Resting energy expenditure and carbohydrate oxidation are higher in elderly patients with COPD: a case control study

  • Bruna Rubi Ramires1,

    Affiliated with

    • Erick Prado de Oliveira2, 3, 6Email author,

      Affiliated with

      • Gustavo Duarte Pimentel4,

        Affiliated with

        • Kátia Cristina Portero McLellan3,

          Affiliated with

          • Darlan Muller Nakato5,

            Affiliated with

            • Márcia Maria Faganello5,

              Affiliated with

              • Maurício Longo Galhardo5 and

                Affiliated with

                • Luciene de Souza Venâncio1

                  Affiliated with

                  Nutrition Journal201211:37

                  DOI: 10.1186/1475-2891-11-37

                  Received: 11 January 2012

                  Accepted: 31 May 2012

                  Published: 6 June 2012

                  Abstract

                  Background

                  Elderly patients with chronic obstructive pulmonary disease (COPD) usually have a compromised nutritional status which is an independent predictor of morbidity and mortality. To know the Resting Energy Expenditure (REE) and the substrate oxidation measurement is essential to prevent these complications. This study aimed to compare the REE, respiratory quotient (RQ) and body composition between patients with and without COPD.

                  Methods

                  This case–control study assessed 20 patients with chronic obstructive pulmonary disease attending a pulmonary rehabilitation program. The group of subjects without COPD (control group) consisted of 20 elderly patients attending a university gym, patients of a private service and a public healthy care. Consumption of oxygen (O2) and carbon dioxide (CO2) was determined by indirect calorimetry and used for calculating the resting energy expenditure and respiratory quotient. Body mass index (BMI) and waist circumference (WC) were also measured. Percentage of body fat (%BF), lean mass (kg) and muscle mass (kg) were determined by bioimpedance. The fat free mass index (FFMI) and muscle mass index (MMI) were then calculated.

                  Results

                  The COPD group had lower BMI than control (p = 0.02). However, WC, % BF, FFMI and MM-I did not differ between the groups. The COPD group had greater RQ (p = 0.01), REE (p = 0.009) and carbohydrate oxidation (p = 0.002).

                  Conclusions

                  Elderly patients with COPD had higher REE, RQ and carbohydrate oxidation than controls.

                  Keywords

                  Chronic obstructive pulmonary disease Resting energy expenditure Elderly Carbohydrate oxidation

                  Introduction

                  Chronic obstructive pulmonary disease (COPD) is characterized by an obstructed or chronically limited airflow which progresses slowly and irreversibly. The main cause of COPD is the combination of chronic bronchitis and pulmonary emphysema, due mainly to smoking [1].

                  Patients with COPD usually have a compromised nutritional status which is an independent predictor of morbidity and mortality [2, 3]. Malnutrition affects approximately one-third of the adult patients with this disease [2], mainly in elderly [4]. The fat-free mass decreases and body fat increases but body mass index (BMI) remains unchanged, suggesting that one body compartment is replaced by another [5]. Malnutrition in patients with COPD is associated with increased energy expenditure due to hypermetabolism, which in turn is caused by greater respiratory muscle effort, oxygen requirement and inflammation and lower food intake [6].

                  It is essential to determine resting energy expenditure (REE) to prevent a negative caloric balance and consequently malnutrition, since REE is the main component of total energy expenditure (TEE) [7] and is vital for adequate food intake [8]. Additionally, it is also critical to know which energy substrate is the most oxidized so that appropriate dietary adjustments can be made.

                  Changes in energy metabolism stemming from patients with COPD can be detected by indirect calorimetry, which measures oxygen consumption (O2) and elimination of carbon dioxide (CO2), thus determining REE and respiratory quotient (RQ). RQ depends on the mixture of energy substrates (carbohydrates, fats and proteins) that is the mixture metabolized during rest or exercise. In patients with COPD, a RQ < 1.0 is desirable since the patient will be exhaling less carbon dioxide [9]. However, no study assessed carbohydrate and fat oxidation separately in this group of patients (with COPD), and this is essential for understanding the energy metabolism of these individuals. An appropriate nutritional strategy for treating malnutrition in patients with COPD has not yet been established because, despite extensive studies on their energy metabolism, not much data is available on their oxidative capacity [10].

                  Hence, the aim of the present study was to compare the oxidation amount of energy substrates and REE of elderly patients with and without COPD.

                  Methodology

                  Sample

                  The study was conducted from December 2008 to February 2009. Forty elderly individuals living in the same area were recruited and divided into two groups: a COPD group (16 males and 4 females) and a control group (16 males and 4 females). Patients in the COPD group were diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease – (Gold) [11] criteria and were attending a pulmonary rehabilitation program provided by a private healthcare service. The controls and COPD patients were paired by gender and age.

                  The study was approved by the Methodist University of Piracicaba Research Ethics Committee under protocol number 40/09. All study participants signed a free and informed consent form.

                  Study design

                  A case–control study was done to compare the body composition, REE and RQ of individuals with and without COPD.

                  The inclusion criteria for the COPD patients were: age ≥ 60 years and the presence of pulmonary emphysema and/or chronic bronchitis. The inclusion criteria for the control group were: age ≥ 60 years and not having pulmonary diseases.

                  Assessment of body composition

                  Weight (kg) and height (cm) were measured for determining body mass index (BMI). Nutritional status was classified according to the World Health Organization (WHO) [12]. Waist circumference was measured midway between the lowest rib and the iliac crest with an inelastic tape measure and classified according to the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP-ATPIII) [13]. Bioelectrical impedance (BioDynamics model 310) was used for determining fat and muscle masses. Absolute fat and fat-free mass (FFM) were calculated by the Segal et al. (1988) equations [14]. Muscle mass (MM) was calculated by the Janssen et al. (2000) equation [15]. Then, the muscle mass index (MM-I) was calculated by dividing MM by the square of the height and were classified the sarcopenia [16].

                  Assessment of REE and substrate oxidation

                  Indirect calorimetry (Metalyzer 3B – R2 (Cortex), breath by breath) was used for determining REE, RQ and carbohydrate and fat oxidation after calibration of barometric pressure (960 mbar) and room air (O2: 20.93/CO2: 0.03 Vol%) against a known gas mixture (White Martins, O2: 15.94/CO2: 5.01 Vol%) and volume (3-liter Hans Hudolph syringe, V = 3.0 L). REE was determined by the Weir (1949) [17] equation after measuring oxygen consumption (VO2) and production of carbon dioxide (VCO2). RQ was determined by the respiratory exchange ratio (VCO2/VO2). The Jeukendrup & Wallis (2005) [18] equation was used for determining carbohydrate and fat oxidation separately.

                  For the measurements, the fasting participants were asked to lie on their backs using a mask and remain still and silent until the steady state condition was reached over a 5-minute period and 20% variation of VO2, 12% variation of VCO2 and 10% variation of RQ. Both room temperature (25.0°C ± 2.0) and relative humidity (47.0 ± 4.5%) were controlled.

                  None of the individuals presented the flu, cold or cough during the assessment and all individuals were asked to avoid exercise and caffeinated or alcoholic beverages consumption during the 48 hours that preceded the assessment.

                  Statistical analysis

                  The results were expressed as mean ± standard deviation and percentage. The software Statistica 6.0 was used for the statistical analyses. The qualitative variables (age, gender, race/color, marital status, occupation, education level, place of residence, nutritional status, smoking status, high blood pressure, presence of diabetes mellitus type 2 and level of physical activity) were compared by the chi-square or Fisher’s exact test. The Shapiro-Wilk test was used for testing for normality. Since all variables were normal, the unpaired Student’s t-test was used for comparing the quantitative variables of both groups. The significance level was set at 5%.

                  Results

                  Sociodemographic and clinical assessment

                  The study sample consisted of elderly, white, non-working individuals, mostly males. The COPD group had higher education level and higher percentage of smokers and physically active individuals than the control group (Table 1).
                  Table 1

                  Sociodemographic and clinical characteristics of the chronic obstructive pulmonary disease and control groups

                  Characteristics

                  Control group

                  COPD group

                  p

                  n = 20

                  n = 20

                  n

                  %

                  n

                  %

                  Gender

                      

                  1.000

                  Males

                  16

                  80

                  16

                  80

                  Females

                  4

                  20

                  4

                  20

                  Age

                      

                  0.47

                  (years)

                  75.5± 7.65 (61-86)

                  73.7± 8.0 (61-86)

                  Race/Color

                      

                  1.0000

                  White

                  17

                  85

                  17

                  85

                  Non-white

                  3

                  15

                  3

                  15

                  Marital status

                      

                  0.1504

                  Married

                  16

                  80

                  13

                  65

                  Widowed

                  1

                  5

                  5

                  25

                  Divorced

                  1

                  1

                  2

                  10

                  Single

                  2

                  10

                  -

                  -

                  Occupation

                      

                  0.5483

                  Inactive

                  19

                  95

                  18

                  90

                  Active

                  1

                  5

                  2

                  10

                  Education level

                      

                  0.0274*

                  Illiterate

                  -

                  -

                  3

                  15

                  Elementary school

                  9

                  45

                  11

                  55

                  High school

                  8

                  40

                  1

                  5

                  Higher education

                  3

                  15

                  5

                  25

                  Place of residence

                      

                  0.03501*

                  Lins

                  20

                  100

                  16

                  80

                  Other cities

                  -

                  -

                  4

                  20

                  Nutritional status

                      

                  0.0705

                  Normal weight

                  11

                  55

                  12

                  60

                  Underweight

                  -

                  -

                  3

                  15

                  Overweight

                  5

                  25

                  5

                  25

                  Obese

                  4

                  20

                  -

                  -

                  Duration of COPD

                  -

                  -

                  4.65 ± 2.97

                  -

                  -

                  Smoking status

                      

                  0.00091*

                  Non-smoker

                  12

                  60

                  2

                  10

                  Ex-smoker and smoker

                  8

                  40

                  18

                  90

                  High blood pressure

                  9

                  45

                  9

                  45

                  1.000

                  Diabetes mellitus type 2

                  -

                  -

                  3

                  15

                  0.0717

                  Physical activity

                      

                  0.03501*

                  Active

                  16

                  80

                  20

                  100

                  Inactive

                  4

                  20

                  -

                  -

                   

                  COPD: Chronic obstructive pulmonary disease; *  = p indicates a significant difference between the groups; Gender, race/color, marital status, occupation, education level, nutritional status: chi-square test; place of residence: Fisher’s exact test; age: unpaired Student’s t-test.

                  Assessment of body composition

                  Nutritional status, classified according to BMI, did not differ significantly between the groups (Table 2) but the COPD group had lower BMI than the control group. MM-I, degree of sarcopenia (%), body fat (%), fat-free mass index (FFM-I) and waist circumference (cm) did not differ between the groups, showing that both groups had similar body composition (Table 2).
                  Table 2

                  Body composition of the chronic obstructive pulmonary disease (COPD) and control groups

                   

                  Control

                  COPD

                  p

                  Age (years)

                  75.5 ± 7.7

                  73.7 ± 8.0

                  0.47

                  Weight (kg)

                  68.1 ± 12.4

                  61.0 + 12.1

                  0.054

                  Height (cm)

                  162.8 ± 6.5

                  163.7 ± 7.9

                  0.70

                  BMI (kg/m 2 )

                  25.6 ± 4.1

                  22.8 ± 3.4

                  0.02

                  WC (cm)

                  94 ± 10.9

                  89.7 ± 14.2

                  0.28

                  % body fat

                  28.9 ± 3.4

                  26.9 ± 3.3

                  0.07

                  Muscle mass (kg)

                  22.3 ± 5

                  21.4 ± 5

                  0.57

                  MM-I (kg/m 2 )

                  8.4 ± 1.5

                  7.9 ± 1.5

                  0.32

                  BMI: body mass index; WC: waist circumference; MM-I: muscle mass index.

                  Assessment of REE and substrate oxidation

                  Individuals with COPD had higher REE, carbohydrate oxidation and RQ than the controls. Fat oxidation did not differ between the groups (Figure 1).
                  http://static-content.springer.com/image/art%3A10.1186%2F1475-2891-11-37/MediaObjects/12937_2012_546_Fig1_HTML.jpg
                  Figure 1

                  Assessment of resting energy expenditure, respiratory quotient and carbohydrate and fat oxidation of chronic obstructive pulmonary disease patients and controls.

                  Discussion

                  In the present study, we found that individuals with COPD had higher REE and resting carbohydrate oxidation than the controls, regardless of body composition, since both groups had similar muscle mass.

                  Other studies have also found that patients with COPD have higher REE (approximately 15 to 26%) [6, 19]. The greater energy expenditure of individuals with COPD is probably due to increased respiratory muscle effort and inflammatory mediators, in addition to the effects of medication (oral or systemic corticosteroids, theophylline, hormones, benzodiazepines and antipsychotics) [1921].

                  This study found that mean RQ and carbohydrate oxidation were higher in the COPD group, while fat oxidation was similar in both groups. Increased carbohydrate oxidation in the COPD group was probably caused by increased anaerobic metabolism due to reduced ability to capture oxygen [22]. When carbohydrates are oxidized in the absence of oxygen, only 2 ATP molecules per millimol of carbohydrates are generated, while the presence of oxygen increases ATP/millimol generation to 36 ATPs [22]. Hence, individuals with COPD need to oxidize greater amounts of carbohydrates than healthy individuals to generate similar amounts of ATP molecules, because COPD patients present a higher ATP cost [23].

                  Moreover, individuals with COPD show depletion of type I muscle fibers (aerobic) and a greater proportion of type IIx fibers, with consequent reduction in the number of mitochondria and oxidative enzymes and lower expression of peroxisome proliferator-activated receptors (PPAR-α) and PGC-1α, molecular markers that are related to mitochondrial biogenesis and higher activation of oxidative metabolism [24]. Although individuals with COPD have lower aerobic metabolism, fats are only oxidized in the presence of oxygen [9], however their fat oxidation was not affected, which is necessary more studies to explain this fact.

                  BMI has been used as a good indicator of the nutritional status of individuals with COPD [25]. However, it is not possible to determine body composition with this index [26]. So this study also determined the body composition, muscle mass index, degree of sarcopenia, percentage of body fat, fat-free mass index and waist circumference of the participants.

                  The results showed that the COPD and control groups had similar body composition, which may be explained by the advanced age of the members of both groups [27]. It is estimated that people lose 5% of their muscle mass per decade after age 40 years and this loss intensifies after age 65 years [27]. The degree of sarcopenia was similar in both groups since both groups presented loss of muscle mass. However, loss was greater in individuals with COPD and class II sarcopenia than in controls. A similar result was found by Sergi et al., 2006, [19] who found a greater prevalence of sarcopenia in individuals with COPD than in healthy controls. COPD can intensify the loss of muscle mass, affecting respiratory and peripheral muscle performance, and thereby reducing ventilation and physical activity [28]. According to the II Brazilian Consensus on COPD [1], patients with moderate COPD may have FFM depletion involving skeletal muscles, which results in weight loss. In the present study, the FFM-I of both groups was similar. Sergi et al., 2006, [19] found that individuals with COPD had lower FFM than healthy controls. Reduced FFM in these patients could be associated with age and particularly regard peripheral skeletal muscles, which may manifest as weakness in individuals with COPD [19].

                  The present and other Brazilian studies have found that COPD affects mainly elderly males with a past or current history of smoking [1, 29]. Another aspect observed in individuals with COPD is the change in nutritional status, such as malnutrition [30]. However, a recent study [19] found a higher prevalence of normal weight individuals. It is important for individuals with COPD not to become underweight since the severity of pulmonary diseases is associated with low BMI, which can result in worse nutritional prognosis and shorter survival [2]. The COPD participants of the present study were attending a pulmonary rehabilitation program and mean duration of disease was 4.65 years, that is, they were in the initial phase of the disease. Hence, this may explain the high prevalence of normal weight or overweight individuals in the present study.

                  Although most patients were normal weight or overweight, the risk of malnutrition was found in 15% of the patients with COPD. This risk was not observed in the control group. Progressive weight loss in these patients may be due to a set of factors, such as release of inflammatory mediators, which can contribute to hypermetabolism and generate an inappropriate response to food intake, and reduced food intake [31]. Moreover, increased serum concentration of leptin has already been observed and now it is known that this hormone promotes greater energy expenditure and consequently, greater weight loss [31]. Recently, Ying et al. (2008) [32] found that underweight individuals with COPD have high serum levels of ghrelin. Ghrelin reduces fat oxidation, which may explain why the COPD participants of the present study did not present more fat oxidation than the controls. However, more studies are necessary to explain these findings.

                  Diet affects nutritional status and may change the progression rate of pulmonary disease [33]. Recent studies do not recommend high-fat diets, but an energy intake that allows individuals to reach or maintain an appropriate nutritional status [3]. A high-fat, low-carbohydrate diet can improve the prognosis of COPD patients with acute exacerbation [34]. Patients with marginal ventilatory reserve might benefit from a high-fat diet [35]. Although the present study did not assess the pulmonary ventilation of the participants, it has found that carbohydrates are the main substrates oxidized. The recommended amount of carbohydrates is 50 to 60% of the total energy expenditure of the patient. Excessive carbohydrate intake could cause lipogenesis with consequent excessive production of carbon dioxide and hepatic steatosis, which in turn increases RQ and production of carbon dioxide, resulting in respiratory failure [36]. Hence, the recommended carbohydrate intake of 50 to 60% of the total energy expenditure seems not to induce hyperventilation and also avoids malnutrition by replacing the burned carbohydrates.

                  In the group studied in this work it is possible to conclude that elderly patients with COPD have higher REE, RQ and carbohydrate oxidation than healthy controls.

                  Abbreviations

                  COPD: 

                  Chronic obstructive pulmonary disease

                  REE: 

                  Resting Energy Expenditure

                  BMI: 

                  Body Mass Index

                  RQ: 

                  Respiratory Quotient

                  NCEP-ATPIII: 

                  Expert Panel on Detection

                   : 

                  Evaluation and Treatment of High Blood Cholesterol in Adults

                  FFM: 

                  Fat-free mass

                  MM: 

                  Muscle mass

                  MM-I: 

                  Muscle mass index

                  WC: 

                  Waist Circumference.

                  Declarations

                  Authors’ Affiliations

                  (1)
                  Universidade Metodista de Piracicaba (UNIMEP)
                  (2)
                  Department of Pathology, São Paulo State University (UNESP)
                  (3)
                  Department of Public Health, Centre for Physical and Nutritional Metabolism (CeMENutri), São Paulo State University (UNESP)
                  (4)
                  Department of Internal Medicine, Campinas State University (UNICAMP)
                  (5)
                  Department of Physiotherapy, Centro Universitário Católico Salesiano Auxilium-Unisalesiano
                  (6)
                  CeMENutri - Faculdade de Medicina, Depto. de Saúde Pública (FMB - UNESP)

                  References

                  1.   : II Consenso Brasileiro sobre Doença Pulmonar Obstrutiva Crônica (DPOC). J Pneumol 2004, 30:1–41.
                  2. Congleton J: The pulmonary cachexia syndrome: aspects of energy balance. Proc Nutr Soc 1999, 58:321–328.View Article
                  3. Sachs A, Lerario MC: Doenças pulmonares. Guia de nutrição clínica no adulto.Volume 2. 2° edição.Editado por Cuppari L, Barueri: Manole; 2005:249–262.
                  4. Pierine DT, Nicola M, de Oliveira EP: Sarcopenia: alterações metabólicas e consequências no envelhecimento. R bras Ci e Mov 2009, 17:96–103.
                  5. Ischaki E, Papatheodorou G, Gaki E, Papa I, Koulouris N, Loukides S: Body mass and fat-free mass indices in COPD: relation with variables expressing disease severity. Chest 2007, 132:164–169.View Article
                  6. Vasconcelos FC, Mota ES, Lopez MFL, Fernandez SSL, Medeiros ZL: Terapia nutricional na doença pulmonar obstrutiva crônica associada à desnutrição proteico calórica. Rev Paraense Med 2002, 16:47–52.
                  7. da Rocha EE, Alves VG, da Fonseca RB: Indirect calorimetry: methodology, instruments and clinical application. Curr Opin Clin Nutr Metab Care 2006, 9:247–256.View Article
                  8. de Oliveira EP, Orsatti FL, Teixeira O, Maesta N, Burini RC: Comparison of predictive equations for resting energy expenditure in overweight and obese adults. J Obes 2011, 2011:534714.
                  9. Anderson L, Diblle MV, Turkki DS, Mitchell PR, Rynbergen HS: Metabolismo energético. Nutrição. 17a ed. Rio de Janeiro: Guanabara; 1988:179–187.
                  10. Schols AM: Nutritional and metabolic modulation in chronic obstructive pulmonary disease management. Eur Respir J Suppl 2003, 46:81s-86s.View Article
                  11. Pauwels RA, Buist AS, Calverley P, Jenkins CR, Hurd SS: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001, 163:1256–1276.
                  12. World Health Organization: Global health risks: mortality and burden of disease attributable to selected major risks. Geneva: World Health Organization; 2009.
                  13.   : Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001, 285:2486–2497.View Article
                  14. Segal KR, Van Loan M, Fitzgerald PI, Hodgdon JA, Van Itallie TB: Lean body mass estimation by bioelectrical impedance analysis: a four-site cross-validation study. Am J Clin Nutr 1988, 47:7–14.
                  15. Janssen I, Heymsfield SB, Baumgartner RN, Ross R: Estimation of skeletal muscle mass by bioelectrical impedance analysis. J Appl Physiol 2000, 89:465–471.
                  16. Janssen I, Baumgartner RN, Ross R, Rosenberg IH, Roubenoff R: Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women. Am J Epidemiol 2004, 159:413–421.View Article
                  17. Weir JB: New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 1949, 109:1–9.
                  18. Jeukendrup AE, Wallis GA: Measurement of substrate oxidation during exercise by means of gas exchange measurements. Int J Sports Med 2005,26(Suppl 1):S28-S37.View Article
                  19. Sergi G, Coin A, Marin S, Vianello A, Manzan A, Peruzza S, Inelmen EM, Busetto L, Mulone S, Enzi G: Body composition and resting energy expenditure in elderly male patients with chronic obstructive pulmonary disease. Respir Med 2006, 100:1918–1924.View Article
                  20. Planas M, Alvarez J, Garcia-Peris PA, de la Cuerda C, de Lucas P, Castella M, Canseco F, Reyes L: Nutritional support and quality of life in stable chronic obstructive pulmonary disease (COPD) patients. Clin Nutr 2005, 24:433–441.View Article
                  21. Kao CC, Hsu JW, Bandi V, Hanania NA, Kheradmand F, Jahoor F: Resting energy expenditure and protein turnover are increased in patients with severe chronic obstructive pulmonary disease. Metabolism 2011, 60:1449–1455.View Article
                  22. Marzzoco A, Torres BB: Metabolismo de carboidratos: glicólise e formação de acetil-coa. Bioquímica Básica. 2a ed. Rio de Janeiro: Guanabara Koogan; 1999:119–129.
                  23. Layec G, Haseler LJ, Hoff J, Richardson RS: Evidence that a higher ATP cost of muscular contraction contributes to the lower mechanical efficiency associated with COPD: preliminary findings. Am J Physiol Regul Integr Comp Physiol 2011, 300:R1142-R1147.View Article
                  24. Sathyapala SA, Kemp P, Polkey MI: Decreased muscle PPAR concentrations: a mechanism underlying skeletal muscle abnormalities in COPD? Eur Respir J 2007, 30:191–193.View Article
                  25. Marti S, Munoz X, Rios J, Morell F, Ferrer J: Body weight and comorbidity predict mortality in COPD patients treated with oxygen therapy. Eur Respir J 2006, 27:689–696.View Article
                  26. Fernandes AC, Bezerra OM: Nutrition therapy for chronic obstructive pulmonary disease and related nutritional complications. J Bras Pneumol 2006, 32:461–471.View Article
                  27. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD: Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998, 147:755–763.View Article
                  28. Montes De Oca M, Celli BR: Respiratory muscle recruitment and exercise performance in eucapnic and hypercapnic severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000, 161:880–885.
                  29. Francisco PM, Donalisio MR, de Azevedo Barros MB, Cesar CL, Carandina L, Goldbaum M: [Factors associated with pulmonary disease among the elderly]. Rev Saude Publica 2006, 40:428–435.View Article
                  30. Silva AB, Costa D, Baldissera V, Cardello L, Demonte A: Correlações entre os níveis de L-carnitina plasmática, o estado nutricional e a função ventilatória de portadores de doença pulmonar obstrutiva crônica. Rev Nutr 2005, 18:349–356.View Article
                  31. Dourado VZ, Tanni SE, Vale SA, Faganello MM, Sanchez FF, Godoy I: Systemic manifestations in chronic obstructive pulmonary disease. J Bras Pneumol 2006, 32:161–171.View Article
                  32. Ying BW, Song XB, Fan H, Wang LL, Li YS, Cheng Z, Cheng H, Wen FQ: Plasma ghrelin levels and weight loss in Chinese Uygur patients with chronic obstructive pulmonary disease. J Int Med Res 2008, 36:1371–1377.
                  33. Aniwidyaningsih W, Varraso R, Cano N, Pison C: Impact of nutritional status on body functioning in chronic obstructive pulmonary disease and how to intervene. Curr Opin Clin Nutr Metab Care 2008, 11:435–442.View Article
                  34. Tümer G, Mercanligil SM, Uzun O, Aygün C: The Effects of a High-Fat, Low-Carbohydrate Diet on the Prognosis of Patients with an Acute Attack of Chronic Obstructive Pulmonary Disease. Turkiye Klinikleri J Med Sci 2009, 29:895–904.
                  35. Ferreira I, Brooks D, Lacasse Y, Goldstein R: Nutritional intervention in COPD: a systematic overview. Chest 2001, 119:353–363.View Article
                  36. Vianna R, Maia F, Waitzberg DL: Insuficiência respiratória. In Nutrição oral, enteral e parenteral na prática clínica. 3ath edition. Edited by: Waitzberg DL. São Paulo: Atheneu; 2000:1199–1208.

                  Copyright

                  © Ramires et al.; licensee BioMed Central. 2012

                  This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.