Systemic inflammation in chronic obstructive pulmonary disease: a population-based study

Abstract

Background: Elevated circulating levels of several inflammatory biomarkers have been described in selected patient populations with COPD, although less is known about their population-based distribution. The aims of this study were to compare the levels of several systemic biomarkers between stable COPD patients and healthy subjects from a population-based sample, and to assess their distribution according to clinical variables.

Methods: This is a cross-sectional study design of participants in the EPI-SCAN study (40-80 years of age). Subjects with any other condition associated with an inflammatory process were excluded. COPD was defined as a post-bronchodilator FEV1/FVC < 0.70. The reference group was made of non-COPD subjects without respiratory symptoms, associated diseases or prescription of medication. Subjects were evaluated with quality-of-life questionnaires, spirometry and 6-minute walk tests. Serum C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, interleukins (IL-6 and IL-8), alpha1-antitrypsin, fibrinogen, albumin and nitrites/nitrates (NOx) were measured.

Results: We compared 324 COPD patients and 110 reference subjects. After adjusting for gender, age, BMI and tobacco consumption, COPD patients showed higher levels of CRP (0.477 +/- 0.023 vs. 0.376 +/- 0.041 log mg/L, p = 0.049), TNF-alpha (13.12 +/- 0.59 vs. 10.47 +/- 1.06 pg/mL, p = 0.033), IL-8 (7.56 +/- 0.63 vs. 3.57 +/- 1.13 pg/ml; p = 0.033) and NOx (1.42 +/- 0.01 vs. 1.36 +/- 0.02 log nmol/l; p = 0.048) than controls. In COPD patients, serum concentrations of some biomarkers were related to severity and their exercise tolerance was related to serum concentrations of CRP, IL-6, IL-8, fibrinogen and albumin.

Conclusions: Our results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects.

Figure 1

Flow-chart for the constitution of study groups.

Figure 2

Box-and-whisker plots of the systemic biomarker crude distribution in COPD and reference groups. The top of the box represents the 75 th percentile, the bottom of the box represents the 25 th percentile, and the line in the middle represents the 50 th percentile. The whiskers represent the highest and lowest values that are not outliers or extreme values. Outliers (values that are between 1.5 and 3 times the interquartile range) and extreme values (values that are more than 3 times the interquartile range) are represented by circles and asterisks beyond the whiskers. Abbreviations: TNF = tumor necrosis factor; IL = interleukin. Comparisons between groups by U-Mann-Whitney test or t-Student test depending on the distribution.

Figure 3

Serum concentrations of systemic biomarkers in COPD patients and control subjects. Data are presented as mean adjusted for age, sex, pack-years of smoking and body-mass index (standard error of the mean). A logarithmic transformation was used for CRP and NO_x. Abbreviations: CRP = C-reactive protein; TNF = tumor necrosis factor; IL = interleukin; A1AT = alpha-1 antitrypsin; NO_x = nitrites/nitrates.

Figure 4

Relationship between serum concentrations of biomarkers and distance walked in 6-minutes in COPD patients. Abbreviations: CRP = C-reactive protein; IL = interleukin; r = Pearson's linear bivariate correlation coefficient.