Pathway discovery using transcriptomic profiles in adult-onset severe asthma
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 tec...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2018
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| Online Access: | https://eprints.nottingham.ac.uk/51853/ |
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| author | Hekking, Pieter-Paul Loza, Matt J. Pavlidis, Stelios de Meulder, Bertrand Lefaudeux, Diane Baribaud, Fred Auffray, Charles Wagener, Ariane H. Brinkman, Paul Lutter, Rene Bansal, Aruna T. Sousa, Ana R. Bates, Steve A. Pandis, Yannis Fleming, Louise J. Shaw, Dominique E. Fowler, Stephen J. Guo, Y. Meiser, Andrea Sun, Kai Corfield, Julie Howarth, Peter H. Bel, Elisabeth H. Adcock, Ian M. Chung, Kian Fan Djukanovic, Ratko Sterk, Peter J. |
| author_facet | Hekking, Pieter-Paul Loza, Matt J. Pavlidis, Stelios de Meulder, Bertrand Lefaudeux, Diane Baribaud, Fred Auffray, Charles Wagener, Ariane H. Brinkman, Paul Lutter, Rene Bansal, Aruna T. Sousa, Ana R. Bates, Steve A. Pandis, Yannis Fleming, Louise J. Shaw, Dominique E. Fowler, Stephen J. Guo, Y. Meiser, Andrea Sun, Kai Corfield, Julie Howarth, Peter H. Bel, Elisabeth H. Adcock, Ian M. Chung, Kian Fan Djukanovic, Ratko Sterk, Peter J. |
| author_sort | Hekking, Pieter-Paul |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 5 83), nasal brushings (n 5 41), and endobronchial brushings (n 5 65) and biopsies (n 5 47) (Affymetrix HT HG-U1331 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. |
| first_indexed | 2025-11-14T20:22:10Z |
| format | Article |
| id | nottingham-51853 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:22:10Z |
| publishDate | 2018 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-518532024-08-15T15:28:21Z https://eprints.nottingham.ac.uk/51853/ Pathway discovery using transcriptomic profiles in adult-onset severe asthma Hekking, Pieter-Paul Loza, Matt J. Pavlidis, Stelios de Meulder, Bertrand Lefaudeux, Diane Baribaud, Fred Auffray, Charles Wagener, Ariane H. Brinkman, Paul Lutter, Rene Bansal, Aruna T. Sousa, Ana R. Bates, Steve A. Pandis, Yannis Fleming, Louise J. Shaw, Dominique E. Fowler, Stephen J. Guo, Y. Meiser, Andrea Sun, Kai Corfield, Julie Howarth, Peter H. Bel, Elisabeth H. Adcock, Ian M. Chung, Kian Fan Djukanovic, Ratko Sterk, Peter J. 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 5 83), nasal brushings (n 5 41), and endobronchial brushings (n 5 65) and biopsies (n 5 47) (Affymetrix HT HG-U1331 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. Elsevier 2018-04-30 Article PeerReviewed Hekking, Pieter-Paul, Loza, Matt J., Pavlidis, Stelios, de Meulder, Bertrand, Lefaudeux, Diane, Baribaud, Fred, Auffray, Charles, Wagener, Ariane H., Brinkman, Paul, Lutter, Rene, Bansal, Aruna T., Sousa, Ana R., Bates, Steve A., Pandis, Yannis, Fleming, Louise J., Shaw, Dominique E., Fowler, Stephen J., Guo, Y., Meiser, Andrea, Sun, Kai, Corfield, Julie, Howarth, Peter H., Bel, Elisabeth H., Adcock, Ian M., Chung, Kian Fan, Djukanovic, Ratko and Sterk, Peter J. (2018) Pathway discovery using transcriptomic profiles in adult-onset severe asthma. Journal of Allergy and Clinical Immunology, 141 (4). pp. 1280-1290. ISSN 0091-6749 Adult-onset asthma severe asthma gene set variation analysis phenotyping transcriptomics mechanisms eosinophils mast cells ILC3 https://www.jacionline.org/article/S0091-6749(17)31195-8/abstract doi:10.1016/j.jaci.2017.06.037 doi:10.1016/j.jaci.2017.06.037 |
| spellingShingle | Adult-onset asthma severe asthma gene set variation analysis phenotyping transcriptomics mechanisms eosinophils mast cells ILC3 Hekking, Pieter-Paul Loza, Matt J. Pavlidis, Stelios de Meulder, Bertrand Lefaudeux, Diane Baribaud, Fred Auffray, Charles Wagener, Ariane H. Brinkman, Paul Lutter, Rene Bansal, Aruna T. Sousa, Ana R. Bates, Steve A. Pandis, Yannis Fleming, Louise J. Shaw, Dominique E. Fowler, Stephen J. Guo, Y. Meiser, Andrea Sun, Kai Corfield, Julie Howarth, Peter H. Bel, Elisabeth H. Adcock, Ian M. Chung, Kian Fan Djukanovic, Ratko Sterk, Peter J. Pathway discovery using transcriptomic profiles in adult-onset severe asthma |
| title | Pathway discovery using transcriptomic profiles in adult-onset severe asthma |
| title_full | Pathway discovery using transcriptomic profiles in adult-onset severe asthma |
| title_fullStr | Pathway discovery using transcriptomic profiles in adult-onset severe asthma |
| title_full_unstemmed | Pathway discovery using transcriptomic profiles in adult-onset severe asthma |
| title_short | Pathway discovery using transcriptomic profiles in adult-onset severe asthma |
| title_sort | pathway discovery using transcriptomic profiles in adult-onset severe asthma |
| topic | Adult-onset asthma severe asthma gene set variation analysis phenotyping transcriptomics mechanisms eosinophils mast cells ILC3 |
| url | https://eprints.nottingham.ac.uk/51853/ https://eprints.nottingham.ac.uk/51853/ https://eprints.nottingham.ac.uk/51853/ |