Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management

Journal of Translational Medicine

Review

Dieter Maier¹  Francesco Falciani²  Judith Garcia-Aymerich³  Esther Barreiro⁴  Peter Wagner⁵  Igor Marin De Mas⁶  Vitaly Selivanov⁶  Isaac Cano⁶  Claudia Vargas⁶  Susana Kalko⁶  Joan Escarrabill⁷  Josep Roca⁷  Alvar Agustí⁷  Marta Cascante⁸  Jesper Tegnér⁹  David Gomez-Cabrero⁹ 

[1] Biomax Informatics AG, 282152, Planegg, Germany;Centre for Computational Biology and Modeling (CCBM), Institute of Integrative Biology. University of Liverpool, Crown Street, L69 7ZB, UK;Centre for Research in Environmental Epidemiology (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP). Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut Barcelona, Spain;Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Bunyola, Balearic Islands;Pulmonology Department-Muscle and Respiratory System Research Unit (URMAR), IMIM-Hospital del Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Parc de Recerca Biomédica de Barcelona (PRBB), Barcelona, Catalonia, Spain;Division of Physiology, Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, CA, USA;IDIBAPS, Hospital Clínic. Facultat de Medicina, 08036, Barcelona, Catalunya, Spain;IDIBAPS, Hospital Clínic. Facultat de Medicina, 08036, Barcelona, Catalunya, Spain;Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Bunyola, Balearic Islands;IDIBAPS, Hospital Clínic. Facultat de Medicina, 08036, Barcelona, Catalunya, Spain;Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Bunyola, Balearic Islands;Departament de Bioquimica i Biologia Molecular i IBUB, Facultat de Biologia, Universitat de Barcelona, 08028, Barcelona, Spain;Unit of Computational Medicine, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden;

关键词: Chronic diseases;    COPD;    Disease heterogeneity;    Integrated Care;    Predictive Medicine;    Redox disequilibrium;    Systems Medicine;    VOmax;   

DOI  :  10.1186/1479-5876-12-S2-S3

来源: Springer

【 摘 要 】

Background and hypothesisHeterogeneity 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 methodTo 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Roca et al.; licensee BioMed Central Ltd. 2014