Diagnosis of Cystic Fibrosis

Because CF is a genetic disease and researchers know which gene causes CF, one might think that the first and obvious way to find out if somebody has CF is to test their DNA for "the CF gene." The problem with this approach is that there are nearly 400 different variations of the CF gene, not all of which can be identified by DNA analysis. Instead, the diagnosis depends largely on a clinical test known as the sweat test, which provides a measure of Cl- (chloride ion) in the sweat and an indication of glandular dysfunction. Most, 98% to 99% of CF patients can be positively diagnosed using the sweat test.

Other diagnostics for CF include:

Prenatal CF Diagnosis

Prenatal genetic testing can be used to determine whether an unborn baby has CF, although the testing is not foolproof, many of the nearly 400 different mutations that can lead to CF cannot be detected.

Because prenatal genetic testing is expensive and carries some risk to the mother, not all women who are CF carriers choose to have the tests done.

Prenatal testing involves either amniocentesis or a chorionic villus biopsy. In the former, cells are removed from the amniotic fluid—the fluid that surrounds the fetus. A chorionic villus biopsy involves sampling tissue that develops into the placenta.

Medical History & CF Diagnosis

The medical history, beginning in infancy, is essential to diagnose CF. Several symptoms provide the physician with important clues (see Symptoms).

Family History & CF Diagnosis

Because CF is an inherited disorder, any family history of CF suggests that the gene is present in the lineage.

Sweat Test & CF Diagnosis

A sweat test, also known as a sweat chloride test or a sweat electrolyte test, provides a measure of the amount of salt in the sweat that comes from the skin and is the most common test for CF. It involves using a chemical (pilocarpine) and a mild electric current to make a part of the skin sweat, wrapping the area with plastic and a pad to absorb the sweat, and then collecting the sweat about one-half an hour later.

In children, if the concentration of Cl- (chloride) is greater than 60 mmol per litre (a mmol is a chemical unit of quantity), this is an indication that the patient has CF.

Many adults who do not have CF have a fairly high Cl- level in their blood. So, for adults, if the concentration of Cl- is greater than 80 mmol/L, this is highly suggestive of CF.

Newborn babies usually cannot produce enough sweat for a sweat test (at least 50 mg needs to be collected in a 45-minute period), so an IRT (immunoreactive trypsinogen test) may be done instead. If enough sweat can be collected from a newborn or infant less than 3 months old, a concentration greater than 40 mmol per litre is indicative of CF.

A very small percentage of CF patients have normal salt levels in their sweat, in which case they have to be genetically tested to determine the presence of the defective gene.

About 10% to 15% of all positive sweat tests are false positives, meaning that even though the test results suggest that the patient has CF, they do not in fact have the disease. There are many conditions not related to CF that can cause false positive sweat test results. All positive tests should be repeated, usually the next day, and/or patients should be genetically screened.

Immunoreactive Trypsinogen Test (IRT) & CF Diagnosis

In newborn babies who cannot produce enough sweat for a sweat test, an IRT may be done. An IRT is a blood test that involves drawing blood a couple of days after birth and evaluating the presence of the protein trypsinogen. If the test is positive, it should be confirmed by a mutation analysis (i.e., genetic testing). The combination of an IRT and a mutation analysis is sensitive 90% to 100% of the time.

Nasal Potential Difference (NPD) Measurement & CF Diagnosis

As Na+ (sodium) and Cl- ions move across the membranes of the cells lining the airway, they generate what is called an electric potential difference (the amount of energy required to move an electrical charge from one point to another). In the nasal passages, this electric potential difference is known as the nasal potential difference (NPD), and it can be easily measured with a surface electrode. Because Na+ and Cl- transport is abnormal in CF patients, NPD measurements are very different in CF patients than in people who do not have CF.

This test is especially helpful when the sweat electrolyte test and/or the genetic tests are inconclusive. However, the success of the test is highly dependent on the skill of the technician, and should be done in a special center.

Genetic Testing & CF Diagnosis

A genetic test, also known as a genotype test or mutation analysis, is designed to analyze DNA for the presence of one of the several hundred mutations that can cause CF. The test involves collecting a sample of the patient's blood. The test cannot detect all of the mutations that can cause CF, however, so its sensitivity is only about 80% to 85%. Genetic testing cannot be used to predict the severity of symptoms. There is no way to know, based on a person's genotype, whether CF will be fatal or mild.

Generally, a genetic test is done if a patient's sweat test is negative and there is still high suspicion that the patient has CF.

Pulmonary Function Tests & CF Diagnosis

Pulmonary function tests may be done to assess the patient's respiratory dysfunction and whether the patient is healthy enough to receive a lung transplant, if necessary.

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 01 Jun 2000

Last Modified: 10 Jun 2011