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

Background: Dysfunction of the bronchial epithelium plays an important role in asthma; however, its measurement is challenging. Columnar epithelial cells are often quantified, yet rarely analysed, in induced sputum studies. Objective: We aimed to test whether sputum columnar epithelial cell proportion and count are altered in asthma, and whether they are associated with clinical and inflammatory variables. We aimed to test whether sputum‐based measures could provide a relatively non‐invasive means through which to monitor airway epithelial activation status. Methods: We examined the relationship of sputum columnar epithelial cells with clinical and inflammatory variables of asthma in a large retrospective cross‐sectional cohort (901 participants with asthma and 138 healthy controls). In further studies, we used flow cytometry, microarray, qPCR and ELISA to characterize sputum columnar epithelial cells and their products. Results: Multivariate analysis and generation of 90th centile cut‐offs (≥11% or ≥18.1 × 104/mL) to identify 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. An epithelial 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. Conclusions & Clinical Relevance: Sputum columnar epithelial cells are related to important clinical and inflammatory variables in asthma. Measurement of epithelial biomarkers in sputum samples could allow non‐invasive assessment of altered bronchial epithelium status in asthma.