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Transcriptomic Profiles in Nasal Epithelium and Asthma Endotypes in Youth
Molin Yue1,2, Kristina Gaietto1, Yueh Ying Han1
1Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania.
JAMA
|January 2, 2025
Summary
Three distinct asthma endotypes, T helper 2 high, T helper 17 high, and low expression, were identified in diverse youth populations. These profiles, characterized by specific gene expressions, are crucial for targeted asthma therapies.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- T helper 2 (T2) and T helper 17 (T17) cells are CD4+ T cell subtypes implicated in asthma pathogenesis.
- Understanding asthma endotypes in diverse pediatric populations is vital for developing effective, targeted therapies.
Purpose of the Study:
- To identify and characterize asthma endotypes in school-aged youths (6-20 years) using nasal epithelial transcriptomic profiles.
- To examine the distribution and clinical correlates of these endotypes across different studies.
Main Methods:
- Cross-sectional analysis of nasal epithelial samples from three independent studies (STAR, EVA-PR, VDKA) involving 459 youths with asthma.
- Primary outcome: transcriptomic profiles of T2 and T17 pathway genes.
- Comparison of clinical characteristics, IgE levels, blood eosinophils, and lung function across identified profiles.
Main Results:
- Three transcriptomic profiles were identified: T2-high (23-29%), T17-high (35-47%), and T2-low/T17-low (30-38%).
- T2-high profiles showed significantly higher total IgE and blood eosinophils compared to T2-low profiles.
- T17-high profiles were associated with IL-17 and neutrophil signaling; T2-high profiles with IL-13 signaling.
Conclusions:
- Nasal transcriptomic profiles defining T2-high, T17-high, and T2-low/T17-low asthma endotypes are consistently distributed across diverse, minority youth populations.
- Most participants presented with T2-low asthma endotypes, with common allergen sensitization observed across all endotypes.
- These findings support the utility of transcriptomic profiling for endotyping pediatric asthma and informing personalized treatment strategies.
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