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      Unravelling the mechanisms driving multimorbidity in COPD to develop holistic approaches to patient-centred care

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      European Respiratory Review
      European Respiratory Society

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          Abstract

          COPD is a major cause of morbidity and mortality worldwide. Multimorbidity is common in COPD patients and a key modifiable factor, which requires timely identification and targeted holistic management strategies to improve outcomes and reduce the burden of disease.

          We discuss the use of integrative approaches, such as cluster analysis and network-based theory, to understand the common and novel pathobiological mechanisms underlying COPD and comorbid disease, which are likely to be key to informing new management strategies.

          Furthermore, we discuss the current understanding of mechanistic drivers to multimorbidity in COPD, including hypotheses such as multimorbidity as a result of shared common exposure to noxious stimuli ( e.g. tobacco smoke), or as a consequence of loss of function following the development of pulmonary disease. In addition, we explore the links to pulmonary disease processes such as systemic overspill of pulmonary inflammation, immune cell priming within the inflamed COPD lung and targeted messengers such as extracellular vesicles as a result of local damage as a cause for multimorbidity in COPD.

          Finally, we focus on current and new management strategies which may target these underlying mechanisms, with the aim of holistic, patient-centred treatment rather than single disease management.

          Abstract

          Multimorbidity is common in COPD and is a global health priority. Using novel approaches to understand the complex mechanisms underlying multimorbidity is key to developing targeted, patient-centred management strategies to improve outcomes. https://bit.ly/3fUUkWB

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          Most cited references260

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Extracellular vesicles: Exosomes, microvesicles, and friends

            Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.
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              Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study.

              Long-term disorders are the main challenge facing health-care systems worldwide, but health systems are largely configured for individual diseases rather than multimorbidity. We examined the distribution of multimorbidity, and of comorbidity of physical and mental health disorders, in relation to age and socioeconomic deprivation. In a cross-sectional study we extracted data on 40 morbidities from a database of 1,751,841 people registered with 314 medical practices in Scotland as of March, 2007. We analysed the data according to the number of morbidities, disorder type (physical or mental), sex, age, and socioeconomic status. We defined multimorbidity as the presence of two or more disorders. 42·2% (95% CI 42·1-42·3) of all patients had one or more morbidities, and 23·2% (23·08-23·21) were multimorbid. Although the prevalence of multimorbidity increased substantially with age and was present in most people aged 65 years and older, the absolute number of people with multimorbidity was higher in those younger than 65 years (210,500 vs 194,996). Onset of multimorbidity occurred 10-15 years earlier in people living in the most deprived areas compared with the most affluent, with socioeconomic deprivation particularly associated with multimorbidity that included mental health disorders (prevalence of both physical and mental health disorder 11·0%, 95% CI 10·9-11·2% in most deprived area vs 5·9%, 5·8%-6·0% in least deprived). The presence of a mental health disorder increased as the number of physical morbidities increased (adjusted odds ratio 6·74, 95% CI 6·59-6·90 for five or more disorders vs 1·95, 1·93-1·98 for one disorder), and was much greater in more deprived than in less deprived people (2·28, 2·21-2·32 vs 1·08, 1·05-1·11). Our findings challenge the single-disease framework by which most health care, medical research, and medical education is configured. A complementary strategy is needed, supporting generalist clinicians to provide personalised, comprehensive continuity of care, especially in socioeconomically deprived areas. Scottish Government Chief Scientist Office. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Eur Respir Rev
                Eur Respir Rev
                ERR
                errev
                European Respiratory Review
                European Respiratory Society
                0905-9180
                1600-0617
                30 June 2021
                02 June 2021
                : 30
                : 160
                : 210041
                Affiliations
                [1 ]School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
                [2 ]University Hospitals Southampton NHS Foundation Trust, Southampton, UK
                [3 ]NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK
                Author notes
                Corresponding author: Hannah Burke ( H.Burke@ 123456soton.ac.uk )
                Article
                ERR-0041-2021
                10.1183/16000617.0041-2021
                9488970
                34415848
                62e47dee-4417-4862-8f9a-0930d6d3921b
                Copyright ©The authors 2021

                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@ersnet.org

                History
                : 16 February 2021
                : 6 April 2021
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