Sweattest

Question

Dear CF-experts,

I am 29 years old and have cystic fibrosis with the homozygous Delta F508 mutation. Overall, I have a mild course of the disease. Fortunately, I have no lung-related issues, and my FEV1 stands at 112%. My symptoms are predominantly gastrointestinal. Additionally, I have CF-related diabetes.

My diagnosis has been genetically confirmed via blood testing since 1997. At that time, my sweat test result fell within the "gray zone" at 52 mmol/L; however, insufficient sweat was collected, rendering the result uninterpretable.

Recently, I underwent another sweat test, and my current result—at 109 mmol/L—is significantly elevated. Given the mild nature of my condition, I honestly expected a lower value. Consequently, I feel somewhat unsettled.

What is the significance and diagnostic value of the sweat chloride level? Does it provide any insight into the progression or severity of the disease?

Thank you very much for your advice!

Best regards,

Answer

Dear patient,
If your genetic report indicates that you are homozygous for the Delta F508 mutation, this means that you carry a mutation—specifically a so-called Class II mutation—on both alleles (these are the corresponding gene loci; you inherited one from your father and one from your mother). Due to faulty protein folding, this mutation results in little to no CFTR channel being transported to the cell membrane to perform its function there.
Genetically, this would result in a typical—or "severe"—form of CF, accompanied by pancreatic insufficiency. The sweat test results for such patients (approximately 50% of all CF patients share the same mutation combination as you, meaning there is a wealth of data available) typically show chloride concentrations around 100 mmol/L; therefore, a result of 109 is absolutely to be expected if you are not taking a modulator. The value of 52 mmol/L was almost certainly unreliable and would be highly unusual; although, in rare cases, it does happen that an initial reading is low but subsequently rises over time to reach the aforementioned level.
However, it is also known that in cases of genetically typical CF, while pancreatic insufficiency is highly predictable, the severity of lung-related issues can actually vary significantly, even among patients with the exact same mutation combination. While one might typically expect more severe lung problems—such as those caused by thick, tenacious mucus—we also encounter very mild pulmonary cases. These include patients like yourself who, despite their specific mutation combination, maintain excellent lung function over a long period—particularly when adhering diligently to a regimen of exercise, physiotherapy, and inhalation therapy. However, the sweat test confirms that your chloride channel is functioning very poorly, if at all. It is now understood that by restoring—or at least improving—chloride channel function (via modulators!), the progression of the disease can be significantly mitigated. Furthermore, many existing problems can be alleviated (e.g., improved weight gain, better lung function, reduced colonization by problematic pathogens such as Pseudomonas, and regression of nasal polyps), while others may not develop to the same extent later in the disease course—for instance, lung function tends to remain stable for longer periods.
Therefore, current medical practice dictates that through therapy with modulators (in your case, this would be Kaftrio/Kalydeco® or, more recently, Alfytrek®), the sweat test values ​​should be driven down as low as possible. This means that even if you currently have good lung function, initiating modulator therapy is strongly recommended—particularly given such high sweat test values. Studies have shown that Alfytrek, on average, achieves the greatest reduction in sweat test values; therefore, you should discuss initiating this therapy with your medical team.
If modulators are administered early enough—specifically in infants (who may have already been exposed to Kaftrio "in utero" via maternal intake) or in toddlers (who can receive Orkambi starting at age 1, or Kaftrio starting at age 2)—it is possible in some cases to prevent, or even improve or reverse, pancreatic insufficiency. This demonstrates just how effective these medications truly are.
In your specific case, it is unlikely that there will be any change regarding your pancreatic insufficiency; however, your lungs can certainly be protected over the long term.
I hope this information has been helpful.
Sincerely,
Daniela d'Alquen

17.05.2026