Identification of patients with chronic obstructive pulmonary disease (COPD) by measurement of plasma biomarkers.

INTRODUCTION: Inflammation is an important constituent of the pathology of chronic obstructive pulmonary disease (COPD), leading to alveolar destruction and airway remodelling. OBJECTIVE: The aim of this study was to assess the difference in plasma biomarkers of inflammation between asymptomatic smokers and patients with COPD. METHODS: We used commercially available enzyme-linked immunosorbent assay kits to measure the plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), monocyte chemotactic protein-1 (MCP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) on two occasions with a 2-week interval in patients with COPD (n = 20), asymptomatic smokers (n = 10) and healthy lifelong non-smokers (n = 10). The participants were characterised clinically, physiologically and by quantitative computed tomography by measuring the relative area of emphysema below -910 Hounsfield units (RA-910). RESULTS: The results of the biomarker measurements on the two occasions were highly reproducible. Patients with COPD had significantly higher plasma levels of IL-8 (P = 0.004) and significantly lower levels of TIMP-1 (P = 0.02) than smokers and non-smokers. There was no statistically significant difference between the three groups in the level of TNF-alpha, MMP-9, MCP-1 and TIMP-2. The IL-8/TIMP-1 ratio correlated significantly with the degree of airway obstruction measured as forced expiratory volume in 1 second (FEV(1)) % predicted (r = -0.47, P < 0.01); with the diffusion capacity (r = -0.41, P < 0.01); and with the grade of emphysema measured as RA-910 (r = 0.39, P = 0.01). CONCLUSION: These findings suggest that the measurement of plasma biomarkers, such as IL-8/TIMP-1, may aid to discriminate patients with COPD from smokers at lower risk of developing COPD.

alphaEbeta7 expression on CD8+ T-cells in COPD BAL fluid and on TGF-beta stimulated T-cells in vitro.

The airway inflammation in patients with COPD shows increased numbers of CD8+ T-cells. Until now few studies have shown any functional data indicating a role for these cells in the pathogenesis of COPD. This paper focuses on a subset of CD8+ T-cells present in human lung, the intra-epithelial lymphocytes expressing the integrin alphaEbeta7, and their presence in bronchoalveolar lavage fluid from COPD patients. In this study we demonstrate that 64-89% of the CD8+ T-cells in bronchoalveolar lavage fluid from COPD patients are positive for CD103, the alpha subunit of alphaEbeta7. We also present an in vitro system in which it is possible to differentiate peripheral T-cells into a phenotype resembling the one found in bronchoalveolar lavage fluid, i.e., CD8+ CD103+. In this in vitro system we demonstrate that, in addition to TGF-beta1, cell-to-cell interaction between the T-cell and an antigen-presenting cell represented here by the monocyte, is crucial for a rapid, high and sustained expression of CD103. The signal provided by the monocytes is shown to be mediated through LFA-1 on the T-cell. Furthermore, differentiation of CD8+ T-cells by TGF-beta1 and monocytes results in down regulation of INF-gamma, TNF-alpha and GM-CSF production. IL-8 production is, however, retained in the alphaEbeta7 expressing cells. We see this work as an initiation on the quest for a functional characterization of one of the different types of CD8+ T cells present in COPD. In the longer perspective we hope this can lead to an increased understanding of how these cells can contribute to the disease pathology.