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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, infant or child 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, following abnormal results in the newborn screening (blood spot) test for CF.

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. Chloride's level usually mirrors that of sodium.

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 elevated immunoreactive trypsinogen (IRT) and CFTR gene mutations routinely 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 by specially trained staff. Sweat production is stimulated with a chemical the sweat glands called pilocarpine delivered to these glands by an electrical current. The sweat produced for approximately 30 minutes following stimulation is collected and sent to laboratory for analysis. This should be a painless procedure that may create a tingling or warm sensation. 

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

No test preparation is needed. However, you may be instructed to avoid applying creams or lotions to your skin 24 hours before the test. It is also important to be well-hydrated by drinking plenty of water before undergoing the procedure.

The Test

How is it used?

The sweat 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  from a blood spot in the Newborn Screening Program. 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 sweat chloride 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 or has a positive or equivocal (uncertain) result from a blood spot in the Newborn Screening Program. It is not used to monitor CF since elevated levels do not correlate with the severity of the disease or its symptoms.

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 sweat chloride 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. 

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 anorexia nervosa, Addison 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 oedema (build up of fluid) 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

Can I have a sweat chloride test done at my doctor's office?

It is unlikely because this test should only be performed at specialised centres with staff specifically trained in the this test.

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

You are best to talk to your doctor and a genetic counsellor about testing the other siblings for CF gene mutations, regardless of whether they have symptoms or not, to determine whether they are carriers.

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: January 10, 2023

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