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Pathway discovery using transcriptomic profiles in adult-onset severe asthma

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...

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Published in:	Journal of allergy and clinical immunology 2018-04, Vol.141 (4), p.1280-1290
Main Authors:	Hekking, Pieter-Paul, Loza, Matt J., Pavlidis, Stelios, de Meulder, Bertrand, Lefaudeux, Diane, Baribaud, Fred, Auffray, Charles, Brinkman, Paul, Lutter, Rene, Bansal, Aruna T., Sousa, Ana R., Bates, Steve A., Pandis, Yannis, Fleming, Louise J., Shaw, Dominique E., Fowler, Stephen J., Meiser, Andrea, Sun, Kai, Corfield, Julie, Howarth, Peter H., Bel, Elisabeth H., Adcock, Ian M., Chung, Kian Fan, Djukanovic, Ratko, Adcock, I.M., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Bucchioni, E., Burg, D., Caruso, M., Chanez, P., Chung, F.K., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., De Meulder, B., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Formaggio, E., Frey, U., Gahlemann, M., Geiser, T., Hashimoto, S., Haughney, J., Hedlin, G., Hohlfeld, J.M., Holweg, C., Horváth, I., Howarth, P., Knowles, R., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Matthews, J.G., Mazein, A., Middelveld, R.J.M., Mores, N., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powel, P., Praticò, G., Valls, M Puig, Rao, N., Riley, J., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J.
Format:	Article
Language:	English
Subjects:	Adult Adult-onset asthma Age Age of Onset Asthma Asthma - genetics Asthma - immunology Biopsy Children Cross-Sectional Studies Data collection Enrichment eosinophils Female Gene expression Gene Expression Profiling gene set variation analysis Genetic Markers Humans ILC3 Inflammation Leukocytes (eosinophilic) Lungs Lymphoid cells Male Mast cells mechanisms Medical treatment Middle Aged Neutrophils Oligonucleotide Array Sequence Analysis Patients Phenotype phenotyping Quality control Quality of life Respiratory tract Respiratory tract diseases Ribonucleic acid RNA severe asthma Severity of Illness Index Sputum Statistical analysis Statistical methods Transcriptome - immunology transcriptomics
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container_title	Journal of allergy and clinical immunology
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creator	Hekking, Pieter-Paul Loza, Matt J. Pavlidis, Stelios de Meulder, Bertrand Lefaudeux, Diane Baribaud, Fred Auffray, Charles Brinkman, Paul Lutter, Rene Bansal, Aruna T. Sousa, Ana R. Bates, Steve A. Pandis, Yannis Fleming, Louise J. Shaw, Dominique E. Fowler, Stephen J. Meiser, Andrea Sun, Kai Corfield, Julie Howarth, Peter H. Bel, Elisabeth H. Adcock, Ian M. Chung, Kian Fan Djukanovic, Ratko Adcock, I.M. Auffray, C. Bakke, P. Bansal, A.T. Baribaud, F. Bates, S. Bel, E.H. Bigler, J. Bisgaard, H. Boedigheimer, M.J. Bønnelykke, K. Brandsma, J. Bucchioni, E. Burg, D. Caruso, M. Chanez, P. Chung, F.K. Compton, C.H. Corfield, J. D'Amico, A. Dahlen, S.E. De Meulder, B. Erpenbeck, V.J. Erzen, D. Fichtner, K. Fitch, N. Formaggio, E. Frey, U. Gahlemann, M. Geiser, T. Hashimoto, S. Haughney, J. Hedlin, G. Hohlfeld, J.M. Holweg, C. Horváth, I. Howarth, P. Knowles, R. Krug, N. Lefaudeux, D. Loza, M.J. Lutter, R. Manta, A. Matthews, J.G. Mazein, A. Middelveld, R.J.M. Mores, N. Myles, D. Pahus, L. Pandis, I. Pavlidis, S. Powel, P. Praticò, G. Valls, M Puig Rao, N. Riley, J. Roberts, G. Rowe, A. Sandström, T. Seibold, W. Selby, A. Sigmund, R. Singer, F. Skipp, P.J. Sousa, A.R. Sterk, P.J. Sun, K. Thornton, B. van Geest, M. Vestbo, J. Vissing, N.H. Wagener, A.H. Wagers, S.S. Weiszhart, Z. Wheelock, C.E. Wilson, S.J.
description	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. We sought to identify gene profiles associated with adult-onset severe asthma. 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 (
doi_str_mv	10.1016/j.jaci.2017.06.037
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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. We sought to identify gene profiles associated with adult-onset severe asthma. 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. 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. 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. [Display omitted]</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2017.06.037</identifier><identifier>PMID: 28756296</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Adult-onset asthma ; Age ; Age of Onset ; Asthma ; Asthma - genetics ; Asthma - immunology ; Biopsy ; Children ; Cross-Sectional Studies ; Data collection ; Enrichment ; eosinophils ; Female ; Gene expression ; Gene Expression Profiling ; gene set variation analysis ; Genetic Markers ; Humans ; ILC3 ; Inflammation ; Leukocytes (eosinophilic) ; Lungs ; Lymphoid cells ; Male ; Mast cells ; mechanisms ; Medical treatment ; Middle Aged ; Neutrophils ; Oligonucleotide Array Sequence Analysis ; Patients ; Phenotype ; phenotyping ; Quality control ; Quality of life ; Respiratory tract ; Respiratory tract diseases ; Ribonucleic acid ; RNA ; severe asthma ; Severity of Illness Index ; Sputum ; Statistical analysis ; Statistical methods ; Transcriptome - immunology ; transcriptomics</subject><ispartof>Journal of allergy and clinical immunology, 2018-04, Vol.141 (4), p.1280-1290</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Inc.</rights><rights>Copyright Elsevier Science Ltd. Apr 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-e0ee94f95e3edde9ac9f7710d9749ccb4ce4bcdfdd9dd3903bb0a8c5793c31a03</citedby><cites>FETCH-LOGICAL-c532t-e0ee94f95e3edde9ac9f7710d9749ccb4ce4bcdfdd9dd3903bb0a8c5793c31a03</cites><orcidid>0000-0002-2533-5937 ; 0000-0003-2101-8843 ; 0000-0002-3538-0889 ; 0000-0003-4106-8469 ; 0000-0002-7262-6534 ; 0000-0002-8609-118X ; 0000-0002-3075-2161</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28756296$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hekking, Pieter-Paul</creatorcontrib><creatorcontrib>Loza, Matt J.</creatorcontrib><creatorcontrib>Pavlidis, Stelios</creatorcontrib><creatorcontrib>de Meulder, Bertrand</creatorcontrib><creatorcontrib>Lefaudeux, Diane</creatorcontrib><creatorcontrib>Baribaud, Fred</creatorcontrib><creatorcontrib>Auffray, Charles</creatorcontrib><creatorcontrib>Brinkman, Paul</creatorcontrib><creatorcontrib>Lutter, Rene</creatorcontrib><creatorcontrib>Bansal, Aruna T.</creatorcontrib><creatorcontrib>Sousa, Ana R.</creatorcontrib><creatorcontrib>Bates, Steve A.</creatorcontrib><creatorcontrib>Pandis, Yannis</creatorcontrib><creatorcontrib>Fleming, Louise J.</creatorcontrib><creatorcontrib>Shaw, Dominique E.</creatorcontrib><creatorcontrib>Fowler, Stephen J.</creatorcontrib><creatorcontrib>Meiser, Andrea</creatorcontrib><creatorcontrib>Sun, Kai</creatorcontrib><creatorcontrib>Corfield, Julie</creatorcontrib><creatorcontrib>Howarth, Peter H.</creatorcontrib><creatorcontrib>Bel, Elisabeth H.</creatorcontrib><creatorcontrib>Adcock, Ian M.</creatorcontrib><creatorcontrib>Chung, Kian 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S.E.</creatorcontrib><creatorcontrib>De Meulder, B.</creatorcontrib><creatorcontrib>Erpenbeck, V.J.</creatorcontrib><creatorcontrib>Erzen, D.</creatorcontrib><creatorcontrib>Fichtner, K.</creatorcontrib><creatorcontrib>Fitch, N.</creatorcontrib><creatorcontrib>Formaggio, E.</creatorcontrib><creatorcontrib>Frey, U.</creatorcontrib><creatorcontrib>Gahlemann, M.</creatorcontrib><creatorcontrib>Geiser, T.</creatorcontrib><creatorcontrib>Hashimoto, S.</creatorcontrib><creatorcontrib>Haughney, J.</creatorcontrib><creatorcontrib>Hedlin, G.</creatorcontrib><creatorcontrib>Hohlfeld, J.M.</creatorcontrib><creatorcontrib>Holweg, C.</creatorcontrib><creatorcontrib>Horváth, I.</creatorcontrib><creatorcontrib>Howarth, P.</creatorcontrib><creatorcontrib>Knowles, R.</creatorcontrib><creatorcontrib>Krug, N.</creatorcontrib><creatorcontrib>Lefaudeux, D.</creatorcontrib><creatorcontrib>Loza, M.J.</creatorcontrib><creatorcontrib>Lutter, R.</creatorcontrib><creatorcontrib>Manta, A.</creatorcontrib><creatorcontrib>Matthews, J.G.</creatorcontrib><creatorcontrib>Mazein, A.</creatorcontrib><creatorcontrib>Middelveld, R.J.M.</creatorcontrib><creatorcontrib>Mores, N.</creatorcontrib><creatorcontrib>Myles, D.</creatorcontrib><creatorcontrib>Pahus, L.</creatorcontrib><creatorcontrib>Pandis, I.</creatorcontrib><creatorcontrib>Pavlidis, S.</creatorcontrib><creatorcontrib>Powel, P.</creatorcontrib><creatorcontrib>Praticò, G.</creatorcontrib><creatorcontrib>Valls, M Puig</creatorcontrib><creatorcontrib>Rao, N.</creatorcontrib><creatorcontrib>Riley, J.</creatorcontrib><creatorcontrib>Roberts, G.</creatorcontrib><creatorcontrib>Rowe, A.</creatorcontrib><creatorcontrib>Sandström, T.</creatorcontrib><creatorcontrib>Seibold, W.</creatorcontrib><creatorcontrib>Selby, A.</creatorcontrib><creatorcontrib>Sigmund, R.</creatorcontrib><creatorcontrib>Singer, F.</creatorcontrib><creatorcontrib>Skipp, P.J.</creatorcontrib><creatorcontrib>Sousa, A.R.</creatorcontrib><creatorcontrib>Sterk, P.J.</creatorcontrib><creatorcontrib>Sun, K.</creatorcontrib><creatorcontrib>Thornton, B.</creatorcontrib><creatorcontrib>van Geest, M.</creatorcontrib><creatorcontrib>Vestbo, J.</creatorcontrib><creatorcontrib>Vissing, N.H.</creatorcontrib><creatorcontrib>Wagener, A.H.</creatorcontrib><creatorcontrib>Wagers, S.S.</creatorcontrib><creatorcontrib>Weiszhart, Z.</creatorcontrib><creatorcontrib>Wheelock, C.E.</creatorcontrib><creatorcontrib>Wilson, S.J.</creatorcontrib><creatorcontrib>U-BIOPRED Study Group</creatorcontrib><title>Pathway discovery using transcriptomic profiles in adult-onset severe asthma</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>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. We sought to identify gene profiles associated with adult-onset severe asthma. 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. 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. 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. [Display omitted]</description><subject>Adult</subject><subject>Adult-onset asthma</subject><subject>Age</subject><subject>Age of Onset</subject><subject>Asthma</subject><subject>Asthma - genetics</subject><subject>Asthma - immunology</subject><subject>Biopsy</subject><subject>Children</subject><subject>Cross-Sectional Studies</subject><subject>Data collection</subject><subject>Enrichment</subject><subject>eosinophils</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>gene set variation analysis</subject><subject>Genetic Markers</subject><subject>Humans</subject><subject>ILC3</subject><subject>Inflammation</subject><subject>Leukocytes (eosinophilic)</subject><subject>Lungs</subject><subject>Lymphoid cells</subject><subject>Male</subject><subject>Mast cells</subject><subject>mechanisms</subject><subject>Medical treatment</subject><subject>Middle Aged</subject><subject>Neutrophils</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Patients</subject><subject>Phenotype</subject><subject>phenotyping</subject><subject>Quality control</subject><subject>Quality of life</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>severe asthma</subject><subject>Severity of Illness Index</subject><subject>Sputum</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Transcriptome - immunology</subject><subject>transcriptomics</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kEtr3DAUhUVpSaZp_kAXxdBNNnb0sCVfyKaE9AED6SJdC1m6bmT8mEhywvz7aJgkiy66ulz4zuHwEfKZ0YpRJi-HajDWV5wyVVFZUaHekQ2joErZ8uY92VAKrJSqhlPyMcaB5l-0cEJOeasayUFuyPa3SfdPZl84H-3yiGFfrNHPf4sUzBxt8Lu0TN4Wu7D0fsRY-Lkwbh1TucwRUxExZ7AwMd1P5hP50Jsx4vnLPSN_vt_cXf8st7c_fl1_25a2ETyVSBGh7qFBgc4hGAu9Uow6yFOt7WqLdWdd7xw4J4CKrqOmtY0CYQUzVJyRi2NvXvWwYkx6yutxHM2Myxo1A163bQuSZfTrP-iwrGHO6zSnnEkQCg4UP1I2LDEG7PUu-MmEvWZUH1zrQR9c64NrTaXOrnPoy0v12k3o3iKvcjNwdQQwu3j0GHS0HmeLzge0SbvF_6__GarvkYE</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>Hekking, Pieter-Paul</creator><creator>Loza, Matt J.</creator><creator>Pavlidis, Stelios</creator><creator>de Meulder, Bertrand</creator><creator>Lefaudeux, Diane</creator><creator>Baribaud, Fred</creator><creator>Auffray, 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Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2533-5937</orcidid><orcidid>https://orcid.org/0000-0003-2101-8843</orcidid><orcidid>https://orcid.org/0000-0002-3538-0889</orcidid><orcidid>https://orcid.org/0000-0003-4106-8469</orcidid><orcidid>https://orcid.org/0000-0002-7262-6534</orcidid><orcidid>https://orcid.org/0000-0002-8609-118X</orcidid><orcidid>https://orcid.org/0000-0002-3075-2161</orcidid></search><sort><creationdate>20180401</creationdate><title>Pathway discovery using transcriptomic profiles in adult-onset severe asthma</title><author>Hekking, Pieter-Paul ; Loza, Matt J. ; Pavlidis, Stelios ; de Meulder, Bertrand ; Lefaudeux, Diane ; Baribaud, Fred ; Auffray, Charles ; Brinkman, Paul ; Lutter, Rene ; Bansal, Aruna T. ; Sousa, Ana R. ; Bates, Steve A. ; Pandis, Yannis ; Fleming, Louise J. ; Shaw, Dominique E. ; Fowler, Stephen J. ; Meiser, Andrea ; Sun, Kai ; Corfield, Julie ; Howarth, Peter H. ; Bel, Elisabeth H. ; Adcock, Ian M. ; Chung, Kian Fan ; Djukanovic, Ratko ; Adcock, I.M. ; Auffray, C. ; Bakke, P. ; Bansal, A.T. ; Baribaud, F. ; Bates, S. ; Bel, E.H. ; Bigler, J. ; Bisgaard, H. ; Boedigheimer, M.J. ; Bønnelykke, K. ; Brandsma, J. ; Bucchioni, E. ; Burg, D. ; Caruso, M. ; Chanez, P. ; Chung, F.K. ; Compton, C.H. ; Corfield, J. ; D'Amico, A. ; Dahlen, S.E. ; De Meulder, B. ; Erpenbeck, V.J. ; Erzen, D. ; Fichtner, K. ; Fitch, N. ; Formaggio, E. ; Frey, U. ; Gahlemann, M. ; Geiser, T. ; Hashimoto, S. ; Haughney, J. ; Hedlin, G. ; Hohlfeld, J.M. ; Holweg, C. ; Horváth, I. ; Howarth, P. ; Knowles, R. ; Krug, N. ; Lefaudeux, D. ; Loza, M.J. ; Lutter, R. ; Manta, A. ; Matthews, J.G. ; Mazein, A. ; Middelveld, R.J.M. ; Mores, N. ; Myles, D. ; Pahus, L. ; Pandis, I. ; Pavlidis, S. ; Powel, P. ; Praticò, G. ; Valls, M Puig ; Rao, N. ; Riley, J. ; Roberts, G. ; Rowe, A. ; Sandström, T. ; Seibold, W. ; Selby, A. ; Sigmund, R. ; Singer, F. ; Skipp, P.J. ; Sousa, A.R. ; Sterk, P.J. ; Sun, K. ; Thornton, B. ; van Geest, M. ; Vestbo, J. ; Vissing, N.H. ; Wagener, A.H. ; Wagers, S.S. ; Weiszhart, Z. ; Wheelock, C.E. ; Wilson, S.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-e0ee94f95e3edde9ac9f7710d9749ccb4ce4bcdfdd9dd3903bb0a8c5793c31a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Adult-onset asthma</topic><topic>Age</topic><topic>Age of Onset</topic><topic>Asthma</topic><topic>Asthma - genetics</topic><topic>Asthma - immunology</topic><topic>Biopsy</topic><topic>Children</topic><topic>Cross-Sectional Studies</topic><topic>Data collection</topic><topic>Enrichment</topic><topic>eosinophils</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>gene set variation analysis</topic><topic>Genetic Markers</topic><topic>Humans</topic><topic>ILC3</topic><topic>Inflammation</topic><topic>Leukocytes (eosinophilic)</topic><topic>Lungs</topic><topic>Lymphoid cells</topic><topic>Male</topic><topic>Mast cells</topic><topic>mechanisms</topic><topic>Medical treatment</topic><topic>Middle Aged</topic><topic>Neutrophils</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Patients</topic><topic>Phenotype</topic><topic>phenotyping</topic><topic>Quality control</topic><topic>Quality of life</topic><topic>Respiratory tract</topic><topic>Respiratory tract diseases</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>severe asthma</topic><topic>Severity of Illness Index</topic><topic>Sputum</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Transcriptome - immunology</topic><topic>transcriptomics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hekking, Pieter-Paul</creatorcontrib><creatorcontrib>Loza, Matt J.</creatorcontrib><creatorcontrib>Pavlidis, Stelios</creatorcontrib><creatorcontrib>de Meulder, Bertrand</creatorcontrib><creatorcontrib>Lefaudeux, Diane</creatorcontrib><creatorcontrib>Baribaud, Fred</creatorcontrib><creatorcontrib>Auffray, Charles</creatorcontrib><creatorcontrib>Brinkman, Paul</creatorcontrib><creatorcontrib>Lutter, Rene</creatorcontrib><creatorcontrib>Bansal, Aruna T.</creatorcontrib><creatorcontrib>Sousa, Ana R.</creatorcontrib><creatorcontrib>Bates, Steve A.</creatorcontrib><creatorcontrib>Pandis, Yannis</creatorcontrib><creatorcontrib>Fleming, Louise J.</creatorcontrib><creatorcontrib>Shaw, Dominique E.</creatorcontrib><creatorcontrib>Fowler, Stephen J.</creatorcontrib><creatorcontrib>Meiser, 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(Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hekking, Pieter-Paul</au><au>Loza, Matt J.</au><au>Pavlidis, Stelios</au><au>de Meulder, Bertrand</au><au>Lefaudeux, Diane</au><au>Baribaud, Fred</au><au>Auffray, Charles</au><au>Brinkman, Paul</au><au>Lutter, Rene</au><au>Bansal, Aruna T.</au><au>Sousa, Ana R.</au><au>Bates, Steve A.</au><au>Pandis, Yannis</au><au>Fleming, Louise J.</au><au>Shaw, Dominique E.</au><au>Fowler, Stephen J.</au><au>Meiser, Andrea</au><au>Sun, Kai</au><au>Corfield, Julie</au><au>Howarth, Peter H.</au><au>Bel, Elisabeth H.</au><au>Adcock, Ian M.</au><au>Chung, Kian Fan</au><au>Djukanovic, Ratko</au><au>Adcock, I.M.</au><au>Auffray, C.</au><au>Bakke, P.</au><au>Bansal, A.T.</au><au>Baribaud, F.</au><au>Bates, S.</au><au>Bel, E.H.</au><au>Bigler, J.</au><au>Bisgaard, H.</au><au>Boedigheimer, M.J.</au><au>Bønnelykke, K.</au><au>Brandsma, J.</au><au>Bucchioni, E.</au><au>Burg, D.</au><au>Caruso, M.</au><au>Chanez, P.</au><au>Chung, F.K.</au><au>Compton, C.H.</au><au>Corfield, J.</au><au>D'Amico, A.</au><au>Dahlen, S.E.</au><au>De Meulder, B.</au><au>Erpenbeck, V.J.</au><au>Erzen, D.</au><au>Fichtner, K.</au><au>Fitch, N.</au><au>Formaggio, E.</au><au>Frey, U.</au><au>Gahlemann, M.</au><au>Geiser, T.</au><au>Hashimoto, S.</au><au>Haughney, J.</au><au>Hedlin, G.</au><au>Hohlfeld, J.M.</au><au>Holweg, C.</au><au>Horváth, I.</au><au>Howarth, P.</au><au>Knowles, R.</au><au>Krug, N.</au><au>Lefaudeux, D.</au><au>Loza, M.J.</au><au>Lutter, R.</au><au>Manta, A.</au><au>Matthews, J.G.</au><au>Mazein, A.</au><au>Middelveld, R.J.M.</au><au>Mores, N.</au><au>Myles, D.</au><au>Pahus, L.</au><au>Pandis, I.</au><au>Pavlidis, S.</au><au>Powel, P.</au><au>Praticò, G.</au><au>Valls, M Puig</au><au>Rao, N.</au><au>Riley, J.</au><au>Roberts, G.</au><au>Rowe, A.</au><au>Sandström, T.</au><au>Seibold, W.</au><au>Selby, A.</au><au>Sigmund, R.</au><au>Singer, F.</au><au>Skipp, P.J.</au><au>Sousa, A.R.</au><au>Sterk, P.J.</au><au>Sun, K.</au><au>Thornton, B.</au><au>van Geest, M.</au><au>Vestbo, J.</au><au>Vissing, N.H.</au><au>Wagener, A.H.</au><au>Wagers, S.S.</au><au>Weiszhart, Z.</au><au>Wheelock, C.E.</au><au>Wilson, S.J.</au><aucorp>U-BIOPRED Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathway discovery using transcriptomic profiles in adult-onset severe asthma</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>141</volume><issue>4</issue><spage>1280</spage><epage>1290</epage><pages>1280-1290</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><abstract>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. We sought to identify gene profiles associated with adult-onset severe asthma. 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. 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. 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. [Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28756296</pmid><doi>10.1016/j.jaci.2017.06.037</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2533-5937</orcidid><orcidid>https://orcid.org/0000-0003-2101-8843</orcidid><orcidid>https://orcid.org/0000-0002-3538-0889</orcidid><orcidid>https://orcid.org/0000-0003-4106-8469</orcidid><orcidid>https://orcid.org/0000-0002-7262-6534</orcidid><orcidid>https://orcid.org/0000-0002-8609-118X</orcidid><orcidid>https://orcid.org/0000-0002-3075-2161</orcidid><oa>free_for_read</oa></addata></record>
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subjects	Adult Adult-onset asthma Age Age of Onset Asthma Asthma - genetics Asthma - immunology Biopsy Children Cross-Sectional Studies Data collection Enrichment eosinophils Female Gene expression Gene Expression Profiling gene set variation analysis Genetic Markers Humans ILC3 Inflammation Leukocytes (eosinophilic) Lungs Lymphoid cells Male Mast cells mechanisms Medical treatment Middle Aged Neutrophils Oligonucleotide Array Sequence Analysis Patients Phenotype phenotyping Quality control Quality of life Respiratory tract Respiratory tract diseases Ribonucleic acid RNA severe asthma Severity of Illness Index Sputum Statistical analysis Statistical methods Transcriptome - immunology transcriptomics
title	Pathway discovery using transcriptomic profiles in adult-onset severe asthma
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