The “one airway, one disease” concept in light of Th2 inflammation

Abstract

Introduction A pathophysiological continuum was described between nose and bronchus in allergic respiratory diseases. Nasal epithelium brushings are routinely used in clinical practice to diagnose airway diseases in infants, but no study as directly compared gene expression profiles of nasal and bronchial epithelium in a same individual. In this study, we assessed whether bronchial Th2 status, a clinical marker of asthma, can be correctly recapitulated from nasal epithelium, to validate nasal sampling as good surrogates of the bronchi. Methods Thirty-nine patients with allergic rhinitis and asthma (AR, n = 12), isolated allergic rhinitis (R, n = 14) and healthy controls (C, n = 13) were included. Nasal and bronchial cells were collected by brushings. Cellular composition of samples was assessed by flow cytometry. Gene expression was analyzed by RNA-seq. Th2, Th17 and interferon (IFN) signatures compatible for studies of bronchial and nasal epithelia were derived from the literature. For each inflammation signature, z-scores of gene expression were calculated for each gene, and a patient was considered to have high level of inflammation when 75 % of the markers from the signature had a z-score > 0. Results A high level of PMN cells infiltration in nasal samples excluded 30 % of the initial cohort. A signature of 63 transcripts strongly distinguished nasal and bronchial brushings, regardless of their pathological status. Concordance of Th2 status assessment between nose and bronchi was poor, with 71 % concordance in AR and 60 % in R only. Of note, 4/10 R patients had a Th2-high signature in bronchi correlating with asthma history in childhood. Even if most AR patients were correctly predicted based on their nasal gene expression profiles, we observed that nasal cells can hardly be considered as reliable surrogate because of the influence of the Th17 and IFN responses. IFN response in particular was found more frequently elevated in the nose than in the bronchi. IFN and Th17 responses were correlated together, but not with Th2 response. Th2 scores correlated with mastocyte counts and numbers of sensitizations. Th17 score was correlated with PMN counts. Conclusion The large variability of cell composition of nasal brushings and the types of inflammation present in this part of the airways restrict its use as a surrogate to assess bronchial Th2 inflammation in asthmatic patients.