CD4+ Th cell lineages include T-helper type 2 and T-helper type 17 cells, both associated with asthma. In turn, the characterization of patients according to the type of cells involved in the execution of asthma endotypes becomes critical for developing effective therapeutic models against asthma in such individuals as youthful adulthood. In young people aged 6-20 years, there is a preference to use Nasal Epithelial Gene Expression to detect asthma endotypes, but which are the commonly identified endotypes? For more details, refer to this study conducted in JAMA Network.
The goal is to determine how the transcriptomic patterns characterize and describe the distribution of the samples collected from the nasal epithelium of school-aged children, with 6-20 years, using asthma endotypes. Patient cohort studies include STAR (Stress and Treatment Response in Puerto Rican and African American Children with Asthma; N = 156), EVA-PR (Epigenetic Variation and Childhood Asthma in Puerto Ricans; N = 237), and VDKA (Vitamin D Kids Asthma; N = 66).
In STAR, EVA-PR, and VDKA subjects, the mean ages were 14.2 years, 15.4 years, and 10.3 years, respectively. The percentages of female respondents lie between 41% and 53.2% of the studies. Hispanics were the dominant race or ethnic origin in EVA-PR (100%), whereas blacks or African Americans accounted in STAR (71.8%) and VDKA (57.6%). There were 3 distinct transcriptomic profiles: T2HIGH with high expression for T2, T17HIGH with high expression for T17, and low expression for both pathways (T2LOW/T17LOW). T2HIGH was detected in 23-29%, T17HIGH in 35-47%, and T2LOW/T17LOW in 30-38%; the median total IgE and blood eosinophils for the T2HIGH profiles were higher than those for T2LOW profiles in each study: IgE, 584-869 vs 105-382 IU/mL; eosinophils, 343-560 vs 164-413 cells/mL.
From all profiles, at least 50% of participants had at least 1 positive allergen-specific IgE. Meta-analysis of differential expression showed that there were 3516 significant expressed genes in the T2HIGH profile, while 2494 genes were observed in the T17HIGH profile. The interleukin 17 and neutrophil signaling pathways were associated with T17HIGH, while the interleukin 13 signaling pathway was related to T2HIGH.
We have been able to construct up to 3 separate physiological models using 8 biomarkers that can be assessed in nasal epithelial tissue of asthmatic youth from racially/ethnically minoritized backgrounds drawn from 3 different multicentre studies, based on the T2-high, T17-high T2-o/T17 low endotypes identified in these three published datasets, with variation in sample origin or admixture but similar proportions of T2/ T2-high asthma sub-type was described as rare as it made up 23% – 29% in all three studies.
Last observed performance of functional endpoints as nasal epithelium transcription on T2 pathway genes 3 and 5 from T17 pathways. The following were compared with respect to all studies incorporated: clinical features, total IgE and allergen-specific IgE, blood eosinophilia, and spirometry. Nasal transcriptomic profiles seemed to persist at similar levels in three studies using mostly Puerto Rican and African American youngsters with asthma; the majority of whom had T2-low asthma phenotypes.
Three independent studies of racially and ethnically minoritized youths with asthma showed that nasal transcriptomic profiles considered to represent T2-high, T17-high, and T2-low/T17-low endotypes were equally present. The majority of these youth had T2-low asthma endotypes, with sensitization to 1 or more allergens prevalent among these endotypes.
Reference: Yue M, Gaietto K, Han YY, et al. Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth. JAMA. Published online January 02, 2025. doi:10.1001/jama.2024.22684.
