Healthcare and Societal Costs in Patients with COPD and Breathlessness after Completion of a Comprehensive Rehabilitation Program.

Breathlessness is one of the most frequent symptoms in chronic obstructive pulmonary disease (COPD). COPD may result in disability, decreased productivity and increased healthcare costs. The presence of comorbidities increases healthcare utilization. However, the impact of breathlessness burden on healthcare utilization and daily activities is unclear. This study's goal was to analyze the impact of breathlessness burden on healthcare and societal costs. In this observational single-center study, patients with COPD were followed-up for 24 months after completion of a comprehensive pulmonary rehabilitation program. Every three months participants completed a cost questionnaire, covering healthcare utilization and impact on daily activities. The results were compared between participants with low (modified Medical Research Council (mMRC) grade <2; LBB) and high baseline breathlessness burden (mMRC grade ≥2; HBB). Healthcare costs in year 1 were €7302 (95% confidence interval €6476-€8258) for participants with LBB and €10,738 (€9141-€12,708) for participants with HBB. In year 2, costs were €8830 (€7372-€10,562) and €14,933 (€12,041-€18,520), respectively. Main cost drivers were hospitalizations, contact with other healthcare professionals and rehabilitation. Costs outside the healthcare sector in year 1 were €682 (€520-€900) for participants with LBB and €1520 (€1210-€1947) for participants with HBB. In year 2, costs were €829 (€662-€1046) and €1457 (€1126-€1821) respectively. HBB in patients with COPD is associated with higher healthcare and societal costs, which increases over time. This study highlights the relevance of reducing costs with adequate breathlessness relief. When conventional approaches fail to improve breathlessness, a personalized holistic approach is warranted.

Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials.

INTRODUCTION: Exercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD) and, although multifactorial, it is largely caused by lower-limb muscle dysfunction. Research has shown that patients with severe to very severe COPD have significantly lower levels of muscle carnosine, which acts as a pH buffer and antioxidant. Beta-alanine (BA) supplementation has been shown to consistently elevate muscle carnosine in a variety of populations and may therefore improve exercise tolerance and lower-limb muscle function. The primary objective of the current studies is to assess the beneficial effects of BA supplementation in enhancing exercise tolerance on top of two types of exercise training (non-linear periodised exercise (NLPE) training or neuromuscular electrical stimulation (NMES)) in patients with COPD. METHODS AND ANALYSIS: Two randomised, double-blind, placebo-controlled trials have been designed. Patients will routinely receive either NLPE (BASE-TRAIN trial) or NMES (BASE-ELECTRIC trial) as part of standard exercise-based care during their 8-to-10 week pulmonary rehabilitation (PR) programme. A total of 222 patients with COPD (2×77 = 154 patients in the BASE-TRAIN trial and 2×34 = 68 patients in the BASE-ELECTRIC trial) will be recruited from two specialised PR centres in The Netherlands. For study purposes, patients will receive 3.2 g of oral BA supplementation or placebo per day. Exercise tolerance is the primary outcome, which will be assessed using the endurance shuttle walk test (BASE-TRAIN) or the constant work rate cycle test (BASE-ELECTRIC). Furthermore, quadriceps muscle strength and endurance, cognitive function, carnosine levels (in muscle), BA levels (in blood and muscle), markers of oxidative stress and inflammation (in blood, muscles and lungs), physical activity and quality of life will be measured. ETHICS AND DISSEMINATION: Both trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19). TRIAL REGISTRATION NUMBER: NTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC).

Impact of mild-to-moderate exacerbations on outcomes of neuromuscular electrical stimulation (NMES) in patients with COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common among patients attending pulmonary rehabilitation (PR) and may compromise its outcomes. Neuromuscular electrical stimulation (NMES) seems one of the few exercise modalities that can actually be continued during AECOPD, due to its low burden on the impaired respiratory and cardiovascular system. However, the quality of evidence is low. The purpose of this study was to assess the impact of mild-to-moderate AECOPD on adherence/outcomes of a high-frequency (HF) or low-frequency (LF) NMES training program, as part of inpatient PR, in severely dyspneic, weakened individuals with COPD. 62 patients who received NMES as the sole supervised muscle training modality during an 8-week PR program (HF-NMES: n = 33; LF-NMES: n = 29) were analyzed retrospectively. 48.4% experienced ≥1 AECOPD during PR and were classified as exacerbators. Exacerbators completed 75 NMES sessions (interquartile range: 73-78) and were able to increase training intensity with 24 mA (15-39), while non-exacerbators completed 76 sessions (73-79) and increased training intensity with 35 mA (22-50), with no between-group differences (p = 0.474 and p = 0.065, respectively). The median change in 6-min walking distance, cycle endurance time, and isokinetic quadriceps strength and endurance did not differ between the exacerbation and non-exacerbation group. To conclude, the occurrence of mild-to-moderate AECOPD during a PR program primarily focused on NMES, does not affect adherence, intensity, and clinical outcomes in patients with severe COPD. Continuing NMES seems a feasible way to potentially counteract exacerbation-related lower-limb muscle dysfunction and improve outcomes of PR, with HF-NMES being the preferential muscle training modality.

Clinical outcome and cost-effectiveness of a 1-year nutritional intervention programme in COPD patients with low muscle mass: The randomized controlled NUTRAIN trial.

BACKGROUND AND AIMS: The efficacy of nutritional intervention to enhance short- and long-term outcomes of pulmonary rehabilitation in COPD is still unclear, hence this paper aims to investigate the clinical outcome and cost-effectiveness of a 12-month nutritional intervention strategy in muscle-wasted COPD patients. METHODS: Prior to a 4-month pulmonary rehabilitation programme, 81 muscle-wasted COPD patients (51% males, aged 62.5 ± 0.9 years) with moderate airflow obstruction (FEV1 55.1 ± 2.2% predicted) and impaired exercise capacity (Wmax 63.5 ± 2.4% predicted) were randomized to 3 portions of nutritional supplementation per day (enriched with leucine, vitamin D and polyunsaturated fatty acids) [NUTRITION] or PLACEBO (phase 1). In the unblinded 8-month maintenance phase (phase 2), both groups received structured feedback on their physical activity level assessed by accelerometry. NUTRITION additionally received 1 portion of supplemental nutrition per day and motivational interviewing-based nutritional counselling. A 3-month follow-up (phase 3) was included. RESULTS: After 12 months, physical capacity measured by quadriceps muscle strength and cycle endurance time were not different, but physical activity was higher in NUTRITION than in PLACEBO (Δ1030 steps/day, p = 0.025). Plasma levels of the enriched nutrients (p < 0.001) were higher in NUTRITION than PLACEBO. Trends towards weight gain in NUTRITION and weight loss in PLACEBO led to a significant between-group difference after 12 months (Δ1.54 kg, p = 0.041). The HADS anxiety and depression scores improved in NUTRITION only (Δ-1.92 points, p = 0.037). Generic quality of life (EQ-5D) was decreased in PLACEBO but not in NUTRITION (between-group difference after 15 months 0.072 points, p = 0.009). Overall motivation towards exercising and healthy eating was high and did not change significantly after 12 months; only amotivation towards healthy eating yielded a significant between-group difference (Δ1.022 points, p = 0.015). The cost per quality-adjusted life-year after 15 months was EUR 16,750. CONCLUSIONS: Nutritional intervention in muscle-wasted patients with moderate COPD does not enhance long-term outcome of exercise training on physical capacity but ameliorates plasma levels of the supplemented nutrients, total body weight, physical activity and generic health status, at an acceptable increase of costs for patients with high disease burden.

Pulmonary rehabilitation, physical activity, respiratory failure and palliative respiratory care.

The CIRO Academy in Horn (the Netherlands) organised a 2-day meeting to present and discuss the studies published in 2017 pertaining to key priority areas of respiratory and critical care medicine. This review summarises studies focussing on pulmonary rehabilitation and exercise training, physical activity, chronic respiratory failure and palliative respiratory care published in 2017.

Supplementation with Qter® and Creatine improves functional performance in COPD patients on long term oxygen therapy.

BACKGROUND: Skeletal muscle dysfunction and poor functional capacity are important extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), especially in COPD patients on long-term O2 therapy (LTOT). Beside the role of pulmonary rehabilitation, the effect of nutritional interventions is still controversial, and there are knowledge gaps on the effective role of nutraceutical supplementation on hard endpoints. The aim of this study was to investigate the effects of nutritional supplementation with Coenzyme Q10 (QTer®) - a powerful antioxidant with the potential to reduce oxidative stress and improve mitochondrial function - and Creatine on functional, nutritional, and metabolomic profile in COPD patients on long-term O2 therapy. METHODS: One-hundred and eight patients with COPD from 9 Italian hospitals were enrolled in this double-blinded randomized placebo-controlled clinical study. At baseline and after 2 months of therapy, the patients underwent spirometry, 6-minute walk test (6MWT), bioelectrical impedance analysis, and activities of daily living questionnaire (ADL). Also, dyspnea scores and BODE index were calculated. At both time points, plasma concentration of CoQ10 and metabolomic profiling were measured. FINDINGS: Ninety patients, who randomly received supplementation with QTer® and Creatine or placebo, completed the study. Compared with placebo, supplemented patients showed improvements in 6MWT (51 ±â€¯69 versus 15 ±â€¯91 m, p < 0.05), body cell mass and phase angle, sodium/potassium ratio, dyspnea indices and ADL score. The CoQ10 plasma concentration increased in the supplementation group whereas it did not change in the placebo group. The metabolomics profile also differed between groups. Adverse events were similar in both groups. INTERPRETATION: These results show that in patients with COPD, dietary supplementation with CoQ10 and Creatine improves functional performance, body composition and perception of dyspnea. A systemic increase in some anti-inflammatory metabolites supports a pathobiological mechanism as a reason for these benefits. Further trials should help clarifying the role of QTer® and Creatine supplementation in patients with COPD.

COPD stands for complex obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) has extensively been reported as a complex disease affecting patients' health beyond the lungs with a variety of intra- and extrapulmonary components and considerable variability between individuals. This review discusses the assessment of this complexity and underlines the importance of transdisciplinary management programmes addressing the physical, emotional and social health of the individual patient.COPD management is challenging and requires advanced, sophisticated strategies meeting the patient's individual needs. Due to the heterogeneity and complexity of the disease leading to non-linear and consequently poorly predictable treatment responses, multidimensional patient profiling is crucial to identify the right COPD patient for the right treatment. Current methods are often restricted to general, well-known and commonly used assessments neglecting potentially relevant (interactions between) individual, unique "traits" to finally ensure personalised treatment. Dynamic, personalised and holistic approaches are needed to tackle this multifaceted disease and to ensure personalised medicine and value-based healthcare.

COPD patient education and support - Achieving patient-centredness.

BACKGROUND: The art of medicine is undergoing a dramatic shift in focus, evolving to focus on patient involvement as partners in care, transforming the traditional, prescriptive, reactive practice of healthcare into a proactive discipline. The personal and societal burden of chronic diseases is burgeoning and unsustainable in current systems, novel approaches are required to address this. DISCUSSION: Although considerable progress has been made in the development of diagnostics, therapeutics and care guidelines for patients with chronic obstructive pulmonary disease (COPD), questions remain surrounding the implementation of best practice education and support. Current educational programmes, personal limitations and preferences and patient-clinician communication in modification of coping styles and behaviour are discussed. A novel holistic model, the Kaleidoscope Model of Care is proposed to address the barriers to optimal self-care behaviours. CONCLUSION AND PRACTICE IMPLICATIONS: Holistic approaches are essential for optimal self-management and improved outcomes. Guidance on personalised goals for patients to help meeting their therapy priorities is needed to aid healthcare professionals (HCPs) and funders to minimise healthcare burden and costs. The novel KALMOD approach may optimise patient empowerment, exploring whole-life factors that impact COPD care and improve interactions between patients and HCPs for optimised outcomes.

Vitamin K deficiency: the linking pin between COPD and cardiovascular diseases?

Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require anticoagulation therapy. Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used. VKAs induce profound deficiency of vitamin K, a key activator in the coagulation pathway. It is recognized however that vitamin K is also an essential cofactor in the activation of other extrahepatic proteins, such as matrix Gla protein (MGP), a potent inhibitor of arterial calcification. No or insufficient MGP activation by the use of VKAs is associated with a rapid progression of vascular calcification, which may enhance the risk for overt cardiovascular disease. Vitamin K consumption, on the other hand, seems to have a protective effect on the mineralization of arteries. Furthermore, vascular calcification mutually relates to elastin degradation, which is accelerated in patients with COPD associating with impaired survival. In this commentary, we hypothesize that vitamin K is a critical determinant to the rate of elastin degradation. We speculate on the potential link between poor vitamin K status and crucial mechanisms of COPD pathogenesis and raise concerns about the use of VKAs in patients with this disease. Future intervention studies are needed to explore if vitamin K supplementation is able to reduce elastin degradation and vascular calcification in COPD patients.

Integrating the care of the complex COPD patient.

Proceedings of the European Seminars in Respiratory Medicine course, Long-Term Integrated Care of COPD Patients held in Stresa, Italy, on 16-17 June, 2016.

A randomized clinical trial investigating the efficacy of targeted nutrition as adjunct to exercise training in COPD.

BACKGROUND: Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited. The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass. METHODS: Eighty-one COPD patients with low muscle mass, admitted to out-patient pulmonary rehabilitation, randomly received oral nutritional supplementation, enriched with leucine, vitamin D, and omega-3 fatty acids (NUTRITION) or PLACEBO as adjunct to 4 months supervised high intensity exercise training. RESULTS: The study population (51% males, aged 43-80) showed moderate airflow limitation, low diffusion capacity, normal protein intake, low plasma vitamin D, and docosahexaenoic acid. Intention-to-treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass (mean difference ± SEM) (+1.5 ± 0.6 kg, P = 0.01), plasma vitamin D (+24%, P = 0.004), eicosapentaenoic acid (+91%,P < 0.001), docosahexaenoic acid (+31%, P < 0.001), and steps/day (+24%, P = 0.048). After 4 months, both groups improved skeletal muscle mass (+0.4 ± 0.1 kg, P < 0.001), quadriceps muscle strength (+12.3 ± 2.3 Nm,P < 0.001), and cycle endurance time (+191.4 ± 34.3 s, P < 0.001). Inspiratory muscle strength only improved in NUTRITION (+0.5 ± 0.1 kPa, P = 0.001) and steps/day declined in PLACEBO (-18%,P = 0.005). CONCLUSIONS: High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction. Specific nutritional supplementation had additional effects on nutritional status, inspiratory muscle strength, and physical activity compared with placebo.

Vitamin D deficiency and airflow limitation in the Baltimore Longitudinal Study of Ageing.

BACKGROUND: Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD) and has also been linked to comorbidities often present in COPD. AIM: The aim of this study was to investigate whether vitamin D deficiency was related specifically to airflow limitation or whether vitamin D deficiency was determined by conditions that frequently coexist with COPD: insulin resistance, hypertension, anaemia, obesity and hypercholesterolaemia. METHODS: For this cross-sectional analysis, we included 897 subjects from the Baltimore Longitudinal Study of Aging. Subjects taking vitamin D supplements were excluded. Airflow limitation was defined as FEV1 /FVC < lower limit of normal. Logistic regression was used to assess the association between vitamin D deficiency (25-hydroxy vitamin D < 20 ng/mL) and possible determinants. RESULTS: Vitamin D deficiency was not specific for subjects with airflow limitation. Body mass index (BMI) (OR: 1.05, P < 0.03) and obesity (BMI > 30 kg/m(2)) (OR: 1.9, P < 0.002) were significantly associated with vitamin D deficiency in the adjusted multivariate regression analysis. Physical activity was associated with a decreased risk of vitamin D deficiency. CONCLUSIONS: Airflow limitation was not an independent determinant of vitamin D deficiency. The effect of weight loss and increased physical activity on vitamin D levels should be investigated further in intervention studies.

Efficacy of lower-limb muscle training modalities in severely dyspnoeic individuals with COPD and quadriceps muscle weakness: results from the DICES trial.

RATIONALE: Strength training and neuromuscular electrical stimulation (NMES) improve lower-limb muscle function in dyspnoeic individuals with chronic obstructive pulmonary disease (COPD). However, high-frequency NMES (HF-NMES) and strength training have never been compared head-to-head; and effects of low-frequency NMES (LF-NMES) have never been studied in COPD. Therefore, the optimal training modality to improve lower-limb muscle function, exercise performance and other patient-related outcomes in individuals with severe COPD remains unknown. OBJECTIVES: To study prospectively the efficacy of HF-NMES (75 Hz), LF-NMES (15 Hz) or strength training in severely dyspnoeic individuals with COPD with quadriceps muscle weakness at baseline. METHODS: 120 individuals with COPD (FEV1: 33±1% predicted, men: 52%, age: 64.8±0.8 years) were randomised to HF-NMES, LF-NMES or strength training as part of a comprehensive inpatient pulmonary rehabilitation programme. No treadmill walking or stationary cycling was provided. MEASUREMENTS AND MAIN RESULTS: Groups were comparable at baseline. Quadriceps muscle strength increased after HF-NMES (+10.8 Newton-metre (Nm)) or strength training (+6.1 Nm; both p<0.01), but not after LF-NMES (+1.4 Nm; p=0.43). Quadriceps muscle endurance, exercise performance, lower-limb fat-free mass, exercise-induced symptoms of dyspnoea and fatigue improved significantly compared with baseline after HF-NMES, LF-NMES or strength training. The increase in quadriceps muscle strength and muscle endurance was greater after HF-NMES than after LF-NMES. CONCLUSIONS: HF-NMES is equally effective as strength training in severely dyspnoeic individuals with COPD and muscle weakness in strengthening the quadriceps muscles and thus may be a good alternative in this particular group of patients. HF-NMES, LF-NMES and strength training were effective in improving exercise performance in severely dyspnoeic individuals with COPD and quadriceps weakness. TRIAL REGISTRATION: NTR2322.

Silica induces NLRP3 inflammasome activation in human lung epithelial cells.

BACKGROUND: In myeloid cells the inflammasome plays a crucial role in innate immune defenses against pathogen- and danger-associated patterns such as crystalline silica. Respirable mineral particles impinge upon the lung epithelium causing irreversible damage, sustained inflammation and silicosis. In this study we investigated lung epithelial cells as a target for silica-induced inflammasome activation. METHODS: A human bronchial epithelial cell line (BEAS-2B) and primary normal human bronchial epithelial cells (NHBE) were exposed to toxic but nonlethal doses of crystalline silica over time to perform functional characterization of NLRP3, caspase-1, IL-1ß, bFGF and HMGB1. Quantitative RT-PCR, caspase-1 enzyme activity assay, Western blot techniques, cytokine-specific ELISA and fibroblast (MRC-5 cells) proliferation assays were performed. RESULTS: We were able to show transcriptional and translational upregulation of the components of the NLRP3 intracellular platform, as well as activation of caspase-1. NLRP3 activation led to maturation of pro-IL-1ß to secreted IL-1ß, and a significant increase in the unconventional release of the alarmins bFGF and HMGB1. Moreover, release of bFGF and HMGB1 was shown to be dependent on particle uptake. Small interfering RNA experiments using siNLRP3 revealed the pivotal role of the inflammasome in diminished release of pro-inflammatory cytokines, danger molecules and growth factors, and fibroblast proliferation. CONCLUSION: Our novel data indicate the presence and functional activation of the NLRP3 inflammasome by crystalline silica in human lung epithelial cells, which prolongs an inflammatory signal and affects fibroblast proliferation, mediating a cadre of lung diseases.

Vitamin D status is associated with bone mineral density and functional exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with several extrapulmonary effects that contribute to the severity of the disease. Vitamin D is suggested to play a role in COPD and its related extrapulmonary effects. AIMS: To determine the prevalence of vitamin D deficiency and its relation with bone density, muscle strength, and exercise capacity in patients with COPD. METHODS: Our cross-sectional study included patients with moderate to very severe COPD. We collected data on lung function, body composition, bone density, quadriceps muscle strength, 6-minute walking distance, and plasma 25-hydroxyvitamin D (25(OH)D) concentration. Vitamin D deficiency was defined as plasma 25(OH)D concentration below 50 nmol/L. RESULTS: In total, 151 COPD patients were included; 87 patients (58%) had vitamin D deficiency. Plasma 25(OH)D concentration was positively associated with bone density (P = 0.005) and 6-minute walking distance (P < 0.001) after adjustment for potential confounders. Plasma 25(OH)D concentration was not associated with quadriceps muscle strength. CONCLUSIONS: The majority of COPD patients had vitamin D deficiency. Plasma 25(OH)D concentration was positively associated with bone density and exercise capacity. Intervention studies are necessary to determine whether vitamin D supplementation is of benefit in the prevention or treatment of osteoporosis and poor exercise capacity in patients with COPD.

Oxygen uptake, ventilation, and symptoms during low-frequency versus high-frequency NMES in COPD: a pilot study.

Transcutaneous neuromuscular electrical stimulation (NMES) involves the application of an electrical current through electrodes placed on the skin over the targeted muscles. During high-frequency NMES (HF-NMES), oxygen uptake, minute ventilation, and the degree of symptom perception (dyspnea and fatigue) have been shown to be acceptable in chronic obstructive pulmonary disease (COPD). Currently, oxygen uptake and ventilation load have never been assessed during low-frequency NMES (LF-NMES) of the lower-limb muscles. The purpose of this study was to compare prospectively oxygen uptake, ventilation, and symptom perception during a single session of LF-NMES versus a single session of HF-NMES of quadriceps muscles in patients with COPD. In 17 COPD patients (mean FEV(1) = 45% predicted, mean body mass index = 26.2 kg/m(2)), peak exercise capacity, functional exercise capacity, and the Medical Research Council dyspnea grade were evaluated. In addition, oxygen uptake, minute ventilation, heart rate, and Borg symptom scores were assessed during one session of LF-NMES (15 Hz) and one session of HF-NMES (75 Hz) and compared with peak values. Mean oxygen uptake (LF-NMES: 327 ml/min vs. HF-NMES: 315 ml/min), minute ventilation (LF-NMES: 14 L vs. HF-NMES: 15 L), and heart rate (LF-NMES: 86 BPM vs. HF-NMES: 83 BPM) were similar during both NMES frequencies. Patients used a relatively low proportion of their peak aerobic capacity during both NMES sessions (LF-NMES: 34% vs. HF-NMES: 33%; P = 0.397). In addition, symptom Borg scores for dyspnea and leg fatigue were also comparable. Oxygen uptake, ventilation, and symptoms of dyspnea and fatigue were comparable and tolerable during LF-NMES and HF-NMES in patients with COPD. Therefore, LF-NMES and HF-NMES may both be suitable rehabilitative modalities to be used in severely dyspneic patients with lower-limb muscle dysfunction.

Pulmonary rehabilitation and integrated care.

Pulmonary rehabilitation is a multidisciplinary approach that aims to stabilize or reverse both the physio- and the psychopathology of pulmonary diseases and attempts to return the patient to the highest possible capacity allowed by the pulmonary handicap and overall life situation. Three important features of pulmonary rehabilitation include: individualization, multidisciplinarity, and attention to the different components of the disease and their impact on daily life. Current health care systems are still organized based on the acute care paradigm, largely neglecting the management over periods of years or decades, required for optimal approach of patients with chronic conditions. These chronic conditions need to be considered as the result of complex, dynamic, and unique interactions between different components of the overall system. Optimally, pulmonary rehabilitation aims to achieve optimal daily functioning and health status for the individual patient and to achieve and maintain the individual's independence and functioning in the community. As part of the integrated care process, pulmonary rehabilitation is the patient-centered demand-driven process in the care delivery value chain by offering a flexible, creative, holistic, and integrated intervention, based on partnering of different skills to achieve shared individualized patient-related objectives, as well as to achieve improvement in clinically relevant outcomes and to offer added value to the patient and the community.