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

Lefaudeux, fDiane; De Meulder, Bertrand; Loza, Matthew J.; Peffer, Nancy; Rowe, Anthony; Baribaud, Frédéric; Bansal, Aruna T.; Lutter, Rene; Sousa, Ana R.; Corfield, Julie; Pandis, Ioannis; Bakke, Per S.; Caruso, Massimo; Chanez, Pascal; Dahlén, Sven-Erik; Fleming, Louise J.; Fowler, Stephen J.; Horvath, Ildiko; Krug, Norbert; Montuschi, Paolo; Sanak, Marek; Sandstrom, Thomas; Shaw, Dominic E.; Singer, Florian; Sterk, Peter J.; Roberts, Graham; Adcock, Ian M.; Djukanovic, Ratko; Auffray, Charles; Chung, Kian Fan

Authors

fDiane 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 Krug

Paolo Montuschi

Marek Sanak

Thomas Sandstrom

Florian Singer

Peter J. Sterk

Graham Roberts

Ian M. Adcock

Ratko Djukanovic

Charles Auffray

Kian Fan Chung



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.

Citation

Lefaudeux, D., De Meulder, B., Loza, M. J., Peffer, N., Rowe, A., Baribaud, F., …Chung, K. F. (2017). U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics. Journal of Allergy and Clinical Immunology, 139(6), doi:10.1016/j.jaci.2016.08.048

Journal Article Type Article
Acceptance Date Aug 8, 2016
Online Publication Date Oct 20, 2016
Publication Date Jun 30, 2017
Deposit Date May 17, 2018
Journal Journal of Allergy and Clinical Immunology
Print ISSN 0091-6749
Electronic ISSN 0091-6749
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 139
Issue 6
DOI https://doi.org/10.1016/j.jaci.2016.08.048
Public URL http://eprints.nottingham.ac.uk/id/eprint/51856
Publisher URL https://www.sciencedirect.com/science/article/pii/S009167491631185X?via%3Dihub
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0
Additional Information