Nutritional status in chronic obstructive pulmonary disease: role of hypoxia.

In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of "growth hormone resistance." Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation.

[Physical activity in the prevention and control of diabetes]. / L'activité physique dans la prévention et le contrôle du diabète.

Retrospective analyses in the general population habits show that regular exercise is a protection factor for the metabolic syndrome and type 2 diabetes, among many other diseases. Randomized controlled studies in at-risk population have investigated the impact of lifestyle programs, including diet and physical training, on the incidence of diabetes, confirming physical exercise as a cornerstone in the strategy of the prevention and treatment of type 2 diabetes. Although public health recommendations regarding regular physical activity are available, however often little is done by governments to implement them. Finally, the general practitioner is pivotal in counseling patients regarding their lifestyle and therefore in affecting a large number of people.

Body composition in patients with chronic hypercapnic respiratory failure.

STUDY OBJECTIVE: To evaluate the contribution of body composition measurements to clinical assessment in patients on home nasal positive-pressure ventilation for chronic hypercapnic respiratory failure (CHRF), and their relationship to respiratory impairment. METHODS: Patients with CHRF (restrictive lung disease (RLD), n=37; chronic obstructive pulmonary disease (COPD), n=19), during elective yearly evaluations underwent pulmonary function testing (forced expiratory volumes, arterial blood gases, maximal inspiratory and expiratory pressure (PI(max) or PE(max))), and bioelectrical impedance analysis to determine fat-free mass (FFM) index (kg/m(2)) and body fat mass index. RESULTS: When compared with age- and sex-matched healthy controls, RLD patients (OR 5.5, CI 1.9-15.6, P<0.002) and COPD (OR 5.2, CI 1.1-24.9, P=0.04) were significantly more likely to have a low FFM index. Roughly one-half of patients with RLD and one-third with COPD had abnormally low FFM index. Estimation of nutritional status by body mass index (BMI) alone clearly underestimated the prevalence of FFM index depletion. Muscle mass assessed by FFM index explained 26% of variance of PI(max) (P<0.001) and 27% of that of PE(max) (P<0.001). CONCLUSION: BMI alone clearly underestimated FFM depletion, and presence of a very high body fat mass index. Indeed, normal or high BMI can be associated with FFM depletion. Because of its relationship to respiratory muscle strength, an assessment of FFM appears to be valuable in CHRF.

A 3-year longitudinal study on body composition changes in the elderly: role of physical exercise.

BACKGROUND: Cross-sectional data have shown that sarcopenia and fat accumulation are associated with aging and can be limited by structured physical training. However, it is often difficult to maintain a long-term compliance to training programs. It is not clear whether leisure-time physical activity is effective in preventing sarcopenia and fat accumulation. OBJECTIVES: (i) To investigate longitudinal body composition changes in a population of elderly people in good apparent health. (ii) To evaluate the impact of leisure-time physical activity on muscle mass and characteristic as reflected by total body potassium per fat-free soft tissue (TBK/FFST), and on fat accumulation. DESIGN: Longitudinal evaluation over 3 years, of body composition changes in 74 healthy men and 66 women, over 65 years old. Body fat and FFST were analyzed by dual-energy X-ray absorptiometry and TBK by whole-body (40)K counter. Physical activity was analyzed by a specific questionnaire. RESULTS: Despite a stable total body weight, FFST and appendicular skeletal muscle mass slightly decreased (-0.3+/-1.4 and -0.2+/-2.2 kg, P<0.01, respectively) as well as the TBK/FFST (-4.1+/-6.3 mmol/kg, P<0.001), over the 3-year period. Body fat increased significantly (0.6+/-2.2 kg, P<0.0001), and it accumulated mainly in the abdomen (0.4+/-1.5 kg, P<0.01). Multiple regression analysis showed that body composition changes were related mainly to body weight changes. Nevertheless, positive linear correlations were observed between the degree of engagement in leisure-time physical activity and FFST (P<0.01), appendicular skeletal muscle mass (P<0.05), TBK/FFST (P<0.05), whereas negative correlation was observed with total and truncal fat (P<0.01). CONCLUSIONS: Mild but significant decline in muscle mass and its TBK content, and body fat accumulation were observed over a 3-year period in healthy elderly subject: leisure-time physical activity does not seem to prevent them. However, a higher level of physical activity is associated with higher muscle mass and TBK content, and less total and truncal fat.

[Subjective Global Assessment (SGA): evaluation and followup of nutritional state]. / Subjective Global Assessment (SGA): evaluation et suivi de i'etat nutritionnel.

The subjective global assessment (SGA) defines nutritional and functional status of patients with the aim of identifying who could benefit from a nutritional intervention. The SGA was designed to evaluate the nutritional risk of infectious complications among the surgical patients. Later on, it became largely utilized to evaluate the nutritional status of other groups of patients, because it is reliable and easy to use. However, it is important to verify that the SGA is an adequate test also in other clinical situations. This review analyses recent literature regarding the actual utilization of the SGA in clinical situations frequently associated to malnutrition: kidney diseases, AIDS, cancer, aging. The reproducibility of SGA depends on the experience of the caregiver administering it. Its validation compared to more objective parameters like visceral proteins or body composition is not always obvious. In several studies the SGA does not seem enough sensitive to detect a beginning of malnutrition. Its specificity and predictive validity were demonstrated in all of the clinical situations analyzed. In conclusion, the SGA is a tool adequate to identify patients with a nutritional risk and who would benefit of a nutritional intervention aiming at preventing associated complications.

[Screening and treatment of malnutrition: European Council Resolution and its potential application in Switzerland]. / Dépistage et traitement de la dénutrition: Résolution du Conseil de l'Europe et potentiel d'application en Suisse.

The deleterious consequences of hospital malnutrition are progressively being recognized by the public. The Committee of the Ministers of the European Council has released a resolution for food and nutrition and ask the state members to apply national recommendations in their hospitals. The evaluated domains and actions to be undertaken are based on 4 elements: Access to a healthy and varied food supply is a fundamental human right; a high number of patients hospitalized in Europe are malnourished (30-60%); the demonstration that malnutrition of hospitalized patients increases length of hospital stay and medical costs; the demonstrated beneficial effects of a hospital food service and of optimal nutritional care on morbidity, healing and quality of life. The resolution indicates clearly the options to be followed to optimize the actions and decisions at three levels: patient care, support services, and administration. All caregivers must be involved in the implementation of the recommendations in a way to adapt them to the local needs and restrictions. This review summarizes the actions to be taken by medical and other caregivers in order to sensitize them to the above-mentioned problems and to initiate practical options to treat malnourished patients or patients at risk of becoming malnourished.

[Metabolic adaptation to hypoxia: chronic obstructive pulmonary disease and high altitude]. / Adaptation métabolique a l'hypoxie: bronchopneumopathies chroniques obstructives et haute altitude.

The effect of oxygen in modulating metabolism has been largely investigated in vitro and in animal studies, but very little in humans. Body weight loss and muscle fatigability is a common finding in chronic obstructive pulmonary diseases, often difficult to reverse despite an optimal nutritional intake. The aim of this paper is to review recent literature regarding pathological and physiological situations characterized by hypoxia exposure, particularly chronic obstructive pulmonary diseases and high altitude staying.

Chronic hypoxia: common traits between chronic obstructive pulmonary disease and altitude.

PURPOSE OF REVIEW: Loss of body mass and exercise intolerance are common findings in chronic obstructive pulmonary disease and are often difficult to reverse despite optimal nutritional intake. Similar findings have been reported in healthy individuals during high-altitude exposure. The role of hypoxia in modulating metabolism has been largely investigated in vitro and in animal studies. More fragmentary is the knowledge regarding hypoxia effects on in-vivo human metabolism. This paper reviews recent literature regarding the effects of chronic exposure to hypoxia on metabolism, particularly comparing chronic obstructive pulmonary disease patients with humans exposed to high altitude. RECENT FINDINGS: Hypoxia has important metabolic effects. Many oxygen-sensitive regulatory mechanisms work through hypoxia inducible factor 1, and recent literature regarding the hypoxic stimulus and its pathological implications deals largely with hypoxia inducible factor 1-related findings. Hypoxia inducible factor 1 is pivotal in the adaptation to chronic hypoxia: it induces gene expression for fructose-2-6-biphosphatase, an enzyme switching glucose metabolism towards glycolysis, allowing energy production in anaerobic conditions. Hypoxia inducible factor 1 is also involved in the development of anorexia because it induces the promoter of the leptin gene. Particularly important for future therapeutic implications are findings related to hypoxia inducible factor 1 polymorphism and interaction with other molecules, especially estrogens, in the clinical evolution of disease. SUMMARY: Malnutrition is a worsening factor in chronic obstructive pulmonary disease. Similarities between chronic obstructive pulmonary disease and altitude exposure point to the importance of hypoxia in this regard. A better understanding of the underlying mechanisms will help to find alternative therapeutic approaches.

L-ornithine alpha-ketoglutarate in HIV infection: effects on muscle, gastrointestinal, and immune functions.

OBJECTIVES: There have been claims that l-ornithine alpha-ketoglutarate (OKG) exerts anticatabolic, anabolic, and immunomodulating properties. This study aimed at quantifying the effects of OKG on muscle force, body composition, and immune function in outpatients infected with the human immunodeficiency virus (HIV) and presenting weight loss. METHODS: Forty-six HIV(+) patients were included in a double-blind, prospective, randomized, controlled trial for 12 wk (10 g/d of OKG or isonitrogenous placebo and nutritional counseling). Podometry, handgrip strength, step test, triceps skinfold thickness, 50-kHz bioelectrical impedance, 3-d diet record, CD4 cell count, HIV-1 RNA concentration (viral load), and gastrointestinal symptoms were assessed at 0, 4, 8, and 12 wk. RESULTS: At baseline, patients (OKG, n = 22; placebo, n = 24) has similar CD4 counts (338 +/- 172 and 310 +/- 136 cells/mL), viral load (3.6 +/- 1.3 and 3.5 +/- 1.3 log(10) copies/mL), body mass index (20.0 +/- 2.4 and 20.6 +/- 3.0 kg/m(2)), weight loss (9.0 +/- 3.12 and 9.4 +/- 3.0 kg), and food intake (2509 +/- 962 and 2610 +/- 808 kcal/d). Twenty-nine patients completed the protocol. Both groups increased their body mass index (P = 0.02 versus baseline) and triceps skinfold thickness (P < 0.01 versus baseline). They showed a similar positive correlation between handgrip strength and fat-free mass. Frequency of gastrointestinal symptoms increased in the OKG group (86% versus 54% in the placebo group, P = 0.025). No other differences were observed between groups. CONCLUSIONS: All patients increased their body mass index and triceps skinfold thickness due to food supplementation and diet counseling. Oral OKG failed to improve nutritional, functional, or immunologic status in these weight-losing HIV(+) patients and had important gastrointestinal side effects.

The role of visceral proteins in the nutritional assessment of intensive care unit patients.

PURPOSE OF REVIEW: This review analyses the recently published literature focusing on nutritional assessment in intensive care unit patients. The metabolic response to nutritional intervention is difficult to evaluate in critically ill patients whose body weight is influenced largely by massive fluid administration or losses. Visceral protein plasma levels have been proposed for this purpose, because they reflect hepatic synthesis in response to nutrient supply. However, in acute inflammatory states, liver activity is converted to the synthesis of acute-phase response proteins, resulting in a dramatic drop in visceral proteins, despite nutritional support. RECENT FINDINGS: The data regarding visceral protein levels were examined in relation to nutritional supplementation, and compared with other nutritional parameters and clinical outcomes. Transthyretin and retinol-binding protein levels seem to be the most sensitive to nutritional intervention. They are also the earliest to rise at the decrease of acute-phase protein levels, therefore representing a good index of the reversing reprioritization of hepatic protein synthesis. An inconsistent relationship was found between visceral protein plasma levels and clinical outcome in intensive care unit patients, probably because of the difficulty in demonstrating clearly a beneficial effect of nutritional supplementation in highly catabolic conditions. SUMMARY: In the acute stage of critical illness, the bi-weekly measurement of transthyretin together with acute-phase response protein plasma levels seems to be a 'window' on the metabolic condition (anabolism versus catabolism). However, only in the presence of stable inflammatory parameters do transthyretin levels reflect the adequacy of nutritional coverage.

[Awareness on nutritional problems at hospitals: which solutions?]. / Prise de conscience des problèmes nutritionnels dans les hôpitaux: quelles solutions?

Malnutrition is very frequent in hospitalized patients, particularly if they are elderly and suffer of chronic diseases. Many studies show the correlation between the degree of malnutrition and the frequency of complications, the length of hospital stay and the rate of mortality. However, despite the rising interest of scientists for the role of nutrition in the pathogenesis of the diseases, little attention is devoted to the nutritional status of patients. This article reviews the recent literature regarding hospital malnutrition. At hospital admission, 30 to 40% of patients presents a certain degree of malnutrition. However, only a small percentage is recognized to be malnourished and receive an adequate treatment. The reason for this attitude of medical and paramedical teams seems to be a low priority assigned to nutrition. In addition, they seem to lack the most basic knowledge regarding the metabolic needs of their patients. Another finding, reported by several surveys, is that a large portion of hospital food is not consumed by the patients but is wasted. In fact, meals are not sufficiently-adapted to the taste and the appetite of those for whom they are prepared. This article summarizes the recommendation of the Europe Council regarding the nutritional evaluation and treatment of patients.

[Growth hormone and carcinogenesis: the point on the question]. / Hormone de croissance et carcinogenèse: le point sur la question.

Over the past 20 years, the use of recombinant growth hormone (rhGH) has become more frequent and the indications for this therapy extended to more common conditions than primary pituitary dysfunction. GH, a very strong anabolic agent, alters body growth and composition, and metabolic pathways. RhGH therapy seems to be beneficial in certain types of pathologies and surgical procedures, by preventing the deleterious effects due to catabolism and by increasing immune function, healing process and muscular strength. Several types of tumors have been studied to investigate the rhGH-related oncological risks. This article aims at reviewing the clinical studies focused on the possible association between rhGH and cancer.

[Nutrition and tumoral growth]. / Nutrition et croissance tumorale.

Some nutrients, such as glutamine, arginine, omega-3 fatty acids and nucleotides have been shown to modulate the immune and intestinal systems. They affect the synthesis of proteins and the expression of enzymes, as well as the activation and the proliferation of leukocytes and enterocytes. Since these immunonutrients modulate the response of tissues with rapid cell turnover, such as spleen, thymus, bone marrow and intestinal mucosa, they may also affect, such as suggested by some preliminary results, cancer cell proliferation and tumour growth. Therefore, further investigations are needed to understand the underlying mechanisms and to determine possible advantages and limitations of their administration to cancer patients.

Weight-losing HIV-infected patients on recombinant human growth hormone for 12 wk: a national study.

OBJECTIVE: In patients with human immunodeficiency virus, body weight (BW) loss, due mainly to loss of fat-free mass, is associated with progression of disease and mortality. Recombinant human growth hormone (rhGH) may promote BW gain by restoring FFM. METHODS: We investigated the results of adding to highly active antiretroviral therapy of routine rhGH treatment in 34 patients with human immunodeficiency virus who had lost 5% to 20% of their usual BWs. They were recruited by their physicians in Switzerland and were instructed to self-administer the drug. Patients were given 6 mg of rhGH each day for 12 wk. BW and body composition, measured by bioelectrical impedance analysis (50 kHz, tetrapolar), were recorded at baseline and at 4, 8, and 12 wk of treatment. RESULTS: At week 12, BW gain averaged 3.0 +/- 0.5 kg (P < 0.001), fat-free mass gain was 4.8 +/- 0.5 kg (P = 0.001), and body fat mass loss was 1.8 +/- 0.4 kg (P = 0.008). BW and fat-free mass increases and FM decrease were evident by week 4 and tended to plateau by week 8. Therapy was well tolerated; one patient developed carpal tunnel syndrome. Five patients abandoned the study for reasons unrelated to the rhGH treatment. CONCLUSION: Our data strongly support the use of rhGH in the treatment of unintentional BW loss associated with human immunodeficiency virus. The low rate of dropouts and the low incidence of side effects make the use of rhGH suitable for primary care management.

Assessment of nutritional status in organ transplant: is transthyretin a reliable indicator?

Transthyretin has been proposed as a nutritional index to screen for malnutrition and monitor the metabolic response to dietary intervention. In the presence of inflammation, circulating transthyretin levels drop regardless of optimal caloric intake. In this case, due to its rapid turnover, the pattern of transthyretin, monitored by means of repeated measures, could indicate the metabolic status (catabolism vs. anabolism). The aim of this review is to investigate the possible role of transthyretin as a nutritional parameter in organ transplantation. The literature on nutritional assessment in transplantation was reviewed and all the data regarding circulating transthyretin levels were analyzed. It appears that, on the one hand, the transthyretin level reflects closely dietary manipulations; on the other hand, it is affected by the inflammatory status. Consequently, interpretation could be difficult during the acute phase immediately after the transplant. Moreover, the role of transthyretin in monitoring the hepatic synthetic function in liver transplant is discussed. In conclusion, transthyretin is a reliable indicator of nutritional status in transplant candidates and potentially useful in the post-transplant phase if the inflammatory status is taken into account.