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Impaired Hemorheology in Exacerbations of COPD

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Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation. Cardiovascular-related comorbidities are established to contribute to morbidity and mortality especially during exacerbations. The aim of the current study was to determine alterations in hemorheology (erythrocyte aggregation, deformability) in newly diagnosed COPD patients and their response to medical treatment and to compare with values of COPD patients with exacerbations.

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Introduction

Chronic obstructive pulmonary disease (COPD) is a common, preventable, and manageable disease process that is characterized by progressive persistent airflow restrictions and related to increased chronic inflammatory reaction of the airways and lungs against harmful gases and particles [1]. Exacerbations of COPD are defined as the worsening of symptoms such as increment of dyspnea, phlegm volume, and phlegm purulence, usually accompanied by hypoxia and hypercapnia [23]. The most common causes of COPD exacerbations are infections. Inflammation is an important component of the disease [4]. Macrophages and neutrophils play an important role in the inflammatory process [5]. On the other hand, RBC were proposed as biosensors for the stadium of COPD [6]. Nowadays, COPD treatment options include quitting smoking, pharmacological treatment (short-acting anticholinergic, short-acting beta2-agonist, long-acting anticholinergic, long-acting beta2-agonist, and inhaled corticosteroids), and nonpharmacological treatment (pulmonary rehabilitation) [79]. Aim of pharmacological treatment is to improve the quality of life and exercise tolerance beside achieving the reduction of symptoms and attacks [78]. Inhaled corticosteroids specifically reduce the number of COPD exacerbations [10]. In COPD exacerbation first of all, it is important to identify the etiology. Viral and bacterial infections, air pollution, and environmental factors can initiate COPD exacerbation. Thus, antibiotics and oral steroids are choices of treatment [11].

Hemorheology is a branch of biorheology that focuses on blood and its interactions in both macro- and microcirculation under the influence of the applied constraints [12]. Erythrocyte deformability, red blood cell (RBC) aggregation, hematocrit (Hct), and blood viscosity are well-known components of hemorheology [1214]. The flow properties of blood play significant roles in tissue perfusion. These properties are influenced by pathophysiological processes, including a variety of pulmonary diseases, thereby increasing the clinical relevance of blood rheology information [131517]. In COPD patients, RBC were shown to alter morphologically, like cytoskeleton changes, ultrastructural modifications, and reductions of glycophorin A, band 3, and RBC thiols [71819]. Rheological blood properties were demonstrated to progressively deteriorate as pulmonary insufficiency increases in patients with chronic bronchitis [18]. There are limited number of studies exploring hemorheological alterations in COPD [162022]. The results of these studies were obtained either from COPD patients at different stages of the illness and age [182022] or from patients receiving different types of therapy (medication, exercise) [162023]. Additionally, different types of measurement techniques, some being rather old, were used in a variety of the studies mentioned above, which makes it difficult to compare the results [202124]. Thus, we aimed to determine the possible alterations in RBC deformability and aggregation in newly diagnosed COPD patients and their response to medical treatment and to compare these parameters with values of COPD patients with exacerbations for the first time in the literature. The results of the current study are expected to contribute to the formation of alternative treatment options for COPD.

Statistical Analyses

Continuous variables were expressed as mean ± standard deviation (SD), median (minimum–maximum values), and categorical variables as number and percent. Shapiro-Wilk tests were used for testing normality. If parametric test conditions were satisfied, Analysis of Variance (ANOVA) was used for comparisons among groups. The post hoc Tukey test was used when the ANOVA determined a significant difference. If parametric test conditions were not satisfied, the Kruskal-Wallis Variance Analysis was used for comparisons among groups. The post hoc Mann–Whitney  Test with Bonferroni Correction was used when the Kruskal-Wallis Variance Analysis determined a significant difference. For pairwise comparisons, if parametric test conditions were satisfied, Paired Samples -test was used and if parametric test conditions were not satisfied, Wilcoxon signed rank test was used. All statistical analyses were done by SPSS 21.0. Power of the study was found to be over 95% with 95% confidence ( = 0.05).

Conclusion

In overview, the results of the current study indicate that exacerbations of COPD are characterized by significant hemorheological abnormalities known to adversely affect blood flow. The decrement observed in RBC deformability and the increment shown in erythrocyte aggregation during exacerbations might complement other pathophysiologic mechanisms, leading to worsening of oxygenation and thus clinical symptoms. The mechanisms of the hemorheological alterations could not be clarified. Oxidative stress and inflammation may be involved. Therapeutic approaches including antioxidants for normalizing hemorheological parameters during exacerbations of COPD may also be recommended. However, whether therapies to decrease RBC aggregation and enhance deformability directly and specifically can be developed and whether such therapies will relieve the patient’s symptoms remain an area of active investigation. Further research with a larger number of patients to explain the mechanisms of hemorheological alterations may be necessary.

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