Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum.

Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Vernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF. Nutrition and Toxicology Research Institute Maastricht, Department of Pulmonology, Maastricht University, The Netherlands. [email protected] Chronic obstructive pulmonary disease (COPD) is characterized by significant chronic inflammation in the pulmonary compartment as well as in the circulation. This study aimed to elucidate the relationship between local and systemic inflammation in smoking-induced COPD by assessing levels of soluble (s) tumor necrosis factor (TNF) receptors, TNF-alpha, and interleukin-8 (IL-8) in induced sputum and in plasma. Sputum induction was performed in 18 subjects with COPD (FEV(1) 56% predicted) and 17 healthy smokers (FEV(1) 99% predicted). Patients with COPD showed significantly higher percentages of neutrophils and levels of sTNF-R55 and IL-8 in sputum as compared with control subjects, whereas sputum sTNF-R75 levels tended to be higher in COPD. Sputum TNF-alpha levels were similar in both groups. When comparing sTNF receptors in sputum and plasma, no direct correlations were found despite elevation of circulating sTNF-R75 levels in patients with COPD. In addition, sputum sTNF receptors were inversely related to the FEV(1) in patients with COPD, whereas circulating sTNF receptors were not, suggesting different regulation of inflammation in the pulmonary and systemic compartment. When subjects were divided according to their current smoking status, levels of sTNF-R55, sTNF-R75, and IL-8 in sputum were significantly elevated in ex-smoking versus currently smoking patients with COPD, suggesting ongoing inflammation in airways and circulation of patients with COPD after smoking cessatio

Chronic obstructive pulmonary disease is associated with the -1055 IL-13 promoter polymorphism

Chronic obstructive pulmonary disease is associated with the -1055 IL-13 promoter polymorphism. Van Der Pouw Kraan TC, Kucukaycan M, Bakker AM, Baggen JM, Van Der Zee JS, Dentener MA, Wouters EF, Verweij CL. Department of Molecular Cell Biology, Free University, Amsterdam, The Netherlands. IL-13 is strongly implicated in the development of asthma and chronic obstructive polymonary disease (COPD). We previously identified an IL-13 promoter polymorphism (-1055 C to T) that is associated with allergic asthma. We now report an increased frequency of the -1055 T allele in COPD patients compared to healthy controls (P=0.002) and compared to a second control group consisting of smoking individuals with normal lung function (P=0.01). A closely linked IL-13 exon polymorphism is present at normal allelic frequencies (P=0.3 and 0.4, respectively). In addition, we observed a normal distribution of two IL-4 polymorphisms at positions -590 and +33 (P=0.2 and 0.9, respectively). These results could implicate a functional role for the IL-13 promoter polymorphism in the enhanced risk to develop COPD. doi: 10.1038/sj.gene.636389