Asthma progresses through the breakdown of the thin layer of epithelial cells that protect the bronchi, causing the respiratory passages to become damaged and inflamed, according to research led by King's College London that is presented today in the journal Science. Researchers have shown in mice that preventing the destruction of the protective cell layer with a drug prevents the chain reaction of lung damage that chronicles and exacerbates asthma.
The discovery has “the potential to revolutionize how asthma is treated,” highlight Jeffrey Drazen and Jeffrey Fredberg, from Harvard Medical School (USA) in an analysis article in Science.
With almost 300 million people affected in the world, and more than a thousand deaths a day, asthma is one of the chronic diseases with the greatest impact on global health, says the World Health Organization (WHO). In the last century it was thought that asthma was due to excessive contraction of the muscles surrounding the bronchi, causing a narrowing of the airways (or bronchoconstriction). But bronchodilator drugs, although they improve symptoms, do not prevent asthma from progressing in many patients.
More recently it was thought that the cause was inflammation of the airways. But anti-inflammatory treatments also do not break the asthma cycle, which indicates that inflammation is not at the origin of the disease but rather develops later.
The new research has focused on the epithelium, which is a thin layer of cells that covers and protects tissues of the human body such as, in this case, the bronchi. Researchers at King's College had discovered, in previous research, that the epithelia of the human body renew themselves by pushing old cells out of the tissue to make room for new ones. They have now shown that, in the case of asthma, this extrusion is done so violently that lesions remain in the epithelium, because the new cells that must replace them have not yet been formed.
“Whenever there is an asthma attack, there is bronchoconstriction, that is, the airway closes, causing the patient to suffocate. The problem is that, as the airway closes suddenly, the epithelial cells that cover it have no space and are extruded,” Elena Ortiz-Zapater, co-author of the research, from the University of Valencia, explains to La Vanguardia.
The lesions left in the epithelium are vulnerable points through which viruses, bacteria, toxic substances or allergens can damage the bronchi, causing respiratory symptoms and an inflammatory reaction. These symptoms, in turn, can cause the extrusion of more epithelial cells, thereby reinforcing the asthma cycle.
However, experimental drugs that act directly on the epithelium allow it to regenerate, end inflammation and bronchoconstriction, and end the asthma cycle. “We are very excited about the prospect of using gadolinium in people,” says Jody Rosenblatt, director of the research, in an email. In experiments with mice, gadolinium has restored bronchial epithelium without apparent side effects. The compound is already used in patients as a contrast agent to obtain images in magnetic resonance tests, but it remains to be proven that it is safe when administered as therapy to people with asthma.
If it were not safe, “the development of other extrusion inhibitors may be beneficial,” the researchers conclude in Science. “Preventing the mechanical damage caused could pave the way for therapies that stop the entire inflammatory cycle of asthma, rather than treating only the symptoms.”
