Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways

Area of Science:

• Pulmonary Medicine
• Genomics
• Immunology

Background:

• Bronchial brushes reveal asthma gene signatures but require invasive bronchoscopy.
• The
• united airways
• hypothesis suggests upper airway samples may reflect lower airway changes.

Purpose of the Study:

• To investigate if nasal brushes can non-invasively detect asthma-associated transcriptomic changes in the lower airways.
• To evaluate the overlap in gene signatures between nasal and bronchial samples in asthma patients.

Main Methods:

• RNA sequencing of nasal and bronchial brushes from asthma patients and healthy controls (ARMS study).
• Identification of asthma-associated genes and modules using edgeR and Weighted Gene Co-expression Network Analysis (WGCNA).
• Validation of findings in an independent cohort (ATLANTIS study).

Main Results:

• Identified 51 asthma-associated genes in the lower airways; 40 were up-regulated, 11 down-regulated.
• Seven up-regulated genes (CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, DHX35) were consistently found in nasal brushes and validated.
• Two gene modules, reflecting IL-13 inflammation and mast cell activity, were consistently elevated in asthma across both airway sites and cohorts.

Conclusions:

• A limited but biologically coherent overlap exists between upper and lower airway asthma gene signatures.
• Shared signatures highlight IL-13 related inflammation and mast cell activity as key components of type 2 inflammation in asthma.
• Nasal gene signatures provide a non-invasive approach to identify asthma endotypes based on underlying molecular mechanisms.