Elsevier

Metabolism

Volume 60, Issue 10, October 2011, Pages 1449-1455
Metabolism

Resting energy expenditure and protein turnover are increased in patients with severe chronic obstructive pulmonary disease

https://doi.org/10.1016/j.metabol.2011.02.013Get rights and content

Abstract

The mechanisms leading to weight loss in patients with chronic obstructive pulmonary disease (COPD) are poorly understood. Changes in protein metabolism and systemic inflammation may contribute to increased resting energy expenditure (REE) in COPD, leading to an energy imbalance and loss of fat and fat-free mass. The objective of this study was to determine first whether REE was increased in patients with COPD and, second, whether this was associated with increased protein turnover and/or systemic inflammation. Resting energy expenditure was determined using indirect calorimetry in 14 stable outpatients with severe COPD (7 with low and 7 with preserved body mass indices) and 7 healthy controls. Endogenous leucine flux, leucine oxidation, and nonoxidative disposal, indices of whole-body protein breakdown, catabolism, and synthesis, were measured using intravenous infusions of 13C-bicarbonate and 1-13C-leucine. Total body water, from which fat-free mass and fat mass were calculated, was determined using an intravenous bolus of deuterated water. Plasma markers of systemic inflammation were also measured. As a group, subjects with COPD had increased REE adjusted for fat-free mass (P < .001) and faster rates of endogenous leucine flux (P = .006) and nonoxidative leucine disposal (P = .002) compared with controls. There was a significant correlation between REE and both endogenous leucine flux (P = .02) and nonoxidative leucine disposal (P = .008). Plasma concentrations of the inflammatory markers C-reactive protein and interleukin-6 were not different between COPD subjects and controls. Increased rates of protein turnover are associated with increased REE and loss of fat-free mass in COPD.

Introduction

Weight loss and peripheral muscle wasting and dysfunction are common findings in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and are associated with poor quality of life [1], impaired exercise tolerance, and increased mortality [2]. In general, weight loss occurs when there is an imbalance between energy intake and energy expenditure. However, decreased intake does not seem to be the primary cause of weight loss in COPD [3]. Increased resting energy expenditure (REE) has been found in some patients with COPD [4], [5], suggesting that it may also contribute to weight loss.

Increased REE in COPD may result from systemic inflammation. Evidence of systemic inflammation, including increased concentrations of proinflammatory cytokines such as tumor necrosis factor–α (TNF-α) [6] and interleukin-6 (IL-6) and acute phase proteins such as C-reactive protein (CRP) [7], has been found in patients with COPD and muscle wasting. In addition, changes in macronutrient metabolism may also lead to increased REE. Because synthesis and breakdown of muscle protein are primarily responsible for the energy expenditure of resting muscle [8], increased REE in COPD may be associated with increased protein breakdown and/or synthesis. However, studies of in vivo protein metabolism in COPD have had conflicting results. Whereas one study reported that subjects with emphysema had similar rates of protein breakdown but decreased rates of protein synthesis compared with healthy controls [9], another reported increases in both whole-body protein synthesis and breakdown rates, suggesting an overall increase in whole-body protein turnover in subjects with COPD compared with healthy controls [10]. Inflammation and protein breakdown may also be linked, as one study found increased concentrations of inflammatory markers and increased whole-body protein breakdown in COPD patients compared with controls [11]. In this study, we aimed to determine first whether REE was increased in patients with COPD and, second, whether this was associated with increased protein turnover and/or systemic inflammation. Resting energy expenditure, in vivo whole-body protein kinetics, and plasma markers of systemic inflammation were measured in subjects with severe COPD and in healthy controls.

Section snippets

Subjects

Fourteen clinically stable adult outpatients with severe COPD (postbronchodilator forced expiratory volume in 1 second [FEV1] <50% of predicted) were enrolled in the study. Seven subjects had body mass index (BMI) less than 21 kg/m2 (low-BMI group), and 7 subjects had BMI greater than or equal to 21 kg/m2 (preserved-BMI group). In previous studies, this BMI threshold has been associated with increased risk of mortality [12]. Fat-free mass (FFM) was not determined before enrollment in the study.

Results

The general characteristics and anthropometric parameters of all subjects are shown in Table 1. Controls were younger than COPD subjects with low BMI (P = .01 ANOVA, P < .05 post hoc Tukey). Low-BMI subjects had lower FFM than controls (P < .01 ANOVA, P < .05 post hoc Tukey). Both groups of COPD subjects had lower fat-free mass index (FFMI) compared with controls (P < .001 ANOVA, P < .05 post hoc Tukey), and all subjects with COPD but one had low FFMIs (defined as <15 kg/m2 for women and <16

Discussion

The primary goal of this study was to determine first whether REE was increased in patients with COPD and, second, whether this was associated with increased protein turnover and/or systemic inflammation relative to the values of healthy controls. We found that COPD subjects had loss of FFM even with preservation of BMI. Furthermore, our results show that, as a group, COPD subjects had increased REE and faster rates of protein breakdown and synthesis compared with controls. Protein catabolism

Acknowledgment

We are grateful to the nursing staff of the General Clinical Research Center at Baylor College of Medicine for their care of the subjects; Sarah Perusich for her assistance in recruiting subjects; and to Melanie Del Rosario, Margaret Frazer, and Vy Pham for their assistance in laboratory analyses.

Funding: This work was supported in part by The Chest Foundation and ALTANA Pharma, US, and the National Institutes of Health (HL082487). Work at the General Clinical Research Center is supported by

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    Conducted at Baylor College of Medicine, Houston, TX.

    Authors' contributions to manuscript: CK, VB, NH, and FJ designed research; CK, JW-CH, and FJ conducted research; FK provided essential materials; CK and FJ analyzed data; CK, VB, NH, FK, and FJ wrote the paper; CK had primary responsibility for the final content.

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