Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease.

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Abstract
An increase in resting energy expenditure (REE) commonly occurs in patients with chronic obstructive pulmonary disease (COPD), the cause of which is as yet unknown. The objective of this study was to assess the relationship between REE, acute phase proteins, and inflammatory mediators in patients with COPD. Thirty patients were studied and 26 healthy age-matched subjects served as controls. REE was measured by indirect calorimetry and adjusted for fat-free mass (FFM) by bioelectrical impedance analysis. Tumour necrosis factor alpha (TNF-alpha), soluble tumour necrosis receptor (sTNF-R)55 and sTNF-R75, interleukin (IL)-6, IL-8, and lipopolysaccharide binding protein (LBP) were measured by ELISA. Fourteen patients had a normal REE and in 16 it was raised. The mean body mass index and fat mass were significantly lower in the latter but pulmonary function data were similar in the two groups. In the 30 patients with COPD the mean (SD) sTNF-R75 was 1.7 (1.0) ng/ml compared with 1.1 (0.4) ng/ml in the controls; C-reactive protein (CRP) was detectable (> 5 micrograms/ml) in eight patients compared with none of the control subjects, and LBP was 13.2 (7.7) micrograms/ml compared with 8.6 (3.1) micrograms/ml in the controls. The patients with a raised REE had increased mean levels of CRP compared with the patients with a normal REE (median 5.5 micrograms/ml (range 5-193) and < 5 micrograms/ml, respectively); the same was true for LBP (median 12.4 micrograms/ml (range 8.1-39.1) and 9.5 micrograms/ml (range 5.0-16.6), respectively), but sTNF-R55 and R75 and IL-8 were similar in the two groups. Of the 16 patients with a raised REE, the CRP level was increased in eight and normal in eight. In those with an increased level of CRP the FFM was decreased and LBP, IL-8, and sTNF-R55 and R75 were increased compared with those with normal CRP levels. A subset of patients with COPD with an increased REE and decreased FFM have increased levels of acute phase reactant proteins and inflammatory cytokines in their serum; these phenomena may be causally related.