Clinical biomarkers identify T-helper 2 status defined by mucosal CCL26 in the ADEPT-asthma study

Rationale: The ADEPT study aimed to correlate clinical features and accessible biomarkers with molecular characteristics by profiling asthmatics across severities and healthy nonatopic volunteers (HVs). This report focuses on the identification of mucosal Th2 phenotype (based on IL-13 driven gene expression), using accessible biomarkers, such as exhaled nitric oxide (FENO), blood eosinophils (bEOS) and serum analytes. Methods: Assessments included questionnaires, pulmonary function tests, airway hyperresponsiveness, FENO, and biomarkers from sputum, blood, and endobronchial biopsy (EBBX). Th2 phenotype was evaluated by EBBX gene expression of CCL26, periostin, or an IL-13 in vitro gene signature (IVS). Results: Relative to HVs, EBBX gene expression of CCL26 provided the best segregation into Th2-high and Th2-low asthmatics compared to periostin or IL-13 IVS. Most EBBX-Th2-CCL26-high subjects with moderate-severe asthma were FENO≥35ppb (69%) and bEOS≥300/ul (77%), compared to a minority of EBBX-Th2-CCL26-low subjects (24% for each). Classifying subjects to EBBX-Th2-CCL26-high status based on FENO-high or bEOS-high status gave 100% sensitivity but only 64% specificity. Serum CCL17-high status added to FENO/bEOS model improved specificity to 93% for identification of Th2 status, with 85% sensitivity. Conclusions: Combinations of accessible biomarkers (FENO, bEOS, and serum CCL17) can accurately predict Th2 status measured by EBBX expression of CCL26. Eosinophilic inflammation was associated with but not limited to persistent airway Th2 gene expression. The ability to identify distinct asthma phenotypes using accessible biomarkers will be important in developing novel therapeutic agents.