common CFTR mutation is F508del, which accounts for about 70% of the mutations in those of Northern European descent. Testing of F508del in isolation or a panel of 50 common mutations of the CF gene has been developed to screen general or targeted populations for CF and CF carrier status. (The number of mutations screened within the panel varies between laboratories). These panels check the patient’s DNA for each of the selected CF mutations. If two CF mutations are identified, then the patient has CF; if one is located, the patient is either a carrier or has CF with the second mutation unidentified. Further clinical assessment, genetic testing (sequencing of the CF gene) and a sweat test may be performed. An individual of Northern European descent who tests negative for the F508del mutation has about a 1 in 100 chance of being a CF carrier. An individual of Northern European descent who tests negative for a panel of ~50 mutations has about a 1 in 130 chance of being a CF carrier.
Sweat test. This test involves measuring sodium and chloride from a sweat sample collected by a special procedure in which local sweating is stimulated by pilocarpine. The sweat collected is weighed on filter paper and the concentrations of sodium and chloride measured. Since the CFTR protein is altered or missing and chloride travel is restricted, the sweat in a CF person may be up to five times saltier than normal. Positives should be confirmed and followed with CF gene mutation testing. Some people with CF will be diagnosed using only sweat testing, and a few very rare patients with definite CF, often with unusual mutations, may have sweat sodium and chloride levels within the normal range.
Faecal chymotrypsin. Faecal chymotrypsin is a stool test for proteolytic enzymes, produced in an inactive form in the pancreas and then activated in the small intestine to digest food proteins. Low values indicate pancreatic insufficiency in untreated people with CF; in patients on pancreatic enzyme replacement therapy values are usually normal but do not correlate closely with the amount of fat in the stools.
Faecal pancreatic elastase 1. This is a specific human protease produced by the pancreas. Values determined on a small faecal specimen clearly differentiate between sufficient and insufficient pancreatic function and are not influenced by exogenous pancreatic enzyme treatment. This is now the best indirect measure of pancreatic function and it has superseded a number of indirect pancreatic function tests including the bentiromide and pancreolauryl tests.
Immunoreactive trypsin (IRT). This newborn screening test for CF is measured using the blood spots collected on Guthrie screening cards. In CF, thick mucus plugs can obstruct pancreatic ducts and prevent trypsinogen from reaching the intestine. Blood IRT levels will be elevated in most newborns with CF. Using IRT measures has 95-98% sensitivity (some affected babies and those with mild disease may be missed). Elevated IRT in the first few days of life can also be caused by perinatal stress, renal failure, congenital infection, bowel atresia and some aneuploidies. An elevated IRT is usually followed with DNA testing for the F508del mutation for neonatal CF screening. Early diagnosis is essential so that treatment can be started before damage to the lungs with chronic infection occurs and malnutrition becomes established.
Other laboratory tests used to check lung infection, organ function and fertility include:
- Sputum cultures
- Faecal fat microscopy and measurement
- Liver function tests
- Full blood count
- Fat soluble vitamin levels
- Immunoglobulins including IgE
- RAST and precipitins for aspergillus fumigatus
- Pseudomonas antibodies
- Semen analysis
Non-laboratory tests that may be done include respiratory function tests, chest X-rays, lung scans including low-dose CT scan to look for air trapping and early bronchiectasis, bronchoscopies, bone scans, upper GI and small bowel X-rays and other gastrointestinal pancreatic and liver investigations such as ultrasound scans.