Serum biomarkers and outcomes in patients with moderate COPD: a substudy of the randomised SUMMIT trial

Abstract

RationaleSystemic levels of C reactive protein (CRP), surfactant protein D (SPD), fibrinogen, soluble receptor of activated glycogen end-product (sRAGE) and club cell protein 16 (CC-16) have been associated with chronic obstructive pulmonary disease (COPD) outcomes. However, they require validation in different cohorts.ObjectivesRelate systemic levels of those proteins to forced expiratory volume in 1 s (FEV1) decline, exacerbations, hospitalisations and mortality in COPD patients (FEV1 of ≥50 and ≤70% predicted) and heightened cardiovascular risk in a substudy of the Study to Understand Mortality and MorbidITy trial.MethodsParticipants were randomised to daily inhalations of placebo, vilanterol 25 µg (VI), fluticasone furoate 100 µg (FF) or their combination (VI 25/FF 100) and followed quarterly until 1000 deaths in the overall 16 485 participants occurred. Biomarker blood samples were available from 1673 patients. The FEV1 decline (mL/year), COPD exacerbations, hospitalisations and death were determined. Associations between biomarker levels and outcomes were adjusted by age and gender.ResultsSystemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen did not relate to baseline FEV1, FEV1 decline, exacerbations or hospitalisations. Fibrinogen and CRP were related to mortality over a median follow-up of 2.3 years. Only the CC-16 changed with study therapy (VI, FF and FF/VI, p<0.01) at 3 months.ConclusionsIn COPD, systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen were not associated with FEV1 decline, exacerbations or hospitalisations. These results cast doubts about the clinical usefulness of the systemic levels of these proteins as surrogate markers of these COPD outcomes. The study confirms that CRP and fibrinogen are associated with increased risk of death in patients with COPD.Trial registration numberNCT01313676.

<p>FEV₁ is a stronger mortality predictor than FVC in patients with moderate COPD and with an increased risk for cardiovascular disease</p>

“…28 However, analyzing the SUMMIT data, the levels of systemic inflammatory biomarkers did not relate to the frequency of flare-ups. 29 Interestingly we found that the highest FVC quintile was associated with an increased exacerbation risk. This, together with the gradually increased risk for exacerbation with FEV 1 decline suggest that more severe emphysema may be related to higher number of exacerbations.…”

<p>Systemic Cytokine Profiles of CD4+ T Lymphocytes Correlate with Clinical Features and Functional Status in Stable COPD</p>

“…15,16 However, the findings on systemic inflammation biomarkers and clinical characteristics of COPD are contradictory. [15][16][17][18][19][20][21] In this way, it is essential to investigate the cell line responsible for synthesizing cytokines that orchestrate inflammation in stable COPD. 22 In addition, exploring correlations not previously investigated between the intracellular inflammatory profile and clinical characteristics and functional status, may contribute to the management of this heterogeneous group of patients, with more promising results and better outcomes.…”

COPD 2020 Guideliness—What Is New and Why?

“…However, the observed sputum color remains highly sensitive and specific for a high bacterial load during such episodes. The SUMMIT trial failed to show the benefit of using CRP, SPD, s RAGE, CC-16, and fibrinogen to predict forced expiratory volume in 1 st second (FEV 1 ) decline, hospitalization, or exacerbation [4]. Continued cautious and realistic interpretation of the role of biomarkers in the management of identified clinical traits is needed.…”