Background

The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair.

Methods

We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot].

Results

Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05).

Conclusions

In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.

Rationale

Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).

Hypothesis

There are differences in serum biomarker levels between women and men with COPD.

Objective

Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.

Methods

We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD.

Results

The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes.

Conclusions

In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings.

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.