Tumor necrosis factor—alpha serum levels, weight loss and tissue oxygenation in chronic obstructive pulmonary disease

Abstract

Weight loss has been recognized as a feature of advanced emphysema and a factor of poor prognosis, but its mechanisms remain obscure. Studies have demonstrated high serum concentrations of TNF-a (cachexin) in chronic obstructive pulmonary disease (COPD) patients with emphysema. Pink puffers (PP) COPD patients have worse tissue oxygenation when compared with blue bloaters (BB) COPD patients. Consequently, PP patients would become cachectic, whereas BB patients with better tissue oxygenation would not. The aim of this study is to test the hypothesis that malnutrition in emphysema is a cytokine-mediated marker of chronic progressive tissue hypoxia. Thirty male COPD patients, without clinical or laboratory evidence of infection and severe air way obstruction (FEV1 < 1.5 l) were allocated: 16 as pink puffers (PP) and 14 as blue bloaters (BB). Lung function measurements included FEV1, FVC, RV, TLC, DLCO and arterial blood gases on room air. TNF-a serum levels were measured by immunoenzymic method (ELISA). Tissue oxygenation was assessed from oxygen delivery (DO2), PvO2 and oxygen extraction ratio (O2ER) obtained after right heart catheterization with Swan Ganz catheter. PP patients demonstrated lower DLCO and higher TLC, FRC and PaO2 from BB. We found that oxygen delivery was better in our BB than in PP patients (CI 2.9 +/- 0.2 vs 2.5 +/- 0.4 l/min/m2--P < 0.01, DO2 16.1 +/- 2.1 vs 13.1 +/- 0.2 ml/min/kg--P < 0.001) and the same was found for tissue oxygenation (PvO2 34.6 +/- 2.9 vs 31.2 +/- 3.8 mmHg--P < 0.01, O2ER 0.27 +/- 0.02 vs 0.34 +/- 0.06%--P < 0.001). The TNF-a values were higher in PP (31.3 +/- 26 pg/ml vs 15.2 +/- 9.9 pg/ml--P < 0.05) and their percent fat-free mass (%FFM) was 49.6 +/- 11.5 vs 42 +/- 8%--P < 0.001. We found that COPD patients with lower DO2 had increased TNF-a levels; but the correlations between TNF-a serum levels and PvO2 or O2ER were not statistically significant. TNF-a levels were elevated in PP patients with tissue hypoxia and may be a factor contributing to the weight loss of these patients.

Body composition and energy expenditure in patients with chronic obstructive pulmonary disease

“…Eight hyper metabolic patients had elevated CRP, and these patients also had increased levels of soluble TNF receptors 55 and 75 and interleukin-8 (IL-8). These findings have later been confirmed by others (34, 88,99). The role of cytokines in COPD is probably more complex than the possible effects on BMR and we are probably only in the start pit of understanding the relation between inflammation and malnutrition.…”

Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation

“…Since low oxygen tensions stimulate the production of tumour necrosis factor [28,29] which affects (such as reduces) albumin synthesis, an improved oxygen tension can likely contribute to increase body weight/composition and albumin, even though data of the present study does not provide any definitive explanation of the improved saturation of oxygen. It is also presumable that an ameliorated cardiac performance associated with EAAs supplementation [30] could improve the blood distribution throughout the different pulmonary regions.The mechanisms by which EAAs stimulate the FFM growth are both direct and indirect.…”

“…The significant reduction in basal hyperlactatemia after EAAs treatment [28,29,[39][40][41][42] is another important factor further contributing to a better exercise tolerance for at least three reasons. First, the diminution of blood hydrogenions reduces the excess of ventilation particularly during the physical effort.…”

Soluble TNF Receptors and Kidney Dysfunction in the Elderly

“…15 Inflammation identified by sTNFRs may also trigger and promote loss of kidney function due to TNFR-driven development of atherosclerosis 16 and malnutrition. 17 Hyperglycemia has been suggested to affect the levels of oxidative stress and provides one of the main factors explaining the rapid decline in GFR seen in diabetic nephropathy. 18,19 Oxidative stress also increases TNF-a activity, 18 specifically that of TNFR2.…”