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Lviv clinical bulletin 2018, 4(24): 33-38

https://doi.org/10.25040/lkv2018.04.033

Clinical-Functional Characteristics of Patients with Chronic Obstructive Pulmonary Disease Depending on the Parameters of the Red Branch of Blood and the Content of Soluble Transferrin Receptors

A. Kovchun, V. Kmita, L. Prystupa

Medical Institute Sumy State University

Introduction. Chronic obstructive pulmonary disease (COPD) is characterized by a persistent limitation of the speed of the air flow, the severity of which usually increases, and is caused by a chronic inflammatory response of the lungs to the effects of toxic particles or gases [8]. The circulation of inflammatory mediators provokes the systemic manifestations of COPD, which include anemia of chronic disease (ACD), which occurs in patients with acute or chronic immune-active processes [2, 11, 13, 17–19]. The pathogenesis of this anemia is not clear enough, but there are many results of studies, which confirming the effect of inflammatory cytokines on iron homeostasis, hemoglobin content and sensitivity of the bone marrow to erythropoietin [14, 18]. Epidemiological studies in recent years show that 17.0–24.0 % of patients with COPD have anemia and only 6.0–10.0 % have polycythemia [1, 7, 13]. Most authors have noted a significant effect of anemia on the severity of dyspnea, exercise tolerance and mortality in patients with COPD [12, 16].

Purpose of the study. To clarify the clinical and functional features of the course of chronic obstructive pulmonary disease, depending on the parameters of the red branch of blood and the content of soluble transferrin receptors (sTFR).

Materials and research methods. After obtaining consent in accordance with the Helsinki Declaration of the World Medical Association “Ethical principles of medical research involving human subjects as a study” in a randomized way based on the pulmonary department of a municipal institution of the Sumy Regional Council “Sumy Regional Clinical Hospital” and internal medicine department of the municipal institution «Sumy City Clinical Hospital № 4», with a preliminary stratification for the presence of COPD (according to the adapted Clinical setting based on evidence «Chronic obstructive pulmonary disease» of the Ministry of Health of Ukraine № 555 dated 27.06.2013 and GOLD recommendations (2014) [8]), the study included 202 patients (73 women and 129 men) aged over 40 years old. The study was approved by the Commission on Bioethics Compliance in conducting experimental and clinical studies of the Medical Institute of Sumy State University (Protocol № 2/1 of February 14, 2017). The exclusion criteria were: severe concomitant diseases (tuberculosis of the lungs, oncopathology, alcohol and/or drug addiction, AIDS, heart failure (Stage II B, III), decompensated hepatic, renal, etc. deficiency), the presence of a specific source of blood circulation diseases, nonspecific colitis, chronic hemorrhoids, etc.), preliminarily diagnosing of  myeloblastic, aplastic, hemolytic anemias, treatment with angiotensin converting enzyme drugs, the period of pregnancy or lactation, regular reception of systemic corticosteroids.

The degree of obstruction was determined by using computer spirography (forced expiratory volume in the first second – FEV1) recorded 15 minutes after inhalation of 400.0 mcg of salbutamol), degree of dyspnea – according to a modified scale of the Medical Research Council (mMRC), and quality of life – by COPD Assessment Test (CAT).

Anemia was diagnosed in accordance with the WHO recommendations (hemoglobin <130.0 g/l for men and <120.0 g/l for women), and a unified clinical protocol of primary and secondary (specialized) medical care “Iron deficiency anemia” № 709 of 11.02.2015. All examined patients conducted clinical, laboratory and instrumental investigations. In accordance with the above protocol, differential diagnosis of anemia was performed, namely, ACD and iron deficiency anemia (IDA). The diagnosis of ACD was established in case of detection sTFR content within the reference values ​​(8.7 – 28.1 nmol/l), IDA – if the sTFR content exceeded the reference values.

Patients with COPD were divided into four groups depending on the parameters of the red branch of blood and sTFR content: the 1st group consisted of patients without anemia, the 2nd one with ACD, the 3rd one with erythrocytosis, the 4th one with IDA.

The control groups included 62 practically healthy individuals (25 women, 37 men) aged over 40 years.

For statistical data processing the program SPSS-21 was used. Mean values ​​are given as M ± m, where M is the average value of the parameter, m is the standard error. The significance of differences between the mean values ​​of several groups was determined by using analysis of variance (ANOVA) with the Fisher criterion and Bonferroni correction, the value p < 0.05 was considered statistically significant. As a correlation coefficient between the interval scale values, the Pearson correlation coefficient was applied with the determination of statistical significance (p < 0.05).

The results of the study and discussion. According to the classification given in the recommendations GOLD (2014), the I stage of bronchial obstruction were verified (85.4 ± 2.7%) in 37 (18.3 %) patients, the ІІ stage (65.7 ± 7.31 %) – in 85 cases (42.1%), ІІІ stage (42.8 ± 4.3 %) – in 79 (39.1%) patients, ІV stage (27.9 %) – in 1 (0.5%) patient.

After analyzing the results of a clinical blood analysis, we found out that 46 patients (22.7 %) had anemia, 12 (5.9 %) patients had erythrocytosis, and it coincides with the results of A. Chambellan, C. Cote, S. Parveen, M. Halpern [5, 6, 9, 15], who showed anemia in 12.6 – 21.0 % of patients with COPD. As a result of a detailed analysis of the anamnesis, objective examination and laboratory results, 13 (6.5 %) patients were diagnosed with IDA and associated diseases were found (in 5 patients chronic non-atrophic gastritis, in 4 – chronic gastroduodenitis, in 2 – peptic ulcer of the stomach, in 1 – duodenal ulcer, and in 1 – chronic gastroduodenitis and chronic pancreatitis with exocrine insufficiency), which led to impaired absorption of iron and, as a result, the occurrence of IDA.

Some researchers have studied the type of anemia in patients with COPD. Thus, in one study of patients with COPD [7], anemia was found in 19.6 %. According to the authors, only in 70.0 % of patients anemia had a pathogenetic relationship with COPD, other patients had anemia caused by iron deficiency. A. K. Boutou et al. [3] found that mild ACD occurs in 10.24 % of COPD patients, the researchers excluded any other causes of anemia.

According to the planned design of the study, all patients with COPD were divided into four groups depending on the parameters of the red branch of blood and the sTFR content. The 1st group consisted of 144 patients without anemia, the 2nd – 33 with ACD, the 3rd – 12 with erythrocytosis, the 4th – 13 with IDA.

To find out the frequency of anemia depending on the stage of obstruction, the distribution of all patients with COPD was analyzed depending on the stage of obstruction, the red branch of blood and the sTFR content (Table 1).

Table 1

The distribution of patients with chronic obstructive pulmonary disease, depending on the degree of obstruction, indicators of the red branch of blood and the content of soluble transferrin receptors

Thus, ACD was shown in patients with COPD II – IV stages of obstruction and was not fixed among patients with COPD with I stage of obstruction. ACD is present in 9.5 % of patients with II stage of obstruction, in 30.0 % – with III stage, and in 100.0 % – with stage IV. So, the frequency of ACD increases according to the stage of obstruction, which coincides with the results of the study by A. Fidan and others [7], who observed an increase in the frequency of anemia as the stage of obstruction increases (not detected in patients with stage I and detected in most patients with stage IV).

To determine the presence of significant differences between FEV1 in patients with COPD depending on the red branch of blood, we analyzed the FEV1 depending on the stage of obstruction (Table 2).

Table 2

Spirogram indicators in patients with chronic obstructive pulmonary disease depends on the red branch of blood and the content of soluble transferrin receptors

Notes: p1 – statistical significance of differences (p <0.05) between the 1st and 2nd groups; p2 – statistical significance of differences (p <0.05) between the 1st and the 3rd groups; p3 – statistical significance of differences (p <0.05) between the 2nd and the 3rd groups; p4 – statistical significance of differences (p <0.05) between the 2nd and 4th groups; p5 – statistical significance of differences (p <0.05) between the 3rd and 4th groups; F – Fisher criterion.

Thus, patients with COPD and anemia (ACD or IDA) had significantly lower FEV1 rates compared with patients without anemia and with erythrocytosis.

The results of assessing the level of dyspnea are given in table. 3.

Table 3

The results of assessing the severity of dyspnea according to a modified scale of the Medical Research Council and the quality of life according to COPD Assessment Test depends on the red branch of blood and the content soluble transferrin receptors

 

Notes: p1 – statistical significance of differences (p <0.05) between the 1st and 2nd groups; p2 – statistical significance of differences (p <0.05) between the 1st and the 3rd groups; p3 – statistical significance of differences (p <0.05) between the 2nd and the 3rd groups; p4 – statistical significance of differences (p <0.05) between the 2nd and 4th groups; p5 – statistical significance of differences (p <0.05) between the 3rd and 4th groups; F – Fisher criterion.

Consequently, no statistically significant difference between the severity of dyspnea the red branch of blood and the sTFR content was found in patients with COPD. It was also found that patients with COPD and ACD and COPD with IDA had a higher rate according to a survey for COPD and correspondingly low quality of life compared with patients without anemia and with erythrocytosis.

A study of correlations between the stage of obstruction, the results of assessing the severity of dyspnea by mMRC and the quality of life and health by using CAT in patients with COPD and ACD. Correlation analysis showed that there is an inverse correlation between the degree of obstruction and mMRC indicators (r = -0.591; p = 0.001) and CAT (r = -0.608; p = 0.001). So, with an increase the stage of obstruction, dyspnea significantly increases and the quality of life and health of patients with COPD and ACD worsens.

According to the GOLD recommendations, which provide for the definition of patients categories A, B, C and D, Groups A formed from 30 (14.9%) patients, Groups B – 91 (45.0%), Groups C – from 78 (38, 6% ), Group D – from 3 (1.5%).

In order to investigate the relationship between the severity of COPD and the frequency of ACD, the frequency of ACD in patients with COPD was determined depending on the severity of the underlying disease, which is shown in the figure.

The frequency of anemia of chronic disease in patients with chronic obstructive pulmonary disease depending on the severity of the disease.

It is established that the frequency of ACD grows in accordance with the severity of the underlying disease. Consequently, the risk of adverse events and exacerbations in the future in patients with COPD and ACD is increasing in accordance with the severity of the underlying disease. The results obtained by us coincide with the results of A. Chambellan and G. Jian [4, 10], which proved the negative impact of anemia on dyspnea, physical activity and quality of life, as well as the results of the A. Boutou study, which found that ACD enhances shortness of breath and limits physical activity [3].

The analysis of the frequency of exacerbations in patients of the studied groups over the past year. The research results are summarized in table 4.

Table 4

The frequency of exacerbations over the past year in patients with chronic obstructive pulmonary disease depends on the red branch of blood and the content of soluble transferrin receptors

It has been established that in patients with COPD and ACD exacerbations occur more often than in patients with other groups during the last year.

Conclusions. Anemia is detected in 22.7 % of patients with chronic obstructive pulmonary disease, in particular, iron deficiency anemia – in 6.4 %, and anemia of chronic disease – in 16.3 %. Patients with chronic obstructive pulmonary disease with anemia (anemia of a chronic disease or iron deficiency anemia) have a significantly lower indicator of forced expiratory volume in 1st second than patients without anemia and with erythrocytosis. Anemia worsens the quality of life of patients with chronic obstructive pulmonary disease, moreover, with an increase in the degree of obstruction in patients with chronic obstructive pulmonary disease and anemia of chronic disease, the dyspnea is significantly increased, the quality of life and health – deteriorates. The frequency of anemia of chronic disease increases as the stage of obstruction and the severity of chronic obstructive pulmonary disease increases. In patients with chronic obstructive pulmonary disease in combination with anemia of chronic disease, a greater frequency of exacerbations was recorded than in patients of other groups.

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