Plasma levels of amino acids and hypermetabolism in patients with chronic obstructive pulmonary disease

Abstract

Plasma levels of amino acids were measured by ion-exchange, high-pressure liquid chromatography in 30 ambulatory patients with chronic obstructive pulmonary disease (COPD; mean ± SD: age 64 ± 13 y and forced expiratory volume in 1 s [FEV₁] 0.85 ± 0.25 L) and 30 age- and sex-matched healthy control subjects with regard to nutritional status, resting energy expenditure (REE), and pulmonary function. The ratio of branched-chain amino acids to aromatic amino acids was significantly (P < 0.001) decreased in COPD patients and was significantly correlated with percentage of ideal body weight (r = 0.403, P < 0.05), percentage of arm-muscle circumference (r = 0.492, P < 0.01), and %FEV₁ (r = 0.467, P < 0.05). Plasma levels of alanine and cysteine were decreased, whereas levels of glutamine, aspartic acid, serine, and ornithine were elevated in COPD patients as opposed to control subjects. The ratio of resting energy expenditure to predicted resting energy expenditure was negatively correlated with the ratio of branched-chain to aromatic amino acids (r = −0.716, P < 0.01), percentage of arm-muscle circumference (r = −0.770, P < 0.05), %FEV₁ (r = −0.839, P < 0.01), and the maximal inspiratory pressure (r = −0.803, P < 0.001). Underweight COPD patients also exhibited a greater degree of hyperinflation (percentage of residual volume = 205 ± 15 for underweight patients and 156 ± 8 for normal-weight patients). In conclusion, a decrease in plasma levels of branched-chain amino acids in relation to hypermetabolism, possibly resulting from the severity of COPD and respiratory muscle weakness, and various disturbances in plasma amino-acid levels were found in underweight COPD patients.

Introduction

Weight loss is common in patients with chronic obstructive pulmonary disease (COPD).1 Epidemiologic studies have suggested that weight loss is generally associated with high rates of mortality and morbidity.1, 2 Therefore, nutritional assessment and nutritional support should be parts of the management of patients with COPD. Recent studies have suggested that nutritional intervention may correct the weight loss associated with improvement in respiratory muscle function.3, 4, 5 In patients with COPD, muscle weakness and an impaired exercise tolerance also occur,6 suggesting disturbances in intermediary protein metabolism. However, no specific nutritional regimen in terms of protein or nitrogen sources has been recommended because the characteristic nutritional and metabolic abnormalities related to protein metabolism have not been clearly identified in COPD patients. A previous study has shown that the serum level of albumin is normal or only marginally decreased in COPD patients.7 A recent study by our laboratory demonstrated a significant decrease in lean body mass evaluated by dual-energy x-ray absorptiometry in COPD patients.8

Because amino acids are basic units of proteins and they mediate intermediary metabolism, analysis of the plasma levels of free amino acids may be useful for determining the characteristics of nitrogen metabolism and thus of protein malnutrition. However, data on the plasma levels of amino acids in patients with COPD are limited.9, 10 Moreover, the number of subjects in the previous studies was small and the results were inconsistent. Studies on the pathophysiologic role of branched-chain amino acids (BCAAs) suggest that they may serve as an energy substrate and may regulate the degradation and synthesis of muscle protein in hepatic disorders and a variety of stress-related conditions.11, 12 Our preliminary study7 suggested a decreased level of BCAAs in patients with COPD, but possible roles of BCAAs in relation to pathophysiology remain undefined. Previous studies4, 13, 14 have also suggested that a hypermetabolic state in part contributes to weight loss in COPD patients, but its relation to amino-acid levels and weight loss has not been fully clarified. In the present study, we evaluated the nutritional status and measured the plasma levels of amino acids to determine the relation between these factors and pulmonary function and the derangement in energy metabolism, assessed in terms of the resting energy expenditure (REE), in patients with stable COPD.