Original articleHemoglobin, erythropoietin and systemic inflammation in exacerbations of chronic obstructive pulmonary disease☆
Introduction
Anemia of chronic disease (ACD) is immune driven and mainly inflammatory in nature. Three possible mechanisms are thought to lead to ACD: shortened RBC survival, iron homeostasis dysregulation, and impaired bone marrow erythropoietic response [1]. Several cytokines and chemokines are involved in the aforementioned mechanisms and interfere in haematopoiesis, having a key role in ACD. The physiologic regulator of red cell production, erythropoietin (EPO), is produced and released by peritubular capillary lining kidney cells [1]. EPO governs day-to-day production of red cells and ambient levels of hormone are measurable in plasma.
Chronic obstructive pulmonary disease (COPD) profoundly affects mortality and morbidity worldwide [2]. Exacerbations of COPD (ECOPD) are associated with worsening of lung function, decreased quality of life, increased systemic inflammation and have a significant impact on survival [3]. During ECOPD there is an up-regulation of airway and systemic inflammation [4], associated with an increase of various biomarkers compared to stable disease [5]. However, several aspects related to the mechanisms of increased systemic inflammation and its consequences during ECOPD remain speculative.
Polycythemia is present in a fraction of untreated hypoxemic COPD patients, while anemia represents a more common problem and is related to poorer prognosis [6]. Moreover, systemic inflammation may represent a possible cause of anemia [7]. Previous data support that anemic patients with COPD present high EPO levels, suggestive of EPO resistance, possibly mediated through inflammatory mechanisms [8].
The aim of the present study was to evaluate the levels of hemoglobin, EPO and biomarkers of systemic inflammation in patients hospitalized for ECOPD, during the acute phase, on resolution and on stable condition. We hypothesized that the increased inflammatory burden during the acute phase of ECOPD would be associated with a decrease in hemoglobin levels, despite the presence of high EPO levels. Possible associations between hemoglobin, EPO and systemic inflammation in the acute and recovery phases of ECOPD were further evaluated.
Section snippets
Study subjects
COPD patients admitted to two university hospitals for ECOPD were evaluated. All patients were diagnosed for COPD according to the Global initiative for Obstructive Lung Diseases (GOLD) guidelines [2], and ECOPD was graded as levels II to III according to the ERS/ATS consensus criteria [9]. Only patients fulfilling the Anthonisen's criteria for type 1 ECOPD were selected [10]. All patients were managed according to the ERS/ATS guidelines, with bronchodilators, systemic corticosteroids (30–40 mg
Results
Fig. 1 presents the flow chart of patients included in the study. Demographic characteristics of the 93 patients included in the final analysis are presented in Table 1. All patients had normal values of reticulocytes in all study phases.
Discussion
In this observational study we have shown a statistically significant negative association between Hb and EPO on admission for an ECOPD. This negative association was subsequently reversed to a positive one during resolution and on the stable phase. The initial negative association is mainly related to the increased IL-6 levels, indicating a possible EPO resistance through mechanisms related to the increased systemic inflammatory response, which is usually up-regulated during the acute phase of
Learning points
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Polycythemia is present in a fraction of untreated hypoxemic COPD patients, while anemia represents a more common problem and is related to poorer prognosis.
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In the present observational study we have shown a statistically significant negative association between Hb and erythropoietin on admission for a COPD exacerbation. This negative association was subsequently reversed to a positive one during resolution and on the stable phase. The initial negative association is mainly related to the
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The study was supported by research grants from the Greek Thorax Foundation and National Kapodistrian Research Program from Athens University.