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

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; Dominick E. Shaw; 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

doi:https://doi.org/10.1183/13993003.02298-2016

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

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, Dominick E. Shaw, Stephen J. Fowler, Yike Guo, Andrea Meiser, Kai SunJulie Corfield, Peter Howarth, Elisabeth H. Bel, Ian M. Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J. Sterk

Research output: Contribution to journal › Article › Academic › peer-review

40 Citations (Scopus)

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-a, 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

Original language	English
Pages (from-to)	1602298
Journal	European respiratory journal
Volume	50
Issue number	3
Early online date	2017
DOIs	https://doi.org/10.1183/13993003.02298-2016
Publication status	Published - 2017

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https://doi.org/10.1183/13993003.02298-2016

Cite this

Hekking, P.-P., Loza, M. J., Pavlidis, S., de Meulder, B., Lefaudeux, D., Baribaud, F., Auffray, C., Wagener, A. H., Brinkman, P., Lutter, R., Bansal, A. T., Sousa, A. R., Bates, S. A., Pandis, I., Fleming, L. J., Shaw, D. E., Fowler, S. J., Guo, Y., Meiser, A., ... Sterk, P. J. (2017). Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma. European respiratory journal, 50(3), 1602298. https://doi.org/10.1183/13993003.02298-2016

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title = "Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma",

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-a, 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",

author = "Pieter-Paul Hekking and Loza, {Matthew J.} and Stelios Pavlidis and {de Meulder}, Bertrand and Diane Lefaudeux and Frederic Baribaud and Charles Auffray and Wagener, {Ariane H.} and Paul Brinkman and Ren{\'e} Lutter and Bansal, {Aruna T.} and Sousa, {Ana R.} and Bates, {Stewart A.} and Ioannis Pandis and Fleming, {Louise J.} and Shaw, {Dominick E.} and Fowler, {Stephen J.} and Yike Guo and Andrea Meiser and Kai Sun and Julie Corfield and Peter Howarth and Bel, {Elisabeth H.} and Adcock, {Ian M.} and Chung, {Kian Fan} and Ratko Djukanovic and Sterk, {Peter J.}",

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doi = "https://doi.org/10.1183/13993003.02298-2016",

language = "English",

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Hekking, P-P, Loza, MJ, Pavlidis, S, de Meulder, B, Lefaudeux, D, Baribaud, F, Auffray, C, Wagener, AH, Brinkman, P , Lutter, R, Bansal, AT, Sousa, AR, Bates, SA, Pandis, I, Fleming, LJ, Shaw, DE, Fowler, SJ, Guo, Y, Meiser, A, Sun, K, Corfield, J, Howarth, P, Bel, EH, Adcock, IM, Chung, KF, Djukanovic, R & Sterk, PJ 2017, 'Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma', European respiratory journal, vol. 50, no. 3, pp. 1602298. https://doi.org/10.1183/13993003.02298-2016

TY - JOUR

T1 - Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma

AU - Hekking, Pieter-Paul

AU - Loza, Matthew J.

AU - Pavlidis, Stelios

AU - de Meulder, Bertrand

AU - Lefaudeux, Diane

AU - Baribaud, Frederic

AU - Auffray, Charles

AU - Wagener, Ariane H.

AU - Brinkman, Paul

AU - Lutter, René

AU - Bansal, Aruna T.

AU - Sousa, Ana R.

AU - Bates, Stewart A.

AU - Pandis, Ioannis

AU - Fleming, Louise J.

AU - Shaw, Dominick E.

AU - Fowler, Stephen J.

AU - Guo, Yike

AU - Meiser, Andrea

AU - Sun, Kai

AU - Corfield, Julie

AU - Howarth, Peter

AU - Bel, Elisabeth H.

AU - Adcock, Ian M.

AU - Chung, Kian Fan

AU - Djukanovic, Ratko

AU - Sterk, Peter J.

PY - 2017

Y1 - 2017

N2 - 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-a, 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

AB - 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-a, 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

U2 - https://doi.org/10.1183/13993003.02298-2016

DO - https://doi.org/10.1183/13993003.02298-2016

M3 - Article

C2 - 28954779

SN - 0903-1936

VL - 50

SP - 1602298

JO - European respiratory journal

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