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

U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics
U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics
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.
0091-6749
1797-1807
Lefaudeuz, D.
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de Meulder, B.
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Loza, M.J.
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Peffer, N.
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Rowe, A.
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Baribaud, F.
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Bansal, A.T.
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Lutter, R.
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Sousa, A.R.
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Corfield, J.
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Pandis, I.
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Bakke, P.S.
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Caruso, M.
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Chanez, P.
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Dahlen, S.E.
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Fleming, L.J.
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Fowler, S.J.
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Horvath, I.
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Krug, N.
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Montuschi, P.
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Sanak, M.
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Sandstrom, T.
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Shaw, D.E.
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Singer, F.
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Sterk, P.J.
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Roberts, G.
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Adcock, I.M.
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Djukanovic, R.
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Auffray, C.
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Chung, K.F.
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Lefaudeuz, D.
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de Meulder, B.
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Loza, M.J.
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Peffer, N.
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Rowe, A.
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Baribaud, F.
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Bansal, A.T.
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Lutter, R.
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Sousa, A.R.
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Corfield, J.
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Pandis, I.
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Bakke, P.S.
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Caruso, M.
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Chanez, P.
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Dahlen, S.E.
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Fleming, L.J.
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Fowler, S.J.
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Horvath, I.
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Krug, N.
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Montuschi, P.
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Sanak, M.
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Sandstrom, T.
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Shaw, D.E.
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Singer, F.
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Sterk, P.J.
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Roberts, G.
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Adcock, I.M.
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Djukanovic, R.
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Auffray, C.
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Chung, K.F.
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Lefaudeuz, D., de Meulder, B., Loza, M.J., Peffer, N., Rowe, A., Baribaud, F., Bansal, A.T., Lutter, R., Sousa, A.R., Corfield, J., Pandis, I., Bakke, P.S., Caruso, M., Chanez, P., Dahlen, S.E., Fleming, L.J., Fowler, S.J., Horvath, I., Krug, N., Montuschi, P., Sanak, M., Sandstrom, T., Shaw, D.E., Singer, F., Sterk, P.J., Roberts, G., Adcock, I.M., Djukanovic, R., Auffray, C. and 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), 1797-1807. (doi:10.1016/j.jaci.2016.08.048).

Record type: Article

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.

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More information

Accepted/In Press date: 8 August 2016
e-pub ahead of print date: 20 October 2016
Published date: June 2017
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 400695
URI: http://eprints.soton.ac.uk/id/eprint/400695
ISSN: 0091-6749
PURE UUID: e4238e88-be1d-43b7-8016-745d5281a3bf
ORCID for G. Roberts: ORCID iD orcid.org/0000-0003-2252-1248
ORCID for R. Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 26 Sep 2016 12:09
Last modified: 15 Mar 2024 05:54

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Contributors

Author: D. Lefaudeuz
Author: B. de Meulder
Author: M.J. Loza
Author: N. Peffer
Author: A. Rowe
Author: F. Baribaud
Author: A.T. Bansal
Author: R. Lutter
Author: A.R. Sousa
Author: J. Corfield
Author: I. Pandis
Author: P.S. Bakke
Author: M. Caruso
Author: P. Chanez
Author: S.E. Dahlen
Author: L.J. Fleming
Author: S.J. Fowler
Author: I. Horvath
Author: N. Krug
Author: P. Montuschi
Author: M. Sanak
Author: T. Sandstrom
Author: D.E. Shaw
Author: F. Singer
Author: P.J. Sterk
Author: G. Roberts ORCID iD
Author: I.M. Adcock
Author: R. Djukanovic ORCID iD
Author: C. Auffray
Author: K.F. Chung

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