Pathway discovery using transcriptomic profiles in adult-onset severe asthma

U-BIOPRED Study Group; I M Adcock; H Ahmed; C Auffray; Hans Bisgaard; Klaus Bønnelykke; Jonathan Thorsen; Nadja Vissing; Yu Wen; Wilhelm Zetterquist; Koos Zwinderman

doi:10.1016/j.jaci.2017.06.037

Pathway discovery using transcriptomic profiles in adult-onset severe asthma

U-BIOPRED Study Group, I M Adcock, H Ahmed, C Auffray, Hans Bisgaard, Klaus Bønnelykke, Jonathan Thorsen, Nadja Vissing, Yu Wen, Wilhelm Zetterquist, Koos Zwinderman

Department of Clinical Medicine

57 Citations (Scopus)

Abstract

Background: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. Objective: We sought to identify gene profiles associated with adult-onset severe asthma. Methods: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways. Results: Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma. Conclusions: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.

Original language	English
Journal	The Journal of allergy and clinical immunology
Volume	141
Issue number	4
Pages (from-to)	1280-1290
ISSN	0091-6749
DOIs	https://doi.org/10.1016/j.jaci.2017.06.037
Publication status	Published - 1 Apr 2018

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10.1016/j.jaci.2017.06.037

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@article{e76a867ad94b4c4787be674a86e8d67f,

title = "Pathway discovery using transcriptomic profiles in adult-onset severe asthma",

abstract = "Background: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. Objective: We sought to identify gene profiles associated with adult-onset severe asthma. Methods: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways. Results: Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma. Conclusions: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.",

author = "Pieter-Paul Hekking and Loza, {Matt J} and Stelios Pavlidis and {de Meulder}, Bertrand and Diane Lefaudeux and Fred Baribaud and Charles Auffray and Wagener, {Ariane H} and Paul Brinkman and Rene Lutter and Bansal, {Aruna T} and Sousa, {Ana R} and Bates, {Steve A} and Yannis Pandis and Fleming, {Louise J} and Shaw, {Dominique E} and Fowler, {Stephen J} and Y Guo and Andrea Meiser and Kai Sun and Julie Corfield and Howarth, {Peter H} and Bel, {Elisabeth H} and Adcock, {Ian M} and Chung, {Kian Fan} and Ratko Djukanovic and Sterk, {Peter J} and {U-BIOPRED Study Group} and Adcock, {I M} and H Ahmed and C Auffray and Hans Bisgaard and Klaus B{\o}nnelykke and Jonathan Thorsen and Nadja Vissing and Yu Wen and Wilhelm Zetterquist and Koos Zwinderman",

note = "Copyright {\textcopyright} 2017. Published by Elsevier Inc.",

year = "2018",

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doi = "10.1016/j.jaci.2017.06.037",

language = "English",

volume = "141",

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TY - JOUR

T1 - Pathway discovery using transcriptomic profiles in adult-onset severe asthma

AU - Hekking, Pieter-Paul

AU - Loza, Matt J

AU - Pavlidis, Stelios

AU - de Meulder, Bertrand

AU - Lefaudeux, Diane

AU - Baribaud, Fred

AU - Auffray, Charles

AU - Wagener, Ariane H

AU - Brinkman, Paul

AU - Lutter, Rene

AU - Bansal, Aruna T

AU - Sousa, Ana R

AU - Bates, Steve A

AU - Pandis, Yannis

AU - Fleming, Louise J

AU - Shaw, Dominique E

AU - Fowler, Stephen J

AU - Guo, Y

AU - Meiser, Andrea

AU - Sun, Kai

AU - Corfield, Julie

AU - Howarth, Peter H

AU - Bel, Elisabeth H

AU - Adcock, Ian M

AU - Chung, Kian Fan

AU - Djukanovic, Ratko

AU - Sterk, Peter J

AU - U-BIOPRED Study Group

AU - Adcock, I M

AU - Ahmed, H

AU - Auffray, C

AU - Bisgaard, Hans

AU - Bønnelykke, Klaus

AU - Thorsen, Jonathan

AU - Vissing, Nadja

AU - Wen, Yu

AU - Zetterquist, Wilhelm

AU - Zwinderman, Koos

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. Objective: We sought to identify gene profiles associated with adult-onset severe asthma. Methods: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways. Results: Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma. Conclusions: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.

AB - Background: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples. Objective: We sought to identify gene profiles associated with adult-onset severe asthma. Methods: This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways. Results: Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma. Conclusions: Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.

U2 - 10.1016/j.jaci.2017.06.037

DO - 10.1016/j.jaci.2017.06.037

M3 - Journal article

C2 - 28756296

SN - 0091-6749

VL - 141

SP - 1280

EP - 1290

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 4

ER -

Pathway discovery using transcriptomic profiles in adult-onset severe asthma

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