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Short Physical Performance Battery: Response to Pulmonary Rehabilitation and Minimal Important Difference Estimates in Patients With Chronic Obstructive Pulmonary Disease

  • Author Footnotes
    ⁎ Stoffels and De Brandt contributed equally to this work.
    Anouk A. Stoffels
    Correspondence
    Corresponding author Anouk A. Stoffels, MSc, Department Pulmonary Diseases, Dekkerswald Radboud University Medical Center, Radboud Institute for Health Sciences, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands.
    Footnotes
    ⁎ Stoffels and De Brandt contributed equally to this work.
    Affiliations
    Department of Pulmonary Diseases, Dekkerswald Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, the Netherlands

    Department of Research and Development, CIRO, Horn, the Netherlands

    Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, The Netherlands
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  • Author Footnotes
    ⁎ Stoffels and De Brandt contributed equally to this work.
    Jana De Brandt
    Footnotes
    ⁎ Stoffels and De Brandt contributed equally to this work.
    Affiliations
    REVAL–Rehabilitation Research Center, BIOMED–Biomedical Research Institute, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium
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  • Roy Meys
    Affiliations
    Department of Research and Development, CIRO, Horn, the Netherlands

    Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, The Netherlands
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  • Hieronymus W. van Hees
    Affiliations
    Department of Pulmonary Diseases, Dekkerswald Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
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  • Anouk W. Vaes
    Affiliations
    Department of Research and Development, CIRO, Horn, the Netherlands
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  • Peter Klijn
    Affiliations
    Department of Pulmonology, Merem Pulmonary Rehabilitation Centre, Hilversum, the Netherlands

    Department of Pulmonary, Amsterdam University Medical Centre, Amsterdam, the Netherlands
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  • Chris Burtin
    Affiliations
    REVAL–Rehabilitation Research Center, BIOMED–Biomedical Research Institute, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium
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  • Frits M. Franssen
    Affiliations
    Department of Research and Development, CIRO, Horn, the Netherlands

    Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, The Netherlands
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  • Bram van den Borst
    Affiliations
    Department of Pulmonary Diseases, Dekkerswald Radboud University Medical Centre, Radboud Institute for Health Sciences, Nijmegen, the Netherlands
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  • Maurice J. Sillen
    Affiliations
    Department of Research and Development, CIRO, Horn, the Netherlands
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  • Daisy J. Janssen
    Affiliations
    Department of Research and Development, CIRO, Horn, the Netherlands

    Department of Health Services Research, Care and Public Health Research Institute, Faculty of Health Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
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  • Martijn A. Spruit
    Affiliations
    Department of Research and Development, CIRO, Horn, the Netherlands

    Department of Respiratory Medicine, Maastricht University Medical Centre (MUMC+), NUTRIM School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, The Netherlands

    REVAL–Rehabilitation Research Center, BIOMED–Biomedical Research Institute, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium
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  • on behalf of theBASES Consortium
  • Author Footnotes
    ⁎ Stoffels and De Brandt contributed equally to this work.
Open AccessPublished:June 24, 2021DOI:https://doi.org/10.1016/j.apmr.2021.05.011

      Abstract

      Objective

      To determine the response to a pulmonary rehabilitation (PR) program and minimal important differences (MIDs) for the Short Physical Performance Battery (SPPB) subtests and SPPB summary score in patients with chronic obstructive pulmonary disease (COPD).

      Design

      Retrospective analysis using distribution- and anchor-based methods.

      Setting

      PR center in the Netherlands including a comprehensive 40-session 8-week inpatient or 14-week outpatient program.

      Participants

      A total of 632 patients with COPD (age, 65±8y; 50% male; forced expiratory volume in the first second=43% [interquartile range, 30%-60%] predicted).

      Interventions

      Not applicable.

      Main Outcome Measure

      Baseline and post-PR results of the SPPB, consisting of 3 balance standing tests, 4-meter gait speed (4MGS), and 5-repetition sit-to-stand (5STS). The chosen anchors were the 6-Minute Walk Test and COPD Assessment Test. Patients were stratified according to their SPPB summary scores into low-performance, moderate-performance, and high-performance groups.

      Results

      5STS (∆=−1.14 [−4.20 to −0.93]s) and SPPB summary score (∆=1 [0-2] points) improved after PR in patients with COPD. In patients with a low performance at baseline, balance tandem and 4MGS significantly increased as well. Based on distribution-based calculations, the MID estimates ranged between 2.19 and 6.33 seconds for 5STS and 0.83 to 0.96 points for SPPB summary score.

      Conclusions

      The 5STS and SPPB summary score are both responsive to PR in patients with COPD. The balance tandem test and 4MGS are only responsive to PR in patients with COPD with a low performance at baseline. Based on distribution-based calculations, an MID estimate of 1 point for the SPPB summary score is recommended in patients with COPD. Future research is needed to confirm MID estimates for SPPB in different centers.

      Keywords

      List of abbreviations:

      4MGS (4-meter gait speed), 5STS (5-repetition sit-to-stand), 6MWT (6-Minute Walk Test), CAT (COPD Assessment Test), COPD (chronic obstructive pulmonary disease), FFM (fat-free mass), GOLD (Global Initiative for Chronic Obstructive Lung Disease), HP (high-performance), ICC (intraclass correlation coefficient), LP (low-performance), MID (minimal important difference), MP (moderate-performance), PR (pulmonary rehabilitation), SPPB (Short Physical Performance Battery)
      The Short Physical Performance Battery (SPPB) is an easy-to-perform measure for assessment of mobility and balance and its use is intended and recommended for older persons (>65y).
      European Medicines Agency
      Reflection paper on physical frailty: instruments for baseline characterisation of older populations in clinical trials.
      However, there is an increasing interest in SPPB performance for diseased populations, including individuals with chronic obstructive pulmonary disease (COPD). COPD is defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as “a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities caused by significant exposure to noxious particles or gases.”

      GOLD. 2021 Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at https://goldcopd.org/2021-gold-reports/. Accessed March 4, 2021

      Patients with COPD have an increased risk of mortality and readmission and exhibit poorer physical function and health status,
      • Brighton LJ
      • Bristowe K
      • Bayly J
      • et al.
      Experiences of pulmonary rehabilitation in people living with chronic obstructive pulmonary disease and frailty. A qualitative interview study.
      which emphasizes the clinical relevance of SPPB performance.
      The SPPB summary score has a good interobserver reliability
      • Medina-Mirapeix F
      • Bernabeu-Mora R
      • Llamazares-Herran E
      • Sanchez-Martinez MP
      • Garcia-Vidal JA
      • Escolar-Reina P
      Interobserver reliability of peripheral muscle strength tests and Short Physical Performance Battery in patients with chronic obstructive pulmonary disease: a prospective observational study.
      and has been used to classify patients as having low, moderate, or high performance in mobility and balance.
      • Stoffels AAF
      • De Brandt J
      • Meys R
      • et al.
      Phenotypic characteristics of patients with chronic obstructive pulmonary disease after stratification for the Short Physical Performance Battery summary score.
      • Bernabeu-Mora R
      • Gimenez-Gimenez LM
      • Montilla-Herrador J
      • Garcia-Guillamon G
      • Garcia-Vidal JA
      • Medina-Mirapeix F
      Determinants of each domain of the Short Physical Performance Battery in COPD.
      • Patel MS
      • Mohan D
      • Andersson YM
      • et al.
      Phenotypic characteristics associated with reduced Short Physical Performance Battery score in COPD.
      Furthermore, its potential as an alternative to the 6-Minute Walk Test (6MWT) in the BODE index has recently been reported
      • Fermont JM
      • Mohan D
      • Fisk M
      • et al.
      Short Physical Performance Battery as a practical tool to assess mortality risk in chronic obstructive pulmonary disease.
      and physical and emotional correlates of the SPPB summary score have been identified.
      • Stoffels AAF
      • De Brandt J
      • Meys R
      • et al.
      Phenotypic characteristics of patients with chronic obstructive pulmonary disease after stratification for the Short Physical Performance Battery summary score.
      ,
      • Patel MS
      • Mohan D
      • Andersson YM
      • et al.
      Phenotypic characteristics associated with reduced Short Physical Performance Battery score in COPD.
      The latter might suggest a positive effect of pulmonary rehabilitation (PR) on the SPPB summary score. To date, the response of the SPPB summary score to PR has only been described in 1 peer-reviewed manuscript
      • Larsson P
      • Borge CR
      • Nygren-Bonnier M
      • Lerdal A
      • Edvardsen A
      An evaluation of the Short Physical Performance Battery following pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.
      and 2 congress abstracts,
      • Carrington D
      • Jones S
      • Canavan J
      • et al.
      Responsiveness of the Short Physical Performance Battery (SPPB) in severely dyspnoeic patients with COPD.
      ,
      • Patel MS
      • Clark AL
      • Ingram KA
      • et al.
      S74 Effect of pulmonary rehabilitation on the Short Physical Performance Battery (SPPB) in COPD.
      which all reported a significant increase.
      Estimated minimal important differences (MIDs) are available for the SPPB subtests 4-meter gait speed (4MGS)
      • Kon SS
      • Canavan JL
      • Nolan CM
      • et al.
      The 4-metre gait speed in COPD: responsiveness and minimal clinically important difference.
      and 5-repetition sit-to-stand (5STS) in patients with COPD
      • Jones SE
      • Kon SS
      • Canavan JL
      • et al.
      The five-repetition sit-to-stand test as a functional outcome measure in COPD.
      but are currently lacking for the SPPB summary score. This complicates the evaluation of intervention efficacy using the SPPB.
      • Mouelhi Y
      • Jouve E
      • Castelli C
      • Gentile S
      How is the minimal clinically important difference established in health-related quality of life instruments? Review of anchors and methods.
      ,
      • Woaye-Hune P
      • Hardouin JB
      • Lehur PA
      • Meurette G
      • Vanier A
      Practical issues encountered while determining minimal clinically important difference in patient-reported outcomes.
      Thus, to improve the interpretation of intervention efficacy at individual and group levels, the aims of the present study were to determine the response to a PR program on the SPPB subtests and summary score in patients with COPD and to estimate MIDs for the SPPB subtests and summary score in patients with COPD.

      Methods

      In this observational study, a retrospective analysis was performed on baseline and post-PR data of 953 patients between January 2016 and January 2018 in CIRO, a specialized PR center in the Netherlands.
      • Spruit MA
      • Vanderhoven-Augustin I
      • Janssen PP
      • Wouters EF
      Integration of pulmonary rehabilitation in COPD.
      This study was performed in accordance with the principles of the Declaration of Helsinki and was approved by the board of directors. The authors were informed by the Medical Ethics Committee of Maastricht University that the Medical Research Involving Human Subjects Act does not apply and no official approval was required (MEC no. 2018-0541). Therefore, no informed consent from participants was obtained.
      The following inclusion criteria were applied: primary diagnosis of COPD according to the GOLD criteria

      GOLD. 2021 Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at https://goldcopd.org/2021-gold-reports/. Accessed March 4, 2021

      and complete SPPB data (baseline and post-PR) available. Participants younger than 40 years old, participation in the PR program more than once, or a baseline SPPB summary score of 12, because of a possible ceiling effect,
      • Larsson P
      • Borge CR
      • Nygren-Bonnier M
      • Lerdal A
      • Edvardsen A
      An evaluation of the Short Physical Performance Battery following pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.
      were excluded from further analyses. Baseline findings have been published previously.
      • Stoffels AAF
      • De Brandt J
      • Meys R
      • et al.
      Phenotypic characteristics of patients with chronic obstructive pulmonary disease after stratification for the Short Physical Performance Battery summary score.

      Patients’ characteristics

      Baseline characteristics including age, sex, weight, body mass index, exacerbation and hospitalization frequency in the last 12 months, Charlson Comorbidity Index, and use of long-term oxygen therapy were systematically collected during an extensive PR assessment. Furthermore, forced expiratory volume in 1 second and its ratio to forced vital capacity were assessed in accordance with the European Respiratory Society recommendations
      • Quanjer PH
      • Tammeling GJ
      • Cotes JE
      • Pedersen OF
      • Peslin R
      • Yernault JC
      Lung volumes and forced ventilatory flows. report working party standardization of lung function tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society.
      using spirometry (MasterScreen PFT/Bodya). The degree of airflow limitation was classified according to GOLD classification.

      GOLD. 2021 Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at https://goldcopd.org/2021-gold-reports/. Accessed March 4, 2021

      Short Physical Performance Battery

      Baseline and post-PR performance of the SPPB was in accordance with the National Institute on Aging protocol.
      • Guralnik JM
      • Simonsick EM
      • Ferrucci L
      • et al.
      A Short Physical Performance Battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      The SPPB includes 3 subtests: the standing balance test, 4MGS, and 5STS. During the standing balance test the patient was instructed to maintain 3 stances (feet placed side by side, semi-tandem, tandem) for 10 seconds. Secondly, the 4MGS was performed in duplicate to obtain the habitual gait speed over 4 m (normal walking aids were allowed). In the 5STS, the patient was required to perform 5 sit-to-stand maneuvers as fast as possible with arms folded in front of their chest. Each of the 3 components was scored from 0 (extreme mobility impairment) to 4 points (no mobility impairment), resulting in a SPPB summary score ranging from 0-12 points (table E1, available online only at http://www.archives-pmr.org/). A flowchart of the SPPB subtests and its scoring system was previously reported by Nogueira et al.
      • Nogueira A
      • Alvarez G
      • Russo F
      • San-Jose B
      • Sanchez-Tomero JA
      • Barril G
      Is SPPB useful as a screening method of functional capacity in patients with advanced chronic kidney disease?.
      According to their baseline SPPB summary score, patients were classified as low performance (LP; 0-6 points), moderate performance (MP; 7-9 points), or high performance (HP; 10-12 points).
      • Guralnik JM
      • Ferrucci L
      • Simonsick EM
      • Salive ME
      • Wallace RB
      Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability.

      Clinical outcomes

      Fat-free mass (FFM) was measured using dual-energy x-ray absorptiometry (Lunar iDXAb).
      • Coin A
      • Sergi G
      • Minicuci N
      • et al.
      Fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20-80 year-old Italian population.
      The FFM index was calculated by dividing FFM by height squared. The modified Medical Research Council dyspnoea scale
      • Bestall JC
      • Paul EA
      • Garrod R
      • Garnham R
      • Jones PW
      • Wedzicha JA
      Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease.
      was used to evaluate shortness of breath and a cutoff of ≥2 was used to identify patients with “more breathlessness.”
      • Lopez-Campos JL
      • Soler-Cataluna JJ
      • Miravitlles M
      Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2019 report: future challenges.
      The COPD Assessment Test (CAT) assessed the health status of the patients and a threshold of ≥18 points indicated patients who were highly symptomatic.
      • Smid DE
      • Franssen FME
      • Gonik M
      • et al.
      Redefining cut-points for high symptom burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 patients with chronic obstructive pulmonary disease.
      The 6MWT and incremental cardiopulmonary exercise test (Ergoselectc) were performed to determine physical capacity, both in accordance with the corresponding guidelines.
      • Holland AE
      • Spruit MA
      • Troosters T
      • et al.
      An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease.
      • Hernandes NA
      • Wouters EF
      • Meijer K
      • Annegarn J
      • Pitta F
      • Spruit MA
      Reproducibility of 6-minute walking test in patients with COPD.
      • Radtke T
      • Crook S
      • Kaltsakas G
      • et al.
      ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases.
      Exercise tolerance was assessed with the constant work rate test, performed at 75% of the predetermined maximal workload, during which patients cycled until symptom limitation (with a maximum test duration of 20 min).
      • van't Hul A
      • Gosselink R
      • Kwakkel G
      Constant-load cycle endurance performance: test-retest reliability and validity in patients with COPD.
      Isokinetic quadriceps peak torque and total work of the right leg (or left leg in case of complications with the right leg) were assessed with a computerized dynamometer (Biodex Multi-joint System 3d). Patients performed a set of 30 repetitions at an angular speed of 90°/s. Reference values from Borges were used.
      • Borges O
      Isometric and isokinetic knee extension and flexion torque in men and women aged 20-70.
      Symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale with a cutoff value of ≥10 points for each domain
      • Zigmond AS
      • Snaith RP
      The hospital anxiety and depression scale.
      to classify patients with indications for anxiety or depression.

      Pulmonary rehabilitation

      The 8-week inpatient and 14-week outpatient PR programs were in line with the American Thoracic Society/European Respiratory Society Statement on PR
      • Spruit MA
      • Singh SJ
      • Garvey C
      • et al.
      An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation.
      and consisted of 40 sessions. Patients were supervised by an interdisciplinary team, including a chest physician, respiratory nurse, dietician, occupational therapist, physiotherapist, psychologist, and social worker. The cornerstone of the patient-tailored PR program was physical exercise training consisting mainly of exercises to strengthen muscles of the upper and lower extremities, treadmill walking, stationary cycling, flexibility exercises, and daily supervised outdoor walks.
      • Liu WY
      • Meijer K
      • Delbressine JM
      • Willems PJ
      • Wouters EF
      • Spruit MA
      Effects of pulmonary rehabilitation on gait characteristics in patients with COPD.
      Furthermore, the program included (if indicated) nutritional support, psychological counseling, and educational sessions.
      • Liu WY
      • Meijer K
      • Delbressine JM
      • Willems PJ
      • Wouters EF
      • Spruit MA
      Effects of pulmonary rehabilitation on gait characteristics in patients with COPD.
      • Stoilkova A
      • Janssen DJ
      • Franssen FM
      • Spruit MA
      • Wouters EF
      Coping styles in patients with COPD before and after pulmonary rehabilitation.
      • Spruit MA
      • Augustin IM
      • Vanfleteren LE
      • et al.
      Differential response to pulmonary rehabilitation in COPD: multidimensional profiling.
      Further description of the PR program was provided by Spruit et al.
      • Spruit MA
      • Augustin IM
      • Vanfleteren LE
      • et al.
      Differential response to pulmonary rehabilitation in COPD: multidimensional profiling.

      Statistical analyses

      Statistical analyses were performed using SPSS statistical softwaree, v25.0. Data were presented and/or tested as appropriate. Descriptive data are presented as means ± SD, medians (interquartile 1-interquartile 3), or percentages. Baseline and delta differences between 2 groups were tested by independent t test or Mann-Whitney U test. Categorical data were tested with Fisher exact test or chi-square test of homogeneity. Differences between baseline and post-PR data were tested by paired sample t test or Wilcoxon signed-rank test, and categorical data were tested with McNemar's test or related samples marginal homogeneity test. Differences in deltas between 3 groups were tested by 1-way analysis of variance, Kruskal-Wallis test, or chi-square test of homogeneity. When a statistically significant difference was obtained, pairwise Tukey's post hoc test was performed and Bonferroni correction was applied for multiple comparisons. Because of the many statistical tests performed in this study, P≤.01 was considered significant.
      As recommended,
      • Mouelhi Y
      • Jouve E
      • Castelli C
      • Gentile S
      How is the minimal clinically important difference established in health-related quality of life instruments? Review of anchors and methods.
      ,
      • Woaye-Hune P
      • Hardouin JB
      • Lehur PA
      • Meurette G
      • Vanier A
      Practical issues encountered while determining minimal clinically important difference in patient-reported outcomes.
      both distribution-based and anchor-based techniques were used to determine MID estimates for the SPPB subtests and summary score. Four distribution-based techniques were applied: SEM=SDbaseline*1intraclasscorrelationcoefficient; empirical rule effect size=0.08*6*SDdelta; Cohen's effect size=0.5*SDdelta; 0.5*SDbaseline.
      • Demeyer H
      • Burtin C
      • Hornikx M
      • et al.
      The minimal important difference in physical activity in patients with COPD.
      The intraclass correlation coefficients (ICCs) were derived from previous studies (interobserver ICCSPPB=0.81
      • Medina-Mirapeix F
      • Bernabeu-Mora R
      • Llamazares-Herran E
      • Sanchez-Martinez MP
      • Garcia-Vidal JA
      • Escolar-Reina P
      Interobserver reliability of peripheral muscle strength tests and Short Physical Performance Battery in patients with chronic obstructive pulmonary disease: a prospective observational study.
      and test-retest ICC4MGS=0.97
      • Kon SS
      • Canavan JL
      • Nolan CM
      • et al.
      The 4-metre gait speed in COPD: responsiveness and minimal clinically important difference.
      and ICC5STS=0.97
      • Jones SE
      • Kon SS
      • Canavan JL
      • et al.
      The five-repetition sit-to-stand test as a functional outcome measure in COPD.
      ). The SEM method could not be performed for the standing balance tests because no ICCs have been determined in patients with COPD or in older persons.
      To perform anchor-based methods, at least a moderate correlation between the anchors and change in SPPB subtests or summary score (r≥0.3, P<.05)
      • Mouelhi Y
      • Jouve E
      • Castelli C
      • Gentile S
      How is the minimal clinically important difference established in health-related quality of life instruments? Review of anchors and methods.
      ,
      • Woaye-Hune P
      • Hardouin JB
      • Lehur PA
      • Meurette G
      • Vanier A
      Practical issues encountered while determining minimal clinically important difference in patient-reported outcomes.
      was required. The chosen anchors were CAT and 6MWT,
      • Smid DE
      • Franssen FM
      • Houben-Wilke S
      • et al.
      Responsiveness and MCID estimates for CAT, CCQ, and HADS in patients with COPD undergoing pulmonary rehabilitation: a prospective analysis.
      ,
      • Wise RA
      • Brown CD
      Minimal clinically important differences in the six-minute walk test and the incremental shuttle walking test.
      with known MIDs and expected correlations with the change in SPPB. In the presence of a sufficient correlation, linear regression and receiver operating characteristic analyses were performed between the change in SPPB as the dependent variable and the anchors as independent variables. For the receiver operating characteristic analyses, an area under the curve >0.7 was accepted as a meaningful relationship.
      • Copay AG
      • Subach BR
      • Glassman SD
      • Polly Jr, DW
      • Schuler TC
      Understanding the minimum clinically important difference: a review of concepts and methods.
      MID estimates of SPPB summary score and SPPB subtests were only determined for tests that are responsive to PR on group level compared with baseline values.

      Results

      Of the 953 patients with COPD, 632 patients were eligible for analysis. Patients were excluded due to absence of baseline SPPB data (n=1), age younger than 40 years (n=5), and participation in the PR program for the second time (n=20). In addition, 27 patients were excluded because download of the data export showed multiple baseline values for 1 or more attributes. The exclusion of patients corresponds to the baseline study reported by Stoffels et al.
      • Stoffels AAF
      • De Brandt J
      • Meys R
      • et al.
      Phenotypic characteristics of patients with chronic obstructive pulmonary disease after stratification for the Short Physical Performance Battery summary score.
      Furthermore, patients with missing post-PR assessment SPPB data (n=216) and a baseline SPPB summary score of 12 (n=52) were excluded.
      A greater number of patients included in the study had a dyspnoea grade ≥2 and a different distribution of GOLD classification (n=632) than excluded patients (n=321; P=.002 and P=.008, respectively) (table E2, available online only at http://www.archives-pmr.org/).

      Adherence and type of PR program

      Adherence to the PR program was high in the included patients (completed sessions=40 sessions
      • Beauchamp MK
      Balance assessment in people with COPD: An evidence-based guide.
      ,
      • Marques A
      • Jacome C
      • Cruz J
      • Gabriel R
      • Figueiredo D
      Effects of a pulmonary rehabilitation program with balance training on patients with COPD.
      ). There were no differences in adherence between patients in the inpatient and outpatient programs (P=.209) or between LP, MP, and HP groups (P=.788).
      Most patients participated in the inpatient PR program (61%). A larger percentage of these patients were females and experienced more severe symptoms, characterized by higher dyspnoea scores, poorer health status and pulmonary function, larger number of exacerbations and hospitalizations, and more frequent oxygen use compared with patients who participated in the outpatient program (table E3, available online only at http://www.archives-pmr.org/).

      Baseline characteristics

      The 632 patients with COPD had a severe degree of airflow limitation, an equal male-to-female ratio, and a normal body mass index. After stratification for SPPB summary score in LP (n=69), MP (n=300), and HP (n=263) groups, patients in the LP group were older and experienced higher levels of dyspnoea compared with the MP and HP groups. More clinical characteristics and pulmonary function data are shown in table 1.
      Table 1Baseline characteristics of all patients with COPD and after stratification for SPPB summary score
      CharacteristicShort Physical Performance Battery
      All Patients With COPD (n=632)Low-Performance (n=69)Moderate-Performance (n=300)High-Performance (n=263)
      Age (y)65±8

      (n=632)
      69±8
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      66±8

      (n=300)
      64±8

      (n=263)
      Sex (male, %)50

      (n=632)
      48

      (n=69)
      50

      (n=300)
      51

      (n=263)
      Weight (kg)72 (60-86)

      (n=630)
      70 (59-90)

      (n=69)
      73 (60-87)

      (n=298)
      70 (60-85)

      (n=263)
      BMI (kg/m2)25 (22-30)

      (n=630)
      25 (21-33)

      (n=69)
      26 (22-31)

      (n=298)
      25 (22-29)

      (n=263)
      mMRC score3 (2-3)

      (n=631)
      4 (3-4)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      3 (2-3)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.


      (n=300)
      2 (2-3)

      (n=262)
      mMRC≥2 (% patients)90

      (n=631)
      100
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      93
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.


      (n=300)
      83

      (n=262)
      CAT score22±6

      (n=593)
      25±6
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=62)
      22±6
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.


      (n=283)
      20±6

      (n=248)
      CAT≥18 (% patients)77

      (n=593)
      92
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=62)
      79

      (n=283)
      71

      (n=248)
      Exacerbations in the past 12 mo: 0/1/2/3/4/>4 (% patients)18/17/22/14/8/21

      (n=627)
      7/13/10/22/6/42
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      19/18/21/14/9/19

      (n=297)
      21/17/26/11/7/18

      (n=261)
      ≥2 exacerbations in the past 12 mo (% patients)64

      (n=627)
      80

      (n=69)
      63

      (n=297)
      63

      (n=261)
      Hospitalizations in the past 12 mo: 0/1/2/3/4/>4 (% patients)53/27/9/6/2/3

      (n=630)
      37/24/9/16/4/10
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=68)
      54/27/11/3/1/4

      (n=299)
      57/27/6/6/3/1

      (n=263)
      ≥1 hospitalization in the past 12 mo (% patients)47

      (n=630)
      63

      (n=68)
      47

      (n=299)
      43

      (n=263)
      CCI (points)1 (1-2)

      (n=632)
      2 (1-3)

      (n=69)
      1 (1-2)

      (n=300)
      1 (1-2)

      (n=263)
      CCI≥2 (% patients)45

      (n=632)
      51

      (n=69)
      45

      (n=300)
      44

      (n=263)
      Long-term O2 use (yes, % patients)24

      (n=620)
      42
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      24

      (n=295)
      20

      (n=256)
      GOLD I/II/III/IV (% patients)9/28/37/26

      (n=632)
      3/35/27/35

      (n=69)
      10/27/38/25

      (n=300)
      8/29/39/24

      (n=263)
      GOLD A/B/C/D (% patients)3/24/7/66

      (n=625)
      0/15/0/85
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=68)
      2/26/5/67

      (n=297)
      5/24/11/60

      (n=260)
      FEV1 (% predicted)43 (30-62)

      (n=632)
      34 (24-60)

      (n=69)
      42 (30-63)

      (n=300)
      43 (31-63)

      (n=263)
      FEV1/FVC (%)35 (27-47)

      (n=632)
      35 (25-48)

      (n=69)
      36 (28-48)

      (n=300)
      35 (27-46)

      (n=263)
      SPPB summary score9 (8-10)

      (n=632)
      5 (4-6)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      9 (8-9)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.


      (n=300)
      10 (10-11)

      (n=263)
      Balance side-by-side (s)10 (10-10)

      (n=632)
      10 (10-10)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      10 (10-10)

      (n=300)
      10 (10-10)

      (n=263)
      Balance semi-tandem (s)10 (10-10)

      (n=632)
      10 (10-10)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      10 (10-10)

      (n=300)
      10 (10-10)

      (n=263)
      Balance tandem (s)10 (8-10)

      (n=632)
      0 (0-4)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      10 (6-10)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.


      (n=300)
      10 (10-10)

      (n=263)
      4MGS (m/s)1.0 (0.9-1.2)

      (n=632)
      0.6 (0.5-0.7)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      1.0 (0.8-1.1)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.


      (n=300)
      1.2 (1.0-1.3)

      (n=263)
      5STS (s)16 (14-20)

      (n=632)
      60 (23-60)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=69)
      19 (17-22)
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.


      (n=300)
      14 (12-15)

      (n=263)
      NOTE. Data are presented as mean ± SD, median (Q1 - Q3), or percentages.
      Abbreviations: BMI, body mass index; CCI, Charlson Comorbidity Index; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; mMRC, modified Medical Research Council.
      low asterisk Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 7-9.
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 0-6 and SPPB summary scores 10-12.
      Indicates a significant difference after Bonferroni post hoc correction between SPPB summary scores 7-9 and SPPB summary scores 10-12.

      Response to PR in clinical characteristics

      Health status, dyspnoea, body composition, symptoms of anxiety and depression, and physical status improved in all patients with COPD who participated in PR (all P<.001) (table E4, available online only at http://www.archives-pmr.org/).
      After stratification for baseline SPPB summary score, significant improvements in these clinical characteristics were observed in all 3 SPPB performance groups, with the exception of the anxiety subscale of the Hospital Anxiety and Depression Scale in the LP group, which did not improve after PR (P=.020). The ∆6MWT was the greatest in the LP group (47±78 m) in comparison to the MP group (24±53 m) and the HP group (12±49 m; P<.001) (table E5, available online only at http://www.archives-pmr.org/).
      Differences in changes in clinical characteristics between patients participating in the inpatient and outpatient programs are depicted in table E6 (available online only at http://www.archives-pmr.org/).

      Response to PR in SPPB

      The 5STS was the only SPPB subtest responsive to PR, with a median ∆5STS of −1.14 (−4.20 to −0.93) seconds in patients with COPD (P<.001). Furthermore, SPPB summary score improved significantly from 9 (8-10) to 10 (9-11) points after PR (P<.001) (fig 1).
      Fig 1
      Fig 1Box plots of the baseline and post-PR (A) SPPB summary score, (B) balance side-by-side, (C) semi-tandem, (D) tandem, (E) 4MGS, and (F) 5STS for all patients and the LP, MP, and HP group. *Indicates a significant difference at P<.01; **indicates a significant difference at P<.001. The boxes in (B) and (C) are displayed as lines at the top because almost all patients maintained the balance side-by-side and semi-tandem positions for the maximum of 10 seconds.
      The baseline LP group showed improvements in balance tandem (median ∆=0.00 [0.00-10.00]s and mean ∆=3.36±4.96s), 4MGS (∆=0.81 [0.37-1.40] m/s), and 5STS (∆=−6.16 [−35.00 to 0.00]s) subtests of the SPPB after PR (all P<.001). The MP group showed a significant effect of PR on 4MGS (∆=0.06 [−0.18 to 0.33] m/s) and 5STS (∆=−2.40 [−6.40 to 0.17]s) subtests. The HP group only improved on 5STS (∆=−0.74 [−2.40 to 1.00]s, P<.001) and even showed a decline in 4MGS (∆=−0.27 [−0.44 to −0.05] m/s, P<.001). Improvements in the LP group were significant larger in contrast to MP and HP groups, which resulted in a larger increase in SPPB summary score for the LP group than the MP and HP groups (see fig 1). A maximum post-PR SPPB summary score of 12 was obtained in 23 patients in the MP group and 63 patients in the HP group.
      Furthermore, baseline and post-PR proportion of patients per performance group were significantly different (P<.001). The flow and direction of this change in performance group classification is presented in figure 2.
      Fig 2
      Fig 2Sankey diagram depicting the flow and distribution of the SPPB summary score for the different performance groups at baseline and post-PR.
      Because differences in the type of PR program could potentially influence the SPPB response to PR, comparisons between changes in SPPB subtests and summary scores were made for patients participating in inpatient and outpatient PR programs. Changes in SPPB subtests were not significantly different between the 2 types of PR programs, except for the change in 4MGS (outpatient=−0.2 [−0.4 to 0] m/s vs. inpatient=0.1 [−0.2 to 0.4] m/s; P<.001). However, this difference did not affect the change in SPPB summary score, which was comparable between both groups (table E7, available online only at http://www.archives-pmr.org/).

      MID

      Because only 5STS and SPPB summary score were responsive to PR, MID estimates were not determined for the balance tests and 4MGS. Using distribution-based techniques, the MID of the 5STS ranged between 2.19-6.33 seconds and between 0.83-0.96 points for the SPPB summary score (table 2).
      Table 2Distribution-based methods to estimate the minimal important difference in 5STS and SPPB summary score in patients with COPD
      MethodFormula5STS (s)SPPB Summary Score (Points)
      SEMSDbaseline ×1ICC2.190.83
      Empirical rule effect size0.08 × 6 × SDdelta4.050.86
      Cohen's effect size0.5 × SDdelta4.220.89
      0.5*SDbaseline0.5 × SDbaseline6.330.96
      MID range2.19-6.330.83-0.96
      Table E1The scoring system of the standing balance tests, 4MGS and 5STS.
      ScoresBalance

      Side-by-Side Test (s)
      Balance

      Semi-Tandem Test (s)
      Balance

      Tandem Test (s)
      4MGS (s)5STS (s)
      4<4.82<11.20
      34.82–6.2011.20–13.69
      210.006.21–8.7013.70–16.69
      110.0010.003.00-9.99>8.7016.70–60.00
      0<10.00<10.00<3.00UnableUnable (>60.00)
      Abbreviations: 4MGS, 4-m gait speed; 5STS, 5-repetition sit-to-stand.
      Table E2Differences in baseline characteristics between included and excluded patients.
      Included (n=632)Excluded (n=321)P Value
      Age (years)65±8

      (n=632)
      65±9

      (n=321)
      0.154
      Gender (male, %)50

      (n=632)
      54

      (n=321)
      0.373
      Weight (kg)72 (60-86)

      (n=630)
      73 (60-86)

      (n=298)
      0.968
      BMI (kg/m2)25 (22-30)

      (n=630)
      25 (22-30)

      (n=298)
      0.791
      mMRC score3 (2-3)

      (n=631)
      2 (2-3)

      (n=321)
      0.282
      mMRC≥2 (% patients)90

      (n=631)
      82

      (n=321)
      0.002
      CAT score22±6

      (n=593)
      21±7

      (n=300)
      0.383
      CAT≥18 (% patients)77

      (n=594)
      72

      (n=300)
      0.100
      Exacerbations in the past 12 months (0/1/2/3/4/>4, % patients)18/17/22/14/8/21

      (n=627)
      23/16/16/13/8/24

      (n=321)
      0.258
      ≥2 exacerbations in the past 12 months (% patients)64

      (n=627)
      62

      (n=321)
      0.434
      Hospitalizations in the past 12 months (0/1/2/3/4/>4, % patients)53/27/9/6/2/3

      (n=630)
      61/22/9/6/2/0

      (n=299)
      0.295
      ≥1 hospitalization in the past 12 months (% patients)47

      (n=630)
      39

      (n=299)
      0.064
      CCI (points)1 (1-2)

      (n=632)
      1 (1-2)

      (n=321)
      0.280
      CCI≥2 (% patients)45

      (n=632)
      42

      (n=321)
      0.370
      Long-term O2 use (yes, % patients)24

      (n=620)
      19

      (n=316)
      0.115
      GOLD I/II/III/IV (% patients)9/28/37/26

      (n=632)
      10/27/41/22

      (n=320)
      0.555
      GOLD A/B/C/D (% patients)3/24/7/66

      (n=625)
      10/28/8/54

      (n=297)
      0.008
      FEV1 (% predicted)43 (30-62)

      (n=632)
      43 (32-59)

      (n=320)
      0.691
      FEV1/FVC (%)35 (27-47)

      (n=632)
      34 (28-48)

      (n=320)
      0.842
      Data is presented as mean ± SD, median (Q1 – Q3), or percentages. Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; CCI, Charlson Comorbidity Index; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified Medical Research Council.
      Table E3Differences in baseline characteristics between patients following an in- and outpatient program.
      Inpatient (n=387)Outpatient (n=238)P Value
      Age (years)66±8

      (n=387)
      65±8

      (n=238)
      0.252
      Gender (male, %)45

      (n=387)
      59

      (n=238)
      0.001
      Weight (kg)71 (59-86)

      (n=386)
      75 (62-88)

      (n=237)
      0.081
      BMI (kg/m2)25 (21-31)

      (n=386)
      25 (22-30)

      (n=237)
      0.575
      mMRC score3 (2-4)

      (n=387)
      2 (2-3)

      (n=237)
      <0.001
      mMRC≥2 (% patients)95

      (n=387)
      80

      (n=237)
      0.002
      CAT score23±6

      (n=364)
      19±6

      (n=223)
      <0.001
      CAT≥18 (% patients)87

      (n=364)
      60

      (n=223)
      <0.001
      Exacerbations in the past 12 months (0/1/2/3/4/>4, % patients)14/15/22/15/9/25

      (n=385)
      26/20/22/12/6/14

      (n=235)
      <0.001
      ≥2 exacerbations in the past 12 months (% patients)71

      (n=385)
      54

      (n=235)
      <0.001
      Hospitalizations in the past 12 months (0/1/2/3/4/>4, % patients)48/27/10/7/3/5

      (n=386)
      63/26/5/3/2/1

      (n=237)
      <0.001
      ≥1 hospitalization in the past 12 months (% patients)52

      (n=386)
      37

      (n=237)
      <0.001
      CCI (points)1 (1-2)

      (n=387)
      1 (1-2)

      (n=238)
      0.972
      CCI≥2 (% patients)45

      (n=387)
      46

      (n=238)
      0.741
      Long-term O2 use (yes, % patients)33

      (n=379)
      10

      (n=234)
      <0.001
      GOLD I/II/III/IV (% patients)6/23/39/32

      (n=387)
      13/37/35/15

      (n=238)
      <0.001
      GOLD A/B/C/D (% patients)1/21/4/74

      (n=384)
      8/29/12/51

      (n=234)
      <0.001
      FEV1 (% predicted)38 (28-54)

      (n=387)
      51 (38-70)

      (n=238)
      <0.001
      FEV1/FVC (%)33 (26-46)

      (n=387)
      39 (31-50)

      (n=238)
      <0.001
      Data is presented as mean ± SD, median (Q1 – Q3), or percentages.  Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; CCI, Charlson Comorbidity Index; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified Medical Research Council.
      Table E4Baseline, post and delta (post minus baseline) pulmonary rehabilitation data of all patients with COPD.
      BaselinePost PRDeltaP Value
      Symptom burden and health status
      mMRC score3 (2-3)

      (n=591)
      2 (1-2)

      (n=591)
      -1 (-1-0)

      (n=591)
      <0.001
      mMRC≥2 (% patients)89

      (n=591)
      64

      (n=591)
      -25

      (n=591)
      <0.001
      CAT score22±6

      (n=560)
      19±7

      (n=560)
      -3±6

      (n=560)
      <0.001
      CAT≥18 (% patients)77

      (n=560)
      58

      (n=560)
      -19

      (n=560)
      <0.001
      Body composition
      FFM index16.5±2.5

      (n=620)
      17.0±2.4

      (n=620)
      0.4±0.6

      (n=620)
      <0.001
      FFM legs (kg)15.1 (12.1–17.7)

      (n=621)
      15.5 (12.7–18.3)

      (n=621)
      0.5 (0.0-1.1)

      (n=621)
      <0.001
      Emotional status
      HADS anxiety score7 (4-10)

      (n=557)
      6 (3-9)

      (n=557)
      -1 (-3-1)

      (n=557)
      <0.001
      HADS anxiety≥10 (% patients)28

      (n=557)
      22

      (n=557)
      -6

      (n=557)
      0.001
      HADS depression score7 (4-10)

      (n=557)
      5 (3-8)

      (n=557)
      -1 (-3-0)

      (n=557)
      <0.001
      HADS depression≥10 (% patients)30

      (n=557)
      16

      (n=557)
      -14

      (n=557)
      <0.001
      Physical status
      6MWD (m)370±109

      (n=618)
      391±109

      (n=618)
      22±56

      (n=618)
      <0.001
      CWRT TTE (s)230 (166-329)

      (n=546)
      328 (215-660)

      (n=546)
      112 (14-347)

      (n=546)
      <0.001
      Isokinetic quadriceps peak torque (Nm)82 (60-105)

      (n=456)
      89 (70-115)

      (n=456)
      9 (2-17)

      (n=456)
      <0.001
      Isokinetic quadriceps peak torque (% predicted)61 (47-72)

      (n=456)
      69 (56-80)

      (n=456)
      7 (2-13)

      (n=456)
      <0.001
      Isokinetic quadriceps total work (J)1389 (994-1836)

      (n=456)
      1676 (1248-2109)

      (n=456)
      247 (107-418)

      (n=456)
      <0.001
      Data is presented as mean ± SD, median (Q1 – Q3), or percentages. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.
      Table E5Baseline, post and delta (post minus baseline) pulmonary rehabilitation data of the LP, MP and HP group.
      Low-Performance (n=69)Moderate-Performance (n=300)High-Performance (n=263)
      BaselinePost PRDeltaBaselinePost PRDeltaBaselinePost PRDelta
      Symptom burden and health status
      mMRC score4 (3-4)

      (n=63)
      2 (2-3)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=63)
      -1 (-2-0)

      (n=63)
      3 (2-3)

      (n=278)
      2 (1-2)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=278)
      -1(-1-0)

      (n=278)
      2 (2-3)

      (n=250)
      2 (1-2)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=250)
      -1 (-1-0)

      (n=250)
      mMRC≥2 (% patients)100

      (n=63)
      91

      (n=63)
      -9
      indicates a significant difference after Bonferroni post-hoc correction between the delta's SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      indicates a significant difference after Bonferroni post-hoc correction between the delta's of SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=63)
      92

      (n=278)
      67
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=278)
      -25
      indicates a significant difference after Bonferroni post-hoc correction between the delta's of SPPB summary scores 7-9 and SPPB summary scores 10-12. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=278)
      83

      (n=250)
      54
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=250)
      -29

      (n=250)
      CAT score25±6

      (n=57)
      22±6
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=57)
      -3±5

      (n=57)
      22±6

      (n=266)
      19±7
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=266)
      -3±6

      (n=266)
      20±6

      (n=237)
      18±7
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=237)
      -2±6

      (n=237)
      CAT≥18 (% patients)91

      (n=57)
      79

      (n=57)
      -12

      (n=57)
      79

      (n=266)
      60
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=266)
      -19

      (n=266)
      70

      (n=237)
      50
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=237)
      -20

      (n=237)
      Body composition
      FFM index16.6±2.7

      (n=68)
      17.0±2.5
      indicates a significant difference between baseline and post PR of p<0.01,


      (n=68)
      0.4±0.9

      (n=68)
      16.5±2.6

      (n=293)
      17.0±2.5
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=293)
      0.5±0.7

      (n=293)
      16.5±2.4

      (n=259)
      16.9± 2.3
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=259)
      0.4±0.5

      (n=259)
      FFM legs (kg)14.4 (11.7-17.5)

      (n=68)
      14.9 (12.2-17.3)
      indicates a significant difference between baseline and post PR of p<0.01,


      (n=68)
      0.5 (-0.0-1.2)

      (n=68)
      15.0 (12.0-17.7)

      (n=294)
      15.4 (12.6-18.2)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=294)
      0.5 (-0.1-1.1)

      (n=294)
      15.3 (12.3-17.9)

      (n=259)
      15.8 (12.8-18.6)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=259)
      0.5 (0.2-1.1)

      (n=259)
      Emotional status
      HADS anxiety score9 (6-13)

      (n=55)
      7 (5-11)

      (n=55)
      -2 (-4-2)

      (n=55)
      8 (5-10)

      (n=265)
      6 (4-9)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=265)
      -2 (-3-1)

      (n=265)
      7 (4-9)

      (n=237)
      5 (3-9)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=237)
      -2 (-3-1)

      (n=237)
      HADS anxiety≥10 (% patients)47

      (n=55)
      33

      (n=55)
      -14

      (n=55)
      29

      (n=265)
      23

      (n=265)
      -6

      (n=265)
      23

      (n=237)
      18

      (n=237)
      -5

      (n=237)
      HADS depression score10 (5-13)

      (n=55)
      8 (4-10)**

      (n=55)
      -2 (-5-1)

      (n=55)
      7 (5-10)

      (n=265)
      6 (4-9)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=265)
      -1 (-3-1)

      (n=265)
      6 (4-9)

      (n=237)
      5 (2-8)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=237)
      -1 (-3-0)

      (n=237)
      HADS depression≥10 (% patients)56

      (n=55)
      26
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=55)
      -30
      indicates a significant difference after Bonferroni post-hoc correction between the delta's SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      indicates a significant difference after Bonferroni post-hoc correction between the delta's of SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=55)
      29

      (n=265)
      18
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=265)
      -11

      (n=265)
      25

      (n=237)
      12
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=237)
      -13

      (n=237)
      Physical status
      6MWD (m)213±84

      (n=65)
      260±110
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=65)
      47±78
      indicates a significant difference after Bonferroni post-hoc correction between the delta's SPPB summary scores 0-6 and SPPB summary scores 7-9.
      ,
      indicates a significant difference after Bonferroni post-hoc correction between the delta's of SPPB summary scores 0-6 and SPPB summary scores 10-12.


      (n=65)
      356±91

      (n=294)
      380±94
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=294)
      24±53

      (n=294)
      425±89

      (n=259)
      437±94
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=259)
      12±49

      (n=259)
      CWRT TTE (s)148 (104-260)

      (n=40)
      300 (175-656)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=40)
      156 (16-383)

      (n=40)
      217 (159-314)

      (n=261)
      313 (215-635)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=261)
      108 (15-304)

      (n=261)
      251 (189-344)

      (n=245)
      390 (230-763)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=245)
      112 (6-435)

      (n=245)
      Isokinetic quadriceps peak torque (Nm)52 (41-78)

      (n=38)
      63 (52-80)
      indicates a significant difference between baseline and post PR of p<0.01,


      (n=38)
      8 (-1-18)

      (n=38)
      76 (59-101)

      (n=206)
      87 (67-114)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=206)
      9 (3-17)

      (n=206)
      88 (69-111)

      (n=212)
      97 (80-118)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=212)
      9 (2-17)

      (n=212)
      Isokinetic quadriceps peak torque (% predicted)45 (34-62)

      (n=38)
      52 (44-65)
      indicates a significant difference between baseline and post PR of p<0.01,


      (n=38)
      8 (0-13)

      (n=38)
      58 (43-70)

      (n=206)
      65 (52-80)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=206)
      7 (2-13)

      (n=206)
      65 (52-74)

      (n=212)
      73 (61-82)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=212)
      6 (2-13)

      (n=212)
      Isokinetic quadriceps total work (J)791 (569-1138)

      (n=38)
      1115 (857-1372)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=38)
      248 (-26-488)

      (n = 38)
      1313 (914-1808)

      (n=206)
      1577 (1156-2016)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=206)
      258 (95-433)

      (n=206)
      1555 (1179-1928)

      (n=212)
      1789 (1492-2245)
      indicates a significant difference between baseline and Post PR of p<0.001.


      (n=212)
      236 (112-412)

      (n=212)
      Data is presented as mean ± SD, median (Q1 – Q3), or percentages.
      low asterisk indicates a significant difference between baseline and post PR of p<0.01,
      low asterisklow asterisk indicates a significant difference between baseline and Post PR of p<0.001.
      a indicates a significant difference after Bonferroni post-hoc correction between the delta's SPPB summary scores 0-6 and SPPB summary scores 7-9.
      b indicates a significant difference after Bonferroni post-hoc correction between the delta's of SPPB summary scores 0-6 and SPPB summary scores 10-12.
      c indicates a significant difference after Bonferroni post-hoc correction between the delta's of SPPB summary scores 7-9 and SPPB summary scores 10-12.Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.
      Table E6Baseline, post and delta (post minus baseline) pulmonary rehabilitation data of patient following an in- or outpatient program.
      Inpatient (n=384)Outpatient (n=238)Differences in Delta's
      BaselinePost PRDeltaBaselinePost PRDeltaP Value
      Symptom burden and health status
      mMRC score3 (2-4)

      (n=363)
      2 (1-3)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=363)
      -1 (-2-0)

      (n=363)
      2 (2-3)

      (n=222)
      2 (1-2)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=222)
      0 (-1-0)

      (n=222)
      <0.001
      mMRC≥2 (% patients)95

      (n=363)
      70
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=363)
      -25

      (n=363)
      79

      (n=222)
      54
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=222)
      -25

      (n=278)
      0.805
      CAT score23±6

      (n=347)
      20±6
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=347)
      -3±6

      (n=347)
      19±6

      (n=208)
      17±7
      indicates a significant difference between baseline and post PR of p<0.01,


      (n=208)
      -1±6

      (n=208)
      <0.001
      CAT≥18 (% patients)87

      (n=347)
      66
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=347)
      -21

      (n=347)
      59

      (n=208)
      45
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=208)
      -14

      (n=208)
      0.133
      Body composition
      FFM index16.3±2.5

      (n=378)
      16.8±24
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=378)
      0.5±0.7

      (n=378)
      17.0±2.5

      (n=235)
      17.3±2.5
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=235)
      0.3±0.5

      (n=235)
      0.004
      FFM legs (kg)14.5 (11.8-17.0)

      (n=379)
      15.0 (12.4-17.4)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=379)
      0.6 (0.1-1.1)

      (n=379)
      16.0 (13.1-18.8)

      (n=235)
      16.4 (13.4-19.3)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=235)
      0.5 (0-0.9)

      (n=235)
      0.271
      Emotional status
      HADS anxiety score8 (5-11)

      (n=345)
      6 (4-9)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=345)
      -1 (-3-1)

      (n=345)
      6 (3-8)

      (n=208)
      5 (3-8)

      (n=208)
      -1 (-2-1)

      (n=208)
      0.001
      HADS anxiety ≥10 (% patients)34

      (n=345)
      24
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=345)
      -10

      (n=345)
      19

      (n=208)
      18

      (n=208)
      -1

      (n=208)
      0.017
      HADS depression score8 (5-11)

      (n=345)
      6 (3-9)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=345)
      -2 (-4-0)

      (n=345)
      6 (4-9)

      (n=208)
      5 (3-7)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=208)
      -1 (-2-1)

      (n=208)
      <0.001
      HADS depression≥10 (% patients)37

      (n=345)
      18
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=345)
      -15

      (n=345)
      18

      (n=208)
      13

      (n=208)
      -5

      (n=208)
      <0.001
      Physical status
      6MWD (m)332±102

      (n=377)
      358±106
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=377)
      26±59

      (n=377)
      432±88

      (n=234)
      444±92
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=234)
      13±47

      (n=234)
      0.002
      CWRT TTE (s)201 (148-300)

      (n=312)
      318 (212-654)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=312)
      126 (34-398)

      (n=312)
      272 (197-378)

      (n=227)
      349 (217-676)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=227)
      77 (-24-272)

      (n=227)
      0.001
      Isokinetic quadriceps peak torque (Nm)74 (55-94)

      (n=268)
      84 (65-105)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=268)
      9 (3-18)

      (n=268)
      92 (73-120)

      (n=183)
      102 (83-129)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=183)
      8 (2-17)

      (n=183)
      0.729
      Isokinetic quadriceps peak torque (% predicted)57 (42-69)

      (n=268)
      65 (51-77)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=268)
      7 (2-13)

      (n=268)
      67 (55-77)

      (n=183)
      74 (62-83)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=183)
      6 (1-12)

      (n=183)
      0.284
      Isokinetic quadriceps total work (J)1202 (872-1586)

      (n=268)
      1492 (1108-1889)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=268)
      250 (92-437)

      (n=268)
      1638 (1306-2194)

      (n=183)
      1863 (1530-2402)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.


      (n=183)
      234 (119-383)

      (n=183)
      0.764
      Data is presented as mean ± SD, median (Q1 – Q3), or percentages.
      low asterisk indicates a significant difference between baseline and post PR of p<0.01,
      low asterisklow asterisk indicates a significant difference between baseline and Post PR of p<0.001.Abbreviations: CAT, COPD Assessment Test; CWRT, Constant Work Rate Test; FFM, Fat-free mass; HADS, Hospital Anxiety and Depression Scale; mMRC, modified Medical Research Council; TTE, Time-To-Exhaustion; 6MWD, 6-Minute Walk Test distance.
      Table E7Baseline, post PR and delta (post PR minus baseline) data of the SPPB subtests and summary score in patient following an in- or outpatient program.
      Inpatient (n = 387)Outpatient (n = 238)Differences in Delta's
      BaselinePost PRDeltaBaselinePost PRDeltaP Value
      Side-by-side (s)10 (10-10)10 (10-10)0 (0-0)10 (10-10)10 (10-10)0 (0-0)0.823
      Semi-tandem (s)10 (10-10)10 (10-10)0 (0-0)10 (10-10)10 (10-10)0 (0-0)0.723
      Tandem (s)10 (7-10)10 (8-10)0 (0-0)10 (10-10)10 (10-10)
      indicates a significant difference between baseline and post PR of p<0.01,
      0 (0-0)0.144
      4MGS (m/s)1.0 (0.8-1.1)1.1 (0.9-1.3)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: 4MGS: 4-meter gait speed, 5STS: 5-repetition sit-to-stand, SPPB: Short Physical Performance Battery.
      0.1 (-0.2-0.4)1.1 (1.0-1.3)0.9 (0.8-1.0)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: 4MGS: 4-meter gait speed, 5STS: 5-repetition sit-to-stand, SPPB: Short Physical Performance Battery.
      -0.2 (-0.4-0)<0.001
      5STS (s)17 (14-23)16 (13-20)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: 4MGS: 4-meter gait speed, 5STS: 5-repetition sit-to-stand, SPPB: Short Physical Performance Battery.
      -1 (-4-1)15 (13-18)13 (11-16)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: 4MGS: 4-meter gait speed, 5STS: 5-repetition sit-to-stand, SPPB: Short Physical Performance Battery.
      -1 (-4-0)0.256
      SPPB summary score9 (8-10)9 (8-10)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: 4MGS: 4-meter gait speed, 5STS: 5-repetition sit-to-stand, SPPB: Short Physical Performance Battery.
      0 (0-2)10 (9-11)10 (9-11)
      indicates a significant difference between baseline and Post PR of p<0.001. Abbreviations: 4MGS: 4-meter gait speed, 5STS: 5-repetition sit-to-stand, SPPB: Short Physical Performance Battery.
      1 (0-2)0.092
      Data is presented as median (Q1 – Q3).
      low asterisk indicates a significant difference between baseline and post PR of p<0.01,
      low asterisklow asterisk indicates a significant difference between baseline and Post PR of p<0.001.Abbreviations: 4MGS: 4-meter gait speed, 5STS: 5-repetition sit-to-stand, SPPB: Short Physical Performance Battery.
      Furthermore, the change in 6MWT and CAT was not correlated or only weakly correlated with the change in 5STS and SPPB summary score and could therefore not be used as reliable anchors to determine the MIDs (table E8, available online only at http://www.archives-pmr.org/).
      Table E8Correlations between change in CAT score and 6MWT (m) with the change in 5STS and SPPB summary score for patients with COPD.
      ∆CAT score∆6MWT (m)
      Correlation CoefficientP ValueCorrelation CoefficientP Value
      ∆5STS (s)0.0840.047-0.1200.003
      ∆SPPB summary score-0.151<0.0010.183<0.001
      Abbreviations: CAT, COPD Assessment Test; SPPB, short physical performance battery; 5STS, 5-repetition sit-to-stand; 6MWT, 6-minute walk test

      Discussion

      Generally, the SPPB subtest 5STS and the SPPB summary score are responsive to PR in patients with COPD. In patients with a low performance at baseline, balance tandem and 4MGS are responsive to PR as well. Based on distribution-based calculations, the MID estimates range between 2.19-6.33 seconds for 5STS and 0.83-0.96 points for SPPB summary score.
      In accordance with previous studies, 5STS and SPPB summary score were responsive to PR in patients with COPD.
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      • Canavan JL
      • et al.
      The five-repetition sit-to-stand test as a functional outcome measure in COPD.
      However, the current study did not show an improvement in 4MGS in all patients with COPD as was expected based on previous studies.
      • Carrington D
      • Jones S
      • Canavan J
      • et al.
      Responsiveness of the Short Physical Performance Battery (SPPB) in severely dyspnoeic patients with COPD.
      ,
      • Kon SS
      • Canavan JL
      • Nolan CM
      • et al.
      The 4-metre gait speed in COPD: responsiveness and minimal clinically important difference.
      Only LP and MP patients improved their 4MGS. A possible explanation for the decline in 4MGS in the HP group could be a ceiling effect; Kon et al
      • Kon SS
      • Canavan JL
      • Nolan CM
      • et al.
      The 4-metre gait speed in COPD: responsiveness and minimal clinically important difference.
      have reported that patients with a better baseline 4MGS were less responsive to PR than patients with a worse baseline 4MGS. Furthermore, only the LP group improved balance tandem time after PR but had a change of 0 (0-10) seconds (or mean change of 3.36±4.96s), which makes the clinical significance of the improvement questionable. No performance group showed an effect of PR in balance side-by-side or semi-tandem. Although balance impairments are common in patients with COPD,
      • Beauchamp MK
      Balance assessment in people with COPD: An evidence-based guide.
      most participants were able to complete the balance tests without difficulty. These results imply that standing balance tests are less useful and effective and perhaps not adequality sensitive in evaluating the effectiveness of PR in patients with COPD, suggesting the use of more complex balance tests like Berg Balance Scale or Balance Evaluation Systems Test.
      • Beauchamp MK
      Balance assessment in people with COPD: An evidence-based guide.
      Another possible explanation could be the minor focus on balance issues during PR; Marques et al highlighted the value of balance training during PR.
      • Marques A
      • Jacome C
      • Cruz J
      • Gabriel R
      • Figueiredo D
      Effects of a pulmonary rehabilitation program with balance training on patients with COPD.
      The mean 5STS MID estimates (2.19-6.33s) are larger than the MID estimate by Jones et al (1.7s) in patients with COPD after an 8-week outpatient PR program in the United Kingdom.
      • Jones SE
      • Kon SS
      • Canavan JL
      • et al.
      The five-repetition sit-to-stand test as a functional outcome measure in COPD.
      The current SPPB summary score MID estimates (0.83-0.96 points) are comparable with the study of Perera et al, who reported a small meaningful change of 0.5 points and a substantial change of 1.0 point for SPPB summary scores in older patients.
      • Perera S
      • Mody SH
      • Woodman RC
      • Studenski SA
      Meaningful change and responsiveness in common physical performance measures in older adults.
      Because the SPPB summary score is reported in whole numbers, it seems reasonable to conclude that an improvement of 1 point on the SPPB summary score can be taken as the MID in patients with COPD after PR. This MID can be interpreted and applied at individual and group levels to determine whether patients improve after PR.

      Study limitations

      Analyses were performed on a selected population of patients with COPD referred for PR. Including a more diverse group of patients could complicate the interpretation of results and conclusions. These results should be applied with caution in other populations or settings, because differences in interventions, context, and population characteristics are known to influence the response and MID estimates.
      • Pepin V
      • Laviolette L
      • Brouillard C
      • et al.
      Significance of changes in endurance shuttle walking performance.
      • Wright A
      • Hannon J
      • Hegedus EJ
      • Kavchak AE
      Clinimetrics corner: a closer look at the minimal clinically important difference (MCID).
      • Lauridsen HH
      • Hartvigsen J
      • Manniche C
      • Korsholm L
      • Grunnet-Nilsson N
      Responsiveness and minimal clinically important difference for pain and disability instruments in low back pain patients.
      • Mroczek B
      • Sitko Z
      • Augustyniuk K
      • Pierzak-Sominka J
      • Wroblewska I
      • Kurpas D
      Socioeconomic indicators shaping quality of life and illness acceptance in patients with chronic obstructive pulmonary disease.
      • Revicki D
      • Hays RD
      • Cella D
      • Sloan J
      Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes.
      In addition, 86 patients achieved a maximum post-PR SPPB score of 12, which could indicate a ceiling effect.
      Inpatient and outpatient PR programs were combined in the analyses performed in this study. Although the Δ SPPB summary score was comparable between groups, differences were found in other attributes, which partly may be explained by differences at baseline. Indeed, patients with the most severe limitations participated in the inpatient program. Furthermore, due to the retrospective design, it was not possible to regain details of the actual content of the program.
      Despite the intent to use anchor- and distribution-based methods to calculate MID estimates, only distribution-based calculations could be performed. Therefore, the obtained MIDs provide no clinical significance but statistical significance only. It is highly recommended that multiple anchor-based approaches be used in future MID estimations, such as the incremental shuttle walk test or patient's self-reported improvement, which were used in previous studies.
      • Kon SS
      • Canavan JL
      • Nolan CM
      • et al.
      The 4-metre gait speed in COPD: responsiveness and minimal clinically important difference.
      ,
      • Jones SE
      • Kon SS
      • Canavan JL
      • et al.
      The five-repetition sit-to-stand test as a functional outcome measure in COPD.
      ,
      • Perera S
      • Mody SH
      • Woodman RC
      • Studenski SA
      Meaningful change and responsiveness in common physical performance measures in older adults.

      Conclusions

      The SPPB subtest 5STS and summary score are both responsive to PR in patients with COPD after PR. The balance tandem test and 4MGS are only responsive to PR in patients with COPD with a low performance at baseline. Based on distribution-based calculations, an MID estimate of 1 point for the SPPB summary score is recommended in patients with COPD. Future research is needed to confirm MID estimates for the SPPB in different centers using anchor-based methods as well.

      Suppliers

      • a.
        MasterScreen PFT/Body, Jaeger.
      • b.
        Lunar iDXA, DEXAtech Benelux BV.
      • c.
        Ergoselect, Ergoline.
      • d.
        Biodex Multi-joint System 3; Biometrics Motion B.V.
      • e.
        SPSS, version 25.0; IBM.

      Acknowledgment

      We thank Prof. Wim Derave (Ghent University) for his input and collaboration within the BASES Consortium, in the context of which the current article was written.

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