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American Journal of Clinical Nutrition, Vol. 82, No. 5, 1059-1064, November 2005
© 2005 American Society for Clinical Nutrition


ORIGINAL RESEARCH COMMUNICATION

Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1ß –511 single nucleotide polymorphism1,2,3

Roelinka Broekhuizen, Robert F Grimble, W Martin Howell, Dennis J Shale, Eva C Creutzberg, Emiel F Wouters and Annemie M Schols

1 From the Department of Respiratory Medicine, University Hospital Maastricht, Netherlands (RB, EFW, and AMS); the School of Medicine, University of Southampton, Southampton, United Kingdom (RFG and WMH); the Section of Respiratory Medicine, Cardiff University, Cardiff, United Kingdom (DJS); and the Asthma Centre Hornerheide, Horn, Netherlands (ECC)

Background: Cachexia is common in chronic obstructive pulmonary disease (COPD) and is thought to be linked to an enhanced systemic inflammatory response.

Objective: We investigated differences in the systemic inflammatory profile and polymorphisms in related inflammatory genes in COPD patients.

Design: A cross-sectional study was performed in 99 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages II–IV), who were stratified by cachexia based on fat-free mass index (FFMI; in kg/m2: <16 for men and <15 for women) and compared with healthy control subjects (HCs). Body composition was determined by bioelectrical impedance analysis. Plasma concentrations and gene polymorphisms of interleukin 1ß (IL-1ß –511), IL-6 (IL-6 –174), and the tumor necrosis factor system (TNF-{alpha} –308 and lymphotoxin-{alpha} +252) were determined. Plasma C-reactive protein, leptin, and urinary pseudouridine (as a marker of cellular protein breakdown) were measured.

Results: Fat mass, leptin, and pseudouridine were significantly different (P < 0.001) between noncachectic patients (NCPs) and cachectic patients (CPs: n = 35); the systemic inflammatory cytokine profile was not. NCPs had a body compositional shift toward a lower fat-free mass and a higher fat mass compared with HCs. CPs and NCPs had a greater systemic inflammatory response (P < 0.05) than did HCs, as reflected in C-reactive protein, soluble TNF-R75, and IL-6 concentrations. The overall distribution of the IL-1ß –511 polymorphism was significantly different between the groups (P < 0.05).

Conclusions: In COPD patients, who are characterized by an elevated systemic inflammatory response, cachexia is not discriminatory for the extent of increase in inflammatory status. This study, however, indicates a potential influence of genetic predisposition on the cachexia process.

Key Words: Chronic obstructive pulmonary disease • COPD • body composition • inflammation • polymorphism • cachexia • protein breakdown • leptin




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