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Hekking, Pieter-Paul and Loza, Matthew J. and Pavlidis, Stelios and De Meulder, Bertrand and Lefaudeux, Diane and Baribaud, Frederic and Auffray, Charles and Wagener, Ariane H. and Brinkman, Paul and Lutter, René and Bansal, Aruna T. and Sousa, Ana R. and Bates, Stewart A. and Pandis, Ioannis and Fleming, Louise J. and Shaw, Dominick E. and Fowler, Stephen J. and Guo, Yike and Meiser, Andrea and Sun, Kai and Corfield, Julie and Howarth, Peter and Bel, Elisabeth H. and Adcock, Ian M. and Chung, Kian Fan and Djukanovic, Ratko and Sterk, Peter J. (2017) Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma. European Respiratory Journal, 50 (3). p. 1602298. ISSN 1399-3003

Abstract

A proportion of severe asthma patients suffers from persistent airflow limitation (PAL), often associated with more symptoms and exacerbations. Little is known about the underlying mechanisms. Here, our aim was to discover unexplored potential mechanisms using Gene Set Variation Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous samples.

Severe asthma patients from the U-BIOPRED cohort with PAL (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal) were compared with those without PAL. Gene expression was assessed on the total RNA of sputum cells, nasal brushings, and endobronchial brushings and biopsies. GSVA was applied to identify differentially enriched predefined gene signatures based on all available gene expression publications and data on airways disease.

Differentially enriched gene signatures were identified in nasal brushings (n=1), sputum (n=9), bronchial brushings (n=1) and bronchial biopsies (n=4) that were associated with response to inhaled steroids, eosinophils, interleukin-13, interferon-α, specific CD4+ T-cells and airway remodelling.

PAL in severe asthma has distinguishable underlying gene networks that are associated with treatment, inflammatory pathways and airway remodelling. These findings point towards targets for the therapy of PAL in severe asthma.

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