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Clustering analysis of clinical variables in U-BIOPRED adult asthma cohort

Diane Lefaudeux, Bertrand De Meulder, Kian Fan Chung, Graham Roberts, Matthew J. Loza, Frédéric Baribaud, Ana Sousa, Aruna T. Bansal, Anthony Rowe, Ioannis Pandis, Alun Bedding, Amphun Chaiboonchoe, Hassan Ahmed, Charles Auffray, Chris H. Compton, David Myles, Ratko Djukanovic, Dominic E. Shaw, Ildiko Horvath, Jacek Musial, Julie Corfield, Pascal Chanez, Norbert Krug, Paolo Montuschi, Per Bakke, Peter J. Sterk, Riccardo Polosa, Scott S. Wagers, Florian Singer, Stephen J. Fowler, Sven-Erik Dahlen, Thomas Sandström, Timothy Higenbottam, Ulf Nihlén, Urs Frey, Wolfgang Seibold, The U-BIOPRED Study Group
European Respiratory Journal 2014 44: 225; DOI:
Diane Lefaudeux
1EISBM, CNRS, Lyon, France
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Bertrand De Meulder
1EISBM, CNRS, Lyon, France
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Kian Fan Chung
2National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Graham Roberts
3Faculty of Medicine, University of Southampton, Southampton, United Kingdom
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Matthew J. Loza
4Janssen R&D, Janssen, Springhouse,
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Frédéric Baribaud
4Janssen R&D, Janssen, Springhouse,
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Ana Sousa
5Discovery Medicine, GlaxoSmithKline, Uxbridge, United Kingdom
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Aruna T. Bansal
6Acclarogen, Acclarogen Ltd, Cambridge, United Kingdom
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Anthony Rowe
7Janssen, Janssen, Buckinghamshire, United Kingdom
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Ioannis Pandis
8Department of Computing, Imperial College London, London, United Kingdom
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Alun Bedding
5Discovery Medicine, GlaxoSmithKline, Uxbridge, United Kingdom
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Amphun Chaiboonchoe
1EISBM, CNRS, Lyon, France
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Hassan Ahmed
1EISBM, CNRS, Lyon, France
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Charles Auffray
1EISBM, CNRS, Lyon, France
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Chris H. Compton
9Respiratory Development, Novartis Pharma, Redhill, United Kingdom
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David Myles
5Discovery Medicine, GlaxoSmithKline, Uxbridge, United Kingdom
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Ratko Djukanovic
10NIHR Respiratory BioMedical Research Unit, University of Southampton, Southampton, United Kingdom
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Dominic E. Shaw
11Nottingham University Hospital, Nottingham University Hospital, Nottingham, United Kingdom
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Ildiko Horvath
12Semmelweis University, Semmelweis University, Budapest, Hungary
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Jacek Musial
13Allergy and Immunology, Jagiellonian University, Krakow, Poland
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Julie Corfield
14Areteva, Areteva Ltd, Nottingham, United Kingdom
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Pascal Chanez
15Clinique des Bronches, Allergie et Sommeil, Université de la Méditerranée, Marseille, France
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Norbert Krug
16Immunology, Allergology and Clinical Inhalation, Fraunhofer Institute, Hannover, Germany
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Paolo Montuschi
17Pharmacology, Università Cattolica del Sacro Cuore, Rome, Italy
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Per Bakke
18Thoracic Medicine, Haukeland University Hospital, Bergen, Sweden
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Peter J. Sterk
19Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
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Riccardo Polosa
20Internal Medicine and clinical Immunology, University of Catania, Catania, Italy
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Scott S. Wagers
21BioSci Consulting, BioSci Consulting, Maasmechelen, Belgium
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Florian Singer
22Paediatric Respiratory Medicine, University Hospital, Inselspital, Bern, Switzerland
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Stephen J. Fowler
23Respiratory Research Group, University of Manchester, Manchester, United Kingdom
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Sven-Erik Dahlen
24Experimental Asthma and Allergy Research, Karolinska Institutet, Stockhlom, Sweden
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Thomas Sandström
25Pulmonology, University Hospital, Umea, Sweden
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Timothy Higenbottam
26Corporate Clinical Development, Chiesi Pharmaceutics Ltd, Cheadle, United Kingdom
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Ulf Nihlén
27AstraZeneca R&D, AstraZeneca, Södertälje, Sweden
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Urs Frey
22Paediatric Respiratory Medicine, University Hospital, Inselspital, Bern, Switzerland
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Wolfgang Seibold
28Boehringer Ingelheim, Boehringer Ingelheim Corporation, Ingelheim am Rhein, Germany
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The U-BIOPRED Study Group
1EISBM, CNRS, Lyon, France
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Abstract

Background: Asthma is now recognized as a heterogeneous collection of distinct phenotypes. We aimed to uncover potential asthma phenotypes through clustering of clinical variables in the pan-European U-BIOPRED cohort.

Methods: Clinical data from subjects classified as severe (n=209) or non-severe (n=51) asthmatics [Bel et al. Thorax 2011] were analyzed through hierarchical clustering, k-means or partitioning around medoids. Quality of the results was assessed by bootstrapping analysis, also known as consensus clustering [Monti et al.Machine Learning 2003].

Results: Using a reduced set of 16 clinical variables, stable preliminary results were obtained, indicative of potentially new asthma phenotypes. K-means analysis of the 260 mild to severe asthma subjects identified 4 stable clusters (Table), defined mainly by baseline lung function, bronchodilator response and asthma control.

View this table:
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Table: U-BIOPRED clusters with the most discriminating variables

Conclusion: This preliminary analysis shows that clinical variables from the U-BIOPRED cohort can be used to derive phenotypic asthma clusters that are similar but not identical to previously published ones. The significance and stability of these clusters are being benchmarked through topology data analysis and will be further examined in an unrelated asthma cohort, ADEPT.

Funded by the Innovative Medicines Initiative (U-BIOPRED n°115010; eTRIKS n°115446).

  • Asthma - diagnosis
  • © 2014 ERS
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Clustering analysis of clinical variables in U-BIOPRED adult asthma cohort
Diane Lefaudeux, Bertrand De Meulder, Kian Fan Chung, Graham Roberts, Matthew J. Loza, Frédéric Baribaud, Ana Sousa, Aruna T. Bansal, Anthony Rowe, Ioannis Pandis, Alun Bedding, Amphun Chaiboonchoe, Hassan Ahmed, Charles Auffray, Chris H. Compton, David Myles, Ratko Djukanovic, Dominic E. Shaw, Ildiko Horvath, Jacek Musial, Julie Corfield, Pascal Chanez, Norbert Krug, Paolo Montuschi, Per Bakke, Peter J. Sterk, Riccardo Polosa, Scott S. Wagers, Florian Singer, Stephen J. Fowler, Sven-Erik Dahlen, Thomas Sandström, Timothy Higenbottam, Ulf Nihlén, Urs Frey, Wolfgang Seibold, The U-BIOPRED Study Group
European Respiratory Journal Sep 2014, 44 (Suppl 58) 225;

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Clustering analysis of clinical variables in U-BIOPRED adult asthma cohort
Diane Lefaudeux, Bertrand De Meulder, Kian Fan Chung, Graham Roberts, Matthew J. Loza, Frédéric Baribaud, Ana Sousa, Aruna T. Bansal, Anthony Rowe, Ioannis Pandis, Alun Bedding, Amphun Chaiboonchoe, Hassan Ahmed, Charles Auffray, Chris H. Compton, David Myles, Ratko Djukanovic, Dominic E. Shaw, Ildiko Horvath, Jacek Musial, Julie Corfield, Pascal Chanez, Norbert Krug, Paolo Montuschi, Per Bakke, Peter J. Sterk, Riccardo Polosa, Scott S. Wagers, Florian Singer, Stephen J. Fowler, Sven-Erik Dahlen, Thomas Sandström, Timothy Higenbottam, Ulf Nihlén, Urs Frey, Wolfgang Seibold, The U-BIOPRED Study Group
European Respiratory Journal Sep 2014, 44 (Suppl 58) 225;
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