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Maria Minter,1,2 Jenny van Odijk,1 Hanna Augustin,1 Felipe VC Machado,3,4 Frits ME Franssen,5,6 Martijn A Spruit,5,6 Lowie EGW Vanfleteren1,5 1Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 405 30, Sweden; 2Department of Lung Medicine, Angered Hospital, SV Hospital Group, Angered, 424 22, Sweden; 3Rehabilitation Research Center (REVAL), Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium; 4Biomedical Research Institute (BIOMED), Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium; 5Department of Research and Development, Ciro, Horn, the Netherlands; Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands; 6Department of Respiratory Medicine, School of Nutrition and Translational Research in Metabolism (NUTRIM), Faculty of Health, Medicine, and Life Sciences, Maastricht University Medical Centre+, Maastricht, the NetherlandsCorrespondence: Maria Minter, Department of Lung Medicine, Angered Hospital, SV Hospital Group, Angered, 424 22, Sweden, Email maria.minter@gu.seBackground: Alterations in body weight and composition are common in patients with chronic obstructive pulmonary disease (COPD) and are independent predictors for morbidity and mortality. Low vitamin D status is also more prevalent in patients with COPD compared to controls and has been related to lower lung function, muscle atrophy and impaired musculoskeletal function. This study aimed to evaluate the association between vitamin D levels and status with body composition (BC), as well as with its changes over time.Patients and Methods: Patients with COPD and controls without COPD, participating in the Individualized COPD Evaluation in relation to Ageing (ICE‐Age) study, a prospective observational study, were included. Plasma 25-hydroxyvitamin D (25(OH)D) was measured at baseline and BC was measured by dual‐energy X‐ray absorptiometry scan, at baseline and after two years of follow-up. Multiple linear regression analyses were performed to assess the relationships between 25(OH)D (nmol/l) and longitudinal changes in BMI, fat-free mass index (FFMI), fat mas index (FMI) and bone mineral density (BMD).Results: A total of 192 patients with COPD (57% males, mean ± SD age, 62 ± 7, FEV1, 49 ± 16% predicted) and 199 controls (45% males, mean ± SD age 61 ± 7) were included in this study. Vitamin D levels were significantly lower in patients with COPD (64 ± 26 nmol/L, 95% CI 60– 68 nmol/L versus 75 ± 25 nmol/L, 95% CI 72– 79 nmol/L) compared to controls. Both patients and controls presented a significant decline in FFMI and T-score hip, but vitamin D level or status did not determine differences in BC or changes in BC over time in either COPD or controls.Conclusion: Vitamin D status was not associated with BC or longitudinal changes in BC. However, vitamin D insufficiency and low BMD were more prevalent in patients with COPD compared to controls.Keywords: chronic obstructive pulmonary disease, body composition, vitamin D, longitudinal changes, fat-free mass, bone mineral density

Rein Posthuma,1– 3 Lowie EGW Vanfleteren,4,5 Swetlana Gaffron,6 Anouk W Vaes,1 Frits ME Franssen,1– 3 Martijn A Spruit1– 3 1Department of Research and Development, CIRO+, Center of Expertise for Chronic Organ Failure, Horn, the Netherlands; 2NUTRIM, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands; 4COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 6Viscovery Software GmbH, Vienna, AustriaCorrespondence: Rein Posthuma, CIRO+, Center of expertise for chronic organ failure, Hornerheide 1, Horn, 6085 NM, the Netherlands, Email reinposthuma@ciro-horn.nlPurpose: Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM).Materials and Methods: This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 μg) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O.Results: Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline.Conclusion: Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD.Keywords: COPD, long-acting bronchodilators, outcomes

Maud Koopman,1– 3 Frits ME Franssen,1– 3 Swetlana Gaffron,4 Henrik Watz,5 Thierry Troosters,6,7 Judith Garcia-Aymerich,8– 10 Pierluigi Paggiaro,11 Eduard Molins,12 Miguel Moya,12 Lindy van Burk,13 Dieter Maier,14 Esther Garcia Gil,12 Emiel FM Wouters,1,3,15 Lowie EGW Vanfleteren,16 Martijn A Spruit1– 3 1Department of Research and Development, CIRO+, Center of Expertise for Chronic Organ Failure, Horn, the Netherlands; 2NUTRIM, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands; 4Viscovery Software GmbH, Vienna, Austria; 5Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 6Department of Rehabilitation Sciences, KU Leuven – University of Leuven, Leuven, Belgium; 7Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; 8Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; 9Universitat Pompeu Fabra (UPF), Barcelona, Spain; 10CIBER Epidemiología y Salud Publica (CIBERESP), Madrid, Spain; 11Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa, Italy; 12AstraZeneca, Barcelona, Spain; 13AstraZeneca, Den Haag, the Netherlands; 14Biomax Informatics AB, Planegg, 82152, Germany; 15Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; 16COPD Center, Sahlgrenska University Hospital, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenCorrespondence: Maud Koopman, CIRO+, Center of Expertise for Chronic Organ Failure, Hornerheide 1, Horn, 6085 NM, the Netherlands, Email maudkoopman@gmail.comRationale: It is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD.Methods: In the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate (AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups.Results: A total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients.Conclusion: Individual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy.Clinical Trial Registration: The original ACTIVATE study was registered on ClinicalTrials.gov, registration number NCT02424344.Keywords: COPD, hyperinflation, physical activity

Revathy Munuswamy,1,* Jana De Brandt,2,* Chris Burtin,2 Wim Derave,3 Joseph Aumann,4 Martijn A Spruit,5,6,* Luc Michiels1,* 1Faculty of Medicine and Life Sciences, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 2Faculty of Rehabilitation Sciences, Rehabilitation Research Center REVAL, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 3Department of Movement and Sports Sciences, Ghent University, Ghent, Belgium; 4Department of Pneumology, Jessa Hospital, Hasselt, Belgium; 5Department of Research and Development, CIRO, Horn, the Netherlands; 6Department of Respiratory Medicine, Maastricht University Medical Centre, Faculty of Health, Medicine and Life Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands*These authors contributed equally to this workCorrespondence: Luc Michiels Email luc.michiels@uhasselt.beAbstract: Chronic low-grade systemic inflammation is frequently observed in patients with chronic obstructive pulmonary disease (COPD), e.g., elevated pentameric CRP (pCRP). However, pCRP can dissociate to form monomeric CRP (mCRP) which exhibits a clear pro-inflammatory behaviour in contrast to the more anti-inflammatory properties of pCRP. Therefore, mCRP may be an informative biomarker to demonstrate chronic low-grade systemic inflammation. This was confirmed by analysing serum samples from 38 patients with COPD and 18 non-COPD control persons (NCCP). mCRP was significantly elevated in patients with COPD vs. NCCP, indicating that mCRP might be considered as a new sensitive marker of chronic low-grade systemic inflammation.Keywords: COPD, low-grade systemic inflammation, pCRP, mCRP

Peter Ascanius Jacobsen,1,2 Kristian Hay Kragholm,2,3 Christian Torp-Pedersen,4 Daisy JA Janssen,5,6 Martijn A Spruit,5,7,8 Ulla Møller Weinreich1,2 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2The Clinical Institute, Aalborg University, Aalborg, Denmark; 3Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; 4Department of Clinical Research, Hillerød Hospital, Hillerød, Denmark; 5Department of Research and Development, Ciro, Horn, the Netherland; 6Department of Health Services Research, Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; 7Nutrim School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands; 8Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, the NetherlandsCorrespondence: Peter Ascanius JacobsenDepartment of Respiratory Diseases, Aalborg University Hospital, Aalborg, DenmarkTel +45 97 66 48 00Email peter.jacobsen@rn.dkIntroduction: The understanding of whether and to what extent employment status affects readmission and mortality is limited in patients with COPD.Aim: To explore how employment status affects readmission and mortality after first admission to the hospital with acute exacerbation of COPD (AECOPD).Methods: This study used Danish national registry-based data. All patients admitted for the first time to the hospital between 1999 and 2014 with a diagnosis of AECOPD, age 35– 59, without a previous asthma diagnosis were included in the study. Employment status effect on 30-, 90-, and 365-day readmission and mortality was examined using logistic regression, adjusting for relevant confounders.Results: A total of 11,850 COPD patients were included in the study of which 3563 (30%) were working, 1368 (12%) unemployed, 840 (7%) on sick leave, and 6079 (51%) receiving early retirement. Patients receiving early retirement had, compared to patients working, an adjusted increased likelihood of readmission at 30, 90, and 365 days (odds ratio (OR) 1.26 (CI95% (1.06– 1.49)), 1.33 (CI95% (1.16– 1.53)), and 1.48 (CI95% (1.33– 1.66)), respectively). An increased likelihood was also seen in unemployed at 365 days follow-up (OR 1.44 (CI95% (1.22– 1.68))). Early retirement was associated with an increased mortality at 30, 90, and 365 days (OR 1.39 (CI95% (1.07– 1.80)) 1.37 (CI95% (1.09– 1.79)) and 1.48 (CI95% (1.25– 1.75)), respectively). An increased likelihood was also seen in patients receiving sick leave (OR 1.57 (CI95% (1.21– 2.04))).Conclusion: Patients with COPD who are not working at the time of first admission have a higher likelihood of readmission and mortality.Keywords: chronic obstructive pulmonary disease, employment, mortality, readmission

Frits ME Franssen1,2, Peter Alter,3 Nadav Bar,4 Birke J Benedikter5,6, Stella Iurato,7 Dieter Maier,8 Michael Maxheim,3 Fabienne K Roessler,4 Martijn A Spruit,1–2,9 Claus F Vogelmeier,3 Emiel FM Wouters1,2, Bernd Schmeck3,5 On behalf of the SysMed-COPD consortium 1Department of Research and Education, CIRO, Horn, The Netherlands; 2Department of Respiratory Medicine, Maastricht University Medical Centre, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands; 3Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps University of Marburg (UMR), Member of the German Center for Lung Research (DZL), Marburg, Germany; 4Department of Chemical Engineering, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 5Institute for Lung Research, Universities of Giessen and Marburg Lung Centre, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany; 6Department of Medical Microbiology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands; 7Viscovery Software GmbH, Vienna, Austria; 8Biomax Informatics AG, Planegg, Germany; 9REVAL - Rehabilitation Research Center, BIOMED - Biomedical Research Institute, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, BelgiumAbstract: Chronic airflow limitation is the common denominator of patients with chronic obstructive pulmonary disease (COPD). However, it is not possible to predict morbidity and mortality of individual patients based on the degree of lung function impairment, nor does the degree of airflow limitation allow guidance regarding therapies. Over the last decades, understanding of the factors contributing to the heterogeneity of disease trajectories, clinical presentation, and response to existing therapies has greatly advanced. Indeed, diagnostic assessment and treatment algorithms for COPD have become more personalized. In addition to the pulmonary abnormalities and inhaler therapies, extra-pulmonary features and comorbidities have been studied and are considered essential components of comprehensive disease management, including lifestyle interventions. Despite these advances, predicting and/or modifying the course of the disease remains currently impossible, and selection of patients with a beneficial response to specific interventions is unsatisfactory. Consequently, non-response to pharmacologic and non-pharmacologic treatments is common, and many patients have refractory symptoms. Thus, there is an ongoing urgency for a more targeted and holistic management of the disease, incorporating the basic principles of P4 medicine (predictive, preventive, personalized, and participatory). This review describes the current status and unmet needs regarding personalized medicine for patients with COPD. Also, it proposes a systems medicine approach, integrating genetic, environmental, (micro)biological, and clinical factors in experimental and computational models in order to decipher the multilevel complexity of COPD. Ultimately, the acquired insights will enable the development of clinical decision support systems and advance personalized medicine for patients with COPD.Keywords: chronic obstructive pulmonary disease, personalized medicine, systems medicine, review

Nienke Nakken,1 Daisy JA Janssen,1,2 Monique van Vliet,3 Geeuwke J de Vries,4 Giny AL Clappers-Gielen,5 Arent Jan Michels,6 Jean WM Muris,7 Jan H Vercoulen,8 Emiel FM Wouters,1,9 Martijn A Spruit1 1Department of Research and Education, CIRO, Horn, 2Centre of Expertise for Palliative Care, Maastricht University Medical Centre+ (MUMC+), Maastricht, 3Department of Respiratory Medicine, Zuyderland, Heerlen, 4Department of Respiratory Medicine, Zuyderland, Sittard-Geleen, 5Department of Respiratory Medicine, Elkerliek Hospital, Helmond, 6Department of Respiratory Medicine, St Anna Hospital, Geldrop, 7Department of Family Medicine, CAPHRI School of Public Health and Primary Care, Maastricht University, Maastricht, 8Department of Medical Psychology and Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, 9Department of Respiratory Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands Background/objectives: Chronic obstructive pulmonary disease (COPD) not only affects patients but also their partners. Gender-related differences in patients with COPD are known, for instance regarding symptoms and quality of life. Yet, research regarding gender differences in partners of patients with COPD has been conducted to a lesser extent, and most research focused on female partners. We aimed to investigate differences between male and female partners of patients with COPD regarding their own characteristics and their perceptions of patients’ characteristics.Design: Cross-sectional study.Setting: Four hospitals in the Netherlands.Participants: One hundred and eighty-eight patient–partner couples were included in this cross-sectional study.Measurements: General and clinical characteristics, health status, care dependency, symptoms of anxiety and depression, social support, caregiver burden, and coping styles were assessed during a home visit.Results: Female partners had more symptoms of anxiety and a worse health status than male partners. Social support and caregiver burden were comparable, but coping styles differed between male and female partners. Female partners thought that male patients were less care dependent and had more symptoms of depression, while these gender differences did not exist in patients themselves.Conclusion: Health care providers should pay attention to the needs of all partners of patients with COPD, but female partners in particular. Obtaining an extensive overview of the patient–partner couple, including coping styles, health status, symptoms of anxiety, and caregiver burden, is necessary to be able to support the couple as effectively as possible. Keywords: COPD, family caregiving, gender, partners

Fiona AHM Cleutjens,1 Frits ME Franssen,1 Martijn A Spruit,1 Lowie EGW Vanfleteren,1 Candy Gijsen,1 Jeanette B Dijkstra,2 Rudolf WHM Ponds,2 Emiel FM Wouters,1,3 Daisy JA Janssen1 1Department of Research and Education, CIRO, Centre of Expertise for Chronic Organ Failure, Horn, 2Department of Medical Psychology, Maastricht UMC+/School for Mental Health and Neurosciences (MHeNS), 3Department of Respiratory Medicine, Maastricht UMC+, Maastricht, the Netherlands Abstract: Impaired cognitive function is increasingly recognized in COPD. Yet, the prevalence of cognitive impairment in specific cognitive domains in COPD has been poorly studied. The aim of this cross-sectional observational study was to compare the prevalence of domain-specific cognitive impairment between patients with COPD and non-COPD controls. A neuropsychological assessment was administered in 90 stable COPD patients and 90 non-COPD controls with comparable smoking status, age, and level of education. Six core tests from the Maastricht Aging Study were used to assess general cognitive impairment. By using Z-scores, compound scores were constructed for the following domains: psychomotor speed, planning, working memory, verbal memory, and cognitive flexibility. General cognitive impairment and domain-specific cognitive impairment were compared between COPD patients and controls after correction for comorbidities using multivariate linear and logistic regression models. General cognitive impairment was found in 56.7% of patients with COPD and in 13.3% of controls. Deficits in the following domains were more often present in patients with COPD after correction for comorbidities: psychomotor speed (17.8% vs 3.3%; P

Dionne CW Braeken,1,2 Sarah Houben-Wilke,1 Dionne E Smid,1 Gernot GU Rohde,2 Jesse JC Drijkoningen,2 Emiel FM Wouters,1,2 Martijn A Spruit,1 Frits ME Franssen1,2 1Department of Research and Education, CIRO, Horn, the Netherlands; 2Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands Background: Spontaneous sputum production occurs in a subset of COPD patients; however, its clinical relevance has not been established. Differences in health status and clinical outcomes between patients with and without positive sputum cultures are unknown.Objective: To compare clinical characteristics and health status of spontaneous sputum producers with a positive culture (SC+) and negative culture (SC-) with nonsputum producers (NP) in a cohort of COPD patients referred for pulmonary rehabilitation.Methods: In total, 518 clinically stable patients with mild-to-very severe COPD were recruited (mean age: 64.1±9.1 years, 55.6% males, forced expiratory volume in 1 second 48.6%±20.0% predicted). Health status was measured using COPD Assessment Test, St George’s Respiratory Questionnaire, and the Clinical COPD Questionnaire. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Exercise capacity was measured using the 6-minute walking distance. Spontaneously expectorated sputum was cultured for microbiology.Results: Almost one-third of patients spontaneously produced sputum (n=164, 31.7%). Despite comparable lung function, SC+ reported more frequent exacerbations than NP (≥2 exacerbations

Reem Kayyali,1 Bassel Odeh,1 Inéz Frerichs,2 Nikki Davies,3 Eleni Perantoni,4 Shona D’arcy,5 Anouk W Vaes,6 John Chang,3 Martijn A Spruit,6 Brenda Deering,7 Nada Philip,1 Roshan Siva,3 Evangelos Kaimakamis,8 Ioanna Chouvarda,8 Barbara Pierscionek,1 Norbert Weiler,2 Emiel FM Wouters,6 Andreas Raptopoulos,9 Shereen Nabhani-Gebara1 1Faculty of Science, Engineering and Computing, Kingston University, Kingston-Upon-Thames, UK; 2Department of Anaesthesiology and Intensive Care Medicine, University Medical Centre Schleswig-Holstein, Kiel, Germany; 3Chest Clinic and Research and Development, Croydon University Hospital, Croydon, UK; 4Pulmonary Clinic, AHEPA University Hospital, Thessaloniki, Greece; 5Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; 6Research and Education, CIRO – Centre of Expertise for Chronic Organ Failure, Horn, the Netherlands; 7COPD Outreach, Beaumont Hospital, Dublin, Ireland; 8Medical School, Aristotle University, Thessaloniki, 9Research and Development, Exodus Information Technology SA, Athens, Greece Background: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services.Objective: The aim of this study was to compare COPD patients’ care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals’ (HCPs) perceptions about the current pathways.Methods: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview.Results: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers.Conclusion: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients’ engagement could optimize current care pathways resulting in a better integrated system. Keywords: COPD, comorbidities, care delivery pathway, comparative analysis

Frits ME Franssen1, Martijn A Spruit1, Emiel FM Wouters1,2 1Program Development Center, CIRO+, Center of Expertise for Chronic Organ Failure, Horn, The Netherlands; 2Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, The Netherlands Background: Polypharmacy of respiratory medications is commonly observed in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to investigate determinants of polypharmacy and to study the consistency of actual respiratory drug use with current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in pulmonary rehabilitation candidates with COPD. Methods: Data were extracted from the records of all patients with a diagnosis of COPD referred for pulmonary rehabilitation to CIRO+ between 2005 and 2009. Use of respiratory medications, self-reported COPD exacerbations, lung function, blood gases, exercise capacity, Medical Research Council (MRC) dyspnea grade, and St George’s Respiratory Questionnaire (SGRQ) were recorded as part of assessment of health status. Results: In total, 1859 COPD patients of mean age (± standard deviation) 64.3 ± 9.7 years and with a forced expiratory volume in one second (FEV1) of 44.7% ± 18.2% were included. On average, patients used 3.5 ± 1.5 respiratory medications; this number increased with increasing GOLD stage, MRC score, and SGRQ scores. FEV1 (% predicted), SGRQ, and number of recent exacerbations were independent determinants of polypharmacy. Use of long-acting bronchodilators and inhaled corticosteroids was substantial and comparable in all GOLD stages. Use of corticosteroids was not restricted to patients with frequent exacerbations. Conclusion: Polypharmacy of respiratory medications is common in COPD patients with persistent symptoms. In addition to severity of disease, health status is an independent predictor of polypharmacy. Actual drug use in COPD patients referred for pulmonary rehabilitation is partially inconsistent with current GOLD guidelines. Keywords: chronic obstructive pulmonary disease, management, pharmacotherapy, polypharmacy, pulmonary rehabilitation, respiratory drug use

Background: Generally, the use of a rollator improves mobility in patients with COPD. Nevertheless, not all patients benefit from its use, and many patients feel embarrassed about using it. Therefore, other walking aids are worthwhile to consider. We compared the direct effects of a "new" ambulation aid (a modern draisine) with the effects of a rollator on 6-min walk distance (6MWD) in patients with COPD.Methods: Twenty-one patients with COPD performed two 6-min walk tests (6MWTs) during prerehabilitation assessment (best 6MWD: 369 ± 88 m). Additionally, two extra 6MWTs were performed on two consecutive days in random order: one time with a rollator and one time with a modern draisine. Walking pattern (n = 21) was determined using an accelerometer, and metabolic requirements (n = 10) were assessed using a mobile oxycon.Results: Walking with the modern draisine resulted in a higher 6MWD compared with walking with the rollator (466 ± 189 m vs 383 ± 85 m). Moreover, patients had fewer strides (245 ± 61 vs 300 ± 49) and a greater stride length (1.89 ± 0.73 m vs 1.27 ± 0.14 m) using the modern draisine compared with the rollator (all P ≤ .001). Oxygen uptake, ventilation, heart rate, oxygen saturation, and Borg symptom scores were comparable between both walking aids. Ten percent of the patients felt embarrassed using the modern draisine compared with 19% for the rollator, and a significantly smaller proportion of patients would use the modern draisine in daily life.Conclusions: The mean difference in 6MWD between a modern draisine and a rollator seems clinically relevant, with the same metabolic requirements and symptom Borg scores. Therefore, this "new" ambulation aid could be a good alternative to the rollator to improve functional exercise performance in patients with COPD.Trial Registry: The Netherlands National Trial Registry; No.: NTR1542; URL: www.trialregister.nl. [ABSTRACT FROM AUTHOR]

Purpose: Aims of this cross-sectional study were to assess health status and care dependency in patients with advanced chronic obstructive pulmonary disease (COPD) or chronic heart failure (CHF) and to identify correlates of an impaired health status.Methods: The following outcomes were assessed in outpatients with advanced COPD (n = 105) or CHF (n = 80): clinical characteristics; general health status (EuroQol-5 Dimensions (EQ-5D); Assessment of Quality of Life instrument (AQoL); Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)); disease-specific health status (St. Georges Respiratory Questionnaire (SGRQ), Minnesota Living with Heart Failure Questionnaire (MLHFQ)); physical mobility (timed 'Up and Go' test); and care dependency (Care Dependency Scale).Results: Patients with advanced COPD or CHF have an impaired health status and may be confronted with care dependency. Multiple regression analyses have shown that physical and psychological symptoms, care dependency and number of drugs were correlated with impaired health status in advanced COPD or CHF, while demographic and clinical characteristics like age, gender, disease severity and co-morbidities were not correlated.Conclusions: Clinical care should regularly assess symptom burden and care dependency to identify patients with advanced COPD or CHF at risk for an impaired health status. [ABSTRACT FROM AUTHOR]

Background: Patients with COPD generally have a poor peak aerobic capacity and, therefore, may experience more inconvenience during domestic activities of daily life (ADLs). Yet, task-related oxygen uptake and symptom perception during ADLs have been studied rarely in COPD. Therefore, it remains unknown whether and to what extent differences may exist in task-related oxygen uptake and symptom perception during ADLs in patients with COPD after stratification for sex; GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage; Medical Research Council (MRC) dyspnea grade; or score on the BMI, obstruction, dyspnea, exercise capacity (BODE) index.Methods: Ninety-seven patients with COPD and 20 healthy elderly subjects performed the following five self-paced domestic ADLs with 4-min rest intervals: putting on socks, shoes, and vest; folding eight towels; putting away groceries; washing four dishes, cups, and saucers; and sweeping the floor for 4 min. Task-related oxygen uptake was assessed using an Oxycon Mobile device, whereas Borg scores were used to assess task-related dyspnea and fatigue.Results: Patients with COPD used a significantly higher proportion of their peak aerobic capacity and ventilation to perform ADLs than did the healthy subjects, accompanied by higher task-related Borg dyspnea scores. Patients with GOLD stage IV, MRC dyspnea grade 5, or BODE score ≥ 6 points had the highest task-related oxygen uptake and dyspnea perception during the performance of domestic ADLs. Results showed no sex-related differences.Conclusion: Patients with COPD experience a relatively high metabolic load and symptom perception during the performance of ADLs that is not the same as seen in their healthy peers, particularly in patients with GOLD stage IV, MRC dyspnea grade 5, or BODE score ≥ 6 points. [ABSTRACT FROM AUTHOR]

Rationale: Circulating levels of testosterone and gonadotrophins of patients with chronic obstructive pulmonary disease (COPD) have never been compared with those of elderly men with normal pulmonary function. Moreover, the relationship of hypogonadism with quadriceps muscle weakness and exercise intolerance has been studied scarcely in men with COPD.Objectives: To compare circulating levels of hormones of the pituitary-gonadotrophic axis of men with COPD with those of age-matched control subjects. Moreover, to study the relationship of hypogonadism with quadriceps muscle force, 6-min walking distance, and systemic markers of inflammation in the patients.Methods and Measurements: Circulating levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and sex homone-binding globulin were determined, and free testosterone was calculated in 78 patients (FEV[1]: 44 +/- 17% of the predicted values) and 21 control subjects. Moreover, quadriceps muscle force, 6-min walking distance, number of pack-yr, and systemic inflammation were determined.Main Results: Follicle-stimulating hormone and luteinizing hormone were higher in the patients, whereas testosterone was lower (p

Quantification of physical activities in daily life in patients with chronic obstructive pulmonary disease has increasing clinical interest. However, detailed comparison with healthy subjects is not available. Furthermore, it is unknown whether time spent actively during daily life is related to lung function, muscle force, or maximal and functional exercise capacity. We assessed physical activities and movement intensity with the DynaPort activity monitor in 50 patients (age 64 +/- 7 years; FEV[1] 43 +/- 18% predicted) and 25 healthy elderly individuals (age 66 +/- 5 years). Patients showed lower walking time (44 +/- 26 vs. 81 +/- 26 minutes/day), standing time (191 +/- 99 vs. 295 +/- 109 minutes/day), and movement intensity during walking (1.8 +/- 0.3 vs. 2.4 +/- 0.5 m/second[2]; p < 0.0001 for all), as well as higher sitting time (374 +/- 139 vs. 306 +/- 108 minutes/day; p = 0.04) and lying time (87 +/- 97 vs. 29 +/- 33 minutes/day; p = 0.004). Walking time was highly correlated with the 6-minute walking test (r = 0.76, p < 0.0001) and more modestly to maximal exercise capacity, lung function, and muscle force (0.28 < r < 0.64, p < 0.05). Patients with chronic obstructive pulmonary disease are markedly inactive in daily life. Functional exercise capacity is the strongest correlate of physical activities in daily life. [ABSTRACT FROM AUTHOR]

Abstract Background Longitudinal studies analyzing the correlations between disease-specific and generic health status questionnaires at different time points in patients with advanced COPD are lacking. The aim of this study was to determine whether and to what extent a disease-specific health status questionnaire (Saint George’s Respiratory Questionnaire, SGRQ) correlates with generic health status questionnaires (EuroQol-5-Dimensions, EQ-5D; Assessment of Quality of Life instrument, AQoL; Medical Outcomes Study 36-Item Short-Form Health Survey, SF-36) at four different time points in patients with advanced COPD; and to determine the correlation between the changes in these questionnaires during one-year follow-up. Methods Demographic and clinical characteristics were assessed in 105 outpatients with advanced COPD at baseline. Disease-specific health status (SGRQ) and generic health status (EQ-5D, AQoL, SF-36) were assessed at baseline, four, eight, and 12 months. Correlations were determined between SGRQ and EQ-5D, AQoL, and SF-36 scores and changes in these scores. Agreement in direction of change was assessed. Results Eighty-four patients (80%) completed one-year follow-up and were included for analysis. SGRQ total score and EQ-5D index score, AQoL total score and SF-36 Physical Component Summary measure (SF-36 PCS) score were moderately to strongly correlated. The correlation of the changes between the SGRQ total score and EQ-5D index score, AQoL total score, SF-36 PCS, and SF-36 Mental Component Summary measure (SF-36 MCS) score were weak or absent. The direction of changes in SGRQ total scores agreed slightly with the direction of changes in EQ-5D index score, AQoL total score, and SF-36 PCS score. Conclusions At four, eight and 12 months after baseline, SGRQ total scores and EQ-5D index scores, AQoL total scores and SF-36 PCS scores were moderately to strongly correlated, while SGRQ total scores were weakly correlated with SF-36 MCS scores. The correlations between changes over time were weak or even absent. Disease-specific health status questionnaires and generic health status questionnaires should be used together to gain complete insight in health status and changes in health status over time in patients with advanced COPD.

Abstract Background In patients with COPD progressive dyspnoea leads to a sedentary lifestyle. To date, no studies exist investigating the effects of Nordic Walking in patients with COPD. Therefore, the aim was to determine the feasibility of Nordic Walking in COPD patients at different disease stages. Furthermore we aimed to determine the short- and long-term effects of Nordic Walking on COPD patients' daily physical activity pattern as well as on patients exercise capacity. Methods Sixty COPD patients were randomised to either Nordic Walking or to a control group. Patients of the Nordic Walking group (n = 30; age: 62 ± 9 years; FEV1: 48 ± 19% predicted) underwent a three-month outdoor Nordic Walking exercise program consisting of one hour walking at 75% of their initial maximum heart rate three times per week, whereas controls had no exercise intervention. Primary endpoint: daily physical activities (measured by a validated tri-axial accelerometer); secondary endpoint: functional exercise capacity (measured by the six-minute walking distance; 6MWD). Assessment time points in both groups: baseline, after three, six and nine months. Results After three month training period, in the Nordic Walking group time spent walking and standing as well as intensity of walking increased (Δ walking time: +14.9 ± 1.9 min/day; Δ standing time: +129 ± 26 min/day; Δ movement intensity: +0.40 ± 0.14 m/s2) while time spent sitting decreased (Δ sitting time: -128 ± 15 min/day) compared to baseline (all: p < 0.01) as well as compared to controls (all: p < 0.01). Furthermore, 6MWD significantly increased compared to baseline (Δ 6MWD: +79 ± 28 meters) as well as compared to controls (both: p < 0.01). These significant improvements were sustained six and nine months after baseline. In contrast, controls showed unchanged daily physical activities and 6MWD compared to baseline for all time points. Conclusions Nordic Walking is a feasible, simple and effective physical training modality in COPD. In addition, Nordic Walking has proven to positively impact the daily physical activity pattern of COPD patients under short- and long-term observation. Clinical trial registration Nordic Walking improves daily physical activities in COPD: a randomised controlled trial - ISRCTN31525632

Abstract COPD is nowadays the main indication for lung transplantation. In appropriately selected patients with end stage COPD, lung transplantation may improve quality of life and prognosis of survival. However, patients with end stage COPD may die while waiting for lung transplantation. Palliative care is important to address the needs of patients with end stage COPD. This case report shows that in a patient with end stage COPD listed for lung transplantation offering palliative care and curative-restorative care concurrently may be problematic. If the requirements to remain a transplantation candidate need to be met, the possibilities for palliative care may be limited. Discussing the possibilities of palliative care and the patient's treatment preferences is necessary to prevent that end-of-life care needs of COPD patients dying while listed for lung transplantation are not optimally addressed. The patient's end-of-life care preferences may ask for a clear distinction between the period in which palliative and curative-restorative care are offered concurrently and the end-of-life care period. This may be necessary to allow a patient to spend the last stage of life according to his or her wishes, even when this implicates that lung transplantation is not possible anymore and the patient will die because of end stage COPD.

Abstract Background Elevated circulating levels of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen (FG) have been repeatedly associated with many adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). To date, it remains unclear whether and to what extent systemic inflammation is primary or secondary in the pathogenesis of COPD. The aim of this study was to examine the association between haplotypes of CRP, IL6 and FGB genes, systemic inflammation, COPD risk and COPD-related phenotypes (respiratory impairment, exercise capacity and body composition). Methods Eighteen SNPs in three genes, representing optimal haplotype-tagging sets, were genotyped in 355 COPD patients and 195 healthy smokers. Plasma levels of CRP, IL-6 and FG were measured in the total study group. Differences in haplotype distributions were tested using the global and haplotype-specific statistics. Results Raised plasma levels of CRP, IL-6 and fibrinogen were demonstrated in COPD patients. However, COPD population was very heterogeneous: about 40% of patients had no evidence of systemic inflammation (CRP < 3 mg/uL or no inflammatory markers in their top quartile). Global test for haplotype effect indicated association of CRP gene and CRP plasma levels (P = 0.0004) and IL6 gene and COPD (P = 0.003). Subsequent analysis has shown that IL6 haplotype H2, associated with an increased COPD risk (p = 0.004, OR = 4.82; 1.64 to 4.18), was also associated with very low CRP levels (p = 0.0005). None of the genes were associated with COPD-related phenotypes. Conclusion Our findings suggest that common genetic variation in CRP and IL6 genes may contribute to heterogeneity of COPD population associated with systemic inflammation.

Abstract Background Recent research shows that the prevalence of patients with very severe chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and chronic renal failure (CRF) continues to rise over the next years. Scientific studies concerning self-perceived symptoms and care needs in patients with severe to very severe COPD, CHF and CRF are scarce. Consequently, it will be difficult to develop an optimal patient-centred palliative care program for patients with end-stage COPD, CHF or CRF. The present study has been designed to assess the symptoms, care needs, end-of-life care treatment preferences and communication needs of patients with severe to very severe COPD, CHF or CRF. Additionally, family distress and care giving burden of relatives of these patients will be assessed. Methods/design A cross-sectional comparative and prospective longitudinal study in patients with end-stage COPD, CHF or CRF has been designed. Patients will be recruited by their treating physician specialist. Patients and their closest relatives will be visited at baseline and every 4 months after baseline for a period of 12 months. The following outcomes will be assessed during home visits: self-perceived symptoms and care needs; daily physical functioning; general health status; end-of-life care treatment preferences; end-of-life care communication and care-giver burden of family caregivers. Additionally, end-of-life care communication and prognosis of survival will be assessed with the physician primarily responsible for the management of the chronic organ failure. Finally, if patients decease during the study period, the baseline preferences with regard to life-sustaining treatments will be compared with the real end-of-life care. Discussion To date, the symptoms, care needs, caregiver burden, end-of-life care treatment preferences and communication needs of patients with very severe COPD, CHF or CRF remain unknown. The present study will increase the knowledge about the self-perceived symptoms, care-needs, caregiver burden, end-of-life care treatment preferences and communication needs from the views of patients, their loved ones and their treating physician. This knowledge is necessary to optimize palliative care for patients with COPD, CHF or CRF. Here, the design of the present study has been described. A preliminary analysis of the possible strengths, weaknesses and clinical consequences is outlined.

Purpose: This review presents an overview of the safety and efficacy of alternative modes of pulmonary rehabilitation (PR) in people with chronic obstructive pulmonary disease (COPD)., Review Methods: We identified recently published systematic reviews, meta-analyses, and guidelines, as well as relevant studies, exploring the safety and effectiveness of community-based PR, home-based PR, telerehabilitation, and web-based rehabilitation in people with COPD. A narrative summary of the main findings is presented., Summary: Although evidence suggests that community-based PR, home-based PR, telerehabilitation, and web-based rehabilitation are effective alternatives to center-based PR, it requires a careful interpretation as several of these programs do not comply with PR definition and have been compared with center-based PR programs that do not reach the minimal clinically important differences. Moreover, there is a huge heterogeneity among programs, and the confidence and quality of the evidence is mostly low. Hence, these novel modes of PR and center-based PR are not interchangeable. Instead, these are alternative modes aiming to increase access to PR. Questions remain regarding the most efficient way of implementing each PR mode, level of access, reimbursement policies, and data privacy in the use of technology. Standard protocols on how to set up each alternative PR mode need to be developed. Future research needs to explore how to use the treatable traits approach in combination with individual preferences and needs, program availability, safety, social support network, digital literacy, and health system context to identify the optimal PR program for each patient., Competing Interests: Conflicts of interest: All authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Physical activity (PA), sleep, and sedentary time (SST) are important outcomes to monitor and to improve as part of patients' asthma management. This study aimed to assess the number of measurement days needed to reliably measure PA and SST. Secondly, the influence of external factors on the reliability of measuring PA and SST was studied., Methods: Adult patients with stable asthma were asked to wear a triaxial accelerometer for at least four days, with at least 22.5 h of wear time per day. The Intraclass Correlation Coefficients (ICCs) between different number of measurement days were used to determine reliability. Values ≥0.75 indicated good reliability., Results: Data from 452 patients were analyzed (63% women; age: 49 ± 16 years; FEV 1 : 87 ± 17% predicted). PA could reliably be measured with four valid measurement days (ICC 0.761). For SST, three days were needed (ICC 0.778). In summer and autumn, three days were needed to reliably measure PA, in winter four, in spring six. For SST, five days were needed in spring for good reliability, and two in all other seasons., Conclusion: Based on data from four valid days, PA and SST can reliably be measured with an accelerometer in patients with asthma. Seasonal influences are present, especially during spring. When measuring for four days, using only weekdays or three weekdays and one weekend day is recommended. The degree of asthma control, dyspnea or spirometric values did not influence the reliability.

Topic Importance: Cognitive and physical limitations are common in individuals with chronic lung diseases, but their interactions with physical function and activities of daily living are not well characterized. Understanding these interactions and potential contributors may provide insights on disability and enable more tailored rehabilitation strategies., Review Findings: This review summarizes a 2-day meeting of patient partners, clinicians, researchers, and lung associations to discuss the interplay between cognitive and physical function in people with chronic lung diseases. This report covers four areas: (1) cognitive-physical limitations in patients with chronic lung diseases; (2) cognitive assessments; (3) strategies to optimize cognition and motor control; and (4) future research directions. Cognitive and physical impairments have multiple effects on quality of life and daily function. Meeting participants acknowledged the need for a standardized cognitive assessment to complement physical assessments in patients with chronic lung diseases. Dyspnea, fatigue, and age were recognized as important contributors to cognition that can affect motor control and daily physical function. Pulmonary rehabilitation was highlighted as a multidisciplinary strategy that may improve respiratory and limb motor control through neuroplasticity and has the potential to improve physical function and quality of life., Summary: There was consensus that cognitive function and the cognitive interference of dyspnea in people with chronic lung diseases contribute to motor control impairments that can negatively affect daily function, which may be improved with pulmonary rehabilitation. The meeting generated several key research questions related to cognitive-physical interactions in individuals with chronic lung diseases., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: D. R. reports financial support was provided by Canadian Institutes of Health Research, Sandra Faire and Ivan Fecan Professorship in Rehabilitation Medicine and Temerty Faculty of Medicine. W. D. R. reports financial support was provided by Canadian Institutes of Health Research and Canadian Lung Association. A. G. K. reports funding for advisory board or speakers bureau roles for AstraZeneca, Belus, Boehringer Ingelheim, Eisai, GSK, Idorsia, Merck Frosst, Moderna, Novo Nordisk, Pfizer, Respiplus, Sanofi, Teva, Trudel, and Valeo. D. D. M. is an outreach Editor for CHEST. M. A. S. reports grants from Netherlands Lung Foundation, Stichting Astma Bestrijding, Chiesi, AstraZeneca, TEVA, and Boehringer Ingelheim, outside the submitted work; and fees from Boehringer Ingelheim, GSK, and AstraZeneca, outside the submitted work that includes funding grants. M. K. S. is on the COPD Editorial Board for CHEST. None declared (P. C., J. L. C., G. D., P. W. D., H. E., J. H. F., J. A. G., D. Gold, R. S. G., D. Goodridge, T. J.-F., D. L., B. M., A. O.-C., J. O.-A., V. P., P. R., S. R., C. R., M. B. S., J. T., K. W.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: COPD is a disease characterised by skeletal muscle dysfunction. A spatial relationship exists between satellite cells and muscle fibre capillaries, which has been suggested to be of major importance for satellite cell function. In the present study we compared the spatial relationship between satellite cells and capillaries in patients with COPD and age-matched healthy older adults., Methods: Muscle biopsies were obtained from the vastus lateralis of n=18 patients with COPD (8 female, 10 male; age 66±5 years, mild-to-severe airflow obstruction) and n=18 age-, sex- and body mass index-matched healthy control adults (8 female, 10 male; age 68±5 years). Immunohistochemistry was used to assess type I/II muscle fibre size, distribution, myonuclear content, satellite cell number and fibre capillarisation. In addition, type I/II muscle fibre satellite cell distance to its nearest capillary was assessed., Results: The percentage of type II muscle fibres was significantly greater in patients with COPD (62±10%) compared with controls (50±12%, p<0.05). Muscle fibre capillarisation was significantly lower in patients with COPD compared with controls (p<0.05). While satellite cell content was not different between groups, type I and type II satellite cell distance to its nearest capillary was significantly greater in patients with COPD (type I: 21.3±4.8 µm; type II: 26.7±9.3 µm) compared with controls (type I: 16.1±3.5 µm; type II: 22.7±5.8 µm; p<0.05)., Conclusion: Satellite cells are located at a greater distance from their nearest capillary in patients with COPD compared with age-matched controls. This increased distance could play a role in impaired satellite cell function in patients with COPD., Competing Interests: Conflict of interest: All authors report no conflict of interest., (Copyright ©The authors 2024.)