Profiling serum biomarkers in patients with COPD: associations with clinical parameters

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with significant systemic consequences. Recognition of the systemic manifestations has stimulated interest in identifying circulating biomarkers in these patients. A systematic analysis was undertaken of multiple protein analytes in the serum of well characterised patients with COPD and matched controls using novel protein microarray platform (PMP) technology. Methods: Forty-eight patients (65% men) with COPD (forced expiratory volume in 1 s ,55%) and 48 matched controls were studied. Anthropometric parameters, pulmonary function tests, 6-minute walk distance, the BODE index and the number of exacerbations were measured and the association of these outcomes with the baseline levels of 143 serum biomarkers measured by PMP was explored. Results: Thirty biomarker clusters were identified and ranked by computing the predictive value of each cluster for COPD (partial least squares discriminant analysis). From the 19 best predictive clusters, 2-3 biomarkers were selected based on their pathophysiological profile (chemoattractants, inflammation, tissue destruction and repair) and the statistical significance of their relationship with clinically important end points was tested. The selected panel of 24 biomarkers correlated (p,0.01) with forced expiratory volume in 1 s, carbon monoxide transfer factor, 6-minute walk distance, BODE index and exacerbation frequency. Conclusion: PMP technology can be useful in identifying potential biomarkers in patients with COPD. Panels of selected serum markers are associated with important clinical predictors of outcome in these patients.

The Expanding Role of Biomarkers in the Assessment of Smoking-Related Parenchymal Lung Diseases

“…[5][6][7][8] Finally, peripheral blood biomarkers have been shown to correlate with mortality and other important clinical outcome measures ( Table 2 ). [9][10][11] Of note, although there is emerging research exploring other innovative peripheral blood-based biomarkers, such as changes in cell populations (fi brocytes, 12 T-cell subtypes, 13 monocytes), transcriptional changes (genes, microRNAs, noncoding RNA), autoantibodies, mark ers of oxidative stress, proteomics, and metabolomics, these areas are beyond the scope of this review. Throughout the rest of this perspective, we use the term "biomarker" to refer exclusively to a peripheral blood protein biomarker.…”

“…It is important to note that because of the cross-sectional nature of this study, the proteomic profi le was not shown to be related to mortality. 11 We also showed in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study that a combination of candidate biomarkers can improve the accuracy of predicting the risk of death in patients with COPD when added to clinical variables, such as age, FEV 1 , BODE index, and hospitalizations, known to predict mortality in COPD. 10 The addition of fi brinogen, CCL-18, SP-D, CRP, Clara cell protein-16, IL-6, IL-8, and TNF-a to clinical variables significantly improved the predictive model for mortality, with IL-6 having the greatest impact.…”

“…10,11,38 CCL-18 is also associated with clinical outcomes, including cardiovascular morbidity, overall mortality and response to treatment. 38,39 However, it is unclear what role this chemokine may play in disease pathogenesis.…”

“…Assessment of COPD exacerbations relies mostly on clinical 43,44,[58][59][60] ; MMP 5 matrix metalloproteinase 11,40,[49][50][51]53 ; MPIF-1 5 myeloid progenitor inhibitory factor-1 61 ; S100A12 53 ; SP 5 surfactant protein 10,[34][35][36][37]46,48,62,[58][59][60] ; TNF-a 5 tumor necrosis factor-a 10,26 ; TNFRSF1A 5 tumor necrosis factor receptor superfam ily, member 1A 51 ; VCAM-1 5 vascular cell adhesion moledule-1 53 ; YKL-40. 56 to identify clinical phenotypes such as rapid decliners and frequent exacerbators.…”

Blood Specimen Biomarkers of Inflammation, Matrix Degradation, Angiogenesis, and Cardiac Involvement: a Future Useful Tool in Assessing Clinical Outcomes of COPD Patients in Clinical Practice?

“…In a small study of patients with mild to moderate COPD, serum pulmonary and activation-regulated chemokine/CC-chemokine ligand-18 (PARC/CCL-18) was significantly associated with reduced FEV1, increased risk of exacerbations, and an increased BODE index (Pinto-Plata et al 2007). There is also recent evidence that elevated levels of PARC/CCL-18 are associated with increased risk of cardiovascular hospitalizations or mortality in the lung health study (LHS) cohort and with total mortality in the ECLIPSE cohort (Sin et al 2011).…”