Chest
Volume 145, Issue 3, March 2014, Pages 542-550
Journal home page for Chest

Original Research: COPD
Daily Step Count Is Associated With Plasma C-Reactive Protein and IL-6 in a US Cohort With COPD

https://doi.org/10.1378/chest.13-1052Get rights and content

Background

Physical activity is an important clinical marker of disease status in COPD. COPD is also characterized by low-grade systemic inflammation. However, the relationship between physical activity and systemic inflammation in COPD is unclear.

Methods

We monitored daily step count, a directly measured physical activity, using the StepWatch Activity Monitor, an ankle-worn accelerometer, in 171 people with stable COPD. Exercise capacity was assessed with the 6-min walk test (6MWT). We measured plasma C-reactive protein (CRP) and IL-6 levels. Linear regression models examined the cross-sectional associations of daily step count and 6MWT distance with CRP and IL-6 levels.

Results

Subjects had a mean age 72 ± 8 years and mean FEV1 1.5 ± 0.57 L (54 ± 20% predicted). Median daily step count was 5,203 (interquartile range [IQR], 3,627-7,024], CRP level was 2.4 mg/L (IQR, 1.2-5.0), and IL-6 level was 2.9 pg/mL (IQR, 2.0-5.1). Each 1,000-step increase in daily step count was associated with a 0.94 mg/L and 0.96 pg/mL decrease in CRP (P = .020) and IL-6 (P = .044) levels, respectively, adjusting for age, FEV1 % predicted, pack-years smoked, cardiac disease, current statin use, history of acute exacerbations, and season. There was a significant linear trend of increasing daily step count by quartiles and decreasing CRP (P = .0007) and IL-6 (P = .023) levels. Higher 6MWT distance was also significantly associated with lower CRP and IL-6 values.

Conclusion

People with COPD who walked the most had the lowest plasma CRP and IL-6 levels. These results provide the conceptual basis to study whether an intervention to promote walking will reduce systemic inflammation in people with COPD.

Section snippets

Materials and Methods

COPD, a major cause of global morbidity, is projected to become the third leading cause of death in the world by 2020.1, 2 Level of physical activity (PA) is an important clinical marker of disease status in COPD. Higher levels of PA are associated with better functional status, fewer hospital admissions, and lower mortality.3, 4, 5, 6, 7 Daily step count is a direct measure of PA that is easy to understand, can be accurately monitored, and can be potentially targeted for intervention.8, 9, 10

Study Design and Participants

Between January 2009 and November 2011, 176 participants with COPD were enrolled from the general pulmonary clinics. All 176 subjects had one assessment; in addition, 98 of the 176 subjects had a second assessment a median of 3.9 months after the first assessment as part of a previously published observational study characterizing daily step count in COPD.8, 11 Clinical variables, inflammatory biomarkers, and PA were measured at each assessment.

Eligible participants were aged > 40 years and had

Clinical Variables

We measured weight and height to calculate BMI. We obtained a medical history of cigarette use; coronary artery disease; congestive heart failure; medication use, including statins, inhaled corticosteroids, and nonsteroidal antiinflammatory drugs (NSAIDs); prior participation in pulmonary rehabilitation; and occurrence of AE in the year prior to enrollment.11, 30 At each assessment, participants underwent measurement of FEV1 using an Eaglet spirometer (nSpire Health, Inc).31 The 6MWT was

Inflammatory Biomarkers

Peripheral blood was collected by venipuncture into vacutainer tubes with ethylenediaminetetraacetic acid anticoagulant. Blood was collected between 9:30 am and 3:00 pm at each in-clinic assessment. Plasma was obtained by centrifugation of tubes at 1,459 × g for 15 min. The samples were stored at −80°C until analyzed. Plasma CRP and IL-6 levels were measured by the Clinical & Epidemiologic Research Laboratory, Children's Hospital, Boston, Massachusetts. CRP and IL-6 levels were determined using

Physical Activity Assessment

The StepWatch Activity Monitor (SAM) (Orthocare Innovations LLC), an ankle-worn accelerometer, accurately measures step counts in people with COPD.8 After each in-clinic assessment, participants were sent home to wear the SAM for 14 consecutive days and were instructed to perform their usual PAs. Subjects were blinded to step-count data, since the instrument does not provide feedback. Subjects returned the SAM by mail and staff downloaded date- and time-stamped step-count data via a docking

Statistical Analysis

Descriptive results at study entry for 171 subjects are reported as median (interquartile range [IQR]), mean ± SD, or percentage, as appropriate. Levels of CRP and IL-6 were converted to the natural logarithmic values to best approximate a normal distribution. To analyze all collected data and maximize power, the final linear regression models included 269 assessments (171 assessments in all subjects plus 98 assessments in those who had a second assessment). The statistical approach used

Results

Mean age was 72 ± 8 years, there were two female subjects, and mean FEV1 was 1.5 ± 0.57 L (54 ± 20% predicted36) (Table 1). All four GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages were represented, predominantly GOLD II (45%) and GOLD III (34%).2 Median daily step count was 5,203 (IQR, 3,627-7,024). Of 3,766 days monitored [(171 × 14) + (98 × 14)], only 3% (n = 122) met the definition of a no-wear day. Daily step count was moderately correlated with 6MWT distance (Pearson

Discussion

We show that people with COPD who have higher PA have significantly lower levels of markers of systemic inflammation. Specifically, those who had the highest daily step counts had the lowest plasma CRP and IL-6 levels, independent of age, FEV1 % predicted, pack-years, cardiac disease, current statin use, history of AE, and season. These novel findings are supported by the significant associations over the entire range of daily step counts with CRP and IL-6 levels. Our results are further

Acknowledgments

Author contributions: Dr Moy had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. Dr Moy assumes full responsibility for the integrity of the submission as a whole, from inception to published article.

Dr Moy: contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript.

Ms Teylan: contributed substantially to the

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    Funding/Support: This research was supported by the Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award to Dr Moy. It also was supported in part by the Center for Integration of Medicine and Innovative Technology, Boston, MA (Dr Moy), and in part by the VA Rehabilitation Research and Development Service [Grant B6618R to Dr Garshick].

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

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