The dissertation is devoted to improving the differential diagnosis of anemia in patients with chronic obstructive pulmonary disease (COPD) based on the determination of the hepcidin content and optimization of the treatment of anemia of chronic disease (ACD).
The study involved patients with exacerbation of COPD. ACD was diagnosed at the level of hemoglobin lower than the reference values, soluble transferrin receptors (sTfR) within the reference values, iron deficiency anemia (IDA) – sTfR above the reference values.
The study was carried out in two stages: 1st was devoted to the study of laboratory and clinical features of the course of COPD in the presence of ACD (included 202 patients with COPD in exacerbation); 2nd – determination of effective treatment regimens for ACD in patients with COPD. To conduct the 2nd stage of study 120 patients with COPD in exacerbation were examined, of which 21 patients were with ACD, but only 19 patients agreed to participate in the study a study to treat their anemia. The control group consisted of 62 apparently healthy individuals.
All patients underwent general clinical, laboratory and instrumental studies which included the determination of sTfR, hepcidin and C-reactive protein (C-RP), bronchodilation test, COPD assessment test and dyspnea level. Statistical data were processed using SPSS-21 program.
After analyzing the data of the clinical blood test, we obtained four study groups: group 1 – 144 patients without anemia, group 2 – 33 patients with ACD, group 3 – 12 patients with erythrocytosis, group 4 – 13 patients with IDA. Thus, the incidence of anemia in patients with COPD was 22.7 %, among which 28.2 % had IDA, and 71.8% had ACD, while erythrocytosis was detected in 6 % of patients.
Patients with COPD and ACD were more likely to have cough, shortness of breath, diffuse wheezing compared to other groups and the level of FEV1 was lower than in patients without anemia. In the presence of anemia (ACD or IDA), the number of points by CAT was higher compared with another patients without anemia however, no differences in the level of dyspnea were found.
It was found that the frequency of ACD increases according to the degree of obstruction and severity of the COPD. We haven’t found statistically significant differences in the incidence of anemia depending on BMI.
Patients with COPD and IDA had significantly lower levels of serum iron (SI) and ferritin. In the group of COPD patients with ACD, the content of SI was significantly lower than in patients without anemia and erythrocytosis and significantly higher than in patients with IDA.
Determination of the content of hepcidin, C-RP and ferritin in patients with COPD and ACD demonstrated their significantly higher content compared with patients of other groups. It was found the negative correlation between the content of hepcidin and hemoglobin and positive correlations between hepcidin and ferritin, C-RP.
According to the analysis of EPO content in patients with ACD and IDA, patients with ACD had significantly lower EPO content compared with patients with IDA and control group.
Patients with COPD and ACD were divided into 3 treatment subgroups: A, B and C. Patients of group A in addition to basic treatment received 80 mg of ferrous iron twice a day for 4 weeks, B – 100 mg of sucrose complex of iron (III) hydroxide three times a week for 4 weeks, C – 100 mg sucrose complex of iron (III) hydroxide and recombinant human EPO 3000 IU subcutaneously three times a week for 4 weeks. Determination of the content of hemoglobin, SI, ferritin, hepcidin and C-RP was carried out before treatment, after the end of exacerbation treatment (8th day) and antianemic treatment (36th day); the EPO content was determined before treatment. The assessment of the clinical symptoms of COPD and ACD, the determination the number of points by the CAT, the level of dyspnea and FEV1 were carried out on the 1st and 36th days of treatment.
Evaluation of the EPO content in patients with COPD and ACD showed us the absence of significant differences between groups A – C. The risk of DVT and PE was assessed on the Walls criteria for patients in this group at visit 2 and at the end of each week of EPO treatment.
We found that the inclusion of a sucrose complex of iron (III) hydroxide and EPO in the treatment of patients with COPD contributed to a decrease in the hepcidin content, C-RP and ferritin, compared with other patients, which may be due to the pleiotropic anti-inflammatory effect of EPO. In addition, combined treatment increased the hemoglobin and SI compared with other groups.
Higher anti-inflammatory and antianemic efficacy of the combined treatment of ACD is associated with a significant decrease in the level of dyspnea by mMRC, an increase in the FEV1, improvement the number of points by the CAT compared with patients who receiving monotherapy drugs of iron.
