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Extrapulmonary Effects of Chronic Obstructive Pulmonary Disease on Physical Activity

A Cross-sectional Study
Henrik Watz1, Benjamin Waschki1, Corinna Boehme1, Martin Claussen2, Thorsten Meyer3, and Helgo Magnussen1,2
1 3

Pulmonary Research Institute, 2Center for Pneumology and Thoracic Surgery, Hospital Grosshansdorf, Grosshansdorf, Germany; and Institute of Social Medicine, Medical University Luebeck, Luebeck, Germany

Rationale: Physical activity is reduced in patients with chronic obstructive pulmonary disease (COPD). COPD has a systemic component that includes significant extrapulmonary effects that may contribute to its severity in individual patients. Objectives: To investigate the association of extrapulmonary effects of the disease and its comorbidities with reduced physical activity in patients with COPD. Methods: In a cross-sectional study, 170 outpatients with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages I–IV; BODE [body mass index, airway obstruction, dyspnea, and exercise capacity] score 0–10) underwent a series of tests. Physical activity was assessed over 5 to 6 consecutive days by using a multisensor accelerometer armband that records steps per day and the physical activity level (total daily energy expenditure divided by whole-night sleeping energy expenditure). Cardiovascular status was assessed by echocardiography, vascular Doppler sonography, and levels of N-terminal pro–B-type natriuretic peptide. Mental status, metabolic/muscular status, systemic inflammation, and anemia were assessed by Beck Depression Inventory, bioelectrical impedance analysis, handgrip strength, high-sensitivity C-reactive protein/fibrinogen, and hemoglobin, respectively. Measurements and Main Results: In a multivariate linear regression analysis using either steps per day or physical activity level as a dependent variable, the extrapulmonary parameters that were associated with reduced physical activity in patients with COPD independently of GOLD stages or BODE score were N-terminal pro– B-type natriuretic peptide levels, echocardiographically measured left ventricular diastolic function, and systemic inflammation. Conclusions: Higher values of systemic inflammation and left cardiac dysfunction are associated with reduced physical activity in patients with COPD. Keywords: pulmonary disease, chronic obstructive; ventricular function, left; acute phase reaction; activities of daily living

AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject

Physical activity is reduced in patients with moderate to severe chronic obstructive pulmonary disease compared with healthy subjects.
What This Study Adds to the Field

Higher values of systemic inflammation and left cardiac dysfunction are associated with reduced physical activity in patients with chronic obstructive pulmonary disease.

Physical activity is a parameter of increasing clinical interest. Lower levels of physical activity are associated with a higher risk for diseases such as cardiovascular disease (1), type 2 diabetes mellitus (2), mental disorders (3, 4), cancer (5), and chronic obstructive pulmonary disease (COPD) (6). In COPD, regular physical activity modifies smoking-related lung function decline and is associated with lower mortality (6, 7).

COPD has been defined as a preventable and treatable disease with significant extrapulmonary effects that may contribute to its severity in individual patients (8). Cardiovascular, mental, and musculoskeletal comorbidities, as well as elevated markers of systemic inflammation and anemia, can frequently be found in patients with COPD and have an impact on mortality in this population (9–12). Physical activity has been shown to be reduced in patients with COPD (13, 14). We hypothesized that this reduction in physical activity may be explained by the extrapulmonary effects of COPD and its comorbidities. Thus, the rationale of our study was to assess the association of extrapulmonary effects and comorbidities in patients with COPD with reduced physical activity as measured by an accelerometer. We used multivariate linear regression analysis, the clinical stages of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (8), and the BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) index (15) to analyze the data. We previously presented the methodologic aspects of accelerometer measurement in abstract form in this journal (16).

METHODS
Study Population
One hundred seventy outpatients with stable COPD (128 male, 42 female) were studied between February and November 2006 at the Pulmonary Research Institute at Hospital Grosshansdorf, SchleswigHolstein, Germany. Patients were recruited from the institute’s database that is used for clinical trials in COPD; it consists of 691 ambulatory patients with an established diagnosis of COPD (mean FEV1, 54% predicted; mean age, 62 yr). Patients were contacted by a study nurse, and those who expressed their availability and interest in the study were enrolled. Exclusion criteria were an exacerbation of COPD within the past 2 months, clinical signs of acute heart failure, and severe pain syndromes that could interfere with physical activity. The study was approved by the local ethics committee of SchleswigHolstein, and participants gave their written, informed consent.

(Received in original form July 10, 2007; accepted in final form November 29, 2007 ) Supported by an unrestricted research grant from AstraZeneca. The funding source had no role in the study design, collection, analysis, and interpretation of the data or in the decision to submit the paper for publication. Correspondence and requests for reprints should be addressed to Prof. Dr. Helgo Magnussen, M.D., Pulmonary Research Institute at Hospital Grosshansdorf, Center for Pneumology and Thoracic Surgery, Woehrendamm 80, D-22927 Grosshansdorf, Germany. E-mail: magnussen@pulmoresearch.de This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org
Am J Respir Crit Care Med Vol 177. pp 743–751, 2008 Originally Published in Press as DOI: 10.1164/rccm.200707-1011OC on November 29, 2007 Internet address: www.atsjournals.org

5) 7 (19) 11 (31) 9. n (%) University entrance degree. Metric variables were not centered. Pittsburgh. Because a history of diabetes mellitus has been shown to be a determinant of low physical activity in COPD (28).8) 72 (42) 79 (46) 5 (2–12) 133 (78) 16 (9) 16 (9) GOLD I 34 (20) 66.5 (25) (7. Nutritional depletion was defined as a BMI of 21 kg/m2 or less or a fat-free mass index of 16 kg/m2 or less in men and 15 kg/m2 or less in women (20). n (%) Drinks per week of regular drinkers. the amount of variance (R2) was calculated.2 35 55.744 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 177 2008 Clinical Stages of COPD Patients were classified according to the GOLD staging system (8) and the criteria of the BODE index (15). The BODE index was designed to predict mortality in patients with COPD and has a range of 0 to 10 points. extrapulmonary variables (left ventricular ejection fraction. muscle strength.0. As a second step. n (%) Unemployed.3) (81) (23. * P values were tested by analysis of variance if the variable is stated as mean (SD) or by x2 test if the variable is stated as n (%).6) 128 (75) 51. Educational status. N-terminal pro–B-type natriuretic peptide (NT–proBNP) was used as a systemic biomarker of heart failure (17). 0. n (%) Pack-years of smoking.70 or greater is defined as active. n (%) Age. A TABLE 1.0 (20.3 (5.9 (26. after controlling for possible confounders. Peripheral muscle strength was measured with a handgrip dynamometer.6) 15 (44) 17 (50) 4 (2–7) 27 (79) 3 (9) 3 (9) GOLD II 57 63. IL).78 is strongly associated with a lower risk of mortality in healthy older adults (22). Mental Status The Beck Depression Inventory was used to assess depressive symptoms. weight in kg/height in m2) and fat-free mass index (fat-free mass in kg/height in m2. . In a first step. Therefore. Kruskal-Wallis test (ordinal or nonnormal metric variables). n (%) Regular drinkers. diastolic left heart function (deceleration time of the early transmitral flow and ratio of the peak velocity of the early E-wave to atrial A-wave). yr. Multivariate linear regression analyses were performed using either the physical activity level or steps per day as the dependent variable. High-sensitivity C-reactive protein (hs-CRP) and fibrinogen served as markers of systemic inflammation.0 (6. PATIENT CHARACTERISTICS Total Patients. and systolic pulmonary artery pressure. and physiologic indicators of energy expenditure that enable the investigator to determine the physical activity level. BodyMedia.44 . and a physical activity level greater than 1.20 0.6 23 22 5. BODE index was categorized by quintiles and dummy-coded with the first quintile as the reference category. n (%) 170 (100) 64.81 0. obesity (BMI > 30 kg/m2). age. systolic pulmonary artery pressure. ankle brachial index.05). early retirement. median (IQR) Retired or early retired. sex. As a third step.9 (24.4) (53) (51) (2–14) GOLD IV 36 (21) 63. a stepwise approach to model building was applied. No adjustment for retirement. A physical activity level of 1. or employment status was made. version 14.3 41 50. For each level (confounders. Anemia was defined as a hemoglobin level below 13 g/dl (12). was also assessed. Inc.83 0. IQR 5 interquartile range. it was also recorded.6) 25 (74) 46. fibrinogen or hs-CRP.0 (SPSS. disease severity represented by GOLD stages or BODE index. All extrapulmonary parameters that were shown to be significant at this step of analysis were included in the final multivariate regression model.7 (6. Metabolic and Muscular Status Body mass index (BMI. mean (SD) Current smokers. A more detailed description of the applied clinical methods and the accelerometer measurement is contained in the online supplement. as the variable was skewed. with higher scores indicating a greater risk of death (15). Statistical Analysis Differences between patients in different GOLD stages were analyzed by x2 test (categorical variables). PA) that is worn on the upper right arm over the triceps muscle. Depression was defined as a Beck Depression Inventory score of 15 or greater (19). and analysis of variance (normally distributed metric variables). NT–pro-BNP.5 (3–14) 33 (92) 2 (6) 2 (6) P Value* 0.. and anemia) were added to the model if they were of statistical significance.8) (72) (27. Chicago.2) 27 (75) 54. It was the aim of this analysis to identify extrapulmonary factors that are associated with reduced physical activity independent of the clinical stages of COPD. which is positively correlated with leisure time physical activity (26).74 0. and history of diabetes mellitus) were included in the model if they were of statistical significance (P . Physical Activity Physical activity was measured over 5 to 6 consecutive days using a multisensor armband (SenseWear Pro Armband. we also assessed alcohol consumption (drinks per week) and current smoking status.7 27 29 5 (34) (6.76 40 (70) 6 (11) 7 (12) 33 (77) 5 (12) 4 (9) Definition of abbreviations: GOLD 5 Global Initiative for Chronic Obstructive Lung Disease. Data analysis was performed with the Statistical Package for Social Science. and extrapulmonary parameters are given in Tables 1 to 3. smoking status. Patients quoting pain symptoms that interfered with general activity on the ‘‘interference with function scale’’ of the Brief Pain Inventory (27) were recorded.15 0. measured by bioelectrical impedance analysis) were determined. The potential confounders (drinks per week. Cardiovascular Status and Systemic Inflammation Echocardiography was performed to measure systolic left heart function (left ventricular ejection fraction). GOLD stages were dummycoded with GOLD I as a reference category. as these conditions could also be the result of disease severity. Vascular Doppler sonography was performed to assess the ankle brachial index. P value for drinks per week was tested by Kruskal-Wallis test. Anemia Hemoglobin levels were determined in tubes containing ethylenediaminetetraacetic acid. GOLD stages or BODE index were included in the model. mean (SD) Males. We determined the physical activity level by dividing total daily energy expenditure by whole-night sleeping energy expenditure (21).01 0. It incorporates a biaxial accelerometer that records steps per day.11 0. Skewed data were log transformed to yield normal distributions. measurements of physical activity. deceleration time of the early transmitral flow or ratio of the peak velocity of the early E-wave to atrial A-wave. Assessment of Potential Confounders of Physical Activity Because of the potential interaction of lifestyle with physical activity (23–25). RESULTS Characteristics of patients. nutritional depletion. pain symptoms. and arterial hypertension were included in the model independent of statistical significance. extrapulmonary factors).0) (47) (51) (2–10) GOLD III 43 63. educational status. which is an accurate measurement of peripheral arterial disease (18).

19 0.001 . Boehme.284) (0.370) 1.001 .0 (5.28) 37 (22) GOLD I 114.7) 35 (21) 35.15 .7) 36. Twenty-two percent of the patients had a physical activity level of 1.0.4) 5 (14) Definition of abbreviations: GOLD 5 Global Initiative for Chronic Obstructive Lung Disease. P values for E-wave/A-wave.0 (1. NT– pro-BNP 5 N-terminal pro–B-type natriuretic peptide. GOLD stages or BODE score accounted for two-thirds of the explained variance of the physical activity level.7) 8 (14) 34.† mm Hg Capillary PCO2.7 (1.4) (7. mean (SD) Capillary PO2.0.8) 12 (33) 33. no hypertension).8 (8. Results of the multivariate analysis for the physical activity level are given in Tables 4 and 5: The total explained variance of the physical activity level (total R2) was 37% for the model that included GOLD stages plus extrapulmonary effects and 36% for the model that included BODE score plus extrapulmonary effects.6 (5.6 (9. ‡ Nutritional depletion was defined as body mass index < 21 kg/m2 and/or fat-free mass index <16 kg/m2 in men and <15 kg/m2 in women.9 (6.19 0.4) 8 (19) 25.66 0. hs-CRP 5 high-sensitivity C-reactive protein.6) 14.1 (0. nutritional depletion (n 5 5).6 for hypertension vs. median (IQR) NT–pro-BNP .9 73 10 0.684) 1. Figures 1A–1F depict the impact of the extrapulmonary effects that were significant in the multivariate analysis on steps per day according to the clinical stages provided by GOLD and BODE.20) (19) GOLD III 1 (2) 253 (48) 0. LUNG FUNCTION. n (%) Metabolic status Body mass index. † P values were tested by analysis of variance if the variable is stated as mean (SD) or by x2 test if the variable is stated as n (%).8 (2. % pred.45 (0.8) 0 (0 . log ratio of the peak velocity of the early E-wave to atrial A-wave.0) 39.160 1. Waschki. mean (SD) NT–pro-BNP. Deceleration time of the early transmitral flow had a stronger effect on the model than did the ratio of the peak velocity of the early E-wave to atrial A-wave (Tables 4 and 5). diastolic left ventricular function.91 14 (0) (59) (0.90 30.6) (5.897) (0.27) (32) GOLD III 84. no hypertension. 2) (3.87 0. GOLD 5 Global Initiative for Chronic Obstructive Lung Disease. mean (SD) Fat-free mass index.0. P values for FEV1 and steps per day were tested by Kruskal-Wallis test.2 60.: Physical Activity in COPD TABLE 2.04 436 (97) 2.1) 69 (47–102) 7 (21) 0. kg/m2. IQR 5 interquartile range.6 (1. BODE SCORE.2) 67 (36–117) 10 (23) 0.3 (4. n (%) Deceleration time of the E-wave.773 1.9 (1. n (%) Systemic inflammation Fibrinogen.9. Fibrinogen had a stronger effect than hs-CRP (Tables 4 and 5). x Physical activity level > 1. as the homogeneity of variance was not given.0) 33 (19) 26.3 (9. airway obstruction.7) (3.17) (3) 745 P Value* .06 0.0 (8.70.6 (5.0) 17.0 (13.0.5) 4 (12) 36.79–1.8) 38. deceleration time of the E-wave (n 5 12).5) (46–130) (28) (0.001 .8) 14.6 (2.8) 90.7 1 7.2) 9 (5) 431 (98) 3.8 (1. P 5 0. .03 0.8) (6. mean (SD) Ankle brachial index . they accounted for another third of the explained variance of the TABLE 3. median (IQR) Steps per day.0.5) (38–108) (21) (0.97 43 (3) (56) (0. mean (SD) hs-CRP.0.9) 0 (0) GOLD IV 0 299 0.0 (0. mean (SD) E-wave/A-wave. as the variable was skewed.2 (14.8 32.23 0.2) 48.25) 9 (26) GOLD II 96. and exercise capacity.126 (3.001 .2) 18.692) 1. Arterial hypertension did not affect echocardiographic parameters of diastolic function of the left ventricle in our cohort (deceleration time of the early transmitral flow.3 63.70–0.93) (9.001 .01 Definition of abbreviations: BODE 5 body mass index.2) 18.0 (3.0) 5 (9) 27.9 (21. The extrapulmonary factors that significantly contributed to the model independently of GOLD stage or BODE score were NT–pro-BNP.0.1 (2. as the variables were skewed. pg/ml.001 . as the homogeneity of variance was not given.19 .5 (6.3) 17.01 0.97 (0. mg/dl.89 (0. Similar results of the multivariate analysis for steps per day are given in Tables 6 and 7.27 1 (20.’’ more detailed description of patients’ characteristics can be found in the online supplement (Tables E1 and E2).7 (16.7) 15.x n (%) 91.8–9.2) 3 (2–4) 5. P value for BODE score was tested by Kruskal-Wallis test.3) 18. GOLD I 3 (9) 256 (51) 0. * P values were tested by analysis of variance if the variable is stated as mean (SD) or by x2 test if the variable is stated as n (%).0. and systemic inflammation.8) (1.72 for hypertension vs.6–6. mean (SD) FEV1. systolic pulmonary artery pressure (n 5 47).0 (6. kg/m2.0.9–4. n (%) Ankle brachial index.22) (39) P Value† 0. IQR 5 interquartile range.882 (3. Together.Watz.0.0) 40. median (IQR) Systolic pulmonary artery pressure.85–4.9 (7.2) 68.04) 29.4 42.01 .0 (3.50 (0.70 is defined as ‘‘active.0 (4.82 30.01 . ‡ Physical activity level is defined as total daily energy expenditure divided by whole-night sleeping energy expenditure. g/dl. and handgrip strength (n 5 1). mean (SD) Nutritional depletion.45 0.78 0. mean (SD) Hemoglobin .20) (25) physical activity level.4 (2. * Data are missing for the following variables: left ventricular ejection fraction (n 5 3).3 (22.1) 38.0.70 or greater (Table 2).0 (1. et al.3 (2.6) 2 (1–4) 5.20) 10 (23) 468 (115) 4. MEASUREMENTS OF EXTRAPULMONARY PARAMETERS* Total Cardivascular disease Left ventricular ejection fraction < 50%.1 (8.79–1.0.0. 13 g/dl.6 67 39 0.3 (5.001 . mm Hg.0 (1. P value for hemoglobin was tested by Kruskal-Wallis test.8 62 12 0.92 (0.84–1.04) (6. median (IQR) Mental status Beck Depression Inventory > 15.4 (8.92 29. mean (SD) FEV1/FVC.001 0. P 5 0.‡ mean (SD) Physical activity level > 1.† mm Hg BODE score.8 (5. dyspnea.5 37.8 36.990 (3.0) 2 (6) GOLD II 1 250 0. mg/L. mean (SD) Anemia Hemoglobin.05) 31. 125 pg/ml.63 (0.3) 69.7) 71.0.62 18 (16.7) (11.‡ n (%) Muscle strength Handgrip strength.99 (0. % pred.5) 14.8 (6.1) (9.99 11 (2) (55) (0.9) 56. 0.9 (7.19) 8 (24) 395 (64) 2.7) 15. mean (SD) Physical activity level.4) (8. E-wave/A-wave (n 5 8).001 .9) 11 (28) 36.2–6. AND PHYSICAL ACTIVITY Total FVC. kg.25) 9 (21) GOLD IV 72.0 53.3) (40–117) (23) (0.0) 7.3 (11.7) 62. NT–proBNP and hs-CRP were tested by Kruskal-Wallis test.79–1.3) 2 (4) 444 (89) 2. ms.3) 5 (15) 27.1 (0.1) (8.1) (4–7) (1.01 .6 6 2.35) 15 (42) 24. † Data are missing for seven patients.02) (7.2 71. n (%) 5 262 0.

001 20. a patient has a reduction of physical activity level of 0.27 0. yr Hypertension BMI > 30 BODE score Quintile 2 Quintile 3 Quintile 4 Quintile 5 Fibrinogen.† ms B 2.035 0. SE.211. 0. A value of –0.176 0. 14).75 0.028 . and extrapulmonary effects account for an additional 11% of the variance (R2 change.197.21 0.026 0.032 20.0.001 0.023 20. .030 20. age.001 SE 0.001.02 R2 Change 0.037.11).34 0.043 0. Airway obstruction.004 R2 0.0.001 for the unstandardized regression coefficient B for DcT means that. –0.050 20.142 . pg/ml DcT.0. BODE SCORE AND EXTRAPULMONARY PARAMETERS AS PREDICTORS OF PHYSICAL ACTIVITY LEVEL IN A MULTIVARIATE LINEAR REGRESSION ANALYSIS (n 5 158 PATIENTS) Unstandardized Regression Coefficients Predictive Parameter Constant Female sex Age.061 .048 20. DISCUSSION The main finding of our study is that higher values of systemic inflammation and left cardiac dysfunction are associated with reduced physical activity in patients with COPD. DcT 5 deceleration time of the early transmitral flow.001 20.009 20.0.070 0. For an explanation of BODE quintiles.048 0.001.054 0.068.043 0.003 20.02 R2 Change 0. A weak but significant correlation between NT–pro-BNP and measurements of echocardiography was for left atrial size and NT–pro-BNP (r 5 0.263 20.233 0.282 20. P .022 . NT–pro-BNP 5 N-terminal pro–B-type natriuretic peptide.139 0.242 20. CI 5 confidence interval.11 Definition of abbreviations: BMI 5 body mass index.000 P Value .024. 0. n 5 162). 29) with physical activity.86 0.24 0.37 0.02 0.139 0.252 0. For interpretation of the table. per milligram increase of fibrinogen. 0.20 0.384 20.001 0.0.0.052 0.0. GOLD accounts for 24% of the variance for the physical activity level (R2 change.001 20.* mg/dl log NT–pro-BNP. † log E-wave/A-wave ratio instead of DcT is also significant (unstandardized regression B.001 for the unstandardized regression coefficient B for fibrinogen means that.157 0.014 20.403 20.001 0.001 0.163 0.0.807 20.001 20.006 .003 0.712 0. CI 5 confidence interval.002 Upper Bound 2.049 20. Total explained variance of the model is 37% for physical activity level (R2. A value of –0.14 0.0.128 20. SE. 0.005 20.119 20. SE.002 Upper Bound 2.001 SE 0. Garcia-Aymerich and coworkers found further determinants of physical activity in a TABLE 5.002. pg/ml DcT.146 0.051 20.047 0.003 0. and exercise capacity.160 .0.047 0.* mg/dl log NT–pro-BNP.111 20.792 20.073 20.057 0.001 95% CI Lower Bound 1.002 R2 0. P 5 0. GOLD 5 Global Initiative for Chronic Obstructive Lung Disease.37) with the parameters used in this model.20 0. 0.080 20.040 0. * log high-sensitivity C-reactive protein instead of fibrinogen is also significant (unstandardized regression B.008 0.093 20.000 P Value . P 5 0. The table can be interpreted as follows: Sex.22 0.24).234 0.001 0.001 0.91 0. P 5 0. GOLD STAGES AND EXTRAPULMONARY PARAMETERS AS PREDICTORS OF PHYSICAL ACTIVITY LEVEL IN A MULTIVARIATE LINEAR REGRESSION ANALYSIS (n 5 158 PATIENTS) Unstandardized Regression Coefficients Predictive Parameter Constant Female sex Age. airway obstruction.065 .0. 0. independent of the clinical stages of COPD according to GOLD or the multidimensional BODE index. † log E-wave/A-wave ratio instead of DcT is also significant (unstandardized regression B. a patient has a reduction of physical activity level of 0.007 0. 0.26 0. n 5 162).181 20.0.023 .001 0.048 20. dyspnea. * log high-sensitivity C-reactive protein instead of fibrinogen is also significant (unstandardized regression B.14 Definition of abbreviations: BMI 5 body mass index. 0.746 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 177 TABLE 4.10 0.000 20. per millisecond increase of DcT. BODE 5 body mass index. please refer to the footnote for Table 4. correlates only weakly (14) to moderately (13.093 20.059 0.02).024.094. see the legend to Figure 1. NT–pro-BNP 5 N-terminal pro–B-type natriuretic peptide. arterial hypertension and BMI > 30 account for 2% of the variance for the physical activity level (R2 change.001).186 20.061 .001 .001 0.22 0. n 5 162). yr Hypertension BMI > 30 GOLD stage II III IV Fibrinogen.027 20.065 20. however.001 0.0.000 20. SE. 0.36 0.001 95% CI Lower Bound 1.36.058 0. –0.097.016 20.003 .032.005.073.058 0.730 0. Physical activity has previously been shown to be reduced in patients with moderate to severe COPD compared with healthy subjects (13.050 0.02 2008 0. which implies that there might be additional factors influencing physical activity in patients with COPD.235 20.055 0. P 5 0.044 . 0.093 20.16 0. DcT 5 deceleration time of the early transmitral flow.006 20.268 0. 0. n 5 162).0.† ms B 2.

179.727 28 1.31 0.† ms B 20.32 0. et al.104 22.0.41 0.833 570 40 524 588 693 710 711 745 2 273 4 95% CI Lower Bound 14.15 .* mg/dl log NT–pro-BNP.698. pg/ml DcT. diastolic dysfunction of the left ventricle in COPD is a frequently reported echocardiographic observation (31). cohort of 346 patients with severe COPD (FEV1.16 0. which is known in patients with stable chronic left heart failure (32) and may reflect chronic left ventricular filling pressure (33).001 . P 5 0.003). pg/ml DcT. P 5 0. Using the Minnesota Leisure Time Physical Activity Questionnaire.001 0. In about 50% of these patients.38 0.04 0. SE.528 1.32 0.012. yr Hypertension BMI > 30 BODE score Quintile 2 Quintile 3 Quintile 4 Quintile 5 Fibrinogen.742 22 2130 26 P Value .002 R2 0.874 28 2617 214 SE 2.04 747 0. Even without symptoms of heart failure.563 385 349 21. An increased left ventricular filling pressure leads to an increase in left ventricular wall stretch.: Physical Activity in COPD TABLE 6. BODE SCORE AND EXTRAPULMONARY PARAMETERS AS PREDICTORS OF STEPS PER DAY IN A MULTIVARIATE LINEAR REGRESSION ANALYSIS (n 5 158 PATIENTS) Unstandardized Regression Coefficients Predictive Parameter Constant Female sex Age.774 1.272 27 2677 215 SE 2. GOLD STAGES AND EXTRAPULMONARY PARAMETERS AS PREDICTORS OF STEPS PER DAY IN A MULTIVARIATE LINEAR REGRESSION ANALYSIS (n 5 158 PATIENTS) Unstandardized regression coefficients Predictive Parameter Constant Female sex Age.011).767 24. Our study extended these observations by objectively quantifying systemic components of COPD (10) and their associations with reduced physical activity. which is the predominant pathophysiologic process underlying increased circulating levels of NT–pro-BNP (34).001 R2 0.0. and long-term oxygen therapy were independently associated with a low level of physical activity. P 5 0.16 0.365 22. health-related quality of life.* mg/dl log NT–pro-BNP. SE.155 25.993.401 24 277 25 P Value . 35% predicted) (28). Boehme.† ms B 20. NT–pro-BNP values showed a weak correlation with left atrial size. Waschki.052 26. * log high-sensitivity C-reactive protein instead of fibrinogen is also significant (unstandardized regression B.352 22.273 22. –767. 2.936 587 41 537 630 652 729 774 3 277 5 95% CI Lower Bound 14. Here we show for the first time that echocardiographic parameters indicating impaired diastolic filling processes of the left ventricle are associated with reduced physical activity in patients with COPD.001 0.001 .18 0. † log E-wave/A-wave ratio instead of DcT is also significant (unstandardized regression B. SE.30 0.158 223 Upper Bound 25.35 0. Twenty-three percent of our cohort—nearly 30% of the patients with GOLD stage IV disease—had NT–pro-BNP levels greater than 125 pg/ml.751 22.575 2527 2132 2522 21. For interpretation of the table.726 518 259 501 2859 2939 22. * log high-sensitivity C-reactive protein instead of fibrinogen is also significant (unstandardized regression B.0.225 224 Upper Bound 26.0.001 0.022. yr Hypertension BMI > 30 GOLD stage II III IV Fibrinogen.006 0.20 0.925 2642 2141 2561 22. n 5 162).0. SE. 1.04 R2 change 0.Watz. see Table 4.33 0.06 . please refer to the legend for Table 4.025 0.35 0. 284. they found that socioeconomic status. see the legend to Figure 1.175 600 252 514 2589 2982 21. left ventricular diastolic dysfunction causes the symptoms of heart failure (30).168. For explanation of BODE quintiles.646 24.714 24.001 0.016 0.28 0. n 5 162). 2.10 For definition of abbreviations. 299.346 213 21. P 5 0. history of diabetes. TABLE 7.09 For definition of abbreviations.001 0. Higher levels of NT–proBNP were associated with reduced physical activity in our patients. For interpretation of the table. Left heart failure is present in 20% of elderly patients with COPD (30). . 1. which is an accepted threshold that indicates potential heart failure in patients with COPD (17).45 0.226 24.0.240 23.678 23 1. † log E-wave/A-wave ratio instead of DcT is also significant (unstandardized regression B. please refer to the legend for Table 4.04 R2 Change 0.801 212 21.549 574 388 38 21. see Table 5. –869.

P 5 0. 0.01. BODE quintile 2: BODE score 1. P . See (B) for explanation of BODE quintiles.001.3 pg/ml. interaction effect BODE 3 NT–pro-BNP.57. BODE quintile 5: BODE score 5–10. Two-way ANOVA: main effect GOLD. and exercise capacity) score and fibrinogen level. (D) Steps per day according to BODE score and NT–pro-BNP level.02. P .90. BODE quintile 4: BODE score 3 1 4. The median NT–pro-BNP level in our cohort was 67. 0. (A) Steps per day according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages and fibrinogen level. P .748 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 177 2008 Figure 1. n 5 33 (19%). Two-way analysis of variance (ANOVA): main effect GOLD. P . n 5 33 (19%). P 5 0. P 5 0. interaction effect BODE 3 fibrinogen. Two-way ANOVA: main effect BODE. The mean fibrinogen level in our cohort was 436 mg/dl. n 5 31 (18%).80. 0. P 5 0. 0. (C) Steps per day according to GOLD stages and N-terminal pro–B-type natriuretic peptide (NT–pro-BNP) level.04. dyspnea. main effect fibrinogen. (E) Steps per day according to GOLD stages and . 0. main effect fibrinogen. interaction effect GOLD 3 NT–pro-BNP. P 5 0. BODE quintile 3: BODE score 2. interaction effect GOLD 3 fibrinogen. P . main effect NT–pro-BNP.04.001. BODE quintile 1: BODE score 0.001. airway obstruction. P 5 0. n 5 41 (24%). Twoway ANOVA: main effect BODE. main effect NT–pro-BNP. n 5 32 (19%). (B) Steps per day according to BODE (body mass index.76. P 5 0.001.

0. Depression was not associated with reduced physical activity in our cohort. This observation confirms a previous finding that patients with COPD are markedly inactive in daily life (14). The presence of peripheral arterial disease was not associated with reduced physical activity in our cohort. Furthermore. 40). 43% predicted) attending a Veterans Administration clinic (12). Values less than 0. P 5 0. P 5 0. physical activity is reduced. Two-way ANOVA: main effect BODE.001. P . Two-way ANOVA: main effect GOLD. main effect deceleration time. This possibility. The presence of anemia was not associated with reduced physical activity in our cohort.Watz.9) is not associated with reduced physical activity (18). is subject to further studies. Therefore. is the equivalent of any physical activity performed during the day and has been shown to be a predictor of mortality in a healthy elderly population (22). only limited data about the physical activity levels in COPD are available. and deconditioning (42). Because it was a cross-sectional study.8. Pitta and coworkers showed that both handgrip muscle strength and quadriceps muscle strength correlated moderately with physical activity in a bivariate model (14). impaired endurance time of the quadriceps muscle was shown to be related to physical inactivity (44).9. We cannot confirm the association of handgrip muscle weakness with reduced physical activity in our multivariate model.15 to 1. P . two parameters that are affected by pulmonary and cardiac function (51). 0. we observed a frequency of peripheral arterial disease of 25% in our cohort—nearly 40% in patients with GOLD stage IV. as we recruited our patients from an existing database of patients with COPD who were willing to participate in clinical projects. This result has to be discussed in the context of existing data concerning peripheral muscle weakness in COPD. In a previous study. which included patients with GOLD stages II and III COPD. Slinde and coworkers determined the physical activity levels in 10 underweight patients with COPD using the doubly labeled water method and indirect calorimetry (50). the explained variance of physical activity by the BODE index was similar to the explained variance by GOLD stages.9 indicate peripheral arterial disease (18). was comparable to the reported data in patients with COPD receiving long-term oxygen therapy (46).001. Furthermore. P . which is defined as total daily energy expenditure divided by resting energy expenditure. muscle atrophy. extrapulmonary effects remained significant when added to the BODE index. reliable measure of peripheral arterial disease (18) and is a strong predictor for cardiovascular morbidity and mortality in the general population (36). no causality or directionality of the findings can be inferred. main effect deceleration time. Physical activity levels ranged from 1. In patients with values less than 0. Our study has limitations that need to be addressed. The BODE index is potentially superior to GOLD stages in predicting physical activity in a cohort of patients with more severe COPD and a higher BODE score. Furthermore. . 38). interaction effect BODE 3 deceleration time. This is a surprising result. which are comparable to the range of physical activity levels found in our cohort. as the BODE index incorporates functional exercise capacity and dyspnea. 0. 48). The ankle brachial index is a noninvasive. horizontal lines represent standard error. which clearly affected statistical deceleration time of the early transmitral flow. The SenseWear Pro Armband incorporates several other physiologic sensors that. Of interest. P . higher values of hs-CRP are associated with a reduced exercise capacity in patients with COPD (39. we could only measure systolic pulmonary artery pressure in 72% of our patients (see Table 3 and the online supplement). Systemic inflammation is present in patients with COPD and has an impact on mortality in this population (37. the prevalence of nutritional depletion was 27% (20). only 22% of our patients had a physical activity level of 1. however. It is known from epidemiologic studies that people who report less physical activity have higher values for markers of systemic inflammation (41). however. it was isometric quadriceps force.5. Physical activity is defined as any bodily movement produced by skeletal muscles that results in energy expenditure beyond resting energy (1). which suggests that most patients with COPD have a sedentary lifestyle. Simple accelerometers are inaccurate at estimating total daily energy expenditure from body movement counts only (47. whereas mild to moderate peripheral arterial disease (ankle brachial index. is of limited value in accurately assessing pulmonary hypertension in patients with advanced lung diseases (35). Furthermore. which was not assessed in our study due to the lack of adequate equipment. A possible explanation could be the fact that our cohort had a median of only 2 BODE points. a selection bias has to be considered.5. This methodology. We found no relationship between physical activity and peripheral muscle strength. 0. 0. Peripheral muscle weakness in COPD is considered to be related to loss of fat-free mass (20). is limited by cost and by its unavailability outside specialized centers. At present. Depression is a frequent comorbidity in patients with COPD (19). Anemia is associated with reduced functional exercise capacity and a higher mortality rate in patients with COPD (12). (F) Steps per day according to BODE score and deceleration time of the early transmitral flow.01. the prevalence and magnitude of observed extrapulmonary effects. interaction effect GOLD 3 deceleration time. The ‘‘gold standard’’ to assess total energy expenditure under free-living conditions is the doubly labeled water method (22). which is less than that reported in a cohort of patients with COPD (mean FEV1. Our prevalence data are similar to those from a previous study using the same test (19). Boehme. The prevalence of anemia in our cohort was 5%. bars represent mean values. See (B) for explanation of BODE quintiles. In a landmark study investigating the effect of peripheral muscle weakness on exercise limitations. Therefore. et al. In A–F. in conjunction with the accelerometer recordings. Here we confirm with accelerometer data the association between physical inactivity and systemic inflammation.23. Waschki. The frequency of nutritional depletion in our cohort paralleled GOLD stages. that remained a significant predictor of exercise limitations in a stepwise multiple regression analysis (43). The physical activity level. The prevalence of 14% in our GOLD stage IV patients. give a more valid estimate of total daily energy expenditure (49).15. Preliminary evidence suggests that anemia in patients with COPD may be more prevalent than expected and may be related to systemic inflammation (45).01. In a small study of 16 patients with COPD. On the basis of the values less than 0. We found depression to be prevalent in nearly 20% of our patients according to the Beck Depression Inventory—42% of patients with GOLD stage IV disease.: Physical Activity in COPD 749 We did not find a relationship between physical activity and systolic pulmonary artery pressure estimated by Doppler echocardiography. The mean deceleration time in our cohort was 262 ms. In our multivariate analysis. Doppler echocardiography.5–0. with an overall prevalence of 21%. it seems possible that physical activity may be affected by quadriceps muscle strength. not handgrip force.70 or greater. however. Only 3% of our patients had values less than 0. Nutritional depletion was not associated with reduced physical activity in our cohort. however.

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