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

Paolo Montuschi, Diane Lefaudeux, Bertrand De Meulder, Matthew J. Loza, Nancy Peffer, Anthony Rowe, Frédéric Baribaud, Aruna T. Bansal, Rene Lutter, Ana R. Sousa, Julie Corfield, Ioannis Pandis, Per S. Bakke, Massimo Caruso, Pascal Chanez, Sven-Erik Dahlén, Louise J. Fleming, Stephen J. Fowler, Ildiko Horvath, Norbert KrugMarek Sanak, Thomas Sandstrom, Dominic E. Shaw, Florian Singer, Peter J. Sterk, Graham Roberts, Ian M. Adcock, Ratko Djukanovic, Charles Auffray, Kian Fan Chung, Nora Adriaens, Hassan Ahmed, Antonios Aliprantis, Kjell Alving, Philipp Badorek, David Balgoma, Clair Barber, An Bautmans, Annelie F. Behndig, Elisabeth Bel, Jorge Beleta, Ann Berglind, Alix Berton, Jeanette Bigler, Hans Bisgaard, Grazyna Bochenek, Michael J. Boedigheimer, Klaus Bøonnelykke, Joost Brandsma, Armin Braun, Paul Brinkman, Dominic Burg, Davide Campagna, Leon Carayannopoulos, João P. Carvalho Da Purfição 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, Jessica Edwards, Rosalia Emma, Magnus Ericsson, Veit Erpenbeck, Damijan Erzen, Cornelia Faulenbach, Klaus Fichtner, Neil Fitch, Breda Flood, Urs Frey, Martina Gahlemann, Gabriella Galffy, Hector Gallart, Trevor Garret, Thomas Geiser, Jilaiha Gent, Maria Gerhardsson De Verdier, David Gibeon, Cristina Gomez, Kerry Gove, Neil Gozzard, Yi-Ke Guo, Simone Hashimoto, John Haughney, Gunilla Hedlin, Pieter-Paul Hekking, Elisabeth Henriksson, Lorraine Hewitt, Tim Higgenbottam, Uruj Hoda, Jans Hohlfeld, Cecile Holweg, Peter Howarth, Richard Hu, Sile Hu, Xugang Hu, Val Hudson, Anna J. James, Juliette Kamphuis, Erika J. Kennington, Dyson Kerry, Matthias Klüglich, Hugo Knobel, Richard Knowles, Alan Knox, Johan Kolmert, Jon Konradsen, Maxim Kots, Linn Krueger, Scott Kuo, Maciej Kupczyk, Bart Lambrecht, Ann-Sofie Lantz, Lars Larsson, Nikos 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, Montse Miralpeix, Philips Monk, Clare S. Murray, Jacek Musial, David Myles, Shama Naz, Katja Nething, Ben Nicholas, Ulf Nihlen, Peter Nilsson, Björn Nordlund, Jörgen Östling, Antonio Pacino, Laurie Pahus, Susanna Palkonnen, Stelios Pavlidis, Giorgio Pennazza, Anne Petrén, Sandy Pink, Anthony Postle, Pippa Powel, Malayka Rahman-Amin, Navin Rao, Lara Ravanetti, Emma Ray, Stacey Reinke, Leanne Reynolds, Kathrin Riemann, John Riley, Martine Robberechts, Amanda Roberts, Christos Rossios, Kirsty Russell, Michael Rutgers, Giuseppe Santini, Marco Sentoninco, Corinna Schoelch, James P.R. Schofield, Wolfgang Seibold, Ralf Sigmund, Marcus Sjödin, Paul J. Skipp, Barbara Smids, Caroline Smith, Jessica Smith, Katherine M. Smith, Päivi Söderman, Adesimbo Sogbesan, Doroteya Staykova, Karin Strandberg, Kai Sun, David Supple, Marton Szentkereszty, Lilla Tamasi, 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, Jorgen Vestbo, Anton Vink, Nadja Vissing, Christophe Von Garnier, Arianne Wagerner, Scott Wagers, Frans Wald, Samantha Walker, Jonathan Ward, Zsoka 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

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

125 Citazioni (Scopus)

Abstract

BACKGROUND: 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. OBJECTIVES: We stratified patients with moderate-to-severe asthma based on clinicophysiologic parameters and performed an omics analysis of sputum. METHODS: 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. RESULTS: 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. CONCLUSION: Clustering based on clinicophysiologic parameters yielded 4 stable and reproducible clusters that associate with different pathobiological pathways
Lingua originaleEnglish
pagine (da-a)1797-1807
Numero di pagine11
RivistaJOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume139
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • clustering
  • partition-around-medoids algorithm
  • severe asthma
  • sputum eosinophilia

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