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Original Research: COPD |

Phenotypic Characteristics Associated With Reduced Short Physical Performance Battery Score in COPDDeterminants of Short Physical Performance Battery FREE TO VIEW

Mehul S. Patel, MBBS; Divya Mohan, MBBS; Yvonne M. Andersson, BSc; Manuel Baz, MD; Samantha S. C. Kon, MBBS; Jane L. Canavan, PhD; Sonya G. Jackson, PhD; Amy L. Clark, BSc; Nicholas S. Hopkinson, PhD; Samantha A. Natanek, PhD; Paul R. Kemp, PhD; Piet L. B. Bruijnzeel, PhD; William D.-C. Man, PhD; Michael I. Polkey, PhD
Author and Funding Information

From the NIHR Respiratory Biomedical Research Unit (Drs Patel, Mohan, Baz, Kon, Canavan, Hopkinson, Natanek, and Man and Prof Polkey), Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, London, England; Respiratory, Inflammation, and Autoimmune Diseases (Ms Andersson and Drs Jackson and Bruijnzeel), AstraZeneca, Mölndal, Sweden; Harefield Pulmonary Rehabilitation Unit (Drs Kon, Canavan, Man, and Ms Clark), London, England; and Department of Molecular Medicine (Dr Kemp), Imperial College London, London, England.

Correspondence to: Michael I. Polkey, PhD, Muscle Laboratory, NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust and Imperial College, Fulham Rd, London, SW3 6NP, England; e-mail: m.polkey@rbht.nhs.uk


Funding/Support: This project was supported by an unrestricted grant from AstraZeneca and by the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton & Harefield NHS Foundation Trust and Imperial College London, who partly fund Prof Polkey’s and completely fund Dr Canavan’s salary. Dr Kon is supported by the Medical Research Council. Dr Man is supported by an NIHR Clinician Scientist Award, Medical Research Council New Investigator Grant, and an NIHR Clinical Trials Fellowship.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(5):1016-1024. doi:10.1378/chest.13-1398
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Background:  The Short Physical Performance Battery (SPPB) is commonly used in gerontology, but its determinants have not been previously evaluated in COPD. In particular, it is unknown whether pulmonary aspects of COPD would limit the value of SPPB as an assessment tool of lower limb function.

Methods:  In 109 patients with COPD, we measured SPPB score, spirometry, 6-min walk distance, quadriceps strength, rectus femoris cross-sectional area, fat-free mass, physical activity, health status, and Medical Research Council dyspnea score. In a subset of 31 patients with COPD, a vastus lateralis biopsy was performed, and the biopsy specimen was examined to evaluate the structural muscle characteristics associated with SPPB score. The phenotypic characteristics of patients stratified according to SPPB were determined.

Results:  Quadriceps strength and 6-min walk distance were the only independent predictors of SPPB score in a multivariate regression model. Furthermore, while age, dyspnea, and health status were also univariate predictors of SPPB score, FEV1 was not. Stratification by reduced SPPB score identified patients with locomotor muscle atrophy and increasing impairment in strength, exercise capacity, and daily physical activity. Patients with mild or major impairment defined as an SPPB score < 10 had a higher proportion of type 2 fibers (71% [14] vs 58% [15], P = .04).

Conclusions:  The SPPB is a valid and simple assessment tool that may detect a phenotype with functional impairment, loss of muscle mass, and structural muscle abnormality in stable patients with COPD.

Figures in this Article

The Short Physical Performance Battery (SPPB) is a standardized objective assessment tool that has been recommended by consensus working groups as a primary functional outcome measure in frail older people1 and in screening for sarcopenia.2 Initially developed for community use, it is quick and simple to conduct. It summates three component tests of functional relevance, assessing standing balance, habitual gait speed, and ability to stand. Scored out of 12, in unselected community-dwelling older adults low SPPB scores identify those at risk for mortality, nursing home admission, hospitalization, and disability.3,4 In general older populations, the SPPB relates to functional exercise capacity5 and skeletal muscle function.6

While we have recently validated two components of the SPPB (4-m gait speed and the sit-to-stand test) in COPD,7,8 most studies using the SPPB have been in community-dwelling older adults, only a minority of whom may have respiratory disease, or in community-dwelling individuals with mild COPD.9 The properties of the SPPB have not been systematically evaluated in patients with COPD, in whom respiratory and systemic manifestations may contribute to functional impairment. Specifically, it is unknown whether pulmonary aspects of COPD might make the SPPB an unreliable measure of skeletal muscle function.

The aim of this study was to assess the characteristics of patients with COPD that determine SPPB score. We hypothesized that stratifying according to SPPB score would detect a phenotype with impaired function and abnormal features in a quadriceps biopsy; if confirmed, the SPPB could be a useful biomarker for entry into stratified medicine studies.10 Specifically, we hypothesized that patients with a low SPPB score would have reduced quadriceps strength and bulk, functional exercise capacity, daily physical activity, and evidence of fiber shift.

The data were prospectively collected from four studies with shared protocols investigating the pathophysiologic determinants and associations of skeletal muscle dysfunction in COPD. Each study received ethical committee approval (West London REC 3: 10/H0706/9; North West London REC: 11/LO/1636; North London REC: 11/H0717/3; NRES Committee London–Chelsea: 12/LO/0523); all patients provided written informed consent.

One hundred nine stable patients diagnosed with COPD according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines11 were recruited; by design, we sought to study a range of COPD severity. Exclusion criteria included exacerbation within 4 weeks, unstable cardiac disease, and predominant neurologic or musculoskeletal limitation to mobilizing. Further details of the methodology are provided in e-Appendix 1.

Clinical Predictors of the SPPB

Patients performed the SPPB according to the National Institute on Aging protocol12; scoring for the SPPB is shown in e-Figure 1. The three SPPB components (standing balance, 4-m gait speed, and a five-repetition sit-to-stand test) were scored from 0 to 4, with higher scores indicating better performance. In order of testing, assessments were: spirometry (we report FEV1 % predicted)13; Medical Research Council (MRC) dyspnea score14; St. George’s Respiratory Questionnaire (SGRQ)15; SPPB; fat-free mass (FFM) and FFM index (FFMI)16; dominant leg quadriceps strength (quadriceps maximal voluntary contraction [QMVC]), normalized to BMI (QMVC/BMI)17 and expressed as percent predicted18; rectus femoris cross-sectional area (RFCSA)19,20; 6-min walk distance (6MWD)21; and daily step count (Sensewear; BodyMedia, Inc).22,23 The BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index and the age, dyspnea, and airflow obstruction (ADO) index scores were calculated as composite indexes of mortality.24,25

Biopsy Predictors of the SPPB

A vastus lateralis biopsy was performed26,27 in a subcohort of 31 patients with COPD who in addition to the previous assessments also had plethysmographic lung volumes and carbon monoxide gas transfer measured; from these data, we report the residual volume to total lung capacity ratio (RV:TLC %) and the carbon monoxide gas transfer coefficient corrected for hemoglobin (Kcoc) expressed as % predicted.2830 Immunohistochemistry was performed on the biopsy samples to determine fiber proportions,26 myofiber cross-sectional area (CSA)27 and the mean capillary to fiber ratio (C:Fi).31

Statistical Analysis

Statistical analyses and graphical presentations were performed using GraphPad Prism 5 (GraphPad Software, Inc) or SPSS, version 18 (IBM). Significance was set at a two-tailed P value of ≤ .05. Logistic regression was performed to identify the predictors of SPPB impairment (SPPB < 10). Patients were stratified according to performance cutoffs derived from other populations: minimal limitation (SPPB 10-12), limitation (SPPB 7-9), or major limitation (SPPB < 7); analysis of variance or Kruskal-Wallis with post-hoc correction was used to compare between the groups.

The demographic data, clinical characteristics, and predictors of the SPPB are shown in Table 1; data from the biopsy cohort are shown in Table 2. Daily steps could not be entered into the regression analysis as the data were skewed.

Table Graphic Jump Location
Table 1 —Descriptive Characteristics and Logistic Regression Analyses of the Predictors of SPPB Score

Data are presented as mean (SD), No. (%), or median (interquartile range). Descriptive characteristics and logistic regression analyses of the predictors of SPPB score in the full cohort in whom the SPPB was measured. 6MWD = 6-min walk distance; FFMI = fat-free mass index; MRC = Medical Research Council; QMVC = quadriceps maximal voluntary contraction; RFCSA = rectus femoris cross-sectional area; SGRQ = St. George’s Respiratory Questionnaire; SPPB = Short Physical Performance Battery.

Table Graphic Jump Location
Table 2 —Muscle Parameters and Logistic Regression Analyses of the Predictors of the SPPB

Data are presented as mean (SD) or median (interquartile range). Muscle parameters and logistic regression analyses of the predictors of the SPPB in the subcohort who underwent muscle biopsy. C:Fi = capillary to fiber ratio; CSA = myofiber cross-sectional area. See Table 1 legend for expansion of other abbreviations.

In the full cohort (N = 109), age, MRC dyspnea score, SGRQ, QMVC, RFCSA, and 6MWD were univariate predictors of SPPB score; sex, height, FEV1 % predicted, BMI, and FFMI were not predictors. In a multivariate analysis excluding RFCSA due to the strong colinearity with QMVC, only QMVC (OR, 0.89 [0.82, 0.96; P = .0004]) and 6MWD (OR, 0.99 [0.983, 0.996; P = .003]) were retained as independent predictors. Even when including RFCSA in the analysis (e-Table 1), QMVC and 6MWD remained the only independent predictors.

In the biopsy cohort (n = 31) (e-Table 2), the specimens obtained were not of sufficient size or quality to make fiber-type and CSA measurements in one patient and capillarity measurements in four patients. Fiber-type proportion, type 1 or 2 fiber CSA, and C:Fi were not predictors of SPPB score (Table 2). RV:TLC % was not a univariate predictor (P = .06); however, Kcoc % predicted (OR, 0.969 [0.941, 0.999; P = .04]) was, as were QMVC, RFCSA, and 6MWD, although none were retained in the multivariate model (Table 2, e-Table 3) even when excluding RFCSA from the analysis.

Seventy-one percent of the patients had minimal limitation, 19% had limitation, and 10% had major limitation (e-Fig 2, Table 3). Demographic characteristics were not different between the groups; furthermore, there was no difference in FEV1 % predicted, BMI, FFM, or FFMI. However, patients with limitation had reduced QMVC/BMI, QMVC % predicted, and 6MWD (Figs 1, 2), and higher MRC dyspnea and ADO scores. Those with major limitation also had reduced daily steps, RFCSA, and higher SGRQ and BODE scores. Furthermore, 6MWD was lower in those with major limitation as compared with those with limitation, (Fig 1).

Table Graphic Jump Location
Table 3 —Phenotypic Characteristics of Patients With COPD Stratified According to SPPB Score

ADO = age, dyspnea, and airflow obstruction; ANOVA = analysis of variance; BODE = BMI, airflow obstruction, dyspnea, and exercise capacity; FFM = fat-free mass. See Table 1 legend for expansion of other abbreviations.

a 

P < .05.

b 

P < .001.

c 

P < .01.

Figure Jump LinkFigure 1. A, B, Stratifying patients according to SPPB score identifies patients with (A) reduced exercise capacity and (B) reduced physical activity. 6MWT = 6-min walk test; SPPB = Short Physical Performance Battery.Grahic Jump Location
Figure Jump LinkFigure 2. A, B, Stratifying patients according to SPPB score identifies patients with (A) reduced quadriceps strength and (B) reduced muscle bulk. QMVC/BMI = quadriceps maximal voluntary contraction normalized to BMI; RFCSA = rectus femoris cross-sectional area. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

Only two patients with available biopsy data had an SPPB score < 7; consequently, comparisons were made between patients who scored < 10 and those who scored 10 to 12. Patients with an SPPB score < 10 had a higher proportion of type 2 fibers: 71% (14) vs 58% (15); P = .04; however, fiber CSA (P = .71) and C:Fi (P = .23) were not different (Fig 3). Those with SPPB scores < 10 also had a higher RV:TLC % (P = .04). Stratifying patients according to FEV1 % predicted identified differences in BMI, FFM, FFMI, MRC dyspnea score, SGRQ, daily steps, and 6MWD; however, QMVC/BMI, QMVC % predicted, RFCSA, SPPB (e-Table 4), or fiber preponderance did not differ (e-Fig 3).

Figure Jump LinkFigure 3. A-C, Vastus lateralis biopsy characteristics in patients with COPD stratified according to SPPB score. C:Fi = capillary to fiber ratio; CSA = myofiber cross-sectional area. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

The main finding of this study is that the principal determinants of the SPPB were quadriceps strength and functional exercise capacity rather than lung function as judged by FEV1. In a biopsy substudy, patients with SPPB limitation were also more likely to have fiber shift, suggesting a possible role for the test as a biomarker. The data show that the SPPB remains a valid measure of lower extremity function despite the presence of COPD and that SPPB limitation arises primarily because of skeletal muscle dysfunction. The known utility of the SPPB in unselected elderly populations and its relationship to established scoring systems in COPD suggests a role for the SPPB in identifying functionally impaired patients with COPD.

Critique of the Method

One limitation of this study is the cross-sectional design; it will be necessary to confirm longer term that, as with older adults, the SPPB is predictive of increased adverse outcomes in COPD beyond the impact of lung function impairment.32 This is likely, however, as the SPPB has repeatedly been shown to be predictive of future adverse events in general geriatric populations3,4; conversely, in our hospital-based cohort, we previously found that FEV1 wields little prognostic power once values are < 50% of that predicted.17 The likely prognostic value of the SPPB is further supported by the associations in this study with parameters recognized to be predictive of mortality in COPD, particularly quadriceps strength17 and functional exercise capacity.33

Second, given the hospital-based setting, it is uncertain how our findings apply to the wider COPD population. To mitigate this risk, we sought, by design, a wide range of airflow limitation. Even so, few patients had very low (ie, < 7) SPPB scores; conversely, 40% had the maximal score, demonstrating a ceiling effect. We suggest the SPPB has greater utility as a screening tool to detect those with impairment than for capturing changes in better functioning patients. The value of identifying patients with lower SPPB scores is demonstrated by the observation that these patients have physiologic and functional impairment, and structural muscle abnormality.

Third, we have previously demonstrated reliability and construct validity of two components of the SPPB.7,8 Larger-scale studies of the SPPB will be required to assess whether each of the three domains adds equal value to the assessment of the patient with COPD.

Significance of the Findings

The SPPB has repeatedly been shown to be predictive of future adverse events in general geriatric populations,3,4 contextually, the SPPB is not the only field test of function that has been evaluated in COPD. Puhan et al34 evaluated the number of times patients could move from sitting to standing over 1 min and found that this test was predictive of mortality. This sit-to-stand test is likely to place greater emphasis on quadriceps endurance properties than the test within the SPPB, which assesses the time taken to stand five times. Of the 100 participants that completed the sit-to-stand test within 60 s in our cohort, average completion time was 12.5 s, consistent with our previous findings.8 Because quadriceps endurance relates to muscle phenotype,35 whether fiber shift or oxidative enzyme content predicts differential performance in these two tests is of interest.

The SPPB has been repeatedly shown to be reliable; Ostir et al36 reported an ICC of 0.88 to 0.92 in > 1,000 women. In COPD, data on the SPPB are presently limited to a single large cohort focusing on the causes and associations of functional limitation rather than the SPPB. Eisner et al37 demonstrated that patients with COPD have lower SPPB scores, which may predict future disability.38 They also showed increased lean-to-fat ratio9 and preserved lung function39 related to higher SPPB score. We report findings in an older group of patients, a cohort closer to whom the SPPB was initially developed for. Additionally, given our aim to evaluate the SPPB as an assessment tool in patients already diagnosed with COPD, the patients had a wider range of disease severity; pertinently, nearly one-third of the patients Eisner et al9,39 reported on would no longer be diagnosed with COPD.

Interestingly, while quadriceps strength predicted SPPB score, BMI and FFMI did not, supporting the validity of the SPPB as a specific test of leg dysfunction rather than overall sarcopenia. This is consistent with our previous finding that strength is reduced, but FFMI preserved in patients with early spirometric disease.19 This suggests the need for caution when using FFMI as a measure of sarcopenia where loss of muscle may be regional, as in COPD.

To our knowledge, this is the first study to report the structural biopsy findings that relate to the SPPB score in any population. We have demonstrated that those with SPPB limitation have an increased type 2 fiber preponderance. This validates the utility of the SPPB in COPD where quadriceps muscle dysfunction is characterized by a shift toward type 2 fibers, unlike the type 1 fiber preponderance seen in healthy older individuals. We recently reported that fiber preponderance relates to functional exercise capacity in COPD and established cutoffs (65% for type 2 fibers in women, 68% for men).27 Therefore, the group with limitation had a fiber-type preponderance consistent with a pathologic state, while those without limitation did not. Type 1 and 2 fiber CSA were not different in those with SPPB limitation, consistent with our finding that, in COPD, fiber shift is more relevant than fiber atrophy in determining exercise performance and that fiber CSA is not different except in the minority of type 2x fibers.27

Quadriceps muscle capillarity was not reduced in those with SPPB limitation. Muscle capillarity is less well characterized than fiber type in COPD; in fact, it remains unclear whether capillarity changes are universally present. Whittom et al40 considered quadriceps capillarization relatively preserved in COPD. Conversely, Eliason et al31 showed that tibialis anterior capillarity was impaired in COPD and related to exercise capacity; nonetheless, tibialis muscle dysfunction in COPD is more controversial than quadriceps dysfunction.41,42 Gouzi et al43 extended these findings to show C:Fi related to QMVC and peak oxygen uptake and an impaired capillarity response to pulmonary rehabilitation. Pertinently, in all of these studies, fewer patients with COPD had biopsy procedures than the number we report on presently. Although 6MWD was an independent predictor of SPPB score, quadriceps strength was the major independent predictor: OR, 0.99 (0.983, 0.996) and 0.89 (0.82, 0.96), respectively. The SPPB is less likely to relate to muscle endurance properties than strength, which may explain the apparent disconnect with muscle capillarity. Our data are consistent with other larger general population studies, where grip strength has an OR of 0.86 to 0.89 in predicting SPPB impairment,44 although quadriceps strength is more relevant in COPD.

The majority of patients completed the SPPB in < 4 min in line with other studies,45 confirming the practical utility of the test. Only requiring a short course, stopwatch, and chair, it is attractive as a screening tool that may be applied to community, acute, or outpatient settings. When stratifying according to SPPB score, the differences in 6MWD were more than double the clinically significant minimally important difference of the test46; those most impaired managing less than one-half the distance of better performers. Additionally, unlike those with minimal limitation, patients scoring below 10 had a mean QMVC/BMI of below 1.2 and 6MWD of below 334 m, cutoffs predictive of mortality.17,33 FEV1 % predicted did not differ between the groups when stratifying according to SPPB, indicating that impaired performance occurred irrespective of airflow obstruction.

Because patients with COPD are usually characterized by FEV1 % predicted, the relationship with lung function requires further evaluation. FEV1 % predicted was not a predictor of SPPB score, however, in the smaller biopsy cohort, Kcoc % predicted (which has prognostic value32) was, although not an independent predictor; QMVC and 6MWD were not retained in this multivariate model either. While not a predictor of performance, RV:TLC% was higher in those with SPPB limitation and also has prognostic significance.30 Pertinently, stratifying disease severity according to FEV1 % predicted did not detect differences in SPPB score or important quadriceps parameters including strength, bulk, and fiber preponderance.

In conclusion, the SPPB is a simple and useful tool that relates to measures of quadriceps function in COPD, independent of FEV1. The SPPB may have value as a stratification tool, especially in trials where identifying participants with functional impairment is required. Contextually, the SPPB may be particularly useful in evaluating agents targeting quadriceps bulk or fiber preponderance, especially given that the latter otherwise requires an invasive procedure to establish.

Author contributions: Prof Polkey is the guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article.

Dr Patel: contributed to the design of the study, analysis of data, and preparation of the final manuscript; conceived the idea; recruited patients and collected the data; and drafting of the manuscript.

Dr Mohan: contributed to the drafting and preparation of the final manuscript, recruited patients, and collected the data.

Ms Andersson: contributed to the drafting and preparation of the final manuscript and performed the immunohistochemistry on the vastus lateralis biopsy specimens with subsequent analytical input.

Dr Baz: contributed to the analysis of the immunohistochemistry and the drafting and preparation of the final manuscript.

Dr Kon: contributed to the drafting and preparation of the final manuscript, recruited patients, and collected the data.

Dr Canavan: contributed to the drafting and preparation of the final manuscript, recruited patients, and collected the data.

Dr Jackson: contributed to the drafting and preparation of the final manuscript and performed the immunohistochemistry on the vastus lateralis biopsy specimens with subsequent analytical input.

Ms Clark: contributed to the drafting and preparation of the final manuscript and recruited patients.

Dr Hopkinson: contributed to the drafting and preparation of the final manuscript.

Dr Natanek: contributed to the drafting and preparation of the final manuscript.

Dr Kemp: contributed to the drafting and preparation of the final manuscript.

Dr Bruijnzeel: contributed to the drafting and preparation of the final manuscript and performed the immunohistochemistry on the vastus lateralis biopsy specimens with subsequent analytical input.

Dr Man: contributed to the design of the study, analysis of data, and drafting and preparation of the final manuscript and conceived the idea.

Prof Polkey: contributed to the design of the study, analysis of data, and drafting and preparation of the final manuscript and conceived the idea.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Jackson is an employee of AstraZeneca and owns shares within the company. Dr Natanek has been on an advisory board for Regneron Pharmaceuticals, Inc. Dr Kemp receives grant income from the Medical Research Council, Technology Support Board, and AstraZeneca. Prof Polkey has received personal reimbursement for lecturing or consultancy regarding muscle function in COPD from Novartis Corp and Koninklijke Philips N.V., and discloses institutional reimbursement for consultancy from GlaxoSmithKline, Novartis Corp, Regeneron Pharmaceuticals, Inc, Eli Lilly and Co, BioMarin Pharmaceutical Inc, and Boehringer Ingelheim GmbH and institutional agreements to conduct research with GlaxoSmithKline, Novartis Corp, AstraZeneca, and Koninklijke Philips N.V. Drs Patel, Mohan, Baz, Kon, Canavan, Hopkinson, Bruijnzeel, and Man, and Mss Andersson and Clark have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: Employees of AstraZeneca performed the immunohistochemistry and provided subsequent analytical input in addition to aiding the preparation of the final manuscript. The NIHR Biomedical Research Unit provided the facilities in which patients were recruited and the clinical data were collected. The remaining sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: We thank Winston Banya, MSc, statistical advisor to the NIHR Biomedical Research Unit, for input into the statistical analysis of the data. We also thank Katerina Pardali, PhD, for the methodology used in the fiber-type staining, the lung function departments at the Royal Brompton & Harefield Hospitals, and Rebecca Tanner, Julia Kelly, Cayley Smith, and Sam Clark for their help in assisting with taking some of the vastus lateralis muscle biopsies.

Additional information: The e-Appendix, e-Figures, and e-Tables can be found in the “Supplemental Materials” area of the online article.

6MWD

6-min walk distance

ADO

age, dyspnea, and airflow obstruction

BODE

BMI, airflow obstruction, dyspnea, and exercise capacity

C:Fi

capillary to fiber ratio

CSA

myofiber cross-sectional area

FFM

fat-free mass

FFMI

fat-free mass index

Kcoc

carbon monoxide gas transfer coefficient corrected for hemoglobin

MRC

Medical Research Council

QMVC

quadriceps maximal voluntary contraction

RFCSA

rectus femoris cross-sectional area

RV:TLC

residual volume to total lung capacity ratio

SGRQ

St. George’s Respiratory Questionnaire

SPPB

Short Physical Performance Battery

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Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005-1012. [CrossRef] [PubMed]
 
Lewis A, Riddoch-Contreras J, Natanek SA, et al. Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax. 2012;67(1):26-34. [CrossRef] [PubMed]
 
Natanek SA, Gosker HR, Slot IG, et al. Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (Copd); implications for stratified medicine? Muscle Nerve. 2013;48(4):488-497. [PubMed]
 
Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. Eur Respir J. 2005;26(3):511-522. [CrossRef] [PubMed]
 
Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26(4):720-735. [CrossRef] [PubMed]
 
Moore AJ, Soler RS, Cetti EJ, et al. Sniff nasal inspiratory pressure versus IC/TLC ratio as predictors of mortality in COPD. Respir Med. 2010;104(9):1319-1325. [CrossRef] [PubMed]
 
Eliason G, Abdel-Halim SM, Piehl-Aulin K, Kadi F. Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease. Respir Res. 2010;11:97. [CrossRef] [PubMed]
 
Boutou AK, Shrikrishna D, Tanner RJ, et al. Lung function indices for predicting mortality in COPD. Eur Respir J. 2013;42(3):616-625. [CrossRef] [PubMed]
 
Spruit MA, Polkey MI, Celli B, et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study investigators. Predicting outcomes from 6-minute walk distance in chronic obstructive pulmonary disease. J Am Med Dir Assoc. 2012;13(3):291-297. [CrossRef] [PubMed]
 
Puhan MA, Siebeling L, Zoller M, Muggensturm P, ter Riet G. Simple functional performance tests and mortality in COPD. Eur Respir J. 2013;42(4):956-963. [CrossRef] [PubMed]
 
Swallow EB, Gosker HR, Ward KA, et al. A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans. J Appl Physiol (1985). 2007;103(3):739-746. [CrossRef] [PubMed]
 
Ostir GV, Volpato S, Fried LP, Chaves P, Guralnik JM; Women’s Health and Aging Study. Reliability and sensitivity to change assessed for a summary measure of lower body function: results from the Women’s Health and Aging Study. J Clin Epidemiol. 2002;55(9):916-921. [CrossRef] [PubMed]
 
Eisner MD, Blanc PD, Yelin EH, et al. COPD as a systemic disease: impact on physical functional limitations. Am J Med. 2008;121(9):789-796. [CrossRef] [PubMed]
 
Eisner MD, Iribarren C, Blanc PD, et al. Development of disability in chronic obstructive pulmonary disease: beyond lung function. Thorax. 2011;66(2):108-114. [CrossRef] [PubMed]
 
Eisner MD, Iribarren C, Yelin EH, et al. Pulmonary function and the risk of functional limitation in chronic obstructive pulmonary disease. Am J Epidemiol. 2008;167(9):1090-1101. [CrossRef] [PubMed]
 
Whittom F, Jobin J, Simard PM, et al. Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Med Sci Sports Exerc. 1998;30(10):1467-1474. [CrossRef] [PubMed]
 
Marquis N, Debigaré R, Bouyer L, et al. Physiology of walking in patients with moderate to severe chronic obstructive pulmonary disease. Med Sci Sports Exerc. 2009;41(8):1540-1548. [CrossRef] [PubMed]
 
Seymour JM, Ward K, Raffique A, et al. Quadriceps and ankle dorsiflexor strength in chronic obstructive pulmonary disease. Muscle Nerve. 2012;46(4):548-554. [CrossRef] [PubMed]
 
Gouzi F, Préfaut C, Abdellaoui A, et al. Blunted muscle angiogenic training-response in COPD patients versus sedentary controls. Eur Respir J. 2013;41(4):806-814. [CrossRef] [PubMed]
 
Legrand D, Adriaensen W, Vaes B, Matheï C, Wallemacq P, Degryse J. The relationship between grip strength and muscle mass (MM), inflammatory biomarkers and physical performance in community-dwelling very old persons. Arch Gerontol Geriatr. 2013;57(3):345-351. [CrossRef] [PubMed]
 
Studenski S, Perera S, Wallace D, et al. Physical performance measures in the clinical setting. J Am Geriatr Soc. 2003;51(3):314-322. [PubMed]
 
Polkey MI, Spruit MA, Edwards LD, et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study Investigators. Six-minute-walk test in chronic obstructive pulmonary disease: minimal clinically important difference for death or hospitalization. Am J Respir Crit Care Med. 2013;187(4):382-386. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. A, B, Stratifying patients according to SPPB score identifies patients with (A) reduced exercise capacity and (B) reduced physical activity. 6MWT = 6-min walk test; SPPB = Short Physical Performance Battery.Grahic Jump Location
Figure Jump LinkFigure 2. A, B, Stratifying patients according to SPPB score identifies patients with (A) reduced quadriceps strength and (B) reduced muscle bulk. QMVC/BMI = quadriceps maximal voluntary contraction normalized to BMI; RFCSA = rectus femoris cross-sectional area. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 3. A-C, Vastus lateralis biopsy characteristics in patients with COPD stratified according to SPPB score. C:Fi = capillary to fiber ratio; CSA = myofiber cross-sectional area. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Descriptive Characteristics and Logistic Regression Analyses of the Predictors of SPPB Score

Data are presented as mean (SD), No. (%), or median (interquartile range). Descriptive characteristics and logistic regression analyses of the predictors of SPPB score in the full cohort in whom the SPPB was measured. 6MWD = 6-min walk distance; FFMI = fat-free mass index; MRC = Medical Research Council; QMVC = quadriceps maximal voluntary contraction; RFCSA = rectus femoris cross-sectional area; SGRQ = St. George’s Respiratory Questionnaire; SPPB = Short Physical Performance Battery.

Table Graphic Jump Location
Table 2 —Muscle Parameters and Logistic Regression Analyses of the Predictors of the SPPB

Data are presented as mean (SD) or median (interquartile range). Muscle parameters and logistic regression analyses of the predictors of the SPPB in the subcohort who underwent muscle biopsy. C:Fi = capillary to fiber ratio; CSA = myofiber cross-sectional area. See Table 1 legend for expansion of other abbreviations.

Table Graphic Jump Location
Table 3 —Phenotypic Characteristics of Patients With COPD Stratified According to SPPB Score

ADO = age, dyspnea, and airflow obstruction; ANOVA = analysis of variance; BODE = BMI, airflow obstruction, dyspnea, and exercise capacity; FFM = fat-free mass. See Table 1 legend for expansion of other abbreviations.

a 

P < .05.

b 

P < .001.

c 

P < .01.

References

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Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J. 2009;33(2):262-272. [CrossRef] [PubMed]
 
Waschki B, Spruit MA, Watz H, et al. Physical activity monitoring in COPD: compliance and associations with clinical characteristics in a multicenter study. Respir Med. 2012;106(4):522-530. [CrossRef] [PubMed]
 
Puhan MA, Garcia-Aymerich J, Frey M, et al. Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index. Lancet. 2009;374(9691):704-711. [CrossRef] [PubMed]
 
Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1005-1012. [CrossRef] [PubMed]
 
Lewis A, Riddoch-Contreras J, Natanek SA, et al. Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax. 2012;67(1):26-34. [CrossRef] [PubMed]
 
Natanek SA, Gosker HR, Slot IG, et al. Heterogeneity of quadriceps muscle phenotype in chronic obstructive pulmonary disease (Copd); implications for stratified medicine? Muscle Nerve. 2013;48(4):488-497. [PubMed]
 
Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. Eur Respir J. 2005;26(3):511-522. [CrossRef] [PubMed]
 
Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J. 2005;26(4):720-735. [CrossRef] [PubMed]
 
Moore AJ, Soler RS, Cetti EJ, et al. Sniff nasal inspiratory pressure versus IC/TLC ratio as predictors of mortality in COPD. Respir Med. 2010;104(9):1319-1325. [CrossRef] [PubMed]
 
Eliason G, Abdel-Halim SM, Piehl-Aulin K, Kadi F. Alterations in the muscle-to-capillary interface in patients with different degrees of chronic obstructive pulmonary disease. Respir Res. 2010;11:97. [CrossRef] [PubMed]
 
Boutou AK, Shrikrishna D, Tanner RJ, et al. Lung function indices for predicting mortality in COPD. Eur Respir J. 2013;42(3):616-625. [CrossRef] [PubMed]
 
Spruit MA, Polkey MI, Celli B, et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study investigators. Predicting outcomes from 6-minute walk distance in chronic obstructive pulmonary disease. J Am Med Dir Assoc. 2012;13(3):291-297. [CrossRef] [PubMed]
 
Puhan MA, Siebeling L, Zoller M, Muggensturm P, ter Riet G. Simple functional performance tests and mortality in COPD. Eur Respir J. 2013;42(4):956-963. [CrossRef] [PubMed]
 
Swallow EB, Gosker HR, Ward KA, et al. A novel technique for nonvolitional assessment of quadriceps muscle endurance in humans. J Appl Physiol (1985). 2007;103(3):739-746. [CrossRef] [PubMed]
 
Ostir GV, Volpato S, Fried LP, Chaves P, Guralnik JM; Women’s Health and Aging Study. Reliability and sensitivity to change assessed for a summary measure of lower body function: results from the Women’s Health and Aging Study. J Clin Epidemiol. 2002;55(9):916-921. [CrossRef] [PubMed]
 
Eisner MD, Blanc PD, Yelin EH, et al. COPD as a systemic disease: impact on physical functional limitations. Am J Med. 2008;121(9):789-796. [CrossRef] [PubMed]
 
Eisner MD, Iribarren C, Blanc PD, et al. Development of disability in chronic obstructive pulmonary disease: beyond lung function. Thorax. 2011;66(2):108-114. [CrossRef] [PubMed]
 
Eisner MD, Iribarren C, Yelin EH, et al. Pulmonary function and the risk of functional limitation in chronic obstructive pulmonary disease. Am J Epidemiol. 2008;167(9):1090-1101. [CrossRef] [PubMed]
 
Whittom F, Jobin J, Simard PM, et al. Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Med Sci Sports Exerc. 1998;30(10):1467-1474. [CrossRef] [PubMed]
 
Marquis N, Debigaré R, Bouyer L, et al. Physiology of walking in patients with moderate to severe chronic obstructive pulmonary disease. Med Sci Sports Exerc. 2009;41(8):1540-1548. [CrossRef] [PubMed]
 
Seymour JM, Ward K, Raffique A, et al. Quadriceps and ankle dorsiflexor strength in chronic obstructive pulmonary disease. Muscle Nerve. 2012;46(4):548-554. [CrossRef] [PubMed]
 
Gouzi F, Préfaut C, Abdellaoui A, et al. Blunted muscle angiogenic training-response in COPD patients versus sedentary controls. Eur Respir J. 2013;41(4):806-814. [CrossRef] [PubMed]
 
Legrand D, Adriaensen W, Vaes B, Matheï C, Wallemacq P, Degryse J. The relationship between grip strength and muscle mass (MM), inflammatory biomarkers and physical performance in community-dwelling very old persons. Arch Gerontol Geriatr. 2013;57(3):345-351. [CrossRef] [PubMed]
 
Studenski S, Perera S, Wallace D, et al. Physical performance measures in the clinical setting. J Am Geriatr Soc. 2003;51(3):314-322. [PubMed]
 
Polkey MI, Spruit MA, Edwards LD, et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study Investigators. Six-minute-walk test in chronic obstructive pulmonary disease: minimal clinically important difference for death or hospitalization. Am J Respir Crit Care Med. 2013;187(4):382-386. [CrossRef] [PubMed]
 
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