The aim of this study was to investigate genetic features of patients with cystic fibrosis (CF) according to the National Register findings in Russia. Methods. The study involved 2,131 CF patients living in 74 regions of Russia who were included in the National Register of CF patients in 2014. Results. Genetic testing was performed in 89% of patients. The total mutant allele frequency was 81.2%. One hundred and twenty two mutations were found which comprised 173 genotypes; «mild» mutations took 23%. The most common mutant allele frequencies in the descending order were as follows: F508del, 51.53%; СFTRdele2,3, 5.93%; E92K, 2.62%; 3849+10kbC>T, 2.14%; 2184insA, 1.80%; W1282X, 1.80%; 2143delT, 1.69 %; N1303K, 1.43%; G542X, 1.16%; 1677delTA, 0.98%; L138ins, 0.95%; R334W, 0.85%; 394delTT, 0.85%; 3821delT, 0.42%; 2789+5G>A, 0.37%; S466X, 0.37%; S1196X, 0.37%; 3272-16T>A, 0.34%; W1282R, 0.29%; 3944delGT, 0.21%. Typical features of CFTR mutation distribution in Russian CF patients were lower frequency of mutations which are predominant worldwide, such as F508del, G542X, N1303K, and scarce G551D, 1717-1G>A, 2183AA>G mutations. On contrary, СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins mutations which are quite rare in Western Europe were encountered more often in Russia. «Mild» mutations were more common in Russian population of CF patients compared to European countries and have being increasing last years. Conclusion. Genetic features of Russian CF patients could be provided by Slavic, Turkic and Finno-Ugric genetic influence on Russian population.

Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. An acute exacerbation of COPD great ly contributes to worsening lung function, impairment in quality of life, need for urgent care, and use of medical utilities. Last decade, our under standing of the pathogenesis and treatment of COPD has significantly improved. The guideline accumulated recent information about the prevention of acute exacerbations of COPD. Methods. The American College of Chest Physicians and Canadian Thoracic Society developed evidence based guideline to describe the current knowledge on the prevention of acute exacerbations in a clinically useful manner. The PICO approach (population, intervention, comparator, and outcome) was used which involved nonpharmacologic therapies, inhaled therapies, and oral therapies. To select the most appropriate studies, to extract evidence based data and to grade the level of evidence, evidence based document assessment tools were applied. Results. The guideline was designed as a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD and recommendations were developed to help clinicians in their management of the patient with COPD. Conclusion. This guideline provides an up to date, rigorous, evidence based analysis of current randomized controlled trials on the prevention of COPD exacerbations. 

Novel medications for therapy of chronic obstructive pulmonary disease (COPD), primarily long-acting bronchodilators, could reduce severity of symptoms.
Nevertheless, 50% to 70% of patients continue to experience significant dyspnea despite the therapy. Early diagnosis of COPD is a quite difficult clinical problem, whereas an active treatment is usually required at early-stage disease because of decreasing physical tolerance and, importantly, rapidly declining pulmonary function. Novel fixed combinations of long-acting beta-2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) deliver both the drugs in a single inhaler. These combinations have been shown to be more effective compared to monotherapy with the components. One of new LABA/LAMA combinations is tiotropium/olodaterol combination (Spiolto Respimat). Several large clinical trials (TONADO 1 and 2, ОTEMTO 1 and 2) demonstrated significant improvement in quality of life and dyspnea in patients with COPD taking the tiotropium/olodaterol combination. This combined drug was highly effective in early-stage COPD.

Cough is one of the commonest causes of seeking for medical aid. Cough, especially chronic cough, significantly reduces quality of life, disturbs sleep, physical and intellectual activity. Given the fact that cough is not an independent disease, but is a clinical sign (often the only sign) of a disease or a condition, attempts to resolve this symptom without specifying the nature of cough are incorrect. Unfortunately, the cause of cough cannot be established in some cases; patients suffering from chronic cough of unknown etiology account for 10 to 38% and are treated symptomatically even in countries with a high level of medicine. Physicians should aware of that the therapeutic success is always a result of correct diagnostic work-up.

This is a review of current literature on lung injury which is one of the most hazardous adverse effects of an antiarrhythmic agent amiodarone referred to as amiodarone-induced pulmonary toxicity (AIPT). Finding on AIPT prevalence, risk factors, dose dependence, therapy duration and probability of AIPT occurrence have been analyzed. Issues of clinical pharmacology and the most common adverse effects of amiodarone have been discussed. Pathophysiological and pathological features and clinical manifestations of AIPT including diffuse pneumonitis, bronchiolitis, respiratory failure and acute respiratory distress syndrome have been described. Diagnosis of AIPT is based on routine methods such as lung function tests, chest X-ray, high-resolution computed tomography, and lung tissue biopsy. Management approaches include dose reduction or drug withdrawal and administration of systemic steroids. Preventive measures include baseline spirometry, regular X-ray examination and information about symptoms of this complication provided to the patients.

The aim of this study was to investigate values of pulmonary fibrosis markers alveomucin and KL-16 and the airway damage marker CC-16 for evaluating activity and progressing of extrinsic interstitial lung diseases (ILD) in dependence on etiology. Methods. Levels of Krebs von den Lungen-6 glycoprotein (KL-6), alveomucin and Clara cell protein (CC16) were measured using the ELISA method. The study involved 13 patients with pneumoconiosis, 26 patients with extrinsic allergic alveolitis (EAA) and 20 patients with extrinsic toxic alveolitis (ETA) both in active and stable status. Results. KL-6 and alveomucin were found to be more valuable markers for assessing activity of extrinsic fibrosing alveolitis compared to CC16. Alveomucin had higher specificity but lower sensitivity compared to KL-6. Conclusion. Alveomucin could be used as a screening test in cases with clinical susceptibility for extrinsic alveolitis. On contrary, KL-6 and alveomucin could be used for assessing therapeutic efficacy of EAA and ETA.

The aim of this study was to analyze lung function in multilobar community-acquired pneumonia (CAP) convalescents. Methods. Spirometry, body plethysmography, and lung diffusing capacity were measured according to the joint European Respiratory Society and American Thoracic Society standards (2005). The carbon monoxide lung diffusing capacity was evaluated using a single breath-hold technique and was adjusted for hemoglobin. Results. The complete clinical and radiological resolution of CAP did not accompanied by recovery of lung function in all cases. Obstructive ventilation disorders were diagnosed in 18.2% of patients, restrictive ventilation disorders were diagnosed in 12.1% of patients, and gas exchange abnormalities were diagnosed in 51.5% of the patients. Conclusion. Lung function and gas exchange testing is an important marker of the patient's convalescence after CAP and duration of the recovery; it also could predict the need in subsequent follow-up.

The aim of this study was to investigate reactive oxygen species (ROS) production in the blood and the immune status of patients with community-acquired pneumonia (CAP). The second aim was to evaluate clinical efficacy of immunoglobulin agent Immunovenin in these patients. Methods. ROS level in the blood was measured using the luminol-dependent chemiluminescence. The cellular and humoral immunity, IFN-γ and FNO-α blood concentrations and blood neutrophil phagocytic activity were also assessed. Of 52 patients with CAP, 18 patients were treated with Immunovenin intravenously additionally to the standard therapy and 34 patients were treated with the standard therapy. Results. The blood chemiluminescence intensity was increased and the immune status was abnormal in patients with CAP. Administration of Immunovenin led to reduction in severity of clinical symptoms, decrease in the ROS concentration in the blood and improvement in the immunity. Conclusion. Inclusion of IV immunoglobulin in the complex therapy of CAP could improve the course of the disease and the efficacy of treatment.

The aim of the study was to analyze a relationship between key adipokines expression and the glomerular filtration rate (GFR) in different clinical variants of bronchial asthma (BA). Methods.We examined 178 patients with different clinical variants of BA. The glomerular filtration rate (eGFR) was estimated using CKD-EPI. Plasma concentrations of leptin, adiponectin, resistin, and apelin were measured using the ELISA method. Correlation and factor analyses were performed using the SPSS program for Windows, version 13.0. Results. A relationship between eGFR, key adipokines expression and pSTAT3 transcription factor expression, which is involved in proinflammatory adipokines effect transduction in BA, was found. Moreover, a reverse relationship between eGFR and adipokines (leptin, resistin, adiponectin) expression was mainly typical for allergic BA. Conclusion. Additional risk factors for development and progress of chronic renal disease are probably present in patients with BA even without obesity.

The purpose of the study was to analyze drug compliance and efficacy of tilorone in preventing acute exacerbations and improving quality of life (QoL) in patients with moderate to severe COPD and a history of frequent acute respiratory viral infections (ARVI). Materials and methods. The study involved patients with moderate to severe COPD (n = 94; 35 females, 59 males; mean age, 61.8 ± 0.7 years). A comprehensive examination of patients included drug compliance assessment with a specially developed scale, clinical and laboratory parameters measured at inclusion and in 12 months. Twenty three patients with high compliance were treated with tilorone. A control group consisted of low-compliant patients who did not give a consent to take tilorone (n = 20). Results. The significant 1.95-fold reduction in ARVI episodes incidence within 12 months was registered in the tilorone group that resulted in reduction in COPD exacerbation and hospitalizations rates, improvement in physical component of QoL and decrease in a cost of the therapy by 84%. Conclusion. Six-week therapy with tilorone 125 mg once a week, two courses annually, aimed at prevention ARVI in patients with moderate to severe COPD and a previous history of frequent ARVI could significantly reduce a rate of ARVI episodes followed by reduction in the rate of acute exacerbations of COPD, hospitalizations due to COPD and in improvement in physical component of QoL. Tilorone did not change lung function and physical tolerance of COPD patients.

The aim of this study was to analyze drug supplying for outpatients with chronic obstructive pulmonary disease (COPD) at Krasnoyarsk kray. Methods.Federal and regional regulatory documents and databases of Healthcare Ministry of Krasnoyarsk kray and of the Regional Compulsory Health Insurance Fond were analyzed including the period of 2009 – 2014. We assessed number of receipts prescribed for COPD patients. Results. Despite the growing morbidity of COPD in the Krasnoyarsk kray, number of COPD patients received subsidized treatment has reduced annually and decreased by 14.3% during 2009 – 2014. The cost of subsidized treatment of COPD increased twice: from 2.1 thousand rubles in 2009 to 4.2 thousand rubles in 2014 and a recipe cost increased in 1.8 times: from 522.9 rubles in 2009 to 965.2 rubles in 2014. Every COPD patient receives 4 prescriptions per year in average. Conclusion. The results of this study necessitate thorough analysis of concordance with current guidelines for the prescribed drugs.

The aim of this study was to determine risk factors of chronic non-infectious diseases and early diagnosis of cardiovascular, respiratory and endocrine functional disorders in industrial workers using a mobile cardiorespiratory and metabolic laboratory. Methods. This was a prospective non-comparative observational study in a non-selected population. All participants underwent the following measurements: weight and height, wrist and thigh circumferences, pulse oxymetry, exhaled nitric oxide (NO) and exhaled carbon monooxide (CO), spirometry before and after bronchodilator inhalation, electrocardiogram, arterial stiffness and endothelial dysfunction, blood glucose and blood total cholesterol. Indirect calorimetry with energy expenditure calculation was used in several patients. Validated questionnaires were also used. Results. The study involved 194 industrial workers. High prevalence of risk factors, such as tobacco smoking (45% of active smokers, 31% of ex-smokers), obesity (BMI ≥ 30 kg x m^–2 in 37%), hypercholesterolemia (34%), and endothelial dysfunction (57%), was found. Vascular biomechanics correlated with bronchial patency, systemic arterial pressure and exhaled CO concentration. Bronchial obstruction was found in 56% of subjects, of them, COPD was diagnosed in 13%. Conclusion. Mobile cardiorespiratory and metabolic laboratory allows medical care delivery directly to a working place, and effective detection of risk factors and chronic lung disease.

The aimof this study was development of a model of the lung clearance in order to test an accordance of current sanitary regulations to recent view on mucociliary clearance capacity. Methods. We used a statistical morphometric model of the tracheobronchial tree. The model parameters were chosen to fit for experiments on slowly clearance of the lungs from calibrated-size aerosols. Results. The improved model of the tracheobronchial tree permits assessment of the maximal mass transported by the mucociliary escalator. An accumulation phase has been found which is due to a lack of time for the airway clearance in subjects regularly exposed to the air dust. Moreover, dust exposure standardization should consider not only the air pollution level but duration of pollutant air exposure and time intervals between shifts. The latter should be long enough to eliminate dust particles out of deep (in accordance to the particle size) parts of the tracheobronchial tree. 
Conclusion. These data could be useful for determination of acceptable air pollution and shift work scheduling.