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Systems Medicine and Integrated Care to Combat Chronic Bousquet et al. Genome Medicine 2011, 3:43 http://genomemedicine.com/content/3/7/43 CORRESPONDENCE Open Access Systems medicine and integrated care to combat chronic noncommunicable diseases Jean Bousquet1*, Josep M Anto2, Peter J Sterk3, Ian M Adcock4, Kian Fan Chung5, Josep Roca6, Alvar Agusti6, Chris Brightling7, Anne Cambon-Thomsen8, Alfredo Cesario9, Sonia Abdelhak10, Stylianos E Antonarakis11, Antoine Avignon12, Andrea Ballabio13, Eugenio Baraldi14, Alexander Baranov15, Thomas Bieber16, Joël Bockaert17, Samir Brahmachari18, Christian Brambilla19, Jacques Bringer20, Michel Dauzat21, Ingemar Ernberg22, Leonardo Fabbri23, Philippe Froguel24, David Galas25, Takashi Gojobori26, Peter Hunter27, Christian Jorgensen28, Francine Kaumann29, Philippe Kourilsky30, Marek L Kowalski31, Doron Lancet32, Claude Le Pen33, Jacques Mallet34, Bongani Mayosi35, Jacques Mercier36, Andres Metspalu37, Joseph H Nadeau25, Grégory Ninot38, Denis Noble39, Mehmet Öztürk40, Susanna Palkonen41, Christian Préfaut36, Klaus Rabe42, Eric Renard20, Richard G Roberts43, Boleslav Samolinski44, Holger J Schünemann45, Hans-Uwe Simon46, Marcelo Bento Soares47, Giulio Superti-Furga48, Jesper Tegner49, Sergio Verjovski-Almeida50, Peter Wellstead51, Olaf Wolkenhauer52, Emiel Wouters53, Rudi Balling54, Anthony J Brookes55, Dominique Charron56, Christophe Pison57,58, Zhu Chen59, Leroy Hood25 and Charles Auray56,57,58,60,61 Non-communicable diseases, the major global Abstract health problem of the century We propose an innovative, integrated, cost-eective Chronic diseases are disorders of long duration and health system to combat major non-communicable generally slow progression [1]. ey include four major diseases (NCDs), including cardiovascular, chronic non-communicable diseases (NCDs) listed by the World respiratory, metabolic, rheumatologic and neurologic Health Organization (WHO) [2] – cardiovascular disorders and cancers, which together are the predominant diseases, cancer, chronic respiratory diseases and health problem of the 21st century. This proposed holistic diabetes – as well as other NCDs, such as strategy involves comprehensive patient-centered neuropsychiatric disorders [3] and arthritis. As survival integrated care and multi-scale, multi-modal and multi- rates have improved for infectious and genetic diseases, level systems approaches to tackle NCDs as a common chronic diseases have come to include communicable group of diseases. Rather than studying each disease diseases (such as HIV/AIDS) and genetic disorders (such individually, it will take into account their intertwined as cystic fibrosis). NCDs represent the major global gene-environment, socio-economic interactions health problem of the 21st century [4,5]; they affect all and co-morbidities that lead to individual-specic age groups [6] and their burden is greater than that of complex phenotypes. It will implement a road map for infectious diseases. NCDs are the world leading cause of predictive, preventive, personalized and participatory (P4) disease burden and mortality [2] and are increasing in medicine based on a robust and extensive knowledge prevalence and burden [7], even in low- and middle- management infrastructure that contains individual income countries [8]. Costs incurred by uncontrolled patient information. It will be supported by strategic NCDs are substantial, especially in underserved partnerships involving all stakeholders, including general populations [9] and low- and middle-income countries practitioners associated with patient-centered care. This [10,11]. NCDs are an under-appreciated cause of poverty systems medicine strategy, which will take a holistic and hinder economic development [11]. Importantly, approach to disease, is designed to allow the results to management of NCDs has recently been prioritized be used globally, taking into account the needs and globally (Box 1). specicities of local economies and health systems. Chronic diseases are caused by complex gene- environment interactions acting across the lifespan from *Correspondence: [email protected] 1Department of Respiratory Diseases, Arnaud de Villeneuve Hospital, the fetus to old age (Figure 1). In this context, CHU Montpellier, INSERM CESP U1018, Villejuif, France ‘environment’ includes risk and protective factors Full list of author information is available at the end of the article associated with environment and lifestyle, such as © 2011 Bousquet et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bousquet et al. Genome Medicine 2011, 3:43 Page 2 of 12 http://genomemedicine.com/content/3/7/43 Box 1: Priorities for the prevention and control of NCDs tobacco, nutrition, indoor and outdoor air pollution and sedentary life [2]. May 2008: 61st World Health Assembly. WHO recommended Socio-economic determinants are intertwined with the a worldwide priority policy on NCD prevention and control onset, progression, severity and control of NCDs. There (2008 to 2013), including cardiovascular disease, cancer, chronic are functional interdependencies between molecular respiratory diseases [101] and diabetes, not least because they often have common environmental risk factors [2]. components, reflecting complex network perturbations that link cells, tissues and organs [12]. Early life events May 2010: United Nations (UN) General Assembly unanimously are crucial in the generation of NCDs, and aging adopted Resolution A/RES/64/265: ’Tackling NCDs constitutes increases disease complexity, adding, for example, tissue one of the major challenges for sustainable development in the and cell senescence [13]. Comorbidity refers to the co- 21st century‘ [102]. existence of two or more diseases or conditions in the December 2010: the Council of the European Union adopted same individual that have similar risk factors and/or conclusions based on innovative and global approaches for mechanisms. Most people with NCDs suffer from two or NCDs in public health and healthcare systems to further develop more diseases [14]. Co-morbidity and multi-morbidity population-based and patient-centered policies [1]. are common signatures of NCDs and are associated with 2010: US Center for Disease Control and Prevention (CDC) [103] worse health outcomes [15], complex pharmacological says that ’an essential strategy for keeping older adults healthy is interventions and clinical management, and increased preventing NCDs and reducing associated complications’. healthcare costs [16]. However, little is known about how 19 September 2011: UN General Assembly symposium on NCDs. NCDs truly cluster at the genetic, molecular or mechanistic levels, and there is scant understanding of Socio- Health promotion economic primary prevention determinants Lifestyle - environment Risk and protective factors Tobacco smoking, pollutants, allergens, nutrition, infections, physical exercise, others Gender Genes Systems biology on precise phenotypes Biological expression of chronic diseases Transcripts, proteins, metabolites Target organ local inflammation Systemic inflammation Cell and tissue remodeling Personalized medicine Age • Primary prevention • Secondary prevention • Tertiary prevention Clinical expression of chronic diseases • Treatment Co-morbidities Severity of co-morbidities Persistence remission Long-term morbidity Responsiveness - side effects to treatment Figure 1. NCDs are associated with complex gene-environment interactions modulated by socio-economic determinants, psychological factors, age and gender. The products of these interactions lead to the biological expression of NCDs and further to their clinical expression with co-morbidities. A new definition of NCD phenotypes is needed to understand how a network of molecular and environmental factors can lead to complex clinical outcomes of NCDs for prevention and control. Bousquet et al. Genome Medicine 2011, 3:43 Page 3 of 12 http://genomemedicine.com/content/3/7/43 how specific combinations of NCDs influence prognosis differences that affect coronary heart disease mortality, and treatment [16]. and this should serve as an example to follow for other NCDs are multi-factorial. In addition to environmental NCDs [35]. In May 2009, the 62nd WHO Assembly factors and increased life expectancy, intrinsic host recommended re-orienting health systems globally to responses, such as local and systemic inflammation, promote primary healthcare as the most cost-effective immune responses and remodeling [17], have key roles in strategy [36]. Healthcare often focuses on single diseases, the initiation and persistence of diseases and co- advanced technology, biomedical interventions and morbidities. The recent increase in NCDs has been specialist care. Most healthcare takes place in primary associated in part with biodiversity loss [18], socio- care settings [37], with emphasis on providing a complete economic inequities linked with climate change, and loss range of care, from home to hospital, and on investing of natural environments [19]. A more comprehensive resources rationally. Fragmenting care can reduce the understanding of these links will make it possible to ability of primary care clinicians to ensure that patient propose more effective primary prevention strategies. care is comprehensive, integrated, holistic, and The in utero environment is an
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