American researchers have discovered two molecules whose role is decisive in the development of allergic asthma. They are currently working on finding a treatment capable of preventing these molecules from functioning in order to prevent the development of asthma attacks in the face of an allergen and even limit their recurrent occurrence.

Asthma is a chronic respiratory disease caused by permanent inflammation of the bronchi. It manifests as seizures, characterized by episodes of difficulty breathing, wheezing, dry cough, or a feeling of tightness in the chest. Some asthma is triggered occasionally under very specific conditions: workplaces, contact with an animal, a walk in the country when the pollens are in the air ... it is intermittent asthma. In other cases, asthma is present throughout the year: it is then persistent and more or less severe. The causes are often multiple and the attacks can be short-lived or last for several days.

On this subject, the Asthma & Allergies association specifies that “whatever the triggering mechanism, asthma is recognized today as an inflammatory disease: hence the importance of anti-inflammatory drugs in the daily treatment of asthma and to cure acute attacks. "Thus, an asthmatic should be able to live normally if he is properly monitored and treated. It is with this in mind that researchers at the La Jolla Institute of Immunology (United States) are currently working on a way to prevent asthma attacks from occurring early on, that is, before the person needs use inhalers and fast-acting medications.

"A way to block the inflammatory response"

They claim to have discovered in mice that blocking two immune molecules at the same time is essential to prevent asthma attacks. “We have found a way to block the acute inflammatory asthmatic response, and we have seen a strong lasting reduction in asthma exacerbations,” says Prof. Michael Croft, author of the study published in The Journal of Allergy and Clinical Immunology. When a person with asthma encounters a triggering factor, certain cells of the immune system, T cells, which normally defend the body against viruses and bacteria, build up in the lungs.

Their presence in this organ triggers chronic inflammation that is the root cause of the well-known asthma symptoms and this new study shows how it is possible to limit this process. For the study, the researchers focused on blocking OX40L and CD30L, molecules that are upregulated by allergens and can activate harmful T cells that cause inflammation. To do this, they worked with a mouse model sensitive to mites, a very common asthma trigger, and showed that the simultaneous blocking of these molecules could stop the accumulation of harmful T lymphocytes in the lungs, which reduces inflammation.

A real public health issue

“The combination of suppressing the two sets of signals resulted in a large reduction in the number of these pathogenic T cells, while only neutralizing one or the other had a relatively mild effect. This is quite an important discovery, ”adds Professor Michael Croft. But that's not all, the scientific team also found that the simultaneous blocking of the OX40L and CD30L molecules reduced the number of pathogenic T cells that persisted in the lungs after the asthma attack. However, these so-called “memory” T cells are likely to cause inflammation again when the asthmatic person again encounters an allergen.

Concretely, without these two molecules at work, very few of these harmful T cells remained in the lungs and the mice had a poorer response to the mites for weeks after the initial treatment. For Professor Croft, “this suggests that we have reduced the allergen's immune memory. This discovery is important since, in addition to the treatment of asthma, the researchers hope that this process can act as a long-term treatment for inflammatory and autoimmune diseases linked to these pathogenic T cells. It remains to find in humans the best therapeutic combination to block the two molecules within the same treatment.

According to Inserm, allergic asthma is a public health problem that currently affects 8 to 10% of the world's population and represents 70% of forms of asthma and is responsible for more than 250,000 deaths per year. While this pathology was almost non-existent at the end of the 19th century, its prevalence but also its severity has increased in recent years. “Its resurgence represents a significant economic cost as long as its treatment remains purely symptomatic. », Specifies the organization. However, currently 5 to 10% of patients suffering from allergic asthma are not relieved by the usual treatments such as anti-inflammatory drugs and bronchodilators.