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(Chest. 2003;124:1365-1372.)
© 2003 American College of Chest Physicians

Body Composition and Resting Energy Expenditure in Clinically Stable, Non–Weight-Losing Patients With Severe Emphysema*

Rubin I. Cohen, MD, FCCP; Kamel Marzouk, MD; Patricia Berkoski, RRT; Chris P. O’Donnell, PhD; Vsevolady Y. Polotsky, PhD and Steven M. Scharf, MD, PhD{dagger}

* From the Division of Pulmonary and Critical Care Medicine (Drs. Cohen, Marzouk, and Scharf), The Long Island Jewish Medical Center, The Long Island Campus for The Albert Einstein College of Medicine, New Hyde Park, NY; and Division of Pulmonary and Critical Care Medicine (Drs. O’Donnell and Polotsky), Johns Hopkins University School of Medicine, Baltimore, MD. {dagger} Currently at the Pulmonary and Critical Care Division, University of Maryland, Baltimore, MD.

Correspondence to: Rubin Cohen, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, RM C-20, 270-05 76th Ave, New Hyde Park, NY, 11040; e-mail: rcohen{at}lij.edu


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: To characterize the metabolic status of weight-stable and clinically stable individuals with advanced emphysema.

Patients: Seventy-nine patients with severe emphysema (FEV1, 29 ± 13% of predicted [mean ± SD]) evaluated for enrollment in the National Emphysema Treatment Trial and 20 age-matched healthy subjects were studied.

Setting: Pulmonary function laboratory of university-affiliated teaching hospital.

Interventions: Data collection.

Measurements and results: We measured lung function, body composition, serum leptin levels, serum tumor necrosis factor receptors (sTNF-Rs), resting oxygen consumption (RO2) normalized to weight in kilograms (RO2/kg), and RO2 normalized to fat-free mass (FFM) [RO2/FFM]. The patient group and healthy group had similar age, body mass index (BMI), and body composition. RO2/kg, RO2/FFM, and sTNF-R levels were higher in patients compared to healthy subjects. There were no differences in serum leptin levels between emphysematous and healthy subjects, and there was no correlation between leptin and sTNF-R and RO2/kg. Furthermore, both groups had similar gender-related differences in FFM, percentage of body fat, and serum leptin levels. Patients with lower BMI showed the greatest differences from control subjects in RO2/kg.

Conclusion: In weight-stable subjects with advanced emphysema, RO2/kg and RO2/FFM were higher compared to healthy subjects, especially in those with BMI in the lower end of the normal range. RO2/kg and RO2/FFM did not correlate with leptin or sTNF-R levels. These data show that a higher metabolic rate is found in patients with emphysema who are clinically and weight stable. Thus, hypermetabolism is a feature of the disease and not sufficient to lead to weight loss.

Key Words: body mass index • emphysema • leptin • nutrition • oxygen consumption • tumor necrosis factor receptors


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Weight loss in patients with advanced emphysema has been attributed to derangements in resting energy expenditure (REE) and other factors, such as inflammation and altered levels of the fat hormone leptin. However, weight loss occurs in only a minority of emphysematous patients. Indeed, weight loss and changes in body composition have been reported in only 20% of clinically stable patients, and in 35% of those deemed eligible for pulmonary rehabilitation.1 2 3 4 5 6 7 8 9 10 Thus, it appears that the majority of patients with emphysema are not losing weight.

Prior studies11 12 have also assessed body composition in patients with stable COPD; however, these studies examined all patients with a diagnosis of COPD, and often did not separate patients with clinical/radiologic evidence of emphysema as opposed to chronic bronchitis. Indeed, there are few data on the metabolic status of weight-stable patients with advanced emphysema. Thus, it remains unclear if changes in body composition, hypermetabolism, and inflammation are present only in weight-losing patients, or whether these characteristics are also found in weight-stable patients with emphysema.

We undertook this study to characterize the relationships between lung function, body composition, REE, serum leptin concentrations, and markers of inflammation in a group of weight-stable patients with clinically advanced emphysema. We hypothesized that the metabolic derangements noted in the weight-losing population would also be found in a group of weight-stable patients. We further hypothesized that increased REE would correlate with markers of systemic inflammation and serum leptin level.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The National Emphysema Treatment Trial (NETT) provided an ideal opportunity to examine individuals with severe emphysema who were weight stable. The NETT is a large nationwide trial of lung volume reduction surgery in patients with severe emphysema, the details of which were published elsewhere.13 All patients screened for this study have activity-limiting dyspnea and emphysema. Seventy-nine patients (43 men and 36 women) evaluated for enrollment into the NETT were recruited into this study. None of the patients recruited for this study had a > 10% change in weight within the 6 months prior to enrollment. This inclusion criterion was more strict than that of the NETT, which required weight stability for only 4 months.13 Patients were excluded if they smoked within 6 months of evaluation, or had previously diagnosed pulmonary vascular disease, ischemic heart disease, or congestive heart failure. All were screened for advanced emphysema by pulmonary function tests (PFTs) and high-resolution CT scanning of the lungs. None had clinically ischemic or valvular cardiac disease, and none had significant pulmonary disease, specifically chronic bronchitis (as defined by cough and sputum production for 3 months in the past year). None were hospitalized during the 6 months prior to inclusion in the study. None had other illnesses known to affect either body mass index (BMI), soluble tumor necrosis factor receptors (sTNF-Rs), or leptin levels, such as infection, thyroid disease, cancer, or collagen vascular disease, or had abnormalities in fluid balance manifested by congestive heart failure, ascites, or pleural effusion.

Among these patients, 26 were eventually randomized into the NETT. Reasons for not randomizing patients included the following: PFT results not reaching NETT criteria, BMI too high for participation in the NETT, presence of pulmonary hypertension, homogeneously distributed emphysema judged unresectable for lung reduction, inability to complete exercise testing, exclusion by surgeon, and unwillingness by participant to undergo randomization or further participation in trial.

Twenty volunteers (10 men and 10 women) of ages similar to those of the patients comprised the healthy group. Healthy volunteers were excluded if they had history of smoking, concomitant lung disease, or other serious medical illness. This group underwent measurements of REE, body composition, and leptin and sTNF-R levels.

Weight was measured with a beam scale to the nearest 0.25 kg with the subjects barefoot and lightly clothed. Height was determined to nearest 0.5 cm, and the BMI was calculated. PFTs including spirometry, lung volumes by plethysmography, and single-breath diffusing capacity of the lung for carbon monoxide (DLCO) were performed, and results were expressed as percentage of predicted according to the equations of Crapo et al.14 Blood for measurement of arterial gas tensions and pH was obtained at rest with the subject breathing room air.

Fat-free mass (FFM) was calculated using a specific regression equation,15 16 and was expressed both in kilograms and as percentage of total body weight. Body composition was assessed by bioelectrical impedance (BIA 101 Impedance Analyzer; RJL Systems; Detroit, MI).15 16 REE was assessed as resting oxygen consumption (RO2) in milliliters per minute, and was measured between 9 AM and 11 AM after an overnight fast under standardized conditions using indirect calorimetry (Medgraphics Cardio 2 System, Pitot tube; Medical Graphics; St. Paul, MN). RO2 normalized to total body weight in kilograms (RO2/kg) and RO2 normalized to FFM (RO2/FFM) were also measured. For measurements of RO2, subjects were placed at rest in a 45° semirecumbent position for 5 min breathing through a mouthpiece. Following this run-in period, breath-by-breath measurements of oxygen consumption (O2) and carbon dioxide production were made for 5 more minutes. Values of RO2 were averaged over the entire 5-min measurement period.

We measured levels of sTNF-Rs 55 and 75 in duplicate samples, using an enzyme-linked immunosorbent assay kit (Quantakine; R&D Systems; Minneapolis, MN). These are proteins shed into the circulation and interfere with the binding of tumor necrosis factor (TNF)-{alpha} to its cell-surface receptors.17 The increased sTNF-Rs in patients with emphysema are thought to reflect TNF-{alpha} activation and ongoing inflammation.9 17 Serum leptin concentration18 19 was assessed in duplicates with a radioimmunoassay as described by the manufacturer (Linco Research; St. Louis, MO). The Institutional Review Board of the Long Island Jewish Medical Center approved this study.

Statistical Analysis
Data were collated and expressed as mean ± SD. We used the Sigma Stat 2.03 statistical software (SPSS; Chicago, IL) to analyze data. Data were tested for normality using the Kolmogorov-Smirnov test (with the Lilliefor correction) using p = 0.5 threshold for rejection of normality. Since data in both groups were normally distributed, we compared the healthy group to the patient group using a two-sample t test. For the t test, equality of variance was tested by checking variability about the group means (p = 0.05 for rejection). Univariate regression analysis was performed as indicated. Multiple backward stepwise regression analyses were performed for any given independent variable using variables that were significant predictors on the univariate analysis. The least-square technique was used to obtain the line that best fit the data. Within-group analyses were also examined for gender-related differences in leptin, BMI, percentage of fat mass (FM) [calculated as FM divided by body mass x 100], and other characteristics.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Both patient and healthy groups were comparable in terms of age, BMI, body composition, and leptin levels (Table 1 ). The main differences between the two groups were in RO2, RO2/kg, and RO2/FFM, which were significantly greater in patients than in healthy subjects.


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  		Table 1. Clinical and Laboratory Profiles of Study Population*

 
RO2
Figure 1 demonstrates the relationship between O2 and BMI. In the control subjects, there was a significant positive correlation (r = 0.8, p < 0.001). This was not the case in the patient group, even though mean BMI was the same for the two groups. We further explored the relationships between O2 normalized to weight in kilograms (O2/kg) and BMI in patients and healthy subjects (Fig 2 ). In healthy subjects, O2/kg did not change significantly with BMI. However, O2/kg decreased significantly with increasing BMI in patients (r = 0.5, p < 0.001).



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  		Figure 1. The relationship between RO2 and BMI. Even though BMI was the same in both patient and control groups, there was a significant positive correlation between RO2 and BMI only in the control group. Open circles represent emphysematous patients; dark circles are healthy volunteers.

 


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  		Figure 2. The relationship between RO2/kg and BMI in patients and healthy subjects. In the latter, RO2/kg did not change with BMI. However, O2/kg decreased with increasing BMI in the emphysema group. Open circles represent emphysematous patients; dark circles are healthy volunteers.

 
We determined the correlates of RO2/kg using a backward stepwise regression model (Table 2 ). We found that the strongest correlate of RO2/kg in patients was BMI. Moreover, in this group of weight-stable patients, there was no correlation between BMI and indexes of airflow obstruction such as FEV1 and functional residual capacity (FRC). Indeed, we found no correlation between either FEV1, FRC, or total lung capacity (TLC), and RO2/kg, RO2/FFM, or BMI. However, DLCO was found to be a predictor of BMI. We then classified patients into quartiles based on BMI (Table 2) . The highest quartile of BMI was > 27.7, and the lowest quartile of BMI was < 22. There were no differences between the lowest quartile and highest quartile of BMI with respect to lung function indexes (FEV1, FRC, TLC).


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  		Table 2. Multivariate Analysis of Correlates in Emphysematous Group: Backwards Stepwise Regression - Variables Remaining in Models

 
Since RO2 adjusted to only body weight may not reflect body composition, we also investigated the relationship between RO2 and FFM for both groups (Table 2 , Fig 3 ). RO2 increased in both groups as FFM increased (r = 0.6 and r = 0.7 for patients and healthy subjects, respectively; p < 0.001 for both), but RO2 was greater for any level of FFM in patients compared to healthy subjects (Fig 3 , top, a). We then compared RO2 adjusted to body composition (RO2/FFM) between the emphysema and healthy groups (Fig 3 , bottom) and found that the same relationship held as for RO2/kg. That is, O2 normalized to FFM was greater in patients than normal subjects. However, as FFM increased, there was a decrease in O2 normalized to FFM in the emphysema group (p < 0.001, r = 0.5). This relationship did not hold for the normal group. Although the slope of the regression line was also positive in normal subjects, it was not significantly different from zero.



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  		Figure 3. The relationship between RO2 and FFM in patients and healthy subjects. Top: RO2 increased with increasing FFM in both groups, but the increase was higher in the emphysema group. Bottom: RO2/FFM followed similar pattern as RO2/kg: RO2/kg decreased with increasing BMI only in the emphysema group.

 
sTNF-R
Both sTNF-Rs were higher in the emphysema group compared to healthy control subjects (Table 1) . There was no correlation between sTNF-R and RO2, BMI, or steroid usage. Even when patients in the lowest quartile of BMI were compared to those in the highest quartile, no significant difference was found in the sTNF-R levels.

Leptin Levels
There were no differences in serum leptin between the two groups. Moreover, the increased RO2 in the emphysema group was not associated with serum leptin (p = 0.9, r = 0.01). There was no correlation between sTNF-R and leptin (p = 0.5, r = 0.1 for sTNF-R 55; p = 0.7, r = 0.07 for sTNF-R 75). Additionally, we found no correlation between leptin and steroid usage (p = 0.3, r = 0.1). Using multiple backward stepwise regression, gender, FRC, PCO2, and BMI were independent correlates of leptin (Table 2) .

Gender Differences
Gender is known to play a role in determining body composition; for example, women have higher leptin concentrations than men for any given degree of FM, and changes in anabolic and sex hormones have been documented in men with COPD and could impact on body composition.18 19 We also examined whether known gender-related differences were present in emphysema patients as well. As in normal subjects, we found that leptin levels were higher in women than men, FFM was greater in men, and percentage of body fat was higher in women (Table 3 ). There were no differences between the patient and the healthy groups with respect to the magnitude of gender-related differences. Thus, the occurrence of severe emphysema did not affect gender-related differences in body composition.


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  		Table 3. Gender Differences in Study Populations*

 
Other Factors
Steroid usage (prednisone or equivalent > 5 mg/d in 18 patients) did not correlate with BMI, FFM, or percentage of FM. Similarly, diuretic usage did not impact on these parameters. Additionally, no difference in BMI was noted in those patients who received oxygen for > 12 h/d (46 patients) compared to those who did not.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In this study, we were interested in weight-stable subjects, since these make up the majority of patients with emphysema, and this group has not been studied as carefully as weight-losing patients. Furthermore, we compared these weight-stable patients with severe emphysema to a group of healthy subjects with similar ages. The RO2/kg, RO2/FFM, and sTNF-R levels were higher in patients compared to healthy subjects. However, there were no differences in serum leptin between the two groups. Multivariate backward stepwise regression analysis revealed that BMI was the strongest predictor of RO2/kg in patients. Ravussin and Bogardus20 argued that normalizing RO2 to weight might be misleading, as it does not consider body composition. These authors argued that a somewhat better relationship could be obtained when RO2 is related to FFM. We also compared RO2/FFM between the two groups and found that the same relationship held as for RO2/kg (Fig 3) .

In a study of patients with stable COPD, Creutzberg et al12 showed that FFM depletion was present in one third of the COPD population studied. These authors also found that REE was higher in the COPD group compared to healthy control group after analysis of variance with covariates sex, age, FFM, and FM, prompting these authors to conclude that other factors influence REE in patients with COPD. The increased REE in that study12 was characterized by less hyperinflation as assessed by TLC, thus raising the possibility that hypermetabolism may be different for the COPD subtypes of emphysema and chronic bronchitis. However, Creutzberg et al12 did not distinguish between these two groups. Unlike Creutzberg et al,12 we found no correlation between RO2 (as an index of REE) and TLC. In our study, we examined only patients with emphysema and did not find evidence of FFM depletion in our group of non–weight-losing patients with emphysema. This may be due to the rigid selection criteria and definition of emphysema in our study.

In another study of nonmalnourished, clinically stable patients with COPD, Nguyen et al11 concluded that increased REE was related to plasma TNF concentration. While we found that sTNF-Rs were elevated in our emphysema group, we did not find a correlation between these markers of inflammation and the increased RO2. Such differences may also be due to rigid selection criteria of only emphysema patients who were both weight and clinically stable. Alternatively, the degree to which sTNF-Rs reflect TNF levels could the result of the interaction between receptor shedding and renal excretion, and may not be a simple reflection of the degree of inflammation.

Our results would indicate that increased RO2 in patients with emphysema could play a role in weight regulation in thinner patients, as heavier patients did not have increased energy expenditure. This finding is in agreement with those of prior studies1 2 3 4 5 6 7 8 9 10 in which weight-losing patients have increased REE, but our study extends this finding even to emphysema patients who have maintained their weight. In our patient group, as BMI increased, RO2 remained the same; however, RO2/kg decreased. The reasons are not clear, and this relationship does not necessarily imply cause and effect. However, this finding indicates that RO2 is subject to other influences besides body mass in patients. Such factors may include both increased work of breathing and metabolic effects of airway inflammation that act to make RO2 relatively insensitive to body mass. Interestingly, in our group of weight-stable patients, BMI did not correlate with measurement of airway obstruction such as FEV1 percentage of predicted and FVC percentage of predicted. However, our data indicate that BMI correlated with DLCO (Table 3) , and prior studies8 have shown that the association of malnutrition is more closely related to the presence of anatomic emphysema as judged by DLCO.

After adjustment for FM and oral corticosteroid use as possible confounders, Schols et al21 concluded that in a population of patients with emphysema, leptin was positively correlated to plasma sTNF-R 55, indicating a link between the systemic inflammatory response in emphysema and leptin. Creutzberg et al18 found that plasma leptin levels, adjusted for percentage of FM, were elevated initially in a group of hospitalized patients with COPD; however, the leptin levels decreased after 1 week, but remained higher when compared to a healthy, age-matched population. The authors attributed this to the higher steroid usage in the patient population during hospitalization. These authors also found a correlation between sTNF-R 55 and leptin, and concluded that temporary disturbances in the energy balance in patients with COPD are related to leptin and inflammation. Thus, according to these previous studies, a relationship between leptin and sTNF-R could indicate that a proinflammatory state in emphysema at least partially determines leptin levels.18 19 21 In our study, the use of steroids (> 5 mg/d of prednisone) did not relate to any body composition parameter; neither was there a relationship between steroid usage and leptin or sTNF-Rs. Similarly, another study22 did not find a relationship between steroid usage and leptin in a population of patients with lupus. Differences between our conclusions and those of prior studies may be due to the fact that our patients were clinically stable and not losing weight. Furthermore, the BMI in the study by Schols et al21 (21.6 ± 3.0) was less than the BMI in our patient population (25.7 ± 4.7). Hence, the study by Schols et al21 may have been dealing with patients actively losing weight, making comparisons difficult.

The chief function of leptin is to maintain body fat by signaling the brain that calorie intake and the amounts of energy stored as fat are sufficient. Thus, when FM is reduced, leptin serum concentrations are reduced, evoking compensatory changes in food intake that favor the return to the previous body weight. Accordingly, leptin is postulated to play a role in the remarkable recovery of weight lost after dieting.23 24 Our data in emphysematous patients are consistent with this, in that BMI and FM were the most important determinants of leptin. Unlike our study, Takabatake et al25 found that serum leptin was lower in the COPD group as compared to the healthy group. However, in that study25 the COPD group had significantly lower BMI and percentage of FM than the healthy group. Since our study demonstrates the effect of BMI on leptin, the lower leptin concentrations in the study by Takabatake et al25 appear to be an appropriate reaction to fat loss, rather than a response to emphysema per se.

Persistent airway inflammation has been long recognized in patients with COPD, and is postulated to alter the balance between mechanisms of lung repair and destruction in favor of the latter.26 Several studies have demonstrated increased markers of proinflammatory cytokines in sera of COPD patients, particularly those suffering from weight loss; it is postulated that such augmented systemic inflammation is yet another contributing factor to the hypermetabolism in weight-losing emphysema patients.9 10 21 26 Our findings would suggest that even in patients who are both clinically and weight stable, there is active and ongoing systemic inflammation. The present study does not allow us to determine the relative contributions of increased work of breathing or persistent systemic inflammation in leading to increased RO2. However, the present study does suggest that systemic inflammation could work synergistically with lung mechanics to increase RO2.

We conclude that in patients with weight-stable emphysema, RO2 is increased when compared to normal control subjects. This is especially true in patients with BMI in the lower end of the studied range. Additionally, emphysema patients as a group have increased levels of sTNF-Rs, which may indicate ongoing inflammation. Leptin correlated with BMI and gender in both emphysematous and healthy subjects, but was different between the groups. Although systemic inflammation and elevated RO2 are features of weight-stable emphysema patients, it is possible that any imbalance between RO2 (driven by inflammation and work of breathing) and energy supply (dietary intake), could become great enough to lead to weight loss in this susceptible group.


   Footnotes
 
Abbreviations: BMI = body mass index; DLCO = diffusing capacity of the lung for carbon monoxide; FM = fat mass; FFM = fat-free mass; FRC = functional residual capacity; NETT = National Emphysema Treatment Trial; PFT = pulmonary function test; REE = resting energy expenditure; RO2 = resting oxygen consumption; RO2/FFM = resting oxygen consumption normalized to fat-free mass; RO2/kg = resting oxygen consumption normalized to weight in kilograms; sTNF-R = soluble tumor necrosis factor receptor; TLC = total lung capacity; TNF = tumor necrosis factor; O2 = oxygen consumption; O2/kg = oxygen consumption normalized to weight in kilograms

This study was presented in abstract forms at the American Thoracic Society International Conference Toronto 2000 (May 5–10, 2000) and San Francisco 2001 (May 18–23, 2001).

Supported by the Weisman Pulmonary Research Fund.

Received for publication October 3, 2002. Accepted for publication May 21, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Schols, AM, Fredrix, EW, Soeters, PB, et al (1991) Resting energy expenditure in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 54,983-987[Abstract/Free Full Text]
  2. Schols, AM, Soeters, PB, Mostert, R, et al Energy balance in chronic obstructive pulmonary disease. Am Rev Respir Dis 1991;143,1248-1252[ISI][Medline]
  3. Sahebjami, H, Sathianpitayakul, E Influence of body weight on the severity of dyspnea in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161,886-890[Abstract/Free Full Text]
  4. Landbo, C, Prescott, E, Lange, P, et al Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160,1856-1861[Abstract/Free Full Text]
  5. Muers, MF, Green, JH Weight loss in chronic obstructive pulmonary disease. Eur Respir J 1993;6,729-734[Abstract]
  6. Schols, AM, Soeters, PB, Dingemans, C, et al Prevalence and characteristics of nutritional depletion in patients with stable COPD eligible for pulmonary rehabilitation. Am Rev Respir Dis 1993;147,1151-1156[ISI][Medline]
  7. Wilson, DO, Donahoe, M, Rogers, RM, et al Metabolic rate and weight loss in chronic obstructive lung disease. J Parenteral Enteral Nutr 1990;14,7-11[Abstract]
  8. Donahoe, M Nutritional support in advanced lung disease. Clin Chest Med 1997;18,547-561[CrossRef][ISI][Medline]
  9. Schols, AM, Buurman, WA, Brekel, AJ, et al Evidence for a relationship between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. Thorax 1996;51,819-824[Abstract]
  10. Di Francia, M, Barbier, D, Mege, L, et al Tumor necrosis factor {alpha} levels and weight loss in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994;150,1453-1455[Abstract]
  11. Nguyen, LT, Bedu, M, Beaufrere, B, et al Increased resting energy expenditure is related to plasma TNF-{alpha} concentration in stable COPD patients. Clin Nutr 1999;18,269-274[CrossRef][ISI][Medline]
  12. Creutzberg, EC, Schols, AMWJ, Bothmer-Quaedvlieg, FCM, et al Prevalence of an elevated resting energy expenditure in patients with chronic obstructive pulmonary disease in relation to body composition and lung function. Eur J Clin Nutr 1998;53,396-401
  13. The National Emphysema Treatment Trial Research Group. Rationale and design of the national emphysema treatment trial. Chest 1999;116,1750-1761[Abstract/Free Full Text]
  14. Crapo, RO, Morris, AH, Gardner, RM Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981;121,659-664
  15. Boutlier, A, Fricker, J, Thomasset, A-L, et al Fat-free mass estimation by the two-electrode impedance method. Am J Clin Nutr 1990;52,581-585[Abstract/Free Full Text]
  16. Schols, AM, Wouters, EF, Soeters, PB, et al Body composition by bioelectrical-impedance analysis compared with deuterium dilution and skinfold anthropometry in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 1991;53,421-424[Abstract/Free Full Text]
  17. Diez-Ruiz, A, Tilz, GP, Zangerle, R, et al Soluble receptors for tumor necrosis factor in clinical laboratory diagnosis. Eur J Haematol 1995;45,1-8
  18. Creutzberg, EC, Wouters, EF, Vanderhoven-Augustin, IM, et al Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162,1239-1245[Abstract/Free Full Text]
  19. Sarraf, P, Fredrich, RC, Turner, EM, et al Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med 1997;1,171-175
  20. Ravussin, E, Bogardus, C Relationship of genetics, age, and physical fitness to daily energy expenditure and fuel utilization. Am J Clin Nutr 1989;49,968-975
  21. Schols, AM, Creutzberg, EC, Buurman, WA, et al Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160,1220-1226[Abstract/Free Full Text]
  22. Garcia-Gonzalez, A, Gonzalez-Lopez, L, Valera Gonzalea, IC, et al Serum leptin levels in women with systemic lupus erythematosus. Rheumatol Int 2002;22,138-141[CrossRef][ISI][Medline]
  23. Mantzoros, C The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med 1999;130,671-680[Abstract/Free Full Text]
  24. Jequier, E Leptin signaling, obesity, and energy balance. Ann N Y Acad Sci 2000;967,379-388
  25. Takabatake, N, Nakamura, H, Abe, S, et al Circulating leptin in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159,1215-1219[Abstract/Free Full Text]
  26. Barnes, PJ Novel approaches and targets for treatment of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160,S72-S79[Abstract/Free Full Text]




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