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The interdependency between nutrition and immune function was recognised formally in the 1970s when immunological measures were introduced as part of the assessment of nutritional status [ 1 ]. Both the nutritional status and specific nutrients may affect the immune system directly (e.g., by triggering immune cell activation or altering immune cell interactions) or indirectly (e.g., by changing substrates for DNA synthesis, altering energy metabolism, changing the physiological integrity of cells, or altering signals or hormones) [ 2 ]. Protein-energy malnutrition is accepted as a major cause of immune deficiency worldwide, and the immune response is considered integral to the pathophysiology of many chronic diseases [ 3 ]. Protein-energy malnutrition is associated with a significant impairment of cellmediated immunity, phagocyte function, complement system, secretory immunoglobulin A antibody concentrations and cytokine production.

Functional assessment is at the heart of understanding how a chronic disease and its therapy impact on patients. It puts into tangible terms what the patient is capable of and brings an understandable ‘human context’ to the patient burden. Functional status can be a prognostic indicator. It may also have a role in treatment selection for individual patients and be used to enter and stratify patients in clinical trials. It remains to be seen whether it will be possible and practical to use end-points such as function (and other related end-points such as ‘quality of life’) to direct individual patient management. Using cancer cachexia as a paradigm, this chapter sets out to discuss some of the broader issues in functional patient assessment. New approaches to assessing function and preliminary experience with an emerging technology are also presented.

In medicine, specific combinations of symptoms and signs contribute to establishing a diagnosis. However, symptoms or constellations of symptoms (i.e., syndromes) per se may not be specific for a single disease; rather, they are observed during the clinical course of a number of acute and chronic diseases. Among them, anorexia is a highly prevalent syndrome that heavily impacts on the prognosis of patients suffering from acute (i.e. sepsis) and chronic (i.e. cancer, liver cirrhosis, chronic renal failure, chronic obstructive pulmonary [COPD]) diseases.

Under physiological conditions, body weight remains remarkably stable because of the importance of maintaining energy stores. A complex network of neural and hormonal factors regulates appetite and metabolism. A fundamental role is played by hypothalamic centres of feeding and satiety. Neuropeptides induce anorexia by acting on the satiety centre; gastrointestinal peptides, such as glucagon, somatostatin, and cholecystokinin, induce anorexia by vagal signalling; hypoglycaemia inhibits satiety centre. Leptin, produced by adipose tissue, acts on the hypothalamus to decrease food intake and increase energy expenditure, thus achieving long-term weight homoeostasis [ 1 ].

Despite the long and widespread interest in this topic, there is not an univocal definition for cachexia [ 1 ]. The term derives from the Greek kakòs , which means ‘bad,’ and from hexis , meaning ‘condition.’ The clinical syndrome of cachexia is characterised by anorexia, tissue wasting, loss of body weight accompanied by a decrease in muscle mass and adipose tissue, and poor performance status that often precedes death [ 2 ] [ 5 ]. Cachexia can occur as part of many chronic or end-stage diseases, such as infections, cancer, AIDS, congestive heart failure, rheumatoid arthritis, tuberculosis, chronic obstructive pulmonary disease, cystic fibrosis, and Crohn’s disease. It may develop also in a proportion of elderly persons without obvious diseases. A literature search using the term ‘cachexia’ yielded more than 1000 articles published over the past 5 years [ 1 ].

Lipodystrophies (LDs) are clinically heterogeneous acquired or inherited disorders characterised by a generalised or regional loss of adipose tissue. Generalised LDs, both inherited and acquired, are associated with peripheral insulin resistance, glucose intolerance or overt diabetes, acanthosis nigricans, dyslipidaemia. Bone demineralisation and polycystic ovary syndrome are also part of these diseases. LDs can be classified as acquired or congenital, and generalised or partial (Table 1).

Estimating body compartments is fundamental in performing nutritional assessments. In recent years, highly reliable and minimally invasive methods have become available for quantifying body fluids, fat-free mass and fat mass. These measurements integrate the clinical evaluation, overcoming the drawbacks of anthropometric measurements used as indirect parameters of nutritional status and body composition.

Cachexia is characterised by a specific loss of skeletal muscle, while the non-muscle protein compartment is relatively preserved [ 1 ]. This loss can be very large. Thus in lung cancer patients who had lost 30% of their pre-illness stable weight there was a 75% fall in skeletal muscle protein mass. This leads to a general muscle weakness (asthenia) and death from immobility and hypostatic pneumonia [ 1 ]. For a 70-kg adult, the lean body mass is about 5.8 kg, of which the majority (4.2 kg) is found in muscle and the remainder in cells of the splancnic organs and gut. During total starvation protein is initially broken down at a rate of about 75 g per day, falling to about 20 g per day after 5–6 weeks, which is related to a reduction in the requirement for glucose by the brain. During cachexia of cancer, injury or sepsis there is interference with the normal process of starvation adaption and the rate of protein degradation continues at the high rate.

In this chapter we will review the alterations of lipoprotein metabolism observed in cachexia. Other aspects of lipid metabolism in cachexia, in particular those regarding adipose tissue, are covered in other chapters. Lipoproteins are macromolecules circulating in blood and they are quite easily measured in the clinical chemistry laboratory. For this reason lipoproteins can be used to monitor the alterations of lipid metabolism in several clinical conditions, including cachexia.

In 1919, glucose intolerance became the earliest recognised metabolic abnormality in cancer patients. Prior to the development of severe malnutrition, patients with colon, gastric, sarcoma, endometrial, prostate, localised head, neck and lung cancer had many of the metabolic abnormalities of type II (non-insulin-dependent) diabetes mellitus. These metabolic abnormalities included glucose intolerance, an increase in both hepatic glucose production (HGP) and glucose recycling, and insulin resistance. In a study of over 600 cancer patients, a diabetic pattern of glucose tolerance test was noted in over one-third of the patients [ 1 ].