Portal de Periódicos da CAPES

Pathway discovery using transcriptomic profiles in adult-onset severe asthma

2017; Elsevier BV; Volume: 141; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2017.06.037

1097-6825

Pieter‐Paul Hekking, Matthew J. Loza, Stelios Pavlidis, Bertrand De Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H. Wagener, Paul Brinkman, René Lutter, Aruna T. Bansal, Ana R. Sousa, Steve A. Bates, Yannis Pandis, Louise Fleming, Dominique 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 Djukanović, Peter J. Sterk, Ian M. Adcock, Hassan Ahmed, Charles Auffray, Per Bakke, Aruna T. Bansal, Fred Baribaud, Stewart Bates, Elisabeth H. Bel, Jeanette Bigler, Hans Bisgaard, Michael Boedigheimer, Klaus Bønnelykke, Joost Brandsma, Paul Brinkman, Enrica Bucchioni, Dominic Burg, Andrew Bush, Massimo Caruso, Amphun Chaiboonchoe, Pascal Chanez, F.K. Chung, C.H. Compton, Julie Corfield, A. D’Amico, Sven‐Erik Dahlén, Bertrand De Meulder, Ratko Djukanović, V.J. Erpenbeck, Damijan Eržen, K. Fichtner, Neil Fitch, Louise Fleming, E. Formaggio, Stephen J. Fowler, Urs Frey, Martina Gahlemann, Thomas Geiser, Yike Guo, Simone Hashimoto, John Haughney, Gunilla Hedlin, Pieter‐Paul Hekking, Tim Higenbottam, J.M. Hohlfeld, Cécile Holweg, Ildikó Horváth, Peter Howarth, A.J. James, Richard Knowles, N. Krug, Diane Lefaudeux, Matthew J. Loza, R. Lutter, Alexander Manta, Sarah Masefield, J.G. Matthews, Alexander Mazein, Andrea Meiser, Roelinde Middelveld, M. Miralpeix, Nadia Mores, Clare Murray, J. Musial, David Myles, Laurie Pahus, Ioannis Pandis, Stelios Pavlidis, P. Powel, G. Praticò, M. Puig Valls, Navin Rao, J. Riley, Amanda Roberts, Graham Roberts, Anthony Rowe, Thomas Sandström, Wolfgang Seibold, Anna Selby, Dominick Shaw, Ralf Sigmund, Florian Singer, Paul Skipp, Ana R. Sousa, Peter J. Sterk, Kai Sun, Bob Thornton, W. M. van Aalderen, Marleen van Geest, Jørgen Vestbo, Nadja Hawwa Vissing, Ariane H. Wagener, Scott Wagers, Z. Weiszhart, Craig E. Wheelock, Susan J. Wilson,

Eosinophilic Esophagitis

BackgroundAdult-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.ObjectiveWe sought to identify gene profiles associated with adult-onset severe asthma.MethodsThis 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.ResultsSignificant 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.ConclusionsAdult-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. 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.