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Biomarker-based clustering of patients with chronic obstructive pulmonary disease

Lowie E. G. W. Vanfleteren, Julie Weidner, Frits M.E. Franssen, Swetlana Gaffron, Niki L Reynaert, Emiel F.M. Wouters, Martijn A. Spruit
ERJ Open Research 2022; DOI: 10.1183/23120541.00301-2022
Lowie E. G. W. Vanfleteren
1COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden
2Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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  • ORCID record for Lowie E. G. W. Vanfleteren
  • For correspondence: Lowie.vanfleteren@vgregion.se
Julie Weidner
3Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
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Frits M.E. Franssen
4Department of Research and Development, CIRO+, Horn, The Netherlands
5Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
6NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
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Swetlana Gaffron
7Viscovery Software GmbH, Vienna, Austria
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Niki L Reynaert
5Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
6NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
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Emiel F.M. Wouters
4Department of Research and Development, CIRO+, Horn, The Netherlands
5Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
6NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
8Ludwig Boltzmann Institute for lung Health, Vienna, Austria
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Martijn A. Spruit
4Department of Research and Development, CIRO+, Horn, The Netherlands
5Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
6NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
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Abstract

Rationale COPD has been repeatedly associated with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways.

Objectives This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterization and examine how these differences may relate to altered biological pathways.

Methods Two hundred thirteen patients with moderate to severe COPD in a clinically stable state were recruited and clinically characterized, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster.

Results Four clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV) with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that 3 of the 4 clusters were enriched in RAGE and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterization of clusters ranged from (I) better functional capacity, health status and fewer comorbidities, (II) more underweight, osteoporosis and more static hyperinflation, (III) more metabolically deranged and (IV) older subjects with worse functional capacity and higher comorbidity load.

Conclusions These new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.

Footnotes

This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received June 23, 2022.
  • Accepted October 16, 2022.
  • Copyright ©The authors 2022
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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Biomarker-based clustering of patients with chronic obstructive pulmonary disease
Lowie E. G. W. Vanfleteren, Julie Weidner, Frits M.E. Franssen, Swetlana Gaffron, Niki L Reynaert, Emiel F.M. Wouters, Martijn A. Spruit
ERJ Open Research Jan 2022, 00301-2022; DOI: 10.1183/23120541.00301-2022

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Biomarker-based clustering of patients with chronic obstructive pulmonary disease
Lowie E. G. W. Vanfleteren, Julie Weidner, Frits M.E. Franssen, Swetlana Gaffron, Niki L Reynaert, Emiel F.M. Wouters, Martijn A. Spruit
ERJ Open Research Jan 2022, 00301-2022; DOI: 10.1183/23120541.00301-2022
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