Comasia A. Raguso

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

Purpose of reviewLoss 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 findingsHypoxia 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. SummaryMalnutrition 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.

Management of catabolism in metabolically stressed patients: a literature survey about growth hormone application.

In the effort to improve the long-term outcome in critically ill patients, the utilization of anabolic agents, such as human recombinant growth hormone, has been proposed in order to reduce catabolism and improve nutritional status. A recent multicentre study regarding the use of human recombinant growth hormone in intensive care unit patients showed an unexpected increase in the mortality rate in human recombinant growth hormone-treated patients. This finding is in contrast with previous literature data reporting either no differences or an even lower mortality rate with the administration of human recombinant growth hormone. This review evaluates the possible reasons for this dramatic difference in outcomes between the multicentre study and the existing literature. Articles dealing with human recombinant growth hormone administration either in intensive care unit patients (n = 26) or in postoperative patients (n = 16) have been reviewed. Our analysis suggests that the low caloric intake given to patients enrolled in the multicentre study might have been inadequate to compensate for the hypermetabolism of these patients, and could not support the prolonged and delayed administration of high doses of human recombinant growth hormone. Whether the beneficial metabolic effects of human recombinant growth hormone translate into better clinical outcomes deserves further investigation. In addition, the careful selection of patients to be treated, and close monitoring of both the adequacy of caloric support and modality of human recombinant growth hormone administration would favour the safety of human recombinant growth hormone utilization in critical care settings.

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.

Prevalence of low fat-free mass index and high and very high body fat mass index following lung transplantation.

Abstract.The aim of this study was to determine the prevalence of low fat-free mass index (FFMI) and high and very high body fat mass index (BFMI) after lung transplantation (LTR). A total of 37 LTR patients were assessed prior to and at 1 month, 1 year and 2 years for FFM and compared to 37 matched volunteers (VOL). FFM was calculated by the Geneva equation and normalized for height (kg/m2). Subjects were classified as FFMI “low”, ≤17.4 in men and ≤15.0 in women; BFMI ”high”, 5.2–8.1 in men and 8.3–11.7 in women; or “very high” >8.2 kg/m2 in men and >11.8 kg/m2 in women. In 23 M/14 F, body mass index (BMI) was 22.3±4.4 and 20.1±4.9 kg/m2, respectively. The prevalence of low FFMI was 80% at 1 month and 33% at 2 years after LTR. Prevalence of very high BFMI increased and was higher in patients than VOL after LTR. The prevalence of low FFMI was high prior to and remained important 2 years after LTR, whereas BFMI was lower prior to and higher 2 years after LTR.

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

Abstract 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.

Fat-free mass change to weight change ratio during refeeding following lung transplantation.

Abstract.Malnutrition occurs frequently prior to lung transplantation (LTR), but patients gain weight after LTR. The study aimed to determine the ratio changes of fat-free mass (ΔFFM): changes of body weight (ΔBW) during refeeding. A total of 37 LTR patients were measured for weight and FFM and body fat by bioimpedance analysis at 1 month post-LTR, then annually for 3 years. Linear regressions determined the ratio ΔFFM:ΔBW during refeeding. ΔFFM was: year- 1=1.822+0.389* ΔBW, r2=0.397; yr-2=0.611+0.246* ΔBW, r2=0.441; yr-3=-0.17+0.208 * ΔBW, r2=0.319. Refeeding during year-1 in thin subjects resulted in a ratio ΔFFM:ΔBW of 0.389, whereas the change in ratio ΔFFM:ΔBW during year- 2 and 3 was 0.246 and 0.208, respectively. Refeeding resulted in a larger ratio ΔFFM:ΔBW in thin subjects versus normal and overweight subjects. Thus, refeeding in underweight LTR patients is geared to normalizing depleted FFM, whereas later FFM gains were similar to FFM gains in normal and overweight subjects.