Sweat Chloride Test

At a Glance

Also known as

Sweat electrolytes, Iontophoretic sweat test

Formal Name

Sweat chloride

Related tests

Immunoreactive trypsin (IRT), Stool trypsin, CF gene mutation

Why get tested?

To diagnose cystic fibrosis (CF)

When to get tested?

When a patient has symptoms that suggest CF; as a follow-up, confirmatory test to help diagnose CF

Sample required

A sweat sample collected using a special sweat stimulation procedure

The Test Sample

What is being tested?

The sweat test measures the amount of sodium and chloride in sweat. Sodium and chloride are part of your body’s electrolyte balance, and combine to form the salt found in sweat. They help regulate the fluid balance in your tissues. 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.

Except for sperm cells in males and egg cells (oocytes) in females, every cell in the body has 46 chromosomes, organized in 23 pairs. A gene on chromosome 7 is responsible for the normal production of CFTR. Patients with CF have a mutated gene on each chromosome 7. With the mutation, the CFTR protein may be dysfunctional or totally absent. Since CFTR 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 causes the cells to be impermeable to chloride conductance and results in increased sodium and chloride concentrations in sweat.

Two methods of sweat analysis are most frequently used: chloride concentration and conductivity measurement. The sweat chloride analysis is recommended as the diagnostic test for CF. Sweat conductivity 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. A tiny amount of a 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 analyzed.

The Test

How is it used?

The sweat chloride test is used to test for CF in symptomatic patients. It is also used to help confirm or rule out a diagnosis of CF in patients who have tested positive or indeterminate with 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 ordered?

The sweat chloride test is ordered when a patient has symptoms of CF, and/or has a close relative who has been diagnosed with CF. Symptoms of CF include: noticeably salty sweat; frequent respiratory infections and chronic cough; gastrointestinal symptoms - distal intestinal obstruction (meconium ileus in infants), bulky offensive greasy stools, malnutrition, and male infertility (obstructive azoospermia).

The sweat chloride test may also be ordered to help confirm a diagnosis in patients who have tested positive for CF. So, for example, a doctor might request a sweat chloride for patients based on other tests including a screening sweat test, the immunoreactive trypsin test (IRT), the trypsin test, and the nasal (transepithelial) potential difference (NPD) test.

It may also be ordered in the case of patients who have tested negative with a standard CF gene mutation panel but who are clinically still suspected of having CF. The CF gene mutation panel generally tests for the 25 most common CF gene mutations (of almost 1000 possible mutations). If the panel is negative, then the patient may not have CF or they may have a more rare mutation. Sweat chloride testing can detect CF even if the genetic mutations causing it cannot be identified.

What does the test result mean?

A positive sweat chloride test indicates that there is a good chance that the patient has CF. Positive sweat chloride tests should be repeated for verification and confirmed, wherever possible, by CF gene mutation panel testing.

A few people with CF will have a normal or inconclusive sweat chloride test and will have to be evaluated using other tests, or the diagnosis may be made on clinical grounds alone.

The 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 weeks old. The sweat test may not need to be done if the patient has an elevated IRT and a positive CF gene mutation test.

Is there anything else I should know?

The sweat test will not pick up carriers of cystic fibrosis. It takes two mutated copies of the CFTR gene to cause cystic fibrosis. Those who are only carriers do not have CF and will not have sweat chloride abnormalities.

There are other conditions besides CF that can cause positive sweat tests. These include anorexia nervosa, Addison’s disease, nephrogenic diabetes insipidus, and hypothyroidism. Edema can result in false negatives.

The sweat chloride test should only be performed at specialized centers with experience with this kind of testing. Otherwise, problems in accuracy, including false negatives due to poor collection technique, can arise.

Common Questions

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

   Yes. 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 you 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 counseling before they decide to have children themselves. Some argue that testing on siblings not be done unless they are symptomatic; testing and counseling for reproductive choices can be done later.

2. 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, to find out how severe your child’s CF is. This can guide them in recommending a treatment plan and/or a referral to a special CF center where your child can get expert help, advice, and monitoring.