A RECENT cross-sectional analysis has explored the potential of nasal epithelial gene expression to identify asthma endotypes in youths aged 6 to 20 years. This study analysed samples from three distinct cohorts: the STAR, EVA-PR, and VDKA studies, encompassing predominantly racially and ethnically minoritised youths with asthma. The results revealed three distinct transcriptomic profiles correlating with T helper 2 (T2)-high, T helper 17 (T17)-high, and T2-low/T17-low asthma endotypes.
The T2-high endotype was the least common across all studies, observed in only 23–29% of participants. T17-high was identified in 35–47%, while T2-low/T17-low comprised 30–38% of the cohorts. Despite differences in the racial and ethnic makeup of the studies, Puerto Rican participants predominated in EVA-PR, while STAR and VDKA included mostly Black or African American youths, these proportions remained consistent. This consistency highlights the potential generalisability of these findings across diverse populations.
The T2-high profile was characterised by elevated total and allergen-specific IgE levels and higher blood eosinophil counts compared to the T2-low/T17-low endotype. Median IgE levels ranged from 584 to 869 IU/mL in T2-high participants, significantly higher than the 105 to 382 IU/mL observed in T2-low counterparts. Similarly, blood eosinophil counts were higher in T2-high individuals, indicating a stronger association with allergic responses.
Further meta-analysis identified thousands of differentially expressed genes associated with T2-high and T17-high profiles, highlighting unique immunological pathways. T2-high profiles were linked to interleukin 13 signalling, while T17-high profiles were associated with interleukin 17 and neutrophil signalling pathways.
These findings show the potential of nasal transcriptomic profiling to classify asthma into endotypes, which could inform tailored therapeutic approaches. With most participants demonstrating T2-low asthma endotypes and sensitisation to allergens, the research highlights the need to address these profiles for effective asthma management in diverse paediatric populations. This study marks a step forward in understanding asthma pathophysiology and improving personalised treatment strategies.
Katie Wright, EMJ
Reference
Yue M, Gaietto K, Han YY, et al. Transcriptomic profiles in nasal epithelium and asthma endotypes in youth. JAMA. 2025;DOI:10.1001/jama.2024.22684.
