Sweat Chloride Test

At a Glance

Why Get Tested?

To diagnose cystic fibrosis (CF), an inherited disease caused by a mutation in each of the two copies of the CFTR gene

When To Get Tested?

When an infant has a positive newborn screening test for CF; when you or your child has signs and symptoms that suggest CF or tested positive or indeterminate for CF with other tests

Sample Required?

A sweat sample collected using a special sweat stimulation procedure (see below)

Test Preparation Needed?

None; however, you may be instructed to avoid applying creams or lotions to your skin 24 hours before the test. Also, it is important to be well-hydrated before undergoing the procedure.

Sweat Chloride Sample Collection

A sweat sample is collected using a special sweat stimulation procedure. Below is one example:

The patient’s skin (usually the forearm) is washed with water and patted dry.
A pad soaked in pilocarpine (chemical that stimulates sweat glands) is placed on the skin. An electrode creates a mild current that moves the chemical through the skin into the area where the sweat glands are. This procedure may create a tingling or warm sensation and takes about five minutes.
The electrode and pad are removed. The area of the skin that was stimulated has started to sweat.
A piece of filter paper that was previously weighed is placed over the area.
The area is covered with plastic and tightly bandaged. Sweat is collected for 30 minutes.
The piece of filter paper is now filled with sweat. It will be removed, weighed (to determine how much sweat was obtained), and placed into buffer so that the concentration of chloride can be determined.

For other, similar procedures, sweat may be collected into a plastic coil of tubing or onto a piece of gauze. The sweat obtained is then analyzed.

What is being tested?

The sweat chloride test measures the amount of chloride in sweat. Chloride is part of the body’s electrolyte balance and combines with sodium to form the salt found in sweat. People with cystic fibrosis (CF) have an elevated level of chloride in their sweat.

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 called the cystic fibrosis transmembrane conductance regulator (CFTR). It 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 is an inherited disease 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. With dysfunctional or absent CFTR, chloride does not move out of the ducts into surrounding fluid, resulting in the production of thick, sticky mucus. Since CFTR levels are usually highest in the epithelial cells lining the internal surfaces of the bronchi of the lungs, pancreas, sweat glands, salivary glands, intestine, and reproductive organs, these are the areas most affected by CF.

Dysfunctional or absent CFTR results in increased chloride in sweat, which can be measured with a sweat test. Two methods of sweat analysis are frequently used:

Sweat chloride concentration is recommended as the diagnostic test for CF.
Sweat conductivity testing may be used to screen for CF.

How is the sample collected for testing?

A sweat sample is collected using a special sweat stimulation procedure. (See above)

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

No special 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 before undergoing the procedure.

Common Questions

How is the test used?

The sweat chloride test is often used to help diagnose cystic fibrosis (CF) in infants who have tested positive on a newborn screening test for CF, such as an immunoreactive trypsinogen test (IRT) or CF gene mutation test.

The sweat chloride test may also be used to test for cystic fibrosis in symptomatic older children and adults. It may be used to help confirm or rule out a diagnosis of CF in those who have tested positive or indeterminate with other tests, including a screening sweat test and/or the nasal (transepithelial) potential difference (NPD) test.

It may also be ordered in the case of people who have tested negative with a standard CF gene mutation panel but who are still suspected of having CF due to signs and symptoms. The CF gene mutation panel generally tests for the most common CF gene mutations. If the panel is negative, then the person may not have CF or may have less common mutations not included in the screening panel. Sweat chloride testing may be diagnostic of CF even if the genetic mutations causing it cannot be identified. This testing may also be used to determine if additional mutation analysis is warranted.

When is it ordered?

The sweat chloride test is ordered when an infant has a positive newborn screening test for cystic fibrosis (CF). The sweat test cannot be performed accurately in the first two days after birth. It is typically ordered between 2 and 4 weeks of age. However, it may be difficult to collect enough sweat from some infants for testing, especially premature babies. If an insufficient sample is obtained, then testing should be repeated.

The sweat chloride test may also be ordered when an older child or adult has signs and symptoms of CF and/or has a close relative who has been diagnosed with CF.

Examples of signs and symptoms of CF include:

Frequent coughing, chronic cough producing thick, sticky mucus (sometimes bloody)
Repeated or persistent respiratory infections such as bronchitis or pneumonia
Recurrent sinus infections and nasal congestion caused by nasal polyps
Abdominal pain or discomfort
In newborns, no stools produced soon after birth (meconium ileus)
Chronic diarrhea or foul-smelling, greasy stools
Weight loss or malnutrition
Failure to thrive — large appetite but failure to gain weight or grow at a normal rate
Decreased levels of protein in the blood causing excess fluid accumulation just under the skin or within cavities of the body (edema)

It may also be ordered when someone has tested negative with a standard CF gene mutation panel but is clinically still suspected of having CF.

What does the test result mean?

A positive sweat chloride test indicates that it is likely that the infant or person tested has cystic fibrosis (CF). Positive sweat chloride tests are typically repeated for verification. The results may also be confirmed by CF gene mutation panel testing.

A negative sweat chloride test means that it is unlikely the person tested has CF. However, a few people with CF will have a normal or inconclusive sweat chloride test. The sweat test may be repeated or the person will have to be evaluated using other tests. Sometimes the diagnosis may be made on clinical grounds alone.

Is there anything else I should know?

There are other conditions besides cystic fibrosis that can cause positive sweat chloride tests. These include anorexia nervosa, Addison disease, nephrogenic diabetes insipidus, and hypothyroidism.

Excessive build-up of fluid (edema) can result in a false-negative result.

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

It is unlikely. The sweat chloride test should only be performed at specialized centers that have trained personnel who are experienced with this kind of testing. Otherwise, problems in accuracy, including false negatives due to poor collection technique, can arise.

If one of my children has CF, should my other children be tested?

You may wish to talk to your healthcare provider or a genetic counselor about testing the other siblings for CF gene mutations, regardless of whether they have symptoms, to determine whether they are carriers. Some carriers can experience some symptoms associated with cystic fibrosis. Also, you may want to consider testing and genetic counseling for the siblings so they know whether or not there is a risk that they can pass a mutation to any children they may have in the future.

What other tests might my healthcare provider recommend if my child has CF?

Your health care provider may do other tests, such as chest X-rays as well as lung function tests and pancreas function testing, to determine the severity of your child’s CF. This can guide the healthcare provider in recommending a treatment plan and/or a referral to a special CF center where your child can get expert help, advice, and monitoring.

View Sources

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Timothy S. Uphoff, Ph.D., D(ABMG), MLS(ASCP)^CM. Section Head Molecular Pathology Laboratory, Marshfield Labs, Marshfield Clinic, Marshfield WI.

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