History of Russian pulmonology is described in the article. The rise of this science inRussiawas closely related to Sergey P. Botkin who taught physicians not only to recognize diverse variants of respiratory diseases but also to evaluate the patient's status as a whole. Dmitriy D. Pletnev, who investigated severe and complicated pneumonias; Ippolit V. Davydovskiy, who supposed that several pathological processes could exist in the human's lung contemporarily; Nikolay S. Molchanov and Vladimir P. Sil'vestrov, who investigated slowly-resolved pneumonia, and other investigators contributed significantly to the Russian pulmonology. Establishment of the Federal Pulmonology Research Institute, which became as a cooperating center, and "Russian Respiratory Society" Interregional Public Organization, and other important initiatives were main stages of development of the Russian pulmonology. Scientific and practical activity of the Federal Pulmonology Research Institute during last 25 years has been analyzed in the article. Important achievements in the control of such severe and common diseases, as pneumonia, asthma, chronic obstructive pulmonary disease, cystic fibrosis, tuberculosis, etc., have been discussed in the article. Further investigations that would allow bring the pulmonologist's work in line with the current requirements have been outlined in the article.

Significant improvement in the respiratory care management inRussian Federationduring the previous five years has resulted in improvement in diagnosis of respiratory diseases, quality of outpatient and in-hospital care, and decrease in mortality from respiratory diseases. This is a review of scientific papers, books, and guidelines published by researchers of the Federal Pulmonology Research Institute. The review reflects a contribution of the institute staff to the improvement of respiratory care and the public health inRussia. The main scientific directions of the institute are the public health monitoring and epidemiological studies that evaluate prevalence of respiratory diseases inRussia. Other research directions include improvement in the primary and secondary prevention, improvement in primary and specialized outpatient and in-hospital respiratory care management, and improvement in diagnosis and treatment of work-related respiratory diseases. Novel approaches to respiratory care of advanced disease, post-surgery rehabilitation and orphan respiratory diseases have been described in the article. To improve prevention of the diseases, novel markers of chronic respiratory diseases were searched and new medications were evaluated. The authors concluded that further scientific directions of Russian pulmonology could include molecular investigations of respiratory diseases, prevention and early diagnosis of orphan diseases, personalized management and rehabilitation of patients with chronic respiratory diseases and implementation of innovative methods of diagnosis, treatment and rehabilitation aimed at further decrease in mortality from respiratory diseases.

Current aspects of diagnosis, classification and therapy of pulmonary hypertension (PH) were reviewed in the article. A new classification, including all known clinical variants of PH, and functional classification were presented. A diagnostic algorithm with routine diagnostic methods and highly sensitive innovative techniques (CT-angiography of the lungs, perfusion scintigraphy, the right heart catheterization, etc.) was shown. The author discussed prognostic factors of 1-year survival, general pathogenic mechanisms including endothelin and prostacyclin pathways and a role of nitric oxide and soluble guanylate cyclase stimulators. Assessment criteria of acute vasoreactivity test results were reviewed. Typical therapeutic approaches including calcium channel blockers, oxygen, anticoagulants and diuretics were described. Main classes of specific drugs were listed such as endothelin receptor antagonists, prostacyclins, soluble guanylate cyclase stimulators, phosphodiesterase 5 inhibitors, selective prostacyclin receptor agonists. Current investigations are directed to searching new effective and safe drugs that could improve outcomes, slow down progression of the disease and improve quality of the patient’s life.

Last two decades, active use of non-invasive ventilation (NIV) has provided a significant improvement in the management of chronic obstructive pulmonary disease (COPD), both in patients with acute exacerbation and in stable patients. Currently, NIV is the first-line treatment for patients with acute exacerbation of COPD and acute hypercapnic respiratory failure. This method of respiratory support is also effective after extubation, as it could facilitate weaning from the ventilator and affects positively prevention and treatment of postextubation respiratory failure. Also, NIV has been successfully used in co-morbidity of COPD and sleep apnea syndrome, COPD and pneumonia, and in early postoperative period after thoracic surgery. NIV can be used in COPD patients with chronic respiratory failure. Long-term NIV at home is more reasonable in patients with daytime hypercapnia. The most effective strategy of respiratory support in COPD is thought to be decrease in the partial pressure of carbon dioxide in the arterial blood, i.e. high-intensity NIV. Currently available portable non-invasive ventilators could improve significantly physical activity of patients with severe COPD.

Granulomatous lung disease is a heterogeneous group of diseases with different etiology, clinical symptoms and tissue damage, and different response to therapy. The prevalent histological sign of granulomatous lung disease is granuloma which is the clinical and morphological entity of this disease. The aim of this review was to describe a diversity of granulomatous diseases, key morphological features of infectious and non-infectious granulomatosis, and a diagnostic approach. Granuloma is a result of chronic inflammation involving cells of macrophage system and other inflammatory cells. Antigens activate T-lymphocytes, macrophages, epithelioid cells and polynuclear giant cells which form granuloma. Also, granuloma contains the extracellular matrix that is produced by fibroblasts and is intended to isolate the antigen. Granulomas could be infectious and non-infectious but, according to recent findings, microorganisms could cause granuloma formation in cases considered as non-infectious diseases. Therefore, sometimes it is difficult to estimate infectious or non-infectious origin of the disease.

Respiratory diseases are accompanied by activation of free radical-related processes with enhancement and subsequent suppression of different parts of antioxidant defense. This could result in development of oxidative and nitrosative stresses. General mechanisms of development of oxidative and nitrosative stresses in respiratory diseases as well as antioxidant defense of respiratory system have been described in this review. Markers of oxidative and nitrosative stresses in different respiratory pathology were investigated. Oxidative and nitrosative stresses are multi-level processes with intricate regulation which are closely related to other physiological and pathophysiological processes. Investigation of mechanisms of oxidative and nitrosative stresses could improve diagnostics and contribute to development of new therapeutic approaches and agents.

In 1997, the International Expert group on chronic obstructive pulmonary disease (COPD) has come to decision to initiate the Global Initiative for COPD (GOLD). The first GOLD report was published in 2001 and provided the basis for many national programs for COPD diagnosis and management. Research data accumulated in the next decade allowed to perform complete revision of global strategy in 2011 (updated 2013), considering personalized approach to prognosis and treatment selection in an individual patient. At the end of2016, anew comprehensive reassessment of GOLD report was released. The ABCD assessment tool has been refined; the role of spirometry in COPD management has been updated. Regular assessment of inhaler technique to improve the disease control has been emphasized. New data on therapy with long-acting β2-agonists/long acting anticholinergic combinations and «triple therapy» have been added. Classification of severity of COPD exacerbations was provided and impact of concomitant diseases was stressed. The section on pulmonary rehabilitation has been amplified.

Pneumonia is one of the most common respiratory diseases. The aim of this study was to analyze trends of pneumonia morbidity in adults > 18 years old and in children 0 – 14 years old in 2010 – 2014. Methods. Findings of Federal Statistic Surveillance of the Healthcare Ministry of Russian Federation were used to analyze pneumonia morbidity of adults and children living at different federal districts of Russian Federation in 2010 – 2014. Results. Respiratory diseases are the 2nd leading cause of morbidity in adults and the 1st leading cause of morbidity in children. The highest pneumonia morbidity in both groups was registered in 2010 that was 413.1 per 100,000 of age-adjusted population in adults and 986.1 per 100,000 of ageadjusted population in children. In 2014, the morbidity decreased to 338 cases in adults and 816 cases in children per 100,000 of age-adjusted population. In 2010, the highest pneumonia morbidity in adults and children was registered in the Central Federal District. In 2014, the highest pneumonia morbidity was registered in adult population of the Siberian Federal District and in children of the Far-Eastern Federal District. The overall pneumonia morbidity in Russia decreased in 2010 – 2014 excluding the Siberian Federal District, the Ural Federal District and the Volga Federal District. Conclusion. Average pneumonia morbidity in adults and children inRussia rise in 2010 due to A(H1N1)2009 influenza epidemics and then gradually decreased to 2014, probably due to the improved care and preventive measures.

The aim of this study was to investigate tobacco consumption by adolescents 13 to 15 years of age in Russian cities (Moscow, Khabarovsk, Novosibirsk, Pskov, Cheboksary). Methods. A Russian version of GYTS (Global Youth Tobacco Survey, 2015) questionnaire was used. Results. Equal tobacco consumption by young people was noted in all regions of Russia. The overall consumption of tobacco products by adolescents was 10.4% to 19.7% (11.6% to 22.1% by boys and 10.4% to 17.5% by girls). Overall, 5.5% to 11.2% of adolescents consume cigarettes; of them, 5.2 % to 14.7% of boys and 5.9% to 8.0% of girls. Five to six of 10 adolescents have tried to quit smoking during the previous 12 months. Twenty eight per cent to 40.1% of adolescents exposed to secondhand smoke at home and 33.8% to 39.0% exposed to secondhand smoke inside public space; 35% to 53% of smokers bought cigarettes in shops, stands or in street vendors. The young age in 37.5% to 62.0% of smokers did not preclude from buying cigarettes. In points of sale, 7 – 8 from 10 adolescents noted antismoking information and 3 from 10 found tobacco advertisement or sales promotion. Sixty per cent to 70% of adolescents thought that passive smoking was harmful for them. Conclusion. The overall tendency was common for all Russian regions; it was 2- to 3-fold decrease in tobacco smoking prevalence, two-fold decrease in home secondhand smoke prevalence and 2.5-fold decrease in secondhand smoke prevalence at public spaces and in tobacco products availability. Adolescents increasingly (> 90%) aligned the indoor smoking ban in public places and were aware of tobacco smoking danger. There is a reduction in information pool on tobacco consumption in TV programs and other videos. Nevertheless, there is a tendency to reduction in number of adolescents trying to quit tobacco consumption and those who wants quitting in future. Therefore, new directions and changes in tobacco control strategy are needed.

Investigation of exhaled breath condensate (EBC) is a noninvasive diagnostic method in respiratory diseases. The objective of this study was to compare EBC protein spectrum in healthy volunteers and in patients with chronic obstructive pulmonary disease (COPD), pneumonia and lung cancer (NSCLC), as well as to assess a role of proteomic analysis of EBC for diagnosis and differential diagnosis of these diseases. Methods. We examined 18 patients with COPD, 13 patients with community-acquired pneumonia, 26 patients with lung cancer and 24 healthy non-smoking volunteers. EBC was collected using ECoScreen system (VIASYS Healthcare, Germany) and a standardized method. EBC-samples were lyophilized, hydrolyzed and analyzed by HPLC and tandem mass spectrometry. To identify proteins, we used Mascot (Matrix Science, UK) and IPI-human (version 3.82) databases provided by the European Bioinformatics Institute. Results. Proteomic analysis of EBC identified more than 300 different proteins; most of them were types I and II cytoskeletal keratins. Cytokeratin 5, 6, and 14 concentrations in EBC of NSCLC patients were significantly higher than that in healthy volunteers. Dermcidin, immunoglobulin alpha, kininogen, cytoplasmic actin, serum albumin, and Zn-alpha2-glycoprotein were identified in EBC of healthy volunteers and patients with COPD and pneumonia. High concentration of peroxiredoxin in EBC of COPD patients could be due to severe oxidative stress. High levels of acute-phase and hypoxia proteins (annexins A1 and A2, HSP90B, cystatins M and B, collagen and histones fragments) were detected in EBC of pneumonia patients. Also, β- и α-subunit of hemoglobin, nuclear ubiquitin casein (NUCKS), POTEE, high mobility group protein (HMG-I/HMG-Y) and lactoferrin were identified in EBC of NSCLC patients. Conclusion. We found that EBC in healthy nonsmokers and in patients with COPD, pneumonia and NSCLC had characteristic protein spectrum. Most of the identified proteins could be used for diagnosis of these diseases.

Morbidity of occupational respiratory diseases depends on workplace environmental and individual genotype as well. The aim of our study was to investigate molecular biomarkers of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) in workers exposed to toxic aerosols. The second aim was to develop preventive measures for these diseases. Methods. This was a randomized prospective cohort study that involved workers of food industry. Results. The study involved 159 food industry workers. Lung function abnormalities (29.3%) and hyperresponsiveness to workrelated factors (20.6%) were found in 126 of 159 workers who were at risk of occupational respiratory diseases and were exposed to biological active aerosols. BA and COPD were diagnosed in 17.4% and 11.9% of workers, respectively. Hyposecretory variants (PiMS, PiMZ) of alfa-1-protease inhibitor (API) gene were found in 5.5% of workers. Proportions of workers with deficit of GSTM1 and GSTT1 enzymes were 65% and 60%, respectively. Risk alleles (ID, DD) of the angiotensin converting enzyme (ACE) gene that indicate the susceptibility to cardiovascular diseases and are typical for subjects exposed to dust particles and other hazardous agents were found in 20% of workers. Conclusion. Our results have demonstrated the role of molecular biomarkers of individual susceptibility to occupational factors. Molecular biomarkers could define the risk of occupational respiratory diseases, predict their course and help to choose therapeutic and preventive measures. Identifying the susceptible workers could underlie personalized approach to prevention of respiratory diseases.

The aim of this study was to evaluate changes in lung ventilation and lung diffusing capacity (DLCO) of cystic fibrosis (CF) patients during 1 year after lung transplantation. Methods. Complex lung function was monitored in CF patients underwent bilateral lung transplantation in 2012 – 2016. Results. CF patients (n = 12; mean age, 26.4 ± 4.4 years) were included in the study. Median follow-up after the lung transplantation was 19 (12–57) months. Consistent improvement in lung function parameters and DLCO was observed in 3 months after lung transplantation and maintained during 1 year. The ratio of forced expiratory volume in 1 sec to forced vital capacity was higher the normal level and the bronchial resistance was lower the cut-off values, i.e. the patients did not have bronchial obstruction. The total lung capacity (TLC) decreased to normal according to the anthropometric characteristics of the recipient. Meanwhile, change in the TLC structure, such as non-significant reduction in the vital capacity (VC) together with increase in the functional residual capacity (FRC), residual volume (RV) and RV/TLC ratio, have been developed. Consistent increase in FRC and RV could be explained by changes in the shape and the elasticity of the chest wall after the surgery. DLCO also improved, but was still slightly decreased. Conclusion. The lung function and DLCO improved in a year after bilateral lung transplantation in CF patients. Effects of different factors on postoperative lung function parameters need to be further investigated.

Ultrasound diagnostic methods completely respond to all current requirements for diagnostic procedures and are valuable, safe, and relatively independent on the patient's condition. As ultrasound scanners are improved and new diagnostic regimens are developed, their use in different clinical field is extended. The most common ultrasound methods in pulmonology are echocardiography and ultrasonography of pleural cavities. Ultrasound investigation of the lung parenchyma is limited due to full reflection of ultra-sound from the aerated lung tissue. The lung density is increased in respiratory diseases; this gives an opportunity to use ultrasonography together with radiological methods for diagnosis and, therefore, to decrease radiation dose for the patient.

Continuous growth of proportion of adult patients in the total number of patients with cystic fibrosis (CF) is accompanied by the increasing rate of pulmonary and extrapulmonary complications, mainly secondary osteoporosis. This is a multifactorial disease predominantly associated with chronic microbial and inflammatory processes, vitamin D deficiency, low body mass index, delayed puberty and hypogonadism, and long-term (≥3 months) therapy with oral steroids. Controversal issues of terminology and current diagnostic approach to osteoporosis in CF patients have been discussed in the article. Diagnosis of osteoporosis in CF patients should not be based solely on osteodensitometry findings but also on thorough analysis of clinical signs and symptoms, other image diagnostic investigations and laboratory data. Detection of the risk factors could help to control this disease.

Start of the CFTR modulating therapy is an important and promising step towards better treatments for all cystic fibrosis (CF) patients. Therapy with CFTR potentiator Ivacaftor resulted in dramatic improvements in CFTR function in patients with G551D mutation, later it was prescribed for patients with another 9 gating mutations. We present a case of successful treatment of a CF patient with G461E/N1303К genotype. We have suggested that due to gating mutation G461E, the patient may profit from the treatment with ivacaftor. After six months of treatment, sweat chlorides concentration decreased from 93 mmol/l to normal 50 mmol/l, respiratory function (FEV1) increased from1.44 L(48%pred) to2.0 L(67%pred). The clinical course of the disease has changed significantly. The patient became stable; symptoms of chronic bronchitis diminished. There are other gating mutations in the Russian National Registry that may profit from treatment with ivacaftor.