Why Do Some Children Not Respond to Asthma Medications? A Genetic Test Determines the Treatment

Researchers have stated that some children with asthma do not benefit from a medication used to reduce asthma attacks due to a common genetic variant, which opens the door for the use of genetic testing to select the most suitable treatment for each patient.

The researchers found that children carrying a variant in the SERPINE1 gene, which is present in about 60% of people, show different inflammatory changes in the airways when infected with a viral infection and receiving the drug "Mepolizumab," a biological treatment used by those with severe asthma.

Mepolizumab works by targeting a protein called "Interleukin-5," which is one of the important factors in the growth and activity of a type of immune cell known as "eosinophils," which play a prominent role in inflammation in many asthma patients.

The study published in the Journal of Allergy and Clinical Immunology indicated that the genetic makeup of the patient may affect the nature of the response to this treatment, especially during viral infections, which are among the most common triggers for asthma attacks in children.

The researchers analyzed data and samples taken from the noses of children aged 6 to 17 years, who suffered from asthma prone to recurrent attacks and had participated in previous studies.

The category of children aged between 6 and 11 years old, suffering from severe asthma, has joined the other groups authorized to take the drug "Dupixent" in Europe.

Analyses showed that children carrying the genetic variant produce higher amounts of a protein known as PAI-1 during viral infections, and the increase of this protein is associated with heightened fibrosis processes, or remodeling of the respiratory tract tissues, along with weakened antiviral responses.

When this genetic response was exposed to the influence of "Mepolizumab", researchers observed the activation of additional inflammatory pathways that may contribute to damage in the airway lining, changes that did not appear in the same way in children who do not carry the genetic variant.

The co-researcher in the study, Rajesh Kumar, a professor of pediatrics at Northwestern University in the United States, stated that previous studies have shown that children carrying this variant are more prone to asthma exacerbations during viral infections, but the new study helps explain the biological mechanisms behind this.

He added that the results may help in the future to identify children for whom "Mepolizumab" may be less effective, or who may exhibit other types of inflammation that the drug does not target.

He pointed out that knowing this in advance could allow doctors to consider other treatment options at an earlier stage, supporting the shift towards what is known as precision medicine, which relies on the characteristics of each patient rather than providing the same treatment to all patients.

Researchers emphasized that the results do not mean, for now, that children with the genetic variant should not receive "Mepolizumab."

Kumar explained that the study primarily focused on biological changes within the respiratory tract, and its size was not sufficient to prove that these changes actually lead to worse clinical outcomes, such as an increased number of asthma attacks or reduced treatment effectiveness.

He stated that this requires larger studies that follow patients and compare the actual response to the drug according to genetic makeup.

Asthma is one of the most common chronic diseases in children, but it is not a single disease biologically; the causes of inflammation and immune pathways can vary significantly from one patient to another.

In recent years, precision medicine research has aimed to use genetic and immunological indicators to categorize patients into more accurate groups, allowing for the selection of treatments that target the mechanism responsible for the disease in each patient.

Researchers stated that understanding the relationship between the SERPINE1 gene and viral infections and the response to biological drugs could represent an additional step towards achieving this goal in children with asthma.