Chest
Volume 133, Issue 2, February 2008, Pages 350-357
Journal home page for Chest

Original Research
COPD
Increased Systemic Inflammation Is a Risk Factor for COPD Exacerbations

https://doi.org/10.1378/chest.07-1342Get rights and content

Background

COPD is characterized by episodic increases in respiratory symptoms, so-called exacerbations. COPD exacerbations are associated with an increase in local and systemic inflammation. Data of a previously published study in a well-characterized COPD cohort were analyzed to define predictive factors of acute exacerbations, particularly focusing on systemic inflammation.

Objective

To determine if an elevated systemic inflammatory status measured at baseline is related to the occurrence of acute exacerbations in patients with COPD.

Methods

The occurrence of moderate (requiring oral prednisolone) and severe exacerbations (requiring hospitalization) was prospectively recorded over 1 year. At the beginning of the study, lung function values (FEV1, FVC, functional residual capacity, and diffusion capacity of the lung for carbon monoxide [Dlco]) and serum levels of C-reactive protein, fibrinogen, lipopolysaccharide binding protein, tumor necrosis factor (TNF)-α, and its soluble receptors (soluble TNF receptors 55 and 75) as markers of systemic inflammation were determined.

Results

Two hundred seventy-seven person-years of follow-up were analyzed in the total group of 314 patients: 186 patients were responsible for 411 exacerbations (374 moderate and 37 severe). Multivariate analyses showed that a higher initial fibrinogen level and a lower FEV1 predicted a higher rate of both moderate and severe exacerbations. Additional independent predictors of a severe exacerbation were a higher number of prestudy severe exacerbations and lower Dlco. A higher number of prestudy moderate exacerbations was the only additional independent risk factor for the rate of moderate exacerbations.

Conclusion

This study demonstrates that besides lung function impairment systemic inflammation manifested by elevated fibrinogen levels is an independent risk factor for exacerbations of COPD. Attenuation of systemic inflammation may offer new perspectives in the management of COPD patients to reduce the burden of exacerbations.

Section snippets

Study Design

This study is a secondary study of the COSMIC study (COPD and Seretide: a Multi-Center Intervention and Characterization), a multicenter trial to investigate the effects of steroid withdrawal in comparison with combination therapy (long-acting β2-agonist salmeterol and inhaled steroid fluticasone) during a 1-year follow-up period.18 The COSMIC study had a multicenter, randomized, double-blind, parallel-group design. All patients received combined salmeterol (50 μg) and fluticasone (500 μg) bid

Results

Patient demographic data and baseline characteristics are summarized in Table 1 . During the 1-year follow-up period, 69 patients withdrew. This occurred after a mean follow-up of 23 weeks. Of the total group of 314 patients, a total of 277 person-years was analyzed (mean follow-up, 0.88 years per patient). Of these 314 patients, 128 patients had neither a moderate nor a severe exacerbation during follow-up; 31 patients had a total of 37 severe exacerbations, with the number per patient ranging

Discussion

We investigated which factors predict acute COPD exacerbations and in particular the role of systemic inflammation in the occurrence of these acute events. We found that higher fibrinogen levels are significantly predictive for the occurrence of severe as well as moderate exacerbations. Further independent predictors for severe acute exacerbations were FEV1, Dlco, and the number of prestudy severe exacerbations, whereas FEV1 and the number of prestudy moderate exacerbations were independent

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    Glaxo-Smith-Kline provided funding for this study.

    Dr. Groenewegen has no conflict of interest to declare. Dr. Postma has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Hop is a regular biostatistical consultant to GSK. Dr. Wielders' research institute has received grants for research purposes from AstraZeneca and GSK. Dr. Schloesser has no conflict of interest to declare. Dr. Wouters has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline.

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