Currently, new drugs have being developed with a conceptually new research design based on human genome findings. Mainly, new drugs are intend ed for treatment of chronic noninfectious diseases, primarily, cardiovascular diseases, malignancies and respiratory diseases. One of the fundamental research directions is searching for target molecules including lipid metabolism regulators, anticoagulants, fibrinolytics, and monoclonal antibodies. The former are considered as target therapy in cardiology, dermatology, oncology, rheumatology, allergology, pulmonology, ophthalmology, etc. Another important direction is development of orphan drugs. Further basic knowledge is needed for development of new drug generations.

These clinical recommendations summarized currently available evidence on diagnosis and management of patients with pulmonary embolism. When compared to previous version of recommendations, this document has introduced simplified clinical prognostic scales and a new risk stratification system including intermediate risk. Novel approach to anticoagulant therapy have been also reviewed including systemic thrombolysis, catheterdirected treatment, vitamin K antagonists and new oral anticoagulants.

Aclidinium is a new anticholinergic agent for maintenance therapy of chronic obstructive pulmonary disease (COPD). Pharmacokinetic properties of aclidinium provide higher safety profile and lower risk of extrapulmonary adverse effects. In clinical phase III studies, aclidinium significantly increased lung function, reduced clinical symptoms and improved quality of life in patients with COPD. The aim of this review was to analyze clinical trials evaluating pharmacokinetics, clinical efficacy and safety of inhaled aclidinium bromide.

A review of recent epidemiological surveys of effect of air pollution on respiratory morbidity and mortality is shown in the article. Weighted particles initiate oxidative stress in the respiratory tract followed by chronic inflammation. Cytotoxic effects of weighted particles include apoptosis, reducing transmembrane mitochondrial potential, caspase activation and fragmentation of DNA. These mechanisms underlie carcinogenesis, development of bronchial asthma and chronic obstructive pulmonary disease. In this situation, sufficient antioxidant capacity is crucial to support respiratory system functioning. Nacetylcysteine (NAC) has both direct and indirect antioxidant activity. This drug could inhibit apoptosis in cell culture, prevent inflammation in the airway caused by weighted particles aerosol exposure and inhibit bronchial hyperreactivity caused by inhalation of diesel fuel combustion products. Own results has also demonstrated. Preseasonal therapy with oral NAC 200 mg daily for 30 days significantly decreased total NO metabolite concentration in exhaled air condensate in patients with hay fever with or without asthma compared to healthy volunteers. Therefore, therapy with NAC could be considered as a promising approach to diminish an adverse effect of air pollutants on the respiratory system and to inhibit oxidative stress in allergic patient.

The aim of the study was to investigate enzymatic and chemiluminescent activity in blood neutrophils of patients with moderate and severe communityacquired pneumonia (CAP).

Methods. The study involved 48 patients with moderate CAP and 40 patients with severe CAP; they were examined on admission. Synthesis of primary and secondary reactive oxygen species (ROS) was evaluated using the chemiluminescence assay. Neutrophil NAD(P)dependent dehydrogenase activity was assessed using the bioluminescent method.

Results. The «respiratory burst» was found in neutrophils of CAP patients. Terminal reactions of the anaerobic glycolysis and the tricarbonic acid cycle were intensified in patients with severe CAP only. Increased lipid anabolism activity and substrate outflow from the tricarbonic acid cycle via NADHdependent glutamate dehydrogenase were shown regardless of CAP severity. The canonical analysis showed abnormalities of metabolic mechanisms of the «respiratory burst» in blood neutrophils in CAP.

Conclusion. The metabolic disorders and «respiratory burst» intensity in CAP arize the need for pathogenic correction. High NADHdepend ent dehydrogenase activity and lower chemiluminescent activity in blood neutrophils could be used as additional markers of severe course of CAP.

The aim of this study was to investigate diagnostic and prognostic values of Nterminal proC type natriuretic peptide in patients with stage II – IV chronic obstructive pulmonary disease (COPD) (GOLD, 2011).

Methods. Patients with stage II – IV COPD (n = 47; 44 males, mean age, 59.49 ± 0.63 years; disease duration, 13.7 ± 0.63 years; smoking history, 23.09 ± 0.93 packyears; body mass index, 27.22 ± 9.06 kg / m–2) were involved in the study. The patients were divided according to presence or absence of pulmonary hypertension (PH): patients without PH (n = 21; systolic pulmonary artery pressure (sPAP) < 40 mmHg), patients with mild PH (n = 16, sPAP 40 – 55 mmHg) and patients with severe PH (n = 10; sPAP > 55 mmHg).

Results. NTproCNP levels differed significantly between patients without PH (1.42 ± 0.03 pg / mL), patients with mild PH (4.14 ± 0.51 pg / mL) and patients with severe PH (5.26 ± 0.21 pg / mL) (p1–2 = 0.001; p2–3 = 0.001; p1–3 < 0.001). sPAP was related to NTproCNP level (r = 0.53; p < 0.05).

Conclusion. NTproCNP had a high diagnostic value for predicting severe and nonsevere PH in COPD patients.

The objective of this study was to investigate echocardiographic abnormalities in patients with obstructive sleep apnea syndrome (OSAS).

Methods. The study involved 57 patients with OSAS and 22 healthy control subjects. Respiratory polygraphy and 2D Doppler echocardiography were performed. Apnea/hypopnea index (AHI) was used to quantify the OSAS severity. Both morphology (wall thickness, diameters) and function (ejection fraction, fractional shortening, peak E and A wave velocities, mitral deceleration time) were assessed. Patients with comorbidities which were known to affect the heart structure and function excepting arterial hypertension were excluded from the study.

Results. The results showed that OSAS was associated with left ventricular diastolic dysfunction, left and right ventricular hypertrophy independently of severity. Additionally, severe OSAS could cause the left ventricular systolic dysfunction, enlargement the ascending aorta diameter and mild increase in the right ventricular systolic pressure. Comorbod arterial hypertension could deteriorate these structural and functional abnormalities in patients with OSAS. With increase in frequency of apnea and desaturation during sleep, the heart structural and functional parameters worsen.

The aim of the study was to analyze a potential role of lung function for a comprehensive evaluation of respiratory system in patients undergoing the coronary artery bypass surgery.

Methods. The study involved 662 patients. Spirometry, body plethysmography and the singlebreath diffusing capacity for carbon monoxide (DLCO) were measured in all patients. All patients were divided into three groups according to the results of pulmonary function tests: patients with a known history of respiratory disease (n = 74; 11.2%), patients with newly diagnosed respiratory disease (n = 222; 33.5%) and patients without any respiratory disorders (n = 366, 55.3%). An integral index was calculated which characterizes the comprehensive pulmonary function evaluation based on weight coefficients.

Results. Bronchial obstruction parameters, forced and slow vital capacities and diffusing capacity of alveolarcapillary membrane greatly contributed to the pulmonary function integral index. This index did not differed significantly between patients with newly and previously diagnosed respiratory diseases; however, it was significantly higher in patients without any respiratory disorders.

Conclusion. A correlation analysis of the pulmonary function integral index, clinical and demographic data confirmed an inverse relationship between the pulmonary function integral index and duration of coronary artery disease, hypertension, number of previous myocardial infarctions, functional class of angina pectoris and congestive heart failure along with generally accepted factors affecting pulmonary function such as age, body mass index, smoking, and industrial xenobiotics.

The aim of this study was to determine the optimal therapy of chronic obstructive pulmonary disease (COPD) according to costeffectiveness of Bretaris Genuair, Spiriva Respimat, Spiriva Handihaler or Seebri Breezhaler.

Methods. Pharmacoeconomic evaluation was performed using cost effectiveness analysis, economic impact analysis, and cost analysis. Initially, search of pharmacoeconomic data for treatment with Bretaris Genuair, Spiriva Respimat, Spiriva Handihaler or Seebri Breezhaler was performed using specialized databases Pubmed and Medlink. Then, two clinical situations were modelled. The first situation included a direct comparison between Bretaris Genuair and Spiriva Handihaler. The second situation included comparison between all the studied drugs.

Results. The first clinical situation presumed that all patients treated with Spiriva Handihaler were switched to Bretaris Genuair. This allows saving 695,785 RUB per 100 patients. Therapy with Bretaris Genuair was characterized by the min imal cost per a clinical effectiveness unit, which was lung function improvement, in comparison with Spiriva Respimat, Spiriva Handihaler and Seebri Breezhaler. The second situation presumed that proportion of patients treated with Spiriva Respimat, Spiriva Handihaler and Seebri Breezhaler was equally about 33%. In this situation, switching at least of 10% of patients from each drug to treatment with Bretaris Genuair could save 50,000 to 68,000 RUB.

Conclusion. Therapy of COPD using Bretaris Genuair is superior over the treatment with Spiriva Handihaler, Spiriva Respimat and Seebri Breezhaler in terms of pharmacoeconomic evaluation.

The objective of this trial was to assess clinical efficacy, immunogenicity, and safety of 23valent pneumococcal vaccine (PPV23) in patients with rheumatoid arthritis (RA).

Methods. The trial enrolled 95 patients (75 women and 20 men aged 23 to 70 years) including 68 patients with RA and 27 subjects without systemic inflammatory rheumatic diseases (a control group) who had a recent history of ≥ 2 episodes of lower respiratory tract infection. At enrollment, all the patients received antiinflammatory therapy with methotrexate (MT) (n = 48), leflunomide (LEF) (n = 10), or MT + tumor necrosis factorα (TNFα) inhibitors (n = 10). A single 0.5ml dose of PPV23 (Pneumo23, Sanofi Pasteur) was administered subcutaneously under the regular therapy with MT or LEF or 3–4 weeks before TNFα inhibitor administration. During followup (1 and 3 months and 1 year after the vaccination), the patients underwent physical examination and routine clinical and laboratory investigations. Antipneumococcal capsular polysaccharide antibodies were measured in the serum using ELISA assay with commercial VaccZymeTM AntiPCP IgG Enzyme Immunoassay Kit (The Binding Site Group Ltd, Birmingham, UK).

Results. Noone case of pneumonia was registered in vaccinated patients during 12month followup. A twofold increase in antipneumococcal antibody level was found 1 year after the vaccination in RA patients and the control group. The vaccine was well tolerated by 63 patients (66%); 25 patients (26%) experienced pain, swelling and hyperemia at the area of vaccine injection and 7 patients (8%) had lowgrade fever. Neither RA exacerbation nor new autoimmune disorders were diagnosed during the followup.

Conclusion. The findings suggest that PPV23 showed good clinical efficacy, adequate immunogenicity and good tolerability in RA patients.

Despite recent significant advances thromboembolic complications remain a great problem as the main cause of death and disability of patients in the Russian Federation. Deep vein thrombosis of the lower limbs is the main cause of pulmonary embolism with asymptomatic to fatal clinical course. A particular problem is recurrent nonmassive pulmonary embolism. At the same time more than half of venous thrombotic episodes are asymptomatic and diagnosed later, when complications, such as pulmonary embolism or chronic venous insufficiency, develop. Commonly, the first diagnosis of these complications is made on autopsy. A clinical observation of successful intensive care for a patient with recurrent nonmassive pulmonary embolism is described in this article.

The aim of this article was to investigate respiratory and cardiovascular effects of combined therapy with indacaterol and glycopyrronium bromide in patients with severe chronic obstructive pulmonary disease.

Methods. Two clinical cases are reported in the article. Both patients were treatment with longacting beta2agonist indacaterol for 3 months followed by 3month treatment with combined therapy with indacaterol and glycopyrro nium bromide. We assessed arterial stiffness, pulse wave velocity rate, the heart rhythm variability, used spirometry and echocardiography, CAT and MMRC scales.

Results. Combined inhalation therapy resulted in significant increase in FEV1 and FVC, reduction in dyspnea, improvement in arterial oxygen saturation. Arterial stiffness was not changed, but the heart rhythm autonomic regulation improved in both patients. A tendency to increase in the left heart ejection fraction was also found.

Conclusion. Our data are consistent with results of other clinical trials of indacaterol and glycopyrronium bromide in patients with chronic obstructive pulmonary disease.

A case of granulomatosis with polyangiitis is described in the article. The patient experienced 3year paroxysmal asthmalike syndrome with granulomatous lesion of the subglottic portion of the larynx that further developed into multifocal destructive lesions of the lungs without clinical signs of glomerulonephritis and with positive response to combined therapy with cytostatic agents, rituximab and systemic steroids. The main criteria of granulomatosis with polyangiitis in this patient were high levels of ANCA and antiproteinase3 antibodies. Therefore, granulomatosis with polyangiitis is characterized by polymorphic onset of lung disease with coexisting paroxysmal respiratory syndrome, infiltrative and destructive pulmonary lesions.

Pathogenic relationship between gastrooesophageal reflux disease (GORD) and bronchial asthma (BA) includes local and general mechanisms. One of basic local mechanisms is microaspiration of gastric content to the bronchial tree. Small intestine bacterial overgrowth (SIBO) syndrome can cause general sensitization and supports immune inflammation in the intestinal mucosa. A 50yearold female with BA underwent surgery for GORD resulted in complete elimination of GORD and improvement in BA course. Thus, ileocecal valve dysfunction and chronic duodenum motility disorder are important pathogenic factors of BA. Adequate correction of these conditions, such as ileocecal valve correction and duodenoje junostomy, seem to be a perspective methods for treatment of GORDassociated BA.