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PULMONOLOGIYA

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No 1 (2008)
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https://doi.org/10.18093/0869-0189-2008-0-1

EDITORIAL

CLINICAL GUIDELINES

ORIGINAL STUDIES

29-32 300
Abstract
Generation of active oxygen forms (AOF) in whole blood was studied in 32 patients with bronchial asthma (BA) and 39 patients with chronic obstructive pulmonary disease (COPD) by luminoldependent chemiluminescence (ChL). ChL intensity of blood was decreased in all patients. Halotherapy (HT) was used in 15 patients with BA and 19 patients with COPD. Standard treatment was administered to 17 patients with BA and 20 patients with COPD. Abnormal AOF production and symptoms of disease persisted in patients after standard treatment. HT increased AOF pro duction and improved treatment efficiency in patients with BA and COPD.
33-38 255
Abstract

To evaluate a role of polymorphic variants of metalloproteinase and protease genes for hereditary susceptibility to COPD and its severity, we analyzed polymorphic loci of MMP1, MMP9, MMP12, PI, and AACT genes in COPD patients (n = 318) and healthy persons (n = 319) living at the Bashkortostan Republic. Results showed that frequency of genotypes and alleles of G(-1607)GG gene MMP1, С(-1562)T gene MMP9, A(-82)G gene MMP12, and Ala 15 Thr gene ААСТ did not differ in COPD patients and healthy subjects. The Zand S-mutations of the PI gene were also similar in both the groups. The heterozygous GA genotype of G1237A locus in the 3'-non-translated region of PI gene was associated with COPD occurrence (OR = 2.09; 95 % CI: 1.15–3.81). To determine polymorphic variants associated with severity of clinical course and age of the disease manifestation, a comparative analysis of rates of genotypes and alleles was performed in patients with different COPD stages and of different age. The stage IV COPD patients significantly more often carried rare T allele in С(-1562)T locus of the MMP9 gene (15.89 % vs 8.38 %; χ2 = 7.804; df = 1; p = 0.005; OR = 2.06; 95 % CI: 1.22–3.49). Individuals with rare TT genotype of MMP9 gene were found only among the stage IV COPD patients (3.97 % vs 0 %; χ2 = 4.78; p = 0.029; pcor = 0.058). Moreover, analysis of this locus in patients with early manifestation of COPD (younger the 55 yrs) revealed significantly more frequent rate of T allele in patients with stage IV COPD compared to patients of the same age but less severe COPD (χ2 = 5.26; df = 1; p = 0.022).

39-44 398
Abstract
The aim of this study was to investigate human antioxidant defense at various COPD stages and to substantiate administration of vitamins C and E as a part of complex treatment of COPD at the Far North. We followed-up 92 COPD patients aged 20 to 50 yrs (of them, 42 males). The control group consisted of 58 healthy persons of 20 to 45 yrs of age. A total blood antioxidant activity (TAA) was detected using G.I.Klebanov's method. Superoxide dismutase (SOD) and catalase levels in erythrocyte membrane were assessed with chemiluminescent methods. Lipid peroxide (LPO) activity was measured by malone dialdehyde (MDA) plasma concentration. We also investigated hepatic and renal functions, protein, lipoid, and carbohydrate metabolism. Patients with exacerbation of stage II COPD had increased LPO activity (2.97 ± 0.12 nmol/ml compared to 1.86 ± 0.09 nmol/ml in stable phase and 1.36 ± 0.06 nmol/ml in controls) with TAA increased by 40 %. The stage III COPD patients demonstrated more significant growth of LPO activity (2.04 ± 0.08 nmol/ml in stable phase and 3.44 ± 0.15 nmol/ml in exacerbation; p < 0.05) accompanied by less prominent increase in TAA. Early stages of COPD were characterized by increased levels of antioxidant enzymes (2.44 ± 0.06 μg/g of Hb for SOD and 8.30 ± 0.15 –g/g of Hb for catalase compared to 1.56 ± 0.02 and 7.36 ± 0.10 μg/g Hb in controls). At the later COPD stages, the SOD level was less high and catalase concentration even decreased. COPD patients had increased concentrations of oxyproline (1.76 ± 0.48 g/ml to 2.80 ± 0.50 μg/ml; р<0.05 for both when compared to the controls) and α1-antitripsin (for stage II COPD, 284 ± 47 μg/ml in stable phase and 240 ± 20 μg/ml in exacerbation, for stage III COPD, 245 ± 18 μg/ml and 223 ± 15 μg/ml, respectively). Administration of vitamins C and E 25 mg/kg and 5 mg/kg of body weight, respectively, as a part of a complex therapy of the disease exacerbation resulted in shortening of exacerbation, improvement in clinical status and lung function, TAA activation, and lowering of LPO activity. Therefore, COPD is accompanied by significant activation of oxidantive processes, which depend on the stage and phase of the disease. The results allow including antioxidant vitamins in programs of treatment of COPD to be recommended.
45-50 348
Abstract
We examined 60 patients with chronic obstructive pulmonary disease (COPD) by noninvasive arteriography (arteriograph TensioClinic TL1 (TensioMed, Hungary) to evaluate a place of arterial stiffness in the pathogenesis of COPD. As a whole, central arterial stiffness in COPD patients is higher than in healthy persons and is expressed in increase in aortic pulse wave velocity (aPWV), augmentation index (IA), and the ratio of coronary perfusion indexes. Increase in the arterial stiffness is stable which could be important for pathogenesis of cardiovascular disturbances in such patients. The arterial stiffness does not progress according to severity of COPD. Aortic stiffness naturally raises in the stages I and II of the disease but it decreases in the stage III. The increase in the aortic stiffness in the early stages is thought to be due to influence of pathogenic factors of the disease; in the stage III, the aortic stiffness decreases because of progressive myocardial hypodynamia. According to findings of noninvasive arteriography, the most informative predictor of cardiovascular risk and COPD severity was the ratio of coronary perfusion indexes. It closely correlated with hypoxemia, and duration and severity of disease. Our results partly explain frequent combination of COPD and cardiovascular pathology. The further researches in this field will be needed to specify pathophysiological mechanisms of vascular dysfunction in COPD.
51-56 581
Abstract
Clinical and epidemiological examination of 2 264 residents of highaltitude regions (2 400 to 3 800 m*) and 1 498 inhabitants of lowaltitude regions (760 m*) ages 18 to 75 yrs was performed to estimate prevalence of COPD and its major risk factors. Higher prevalence of COPD among highlanders (7.6 %) was found compared to lowlanders (5.8 %; р < 0.05), especially in men older 40 yrs of age. The growth of COPD spread was observed in population of young persons including women. Leading risk factors for COPD in highlanders were smoking, air pollution inside houses from burn ing of pressed dung (kizyak) used as fuel and acute respiratory infections. Actually, the primary issues to decrease morbidity, mortality and preva lence of COPD in highlanders are preventive measures and early diagnosis of the disease.
57-61 348
Abstract
Levels of inflammatory markers and skin microcirculation were studied in patients with chronic obstructive pulmonary disease. Proinflammatory cytokine concentrations and number of desquamated endothelial cells in blood flow were significant increased during exacerbation compared with controls. The increase in proinflammatory cytokine concentrations in exacerbation was accompanied by increased skin perfusion, increased oscil lation amplitudes in the frequency ranges of respiratory rhythm and higher endothelial activity compared with controls. In stable condition, the lev els of proinflammatory cytokines decreased compared with those in exacerbation. Myogenic activity was decreased twice in patients with stable con dition compared with healthy persons. The endothelialdependent vasodilation did not change and the endothelialindependent vasodilation increased in all patients compared with controls.
62-68 346
Abstract
The aim of the study was to assess efficacy and safety of ipratropium and ipratropium/fenoterol in patients with acute exacerbation of COPD receiving maintenance therapy with tiotropium. Design: prospective, randomized, controlled cross-over study. Patients and methods. Thirty six patients with COPD exacerbation (mean age 66 yrs; mean FEV1 26 %) were included in the study. Patients were randomized to receive either ipratropium or ipratropium/fenoterol on two different test days. The study consisted of two different protocols. In the 1st protocol, the patients received either nebulized solution of ipratropium 500 μg or ipratropium/fenoterol 500/1000 μg. In the 2nd protocol, patients received either ipratropium 80 μg via metered dose inhaler (MDI) and spacer or ipratropium/fenoterol 80/200 μg. Spirometry, clinical and hemodynamic measurements were performed immediately before and at 1 and 4 hours after inhalation of ipratropium or ipratropium/fenoterol. Nebulized therapy with ipratropium or ipratropium/fenoterol resulted in statistically and clinically significant improvement in FEV1 , FVC and IC at 1 and 4 hours after inhalation (р < 0.01). In terms of the bronchodilator effect, add-on therapy with ipratropium/fenoterol was nonsignificantly superior to add-on ipratropium. There were no serious adverse events after inhaled therapy including hemodynamic parameters (BP, ECG, QTc). Only ipratropium/fenoterol resulted in increase of heart rate, approximately by 3.8 beats per minute (bpm) at 1 hour after inhalation (p < 0.001). Inhaled therapy with ipratropium or ipratropium/fenoterol via MDI and spacer led to similar results as nebulized therapy. Heart rate was increased at 1 hour after inhalation of ipratropium/fenoterol via MDI and spacer by 3.7 bpm (p < 0.001). In patients with acute exacerbation of COPD receiving maintenance therapy with tiotropium, the addition of ipratropium or ipratropium / fenoterol provides significant bronchodilator effect without any serious adverse events.
69-74 1201
Abstract
Prevalence and clinical and physiological features of coldinduced bronchial hyperreactivity in patients with respiratory diseases were shown. In patients with chronic bronchitis, coldinduced bronchial hyperreactivity was associated with worsening of lung ability to condition the inspired air. Disorders of respiratory heat exchange in patients with bronchial asthma were not the leading cause of coldinduced bronchoconstriction, which was associated with high sensitivity of airway receptors and IgEdependent mechanisms. A set of diagnostic criteria allowing detection of the dominant mechanism of airway cold hyperreactivity was proposed.
75-80 287
Abstract
Purulent and destructive lung diseases are often complicated by loss of anatomic structure of lung tissue, development of lung cirrhosis with subsequent respiratory and heart failure. We performed pathomorphological examination of operational and post mortem lung tissue specimens from 116 inpatients of 25 to 78 years of age with acute lung abscess or lung gangrene who was treated at a pulmonology center from 1999 to 2005. Acute lung inflammation tending to suppuration was characterized by pronounced cell reaction with no "fibrin blockage" and resulted in extended histolysis and abscess formation. "Young" fibrin was often found. Microvessels were fully passable, full-blooded with no fibrin into lumen. At subacute stage, fibrin was "maturing" with subsequent organization and growth of granulated tissue. Clinically, there were sequestered lung abscesses. Massive deposits of "young" and "maturing" fibrin formed "fibrin cocoon" with macrophages and neutrophils bricked up inside. Cell reaction was weak. There were swelling and desquamation of endothelium of microvessels, massive fibrin deposits into vessel lumen and prominent perivascular impregnation with fibrin. This pathological variant could lead to formation of abscess or pulmonary fibrosis with carnification. In cases of massive subtotal or total, often bilateral lung injury with weak delimiting of purulent and destructive process massive destructive zones with resting lung parenchyma faintly impregnated with fibrin were seen. There were no features of fibrin deposition inside microvessels. Functional activity of neutrophils and macrophages was greatly decreased. Therefore, the most favourable pathohistological variant appears to be formation of fibrin blockage consisted of "young" fibrin deposits; prominent cell reaction and absence of microcirculatory block. Structural changes of cells and stroma should be considered during pathological examination in order to provide optimal treatment strategy.
81-86 250
Abstract
Severe asthma patients admitted to a hospital during a year have been examined. All of them had severe poorly controlled asthma. According to the basic treatment, the patients were divided into 3 groups. The 1st group patients (n = 23, or 31.9 %) were treated with fluticasone / formoterol 1000 / 100 μg daily; the 2nd group patients (n = 25, or 34.7 %) used beclomethasone dipropionate 2000 μg daily plus fenoterol as a rescue medication; and the 3rd group patients (n = 24, or 33.4 %) received budesonide / formoterol 640 / 18 μg daily. The groups were comparable for age. Analysis of clinical status showed that dyspnea increased in all the patients during acute exacerbation of asthma but it was more severe in the 2nd group. The 1st group patients achieved good control of asthma while being at the stable period; their FEV1 significantly improved by 20.8 %. The 2nd group did not achieve asthma control, FEV1 improved by 10 % (non significant). The 3rd group achieved full control of asthma with FEV1 being increased by 25.2 %. Therefore, combination of inhaled corticosteroids and long-acting β2 -agonists helps to achieve full or good asthma control on the contrary to the 2nd group patients who did not achieve control of the disease.
87-92 284
Abstract
The aim of the study was to investigate the effect of diabetes mellitus on the lung diffusing capacity for carbon monoxide (TLCO) and oxygen status of arterial blood in 141 young (of them, 66 female) patients with type 1 diabetes mellitus (IDDM) (mean age, 26.2 ± 6.2 yrs; mean duration of the disease, 12.6 ± 7.3 yrs) in comparison with 36 age-, sex-, weight-, and height-matched healthy controls (C). Diabetic patients were divided into 4 groups: 1) 46 diabetic patients without microvascular complications (DP1); 2) 48 diabetic patients with mild late complications (simple and preproliferative diabetic retinopathy, II to III stage nephropathy (DP2); 3) 34 diabetic patients with advanced late complications (proliferative retinopathy, IV stage nephropathy) (DP3); 4) 13 diabetic patients with end-stage renal failure (V stage nephropathy), not treated with dialysis (DP4). Spirometry with assessment of bronchodilator response, body plethysmography were performed, TLCO and transfer-factor (KCO) were measured in sitting position by the single-breath (TLCOsb) and the steady-state (TLCOss) methods. Gas exchange and lung volumes did not differ between DP1 and C. We found a significant reduction in TLCOsb, TLCOss, KCO in DP2patients compared to controls. Severe diabetic microangiopathy (DP3, DP4) was associated with significant decrease in TLCO and total lung capacity (TLC), progressive fall in arterial pO2 and total oxygen concentration in arterial blood (ctO2). TLCO, TLC, pO2 and ctO2 were particularly low in the group with end-stage renal failure (DP4). Conclusion. Diabetes mellitus alters pulmonary gas exchange and causes reduction in lung volumes. Our data suggest that this abnormalities could be considered as manifestations of late diabetic complications and the lungs are one of the target organs affected by diabetes.
93-100 566
Abstract
This study was aimed to compare clinical and bacteriological efficacy and tolerability of generic levofloxacin (Levoxin®, Shreya Life Sciences) and original levofloxacin (Tavanic®, sanofi-aventis) in patients admitted for communityacquired pneumonia (CAP) or exacerbation of COPD. This open comparative nonrandomized prospective study involved 40 patients with CAP (mean age, 44 ± 13 yrs) and 40 patients with exacerbation of COPD (mean age, 63 ± 7 yrs, smoking history, 38 ± 10 packyrs). Both levofloxacin (L) medications were given 500 mg daily for 7 days or 750 mg daily for 10 days if P. aeruginosa was isolated. Clinical and microbiological efficacy and tolerability were assessed in 3, 7 and 10 days of the antibac terial therapy. To the end of the therapy, clinical efficacy in CAP patients was 95 % for both drugs. Bacteriological efficacy was 91.6 % in generic L group and 90.9 % in original L group. Tolerability of L was good or excellent in 90 % of pneumonia patients. In COPD patients, clinical efficacy was 95 % in both the groups to the end of the study. Bacteriological efficacy in COPD exacerbations was 75 % for generic L and 81.8 % for original L. Complete eradication of S. pneumoniae was reached in 100 % of cases. Generic L was welltolerated or excellently tolerated in 95 % of COPD patients and original L was welltolerated or excellently tolerated in 100 % of COPD patients. Adverse events were rare, mild and transitional.

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ISSN 0869-0189 (Print)
ISSN 2541-9617 (Online)