Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study

Area of Science:

• Respiratory Medicine
• Genomics
• Molecular Biology

Background:

• Asthma is a complex inflammatory airway disease with diverse phenotypes and endotypes.
• Nasal epithelium gene expression is explored as a non-invasive proxy for bronchial epithelium in lung disease research.
• Hypothesis: Upper airway molecular differences reflect lower airway asthma characteristics and clinical presentation.

Purpose of the Study:

• To investigate if nasal epithelial gene expression profiles correlate with asthma.
• To identify molecular asthma endotypes using nasal gene expression data.
• To validate nasal gene expression as a biomarker for lower airway changes in asthma.

Main Methods:

• Analysis of nasal epithelial gene expression in 369 asthma patients and 58 controls.
• Unsupervised hierarchical clustering of asthma-associated genes.
• Replication of gene signatures in independent cohorts using nasal and bronchial brushes data.

Main Results:

• Identified 67 upregulated and 59 downregulated genes in asthma patients' nasal epithelium (FDR<0.05).
• Identified key genes (e.g., CLCA1, CST1, POSTN) correlating with bronchial asthma markers.
• Discovered distinct molecular asthma endotypes with specific clinical features, including eosinophil levels and small airway dysfunction.

Conclusions:

• Nasal epithelial gene expression profiles accurately reflect asthma-related processes in the lower airways.
• Nasal epithelium serves as a valuable non-invasive tool for identifying asthma endotypes.
• This approach can potentially advance personalized asthma management strategies.