Deployment of Novel Integrated Care Services to Promote Healthy Life styles: Physical Activity as a Use Case
Report of the Doctoral Thesis presented by
Anael Barberan Garcia
To get the academic degree of doctor from the University of Barcelona
Under the direction of
Prof. Josep Roca Torrent
and the co-direction of
Dr. Isabel Blanco Vich
Medicine and Translational Research PhD program University of Barcelona 2017
Thesis registered at the Medicine and Translational Research Doctoral Program 2017 Department of Medicine | School of Medicine
In order to remain healthy, the entire day should be devoted exclusively to ways and means of increasing one’s strength and staying healthy, and the best way to do so is through physical exercise. Hippocrates 460-377 BC
Lack of activity destroys the good condition of every human being, while movement and methodical physical exercise save it and preserve it. Plato 427-347 BC
The doctor of the future will give no medication, but will interest his patients in the care of the human frame, diet and in the cause and prevention of diseases. T. Edison 1847-1931
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CONTENTS ACKNOWLEDGEMENTS
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GRANTS AND SUPPORT
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GLOSSARY
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PREFACE
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INTRODUCTION
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HYPOTHESIS
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OBJECTIVES
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PUBLICATIONS
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DISCUSSION
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CONCLUSIONS
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SUMMARY IN ENGLISH
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SUMMARY IN CATALAN
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SUMMARY IN SPANISH
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REFERENCES
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ACKNOWLEDGEMENTS Dedicated to my parents and my grandmother.
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GRANTS AND SUPPORT This PhD thesis was partially supported by:
• CONNECARE – Personalised Connected Care for Complex Chronic Patients (H2020-689802). • NEXTCARE – Innovation in Integrated Care Services for Chronic Patients (COMRDI15-1-0016). • ACT@Scale - Advancing Care Coordination and Telehealth at Scale (HP-PJ-2015, 3HP, 709770). • Sport 4 Health – Sport as a treatment in chronic diseases and healthcare sustainability (EIT-Health-IBI-2017-17143).
• NEXES - Supporting healthier and independent living for chronic patients and elderly (FP7-CIPICT-PSP-2007-1-225025).
• Innovative integrated care services for chronic patients funded by the Institute of Health Carlos III (FIS-PI09/90634).
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GLOSSARY 31
P-MRS
31-Phosphorus Magnetic Resonance Spectroscopy
ACM
Adaptive Case Management
ACT@Scale
Advancing Care Coordination and Telehealth at Scale
COPD
Chronic Obstructive Pulmonary Disease
CPR
Cardiopulmonary rehabilitation
CVD
Cardiovascular diseases
DHF
Digital Health Framework
EIP-AHA
European Innovation Partnership for Active and Healthy Ageing
EIT-Health
European Institute for Technology - Health
HRQoL
Health-Related Quality of Life
ICS
Integrated Care Services
ICT
Information and Communication Technologies
MAST
Model for ASsessment of Telemedicine
NCDs
Non-communicable chronic diseases
NIRS
Near-Infrared Spectrometry
NMES
Neuromuscular electrical stimulation
PCr
Phosphocreatine
PHF
Personal Health Folder
RCT
Randomized Controlled Trial
S4H
Sport 4 Health
WHO
World Health Organization
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PREFACE This PhD thesis is composed by a compendium of published articles in accordance with the policy adopted by the Doctoral Committee of the Barcelona University (UB).
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INTRODUCTION Cardiopulmonary Rehabilitation revisited Cardiopulmonary rehabilitation (CPR) is defined as a “comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education and behaviour change, designed to improve the physical and psychological condition of people with respiratory chronic disorders”[1]. Although this definition refers specifically to patients with chronic respiratory disorders, it can be easily expanded to other non-communicable chronic diseases (NCDs) (i.e. cardiovascular and metabolic disorders) that benefit from enhanced functional status (i.e. aerobic capacity and physical activity). CPR and programs including endurance exercise training have clearly demonstrated efficacy to reduce symptoms, increase aerobic capacity, improve health-related quality of life (HRQoL) and enhance prognosis in patients with different chronic disorders and elderly subjects[1-6]. In that sense, major disease-oriented international clinical guidelines report strong recommendations for extensive implementation of such services. However, well-known constraints of classical CPR are limiting its effectiveness and adoption, namely: i) Low accessibility; ii) Transient physiological effects; iii) Heterogeneity of training-induced responses; iv) High percentage of dropouts; v) Lack of well-defined business models - and poorly defined reimbursement incentives - to facilitate financial sustainability; and, vi) Lack of well-structured interventions fostering daily physical activity through behaviour change techniques[1]. Therefore, there is a need to design innovative services with the potential to overcome such limitations and assure sustainability and effectiveness of the novel interventions. Scientific evidence on efficacy of CPR supports the reshaping of classical outpatient programs into long-term community-based interventions empowering patients for self-management and healthy lifestyles, including promotion of PA as a cornerstone action. The importance to focus on the problem of physical inactivity in NCDs is based on three main aspects. Firstly, physical inactivity appears to be more common in chronic patients (i.e. chronic obstructive pulmonary disease (COPD), coronary artery disease or rheumatoid arthritis) compared with age-matched healthy individuals[7]. Furthermore, physical activity is, a priori, a treatable aspect in many NCDs and clinicians may be underappreciating its importance in chronic patients. Last but not least, physical activity has shown an important predictive value in chronic patients and healthy individuals for prevention of multimorbidity and modulation of disease progress. The concept of CPR emphasizes behaviour change through collaborative self-management, which ideally would lead to healthy lifestyles and greater participation in activities involving physical activity[8]. It is of note, that the inherent holistic approach of CPR offers high potential for stimulating a proactive and participatory attitude of the patients through empowerment for self-management. However, although CPR improves aerobic capacity in different NCDs, this is not often accompanied by an increase in daily-life physical activity. As such, there is a need to reconceptualise the
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paradigm focussing on physical activity and wellness programs. The final aim is to attenuate the deleterious impact of physical inactivity on poor prognosis of NCDs and on patients’ health status and, in general, for prevention of chronic diseases and associated risk factors. It is concluded that, although the conceptual basis of classical CPR is still in force, classical CPR interventions are mostly focused on enhancement of aerobic capacity. Consequently, there is a clear need for changes to foster matching of CPR with evolving healthcare needs, namely: i) Personalization of interventions; ii) Stimulation of a pro-active role of patients for self-management and physical activity; iii) Enhanced flexibility of interventions; iv) Improved accessibility and logistics; and, v) Financial sustainability of the services ensuring long-term adoption of cost-effective healthy lifestyles interventions. To this end, we have identified the following four main areas of action that will be the focus of the current PhD thesis: i) Patient characterization; ii) Assessment of training-induced physiological effects; iii) Training modalities; and, iv) Service re-design toward an integrated care approach. Implicit with this focus is to foster cost-effective preventive interventions associated with promotion of healthy lifestyles, which ultimately will facilitate the transition from classical CPR toward novel modalities of healthcare services overcoming current limitations.
Characterization of candidates Improving patient’s characterisation is a central aspect to optimize CPR outcomes at two levels, namely: i) Physiological requirements; and, ii) Adherence profile. Firstly, better customization of exercise training programs leading to an enhanced aerobic capacity should improve HRQoL, dyspnoea and exercise capacity, but should also facilitate and motivate patients for exercise beyond the supervised training period, engaging in increased physical activity. General principles of exercise training in chronic patients are not different from those for healthy individuals[1]. However, the heterogeneity of the disease and multi-morbidity prompts to adapt the particularities of training (i.e. modalities, length and intensity) to patient’s specificities in terms of medical and physiological requirements. For instance, it has been demonstrated that a short high-intensity endurance exercise program (3 weeks) in severe COPD patients generates abnormal training-induced skeletal muscle adaptive changes due to oxidative stress[9, 10]. On the other hand, a longer high-intensity exercise training program (8 weeks) generates physiological benefits in skeletal muscle both in healthy individuals and in moderate-to-severe COPD patients[11]. However, personalization of CPR does not involve solely biological factors, but determinants of adherence to the intervention should also be taken into account, as indicated by the high rates of dropouts from traditional CPR programs[1, 12] and the lack of translation of exercise training-induced enhancement of aerobic capacity into more active lifestyles. It has been recently reported that the main patient-centred factors to be addressed for improving CPR adherence can be divided into three general areas, namely: i) Building confidence after disease diagnosis; ii) Having perception of
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immediate tangible results; and, iii) Having access to the program. Therefore, a proper characterization of candidates to CPR is necessary to re-address patients for individually tailored rehabilitation programs. It is important to highlight that apart from the classical CPR assessments (i.e. aerobic capacity, HRQoL, etc.) is key to address behavioural aspects (i.e. facilitators and barriers to physical activity, self-efficacy, etc.) to increase physical activity through long-term behavioural change.
Strengths and limitations of exercise training in chronic patients The beneficial impact of exercise training in many NCDs has been clearly stated in terms of HRQoL, symptoms, exercise tolerance, exacerbations and mortality. Moreover, during the last decades, the underlying physiologic mechanisms of exercise training in chronic patients have been widely studied. Exercise training strategies have evolved from constant workload to interval training, combination of resistance and strength training, as well as introduction of novel methods such as neuromuscular electrical stimulation (NMES). This variety of training modalities has emerged as a successful answer to adapt the intervention to specific patient requirements and tolerance achieving a positive impact on clinical and physiological status. For instance, interval exercise training has been shown as a good alternative to constant workload exercise training (especially in severe patients) for improving aerobic capacity at lower symptoms ratings (i.e. dyspnoea and leg discomfort) during the training sessions. The physiological rationale of interval training is underpinned in three main arguments: i) The active recovery intervals allow the partial restore phosphocreatine (PCr) levels; ii) The active recovery intervals allow the oxygen reloading of myoglobin stores having direct impact on mitochondrial respiration; and, iii) The alternation of high intensity and recovery periods activates cardiac output and minute ventilation. Equally, NMES has demonstrated to be an effective and well-tolerated exercise training modality in advanced chronic individuals for strengthening quadriceps and, therefore, it may be a good alternative to active training in these particular groups of patients[13]. During the last years, the amount of physical activity in chronic patients has proven to be an independent prognostic factor for disease exacerbation, disease progress and mortality. On this basis, we can state that the current challenge of CPR relies in overcoming the existing gap between traditional hospital-based CPR programs and long-term community-based interventions fostering adoption of a physically active behaviour in chronic patients. The novel modalities of community-based interventions must be understood and conceived as a core part of self-management strategies within the action plan of chronic patients. From the economical point of view, it is important to highlight that the community-based interventions (i.e. home-based CPR programs) have proven as a cost-saving solution to the limited accessibility of hospital-based programs[14], showing similar physiological effects, requiring less supervision and, consequently, involving less use of resources. During the last years, several initiatives have assessed simple strategies showing positive effects on physical activity enhancement of COPD patients. Moreover, flexible interventions outside the hospital scope are also likely to improve long-term adherence to physical activity while reducing the logistic problems demonstrated in traditional CPR programs and making them accessible to a wider range of patients. These strategies include behaviour change interventions, the use of pedometers and/or the design of walking circuits in community-based environments to encourage the increase of physical activity[15-18].
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Assessment of physiological effects and sustainability over time Traditionally, the assessment of exercise training-induced effects in chronic patients has been based on patient-centred outcomes such as symptoms, HRQoL and exercise performance; being the latter mostly focused on changes occurred in central organs (i.e. peak oxygen uptake, peak ventilation, chronotropic response, etc.) and paying less attention to what happens at peripheral level (i.e. skeletal muscle). Conversely, exercise intolerance cannot be only explained based on oxygen transport limitations, but also skeletal muscle dysfunction has been demonstrated as a relevant driving cause of exercise intolerance in COPD patients. It is well accepted that the interplay among all factors modulating oxygen transport and mitochondrial oxygen utilization, as well as their ratio, determine aerobic capacity[11]. Skeletal muscle metabolism and peripheral oxygenation have shown to be good indicators of training effects in healthy subjects. Moreover, it can be hypothesized that the level of impairment in interactions among tissue oxygenation and metabolic changes may be one of the main factors explaining the wide heterogeneity of training adaptations in chronic patients. However, the evaluation of biochemical features of skeletal muscle is difficult and often requires invasive and/or expensive techniques such as muscle biopsy or measurement of the recovery time for PCr as measured by phosphorus magnetic resonance spectroscopy (31P-MRS)[11, 19]. Near-infrared spectroscopy (NIRS) constitutes a simple (non-invasive and non-expensive) method to quantify muscle oxygenation, oxygen dynamics and oxidative energy metabolism both at rest and during exercise in chronic conditions[20, 21]. A remarkable feature of NIRS is that during the immediate recovery phase after exercise, the kinetics of the underlying muscle re-oxygenation has been shown to be superimposable upon PCr by 31P-MRS measurements. Therefore, NIRS is an emergent methodology that can provide valuable information. Moreover, emergent photonics and miniaturization techniques are novel versatile methodologies to assess new aspects such as tissue oxygenation and the relationship between oxygenation and metabolism[22]. These new techniques are promising candidates to enhance the evaluation of exercise training in chronic patients, prompted by a twofold aim: i) The need for assessment of skeletal muscle during activities of daily life; and, ii) The commitment to understand the underlying mechanisms of abnormal responses to exercise training. Summarizing, new exercise training assessment modalities should cover novel aspects, such as: i) Assessment of peripheral oxygenation in skeletal muscles; and, ii) Being non-invasive, miniaturized and wearable for assessment outside the laboratory setting. It is so, because in many patients with NCDs, the measurement of skeletal muscle training effects through traditional methods may not provide representative results. Moreover, non-invasive measurement with miniaturized, and non-expensive, equipment may facilitate on-site assessment of skeletal muscle function during outdoors exercise.
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Design of innovative services Traditional face-to-face sessions of CPR programs coached by healthcare professionals show several factors that limit effectiveness, particularly if training is basically done only in healthcare institutions (i.e. hospital or outpatient-based settings). Firstly, despite the benefits of CPR described above, the percentage of patients having access to these programs is scarce, ranging from 1 to 2% in COPD patients and from 10 to 30% in subjects suffering from CVD[1, 23-26]. Secondly, once having acceded to CPR, the dropout rate in the program is up to 32% in COPD patients and 24% in CVD patients[1, 27]. Last but not least, there is a lack of standardized cost-effective long-term strategies to maintain exercise training-induced benefits and transfer them into an active lifestyle[15, 28]. Therefore, the design and validation of novel modalities of CPR services overcoming such limitations constitute a highly unmet need. Nowadays, it is well accepted that community-based or hybrid models of CPR are cost-effective interventions[29], and improve adherence[30-33] compared with traditional hospital-based programs. The evolution from hospital-based to community-based settings is postulating informal care providers as potential drivers of the novel services. Facing this challenging situation implies a profound reshaping of the way we approach delivery of care, as well as cultural and behavioural changes in traditional roles of patients, caregivers and healthcare professionals. This is, patients are now placed at the centre of the management as an active actor of the healthcare process, both as co-designer of the interventions and manager of her/his condition. This new way of healthcare delivery fosters a pro-active patient-oriented approach considering the patient with his comorbidities as a whole. Moreover, transition toward the new model of care requires development of appropriate partnership engaging all stakeholders: government, non-governmental organizations and civil society to actively implement actions aiming at increasing healthy lifestyles. In this scenario, modular health services to promote physical activity, with information and communication technologies (ICT) as enabling tools, and to support patient self-management, as well as remote off-line interactions with health professionals, are postulated as a proper solution to overcome the current limitations of traditional CPR programs. Specifically, such novel health services should be underpinned on: i) Adaptive clinical workflows of physical activity services; ii) Patient portal promoting long-term adherence; iii) Professional case management tools; iv) Backend integration with hospital information systems and into regional information exchange solutions; v) Large scale implementation with potential for transferability to other sites; and, vi) Development of adequate business models facilitating financial sustainability of the approach.
Impact of lifestyles: physical activity Healthy behaviours such as tobacco cessation, healthy diet and low alcohol consumption have clearly proven to be effective choices to prevent and treat NCDs, including cardiovascular and respiratory diseases, type 2 diabetes mellitus (T2DM), metabolic syndrome and certain types of cancer, among others. The cornerstone role of healthy lifestyles for NCDs prevention (primary)
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and management (secondary) is already well established. In fact, a growing number of healthcare professionals refer to NCDs as lifestyle-related diseases. On the other hand, less attention has been given to the importance of an active lifestyle for chronic disease prevention. Physical activity is defined as “any bodily movement produced by skeletal muscles which results in energy expenditure and can be characterized by type, intensity, duration, patterns and symptom experience”[34]. It is a complex behaviour affected by diverse factors such as individual (biological and behavioural), social, environmental and policy-related[35]. Physical activity is sometimes confused with the concept of exercise, a subset of physical activity, which is planned, structured, repetitive and purposeful[36]. On the other hand, physical inactivity, which can be simply defined as an absence of physical activity, is commonly used to represent a level of physical activity that is below an optimal or specified threshold. Physical inactivity by itself is a significant public health problem in most regions of the world, which has been identified as the fourth biggest risk factor for global mortality and is a key determinant of NCDs[37]. Worldwide, inactivity imposes economic costs of $67.5 billion per year through healthcare expenditure and productivity losses[38]. Moreover, current projections indicate time spent being physically inactive will continue to increase substantially with major implications for the prevalence of major cardiovascular, metabolic, respiratory and malignant chronic diseases and their risk factors (i.e. weight control, blood pressure, level of high density lipoprotein cholesterol and control of blood glucose in overweight people). Physical inactivity is a common characteristic in many chronic conditions, not only as a cause but also as a consequence[39-44]. The reduction in physiological reserve and systemic effects associated to many NCDs leads an increment of symptoms (i.e. dyspnoea and/or leg discomfort) and the subsequent development or worsening of physical inactivity. It could be argued that the negative impact of physical inactivity on chronic conditions may explain the association between reduced physical activity and higher mortality rates in the elderly[45, 46]. The underlying mechanisms whereby physical inactivity interacts with the age-related physiological decline that contributes to the development and evolution of the disease, with the subsequent morbid-mortality, are only partly known. Sedentarism leads to increased lactic acid production at low exercise intensity, which increases the perception of dyspnoea and, in turn, generates more physical inactivity. This vicious circle is particularly relevant in patients with chronic respiratory disorders and is a well-accepted problem, wherein pharmacological (bronchodilators) and non-pharmacological interventions (skeletal muscle training and physical activity) show high potential synergies. Moreover, it has been shown that lack of physical activity in multi-morbid patients is associated with inflammatory phenomena at systemic level[47]. On the other hand, the positive effects of physical activity on health outcomes are widely demonstrated both in patients with NCDs and subjects at risk[48]. It is important to highlight that the effectiveness of physical activity interventions on health outcomes, both in patients with NCDs and general population, has been demonstrated only in small and scientifically controlled settings[49]. However, the increasing awareness of the burden on healthcare systems generated by insufficient
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levels of physical activity has prompted the interest for scaling-up initiatives promoting healthy exercise behaviour addressed to patients with chronic disorders and citizens at risk[50]. Physical activity has a major role at three levels of preventive healthcare. In primary prevention, the goal of physical activity is to foster exercise health behaviour among citizens to protect them from developing chronic diseases. Moreover, primary prevention of multi-morbidity is also an important aspect to be addressed driven by the early recognition and enhanced management of physically inactive patients who already have one mild NCD and are typically managed at primary healthcare level. Secondary prevention is focused on subjects with early disease in whom risk factors or early stages of the disease have already been diagnosed. This level of prevention implies community-based case-finding procedures, which have been proved feasible and effective strategies, finally leading to early interventions which are more cost-effective than intervening in advanced stages of the disease. Moreover, a recent meta-epidemiological study[51] showed that exercise and many pharmacological interventions might have similar effects in terms of their mortality. Consequently, secondary prevention should look for synergies between pharmacological and non-pharmacological interventions to modulate disease progression in NCDs. Finally yet importantly, tertiary prevention seeks to soften the impact (increase resilience) caused by the disease on patient’s function, progress and HRQoL. This third level of healthcare prevention mainly encompasses traditional CPR programs in multi-morbid patients or those in whom the disease is clearly established and management may require support of specialized healthcare teams. It has been proven that skeletal muscle training and increased physical activity can be beneficial as preventive interventions in specific situations such as prehabilitation programs to diminish complications derived from the surgical process in high-risk patients for major surgery. This is an example of a novel and successful intervention where physical activity and exercise are used as a preventive intervention[52]. The positive effects of physical activity interventions at the three levels of preventive healthcare bring forward healthy lifestyles interventions as an important transversal strategy to implement. However, the standard way used to approach delivery of care shows important conceptual and organizational dysfunctions which can be addressed with adoption of more efficient services aiming at generating positive impacts at healthcare system level. To achieve it, a paradigm shift is required in how we approach NCDs prevention and treatment. Specifically, healthy lifestyle interventions must be acknowledged as highly beneficial healthcare system focused on healthy lifestyles medicine. Scaling-up population-based physical activity interventions is challenging, but feasible. In that sense, the Advancing Care Coordination and Telehealth at Scale (ACT@Scale) project[53] represents an innovative partnership of leading European healthcare regions, industry and academia with true potential to transform healthcare delivery services from experimental pilots or trials to scale-up routine management of chronic patients and frail elderly. The overall goal of ACT@Scale is to identify, transfer and scale-up existing and operational Care Coordination Telehealth good practices with the target of reaching a total of 75,000 care recipients across regions and programmes in different European countries. By using indicators to assess real world services and linking drivers and outcomes, ACT@Scale will provide guidance on changing care service delivery in five European regions (Region of Southern Denmark, Catalonia, Northern Netherlands - Groningen, Basque Country and Northern Ireland) and beyond.
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Integrated care services for chronic patients Healthcare systems worldwide are undergoing deep changes to adapt to novel patient-oriented efficient services necessary to tackle the increasing epidemic of NCDs and their risk factors caused by unhealthy lifestyles and population aging. Facing this challenging situation implies a profound reshaping in the way we approach delivery of care, as well as cultural changes at both citizen and healthcare professional levels. Patient empowerment is an essential part of the healthy lifestyles interventions and the prevention and management of NCDs. The roles of patients and healthcare professionals are evolving to place patients at the centre of the management as an active partner of the healthcare process, both as co-designer of the interventions and manager of her/his condition. The World Health Organization (WHO) defines integrated care as “the organization and management of health services so that people get the care they need, when they need it, in ways that are user friendly, achieve the desired results and provide value for money system”[54]. Despite known uncertainties in the characteristics of on-going deployment processes, the new models of healthcare delivery are prompted toward scaling-up. The WHO defines the term scaling-up as “deliberate efforts to increase the impact of health service innovations successfully tested in pilot or experimental projects so as to benefit more people and to foster policy and program development on a lasting basis”[55]. In summary, the challenge imposed by the epidemic of NCDs constitutes one of the main driving forces that are prompting an extensive European deployment of integrated care services supported by ICT through the European Innovation Partnership for Active and Healthy Aging (EIP-AHA) initiative[56]. The final aim is to enhance health outcomes in a cost-effective manner that allows containment of overall health costs, with a more proactive experience for patients and healthcare professionals. With this scope, the NEXTCARE project[57], one of the umbrella projects of the current PhD thesis, promotes innovation in health services with three main objectives: i) Regional deployment of ICS for chronic patients with personalised medicine approach; ii) Implementation of a test-bed, with international leadership, for assessment of ICS-ICT; and, iii) Development and monetization of novel products and services with high level of transferability to other healthcare systems, contributing to strength the regional industrial competences.
Fostering service scalability Integrated care services are being adopted at different rates and different ways across European regions due to the complexities of transforming healthcare systems. Scalability can only be achieved adopting novel ways of working, which require organisational change. In that sense, the EIP-AHA initiative[58] fosters to answering the following hot issues, namely: i) What actions have the more advanced regions taken in order to be successful?; ii) What can we learn from these pioneers to overcome barriers and accelerate results?; and, iii) Can these lessons be structured into a conceptual “maturity model” that could help aspiring regions to speed their own adoption?
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The EIP-AHA maturity model is conceived to show the level of readiness of healthcare systems in the process of adoption of integrated care services. The model groups into 12 ‘dimensions’ the different phases that need to be managed in order to deliver integrated care. By considering each dimension, assessing the current situation, and allocating a definite measure of maturity within that domain (on a 0-5 scale), a ‘radar diagram’ is developed, which reveals areas of strength and gaps in capability. Therefore, the EIP-AHA maturity model is a tool for comparison among regions/countries that allows both filling gaps in capability and offering knowledge and experience from the strength perspective. As part of the scenario alluded to above, NEXES - Supporting healthier and independent living for chronic patients and the elderly – was an EU project (FP7-CIP-ICT-PSP-2007-225025) that facilitated key developments of the current PhD thesis[59]. It assessed pre-deployment of four integrated care services (i.e. Wellness & Rehabilitation, Enhanced care for frail patients, Home hospitalization & Early discharge, and Remote support to primary care diagnosis therapy) in three European sites: Trondheim (Norway)[60], Barcelona (Catalonia)[61, 62] and Athens (Greece). Overall, NEXES achieved three major outcomes[63]. Firstly, the demonstration of effectiveness, high potential for cost-containment and complementariness of the services assessed in the project, which should be considered as a suite of community-based integrated care services covering most of the spectrum of severity of chronic patients. The second major conclusion was the development and validation of a technological platform for adaptive case management (ACM)[62], which contributed to support the clinical process logics of integrated care services, and facilitates organizational interoperability among actors. Finally, NEXES formulated structured strategies adapted to site heterogeneities that should facilitate adoption of integrated care services across Europe. Specifically, the lessons learnt in the NEXES’ program on Wellness & Rehabilitation had a marked influence on the proposals formulated in the PhD thesis regarding promotion of physical activity in an integrated care scenario.
Promotion of Physical Activity in an integrated care scenario The Chronic Care Model[64] represents a change of paradigm in healthcare delivery. Patient empowerment for self-management and a preventive approach to disease are two core characteristics of the novel approach. Within this conceptual frame, CPR should be considered an intervention not only in moderate-to-severe patients, but also in citizens at risk or at early stages of the disease to effectively prevent or modulate disease progress. Accordingly, classical training-based CPR programs must evolve toward multidimensional interventions implemented as an integral part of the patient’s self-management plan promoting physical activity and, in general, healthy lifestyles. It has been postulated that many of the actions that affect population levels of physical activity might occur outside the health sector and potentially be shaped by megatrends - defined as “major forces in societal development that are likely to shape people’s lives during the next 10-15 years”[65]. One major factor of contemporary societal change is the revolution in ICT which is propitiating new opportunities for healthcare professionals and patients to access, manage and share health information. ICT developments have taken place alongside with the changing in conceptual and
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organizational aspects of healthcare delivery. These technological opportunities have been already identified as a means to better enable patient empowerment and self-management and to enhance accessibility by transferring complexity to the community setting through novel telemonitoring and management tools. Several studies seem to reinforce the role of home-based programs as an alternative to traditional outpatient CPR given under direct supervision, emphasizing the role of ICT to support patient’s empowerment for self-management, as well as the use of remote monitoring for maintenance of exercise training induced benefits, enhancement of healthy exercise behaviours and collaborative self-management. Moreover, ICT-supported home-based programs will allow an increment of accessibility due to its lower requirements for human supervision and the consequently lower use of resources per patient. However, is important to highlight that ICT alone does not generate a significant positive impact on health outcomes[66] unless it is properly integrated as a supporting tool of well-structured clinical processes generating efficiencies[67]. It is of note that design of innovative health services, as well as its evaluation and large scale adoption require a proper alignment of actions on different dimensions, namely: i) Standardization of service workflows; ii) Assessment; iii) Technological (ICT) aspects; and, iv) Business models, as briefly analysed below.
Standardization of service workflows Integrated care covers a variety of different concepts and programmes intended to foster coordination within and between healthcare organizations, with the goal to improve the experience of patients, the outcomes of care and to enhance overall efficiency of health systems. However, too often, lack of standardization of service workflows generates problems of comparability among interventions. A five-stage conceptual model for case management has been proposed to design integrated care workflows: i) Case identification; ii) Case evaluation; iii) Work plan definition; iv) Follow-up and event handling; and, v) Discharge from the service. Case identification refers to the patient’s information required at the entry point. Case evaluation includes assessment of the patient to determine his/ her eligibility in a specific ICS and to capture the information required for the next step, work plan definition. The work plan consists on a set of both timed and non-timed tasks, led by a team of healthcare professionals or the patient itself, aligned with the aims of the service for that specific case. Follow-up and event handling, corresponds to the execution of the working plan. It is of note, that the continuous assessment of the patient during this phase may lead to changes in the work plan triggered by unexpected events. Finally, the case is prepared for his/her discharge from the service. This proposal combines a certain level of standardization with a necessary flexibility facilitating management of unexpected events. The latter is solved with an ACM technological approach.
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Assessment Assessment of efficacy of innovative services at pilot level requires study designs that use randomized controlled trials (RCT) as the gold standard tool to generate evidence. It is of note, however, that RCT show well-identified limitations in terms of generalization of conclusions, as well as for identification of factors modulating effectiveness of large-scale implementation. To this end, a broad spectrum of methodological designs and tools grouped under the name of implementation research seem more adequate than RCT to evaluate the determinants of large-scale implementation of integrated care services[68, 69]. Classical health indicators have shown to be insufficient to evaluate the different dimensions of the chronic care model. To this end, the Triple Aim approach[70, 71] proposes key performance indicators encompassing a comprehensive spectrum of pre-defined outcome variables, namely: i) Health and well-being; ii) Experience with care; and, iii) Costs. The addition of a fourth dimension, professionals’ engagement, seems appropriate for evaluation of large-scale deployment of integrated care, as proposed by the Quadruple Aim approach[72]. Moreover, the complexities associated with the supporting role of ICT have triggered evaluation tools like the Model for ASsessment of Telemedicine (MAST)[73] to address the need of summarizing a multidisciplinary process evaluating information about medical, social, economic and ethical issues related to use of telemedicine in a systematic, unbiased and robust manner.
Technological aspects The term eHealth is used as an umbrella concept that includes classical telehealth services as well as all ICT supporting health in a broad sense[63, 74]. ICT has shown high potential as enabling tool of integrated care services demonstrating clear benefits on important healthcare outcomes in patients with highly prevalent NCDs[75-78]. Over the last years, technological progress has fostered the development of a variety of wearables for self-tracking health aspects mainly including activity trackers and physiological sings sensors that can be linked to tablets, laptops and smartphones. Further, these wearable devices improve upon traditional pedometers (small, portable non-intrusive systems which measure the number of steps performed in a given period of time) as they include accelerometers (portable electronic devices that are worn on the body to detect acceleration and thereby reflect bodily movement in terms of frequency, duration and intensity of physical activity) providing objective additional data which cannot be obtained from pedometers. Moreover, many of these devices also include behaviour change techniques such as goal-setting, social support, social comparison, rewards to improve exercise health behaviour, structured problem solving and relapse’s prevention. Wearables also include complementary questionnaires on physical activity. These questionnaires have been widely used in different scenarios (i.e. epidemiological studies, clinical trials, clinical practice, etc.) because they are inexpensive and easy to use. However, is important to take into account that these
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tools show a clear lack of accuracy for individual assessment when compared with well-validated objective physical activity monitors. As physical activity tracking research evolves, the challenges in clinical measurement, adherence, privacy and clinical integration of these data into the electronic health records need to be addressed before these devices are broadly adopted as clinical self-management tools in an integrated care scenario. The concept of Digital Health Framework (DHF)[79] emerged from the FP7 Synergy-COPD project aiming to address the above challenges. Briefly, the DHF consists of articulation of open and modular ICT components supporting organizational interoperability and appropriate functionalities among three main areas, namely: i) Informal care, which includes any aspect with impact on health (i.e. physical activity derived from wearable trackers); ii) Formal care, which refers to any interaction with health professionals at the different levels of healthcare system; and, iii) Biomedical research, which refers to all research levels, from bench to clinical and public health. This framework can be unfold a building-block approach is considered necessary. The first building-block was tackled with the design and deployment of an open source Information sharing platform supporting integrated care services for chronic patients initiated during the NEXES project. The second building-block was successfully piloted during the life span of NEXES using a personal health folder (PHF) as a supporting tool to promote an exercise healthy behaviour and achieve long-term sustainability of outpatient exercise training-induced benefits. The current PhD thesis will focus on the second building block of the DHF, tackling informal care.
Business models and reimbursement incentives Caring for chronic patients is a challenge not for the dimension of disease per se, but rather because their needs tend to be complex and multidimensional. When subjects develop NCDs they often present comorbidities and special needs requiring coordination of efforts by a plurality of healthcare and social players. Integrated care services hold great expectations for improving both health outcomes and cost-effectiveness. However, concerns of funding and incentive mechanisms constitute two key barriers to extensive deployment. Healthcare market, presents two main characteristics to take into account that makes it different from other competitive markets, namely: i) Limited information that users have of the services they are buying (quality is not observable); because, ii) The heterogeneity of healthcare products and because the separation that exists between the payer (insurance) and the final user of the service (patient). Traditionally, healthcare systems make separate payments to providers for each of the services they supply to payees for a single illness or treatment. This approach leads to fragmented delivery of care with minimal coordination across service providers and healthcare setting. Payment rewards the quantity of services offered by providers rather than the quality of care provided. Research has shown that bundled payments can align incentives for providers – hospitals, post-acute
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care providers, physicians and other practitioners – allowing them to work closely together across all specialities and settings. Hence, bundled payment should be perceived as a way to incentivize collaboration among providers having a double aim: Firstly, the collaborative work among service providers may avoid the coordination inefficiencies of a fragmented healthcare system; and, secondly, service providers would have broader incentives to achieve savings, so that the margins are kept or may even increase. However, practicalities of implementation of business models based on bundle payments generating financial sustainability of health systems and incentives for stakeholders involved in integrated care clearly need further developments.
Summary The analysis of the state of the art indicates a clear need for revisiting several fundamental aspects of the traditional CPR encompassing: i) Clinical and biological characterization of candidates to CPR; ii) Non-invasive measurements of skeletal muscle respiration and metabolism; iii) Novel outdoor exercise training modalities; iv) Analysis of ICT-support to promotion of physical activity; and, v) Strategies for large scale implementation and assessment of innovative CPR in an integrated care scenario.
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HYPOTHESIS The central hypothesis of the current PhD thesis is that well-known limitations of classical cardiopulmonary rehabilitation programs for chronic patients in terms of accessibility, extensive adoption, sustainability of physiological effects, as well as their lack of impact on behavioural changes leading to healthy lifestyles, may be overcome by revisiting key aspects of the traditional approach with innovative and ICT-supported services. The main outcomes of the PhD thesis, after revisiting key identified aspects of the current cardiopulmonary rehabilitation programs, should be the formulation of innovative services with a preventive approach and the elaboration of a roadmap for their extensive adoption at community level.
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OBJECTIVES General objectives The principal objective of the current PhD thesis was to identify and revisit various core aspects of cardiopulmonary rehabilitation for chronic patients with a twofold aim: i) To optimize outcomes of cardiopulmonary rehabilitation; and, ii) To generate novel collaborative self-management physical activity services overcoming current limitations of classical approaches. Hence, this PhD thesis addresses three patient-centred issues (holistic characterization; skeletal muscle performance; and, novel modalities of exercise) and assesses the potential of novel self-management services, with a care coordination approach, to promote physical activity in patients with target chronic disorders.
Specifics objectives OBJECTIVE 1 To optimize characterization of candidates for cardiopulmonary rehabilitation by assessing the impact of modifiable biological factors that may limit training-induced physiological effects in chronic patients Rationale The manuscript assesses the impact of non-anaemic iron deficiency as a hidden factor that may limit both aerobic capacity and training-induced physiological effects in COPD. The ultimate aim being enhanced characterization of these patients prior to cardiopulmonary rehabilitation. Manuscript 1 Barberan-Garcia A, Rodríguez DA, Blanco I, Gea J, Torralba Y, Arbillaga-Etxarri A, Barberà JA, Vilaró J, Roca J, Orozco-Levi M. Non-anaemic iron deficiency impairs response to pulmonary rehabilitation in COPD. Respirology 2015;20(7):1089-95.
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OBJECTIVE 2 To explore non-invasive assessment of endurance training-induced skeletal muscle adaptations in COPD patients Rationale Innovative photonic technologies may facilitate a future non-invasive assessment of endurance training-induced effects on both tissue oxygenation and muscle metabolism with potential impact on personalization of interventions. The second manuscript of the PhD thesis evaluated strengths and weaknesses of classical near-infrared spectrometry (NIRS) technology to assess the effects of endurance training on “vastus lateralis” muscle oxygenation in COPD patients. Manuscript 2 Barberan-Garcia A, Muñoz PA, Villaquirán C, Gimeno-Santos E, Burgos F, Torralba Y, Gistau C, Roca J, Rodríguez DA. Is NIRS useful to evaluate training-induced changes in skeletal muscle in patients with chronic obstructive pulmonary disease? Clin Physiol Funct Imaging 2017 [Submitted]
OBJECTIVE 3 To assess the effects of flexible community-based exercise strategies in COPD patients Rationale Community-based exercise strategies seem to play a complementary role to classical endurance training intervention providing flexibility to collaborative self-management programs aiming at enhancing daily physical activity. The third specific objective was to perform a comparative analysis of the physiological effects generated by different Nordic walking exercise modalities in COPD patients. Manuscript 3 Barberan-Garcia A, Arbillaga-Etxarri A, Gimeno-Santos E, Rodríguez DA, Torralba Y, Roca J, Vilaró J. Nordic walking enhances oxygen uptake without increasing the rate of perceived exertion in patients with chronic obstructive pulmonary disease. Respiration 2015;89(3):221-25.
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OBJECTIVE 4 To evaluate effectiveness and transferability of a novel cardiopulmonary rehabilitation program based on collaborative self-management with ICT support Rationale Sustainability of training-induced effects and triggering behavioural changes leading to active life styles are two unmet needs of classical cardiopulmonary rehabilitation for chronic patients. The fourth manuscript analyses the potential of an ICT-supported integrated care service aiming at enhancing daily-life physical activity. Manuscript 4
Barberan-Garcia A, Vogiatzis I, Solberg HS, Vilaró J, Rodríguez DA, Garåsen HM, Troosters T, Garcia-Aymerich J, Roca J, NEXES Consortium. Effects and barriers to deployment of telehealth wellness programs for chronic patients across 3 European countries. Respir Med 2014;108(4):628-37.
OBJECTIVE 5
To elaborate the roadmap for extensive regional deployment and long-term assessment of a novel collaborative self-management physical activity service in Catalonia. Rationale A comprehensive strategy for large-scale deployment of the novel physical activity service ensuring transferability to other areas will require: i) Workflow characterization; ii) Development of ICT-supported functionalities; iii) Evaluation of outcomes; and, iv) A detailed roadmap for implementation. The fifth manuscript of the PhD thesis reports the protocol for large-scale deployment of the novel collaborative self-management physical activity service in Catalonia to be initiated by early 2016. Manuscript 5 Barberan-Garcia A, Gimeno-Santos E, Blanco I, Cano I, Martínez-Pallí G, Burgos F, Miralles F, Coca M, Murillo S, Sanz M, Steblin A, Ubré M, Benavent J, Vidal J, Sitges M, Roca J. Protocol for regional implementation of collaborative self-management services to promote physical activity. BMC Health Serv Res 2017 [Submitted]
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PUBLICATIONS First manuscript Non-anaemic iron deficiency impairs response to pulmonary rehabilitation in COPD. Barberan-Garcia A, Rodríguez DA, Blanco I, Gea J, Torralba Y, Arbillaga-Etxarri A, Barberà JA, Vilaró J, Roca J, Orozco-Levi M. Published in Respirology 2015;20(7):1089-95. DOI: 10.1111/resp.12591.
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ORIGINAL ARTICLE
Non-anaemic iron deficiency impairs response to pulmonary rehabilitation in COPD ANAEL BARBERAN-GARCIA,1,2,3,* DIEGO AGUSTÍN RODRÍGUEZ,3,4,* ISABEL BLANCO,1,2,3 JOAQUIM GEA,3,4 YOLANDA TORRALBA,1,3 ANE ARBILLAGA-ETXARRI,5,6 JOAN ALBERT BARBERÀ,1,2,3 JORDI VILARÓ,7 JOSEP ROCA1,2,3 AND MAURICIO OROZCO-LEVI3,4,8 1 Hospital Clínic de Barcelona, Thorax Clinic Institute, Respiratory Diagnostic Centre, 2August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, 3Center for Biomedical Network Research in Respiratory Diseases (CIBERES), 4Parc de Salut Mar, Pulmonary Medicine Department, Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University, 5Epidemiology Department, Centre for Research in Environmental Epidemiology (CREAL), 6Center for Biomedical Network Research in Epidemiology and Public Health (CIBERESP) and 7Blanquerna Health Sciences Faculty, Ramon Llull University, Barcelona, Catalonia, Spain, and 8Respiratory Department, Cardiovascular Foundation from Colombia Floridablanca, Santander, Colombia
ABSTRACT Background and objective: Non-anaemic iron deficiency (NAID) might alter the oxygen pathway in health and disease. The current study aims at assessing the impact of NAID on aerobic capacity in patients with chronic obstructive pulmonary disease (COPD). Methods: A prospective sample of 70 non-anaemic COPD patients candidate to participate in an 8-week pulmonary rehabilitation (PR) programme was studied. Incremental cycling exercise to peak oxygen uptake (V’O2peak) and constant work-rate exercise at 80% V’O2peak to exhaustion were assessed pre- and postPR. Training-induced increase of endurance time (ET) ≥33%, which represented the minimal clinically important difference, classified patients as responders to exercise training. Results: The prevalence of NAID was 48% (n = 34) showing no relationship with the Global Initiative for Chronic Obstructive Lung Disease stages (P = 0.209). Patients with NAID showed lower pre-training ET (P = 0.033) and V’O2peak (P = 0.007) than normal iron status (NIS) patients after adjustment for potential covariates. Significant training-induced physiological changes were seen in the NIS group (ΔV’O2peak 68(132) mL/min; P = 0.009), but not in the NAID group (ΔV’O2peak 26 (126) mL/min; P = 0.269). The NAID group showed lower percentage of responders to training (56%) than the NIS group (78%) (P = 0.041). Conclusions: COPD patients with NAID showed lower pre-training aerobic capacity and reduced
Correspondence: Diego Agustín Rodríguez, Parc de Salut Mar, Pulmonary Medicine Department, Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University, Passeig Marítim, 25; 08003 Barcelona, Catalunya, Spain. Email:
[email protected] *These authors contributed equally to the study. Received 31 December 2014; invited to revise 13 March 2015; revised 18 March 2015; accepted 7 April 2015 (Associate Editor: Melissa Benton). © 2015 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE The present study assessed for the first time the impact of non-anaemic iron deficiency (NAID) on aerobic capacity and pulmonary rehabilitation response in COPD patients. NAID showed a high prevalence, and was associated with decreased baseline aerobic capacity and lower exercise training adaptation in COPD patients.
training-induced response than NIS patients after adjusting for potential confounding variables. Key words: aerobic exercise, chronic obstructive pulmonary disease, exercise test, exercise therapy, iron metabolism disorder. Abbreviations: 6MWT, 6-min walking test; BMI, body mass index; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; DLCO, diffusion capacity of the lung for carbon monoxide; ET, endurance time; FEV1, forced expiratory volume in 1 s; FFMI, fat-free mass index; Hb, haemoglobin; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IPAH, idiopathic pulmonary arterial hypertension; MCID, minimal clinically important difference; mMRC, modified Medical Research Council dyspnoea scale; NAID, non-anaemic iron deficiency; NIS, normal iron status; PR, pulmonary rehabilitation; SGRQ, Saint George’s Respiratory Questionnaire; sTfR, serum transferrin receptor.
INTRODUCTION It is well accepted that iron plays a key role in many cellular processes regulating the response to hypoxia, oxidative stress, cellular proliferation and cell metabolism.1 Moreover, iron is an essential nutrient that plays a central role in cellular bioenergetics. Aerobic metabolism is critically dependent on Respirology (2015) doi: 10.1111/resp.12591
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2 iron-containing proteins, such as haemoglobin (Hb) and cytochrome c. The latter facilitates cellular oxygen utilization in the mitochondrial respiratory chain. Consequently, iron deficiency, even in the absence of anaemia (non-anaemic iron deficiency (NAID)), may have a negative impact on aerobic capacity both at baseline2–4 and after exercise training.5,6 In chronic heart failure (CHF) and idiopathic pulmonary arterial hypertension (IPAH), NAID has been demonstrated to be a prevalent comorbidity with deleterious impact on health outcomes and aerobic capacity.7–9 In contrast, in patients with chronic obstructive pulmonary disease (COPD), iron deficiency has only been studied in the context of anaemia.10–12 Patients with COPD often show oxygen delivery impairment during exercise. Moreover, skeletal muscle dysfunction is a well recognized systemic effect of the disease that can be associated to abnormal mitochondrial oxygen utilization.13 The alterations of the oxygen pathway can limit aerobic capacity and compromise health status in COPD.14 Given the potential importance of iron supplementation in patients and its broad cellular functions,1 NAID is a factor that should be taken into account in the analysis of aerobic capacity in COPD patients. Moreover, since pulmonary rehabilitation (PR) is a core component of COPD management,15 the assessment of NAID impact on exercise training response might be relevant to optimize PR outcomes in COPD patients. Therefore, the current study hypothesizes that NAID can be associated with both reduced baseline aerobic capacity and decreased training-induced aerobic response. Accordingly, the aim of the present investigation was to evaluate the relationships between NAID and aerobic capacity in COPD patients before and after a high-intensity, 8-week endurance exercise training programme.
METHODS Study design and population A prospective observational study was carried out in a sample of consecutive non-anaemic COPD patients from the outpatient clinics of Hospital Clinic de Barcelona, participating in an 8-week outpatient PR programme.16 The following were the inclusion criteria: (i) diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria;17 (ii) clinically stable conditions with optimized pharmacological treatment; (iii) no history of lower respiratory track infection and/or COPD exacerbation within 6 weeks prior to initial measurements; (iv) no previous participation in a PR programme for at least 12 months prior to the initial evaluation; and (v) normal Hb values (≥13 g/dL in males and ≥12 g/dL in females) at the time of the evaluation. The following were the exclusion criteria: (i) current anaemia treatment; (ii) suspicion or evidence of blood loss (gastrointestinal, menstrual or urinary); (iii) polycythaemia Respirology (2015)
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(Hb levels >17 and >15 g/dL for males and females, respectively); (iv) cardiovascular, skeletal-muscle or neurological disorders precluding the practice of exercise; and (v) diagnosis of cancer or haematological disorders. The Ethics Committee for Clinical Research of Hospital Clinic de Barcelona approved the study, and the informed consent was signed by all subjects.
Training programme The 8-week outpatient PR programme consisted of 24 sessions (1 h of duration, 3 days per week) of interval exercise training in cycle-ergometer (Jaeger ER 550, Wüerzburg, Germany). Each exercise training session included 5 min of warm-up cycling at 30% of peak work-rate, 40 min of interval training and 5 min of cool-down pedalling at 20% of peak work-rate. The interval training combined 2 min high-intensity pedalling and 3 min of active rest. Work-rate progress during the 8-week period was tailored on individual basis, according to subject’s symptoms, to maximize the training effect. During the first 2 weeks, highintensity pedalling interval was at least 70% of peak work-rate, and the active rest interval was at least 40% of peak work-rate. Thereafter, work-rate was increased by approximately 5% every week up to a maximum of 100% of peak work-rate during the last 2 weeks for the high-intensity period and 50% of peak work-rate for the active rest.
Measurements Standard medical history and physical examination were performed by a specialized respiratory physician. Other measurements included the following: (i) resting pulmonary function testing (MasterScreen; Jaeger); (ii) resting arterial blood gas analysis (Ciba Corning 800, Medfield, MA, USA); (iii) standard cardiopulmonary exercise testing in cycle-ergometer;18 (iv) constant work-rate exercise testing at 80% of V’O2peak in cycle-ergometer;19 (v) 6-min walking test;20 (vi) physical activity assessment by the modified Baecke questionnaire (Baecke);21 (vii) modified Medical Research Council dyspnoea scale; (viii) Saint George’s Respiratory Questionnaire;22 (ix) fat-free mass index using body composition by bioelectrical impedance analysis (Quantum X, RJL Systems, Clinton Township, MI, USA); and (x) routine blood measurements, including serum ferritin level, transferrin level, transferrin saturation and iron. Iron deficiency was defined as a ferritin level
