Hopeful Outlook: New Approach to Reduce Asthma Risk in Children

The causes of childhood asthma still need to be clarified. Researchers from the ALLIANCE (ALL Age Asthma) cohort of the DZL, led by Helmholtz Munich and the Technical University of Munich (TUM), have now been able to show a link between a specific gene variant in children and the development of asthma. This milestone opens up new avenues for therapeutic approaches. The results were published in the renowned American Journal of Respiratory and Critical Care Medicine.

Around one in three children develop an early form of asthma in the first few years of life. Eighty per cent of them have a genetic variant on chromosome 17. These children are prone to repeated viral infections, which could later lead to asthma. The mechanisms behind this genetic variant were previously unknown, meaning that only the symptoms could be treated. "We have now found out why the genetic defect makes the children more susceptible to viral infections, which poses a high risk of developing asthma," says Dr Constanze Jakwerth, first author of the study.

Analysing samples from the nasal cavity

Previous epidemiological studies have indicated that there could be a link between genetic defects and viral infections. The researchers, therefore, analysed 261 children with early asthma. To do this, they took samples of cells from the children's nasal cavities using tiny brushes. This less invasive method makes it possible to analyse the entire transcriptome, i.e. all gene transcripts in the nasal cells. In this way, the scientists could identify specific changes and patterns in gene expression, known as "nasotypes", which differ significantly in children with and without genetic defects.

Increased susceptibility to viral infections

They found an increased expression of the protein GSDMB, which is produced more frequently due to the gene variant. This protein forms pores and is crucial for the children's immune response. Its increased expression due to the gene variant leads to impaired interferon secretion. Interferons play an important role in the immune response to viral infections. There are three different classes of interferons. The researchers found that the nasal cells of children with the genetic defect showed an increased production of type 2 interferons. In contrast, type 1 and type 3 interferons, crucial for the defence against viruses, were present in lower quantities. These observations made it possible to explain why the genetic defect makes children more susceptible to viral infections and increases asthma risk. There were also indications that the balance of natural killer cells was disturbed, negatively affecting the barrier function of the nasal mucosa.

The researchers assume that this leads to children becoming more susceptible to viral infections and allergens being able to penetrate more easily. As a result, asthma can develop in the long term.

Reducing the risk of infection and asthma

"We now know that the genetic defect on chromosome 17 leads to a specific gene expression pattern that we can influence or even correct. Our aim is to correct the defence defect in the children's airways. We are working on new drugs, inhalation sprays, which support the defence against the virus by stimulating the epithelial barrier for a more appropriate response," says Prof. Carsten Schmidt-Weber, who led the study at Helmholtz Munich and TUM.

"Early viral infections appear to alter children's immune system, breaking their tolerance to normally harmless allergens. This, in turn, promotes the development of asthma. So if we can control these infections more efficiently with new drugs that directly target the genetic defect, we are confident that fewer children will develop asthma," says Prof Erika von Mutius, co-author of the study.

Therefore, the research results offer insights into the causes of childhood asthma and open up promising prospects for the development of targeted therapies and preventive measures.

Original publication:

17q21 Variants Disturb Mucosal Host Defence in Childhood Asthma | American Journal of Respiratory and Critical Care Medicine | Articles in Press (atsjournals.org)

Further information:

Press release Helmholtz Munich