Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/114691
Title: Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management
Author: Roca Torrent, Josep
Vargas, Claudia
Cano Franco, Isaac
Selivanov, Vitaly A.
Barreiro, Esther
Maier, Dieter
Falciani, Francesco
Wagner, P. D. (Peter D.)
Cascante i Serratosa, Marta
García Aymerich, Judith
Kalko, Susana
Marín de Mas, Igor Bartolomé
Tegnér, Jesper
Escarrabill Sanglas, Joan
Agustí García-Navarro, Àlvar
Gomez Cabrero, David
Synergy-COPD consortium
Keywords: Malalties pulmonars obstructives cròniques
Comorbiditat
Citoquines
Investigació mèdica
Estrès oxidatiu
Chronic obstructive pulmonary diseases
Comorbidity
Cytokines
Medicine research
Oxidative stress
Issue Date: 28-Nov-2014
Publisher: BioMed Central
Abstract: Background and hypothesis: Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. Objective and method: To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. Results: (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. Conclusions: The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.
Note: Reproducció del document publicat a: https://doi.org/10.1186/1479-5876-12-S2-S3
It is part of: Journal of Translational Medicine, 2014, vol. 12, num. Suppl 2, p. s3
URI: http://hdl.handle.net/2445/114691
Related resource: https://doi.org/10.1186/1479-5876-12-S2-S3
ISSN: 1479-5876
Appears in Collections:Articles publicats en revistes (Medicina)
Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Files in This Item:
File Description SizeFormat 
648313.pdf1.6 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons