How does COPD affect the lungs
COPD - Preventing Deadly Inflammation of the Lungs
Cigarette smoke and heavily polluted air - these are by far the greatest risk factors for chronic obstructive pulmonary disease, COPD for short. COPD causes permanent inflammation in the airways and lung tissue. Those affected suffer from chronic coughing, phlegm and shortness of breath. Because in the long term, both airways and lung tissue are destroyed. As a result, the lungs lose their structure and breathing becomes extremely difficult. According to WHO estimates, COPD is the third leading cause of death worldwide. Since the disease processes are still largely unexplained, therapies can only slow the progression of the disease. Scientists at the German Center for Lung Research (DZL) have now succeeded in deciphering a previously unknown disease mechanism of COPD and preventing it in the laboratory with a drug.
The team around Dr. Ali Önder Yildirim from Helmholtz Zentrum München took a close look at the inflammatory process in the lungs of COPD patients. They concentrated on tertiary lymph nodes in the bronchi, more precisely on the so-called inducible bronchial-associated lymph nodes, iBALT for short. These form in the lungs during an infection, autoimmune disease, or chronic inflammation like COPD. “It is now assumed that the development of iBALT plays a very central role in the worsening of COPD. How and where iBALT are formed in the lungs, however, was unclear so far, ”says Yildirim.
The lymphatic system with the lymph vessels as conduction pathways is the most important transport system in the human body besides the blood circulation. It specializes in the transport of nutrients and waste materials and also dumps pathogens such as bacteria in the lymph nodes. Tertiary lymph nodes later form in the various organs near inflammation, to put it simply as improvised lymph nodes. One form of tertiary lymph nodes are inducible bronchial-associated lymph nodes, iBALT for short. These form in the lungs during an infection, autoimmune disease, or chronic inflammation like COPD.
Oxysterol metabolism: key to the development of COPD?
First, the lung specialists looked for known processes in other lymph tissues. They became aware of the oxysterol metabolism. Oxysterols are derivatives of cholesterol and play a role in many different biological processes, including the migration of immune cells into the lymphatic tissue. "We now wanted to find out whether this is also the case in the area around the lungs and especially in the case of COPD caused by cigarette smoke," explains Yildirim. In fact, both in the animal model and in the lungs of COPD patients, the researchers found increased amounts of the enzymes that are responsible for oxysterol metabolism - accompanied by immune cells migrating into the lung tissue. Immigration of immune cells is a natural response of the human body to inflammation. In the lung tissue, however, the immune cells can release substances that are toxic to the tissue, which destroys the lung tissue. Further experiments showed that the formation of iBALT is inhibited when the oxysterol metabolic enzymes are not present. In this case, the immigration of immune cells was also prevented, and the lungs of the test animals were not damaged despite cigarette smoke.
The researchers then tried to simulate this effect with a drug: To do this, they blocked the oxysterol metabolism with an inhibitor called clotrimazole, an approved antimycotic, i.e. a drug against fungal infections. In fact, the active ingredient was able to prevent the immigration of immune cells in mice after exposure to cigarette smoke and thus also the formation of iBALT. "In the future, our goal will be to transfer these results from the animal model to humans in order to be able to intervene early on in the development of COPD," hopes Yildirim.
German Center for Lung Research
The German Center for Lung Research (DZL), founded in 2011, is one of the six German Centers for Health Research funded by the Federal Ministry of Education and Research and the federal states. In the DZL, excellent scientists and their teams from university and non-university institutions work together in the field of lung research at five locations. Together they have the goal of developing new approaches for the prevention, diagnosis and therapy of lung diseases. The focus is on eight disease areas: asthma and allergies, chronic obstructive pulmonary disease (COPD), cystic fibrosis, pneumonia and acute lung failure, diffuse parenchymal lung diseases, pulmonary hypertension and end-stage lung diseases.
More information: www.dzl.de and www.cpc-munich.de
Dr. Ali Önder Yildirim
Helmholtz Centre Munich
Comprehensive Pneumology Center (CPC-M)
German Center for Lung Research (DZL)
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