Understanding CF Below
 the Surface

Cystic fibrosis (CF) feels a little different for everyone. But it all comes down to a problem with the way salt and water move in and out of the cells. Mutations found on both copies of a specific gene cause proteins throughout the body to be made incorrectly. This results in a buildup of thick, sticky mucus in the lungs and beyond, leading to inflammation and infections that can cause damage, even before it can be felt.

This information can help you understand what causes CF, how it impacts the body in a variety of different ways, and how you and your loved one can stay proactive in care team conversations. It is not meant to be used to diagnose CF or replace discussions with a healthcare professional. Always talk to your doctor to learn more.

What causes CF?

Genes carry the instructions for every part of the body. Sometimes an abnormality or change occurs in these instructions, which can cause certain diseases. These faulty instructions are called “mutations” and there are many different types. The specific gene responsible for CF is called the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene contains the instructions for producing CFTR proteins, which do an important job on the surface of certain cells throughout the body.

Just like other genes, the CFTR gene is inherited from parents. Every person has two copies of this gene (not just people with CF) and gets one copy from each parent. A person who has CF has two copies of the CFTR gene with disease-causing mutations, which means that the CFTR proteins in their body aren’t able to do their job. A person who does not have CF either has two copies of the CFTR gene without disease-causing mutations or is a “carrier”—meaning they have one copy of the CFTR gene with a disease-causing mutation and one copy of the gene without.

Over 2,000 mutations in the CFTR gene have been discovered and more than 1,700 mutations cause the lack of CFTR function that results in CF. Defects vary by mutation but may show up as:

Protein production mutations: The body produces no functional CFTR proteins
Protein processing mutations: The body produces misshapen CFTR proteins that cannot move to the cell surface
Gating mutations: CFTR proteins make it to the cell surface, but the cell gate locks in a closed position so the chloride cannot get through
Conduction mutations: Changes to the structure of the inside of the CFTR protein make it hard for chloride to move through the body easily
Insufficient protein mutations: The body produces a limited amount of CFTR proteins

Normally, CFTR proteins help move chloride (a part of salt) in and out of cells. This process helps the body maintain a healthy balance of salt and water. When CFTR proteins don’t work properly, the balance between water and salt gets thrown off. See how this process can lead to CF progression and other symptoms across specific organs and systems.

The role of sweat chloride

You may have heard about “salty sweat” as a telltale sign of CF. And that’s because people with CF are likely to have saltier sweat because of higher sweat chloride levels.

Chloride is a key component of salt. So, when a lack of CFTR function causes an imbalance of salt and water, more chloride shows up in sweat. That’s why sweat chloride is an indicator of CFTR function and why the sweat test, which measures sweat chloride, is one of the ways to diagnose CF.

So what does sweat chloride signal beyond diagnosis? CFTR function, sweat chloride levels (also known as SwCl concentration), and disease severity are all closely linked. Since increased sweat chloride levels suggest that chloride is not moving through the cells properly, it can be an indicator of poor CFTR function—which can then lead to thickened mucus, inflammation, infection, and eventually, organ damage. Problems with the way chloride moves through the cells is the first step in this process and can demonstrate an impact or decrease of CFTR function before other signs of disease progression appear throughout the body. With this connection to CFTR function, sweat chloride is also used in clinical studies to evaluate the impact of CF medications on CFTR function.

Interested in learning more about the sweat chloride connection? Check out this downloadable resource and consider asking your care team the following questions:

Can you tell me more about CFTR function and how it’s measured?
What do sweat chloride levels indicate at diagnosis?

Why genotype matters

The different forms of the CFTR gene inherited from parents are called alleles. One copy of the gene, or allele, comes from each parent and they can be the same or different. The individual combination of genes is a person's genotype.

Different mutations affect CFTR proteins in various ways. As a result, CF symptoms and when they occur can be different for everyone.

Knowing genotype can help someone with CF: