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 airway 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, DL CO and arterial blood gases on room air. TNF-a serum levels were measured by immunoenzymic method (ELISA). Tissue oxygenation was assessed from oxygen delivery (D O₂), P vO₂ and oxygen extraction ratio (O₂ER) obtained after right heart catheterization with Swan Ganz catheter. PP patients demonstrated lower Dl CO and higher TLC, FRC and P aO₂ from BB. We found that oxygen delivery was better in our BB than in PP patients (Cl 2.9±0.2 vs 2.5±0.4 l/min/m²–P<0.01, D O₂ 16.1±2.1 vs 13.1±0.2 ml/min/kg−P<0.001) and the same was found for tissue oxygenation (P vO₂ 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 D O₂ had increased TNF-a levels; but the correlations between TNF-a serum levels and P vO₂ 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.