Cystic fibrosis drug may help treat pneumonia: study | Health

Pathogens such as SARS-CoV-2 and pneumococcus can cause severe pneumonia. If the airways fill with fluid, the patient is at risk of developing acute respiratory distress syndrome. Researchers at Charite – Universitatsmedizin Berlin have now discovered the molecular mechanism behind fluid accumulation in the lungs. It also led them to discover a potential new therapy: A cystic fibrosis drug proved effective in their lab experiments, raising hopes that it could be used to treat the pneumonia that causes the disease. This study has been published in the journal Science Translational Medicine.

The most common cause of fluid accumulation in the lungs is pneumonia. This condition, called pulmonary edema, results in parts of the airspaces being filled with fluid instead of air, which prevents them from doing their job of exchanging gases. Patients have difficulty breathing and their bodies cannot get enough oxygen. The diagnosis is acute respiratory distress syndrome, or ARDS. “Despite state-of-the-art medical procedures, about 40 percent of patients with ARDS die in intensive care. The problem is that antibiotics, antivirals, and immune-modulating therapies rarely work well,” study leader Professor Dr. Institute of Physiology at Charite. “So we took a very different approach in our study. Instead of focusing on the pathogen, we focused on strengthening the barrier function of the blood vessels in the lungs.” This makes sense, since they are the source of fluid in pulmonary edema. The pulmonary vessels are permeable, allowing fluid from the blood to flow into the surrounding tissues—and thus flood the airspace.

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But what actually causes it? What are the underlying molecular mechanisms? Prof. A Charitable research team led by Kubler set out to answer these questions. They performed experiments using cells, lung tissue and isolated lungs. The study focused on the CFTR chloride channel, which scientists know is found primarily in the mucosal cells of our airways. There, it plays a major role in keeping our mucus thin so that it can be expelled easily. Researchers have now shown for the first time that CFTR is also present in lung blood vessel cells and that its presence is significantly reduced in pneumonia.

To find out what role CFTR plays in pulmonary vessels and what happens at the molecular level when the chloride channel is lost, the researchers blocked the channel with an inhibitor and measured the number of chloride ions in the cells. Then they used a special imaging technique known as immunofluorescence imaging: “We saw that the inhibition of CFTR triggered a molecular cascade that eventually caused the blood vessels in the lungs to become leaky,” said Dr. says Lasti Erfinanda, who also works at the Institute of Physiology. Lead author of the study. “So CFTR plays a very important role in the development of pulmonary edema.”

The study findings indicate that loss of CFTR causes chloride to accumulate in cells because it stops being transported out of them. Excess chloride triggers a signal that ends with an uncontrolled influx of calcium into cells through a calcium channel. “Increased calcium concentration then causes the vascular cells to contract — much like calcium affects muscle cells,” Prof. Kuebler explains. “This results in gaps between the cells — which allow fluid to escape from the blood vessels. So chloride channels are important in maintaining the barrier function of the pulmonary vessels.”

The research team then addressed another question: How might they reduce or prevent pneumonia-induced damage to chloride channels in pulmonary vessels? To answer this, the researchers used a therapeutic agent that is classified as a CFTR modulator and is currently used to treat cystic fibrosis. In cystic fibrosis patients, a genetic mutation prevents the CFTR chloride channel from working properly in the mucosal cells of the airways, causing too much cold mucus. “Ivacaftor is a drug that increases the opening of chloride channels, which helps mucus flow through the airways,” Dr. Erfinanda says. “We wanted to see if it would also have a positive effect on lung blood vessel cells.”

Ivacaftor made the chloride channels more stable: it caused less collapse of the channels that is usually caused by inflammatory processes in the lungs. Experiments in animal models showed the same effect: treatment with ivacaftor increased the chance of surviving severe pneumonia, reduced lung injury, and resulted in much milder symptoms and a much better general condition than without the drug. “We really didn’t expect it to work so well,” Prof. Kubler says. “We hope that our findings will pave the way for clinical trials to test the effectiveness of CFTR modulators in patients with pneumonia. If this promising, pathogen-independent therapy finds its way into clinical practice, it could benefit a large number of patients and prevent pneumonia. can be avoided. even in the case of life-threatening – unknown pathogens.”

Prof. Kuebler and his team are now planning research projects aimed at developing other potential therapies based on the CFTR signaling pathway. They are also going to investigate which patients are at high risk of developing ARDS, so that they can provide preventive, personalized treatment to these patients.

This story is published from the Wire Agency feed without modification to the text.

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