The word asthma comes from Greek, and one of the first written references is to refer to the shortness of breath suffered by the heroes of the Iliad after fighting a fight to the death. A few millennia later, the cause of asthma attacks—a sudden closure of the airways that can be fatal—is far from clear. In Spain, around 5% of the population suffers from this disease.
A study published this Thursday in the magazine Sciencea reference for the best world science, has just revealed a new cause of asthma attacks and suggests the path towards new treatments that not only alleviate the symptoms, but also prevent the serious damage they can cause to the health of people who suffer from it. they suffer.
Until now, it was thought that asthma was a disease of the immune system against an internal, genetic, or external agent, such as pollen or pollution. This immune reaction produced suffocation, inflammation of the respiratory tract, mucus, cough and the rest of the symptoms that characterize the disease. Current treatments are based on this idea and are aimed at opening inflamed airways with inhalers that dilate the bronchi, but do not attack the underlying cause of the disease.
The new work, led by researchers in the United Kingdom and the United States, explores the sudden contraction of the airways, especially their branches within the lungs, the bronchi. The team has analyzed this compression at the cellular level in the lungs of mice suffering from asthma and in respiratory tissue of patients. The results describe a phenomenon known as extrusion, which appears to be to blame for all of asthma's subsequent airway effects.
The Valencian pharmacologist Elena Ortiz-Zapater, a researcher in the biochemistry department of the University of Valencia, was the one who developed the animal models for the study. “We have seen that after the compression caused by asthma, the airways become very small very quickly, which affects the epithelial cells that line the inside of these airways,” explains the scientist. “We are talking about a type of cells that are not as flexible as muscle cells and that are not prepared for such an attack. As a result of the compression, the epithelial cells run out of space and end up dying and disappearing,” she adds.
After the attack, the airways remain “exposed” and allow pollutants or allergic agents to penetrate the body, which explains why asthmatics are more prone to suffer respiratory infections and also details how the vicious cycle of inflammation, obstruction occurs. and shortness of breath that characterizes asthma attacks.
Treatment for the causes
This “discovery is the result of more than ten years of work,” he highlighted. Jody Rosenblatt, a cell biologist at King's College London (United Kingdom) and lead author of the work. “As cell biologists, we have been able to show that the physical constriction of an asthma attack causes widespread destruction of the airway barrier. Without this barrier, asthma patients are much more likely to suffer from long-term inflammation, problems with wound healing in the airways, and infections that lead to more attacks. By understanding this fundamental mechanism, we are now in a better position to prevent all of these events,” Rosenblatt detailed in a note released by her institution.
The study has also tested an experimental treatment that could be the first to attack the causes of asthma and not just relieve its symptoms. Researchers have shown how to prevent this widespread destruction of the cellular barrier of the airways using gadolinium, a compound used as a contrast in MRIs. Researchers have shown that this compound prevents the extrusion of epithelial cells after an airway contraction event, which in turn prevents the inflammatory response, mucus and other symptoms associated with asthma attacks.
Current treatments “such as albuterol open the airways, which is crucial for breathing, but unfortunately do not prevent the damage or symptoms that follow the attack,” details Rosenblatt. “Fortunately, we can use an inexpensive compound, gadolinium, which is frequently used for MRI imaging, to stop airway damage in mice, as well as the inflammation and mucus secretion that follow. And preventing this damage could prevent the buildup of muscle that causes future attacks,” he adds.
It would have to be done, Ortiz-Zapater points out, by looking for a compound that imitates the activity of gadolinium, since this can be toxic if administered too frequently.
This finding “could stop the inflammatory cycle and even revolutionize current treatments for asthma,” say Jeffrey Drazen and Jeffrey Fredberg, environmental health experts at Harvard University (United States), in a commentary on the study also published in Science. The same mechanism, they point out, could be relevant to understanding and treating other diseases such as irritable bowel syndrome, also characterized by damage to epithelial cells due to sudden contractions similar to those caused by asthma in the airways.
“The epithelial layer of the airways provides a first line of defense against foreign antigens and is essential for maintaining tissue homeostasis,” explains José Gregorio Soto Campos, director of the Pulmonology and Allergy Clinical Management Unit at the Hospital de Jerez in statements to the information portal Science Media Center Spain. “It has previously been proposed that this loss of epithelial integrity that compromises the barrier function in asthma would not be secondary, but rather a cause of the pathogenesis of the disease, having important implications for the development of asthma. Studies conducted in the recent past suggest the existence of the asthma exacerbation-prone phenotype. We know that the occurrence of exacerbations in the recent past, requiring emergency services, is a reliable predictor of developing future exacerbations. This study may explain this greater susceptibility to new exacerbations in a group of patients. The experimentation presented in the article defines the role of the extrusion route in controlling the subsequent symptoms of an asthma attack and may open a path for future research into possible therapeutic targets,” he details.
For the future, it remains to be elucidated why this sudden compression of the airways typical of asthma occurs. It is likely, Ortiz-Zapater points out, that it is due to several factors. The mystery of the original cause of the disease that the Greeks described continues.
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