The purpose of this work was to study the central arterial pressure (CAP) and its correlation with peripheral arterial pressure (PAP) and aortic stiffness in patients with bronchial asthma (BА). We examined 45 asthmatic patients and 25 healthy volunteers using noninvasive arteriography (TensioClinic TL1 arteriograph, TensioMed, Hungary). Aortic stiffness parameters and aortic systolic arterial pressure (SAP) were measured. We estimated a difference between the central SAP and the peripheral SAP (ΔSAP) and calculated index of CAP to PAP conformity (IC). According to the indirect arteriography, the central (aortic) SAP was 20 to 40 % higher in majority of patients with exacerbation of severe and moderate BА compared to the normal level. During BА exacerbation, ΔSAP was significantly decreased and IC was increased in comparison with the healthy persons in whom ΔSAP was 10.2 ± 2.1 mm Hg. This indicates abnormal CAP/PAP ratio in BA exacerbation. In stable BA, CAP, PAP, ΔSAP, and IC did not differ from control values; this assumes transitory character of hemodynamic disorders in BA exacerbation. The degree of increase in aortic SAP during BA exacerbation is thought to be closely connected with abnormal mechanical properties of the arterial walls. This was confirmed by significant correlations between aortic SAP and hypoxemia, systemic inflammation, oxidative stress, and hyponitrooxidemia. These factors could play an important role in the pathogenesis of growth in aortic SAP in BA patients.

The aim of this study was to evaluate clinical efficacy and safety of highly concentrated inhaled solution of tobramycin (Bramitob^®, Chiesi Farmaceutici S.p.A., Italy) in patients with cystic fibrosis (CF). This was 24-wk multicenter international double-blind placebo-controlled randomized trial in parallel groups. In this study, 247 patients aged 6–45 yrs with Pseudomonas aeruginosa yielded in sputum and FEV 1 40 % to 80 % pred. were randomized in 2 groups: those inhaling aerosol tobramycin (161 patients, mean age, 14.8 ± 5.7 yrs) or placebo (84 patients, mean age, 14.7 ± 6.6 yrs). Tobramycin 300 mg b.i.d. was given at the time of basic and antipseudomonal therapy. Efficacy criteria were as follows: lung ventilation parameters, sputum culture and yielding P. aeruginosa, rate of exacerbations of pulmonary disease, rate of hospitalisations, number of workoff or school-off days, number of courses of parenteral tobramycin and other antipseudomonal antibiotics, nutritional status (weight, BMI). Safety profile included serum creatinine level, audiometric test, vital signs (heart rate, blood pressure) and adverse events. To the end of the study, FEV1  improved by 7 % in the tobramycin group and by 1 % in the placebo group (p < 0.001), FVC improved by 5.7 and 1.3 %, respectively (p = 0.002), and FEF 25–75 improved by 8.8 % and 0.7 %, respectively (p = 0.001). Frequency of P. aeruginosa eradication differed significantly between the groups to the end of 4th and 20th weeks of the study (30.8 % vs. 14.3 %; p = 0.011, and 33.3 % vs. 16.5 %; p = 0.024, respectively). Exacerbations of pulmonary disease occurred in 39.8 % of tobramycin patients and in 51.2 % of placebo patients (р = 0.09). Hospital admission was required in 18.6 % and 36.9 % of patients, respectively (p = 0.002). Parenteral tobramycin was administered to 6.2 % and 16.7 % of patients, respectively (p = 0.009), other antipseudomonals were given in 55.9 % and 70.2 % of the patients, respectively (p = 0.029). Number of patients with missing work/school days due to exacerbation of pulmonary disease was 32.3 % in tobramycin group and 57.1 % in placebo group (p < 0.001). Serious adverse events related to treatment with tobramycin were not noted. In conclusion, long-term intermittent treatment with inhaled solution of tobramycin additionally to basic and antipseudomonal therapy in CF patients significantly improved lung ventilation and eradication of P. aeruginosa, decreased the rate of exacerbations of pulmonary disease, rate of hospitalisations, and numbers of antipseudomonal courses and missing work days. The treatment was well tolerated and could be recommended for CF patients with P. aeruginosa in culture.

The aim of study was to assess safety and efficacy of cardioselective beta-blockers (nebivolol and metoprolol succinate) in patients with hypertension (H) and/or ischaemic heart disease (IHD) and concomitant bronchoobstructive syndrome. The study involved 50 patients with H and/or IHD and concomitant bronchoobstructive syndrome (as a sign of stable COPD and/or asthma of any severity) and a need in β-blockers. Safety of the treatment was evaluated using respiratory symptoms and bronchial obstruction. Antihypertensive effect of β-blockers was assessed by 24-h blood pressure monitoring, antianginal effect was assessed by clinical signs, dose of nitrates, exercise tolerance (6-minute walking test), and Holter ECGmonitoring. Antiarrhythmic effect of β-blockers was evaluated by ECG monitoring. In patients with COPD or asthma, no deterioration in bronchial obstruction was found during treatment with nebivolol (FEV₁ , 71.12 ± 19.95 % at the baseline and 73.19 ± 21.70 % at the end of the study) or metoprolol succinate (FEV₁ , 81.08 ± 22.57 % and 84.58 ± 23.72 %, respectively). High antihypertensive efficacy of β-blockers was seen during the therapy while being a part of combined antihypertensive therapy or as a single-drug therapy. Both drugs significantly decreased systolic and diastolic blood pressure and reduced frequency and severity of angina attacks. Need in nitrates greatly decreased and exercise tolerance significantly increased in the patients. Antiarrhythmic effect of β-blockers was good. Both nebivolol and metoprolol succinate significantly decreased the heart rate. Thus, the study demonstrated safety of nebivolol and metoprolol succinate in patients with H and/or IHD and concomitant bronchoobstructive syndrome needed in administration of β-blockers. The drugs were also safe in patients with severe COPD or asthma and in exacerbations of the diseases not caused by β-blockers.

Co-morbidity of asthma and COPD requires a special approach to diagnosis and therapy. The aim of this study was to assess clinical and functional features in patients with asthma and COPD. We analysed findings of 21 patients with asthma and COPD (20 males, the average age, 48.5 ± 2.9 yrs, the smoking history, 25.4 ± 6.9 pask-yrs). Spirometry and bronchodilator test with salbutamol, measurement of total serum IgE, absolute count of blood and sputum eosinophils, and SaO₂, and skin allergic tests were performed in all the patients. Some patients underwent challenge test with methacholine. History of dyspnea attacks followed allergic disease in 57.1 % and exertional dyspnea in 85.7 % of the patients. Lung function was worse in patients compared to healthy persons (FEV 1 – 92.7 ± 1.9 % vs. 69.4 ± 6.1 %, respectively; FVC – 92.1 ± 1.9 % vs. 69.7 ± 5.3 %, respectively; р < 0.05). SaO₂ was also lower (94.4 ± 0.79 % compared to 97.0 ± 1.1 in healthy persons; р < 0.05). A positive bronchodilator response was obtained in 57.1 % of the patients. Co-morbidity of asthma and COPD has more severe course and treatment is less effective compared to the single disease.

In this work, use of pulmonary bronchophonography for functional evaluation of respiratory system was analyzed in early-aged patients with bronchial asthma. A computerized acoustic diagnostic complex Pattern-01 was used for this purpose. The breathing pattern was analyzed using amplitude and frequency characteristics of respiratory sound spectrum. The study involved 520 children with asthma aged 1 to 4 yrs (mean age, 2.8 ± 1.1 yrs, 294 males and 226 females) followed-up in the pediatric clinic of Moscow Medical Academy. Fifty healthy children were as controls. We investigated frequency and amplitude spectrum of respiratory sounds in exacerbated and stable asthma. High-frequency acoustic component of work of breathe was significantly different in healthy and in patients with asthma exacerbation. We have selected breathing patterns that could be further applied. Pulmonary bronchophonography allows monitoring lung function and assessing efficacy of treatment in asthma. It is an effective, noninvasive and simple method which is of special importance for detecting functional disorders in early-aged children.

The aim of this study was to evaluate influence of fenspirid on clinical and immune parameters of early-stage COPD. Workers (all were males) from a large machine-building enterprise of Chelyabinsk having stable COPD stage I or II participated in the study. They were randomized in 2 groups: 30 patients received fenspirid 80 mg b.i.d. and 30 patients received placebo (calcium gluconate) b.i.d. during 6 months. We assessed the patients' complaints, severity of cough and dyspnea, sputum volume, lung function parameters, measured saliva concentrations of final NO metabolites using the Griess reaction, lactoferrin, IL-8, and mucins using immune enzyme analysis. To the end of the treatment period, FEV₁ significantly increased in the fenspirid group (from 57.42 ± 1.66 % до 61.93 ± 2.59 %; p < 0.05) whereas it did not change significantly in the placebo group. Clinical improvement (reduction in cough, sputum volume, dyspnea, wheeze) was noted in 26 patients (86.6 %) and 16 patients (53.3 %), respectively. Lactoferrin concentration decreased from 486.01 ± 60.59 to 96.40 ± 10.17 μg ml^–1 (p < 0.05), IL-8 decreased from 111.7 ± 16.68 tо 41.90 ± 6.60 μg ml^–1 (p < 0.05), mucin protein concentration increased from 110.8 ± 13.28 tо 298.4 ± 33.14 μg ml^–1 (p < 0.05), NO_x decreased from 11.21 ± 0.91 tо 6.15 ± 2.06 μmol L^–1 (p < 0.05). These parameters in the placebo group changed nonsignificantly. Exacerbations of COPD occurred in 6 patients (20 %) of fenspirid group and 10 patients (33.3 %) of the placebo group during the study period. Tolerance of the drug was generally good. Thus, fenspirid has significant antiinflammatory effect, improves clinical signs of COPD and FEV₁. The results suggest that fenspirid could be useful in early-stage COPD patients.

Histological and immunohistochemical investigations of lung tissue specimens were performed in 9 patients with COPD underwent lung volume reduction surgery. Lung tissue specimens of died persons without lung and heart pathology were as controls. Tissue expressions of endothelial growth factor (EGF), type 9 matrix metalloproteinase, type 1 matrix metalloproteinase (TIMP-1) tissue inhibitor, and transforming growth factor β1 (TGF β-1) have been studied. Patents with severe emphysema typically had focal interstitial fibrosis, interalveolar septa infiltrated with interstitial macrophages and lymphocytes, hypertrophy of media and proliferation of intima in the vascular wall, and arteriolar muscularization. There was significantly higher expression of EGF and TIMM-1 in the lung tissue of these patients compared with controls; this could confirm the presence of compensatory mechanisms of lung parenchyma destruction. Strong correlations were found between expression of EGF and TGF β-1, EGF and TIMP-1 which demonstrated a relationship between angiogenesis, proteolysis and fibrogenesis in development of emphysema.

Clinical, laboratory, and functional investigations were performed in 279 patients with chronic obstructive pulmonary disease (COPD), mean age, 57.0 ± 2.4 years. According to severity of the disease, the patients were distributed as follows: 52.7 % had mild COPD and 47.3 % had moderatestage COPD. Mild respiratory failure was in 50.5 % of the patients, moderate respiratory failure was in 32.3 %, severe respiratory failure was in 17.2 % of the patients. All the patients were randomized in 8 equal groups. Seven groups of patients were treated with basic medications, balneological and electric therapy, and physiotherapy. The control group patients received physiotherapy and basic drugs. Non-drug treatment strategies have multiple effects not only on respiratory pathology but also on systemic manifestations of COPD; they have long-term post-treatment effect and could be targeted to certain mechanisms of the disease. This makes us to consider the physical therapeutic factors not only as a way to potentiate effects of basic medications but also as an important tool of secondary prevention of exacerbations and progression of COPD. Our clinical findings have been confirmed by morphological results, data of biochemical blood test, sputum microscopy, spirometry, monitoring of immune parameters, central haemodynamics and physical capacity, short-term and long-term assessment of quality of life.

We assessed contribution of genetic factors to the infiltrative pulmonary tuberculosis development using the association analysis. Analysis of polymorphisms in TNFA (-308G>A) (p < 0.01), CYP1A1 (Ile462Val) (p < 0.05), and GSTM1 (deletion) (p < 0.00001) genes revealed statistically significant differences between patients with infiltrative pulmonary tuberculosis and control subjects. This information could be used to form the highrisk group for the pulmonary tuberculosis development and to predict its occurrence.

The aim of the study was to estimate spread of primary and secondary multiple drug resistant Mycobacterium tuberculosis (MBT) and to characterize rpoB, katG, inhA, and ahpC gene mutations of rifampicin (RIF) and isoniazid (INH) resistant MBT strains isolated from tuberculosis patients in Kyrgyz. We obtained 493 specimens from patients with pulmonary tuberculosis which were diagnosed based on clinical, X-ray, and bacteriological examination. Among them, newly diagnosed pulmonary tuberculosis was in 445 patients (90.2 %), and 48 of the patients (9.8 %) have already been treated for tuberculosis. Mutations of rpoB, KatG, inhA, and ahpC genes associated with RIF and INH resistance were detected by biological chip test. Sensitive MBT strains were detected in 47 % and resistant strains were in 53 % of the newly diagnosed patients. Single-drug resistance to RIF only was detected in 3 % of cases; resistance to INH was found in 20 %, resistance to both the drugs was detected in 30 % of the patients. In pre-treated patients single-drug resistance to RIF was defined in 4 % of cases, resistance to INH was in 8 %, resistance to both the drugs was estimated in 75 % of the patients. Therefore, we suppose that there is a high prevalence of multi-drug resistant MBT in Kyrgyz Republic: 30 % among newly diagnosed patients and 75 % among pre-treated patients. The main cause of RIF-resistance of MBT is Ser531→Leu mutation of rpoB gene, and the main cause of INHresistance is Ser315→Thr mutation of katG gene.

The aim of this study was to analyze the course of the disease and efficacy of treatment of pulmonary multidrugresistant (MDR) cavitary tubercu losis in antituberculosis settings of Russian penitentiary system. Drug resistant was studied using the method of absolute concentrations. Among 190 males with MBTpositive cavitary pulmonary tuberculosis followedup in antituberculosis hospitals of Russian penitentiary system in Voronezh in 2003–2006, 79 patients (41.6 ± 3.4 %) were yielded MDR strains resistant to the firstline antimucobacterial drugs and 111 patients (58,4 ± 3,4 %) had strains resistant both to the firstline and the secondline drugs (isoniazid and rifampicin). Moreover, MBT strains resistant to cycloserine and quinolones were found in patients who have not been previously treated with these drugs. Both newly diagnosed patients with pulmonary tubercu losis and those with recurrent cavitary pulmonary tuberculosis had a high rate of primary and secondary MDR to the firstline and the secondline antimicobacterial drugs. Administration of I and IIA chemotherapeutic regimens in these patients resulted in occurrence of additional resistance to a wide spectrum of the firstline and the secondline antibiotics. Patients with chronic pulmonary tuberculosis are at high risk of MDR to combi nations of the firstline and the secondline drugs and need other treatment strategies including surgical interventions. Tuberculosis patients with MDR to combinations of the firstline and the secondline drugs were characterized by more severe chronic course of the disease with extended lesions and large cavities in the lungs. Adverse events to the secondline drugs were seen in 42.6 % of the patients with cavitary tuberculosis. Of them, serious adverse events requiring cancellation of the drug and change in chemotherapeutic regimen were noted in 17.9 % of cases.