The pulmonary cachexia syndrome: aspects of energy balance.

The present paper reviews current knowledge of the pulmonary cachexia syndrome with reference to chronic obstructive pulmonary disease (COPD). Aspects of incidence, aetiology and management are discussed. Malnutrition occurs in approximately one-quarter to one-third of patients with moderate to severe COPD. Both fat mass and fat-free mass become depleted. Loss of fat-free mass is the more important and appears to be due to a depression of protein synthesis. Weight loss is an independent prognostic indicator of mortality, and is associated with increased morbidity and decreased health-related quality of life. The aetiology of malnutrition in COPD is not well understood. Reduced food intake does not seem to be the primary cause. Resting energy expenditure (REE) is elevated in a proportion of patients and probably contributes to negative energy balance. Measurement of actual REE is helpful when considering the adequacy of nutritional supplementation. The underlying reason for a hypermetabolic state is not known. Although weight-losing COPD patients are not catabolic, nutritional supplementation alone does not appear to reverse the loss of fat-free mass. Strategies involving nutritional supplementation in combination with a second intervention are being explored, and there are some encouraging results using anabolic hormones.     

Nutrition and respiratory disease

Weight loss is a frequently occurring complication in patients with chronic obstructive pulmonary disease (COPD) and is a determining factor of functional capacity, health status and mortality. Weight loss in COPD is a consequence of increased energy requirements that are not balanced by dietary intake. Both metabolic and mechanical inefficiency contribute to an elevated total daily energy expenditure. Alterations in anabolic and catabolic mediators resulting in a dysbalance between protein synthesis and protein breakdown may cause a disproportionate depletion of fat-free mass in some patients. Nutritional support is indicated for depleted patients with COPD because it provides not only supportive care, but direct intervention through improvement in respiratory and peripheral skeletal muscle function and in exercise performance. A combination of oral nutritional supplements and exercise or anabolic stimulus appears to be the best approach to obtaining significant functional improvement. Patients responding to this treatment even demonstrated a decreased mortality. Poor response was related to the effects of systemic inflammation on dietary intake and catabolism. The efficacy of anti-catabolic modulation requires further investigation.     

Nutritional modulation as part of the integrated management of chronic obstructive pulmonary disease

Weight loss is a frequent complication in patients with chronic obstructive pulmonary disease (COPD) and is a determining factor for functional capacity, health status and mortality. Weight loss in COPD is a consequence of an inbalance between increased energy requirements and dietary intake. Both metabolic and mechanical inefficiency may contribute to elevated energy expenditure during physical activity, while systemic inflammation has been associated with hypermetabolism at rest. Disease-specific symptoms and systemic inflammation may impair appetite and dietary intake. Altered intermediary metabolism may cause disproportionate wasting of fat-free mass in some patients. A combination of nutritional support and exercise as an anabolic stimulus appears to be the best approach to obtaining marked functional improvement. Patients responding to this treatment even demonstrated a decreased mortality. The effectiveness of anti-catabolic modulation requires further investigation.     

Total daily energy expenditure in wasted chronic obstructive pulmonary disease patients

OBJECTIVES: To investigate total daily energy expenditure in chronic obstructive pulmonary disease (COPD) patients during a rehabilitation programme. DESIGN: Observational study involving a case and a control group. SUBJECTS: Ten COPD patients (six with body mass index (BMI) <18.5 kg/m(2) and four with BMI >18.5 kg/m(2)) were evaluated for their energy expenditure profile. Four additional healthy age-matched volunteers were also included for methodology evaluation. INTERVENTIONS: Measurements of total daily energy expenditure (TEE), resting energy expenditure (REE) and diet-induced thermogenesis (DIT) and energy intake were undertaken by indirect calorimetry and bicarbonate-urea methods and dietary records. RESULTS: REE in COPD patients was not significantly different from that predicted by the Harris-Benedict equation. Before the exercise day the mean TEE was 1508 kcal/day and physical activity level (PAL as calculated by TEE/REE) was 1.52. On the exercise day the TEE increased to 1568 kcal/day and PAL was 1.60, but neither of these changes were significant. The energy cost of increased physical activity during rehabilitation exercise was estimated to be 191 kcal/day. No significant change was found in DIT between the two patient groups. However, overall energy balances were found to be negative (-363 kcal/day). CONCLUSION: The rehabilitation programme did not cause a significant energy demand in COPD patients. TEE in COPD patients was not greater than in free-living healthy subjects. Patients, who were underweight, did not have a higher TEE than patients with normal weight. This suggested that malnutrition in COPD patients was not due to an increased energy expenditure. On the other hand, a significant negative energy balance due to insufficient energy intake was found in seven out of 10 patients.     

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

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.     

Energy balance in depleted ambulatory patients with chronic obstructive pulmonary disease: the effect of physical activity and oral nutritional supplementation

Patients with chronic obstructive pulmonary disease (COPD) often suffer from weight loss. The aim of the present study was to gain insight into the energy balance of depleted ambulatory COPD patients, in relation to their habitual level of physical activity and consumption of oral nutritional supplements. Clinically stable and weight-stable patients (n 20; BMI 19.8+/- SD 2.0 kg/m2) were studied 1 and 3 months after rehabilitation or recovery in the clinic and were at random assigned to a control or intervention group with regard to nutritional supplementation. Energy intake was measured with a 7 d food record. Energy expenditure was estimated from a simultaneous 7 d assessment of physical activity with a tri-axial accelerometer for movement registration in combination with measured BMR. Body mass was measured at several time points. The body mass remained stable in both groups after 1 or 3 months and mean energy balances were comparable for both groups. The mean body-mass change between month 1 and 3 was negatively related to the mean physical activity level (r -0.49; P=0.03). Weight change over the 3 months was negatively associated with the physical activity level. These results suggest that knowledge about the individual physical activity level is necessary for the estimation of the energy need of the COPD patient.     

Efficacy of nutritional supplementation therapy in depleted patients with chronic obstructive pulmonary disease

OBJECTIVE: Weight loss and muscle wasting adversely affect morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Maintenance systemic glucocorticosteroids, prescribed in a substantial number of patients, further contribute to muscle weakness. We investigated the efficacy of oral nutritional supplementation therapy in depleted patients with COPD. METHODS: The therapy consisted of daily two to three oral liquid nutritional supplements (mean +/- standard deviation: 2812 +/- 523 kJ/24 h) incorporated into an 8-wk inpatient pulmonary rehabilitation program in 64 (49 men) depleted patients with COPD. Endpoints were body weight, fat-free mass by bioelectrical impedance analysis, respiratory and peripheral muscle function (maximal inspiratory mouth pressure and handgrip strength, respectively), exercise performance (incremental bicycle ergometry), and disease-specific health status by St. George's Respiratory Questionnaire. Forty-eight percent of the patients were treated with low-dose oral glucocorticosteroids as maintenance medication (dose equivalent to 7.6 +/- 2.5 mg of methylprednisolone per day). RESULTS: Increases in body weight (2.1 +/- 2.1 kg, P < 0.001) and fat-free mass (1.1 +/- 2.0 kg, P < 0.001) were seen. Further, maximal inspiratory mouth pressure (4 +/- 10 cm of H(2)O, P = 0.001), handgrip strength (1.2 +/- 3.1 kg, P = 0.004), and peak workload (7 +/- 11 W, P = 0.001) significantly improved. Clinically significant improvements in the items symptoms (9 +/- 16 points, P < 0.001) and impact (4 +/- 15 points, P = 0.043) of St. George's Respiratory Questionnaire were achieved. Oral glucocorticosteroid treatment significantly impaired the response to nutritional supplementation therapy with respect to maximal inspiratory mouth pressure, peak workload, and St. George's Respiratory Questionnaire symptom score. CONCLUSIONS: Nutritional supplementation therapy implemented in a pulmonary rehabilitation program was effective in depleted patients with COPD. However, oral glucocorticosteroid treatment attenuated the anabolic response to nutritional supplementation.     

Resting energy expenditure and substrate utilisation rate in children with constitutional leanness or obesity

BACKGROUND & AIM: The influence of energy expenditure on body weight regulation, in the absence of organic disease, has never been studied in a paediatric population covering a broad range of body weights. The aim of this study was to investigate resting energy metabolism in children with constitutional leanness, normal body weight, or common obesity. METHODS: Fourteen children with constitutional leanness, 16 children with obesity, and controls were studied. Resting energy expenditure and postabsorptive substrate utilisation rate were measured by indirect calorimetry and body composition was assessed from skinfold thicknesses. RESULTS: As compared to the predicted value calculated from the regression equation of resting energy expenditure on fat-free mass in the controls, resting energy expenditure was decreased in lean children (P=0.002), whereas no difference was found in obese children. In obese children and the overall population, fat mass was positively correlated with fat oxidation rate. In each group and in the overall population, fat oxidation rate was positively correlated to resting energy expenditure. CONCLUSIONS: Constitutionally lean children have a low resting metabolic rate, probably adaptive in nature. In obese children, resting energy expenditure is increased in proportion to the fat-free mass, and fat balance is the main determinant of energy balance. These data suggest a constitutional regulation of body weight.     

The Role of Energy Expenditure in Energy Regulation: Findings from a Decade of Research

The role of energy expenditure in energy regulation remains a subject of continuing controversy. New data have emerged from studies conducted over the last decade demonstrating that energy expenditure is a critical factor contributing to successful energy regulation in normal individuals, as well as to the disregulation of energy balance that characterizes obesity. Reduced energy expenditure appears to facilitate weight gain in individuals susceptible to obesity and also appears to reduce the extent of body energy loss during undereating in both lean and obese individuals. The magnitude of the reduction in energy expenditure during, and perhaps after, weight loss is greater than expected on the basis of the reduction in body weight and appears to occur in response to undefined underlying determinants of energy regulation. In addition, exercise intervention studies and cross-sectional investigations of the relationship between energy expenditure for physical activity and body composition demonstrate an apparent equilibration between physical activity and body fat content. This equilibration is suggestive of a direct influence of physical activity on the underlying metabolic determinants of energy balance.     

Metabolic rate and weight loss in chronic obstructive lung disease

Although weight loss is a common problem in chronic obstructive pulmonary disease (COPD), the precise cause of malnutrition in COPD patients is not known. The purpose of this study was to measure and compare resting energy expenditure (REE) in stable undernourished and adequately nourished COPD. REE was measured in normal, adequately nourished, and undernourished COPD patients by indirect calorimetry and then compared to predicted basal metabolic rate (BMR) calculated from the Harris-Benedict equation. We found that measured REE, compared to predicted, was significantly higher in the undernourished group, (1.15 +/- 0.02) and compared to the adequately nourished COPD (0.99 +/- 0.03) and normal groups (0.93 +/- 0.02) (p less than 0.0001). We conclude that there is a hypermetabolic state in stable malnourished COPD patients which may be a factor in weight loss. This elevated REE also needs to be taken into account when determining caloric requirements for COPD patients.     

Energy expenditure and free-living physical activity in black and white women: comparison before and after weight loss

BACKGROUND: The prevalence of obesity is higher in black than in white women. Differences in energy economy and physical activity may contribute to this difference. OBJECTIVE: The objective of this study was to compare free-living energy expenditure and physical activity in black and white women before and after weight loss. DESIGN: Participants were 18 white and 14 black women with body mass indexes (in kg/m(2)) between 27 and 30. Diet, without exercise, was used to achieve a weight loss of >/=10 kg and a body mass index <25. After 4 wk of energy balance in overweight and normal-weight states, body composition was assessed by using a 4-compartment model, sleeping and resting energy expenditures were assessed by using a chamber calorimeter, physiologic stress of exercise and exercise economy were measured by using standardized exercise tasks, and daily energy expenditure was assessed by using doubly labeled water. RESULTS: Weight loss averaged 12.8 kg. Sleeping and resting energy expenditures decreased in proportion to changes in body composition. Weight reduction significantly improved physiologic capacity for exercise in both groups of women, making it easier for them to be physically active. Black women had lower body composition-adjusted energy requirements than did white women-both before and after weight loss-during sleep (9% lower, 519 kJ/d; P < 0.001), at rest (14% lower, 879 kJ/d; P < 0.001), during exercise (6% lower; P < 0. 05), and as a daily total (9% lower, 862 kJ/d; P < 0.06). By contrast, free-living physical activity was similar between the groups. CONCLUSIONS: Weight-reduced women had metabolic rates appropriate for their body sizes. Black women had lower resting and nonresting energy requirements in both overweight and normal-weight states than did white women and did not compensate with greater physical activity, potentially predisposing them to greater weight regain.     

Validity of the ActiReg system in assessing energy requirement in chronic obstructive pulmonary disease patients

BACKGROUND & AIMS: Malnutrition and weight loss are common in patients with chronic obstructive pulmonary disease (COPD) and effective nutritional support relies on accurate assessment of energy requirement. This could only be performed by measuring energy expenditure using objective methods. The aim of this study was to examine the validity of the ActiReg system in assessing energy requirement in non-hospitalized patients with severe COPD, using doubly labelled water (DLW) as criterion method. METHODS: Total energy expenditure (TEE) was assessed from 14 days DLW analysis in 13 patients. During the first 7 days TEE was simultaneously assessed using the ActiReg system, combining measured resting energy expenditure (REE) with physical activity monitoring. RESULTS: A difference of -88 (782) kJ d(-1) (P = 0.69) was observed between the ActiReg system and DLW. REE explained 52% of the variation in TEE from DLW. Adding physical activity energy expenditure from the ActiReg system (PAEE(AR) = TEE(AR)-REE) increased the explained variation in TEE from DLW with 16%. CONCLUSIONS: The ActiReg system is valid in assessing energy requirement in non-hospitalized patients with severe COPD. The unique feature of being able to discriminate within both the low intensity activity range and moderate-to-high intensity activity range makes the ActiReg system a valuable tool in clinical nutritional support.     

Changes in nitrogen balance of depleted patients with increasing infusions of glucose.

Depleted patients were maintained on intravenous infusions of amino acids and glucose with constant N intake (173 mg/kg body weight), and three different levels of energy intake (15.4, 37.6, and 58.5 kcal/kg) given sequentially for 4 days each. Changes in N balance were abrupt and maximal in 1 to 2 days. Maximal changes in N balance preceded, and were not dependent on maximal changes in fat and glucose metabolism. N retention increased 1.7 mg/kcal of increased energy balance, during both hypocaloric and hypercaloric intakes, a value similar to that observed in normal adults. No increase in resting energy expenditure occurred with increasing energy intake during negative energy balance. During positive energy balance resting energy expenditure increased by 1 kcal for each 5 of intake. It seems likely that increasing energy restores mainly that portion of lean body mass associated with fat deposition; and rapid restoration of lean body mass requires high N intakes. At zero energy balance, N balance in these depleted patients was only slightly positive at an intake of 173 mg N per kilogram. This is about twice the intake of N required to maintain zero N balance in normal adults.     

慢阻肺缓解期患者肺功能与体质量及血清补体的相关分析

目的探讨慢性阻塞性肺疾病(COPD)患者第一秒用力呼气容积占用力肺活量百分比(FEV1%)与体质量及血清补体C     

Energy expenditure, energy intake, and weight loss in Alzheimer disease

Alzheimer disease is one of the leading causes of death among older individuals. Unexplained weight loss and cachexia are frequent clinical findings in patients with Alzheimer disease. Thus, it has been postulated that Alzheimer disease may be associated with dysfunction in body weight regulation. This brief review examines the interrelations among energy intake, energy expenditure, and body composition in Alzheimer disease. We explored whether abnormally high daily energy expenditures, low energy intakes, or both contribute to unexplained weight loss and a decline in nutritional status. Specifically, we considered studies that examined energy intake, body composition, and daily energy expenditure and its components. The application of doubly labeled water and indirect calorimetry to understand the etiology of wasting has increased our knowledge regarding the relation among energy expenditure, physical activity levels, and body composition in Alzheimer disease patients. Although the number of studies are limited, results do not support the notion that a hypermetabolic state contributes to unexplained weight loss in Alzheimer disease, even in cachectic patients. Recent findings are presented suggesting an association between abnormally elevated levels of physical activity energy expenditure and elevated appendicular skeletal muscle mass and energy intake in Alzheimer disease patients. Clinical strategies aimed at developing lifestyle and dietary interventions to maintain adequate energy intake, restore energy balance, and maintain skeletal muscle mass should be a future area of investigation in Alzheimer disease research.     

Energy expenditure in Alzheimer's disease

Alzheimer's disease type dementia is a growing health problem and is one of the leading causes of death among elderly people. Unexplained weight loss and cachexia is a frequent clinical finding in patients with Alzheimer's disease. It has been postulated that Alzheimer's disease may by characterized by dysfunction in body weight regulation. This brief review examines energy intake, energy expenditure and body composition in Alzheimer's disease. We consider whether inappropriately high levels of energy expenditure may contribute to unexplained weight loss and decline in nutritional status. Specifically, we will consider studies that have examined body composition, daily energy expenditure and its components. The application of doubly labeled water and indirect calorimetry to problems of "wasting" has increased our knowledge regarding energy expenditure and physical activity levels in Alzheimer's patients. Although the number of studies are limited, results do not support the notion that a "hypermetabolic" state contributes to unexplained weight loss in Alzheimer's disease, even in cachectic patients. Clinical strategies aimed at developing feeding strategies to maintain adequate caloric intake and the restoration of energy balance should be a future area of investigation in Alzheimer's research.     

Energetic Adaptation to Chronic Disease in the Elderly

Several chronic diseases occur with increased prevalence in the elderly. Body weight loss is a common feature of many chronic diseases. Weight loss increases the risk for morbidity and mortality and contributes to decreased functional independence and poor quality of life. Thus, an understanding of the effect of chronic disease on energy balance has important implications for nutritional supplementation and clinical outcome. This brief review will consider recent studies that have examined the effect of several chronic diseases (i.e., Alzheimer's disease, Parkinson's disease, and congestive heart failure) on daily energy expenditure in elderly individuals. Additionally, we put forth a model to explain the energetic adaptation to chronic disease in the elderly that is based on measurements of daily energy expenditure and its components. Studies suggest that chronic disease decreases daily energy expenditure in elderly individuals due to a marked reduction in physical activity energy expenditure. Moreover, these changes in daily energy expenditure often occur in the presence of increased resting energy expenditure. Thus, the net effect of chronic disease is to decrease daily energy expenditure. These results do not favor the hypothesis that increased energy expenditure contributes to disease-related weight loss. Instead, reduced energy intake appears to be a more likely mediator of the negative energy imbalance and weight loss that frequently accompany chronic disease in the elderly.     

Cancer anorexia and cachexia

Patients with cancer cachexia experience a profound wasting of adipose tissue and lean body mass. Anorexia, although often present, is insufficient to account for tissue wasting because 1) cachexia involves massive depletion of skeletal muscle that does not occur during anorexia, 2) nutritional supplementation cannot replenish the loss of lean body mass, 3) cachexia can occur without anorexia, and 4) food intake might be normal for the lower weight of the cancer patient. Anorexia can arise from 1) decreased taste and smell of food, 2) early satiety, 3) dysfunctional hypothalamic membrane adenylate cyclase, 4) increased brain tryptophan, and 5) cytokine production. Appetite stimulants such as cyproheptadine, medroxyprogesterone acetate, and megestrol acetate do not significantly improve lean body mass. Tumor products might be more important in the development of cachexia. Cachectic patients excrete in their urine a lipid-mobilizing factor that directly stimulates lipolysis in a cyclic AMP-dependent manner and increases energy expenditure. Loss of skeletal muscle in cachexia is caused by upregulation of the ubiquitin-proteasome catabolic pathway. Cachexia-inducing tumors elaborate a sulfated glycoprotein, which directly initiates protein catabolism in skeletal muscle. The action of this proteolysis-inducing factor is attenuated by the polyunsaturated fatty acid eicosapentaenoic acid, which is also effective in preventing loss of skeletal muscle in cancer patients. Antagonists of tumor catabolic factors will provide important new agents in the treatment of cancer cachexia.     

Energy expenditure, physical activity and body-weight control

Regular physical exercise and endurance training are associated with low body weight and low body fat mass. The relationship between exercise and body-weight control is complex and incompletely understood. Regular exercise may decrease energy balance through an increase in energy expenditure or an increase in fat oxidation. It may also contribute to weight loss by modulating nutrient intake. An intriguing question that remains unresolved is whether changes in nutrient intake or body composition secondarily affect spontaneous physical activity. If this were the case, physical activity would represent a major adaptative mechanism for body-weight control.