Why do some children develop persistent asthma after experiencing wheezing early in life, while others become symptom-free? Researchers at the German Center for Lung Research (DZL) have shown that distinct immune programs can already be identified in the nasal mucosa and are associated with subsequent disease trajectories. Many preschool-aged children experience wheezing, a whistling sound when breathing. In some of these children, this develops into persistent asthma. However, the factors influencing this progression are not yet fully understood.
Researchers from the DZL sites ARCN, BREATH, CPC-M, and UGMLC therefore investigated whether distinct immune responses in the airway mucosa can be detected early in life and provide clues about the subsequent development of asthma. Led by DZL principal investigators Constanze Jakwerth and Carsten Schmidt-Weber from the Center of Allergy and Environment (ZAUM/CPC-M), the research team analyzed nasal swabs from 265 children, adolescents, and young adults participating in the DZL's ALLIANCE All Age Asthma cohort. The nasal mucosa is particularly well suited for such investigations because its cells can reveal different immune patterns. At the same time, nasal swabbing is a relatively non-invasive method that is also suitable for young children.
The researchers investigated which genes were active in the cells of the nasal mucosa and which patterns of immune responses could be identified. They then analyzed whether these patterns were associated with the development or persistence of asthma.
The analysis identified three distinct immune programs in the airway mucosa:
In children aged one to three years who experienced wheezing, the E1 and E3 immune programs were predominant. In children aged four to six years, the E2 pattern, which is characteristic of allergic inflammation, was more common.
The E2 program was also associated with established asthma-related markers, including elevated immunoglobulin E (IgE) levels, increased fractional exhaled nitric oxide (FeNO) levels, and higher numbers of eosinophils in the blood.
Children who subsequently developed asthma also showed age-dependent activity patterns across the three immune programs. The findings suggest that distinct immune responses in early childhood are associated with the transition from transient wheezing to persistent asthma. While the E1 program appeared to be associated with a potentially protective pattern, the findings for E3 suggested a link with an increased risk of persistent asthma.
“Wheezing in early childhood is highly heterogeneous, and so far, we have only limited ability to predict which children will go on to develop persistent asthma,” explains first author Constanze Jakwerth. The study results indicate that distinct so-called nasotypes—specific immune programs in the nasal mucosa—can provide clues about different disease trajectories from an early age. In the long term, these findings could help enable a more targeted assessment of the risk of persistent asthma.
In the future, nasal swab analysis could help to:
Further research is needed before this approach can be applied in clinical practice. Nevertheless, the current findings highlight how the development of the immune system and airway mucosa during the first years of life may provide important clues about subsequent disease trajectories.
Last author Carsten Schmidt-Weber emphasizes the importance of collaboration across DZL sites: “The DZL-wide ALLIANCE cohort is extremely valuable. In addition to its direct clinical benefits, it also enables us to identify environmental factors that may play a role in airway health.”
To improve the prediction of asthma trajectories and enable more targeted treatment, the DZL established the ALLIANCE cohort during its first funding period. It now comprises more than 1,000 patients and healthy volunteers aged between six months and 84 years. Following a comprehensive baseline examination, participating patients with asthma generally return to their respective study centers annually. ALLIANCE is one of the DZL's major clinical flagship projects. The participating DZL sites are ARCN (Kiel, Lübeck, Borstel, and Großhansdorf), BREATH (Hannover), CPC-M (Munich), and UGMLC (Gießen, Marburg, and Bad Nauheim), as well as University Hospital Cologne as a partner institution outside the DZL.
Original publication: Jakwerth CA, Illi S, Charles H, Oelsner M, Gabr AA, Zissler UM, Erb A, Feuerherd M, Drost F, Büttner M, Schubert B, Maison N, Omony J, Weckmann M, Grychtol R, Dittrich AM, Foth S, Skevaki C, Trojan T, van Koningsbruggen-Rietschel S, Hansen G, Bahmer T, Rabe KF, Brinkmann F, Kopp MV, Protzer U, Chaker AM, Schaub B, von Mutius E, Schmidt-Weber CB; ALLIANCE Study Group as part of the German Center for Lung Research (DZL). Nasal Epithelial Immune Signatures Are Associated With Age-Dependent Asthma Trajectories in Early Life. Allergy. 2026 Oct;81(10):3533–3553. doi: 10.1111/all.70477. Epub 2026 Sep 6. PMID: 42703035; PMCID: PMC13646873.
