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U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics

2016; Elsevier BV; Volume: 139; Issue: 6 Linguagem: Inglês

10.1016/j.jaci.2016.08.048

1097-6825

Diane Lefaudeux, Bertrand De Meulder, Matthew J. Loza, Nancy J. Peffer, Anthony Rowe, Frédéric Baribaud, Aruna T. Bansal, René Lutter, Ana R. Sousa, Julie Corfield, Ioannis Pandis, Per Bakke, Massimo Caruso, Pascal Chanez, Sven‐Erik Dahlén, Louise Fleming, Stephen J. Fowler, Ildikó Horváth, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandström, Dominick Shaw, Florian Singer, Peter J. Sterk, Graham Roberts, Ian M. Adcock, Ratko Djukanović, Charles Auffray, Kian Fan Chung, Nora Adriaens, Hassan Ahmed, Antonios O. Aliprantis, Kjell Alving, Philipp Badorek, David Balgoma, Clair Barber, An Bautmans, Annelie F. Behndig, Elisabeth H. Bel, Jörge Beleta, A. Berglind, Alix Berton, Jeanette Bigler, Hans Bisgaard, Grażyna Bochenek, Michael Boedigheimer, Klaus Bøonnelykke, Joost Brandsma, Armin Braun, Paul Brinkman, Dominic Burg, Davide Campagna, Leon Carayannopoulos, J.P. Rocha, Amphun Chaiboonchoe, Romanas Chaleckis, Courtney Coleman, Chris Compton, Arnaldo D’Amico, Barbro Dahlén, Jorge De Alba, Pim De Boer, Inge De Lepeleire, Tamara Dekker, Ingrid Delin, Patrick Dennison, Annemiek Dijkhuis, Aleksandra Draper, Jonathan Ward, Rosalia Emma, Magnus Ericsson, Veit J. Erpenbeck, Damijan Eržen, Cornelia Faulenbach, Klaus Fichtner, Neil Fitch, Breda Flood, Urs Frey, Martina Gahlemann, Gabriella Gálffy, Hector Gallart, T. Garret, Thomas Geiser, J. Gent, Maria Gerhardsson de Verdier, David Gibeon, Cristina Gómez, Kerry Gove, Neil Gozzard, Yike Guo, Simone Hashimoto, John Haughney, Gunilla Hedlin, Pieter‐Paul Hekking, Elisabet Welin Henriksson, Lorraine Hewitt, Tim Higgenbottam, Uruj Hoda, J.M. Hohlfeld, Cécile Holweg, Peter Howarth, Richard Hu, Sile Hu, Xugang Hu, Val Hudson, A.J. James, Juliëtte Kamphuis, Erika Kennington, Kerry Dyson, Matthias Klüglich, Hugo Knobel, Richard Knowles, Alan J. Knox, Johan Kolmert, Jon R. Konradsen, Maxim Kots, Linn Krueger, Chih‐Hsi S. Kuo, Maciej Kupczyk, Bart N. Lambrecht, Ann-Sofie Lantz, Lars Larsson, Nikolaos Lazarinis, Saeeda Lone-Satif, Lisa Marouzet, Jane Martin, Sarah Masefield, Caroline Mathon, John G. Matthews, Alexander Mazein, Sally Meah, Andrea Maiser, Andrew Menzies‐Gow, Leanne Metcalf, Roelinde Middelveld, Maria Mikus, M. Miralpeix, Philips Monk, Nadia Mores, Clare Murray, Jacek Musiał, David Myles, Shama Naz, Katja Nething, Ben Nicholas, Ulf Nihlén, Peter Nilsson, Björn Nordlund, Jörgen Östling, Antonio Pacino, Laurie Pahus, Susanna Palkonnen, Stelios Pavlidis, Giorgio Pennazza, Anne Petrén, Sandy Pink, Anthony D. Postle, P. Powel, Malayka Rahman-Amin, Navin Rao, Lara Ravanetti, Emma Ray, Stacey N. Reinke, Leanne Reynolds, Kathrin Riemann‐Campe, John Riley, Martine Robberechts, Amanda Roberts, Christos Rossios, Kirsty Russell, Michael Rutgers, Giuseppe Santini, Marco Sentoninco, Corinna Schoelch, James Schofield, Wolfgang Seibold, Ralf Sigmund, Marcus Sjödin, Paul Skipp, Barbara Smids, Caroline Smith, Jessica Smith, Katherine Smith, P. Söderman, A. Sogbesan, Doroteya K. Staykova, Karin Strandberg, Kai Sun, David Supple, Márton Szentkereszty, Lilla Tamási, Kamran Tariq, John‐Olof Thörngren, Bob Thornton, Jonathan Thorsen, Salvatore Valente, Wim van Aalderenm, Marianne van de Pol, Kees van Drunen, Marleen van Geest, Jenny Versnel, Jørgen Vestbo, Anton Vink, Nadja Hawwa Vissing, Christophe von Garnier, Arianne Wagerner, Scott Wagers, Frans Wald, Samantha Walker, Jonathan Ward, Z. Weiszhart, Kristiane Wetzel, Craig E. Wheelock, Coen Wiegman, Siân Williams, Susan J. Wilson, Ashley Woosdcock, Xian Yang, Elizabeth Yeyashingham, Wen Yu, Wilhelm Zetterquist, Koos Zwinderman,

Bioinformatics and Genomic Networks

Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalized management approach can be provided.We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum.Partition-around-medoids clustering was applied to a training set of 266 asthmatic participants from the European Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) adult cohort using 8 prespecified clinic-physiologic variables. This was repeated in a separate validation set of 152 asthmatic patients. The clusters were compared based on sputum proteomics and transcriptomics data.Four reproducible and stable clusters of asthmatic patients were identified. The training set cluster T1 consists of patients with well-controlled moderate-to-severe asthma, whereas cluster T2 is a group of patients with late-onset severe asthma with a history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chronic airflow obstruction but is composed of nonsmokers. Cluster T4 is predominantly composed of obese female patients with uncontrolled severe asthma with increased exacerbations but with normal lung function. The validation set exhibited similar clusters, demonstrating reproducibility of the classification. There were significant differences in sputum proteomics and transcriptomics between the clusters. The severe asthma clusters (T2, T3, and T4) had higher sputum eosinophilia than cluster T1, with no differences in sputum neutrophil counts and exhaled nitric oxide and serum IgE levels.Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways.