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

Hekking, Pieter-Paul; Loza, Matthew J.; Pavlidis, Stelios; De Meulder, Bertrand; Lefaudeux, Diane; Baribaud, Frederic; Auffray, Charles; Wagener, Ariane H.; Brinkman, Paul; Lutter, René; Bansal, Aruna T.; Sousa, Ana R.; Bates, Stewart A.; Pandis, Ioannis; Fleming, Louise J.; Shaw, Dominick E.; Fowler, Stephen J.; Guo, Yike; Meiser, Andrea; Sun, Kai; Corfield, Julie; Howarth, Peter; Bel, Elisabeth H.; Adcock, Ian M.; Chung, Kian Fan; Djukanovic, Ratko; Sterk, Peter J.

Authors

Pieter-Paul Hekking

Matthew J. Loza

Stelios Pavlidis

Bertrand De Meulder

Diane Lefaudeux

Frederic Baribaud

Charles Auffray

Ariane H. Wagener

Paul Brinkman

René Lutter

Aruna T. Bansal

Ana R. Sousa

Stewart A. Bates

Ioannis Pandis

Louise J. Fleming

Stephen J. Fowler

Yike Guo

Andrea Meiser

Kai Sun

Julie Corfield

Peter Howarth

Elisabeth H. Bel

Ian M. Adcock

Kian Fan Chung

Ratko Djukanovic

Peter J. Sterk



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.

Citation

Hekking, P., Loza, M. J., Pavlidis, S., De Meulder, B., Lefaudeux, D., Baribaud, F., …Sterk, P. J. (2017). Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma. European Respiratory Journal, 50(3), doi:10.1183/13993003.02298-2016

Journal Article Type Article
Acceptance Date Jun 26, 2017
Publication Date Sep 27, 2017
Deposit Date May 17, 2018
Journal European Respiratory Journal
Print ISSN 0903-1936
Electronic ISSN 1399-3003
Publisher European Respiratory Society
Peer Reviewed Peer Reviewed
Volume 50
Issue 3
DOI https://doi.org/10.1183/13993003.02298-2016
Public URL http://eprints.nottingham.ac.uk/id/eprint/51852
Publisher URL https://doi.org/10.1183/13993003.02298-2016
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf