Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Pieter-Paul Hekking; Matt J Loza; Stelios Pavlidis; Bertrand de Meulder; Diane Lefaudeux; Fred Baribaud; Charles Auffray; Ariane H Wagener; Paul Brinkman; Rene Lutter; Aruna T Bansal; Ana R Sousa; Steve A Bates; Yannis Pandis; Louise J Fleming; Dominique E Shaw; Stephen J Fowler; Y Guo; Andrea Meiser; Kai Sun; Julie Corfield; Peter H Howarth; Elisabeth H Bel; Ian M Adcock; Kian Fan Chung; Ratko Djukanovic; Peter J Sterk; U-BIOPRED Study Group; Hans Bisgaard; Nadja Hawwa Vissing; Klaus Bønnelykke

doi:10.1016/j.jaci.2017.06.037

Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Pieter-Paul Hekking, Matt J Loza, Stelios Pavlidis, Bertrand de Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H Wagener, Paul Brinkman, Rene Lutter, Aruna T Bansal, Ana R Sousa, Steve A Bates, Yannis Pandis, Louise J Fleming, Dominique E Shaw, Stephen J Fowler, Y Guo, Andrea Meiser, Kai SunJulie Corfield, Peter H Howarth, Elisabeth H Bel, Ian M Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J Sterk, U-BIOPRED Study Group, Hans Bisgaard (Medlem af forfattergruppering), Nadja Hawwa Vissing (Medlem af forfattergruppering), Klaus Bønnelykke (Medlem af forfattergruppering)

99 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	The Journal of allergy and clinical immunology
Vol/bind	141
Udgave nummer	4
Sider (fra-til)	1280-1290
Antal sider	11
ISSN	0091-6749
DOI	https://doi.org/10.1016/j.jaci.2017.06.037
Status	Udgivet - apr. 2018

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10.1016/j.jaci.2017.06.037

Citationsformater

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, Y., Fleming, L. J., Shaw, D. E., Fowler, S. J., Guo, Y., Meiser, A., ... Bønnelykke, K. (2018). Pathway discovery using transcriptomic profiles in adult-onset severe asthma. The Journal of allergy and clinical immunology, 141(4), 1280-1290. https://doi.org/10.1016/j.jaci.2017.06.037

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, Y, Fleming, LJ, Shaw, DE, Fowler, SJ, Guo, Y, Meiser, A, Sun, K, Corfield, J, Howarth, PH, Bel, EH, Adcock, IM, Chung, KF, Djukanovic, R, Sterk, PJ, U-BIOPRED Study Group, Bisgaard, H, Vissing, NH & Bønnelykke, K 2018, 'Pathway discovery using transcriptomic profiles in adult-onset severe asthma', The Journal of allergy and clinical immunology, bind 141, nr. 4, s. 1280-1290. https://doi.org/10.1016/j.jaci.2017.06.037

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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.",

keywords = "Journal Article",

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 Hans Bisgaard and Vissing, {Nadja Hawwa} and Klaus B{\o}nnelykke",

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

year = "2018",

month = apr,

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

language = "English",

volume = "141",

pages = "1280--1290",

journal = "The Journal of allergy and clinical immunology",

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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

A2 - Bisgaard, Hans

A2 - Vissing, Nadja Hawwa

A2 - Bønnelykke, Klaus

PY - 2018/4

Y1 - 2018/4

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.

KW - Journal Article

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 - The Journal of allergy and clinical immunology

JF - The Journal of allergy and clinical immunology

IS - 4

ER -

Pathway discovery using transcriptomic profiles in adult-onset severe asthma

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