Nasal swabs in children indicate when early wheezing might develop into persistent asthma

Many preschool children experience wheezing. But why do only some of these children develop persistent asthma later in childhood? DZL researchers from the Sites ARCN, BREATH, CPC-M and UGMLC sites sought to determine whether differences in the development of the airway mucosa early in life could explain this phenomenon, and whether distinct immune responses influence the subsequent course of the disease.

To investigate this question, teams led by DZL researchers Constanze Jakwerth and Carsten Schmidt-Weber (DZL site CPC-M) analyzed nasal swab samples from 265 children, adolescents, and young adults participating in the DZL ALLIANCE All Age Asthma cohort. Cells obtained from the nasal mucosa can reveal distinct immune patterns associated with the later risk of persistent asthma. In addition, nasal swabbing is a minimally invasive method that is particularly suitable for young children.

In the current study, the researchers analyzed which genes were active in airway mucosal cells and which immune response patterns could be derived from them. They then assessed whether these patterns were associated with the later development or persistence of asthma.

According to corresponding author Carsten Schmidt-Weber, the study highlights “the importance of the DZL-wide ALLIANCE cohort. In addition to its direct clinical value, it also enables us to identify environmental factors that may play a role in airway fitness.”

 

Asthma or No Asthma? Three Immune Programs Provide Clues to Future Disease Trajectories

The analysis of the nasal swabs revealed three distinct immune programs in the airway mucosa of the children:

• E1: a program primarily associated with antiviral defense mechanisms.
• E2: a program linked to allergic inflammatory responses and so-called type 2 immunity.
• E3: a type-17-associated inflammatory program linked to inflammatory responses of the airway epithelium

Among children aged 1 to 3 years with wheezing, the E1 and E3 programs were predominant. In contrast, among children aged 4 to 6 years, the E2 pattern, which is characteristic of allergic inflammation, was observed more frequently.

The E2 program was also closely associated with established asthma-related features, including elevated IgE levels, increased fractional exhaled nitric oxide (FeNO), and higher numbers of eosinophilic immune cells.

Children who later developed asthma showed different activity patterns of these programs depending on their age. These patterns are therefore associated with the transition from early wheezing to persistent asthma, whereas E1 appeared to function more as a protective immune program, while E3 was associated with an increased risk of persistent asthma.

 

Could Nasal Swabs Enable Earlier Prevention?

“Early-life wheezing is highly heterogeneous, and to date we have only limited ability to predict which children will go on to develop persistent asthma,” explains first author Constanze Jakwerth. The study results therefore show “that distinct ‘nasotypes’, meaning specific immune programs within the nasal mucosa, can already be identified in early childhood and provide indications of different disease trajectories, potentially enabling more precise long-term risk assessment for persistent asthma.”

The analysis of nasal swabs could therefore, in the future, help to:

• identify children at increased risk of asthma at an early stage,
• better distinguish between different asthma trajectories,
• and enable earlier and more targeted preventive or therapeutic interventions.

The findings suggest that the development of the immune system and airway mucosa during the first years of life may play an important role in shaping whether early wheezing resolves or progresses to persistent asthma.

 

About the ALLIANCE Cohort

To improve predictions of asthma progression and optimize treatment strategies, DZL established the ALLIANCE cohort during its first funding period. The cohort now includes more than 1,000 patients and healthy participants ranging in age from six months to 84 years. Following a comprehensive baseline assessment, patients with asthma generally return to their respective study centers on an annual basis. ALLIANCE is one of the DZL’s flagship clinical research projects. Participating sites include ARCN (Kiel/Lübeck/Borstel/Großhansdorf), BREATH (Hannover), CPC-M (Munich), and UGMLC (Giessen/Marburg/Bad Nauheim), as well as the University Hospital Cologne as an external DZL partner.

Read the full publication: Nasal epithelial immune signatures are associated with age-dependent asthma trajectories in early life” –https://onlinelibrary.wiley.com/doi/10.1111/all.70477

/Doris Hammerschmidt (Helmholtz Munich)/jbul

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