Chronic inflammation in people with cystic fibrosis causes damage to lung tissue that can eventually lead to respiratory failure. Researchers are trying to discover ways to dampen the exaggerated immune response that causes chronic inflammation without affecting the body's natural defenses against infection.

What Is Inflammation?

Inflammation is part of your body's immune system response to something harmful or irritating, such as germs or damaged cells. White blood cells, blood, and fluids rush to the affected site to destroy the irritant and flush it from the body, often causing swelling, redness, and heat in that area. In the lungs, an immune response causes swelling that narrows the airways and makes 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 not released or are not plentiful enough to reverse the inflammatory response and prevent the destruction of healthy lung tissue.

Why Is It a Problem in CF?

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, which can eventually lead to respiratory failure.

Although inflammation is typically triggered by an infection, recent studies in infants and toddlers with CF have shown evidence of inflammation in the lungs before any sign of infection is detected. This research suggests that people with CF have chronic inflammation, even between infections. For this reason, CF clinicians believe that early intervention is essential to prevent long-term damage.

What Causes the Excessive Inflammation?

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

  • Excessive inflammatory signals are sent from cells with a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein. Researchers are investigating what causes this excessive signaling and ways they can block those signals.
  • 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.
  • An imbalance of omega-3 and omega-6 fatty acids, which help regulate the immune response, may hinder the ability of cells to resolve 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.

What Treatments Are Being Developed?

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. Deepika Polineni, M.D., MPH, assistant professor of Internal Medicine at the University of Kansas Medical Center and associate adult program director of the University of Kansas CF Care Center, discusses some of these strategies in this video.

Clinical trials are underway for several anti-inflammatory drugs for CF. These drugs aim to accomplish at least one of the following:

  • Increase the production of anti-inflammatory molecules
  • Reduce the production of molecules that increase inflammation
  • Inhibit the function of neutrophil elastase, an enzyme that -- when overproduced -- can break down healthy lung tissue
  • Address the imbalance of omega-3 and omega-6 fatty acids, enabling cells to resolve inflammation

What Current Treatments Do We Have?

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.

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