Dysregulation of sputum columnar epithelial cells and products in distinct asthma phenotypes

<b>Introduction:</b> Dysfunction of the bronchial epithelium plays an important role in asthma, however its measurement is challenging. Columnar epithelial cells are often quantified, yet rarely analyzed, in induced sputum studies. <b>Hypothesis:</b> We hypothesized that sputum columnar epithelial cell count would be associated with clinical and inflammatory variables in asthma, and that sputum analysis could provide a relatively non-invasive measure of airway epithelial activation status. <b>Methods:</b> We examined the relationship of sputum columnar epithelial cells with clinical and inflammatory variables of asthma in a retrospective cross-sectional cohort (901 participants with asthma and 138 healthy controls). In smaller cohorts we used flow cytometry, microarray, qPCR and ELISA to characterize sputum columnar epithelial cells and products. <b>Results:</b> Multivariate analysis and generation of 90th centile cut-offs (≥11% or ≥18.1x104/mL) for columnar epithelial cell “high” asthma revealed a significant relationship between elevated sputum columnar cells and male gender, severe asthma and non-neutrophilic airway inflammation. Flow cytometry showed viable columnar epithelial cells were present in all sputum samples tested. A gene signature (SCGB3A1, LDLRAD1, FOXJ1, DNALI1, CFAP157, CFAP53) was detected in columnar epithelial cell-high sputum. CLCA1 mRNA and periostin protein, previously identified biomarkers of IL-13-mediated epithelial activation, were elevated in columnar epithelial cell-high sputum samples, but only when accompanied by eosinophilia. <b>Conclusions:</b> Measurement of epithelial biomarkers in sputum samples has potential value in non-invasive assessment of altered bronchial epithelium status in asthma.