Research Into Inflammation

Inflammation is part of your body's immune system response to something harmful or irritating, such as germs, irritants (e.g., pollen, pollution) in the airway, or damaged cells. White blood cells, blood, and fluids rush to the affected site to combat and clear infections or irritants from the body, often causing swelling, redness, and heat in that area. In the lungs, an immune response causes swelling and more mucus to be released into the airway. The swelling and mucus narrow the airways and make it harder to breathe. An increased cough is often a sign of inflammation.

When the lungs are infected with bacteria, white blood cells release enzymes, called proteases, to break down the structural proteins in bacteria and eliminate the threat. Once the infection is gone, other chemicals signal the white blood cells to stop the attack. However, in people with cystic fibrosis, these chemical signals often are weaker than expected, which can allow inflammation to continue rather than resolve normally.  

Repeated bouts of infection and inflammation gradually weaken the walls of the airways, causing them to widen, sag, and become scarred. This condition is called bronchiectasis. Bronchiectasis makes it even more difficult to clear out bacterial infections and perpetuates a cycle of worsening mucus buildup, infections that cannot be cleared, and inflammation in the airways that damages the lung tissues. This can eventually lead to an inability of the lungs to function enough to survive. 

Although inflammation is typically triggered by an infection, there is evidence of inflammation in the lungs even when no infections are detected. For this reason, CF clinicians believe that early intervention is essential to prevent long-term damage.

Researchers are not sure why people with CF have chronic inflammation, but they have several hypotheses:

• Thick, abnormal mucus in CF airways does not have the same germ-killing composition of healthy mucus. This environment promotes infections and hinders subsequent attempts to clear the infections, resulting in a loop of continued inflammation.
• Cells with a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein are sending too many inflammatory signals to the immune system, causing inflammation to last longer than necessary. Researchers are investigating what causes this excessive signaling and ways they can block those signals.
• The body's process of regulating the immune response after recovering from an infection may be abnormal and prevent cells from resolving inflammation.
• Massive quantities of enzymes released from a type of white blood cell known as a neutrophil overwhelm signals to stop the immune system's attack. Researchers are looking into potential ways to inhibit these enzymes, one of which is known as neutrophil elastase.

New treatments are being developed to modify or dampen the immune response of people with CF without compromising their ability to fight off infections.

Researchers are investigating different approaches to reduce the inflammatory response and boost the natural processes that help control inflammation. In the video below, Terri Laguna, MD, the director of the cystic fibrosis center at Lurie Children's Hospital of Chicago, discusses two different approaches to tackling inflammation in CF.

Clinical trials are underway for anti-inflammatory drugs for CF. Multiple companies are testing drugs that suppress cathepsin C, a protein in the body that plays a key role in inflammation by helping to activate neutrophil elastase. These drugs are being tested in people with bronchiectasis caused by CF and also by conditions other than CF.  

Clinicians can prescribe antibiotics such as azithromycin, which has anti-inflammatory effects. Steroids, such as prednisone, reduce inflammation but can't be used long-term because of side effects.

High doses of ibuprofen, a non-steroidal anti-inflammatory, have been shown to reduce inflammation in the lungs in people with CF over several years. However, CF doctors don't often prescribe ibuprofen because of side effects associated with high doses, such as kidney problems and ulcers.

Because infections and inflammation are so closely linked, several treatments or areas of research focused on treating infections are expected to also address much of the inflammation that exists in the CF lung. Similarly, because mucus build-up in the airways is also closely tied to both infection and inflammation, drugs such as the CFTR modulators that effectively clear out much of this mucus also reduce inflammation. 

• Research Into Infections
• Research Into Mucus
• Research Into Digestive System Issues
• Research Into Cystic Fibrosis-Related Diabetes