The sweat test is a simple diagnostic tool that measures the amount of chloride in a person’s sweat. Elevated chloride levels in sweat are a hallmark of cystic fibrosis (CF), a genetic disorder affecting various organs in the body. This test is non-invasive and remains the gold standard for accurately diagnosing cystic fibrosis in infants, children, and adults. It is frequently used to follow up on a positive result from a newborn screening blood test or to investigate symptoms suggestive of CF at any age.
The Role of Chloride in Sweat
The sweat test works because of the dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. This protein functions as an ion channel on the surface of epithelial cells in organs like the lungs, pancreas, and sweat glands.
In a healthy person, the CFTR protein in the sweat duct actively moves chloride ions from the sweat back into the body’s cells before the sweat reaches the skin. This reabsorption ensures the sweat excreted onto the skin has only a small concentration of salt.
In people with cystic fibrosis, a genetic mutation causes the CFTR protein to be defective or absent. This faulty ion channel cannot effectively reabsorb the chloride, leading to excessive amounts of chloride being trapped in the sweat. The resulting sweat is abnormally salty, which the test measures to confirm a diagnosis.
How the Sweat Test is Administered
The formal procedure is the Quantitative Pilocarpine Iontophoresis Test (QPIT), which generally takes about one hour.
Stimulation Phase
The test begins with a stimulation phase, usually on the forearm or leg, to encourage sweat production. A colorless drug called pilocarpine is applied to the skin, and a mild electrical current is passed through the area using an electrode, a process called iontophoresis. The current is minor and not painful, though some individuals may feel a slight tingling sensation or warmth for the five minutes it is applied. Pilocarpine stimulates the sweat glands, causing them to produce a measurable amount of sweat.
Collection Phase
The technician then cleans the stimulated area and proceeds to the collection phase, which lasts for approximately 30 minutes. The sweat is gathered using a specialized collection device, such as a small plastic coil, or by placing filter paper or gauze over the site. A sufficient amount of sweat must be collected for accurate analysis; a minimum volume of 15 microliters is typically required for the coil method. Once collected, the sweat is immediately sent to a specialized laboratory where the chloride concentration is measured.
Understanding the Results
Sweat chloride test results are measured in millimoles per liter (mmol/L) and are interpreted based on specific numerical cutoffs. A result is considered normal, or unlikely to indicate cystic fibrosis, if the chloride concentration is 29 mmol/L or less, regardless of age. However, rare forms of CF can still be present even with a normal reading.
A sweat chloride value of 60 mmol/L or higher strongly indicates a cystic fibrosis diagnosis. Results falling in the intermediate range require further investigation. For infants up to six months, this range is 30 mmol/L to 59 mmol/L. For individuals older than six months, the intermediate range is 40 mmol/L to 59 mmol/L.
An intermediate result means CF is possible but not confirmed by the sweat test alone, often prompting a repeat test or the use of other diagnostic methods. The sweat chloride value is generally stable throughout a person’s life and is not significantly affected by temporary illnesses.
Follow-Up After Confirmation
When a sweat test result is positive (60 mmol/L or greater), the diagnosis of cystic fibrosis is highly likely. It is standard practice to confirm this result with a second, independent diagnostic method, often a genetic test. Genetic analysis involves testing a blood sample for mutations in the CFTR gene, which are the root cause of the disorder.
If the sweat test is in the intermediate range, extensive CFTR gene sequencing is necessary to look for two disease-causing mutations. Individuals with a positive newborn screen and an intermediate sweat test result may be classified as having a CFTR-related disorder if the diagnosis cannot be fully resolved.
Once a CF diagnosis is confirmed, the individual is immediately referred to a specialized cystic fibrosis care center. These centers provide comprehensive, multidisciplinary care for managing the condition and developing a long-term treatment plan.