Late Breaking Abstract - The “one airway, one disease” concept at the light of Th2 inflammation

Abstract

Rationale: A pathophysiologic continuum has been described between nose and bronchus in allergic respiratory diseases, but no study has directly compared gene expression profiles of nasal and bronchial epithelium in a same individual. Aims and objectives: To assess whether clinical features of the bronchi, such as Th2 inflammation status, could be recapitulated at the nasal epithelium level, in nasal and bronchial epithelia from the same individual. Methods: Twelve allergic rhinitis and asthma (AR), 14 isolated allergic rhinitis (R) and 13 healthy controls (C) were included. Nasal and bronchial cells were collected by brushings. Cellular composition was assessed by flow cytometry. Gene expression was analyzed by RNA-seq. A Th2 signature compatible for studies of bronchial and nasal epithelia was established using 4 public datasets. Results: A signature of 63 transcripts distinguished nasal and bronchial brushings, regardless of their pathological status. The Th2 specific signature stratified the samples firstly according the tissue of origin, and then according the level of the Th2 signature. Concordance between high and low Th2 status was good in AR (Cohen’s kappa 0.588, p = 0.088) and C (kappa= 1, p=0.0027), but poor for R samples (kappa = 0.161, p-value=0.6). Th2 score correlated in nose and in bronchi with mastocytes counts and number of sensitizations. Of note, 4/10 R patients had a Th2-high signature in bronchi correlating with asthma history in childhood. Conclusions: Nasal and bronchial epithelia display distinct transcriptional signatures. In AR group, but not in R group, nasal cells can be used as bronchial surrogates to assess Th2 inflammation.