Unprecedented research pathways against severe asthma.

Unprecedented research pathways against severe asthma

New tracks are explored to better respond to this disease still difficult to understand.

"Asthma is a disease that is both easy and difficult to treat: easy for the vast majority of patients who need only a mild treatment, and difficult for those whose initial treatment does not control from the outset. disease. "Thus, the New England Journal of Medicine presented a recent study on the treatment of severe asthmatic children. For them, one rule: a tailor-made treatment, regularly evaluated. Failure to do this chronic inflammatory disease, made of crises in which the narrowing of the bronchi limits breathing, may worsen.

Three million French people suffer from asthma, and 350 million people are affected worldwide. "The disease has progressed a lot in 40 years in the industrialized countries, with, it seems, a plateau for three years in adults, while it continues to grow in children. In emerging countries that adopt the Western way of life, its growth is dazzling, "says Professor Michel Aubier, head of the department of pneumology of CHU Bichat (Paris). There are multiple reasons. "To develop asthma requires a genetic predisposition and environmental factors. Air pollution plays a role, but also the indoor environment because we spend 90% of our time in poorly ventilated rooms, rich in various allergens. Our diet has also changed. We consume fewer fresh products, so less protective antioxidants, and more industrial foods containing many allergens: peanut oils, dyes, preservatives ... Finally, the reduction of early childhood infections due to better hygiene orients rather, the development of the immune system towards an allergic profile. "In France, better care has reduced asthma deaths from 2,000 to less than 1,500 a year, but the number of severe cases seems to be increasing.

Asthma is due to immune dysfunction that induces bronchial intolerance to certain antigens or allergens in the environment. Their presence triggers a cascade of "hostile" reactions orchestrated by immune cells, several categories of T lymphocytes, such as those that activate the production of mediators of the allergic reaction or those that are responsible for "supervising" the whole of the implementation. place of defenses.

But above all, asthma appears more and more like a disease of the epithelium, the lining of the bronchi. "There is permanent exchange between it and the underlying tissues," says Pr Aubier. In some severe asthma, the epithelium has an abnormal functioning, sometimes from early childhood, which causes a progressive remodeling bronchial fibrosis, and hypertrophy bronchial smooth muscle, also abnormal. This remodeling, which can not be regressed, is at the origin of bronchial obstruction. Better understanding it to find therapeutic targets is a major issue. "As a result, we begin to wonder if asthma is a single disease. "The 80% mild to moderate asthma is easily controlled with beta2-mimetics that relax the bronchial muscles and inhaled corticosteroids that inhibit the inflammatory response. On condition of following the treatment, regrets Professor Aubier, which is the case for only 30% of patients, resulting in 60% poorly controlled asthma.

New paths of hope

There remain 20% of severe asthma, which represent 80% of the cost of asthma, 1.5 billion euros per year. "Those with a strong allergic component are significantly improved by a new injectable anti-IgE drug, Xolair. Others (with high eosinophilia) may be treated with anti-Il5 antibodies. But some serious non-responders to corticosteroids remain without any new option. We have shown that endothelin 1, a profibrosing factor and proliferator of smooth muscle, was highly overexpressed in the epithelium of nonresponders. An ongoing study evaluates the interest of an antireceptor of endothelin 1, "explains Pr Aubier.

We are trying to dismantle severe asthma into homogeneous groups of patients, to identify relevant biomarkers and to develop targeted treatments for these various groups. New pathways, along with other monoclonal antibodies, are being investigated. Another way, thermoplastics, is to partially destroy the smooth muscle by radiofrequency to reduce its mass. Tested in America, it seems to reduce the frequency of seizures.

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