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cohorts [Text] / D. Valvi et al. // International Journal of Chronic Obstructive Pulmonary Disease. - 2012. - Vol. 7. - P. 173-182.
20. Zhao, H.W. An increase in hyaluronan by lung fibroblasts: a biomarker for intensity and activity of interstitial
pulmonary fibrosis? [Text] / H. W. Zhao, C. J. Lü, R. J. Yu // Respirology. - 1999. - Vol. 4. P. 131-138.
English version: DYNAMICS OF SOME MARKERS OF SYSTEMIC INFLAMMATION AND PULMONARY FIBROSIS AT PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE DURING LONG-
5k
TERM MEDICAL REHABILITATION
Basin a B.O.
State Institution "Dnipropetrovs'k Medical Academy Ministry of Healthcare of Ukraine", Department of Faculty Therapy and Endocrinology Dnipropetrovs'k.
COPD characteristics with violations of airway and lung parenchyma, accompanied by inflammatory responses and reconstructive pulmonary fibrosis. As inflammatory markers in COPD high diagnostic significance of C-reactive protein (CRP) and fibrinogen (F) demonstrated today As a marker of fibrotic remodeling at COPD hyaluronic acid (HA) is studied recently. The aim of our study was to determine the possibility of normalization of persistent chronic systemic inflammation (CRP, F) and pulmonary fibrosis (HA) at patients with COPD during long-term (over one year) adequate treatment according to disease stage. Analysis of the results showed that the inadequate according to the stage of COPD medication of patients in the severity of their chronic systemic inflammation, especially in terms of CRP rather substantial and more significant in patients with severe bronchial obstruction. At all patients with COPD, regardless of the stage of the disease, there is also the strengthening of pulmonary fibrosis that displays with significant increasing of HA. It was also found that prolonged (over one year) adequate medical therapy of patients with COPD leads to normalization of both indicators of systemic inflammation (CRP, F) and marker of pulmonary fibrosis (HA), which indicates the real possibiiity of stablizzation of pathological changes in these patients and slower formation of irreversible manifestations of bronchial obstruction.
Key words: systemic inflammation, pulmonary fibrosis, chronic obstructive pulmonary disease
Nowadays, chronic obstructive pulmonary disease (COPD) is one of the most serious medical and social issues both in our country and worldwide [6]. It has been conclusively proved that COPD is not characterized by a discrete morphofunctional lesion of primary, secondary bronchi or pulmonary parenchyma [5]. This disease is described by the peculiarities of airway obstruction, which is accompanied by inflammatory responses and reparative fibrosis [1]. Contemporary medical science makes it possible to study these processes with the help of identification of plasma levels of various biomarkers [14].
As COPD inflammatory markers, the C-reactive protein (C-RP) and fibrinogen (F) proved to be of high diagnostic utility at present. The C-RP level in the COPD exacerbation in the patients' blood plasma grows quickly and can reach 400-200 mg/l (a generally accepted amount being up to 10 mg/l) [16, 19]. The COPD fibrino-gen also serves a protein of an acute form of inflammation, which enhances pro-inflammatory effects of other factors [1, 2].
The hyaluronic acid (HA) has been used recently as a marker of the COPD fibrosis remodeling [7, 10].
HA (hyaluronate, hyaluronan) is a glycosaminoglycan, which is a part of connective, epithelial and nervous tissues; it is one of the main components of an extracellular
matrix and is found in numerous biological fluids (saliva, synovial fluid etc) [17]. The name "HA" was given to it in 1934 by K. Meyer and J. W. Palmer, who had isolated it from the vitreous body of the eye. As it has emerged later, due to its high content in the extracellular matrix, HA plays an important role in tissue hydrodynamics as well as in the process of cells migration and proliferation [13].
A significant amount of HA is also observed in bronchi and lungs [8], and a disorder of HA content as a component of the extracellular matrix may be an element of the COPD pathogenesis [12] and cause development of fi-brotic changes in lungs and bronchi [20].
In connection with the above-referenced matter, the aim of our work was to identify the possibility of normalization of indicators of the persistent chronic systemic inflammation (C-RP, F) and fibrosis (HA) in patients with COPD upon a long-term (throughout one year) adequate treatment based on the disease stage.
Materials and methods
We have conducted a prospective study of 50 patients with COPD (men - 46 (92.0%), women - 4 (8.0%); average age - 62.5±1.80 years), who, before entering the study, underwent a planned inadequate therapy based
* To cite this English version: Basina B.O. Dynamics of some markers of systemic inflammation and pulmonary fibrosis at patients with chronic obstructive pulmonary disease during long-term medical rehabilitation // Problemy ekologii ta medytsyny. - 2013. - Vol 17, № 1-2. - P. 40 -42.
TOM 17. N 1-2 2013 P.
on the disease stage (did not take chronic bronchodila-tors or took them in inadequate dozes; patients with severe bronchial obstruction as planned did not take chronic inhaled glucocorticosteroids). Depending on the disease stage, the target patients were split into two subgroups: 1 - 15 individuals (average age - 60.9±2.29 years) with stage I I of COPD (FEVi - 70.1±2.33% of due value); 2-35 individuals (average age - 64.9±1.10 years) with stage I I I of COPD (FEV1 - 36.6±1.85% of due value).
On the first stage, all the patients underwent clinical and functional examination; we identified the levels of C-RP, F and HA as well as corrected the pharmaceutical therapy according to the disease stage. All the patients were repeatedly examined after one year of the adequate pharmaceutical treatment.
All the COPD clinical diagnoses were formulated in compliance with the recommendations of the Order of MHCU №128 from 19.03.2007 [4].
All the patients entered the study in the phase of stability of the pathological process; none of them had clinical signs of infective exacerbations of COPD. Not a single patient was excluded from the study ahead of time for any reasons.
A control group consisted of 13 apparently healthy individuals (men - 9 (69.2%), women - 4 (30.8%); average age - 55.5±1.74 years).
All the target patients gave their consent to the clinical study.
The respiratory function test (RFT) with a characteristic of the main bronchial obstruction indicators (forced vital capacity of lungs (FVC), pulmonary forced expiratory
Levels of systemic inflamma
volume in 1 minute (FEV1) was made using computer spirometry with the help of the Master Screen Body/Diff device ("Jager", Germany). The postbronchodilatatory test of reversibility of bronchial obstruction was made using 400 mkg of salbutamol.
The C-RP level was identified in the patients' blood plasma using the immunoturbidimetric method with the help of the automatic analyzer "Cobas e411" (Roche Diagnostics GmbH) [9, 18,].
The fibrinogen level was identified in citrated plasma using the modified Clauss method with the help of the automatic analyzer «Cobas e411» (Roche Diagnostics GmbH) [1, 2].
The HA level was identified in blood plasma using the modified Gold method [11].
Statistical processing of the study materials was made using the methods of biometric analysis, implemented in the EXCEL-2003 (№74017-641-947520157075), STATISTICA 6.0 (№31415926535897) program packages [3]. The difference between the compared values was considered accurate with p<0.05, the tendency of changing was indicated within the range of 0.05<p<0.10.
Results and discussion
The analysis of the obtained results showed that on the stage of entering the study, the C-RP level in patients with COPD group-wide was 49.8% higher than that in control group individuals (Table 1). Furthermore, if on stage II of the disease the indicator only tended to increase, on stage III it increased in a statistically-valid way (by 61.7%) with a high degree of accuracy.
Table 1
indicators in patients with COPD on the stage of entering the study
Groups and sub-groups of target patients Indicators
C-RP (mg/l) F (g/i) HA (mg/ml)
Patients with COPD, 9,35±0,92 3,17±0,10 0,28±0,012
among them:
1 1 stage 7,57±0,72 3,01±0,16 0,31±0,023
stage 10,09±1,26 3,26±0,13 0,27±0,015
Control group 6,24±0,14 2,84±0,16 0,15±0,018
P Pm-c<0,001 Pm-c=0,085 Pm-c<0,001
pii-c=0,081 p i i-c>0,05 pii-c<0,001
p i i i-c<0,01 piii-c<0,05 p ii i-c<0,001
p i i-i i i=0,089 p ii-i i i>0,05 pi i-ii i >0,05
N o t e s: 1. P - accuracy of the difference between the indicators of groups and sub-groups;
2. m - main group of patients with COPD;
3. II, Ill - COPD stages;
4. c - control group.
After a year of the adequate pharmaceutical treatment, the C-RP level in patients with COPD group-wide decreased in a statistically-valid way and reached the value of the control group (Table 2). In patients with stage II of the disease the indicator only tended to decrease, at that, it also reached the values of the control;
considering the fact that before the patients' entering the study the indicator increased insignificantly, its dynamics (even of such a kind) reflects mostly positive result. In patients with stage I I I of COPD, the C-RP level in treatment dynamics decreased by more than 30% and also reached the level of the control group.
npoSAeMH eKOAoriï Ta MejHUHHH
Table 2
Levels of systemic inflammation indicators in patients with COPD after one year of adequate treatment
Groups and sub-groups of target pa- Indicators
tients C-RP (mg/l) F (g/i) HA (mg/ml)
Patients with COPD, 6,5010,34" 2,63±0,09# 0,13±0,008#
among them: 0,14±0,019#
i i stage 6,28±0,70 2,33±0,13
i i i stage 6,62±0,39* 2,78±0,11" 0,13±0,009#
Control group 6,24±0,14 2,84±0,16 0,15±0,018
p Pp-c>0,05 Pm-c>0,05 Pm-c>0,05
Pii-c>0,05 Pii-c<0,05 aii-c>0,05
Pi i i-c>0,05 Pi ii-c>0,05 a i ii-c>0,05
P ii-i i i>0,05 P ii-i ii <0,05 ai i- i i i >0,05
N o t e s: 1. p - accuracy of the difference between the indicators of groups and sub-groups;
2. m - main group of patients with COPD;
3. II, Ill - COPD stages;
4. c - control group;
5.* - accuracy of the difference (p<0,05) after one year of treatment comparing to the stage of entering the study; 7." - accuracy of the difference (p<0,01) after one year of treatment comparing to the stage of entering the study; 7.* - accuracy of the difference (p<0,001) after one year of treatment comparing to the stage of entering the study.
The F level in patients with COPD group-wide on the stage of their entering the study only tended to increase comparing to its level in apparently healthy individuals. Furthermore, if in patients with stage II of the disease the indicator did not differ from the indicator of the control group, in patients with stage III it was higher in a statistically-valid way.
After one year of treatment, the F level both group-wide and in sub-group of patients with stage III of the disease decreased in a statistically-valid way and reached the level of the control group. At the same time, in patients with stage II of COPD it decreased accurately, as well, but with this it became even lower than in healthy individuals (see Table 2).
The HA level in patients with COPD (both group-wide and in sub-groups concerning stages of the disease) on the stage of their entering the study was twice as high as that in healthy individuals (see Table 1).
After a year of the adequate treatment, the HA levels both in the whole group and in sub-groups decreased in a statistically-valid way (almost two times) and reached the control level (see Table 2).
Thus, regardless of the fact that COPD is at present recognized as a disease characterized by the persistent chronic systemic inflammation, upon the long-term adequate pharmaceutical treatment it is possible to achieve normalization of numerous indicators of inflammation and stabilization of pathological process.
Conclusions
1. Under the inadequate (as for the stage of COPD) pharmaceutical treatment of patients, the distinctiveness in them of the chronic systemic inflammation, especially after the C-RP level, is quite essential and more significant in the individuals with severe bronchial obstruction. All patients with COPD, regardless of the disease stage, also reveal enhancement of processes of fibrosis, which is reflected in significant increase in the HA level.
2. Long-term (throughout one year) pharmaceutical therapy of patients with COPD leads to normalization in them of both systemic inflammation indicators (C-RP, F) and fibrosis indicator (HA), which witnesses to a real possibility of stabilization of pathological changes in this category of patients as well as retardation of formation of irreversible manifestations of bronchial obstruction.
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