Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma

Abstract

Rationale: A proportion of severe asthma patients suffers fro m persistent airflow limitation, often associated with more symptoms and exacerbations . Little is known about the underlying mechanisms. Aiming for discovery of unexplored potential mechanisms, we used Gene Set Variation Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous samples. Methods: Severe asthma patients from the U -BIOPRED cohort with persistent airflow limitation (post -bronchodilator FEV 1 /FVC ratio < lower limit of normal) were compared to those without persistent airflow limitation. Gene expression was assessed on the total RNA of sputum cells, nasal brushin gs and endobronchial brushings and biopsies. GSVA was applied to identify differentially - enriched pre -defined gene signatures based on all available gene expression publications and data on airways disease. Results: Differentially -enriched gene signatures were identified in nasal brushings (1), sputum (9), bronchial brushings (1) and bronchial biopsies (4), that were associated with response to inhaled steroids, eosinophils, IL -13, IFN -alpha, specific CD4+ T -cells and airway remodeling. Conclusion: Persiste nt airflow limitation in severe asthma has distinguishable underlying gene networks that are associated with treatment, inflammatory pathways and airway remodeling. These results point towards targets for the therapy of persistent airflow limitation in sev ere asthma.