At a glance

Also known as

Sweat chloride; iontophoretic sweat test

Why get tested?

To diagnose cystic fibrosis (CF)

When to get tested?

When a newborn or infant has symptoms that suggest CF, such as frequent respiratory infections and chronic cough, persistent diarrhoea, foul-smelling bulky greasy stools and malnutrition; and as a follow-up, confirmatory test to help diagnose CF in older patients

Sample required?

A sweat sample collected using a special sweat stimulation procedure

What is being tested?

The chloride sweat test measures the amount of sodium and chloride in sweat. Sodium and chloride are part of the body's electrolyte balance and combine to form the salt found in sweat. They help regulate tissue fluid balance. Normally, chloride travels in and out of the body's cells, helping to maintain electrical neutrality and water balance. This movement occurs through a protein, the cystic fibrosis transmembrane conductance regulator (CFTR) that serves as a channel, letting chloride out of cells and into the surrounding fluid and also reducing sodium absorption. Sodium levels thus usually mirror those of chloride.

Cystic fibrosis (CF) is caused by a mutation in each of the two copies of the CFTR gene (one copy from each parent). With two mutations, the CFTR protein may be dysfunctional or totally absent. Since CFTR protein levels are usually highest in the epithelial cells lining the internal surfaces of the pancreas, sweat glands, salivary glands, intestine, and reproductive organs, these are the areas most affected by CF. Dysfunctional or absent CFTR protein in the exocrine tissues mentioned above causes deranged transport of chloride and other ions such as sodium and bicarbonate. This abnormality causes mucous secretions to become thick and sticky and the sweat much saltier than normal. This elevation in salt in the sweat can be measured, as a chloride sweat test.

Diagnosis of classic CF depends on the presence of clinical disease and an elevated chloride in sweat (≥ 60 mmol/L). There are also people with what is called non-classic CF. They may have milder diseases and only one organ system e.g. the lungs or gut may be affected. They may not be diagnosed until later in childhood or as adults. They often have normal or equivocal chloride sweat test results. In these cases the diagnosis of CF then rests on the results of other tests and the detection of two mutations in the CFTR genes.

Cystic Fibrosis is the most prevalent genetic disorder among Caucasian populations, with a frequency of 1 in 2000-3000 live births. Newborn screening for CFTR gene mutations and Immunoreactive Trypsinogen (IRT) take place in Australia for early detection of Cystic Fibrosis.
 

How is the sample collected for testing?

A sweat sample is collected using a special sweat stimulation procedure. A tiny amount of a clear, sweat-stimulating liquid is applied to a small patch of skin on the arm or leg. An electrode is then placed over the site and a weak electrical current stimulates the area. This is a painless procedure that may create a tingling or warm sensation. After several minutes, the area is cleaned and sweat is collected for about thirty minutes, either into a plastic coil of tubing or onto a piece of gauze or filter paper. The sweat obtained is then sent to the laboratory for analysis.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

The Test

How is it used?

The chloride sweat test is used to test for cystic fibrosis (CF) in symptomatic patients. It is also used to help confirm or rule out a diagnosis of CF in patients who have had positive or equivocal (uncertain) results using other tests. It is not used to monitor CF since elevated levels do not correlate with the severity of the disease or its symptoms.

When is it requested?

The chloride sweat test is performed when a patient (usually an infant) has symptoms of CF, such as noticeably salty sweat, frequent respiratory infections and chronic cough, persistent diarrhoea, foul-smelling bulky greasy stools, or malnutrition, and/or has a close relative who has been diagnosed with CF. The chloride sweat test may also be used to help confirm a diagnosis in patients who have an elevated immunoreactive trypsin test (IRT).

CF gene mutation analysis, tests for the most common CF gene mutations (of almost 1000 possible mutations). If the analysis is negative, then the patient may not have CF or they may have a rarer mutation not tested for. In this situation, sweat chloride testing may detect CF even if the genetic mutations causing it cannot be identified.

What does the test result mean?

If the chloride level in the sweat is above a certain level, this is regarded as a positive chloride sweat test, which means that there is a good chance that the patient has CF. Positive chloride sweat tests are usually repeated for verification and confirmed, wherever possible, with a positive CF gene mutation analysis.

A negative chloride sweat test must be evaluated along with the patient’s clinical findings. A few people with CF will have normal chloride sweat levels and will have to be evaluated using other tests.

The chloride sweat test may not always be useful in newborns. They may not produce enough sweat for a reliable diagnosis, so the test may have to wait until the baby is several months old. Other situations where the chloride sweat test is not recommended would be where the child is dehydrated or where there is a skin problem such as eczema covering the area where sweat would be collected from. The chloride sweat test may not need to be done if the patient has an elevated IRT and a CF gene mutation is identified.

About Reference Intervals

Is there anything else I should know?

The chloride sweat test will not pick up carriers of cystic fibrosis. It takes two mutated (abnormal) copies of the CFTR (cystic fibrosis transmembrane regulator) gene to cause cystic fibrosis. Those who are only carriers, and therefore have one normal and one abnormal gene, will not have sweat chloride abnormalities.

There are other conditions besides CF that can cause positive chloride sweat tests. These include Addison’s disease, nephrogenic diabetes insipidus and hypothyroidism. However, these conditions are not likely to be confused with CF.

On the other hand, the result can be negative even if the patient does have CF, for example, if there is swelling oedema in the skin, or if the sweat has not been collected properly.

The chloride sweat test should only be performed at specialised centres with experience with this kind of testing.

Common Questions

If one of my children has CF and a positive chloride sweat test, should my other children be tested?

Yes, if they are symptomatic. If not and/or if the genetic mutations causing your child’s CF are known, your doctor may prefer to test the other siblings for these specific mutations. This will let them know if your children have CF or are just carriers. Carriers are not ill and do not need treatment, but they may want to consider genetic counselling before they decide to have children themselves. Some doctors do not recommend testing on siblings unless they are symptomatic; testing and counselling for reproductive choices can be done later.

What other tests may my doctor recommend if my child has CF?

Your doctor may do other tests, such as chest X-rays as well as lung function and pancreas function testing, including faecal elastase, to find out how severe your child’s CF is and to guide them in recommending a treatment plan and/or a referral to a special CF centre where your child can get expert help, advice and monitoring.

Last Review Date: December 6, 2016