Shoda T, et al. - Researchers identified the clinical–pathological associations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states. Patients with eosinophilic oesophagitis were stratified into subgroups with potential clinical and therapeutic significance by the new disease classification of the experts. This classification provides a framework for a precision medicine approach to eosinophilic oesophagitis.

Methods

• Experts conducted a cross-sectional study across 10 hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers.
• They evaluated oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts.
• They assessed the histological and endoscopic features by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS).
• Authors analyzed the associations among the various histological, endoscopic, and molecular features by Spearman correlation.
• In a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis, replication of the results was seen.

Results

• Findings suggested that 185 samples were contained in the discovery cohort and the validation cohort comprised 100 specimens.
• Results demonstrated that in the discovery cohort, EDP demonstrated intersite consistency, significant correlation with oesophageal eosinophils (p < 0·0001), and similar findings between paediatric and adult patients.
• As per data, out of 8 HSS domains, basal zone hyperplasia was associated with the EDP (median Spearman ρ 0·47 [IQR 0·36-0·60]).
• Of five EREFS features, an association of distal furrows with the EDP was seen (median Spearman ρ 0·42 [0·32–0·50]).
• Researchers noted that in the discovery cohort by analysing active eosinophilic oesophagitis, the EDP identified 3 clusters related to distinct endotypes (termed EoEe1–3) despite similar eosinophil levels.
• They found an association of EoEe1 with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04-10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09-0·82; p=0·0105) and demonstrated relatively mild histological, endoscopic, and molecular changes.
• An inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11-6·95; p=0·0376) was demonstrated by EoEe2 and it had the highest expression of inflammatory cytokines and steroid-responding genes.
• There was a correlation of EoEe3 with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84-34·64; p=0·0013) and adult onset (2·22, 1·19–4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes.
• Data suggested a replication of these endotypes in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm.