Early changes in children’s immune systems point to later asthma

Researchers at the CPC-M site in Munich of the German Center for Lung Research (DZL) have uncovered evidence that asthma may originate very early in life. Their recent study shows that children who later develop asthma already exhibit measurable differences in their immune systems during toddlerhood compared to healthy children.

A sensitive window in early childhood

Early childhood is considered a critical phase for the development of asthma. During this period, the immune system and lungs mature, and inflammatory processes can be shaped in ways that have long-term effects. Until now, however, it was unclear exactly when asthma-related changes first appear and how they develop over time.

The aim of the study was therefore to examine long-term gene expression in whole blood from children who later develop asthma and to compare it with that of healthy children.

The analysis showed that as early as one year of age, children who were later diagnosed with asthma already differed clearly from their healthy peers. In these children, 42 genes were predominantly more active. These genes were linked to neutrophilic inflammatory processes and to markers of the so-called NLRP3 inflammasome, an important component of the innate immune response. A co-expression analysis confirmed this pattern and identified a distinct neutrophilic gene module that was already associated with asthma at this early stage.

Shift to persistent eosinophilic inflammation

By the age of four and a half years, the picture changed. The neutrophilic signature receded into the background, and instead a new eosinophilic signature pattern emerged, consisting of 40 genes. This eosinophilic gene signature remained elevated in children with asthma until the age of ten and a half.

Here too, co-expression analyses confirmed the findings: eosinophilic gene modules were clearly associated with asthma at ages four and a half, six, and ten and a half years. In line with this, the level of fractional exhaled nitric oxide—a marker of eosinophilic airway inflammation—was associated with the eosinophilic module at six years of age.

Genetic influences and possible targets

In addition, the researchers identified 86 genetic variants (SNPs) that influenced the expression of ten eosinophil-associated genes as well as the asthma risk gene GSDMB. A genetic risk score based on these variants was linked to an asthma diagnosis.

Overall, the results show a clear shift: from an early neutrophilic inflammatory response at one year of age to a persistent eosinophilic inflammation from around four and a half years onwards. The period in between appears to be particularly vulnerable to decisive changes.

Implications for early detection and prevention

The study helps to better understand when and how asthma develops in childhood. In the long term, insights like these could help identify children at increased risk of asthma earlier and support the development of new approaches to prevention and personalized therapies.