Publications by authors named "Thierry Troosters"

177 Publications

COVID-19 recovery: benefits of multidisciplinary respiratory rehabilitation.

BMJ Open Respir Res 2021 09;8(1)

Department of Respiratory Diseases, KU Leuven University Hospitals Leuven, Leuven, Belgium.

Many patients struggle with ongoing symptoms in different domains (physical, mental, cognitive) after hospitalisation for COVID-19, calling out for a multidisciplinary approach. An outpatient multidisciplinary rehabilitation programme, according to a respiratory rehabilitation strategy, was set up for adult patients who were able to attend group sessions during 12 weeks. Results of 22 adult patients with COVID-19, of which 15 had required intensive care, were analysed and some general impressions and challenges of rehabilitation in COVID-19 were reported. Impressive results on physical recovery were determined after 6 weeks and 3 months, with significant improvement of lung function, muscle force and exercise capacity variables. A positive evolution of mental and cognitive burden was present, although less pronounced than the physical recovery. These mental and cognitive consequences seem, next to musculoskeletal and medical complications, the most challenging aspect of rehabilitating patients with COVID-19. These real-world data show feasibility and efficiency of a multidisciplinary respiratory rehabilitation programme after moderate to severe COVID-19 disease.
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http://dx.doi.org/10.1136/bmjresp-2020-000837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423511PMC
September 2021

Objectively Measured Physical Activity in Patients with COPD: Recommendations from an International Task Force on Physical Activity.

Chronic Obstr Pulm Dis 2021 08 25. Epub 2021 Aug 25.

Reval Rehabilitation Research Center, Biomed Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.

Physical activity (PA) is of key importance for health among healthy persons and individuals with COPD. PA has multiple dimensions that can be assessed and quantified objectively using activity monitors. Moreover, as shown in the published literature, variable methodologies have been used to date to quantify PA among individuals with COPD, precluding clear comparisons of outcomes across studies. The present paper aims to provide a summary of the available literature for the rationale behind using objectively measured PA and proposes a standardized methodology for assessment, including standard operating procedures for future research. The present paper therefore describes the concept of PA, reports on the importance of PA, summarizes the dimensions of PA, provides a standard operating procedure how to monitor PA using objective assessments and describes the psychometric properties of objectively measured PA. The present international task force recommends implementation of the standard operating procedure for PA data collection and reporting in the future. This should allow to further clarify the relationship between PA and clinical outcomes, to test the impact of treatment interventions on PA in individuals with COPD and to successfully propose a PA endpoint for regulatory qualification in the future.
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http://dx.doi.org/10.15326/jcopdf.2021.0213DOI Listing
August 2021

Objectively Measured Physical Activity as a COPD Clinical Trial Outcome.

Chest 2021 Jul 1. Epub 2021 Jul 1.

Department of Research and Development, CIRO, Horn, The Netherlands.

Background: Reduced physical activity is common in COPD and is associated with poor outcomes. Physical activity is therefore a worthy target for intervention in clinical trials; however, trials evaluating physical activity have used heterogeneous methods.

Research Question: What is the available evidence on the efficacy and/or effectiveness of various interventions to enhance objectively measured physical activity in patients with COPD, taking into account the minimal preferred methodologic quality of physical activity assessment?

Study Design And Methods: In this narrative review, the COPD Biomarker Qualification Consortium (CBQC) task force searched three scientific databases for articles that reported the effect of an intervention on objectively measured physical activity in COPD. Based on scientific literature and expert consensus, only studies with ≥ 7 measurement days and ≥ 4 valid days of ≥ 8 h of monitoring were included in the primary analysis.

Results: Thirty-seven of 110 (34%) identified studies fulfilled the criteria, investigating the efficacy and/or effectiveness of physical activity behavior change programs (n = 7), mobile or electronic-health interventions (n = 9), rehabilitative exercise (n = 9), bronchodilation (n = 6), lung volume reduction procedures (n = 3), and other interventions (n = 3). Results are generally variable, reflecting the large differences in study characteristics and outcomes. Few studies show an increase beyond the proposed minimal important change of 600 to 1100 daily steps, indicating that enhancing physical activity levels is a challenge.

Interpretation: Only one-third of clinical trials measuring objective physical activity in people with COPD fulfilled the preset criteria regarding physical activity assessment. Studies showed variable effects on physical activity even when investigating similar interventions.
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http://dx.doi.org/10.1016/j.chest.2021.06.044DOI Listing
July 2021

Lung volume reduction in emphysema: a pragmatic prospective cohort study.

ERJ Open Res 2021 Apr 31;7(2). Epub 2021 May 31.

Clinical Dept of Respiratory Diseases, University Hospitals Leuven, BREATHE, Dept CHROMETA, KU Leuven, Leuven, Belgium.

Limited guidance exists for the implementation of lung volume reduction interventions in routine clinical care. We designed a pragmatic study to evaluate a strategy including endoscopic lung volume reduction (ELVR) and lung volume reduction surgery (LVRS) in heterogeneous emphysema. This prospective monocentre cohort study evaluated ELVR no-ELVR, followed by a cohort study evaluating LVRS. Primary outcome was the proportion of subjects with a forced expiratory volume in 1 s (FEV) improvement of ⩾100 mL at 3-month follow-up. Changes in FEV, residual volume (RV), 6-min walk distance (6MWD) and quality of life (St George's Respiratory Questionnaire (SGRQ)) were evaluated at 6-month follow-up. Hospital stay and treatment-related serious adverse events were monitored. From 106 subjects screened, 38 subjects were enrolled comparing ELVR (n=20) with no-ELVR (n=18). After 6 months' follow-up, eligible patients were referred for LVRS (n=16) with another 6-month follow-up. At 3-month follow-up, 70% of ELVR compared to 11% of no-ELVR (p<0.001) and 69% of LVRS had an FEV improvement of ⩾100 mL. Between-group differences (mean±sem) for ELVR no-ELVR at 6-month follow-up were FEV +0.21±0.05 L; RV -0.95±0.21 L; 6MWD 58±17 m and SGRQ -18±5 points. At 6-month follow-up, within-group differences (mean±sem) for LVRS showed FEV +0.27±0.06 L; RV -1.49±0.22 L and 6MWD +75±18 m. Serious adverse events in 81% 45% of subjects (p=0.04) and a median hospital stay of 15 5 days (p<0.001) were observed for LVRS ELVR, respectively. This pragmatic prospective cohort study supports a clinical approach with ELVR as a less invasive first option and LVRS as powerful alternative in severe heterogeneous emphysema.
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http://dx.doi.org/10.1183/23120541.00877-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165372PMC
April 2021

The combination of smoking with vitamin D deficiency impairs skeletal muscle fiber hypertrophy in response to overload in mice.

J Appl Physiol (1985) 2021 07 3;131(1):339-351. Epub 2021 Jun 3.

Department of Life Sciences, Research Center for Musculoskeletal Science and Sports Medicine, Manchester Metropolitan University, Manchester, United Kingdom.

Vitamin D deficiency, which is highly prevalent in the general population, exerts similar deleterious effects on skeletal muscles to those induced by cigarette smoking. We examined whether cigarette smoke (CS) exposure and/or vitamin D deficiency impairs the skeletal muscle hypertrophic response to overload. Male C57Bl/6JolaH mice on a normal or vitamin D-deficient diet were exposed to CS or room air for 18 wk. Six weeks after initiation of smoke or air exposure, sham surgery or denervation of the agonists of the left plantaris muscle was performed. The right leg served as internal control. Twelve weeks later, the hypertrophic response was assessed. CS exposure instigated loss of body and muscle mass, and increased lung inflammatory cell infiltration ( < 0.05), independently of diet. Maximal exercise capacity, whole body strength, in situ plantaris muscle force, and key markers of hypertrophic signaling (Akt, 4EBP1, and FoxO1) were not significantly affected by smoking or diet. The increase in plantaris muscle fiber cross-sectional area in response to overload was attenuated in vitamin D-deficient CS-exposed mice (smoking × diet interaction for hypertrophy, = 0.03). In situ fatigue resistance was elevated in hypertrophied plantaris, irrespective of vitamin D deficiency and/or CS exposure. In conclusion, our data show that CS exposure or vitamin D deficiency alone did not attenuate the hypertrophic response of overloaded plantaris muscles, but this hypertrophic response was weakened when both conditions were combined. These data suggest that current smokers who also present with vitamin D deficiency may be less likely to respond to a training program. Plantaris hypertrophy caused by compensatory overload after denervation of the soleus and gastrocnemius muscles showed increased mass and fiber dimensions, but to a lesser extent when vitamin D deficiency was combined with cigarette smoking. Fatigue resistance was elevated in hypertrophied plantaris, irrespective of diet or smoking, whereas physical fitness, hypertrophic markers, and in situ plantaris force were similar. These data showed that the hypertrophic response to overload is attenuated when both conditions are combined.
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http://dx.doi.org/10.1152/japplphysiol.00733.2020DOI Listing
July 2021

High-Intensity Training for 6 Months Safely, but Only Temporarily, Improves Exercise Capacity in Selected Solid Organ Transplant Recipients.

Transplant Proc 2021 Jul-Aug;53(6):1836-1845. Epub 2021 May 25.

Department of Microbiology, Immunology, and Transplantation, Laboratory of Abdominal Transplantation, KU Leuven, Leuven, Belgium; Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Background: Organ transplantation is a life-saving intervention that improves quality of life of patients with irreversible organ failure. Although exercise training immediately after transplantation has been suggested to be beneficial, such interventions remain rare in stable transplant recipients, whereas effects of high-intensity training (HIT) are even less frequently investigated. Moreover, sustainability of such interventions has not yet been reported. We investigated the effects of a 6-month, cycling-based HIT program on physical performance in long-term stable solid organ transplant (SOT) recipients, with follow-up evaluation after 6 months.

Methods: Forty-two adult, stable, and selected SOT recipients participated in a 6-month individualized home- and group-based HIT program. Exercise capacity (VOmax), maximal power (Wmax), and body mass index were measured before, at the end, and 6 months after completion of the intervention.

Results: The study comprised 12 heart, 7 lung, 8 liver, and 15 kidney recipients (mean age, 41.4 ± 11.1 years; median time posttransplant, 3.4 [1.7-8.0] years). For 6 months, VOmax increased in the heart, lung, and kidney groups, Wmax increased in the heart group, and body mass index decreased in the liver group. Six months after the HIT program, the achieved gain in exercise capacity had disappeared in all groups.

Conclusion: Despite voluntary participation selection bias, our observations indicate that HIT is safe and may result in a beneficial effect on physical performance in selected, stable SOT recipients. However, there was no sustained beneficial effect once training stopped. Larger scale and longer term studies are still required to investigate longevity of improvement and overall beneficial effects on clinical outcomes.
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http://dx.doi.org/10.1016/j.transproceed.2021.03.040DOI Listing
May 2021

Defining Modern Pulmonary Rehabilitation. An Official American Thoracic Society Workshop Report.

Ann Am Thorac Soc 2021 05;18(5):e12-e29

Pulmonary rehabilitation is a highly effective treatment for people with chronic lung disease but remains underused across the world. Recent years have seen the emergence of new program models that aim to improve access and uptake, including telerehabilitation and low-cost, home-based models. This workshop was convened to achieve consensus on the essential components of pulmonary rehabilitation and to identify requirements for successful implementation of emerging program models. A Delphi process involving experts from across the world identified 13 essential components of pulmonary rehabilitation that must be delivered in any program model, encompassing patient assessment, program content, method of delivery, and quality assurance, as well as 27 desirable components. Only those models of pulmonary rehabilitation that have been tested in clinical trials are currently considered as ready for implementation. The characteristics of patients most likely to succeed in each program model are not yet known, and research is needed in this area. Health professionals should use clinical judgment to determine those patients who are best served by a center-based, multidisciplinary rehabilitation program. A comprehensive patient assessment is critical for personalization of pulmonary rehabilitation and for effectively addressing individual patient goals. Robust quality-assurance processes are important to ensure that any pulmonary rehabilitation service delivers optimal outcomes for patients and health services. Workforce capacity-building and training should consider the skills necessary for emerging models, many of which are delivered remotely. The success of all pulmonary rehabilitation models will be judged on whether the essential components are delivered and on whether the expected patient outcomes, including improved exercise capacity, reduced dyspnea, enhanced health-related quality of life, and reduced hospital admissions, are achieved.
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http://dx.doi.org/10.1513/AnnalsATS.202102-146STDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086532PMC
May 2021

Mechanisms associated with increased physical activity in patients undergoing self-management behaviour modification in the randomised PHYSACTO trial.

ERJ Open Res 2021 Jan 29;7(1). Epub 2021 Mar 29.

University of Québec at Montréal/CIUSSS-NIM - Hôpital du Sacré-Coeur de Montréal, Montréal, Canada.

Introduction: In this analysis of the PHYSACTO® study, we assessed the efficacy of a self-management behaviour modification (SMBM) programme to improve physical activity (PA) levels, and the extent to which effects were mediated by readiness to change, motivation and confidence.

Methods: PHYSACTO® was a randomised, partially double-blind, parallel-group, 12-week trial to evaluate the effects of treatment on exercise capacity and PA. COPD patients received placebo, tiotropium 5 µg or tiotropium/olodaterol 5/5 µg, with or without exercise training, all with an SMBM intervention (the Living Well with COPD programme). Changes were assessed in readiness to change (stage of change visual analogue scale [VAS]), motivation (Treatment Self-Regulation Questionnaire [TSRQ]) and confidence (Perceived Competence Scale [PCS]) to engage in PA.

Results: PA was increased in all patients with complete PA data at Week 12 (n=262; +6038 steps·week, p<0.001). Significant increases were observed in patients' readiness to change (VAS 0.7 [0.6-0.8]), autonomous regulation (TRSQ 0.2 [0.1-0.3]) and confidence (PCS 0.5 [0.3-0.6]) (all p<0.01). Of note, 23% of the total effect of SMBM on steps·week was found to be mediated by increases in readiness to change, 5% by TSRQ autonomous regulation and 12% by PCS.

Conclusion: Our study demonstrated that an SMBM programme delivered to COPD patients increased PA, mediated by an improvement of three key hypothesised mechanisms of change: readiness to change, autonomous motivation and confidence. For the first time, this study shows that an SMBM programme can be successful in altering the mechanisms of change targeted by the intervention.
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http://dx.doi.org/10.1183/23120541.00533-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005679PMC
January 2021

Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments.

Thorax 2021 03 21;76(3):228-238. Epub 2021 Jan 21.

Department of Respiratory Diseases, University Hospital Leuven, Leuven, Belgium.

Background: The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation.

Objective: To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries.

Methods: We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID.

Results: We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score.

Conclusions: The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables.
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http://dx.doi.org/10.1136/thoraxjnl-2020-214554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892393PMC
March 2021

Interview with Prof. Dr Richard Casaburi, Presidential Awardee 2020.

Breathe (Sheff) 2020 Dec;16(4):200249

Rehabilitation Clinical Trials Center, Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, USA.

https://bit.ly/3j2aSdr.
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http://dx.doi.org/10.1183/20734735.0249-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792851PMC
December 2020

Muscle Strength and Physical Performance in Patients Without Previous Disabilities Recovering From COVID-19 Pneumonia.

Am J Phys Med Rehabil 2021 02;100(2):105-109

From the Respiratory Rehabilitation of the Institute of Lumezzane, Istituti Clinici Scientifici Maugeri IRCCS, Brescia, Italy (MP, CS, MS, LB, M. Vitacca); Department of Neurosciences, Biomedicine and Movement Sciences, Università di Verona, Verona, Italy (M. Venturelli); Department of Rehabilitation Sciences, University Hospitals Gasthuisberg, Leuven, Belgium (TT); Respiratory Division, KU Leuven, Leuven, Belgium (TT); and Respiratory Rehabilitation of the Institute of Montescano, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy (NA).

Abstract: In this cross-sectional study, we evaluated skeletal muscle strength and physical performance (1-min sit-to-stand and short physical performance battery tests), dyspnea, fatigue, and single-breath counting at discharge from a postacute COVID department, in patients recovering from COVID-19 pneumonia who had no locomotor disability before the infection.Quadriceps and biceps were weak in 86% and 73% of the patients, respectively. Maximal voluntary contraction for quadriceps was 18.9 (6.8) kg and for biceps 15.0 (5.5) kg (i.e., 54% and 69% of the predicted normal value, respectively). The number of chair rises in the 1-min sit-to-stand test was 22.1 (7.3 corresponding to 63% of the predicted normal value), whereas the short physical performance battery score was 7.9 (3.3 corresponding to 74% of the predicted normal value). At the end of the 1-min sit-to-stand test, 24% of the patients showed exercise-induced desaturation. The single-breath counting count was 35.4 (12.3) corresponding to 72% that of healthy controls. Mild-to-moderate dyspnea and fatigue were found during activities of daily living (Borg scale score, median value = 0.5 [0-2] and 1 [0-2]) and after the 1-min sit-to-stand (Borg scale score, median value = 3 [2-5] and 1 [0-3]). Significant correlations were observed between muscle strength and physical performance indices (R = 0.31-0.69).The high prevalence of impairment in skeletal muscle strength and physical performance in hospitalized patients recovering from COVID-19 pneumonia without previous locomotor disabilities suggests the need for rehabilitation programs after discharge.
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http://dx.doi.org/10.1097/PHM.0000000000001641DOI Listing
February 2021

Patterns of Physical Activity Progression in Patients With COPD.

Arch Bronconeumol (Engl Ed) 2021 Mar 8;57(3):214-223. Epub 2020 Oct 8.

ISGlobal, Barcelona, Spain; Pompeu Fabra University (UPF), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address:

Introduction: Although mean physical activity in COPD patients declines by 400-500steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants.

Methods: We pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns.

Results: In 291 COPD patients (mean±SD 68±8 years, 81% male, FEV 59±19%) we identified three distinct physical activity progression patterns: Inactive (n=173 [59%], baseline: 4621±1757 steps/day, 12-month change (Δ): -487±1201 steps/day), ActiveImprovers (n=49 [17%], baseline: 7727±3275 steps/day, Δ:+3378±2203 steps/day) and ActiveDecliners (n=69 [24%], baseline: 11 267±3009 steps/day, Δ: -2217±2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90-0.98] per 10m, P=.001) and a higher mMRC dyspnea score (1.71 [1.12-2.60] per 1 point, P=.012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver.

Conclusions: The natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline.
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http://dx.doi.org/10.1016/j.arbres.2020.08.001DOI Listing
March 2021

COVID-19: Interim Guidance on Rehabilitation in the Hospital and Post-Hospital Phase from a European Respiratory Society and American Thoracic Society-coordinated International Task Force.

Eur Respir J 2020 Aug 13. Epub 2020 Aug 13.

KU Leuven, Department of Rehabilitation Sciences, Leuven, Belgium.

Background: Patients with COVID-19 or post-COVID-19 will most probably have a need for rehabilitation during and directly after the hospitalisation. Data on safety and efficacy are lacking. Healthcare professionals cannot wait for published randomised controlled trials before they can start these rehabilitative interventions in daily clinical practice, as the number of post-COVID-19 patients increases rapidly. The Convergence of Opinion on Recommendations and Evidence process was used to make interim recommendation for the rehabilitation in the hospital and post-hospital phase in COVID-19 and post-COVID-19 patients, respectively.

Methods: 93 experts were asked to fill out 13 multiple choice questions. Agreement of directionality was tabulated for each question. At least 70% agreement on directionality was necessary to make consensus suggestions.

Results: 76 experts (82%) reached consensus on all questions based upon indirect evidence and clinical experience on the need for early rehabilitation during the hospital admission, the screening for treatable traits with rehabilitation in all patients at discharge and 6-8 weeks after discharge, and around the content of rehabilitation for these patients. It advocates for assessment of oxygen needs at discharge and more comprehensive assessment of rehabilitation needs including physical as well as mental aspects 6-8 weeks after discharge. Based on the deficits identified multidisciplinary rehabilitation should be offered with attention for skeletal muscle and functional as well as mental restoration.

Conclusions: This multinational task force recommends early, bedside rehabilitation for patients affected by severe COVID-19. The model of pulmonary rehabilitation may suit as a framework, particularly in a subset of patients with long term respiratory consequences.
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http://dx.doi.org/10.1183/13993003.02197-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427118PMC
August 2020

Fostering the integration of basic respiratory science and translational pulmonary medicine for the future.

Am J Physiol Lung Cell Mol Physiol 2020 09 5;319(3):L538-L540. Epub 2020 Aug 5.

Translational Experimental Pediatrics, Experimental Pulmonology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

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http://dx.doi.org/10.1152/ajplung.00361.2020DOI Listing
September 2020

Accuracy of consumer-based activity trackers as measuring tool and coaching device in patients with COPD and healthy controls.

PLoS One 2020 4;15(8):e0236676. Epub 2020 Aug 4.

Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium.

Background: Consumer-based activity trackers are used to measure and improve physical activity. However, the accuracy of these devices as clinical endpoint or coaching tool is unclear. We investigated the use of two activity trackers as measuring and coaching tool in patients with Chronic Obstructive Pulmonary Disease (COPD) and healthy age-matched controls.

Methods: Daily steps were measured by two consumer-based activity trackers (Fitbit Zip, worn at the hip and Fitbit Alta, worn at the wrist) and a validated activity monitor (Dynaport Movemonitor) in 28 patients with COPD and 14 healthy age-matched controls for 14 consecutive days. To investigate the accuracy of the activity trackers as a clinical endpoint, mean step count per patient were compared with the reference activity monitor and agreement was investigated by Bland-Altman plots. To evaluate the accuracy of activity trackers as coaching tool, day-by-day differences within patients were calculated for all three devices. Additionally, consistency of ranking daily steps between the activity trackers and accelerometer was investigated by Kendall correlation coefficient.

Results: As a measuring tool, the hip worn activity tracker significantly underestimates daily step count in patients with COPD as compared to DAM (mean±SD Δ-1112±872 steps/day; p<0.0001). This underestimation is less prominent in healthy subjects (p = 0.21). The wrist worn activity tracker showed a non-significant overestimation of step count (p = 0.13) in patients with COPD, and a significant overestimation of daily steps in healthy controls (mean±SD Δ+1907±2147 steps/day; p = 0.006). As a coaching tool, both hip and wrist worn activity tracker were able to pick up the day-by-day variability as measured by Dynaport (consistency of ranking resp. r = 0.80; r = 0.68 in COPD).

Conclusion: Although the accuracy of hip worn consumer-based activity trackers in patients with COPD and wrist worn activity trackers in healthy subjects as clinical endpoints is unsatisfactory, these devices are valid to use as a coaching tool.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236676PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402478PMC
October 2020

Walking-related digital mobility outcomes as clinical trial endpoint measures: protocol for a scoping review.

BMJ Open 2020 07 19;10(7):e038704. Epub 2020 Jul 19.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Introduction: Advances in wearable sensor technology now enable frequent, objective monitoring of real-world walking. Walking-related digital mobility outcomes (DMOs), such as real-world walking speed, have the potential to be more sensitive to mobility changes than traditional clinical assessments. However, it is not yet clear which DMOs are most suitable for formal validation. In this review, we will explore the evidence on discriminant ability, construct validity, prognostic value and responsiveness of walking-related DMOs in four disease areas: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease and proximal femoral fracture.

Methods And Analysis: Arksey and O'Malley's methodological framework for scoping reviews will guide study conduct. We will search seven databases (Medline, CINAHL, Scopus, Web of Science, EMBASE, IEEE Digital Library and Cochrane Library) and grey literature for studies which (1) measure differences in DMOs between healthy and pathological walking, (2) assess relationships between DMOs and traditional clinical measures, (3) assess the prognostic value of DMOs and (4) use DMOs as endpoints in interventional clinical trials. Two reviewers will screen each abstract and full-text manuscript according to predefined eligibility criteria. We will then chart extracted data, map the literature, perform a narrative synthesis and identify gaps.

Ethics And Dissemination: As this review is limited to publicly available materials, it does not require ethical approval. This work is part of Mobilise-D, an Innovative Medicines Initiative Joint Undertaking which aims to deliver, validate and obtain regulatory approval for DMOs. Results will be shared with the scientific community and general public in cooperation with the Mobilise-D communication team.

Registration: Study materials and updates will be made available through the Center for Open Science's OSFRegistry (https://osf.io/k7395).
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http://dx.doi.org/10.1136/bmjopen-2020-038704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371223PMC
July 2020

Expanding the spectrum of European Respiratory Society official scientific documents: short documents complement clinical practice guidelines, statements and technical standards.

Eur Respir J 2020 06 4;55(6). Epub 2020 Jun 4.

Institute for Lung Health, NIHR Leicester Biomedical Research Centre, Dept of Respiratory Sciences, University of Leicester, Leicester, UK.

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http://dx.doi.org/10.1183/13993003.01030-2020DOI Listing
June 2020

Effects of downhill walking in pulmonary rehabilitation for patients with COPD: a randomised controlled trial.

Eur Respir J 2020 09 17;56(3). Epub 2020 Sep 17.

Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium

The development of contractile muscle fatigue (CMF) affects training responses in patients with chronic obstructive pulmonary disease (COPD). Downhill walking induces CMF with lower dyspnoea and fatigue than level walking. This study compared the effect of pulmonary rehabilitation (PR) comprising downhill walking training (DT) to PR comprising level walking (conventional training (CT)) in patients with COPD.In this randomised controlled trial, 35 patients (62±8 years; forced expiratory volume in 1 s (FEV) 50±17% predicted) were randomised to DT or CT. Exercise tolerance (6-minute walk test distance (6MWD); primary outcome), muscle function, symptoms, quality-of-life and physical activity levels were assessed before and after PR. Absolute training changes and the proportion of patients exceeding the 30 m 6MWD minimally important difference (MID) were compared between groups. Quadriceps muscle biopsies were collected after PR in a subset of patients to examine physiological responses to long-term eccentric training.No between-group differences were observed in absolute 6MWD improvement (mean 6MWD change 77±46 m DT 56±47 m CT; p=0.45), however 94% of patients in DT exceeded the 6MWD MID compared to 65% in CT (p=0.03). Patients in DT tended to have larger improvements than CT in other outcomes. Muscle biopsy analyses did not differ between groups.PR incorporating downhill walking confers similar magnitudes of effects to PR with conventional walking across clinical outcomes in patients with COPD, however, offers a more reliable stimulus to maximise the achievement of clinically relevant gains in functional exercise tolerance in people with COPD.
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http://dx.doi.org/10.1183/13993003.00639-2020DOI Listing
September 2020

Brain Activations to Dyspnea in Patients With COPD.

Front Physiol 2020 24;11. Epub 2020 Jan 24.

Health Psychology, KU Leuven, Leuven, Belgium.

We compared the perception and neural processing of respiratory sensations between 20 COPD patients and 20 healthy controls by means of respiratory-related evoked potentials (RREP) in the electroencephalogram (EEG). RREPs were induced by short inspiratory occlusions while 129-channel EEG was measured. COPD patients rated the occlusions as more intense and unpleasant ('s < 0.001) and showed higher mean amplitudes for the RREP components P1 ( = 0.0004), N1 ( = 0.024), P2 ( = 0.019), and P3 ( = 0.018). Our results indicate that COPD patients demonstrate greater perception and neural processing of respiratory sensations, which presumably reflects the highly aversive and attention-demanding character of these sensations for COPD patients.
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http://dx.doi.org/10.3389/fphys.2020.00007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992658PMC
January 2020

Two Weeks of Smoking Cessation Reverse Cigarette Smoke-Induced Skeletal Muscle Atrophy and Mitochondrial Dysfunction in Mice.

Nicotine Tob Res 2021 01;23(1):143-151

Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU-Leuven, Leuven, Belgium.

Introduction: Apart from its adverse effects on the respiratory system, cigarette smoking also induces skeletal muscle atrophy and dysfunction. Whether short-term smoking cessation can restore muscle mass and function is unknown. We, therefore, studied the impact of 1- and 2-week smoking cessation on skeletal muscles in a mouse model.

Methods: Male mice were divided into four groups: Air-exposed (14 weeks); cigarette smoke (CS)-exposed (14 weeks); CS-exposed (13 weeks) followed by 1-week cessation; CS-exposed (12 weeks) followed by 2 weeks cessation to examine exercise capacity, physical activity levels, body composition, muscle function, capillarization, mitochondrial function and protein expression in the soleus, plantaris, and diaphragm muscles.

Results: CS-induced loss of body and muscle mass was significantly improved within 1 week of cessation due to increased lean and fat mass. Mitochondrial respiration and protein levels of the respiratory complexes in the soleus were lower in CS-exposed mice, but similar to control values after 2 weeks of cessation. Exposing isolated soleus muscles to CS extracts reduced mitochondrial respiration that was reversed after removing the extract. While physical activity was reduced in all groups, exercise capacity, limb muscle force, fatigue resistance, fiber size and capillarization, and diaphragm cytoplasmic HIF-1α were unaltered by CS-exposure. However, CS-induced diaphragm atrophy and increased capillary density were not seen after 2 weeks of smoking cessation.

Conclusion: In male mice, 2 weeks of smoking cessation reversed smoking-induced mitochondrial dysfunction, limb muscle mass loss, and diaphragm muscle atrophy, highlighting immediate benefits of cessation on skeletal muscles.

Implications: Our study demonstrates that CS-induced skeletal muscle mitochondrial dysfunction and atrophy are significantly improved by 2 weeks of cessation in male mice. We show for the first time that smoking cessation as short as 1 to 2 weeks is associated with immediate beneficial effects on skeletal muscle structure and function with the diaphragm being particularly sensitive to CS-exposure and cessation. This could help motivate smokers to quit smoking as early as possible. The knowledge that smoking cessation has potential positive extrapulmonary effects is particularly relevant for patients referred to rehabilitation programs and those admitted to hospitals suffering from acute or chronic muscle deterioration yet struggling with smoking cessation.
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http://dx.doi.org/10.1093/ntr/ntaa016DOI Listing
January 2021

ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases.

Eur Respir Rev 2019 Dec 18;28(154). Epub 2019 Dec 18.

Paediatric Dept, University Hospital Würzburg, Würzburg, Germany

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.
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http://dx.doi.org/10.1183/16000617.0101-2018DOI Listing
December 2019

Behavioural interventions targeting physical activity improve psychocognitive outcomes in COPD.

ERJ Open Res 2019 Oct 4;5(4). Epub 2019 Nov 4.

Respiratory Epidemiology Clinical Research Unit, Research Institute of the McGill University Health Centre, Montreal, Canada.

This study explored the impact of a self-management behaviour modification (SMBM) programme with/without bronchodilators and with/without exercise training (ExT) to improve daily physical activity on psychological and cognitive outcomes in COPD patients as a secondary analysis of the PHYSACTO trial. A 12-week, four-group, randomised, partially double-blind, placebo-controlled, parallel-group trial of SMBM in addition to tiotropium 5 µg, tiotropium/olodaterol 5/5 µg, tiotropium/olodaterol 5/5 µg plus ExT, or placebo was conducted in 304 patients. Outcomes included anxiety (Hospital Anxiety and Depression Scale (HADS)-A), depression (HADS-D and Patient-Health Questionnaire (PHQ)-9) and cognitive function (Montreal Cognitive Assessment (MoCA)). All outcomes showed statistically and clinically significant improvements after 12 weeks independent of treatment group. However, greater improvements in HADS-A and MoCA were seen in patients who exhibited greater increases in physical activity and exercise capacity, respectively, whereas greater improvements in HADS-D and PHQ-9 were seen in patients who exhibited increases in either physical activity or exercise capacity. The results indicate that SMBM with/without bronchodilators or ExT was associated with improved psychological and cognitive functioning. Anxiety reduced with increased physical activity, cognitive function improved with increased exercise capacity, and depression reduced with increases in either physical activity or exercise capacity. Interventions that increase daily physical activity or exercise capacity may improve psychological and cognitive outcomes in COPD.
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http://dx.doi.org/10.1183/23120541.00013-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826247PMC
October 2019

Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - a post-hoc analysis of the BACE randomized controlled trial.

Respir Res 2019 Oct 29;20(1):237. Epub 2019 Oct 29.

Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Herestraat 49, O&NI, box 706, B-3000, Leuven, Belgium.

Background: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality.

Objectives: (1) To investigate the intervention's effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions.

Methods: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time.

Results: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses.

Conclusions: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy.

Trial Registration: ClinicalTrials.gov number. NCT02135354 .
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http://dx.doi.org/10.1186/s12931-019-1208-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819655PMC
October 2019

ERS Presidential Summit 2018: multimorbidities and the ageing population.

ERJ Open Res 2019 Jul 25;5(3). Epub 2019 Sep 25.

Coimbra University Hospital, Coimbra, Portugal.

As the average age of the population increases, so will the prevalence of chronic respiratory diseases and associated multimorbidity. This will result in a more complex clinical environment. Part of the solution will be to allow patients to be co-creators in the design of their care. It will also require clinicians to shift in their current approaches to care, step out of the disease- or pathology-oriented approach and embrace new ideas. In an effort to prepare the respiratory community for the challenge, we reflect on concepts to empower patients multidisciplinary systems, new technologies and transition from end-of-life care to advanced care planning.
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http://dx.doi.org/10.1183/23120541.00126-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759575PMC
July 2019

Progression of physical inactivity in COPD patients: the effect of time and climate conditions - a multicenter prospective cohort study.

Int J Chron Obstruct Pulmon Dis 2019 3;14:1979-1992. Epub 2019 Sep 3.

National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College, London, UK.

Purpose: Longitudinal data on the effect of time and environmental conditions on physical activity (PA) among COPD patients are currently scarce, but this is an important factor in the design of trials to test interventions that might impact on it. Thus, we aimed to assess the effect of time and climate conditions (temperature, day length and rainfall) on progression of PA in a cohort of COPD patients.

Patients And Methods: This is a prospective, multicenter, cohort study undertaken as part of the EU/IMI PROactive project, in which we assessed 236 COPD patients simultaneously wearing two activity monitors (Dynaport MiniMod and Actigraph GT3X). A multivariable generalized linear model analysis was conducted to describe the effect of the explanatory variables on PA measures, over three time points (baseline, 6 and 12 months).

Results: At 12 months (n=157; FEV% predicted=57.7±21.9) there was a significant reduction in all PA measures (Actigraph step count (4284±3533 vs 3533±293)), Actigraph moderate- to vigorous-intensity PA ratio (8.8 (18.8) vs 6.1 (15.7)), Actigraph vector magnitude units (374,902.4 (265,269) vs 336,240 (214,432)), MiniMod walking time (59.1 (34.9) vs 56.9 (38.7) mins) and MiniMod PA intensity (0.183 (0) vs 0.181 (0)). Time had a significant, negative effect on most PA measures in multivariable analysis, after correcting for climate factors, study center, age, FEV% predicted, 6MWD and other disease severity measures. Rainfall was the only climate factor with a negative effect on most PA parameters.

Conclusion: COPD patients demonstrate a significant decrease in PA over 1 year follow-up, which is further affected by hours of rainfall, but not by other climate considerations.
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http://dx.doi.org/10.2147/COPD.S208826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732558PMC
March 2020

Early-onset airway damage in early-career elite athletes: A risk factor for exercise-induced bronchoconstriction.

J Allergy Clin Immunol 2019 11 26;144(5):1423-1425.e9. Epub 2019 Jul 26.

KU Leuven, Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, Leuven, Belgium; UZ Leuven, Clinical Division of Paediatrics, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2019.07.014DOI Listing
November 2019

Introduction of the harmonised respiratory physiotherapy curriculum.

Breathe (Sheff) 2019 Jun;15(2):110-115

Dept of Physiotherapy, Laboratory of Research in Respiratory Physiotherapy (LFIP), State University of Londrina (UEL), Londrina, Brazil.

Building on the core syllabus for postgraduate training in respiratory physiotherapy, published in 2014, the European Respiratory Society (ERS) respiratory physiotherapy task force has developed a harmonised and structured postgraduate curriculum for respiratory physiotherapy training. The curriculum outlines the knowledge, skills and attitudes which must be mastered by a respiratory physiotherapist working with adult or paediatric patients, together with guidance for minimal clinical exposures, and forms of learning and assessment. This article presents the rationale, methodology and content of the ERS respiratory physiotherapy curriculum. The full curriculum can be found in the supplementary material.
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http://dx.doi.org/10.1183/20734735.0124-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544793PMC
June 2019

A guide for respiratory physiotherapy postgraduate education: presentation of the harmonised curriculum.

Eur Respir J 2019 Jun 5;53(6). Epub 2019 Jun 5.

Dept of Physiotherapy, Laboratory of Research in Respiratory Physiotherapy (LFIP) State University of Londrina (UEL), Londrina, Brazil.

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http://dx.doi.org/10.1183/13993003.00320-2019DOI Listing
June 2019

Health status deterioration in subjects with mild to moderate airflow obstruction, a six years observational study.

Respir Res 2019 May 18;20(1):93. Epub 2019 May 18.

Department of Rehabilitation Sciences, KU Leuven - University of Leuven, Leuven, Belgium.

Background: Patients with COPD need to cope with a disabling disease, which leads to health status impairment.

Aim: To investigate the long term change of health status in subjects with mild to moderate airflow obstruction and to compare this to subjects without airflow obstruction, with and without a smoking history. Second, to investigate the factors potentially associated to rapid health status decline in our total cohort.

Methods: Two hundred and one subjects were included. Generic [Short form 36 health survey (SF36) and EuroQol - 5 dimensions (EQ-5D)] and disease specific [Clinical COPD questionnaire (CCQ) and COPD Assessment Test (CAT)] health status questionnaires were regularly repeated over a six years period. Other functional outcomes comprised measures of lung function, physical fitness, physical activity and emotional state.

Results: On average, health status decline did not differ between groups with the exception of the EQ-5D index, which deteriorated faster in subjects with airflow obstruction compared to the never smoking control group [- 0.018(0.008) versus 0.00006(0.003), p = 0.03]. Subjects presenting at least one exacerbation had faster rate of deterioration measured with CAT [0.91(0.21) versus - 0.26(0.25), p < 0.01]. Characteristics of the fast declining group were older age, worse lung function, physical fitness, physical activity and disease specific baseline health status. Subjects with airflow obstruction had a 2.5 (95% CI 1.36-4.71) higher risk of presenting fast overall health status decline. Fast overall decline was associated with the presence of acute exacerbation(s) (44% of the subjects with exacerbation(s) versus 17% of subjects without exacerbation, p = 0.03). Changes in fat free mass, functional exercise capacity and in symptoms of anxiety and depression correlated weakly to changes in health status measured with all questionnaires.

Conclusion: Subjects with mild airflow obstruction present a significant deterioration of health status, which is generally not much faster compared to smoking and never smoking controls. Subjects with fast decline in overall health status are older and more likely to have airflow obstruction, acute respiratory exacerbation(s), reduced physical fitness, physical activity and impaired COPD specific health status at baseline.

Trial Registration: NCT01314807 - retrospectively registered on March 2011.
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http://dx.doi.org/10.1186/s12931-019-1061-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525445PMC
May 2019

Strategies to Increase Physical Activity in Chronic Respiratory Diseases.

Clin Chest Med 2019 06;40(2):397-404

Department of Rehabilitation Sciences, Laboratory of Pneumology, University Hospitals Leuven, KU Leuven-University of Leuven, Herestraat 49, Onderwijs en Navorsing 1, PO Box 706, Leuven 3000, Belgium; Respiratory Division, University Hospitals Leuven, Leuven, Belgium.

Physical activity is important to maintain health. Patients who reduce their physical activity are at increased risk of developing comorbidities and faster decline in health. Interventions to enhance physical activity require a behavior change from patients and these interventions have become increasingly popular in chronic obstructive pulmonary disease. However, few interventions have shown long-term effects and all focused on enhancing physical activity rather than the maintenance thereof. In patients with very low exercise tolerance or with significant symptom burden, enhancing physical activity be difficult and interventions should first focus on enhancing exercise tolerance.
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http://dx.doi.org/10.1016/j.ccm.2019.02.017DOI Listing
June 2019
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