MicroRNAs (miRNAs) are small noncoding RNA molecules that affect gene expression and thus take part in the epigenetic regulation of almost all physiological and pathological processes. About 1,800 human miRNAs have been discovered to date; however, biological functions and protein targets for the majority remain to be unknown. Within the respiratory system, miRNAs contribute to the lung growth and lifelong maintenance of pulmonary homeostasis. Recently, the leading role of miRNAs in pathogenesis of various pulmonary diseases has been found, including asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Due to a significant progress in studying interactions between genes and their products and environmental factors, a great role of epigenetic variability, which is gene expression change not related to DNA damage, but could be inherited consistently, became apparent. There are three levels of epigenetic regulation corresponding to three main mechanisms: genomic (DNA methylation), proteomic (histone modification) and transcriptomic (regulation through RNA, primarily miRNA). Extending our knowledge on a role of miRNAs for the respiratory system could open new therapeutic targets and diagnostic markers for respiratory diseases, particularly asthma and COPD.

Recently, nutrition and metabolism have been actively investigated in patients with chronic obstructive pulmonary disease (COPD) but clinicians generally underestimate the significance of dietary habits, nutritional status and nutritional interventions in COPD and their influence on progression and outcome of the disease. The European Respiratory Society organized a Task Force Group to review evidence on nutritional status evaluation and nutritional support in COPD patients and to determine future research directions. The Task Force members reviewed the literature on relevant topics. Nutritional status is recognized to be an independent factor influencing outcome of COPD. The Task Force described several metabolic phenotypes of COPD in order to nutritional risk assessment which is important for development clinical trial designs and counselling of the patients. Nutritional interventions could be useful in undernourished COPD patients especially when combined with physical rehabilitation. Evidence of cost-effectiveness of nutritional assessment and intervention are required for social support and reimbursement and for increased availability of this therapy. Generally, current evidence demonstrates that well-balanced nutrition is effective in all COPD patients mostly due to reduction in metabolic and cardiovascular risks.

Streptococcus pneumoniae is the leading pathogen of community-acquired pneumonia (CAP) in adults. Therefore, vaccination is an important preventive measure against CAP. Methods. Clinical and epidemiological features of CAP were studied in young conscript soldiers (n = 114) aged 18 to 26 years who had been vaccinated using the 23-valent polysaccharide pneumococcal vaccine PPV23 (Sanofi Pasteur, France) in previous 30 days and in unvaccinated patients (n = 151). Clinical examination, laboratory blood tests, sputum microbiological examination, quantitative C-reactive protein (CRP) measurement, molecular examination of nasopharyngeal smears using polymerase chain reaction (PCR), chest X-ray and pulse oximetry were used. Pneumococcal antigen was determined in urine using immunochromatography (Binax NOW S. pneumoniae test, USA). Results. Established risk factors of CAP in men were low anthropometric parameters (weight, body mass index, chest circumference), chronic upper airway diseases, history of repeated pneumonias, and being unvaccinated against pneumococcus. In first 100 days of military conscript, the risk of CAP was 6.96 (95%CI: 3.39–14.58; p < 0.001) in unvaccinated men; clinical course was more severe. Vaccination against S.pneumoniae shortened the disease by 2.2 days in average. S. pneumoniae was found in nasopharyngeal smears of 48.8% of CAP patients. Leading pathogens of CAP in vaccinated and unvaccinated patients were Haemophilus influenzae (24.1% vs 20.0%, respectively; p > 0.05), Streptococcus spp. (19.0% vs 36.0%, respectively; р = 0.48), and S. pneumoniae (10.3% vs 4.1%, respectively; p > 0.05) according to sputum microbiological results. The urine pneumococcal antigen test was positive in 2.9% of vaccinated and in 1.4% of unvaccinated CAP patients. Conclusion. Vaccination with PPV23 could reduce the rate of pneumococcal CAP in high-risk patient groups.

The aim of this study was to analyze prevalence, clinical course and pathogenesis of chronic heart failure (CHF) in patients with chronic obstructive pulmonary disease (COPD). Methods. The study involved 309 patients with COPD who underwent spirometry and Doppler echocardiography. Natriuretic peptide level was measured in blood. Results.One hundred and twelve (36.2%) patients had CHF. Patients with comorbidity were older, had higher body mass index, longer and more severe smoking history. Dyspnea as one of the main COPD symptoms existed for longer period in patients with COPD and CHF. CHF was related to severity of the airflow limitation. There was no difference between patients with different origin of CHF. The rate of hypertension was similar in COPD patients with and without CHF, but the duration of hypertension was almost twice as higher in patients with CHF. The left ventricular ejection fraction (LV EF) was significantly lower in COPD patients with CHF compared to those without CHF and was significantly lower in patients with ischaemic CHF compared to CHF of another origin. Also, COPD patients with CHF had significantly lower physical tolerance measured by 6-min walk test and more severe hypoxemia. Conclusion. Prevalence of CHF in COPD patients is quite high. CHF is caused both by concomitant cardiovascular disease (coronary heart disease, hypertension, etc.) and actually by progressive chronic cor pulmonale. Unaffected LV EF is seen more often in COPD patients; however, decreased LV EF is associated with coronary heart disease. Development of CHF in COPD patients is also associated with such risk factors as smoking, severe bronchial obstruction, hypoxemia, and tachycardia.

The aim of this study was to analyze the course of osteoporosis in elderly females with pulmonary diseases. Methods. The study involved females with postmenopausal osteoporosis who did not receive regular treatment with oral steroids. All patients underwent spirometry before and after inhalation of a bronchodilator, bone densitometry with assessment of bone mineral density (BMD) and T-score at the proximal thigh, the lumbal spine and the one third distal forearm. FRAX risk assessment score was also used. Results. We examined 79 patients (mean age, 66.9 ± 1.7 years). Female patients with chronic obstructive pulmonary disease (COPD) had significantly more frequent forearm fractures, significantly lower FEV1, BMD at the forearm, and T-score at the forearm compared to patients with asthma and patients without obstructive pulmonary diseases. Conclusions.COPD contributes to more severe course of postmenopausal osteoporosis.

The aim of this study was to assess prevalence of tobacco smoking in healthy young men and to investigate smoking status, prevalence of respiratory symptoms and respiratory diseases and to measure lung function in smokers and non-smokers. Methods.This was a prospective cohort epidemiological study involving healthy male medical students. The participants fulfilled the GARD questionnaire. All participants underwent spirometry. Physical status was assesses with 1-km race time. Fagerstrom test of nicotine dependence was used in smokers. Results. The prevalence of tobacco smoking in young men was 20.9%. Smoking was started at the age of 16 – 20 years in 72.5%. Most smokers were mild smokers with low nicotine dependence and high motivation to continue smoking. Smokers more often had respiratory symptoms, acute respiratory infections, pneumonias, and allergy compared with healthy non-smokers. Conclusion. Based on the results of this study, thorough medical examinations of healthy young smokers is reasonable. Smoking cessation programs should be developed for this cohort.

The aim of this comparative study was a comprehensive analysis of respiratory health in young smokers. Methods. An acoustic analysis of respiratory sounds, spirometry, the Fagerström Test for Nicotine Dependence, and the Questionnaire of the European Community for Coal and Steel (ECCS) on respiratory symptoms were used in this study. Results. The study involved 158 young subjects aged 18 to 19 years (mean age, 18.4 ± 1.1 years; 91 males). A significant difference in spirometric parameters, prevalence of symptoms of chronic bronchitis and the acoustic work of breathing (AWB) was found between smokers and non-smokers. Nicotine dependence was evaluated as weak with lower to moderate exhaled CO levels. However, motivation to continue smoking was moderate or higher; spirometric and AWB parameters were significantly lower in smokers compared to non-smokers. Conclusion. The acoustic analysis of respiratory sounds could be used for clinical and functional evaluation of respiratory status, predicting COPD development and smoking control along with spirometry, specific questionnaires and smoking status assessment.

The most important symptoms of chronic obstructive pulmonary disease are dyspnea, cough and sputum production. According to results of several studies, 50% – 70% of COPD patients under regular therapy continue to experience dyspnea. Dyspnea has a great prognostic importance, it often correlates to exacerbation rate and the patients’ survival. Symptom reduction is one of the key outcomes of therapy of COPD. Measuring tools for assessment dyspnea are imperfect as dyspnea is a subjective feature. Nevertheless, available quantitative tools allow assessment symptom severity in COPD patients. Such tools (modified Medical Research Council scale and COPD Assessment Test – САТ) should be adopted to a medical care level (primary, secondary or tertiary care). Long-acting bronchodilators are the essential component of treatment COPD independently on COPD phenotype. COPD phenotype should be diagnosed before administration of combined drugs containing inhaled steroids (ICS). Long-term therapy with ICS is appropriate for the following groups of patients: overlap COPD and asthma phenotype; high risk of exacerbations (FEV1 < 50% pred., > 2 non-infectious exacerbations or > 1 hospitalization related to non-infectious exacerbation during the previous year); patients with sputum eosinophilia > 3% and / or blood eosinophilia > 300 cells × ml^-1 with consideration of the disease severity. A physician should consider a risk of adverse events of ICS. ICS should not be administered to COPD patients with FEV1 > 50% pred. or having < 2 acute exacerbations or no one hospitalization related to acute exacerbation of COPD during the previous year. ICS could be withdrawn if their administration did not match these criteria. Patients with persistent symptoms under monotherapy with long-acting bronchodilators, ICS / long-acting b2-agonists and who do not match the criteria for treatment with ICS should be treated with indacaterol / glycopyrronium combination.

A high prevalence and social importance of chronic obstructive pulmonary disease (COPD) contribute to economic burden for healthcare systems in many countries. Annual growth of expenses on management this disease provides a need of cost optimization. According to clinical guidelines, bronchodilators, primarily long-acting beta-2-agonists and anticholinergics, are the optimal maintenance therapy of COPD. A promising current approach to treatment COPD is a combination of these classes of drugs. Foreign pharmacoeconomic studies demonstrated new possibilities to affect clinical outcomes and to reduce expenditures on COPD management while using novel fixed combination of these bronchodilators.

A review of published data on clinical efficacy and safety of a new vilanterol/umeclidinium bromide fixed combination in comparison with its separate components and with other long-acting bronchodilators has been performed in this article. Several randomized controlled large trials demonstrated a higher improvement in the airflow limitation and lung hyperinflation under the treatment with the fixed combination of vilanterol and umeclidinium bromide compared to monotherapy with umeclidinium bromide or vilanterol or tiotropium bromide. Vilanterol/umeclidinium bromide fixed combination also improved exertional dyspnea, quality of life and exercise endurance time in stable patients with moderate to severe or very severe chronic obstructive pulmonary disease (COPD). Good tolerability of the drug was noted in all the studies. Vilanterol/umeclidinium bromide fixed combination is delivered via Ellipta dry powder inhaler which was assessed by most patients as a convenient and easy to use inhaler.

The published data confirmed higher clinical efficacy of dual bronchodilator therapy in patients with COPD of categories B, C and D.

Last decades, several drugs for treatment of pulmonary hypertension have been implemented in clinical practice. Sildenafil selectively inhibits phosphodiesterase-5 (PDE-5), increases cyclic guanosine monophosphate (cGMP) level in the pulmonary vascular wall leading to vasodilation, inhibition of proliferation and other specific effects. Sildenafil is indicated as single therapy and in sequential combination therapy of pulmonary arterial hypertension (PAH) (high-level evidence, high-class recommendation). However, therapeutic response on PDE-5 inhibitors is insufficient in a certain number of patients. Soluble guanylate cyclase (sGC) activators were proposed as a good alternative for such patients. Riociguat has dual mechanism of action: firstly, it is designed to increase cGMP biosynthesis via direct activation of sGC; this pathway resembles that of nitric oxide (NO) but is independent on NO. Secondly, riociguat can sensitise sGC to NO. Riociguat is indicated as single therapy and in sequential combination therapy of PAH and to treatment of chronic thromboembolic pulmonary hypertension (high-level evidence, high-class recommendation). A clinical trial RESPITE has been initiated in February, 2014, which is intended to evaluate efficacy of switching PAH patients from PDE-5 inhibitors to riociguat. Potential advantage of this drug is the mechanism independent of NO and of other PDE enzyme isoforms. Whether this advantage is clinically significant, remains to be seen, probably, in the RESPITE trial.

The aim of this article was to review a possible pathogenic role of ghrelin for bronchial asthma (BA). Ghrelin is a hormone participating in energy metabolism. Ghrelin takes part in embryonic lung growth and modulates inflammation and immunity. Ghrelin level is significantly decreased in patients with BA, especially in those with co-morbid obesity, and could decrease in BA patients after physical exercise. Ghrelin level is also significantly decreased during acute exacerbation of BA compared to stable BA. Ghrelin was shown to be inversely associated with bronchial hyperreactivity; therefore, ghrelin could play a protective role against bronchial hyperreactivity. Ghrelin inhibits synthesis of IgE directly or indirectly acting as a pathogenic link between obesity and allergy. Ghrelin inhibits expression of TNF-α, IL-6 и IL-1β, therefore, it should be considered as anti-inflammatory cytokine. In conclusion, ghrelin signaling pathway in BA was not studied completely. Further investigations could discover new approach to therapy of BA with this hormone including patients with BA and co-morbid obesity.

Despite well-known influenza challenge problem and long-lasting experience of influenza vaccination, several aspects of this medical problem require being resolved. Pregnant women are one of the most important risk groups needed in influenza prevention. Inactivated influenza vaccines are proved to be safe, but vaccination coverage of pregnant women has still been low. Based on the immune system particularities in pregnancy, we discussed cell immune response to vaccination. Data on safety and efficacy of influenza vaccination in pregnancy has also been reviewed. This strategy could increase vaccination efficacy in pregnant women and help to develop an individualized approach for use of commercially available vaccines.

Russian Respiratory Society

A case of early physical rehabilitation of a female patient with severe pandemic influenza А / H1N1 complicated by pneumonia and acute respiratory distress syndrome (ARDS) is described in the article. Lymphatic drainage of the lower extremities and the lungs and the chest vibration were used in the patient under mechanical ventilation after achieving clinical stability at the day 2 of staying in a ICU. Postural drainage in combination with the chest and the upper extremities vibration in the Sims’ position were used at the day 3. Active physical exercise with a stretch band and cognitive therapy (reading books, listening to music, and occupational therapy) were started at the day 4. At the day 5, the intubated patient took few steps near the bed assisted by a physical therapist and a physician. After extubation, the patient walked every day in the ward and along the hospital corridor under a control of HR, BP, and SaO2. She used breathing techniques (diaphragmatic breathing, resistive breathing) and physical training. The rehabilitation sessions continued up to the hospital discharge.

Conclusion. Early physical and occupational therapy was found to reduce a risk of polyneuropathy predictive for unfavorable outcome and can improve the airway clearance with reduction of nosocomial infection risk.

A rare case of colonic adenocarcinoma with metastatic lung lesion in a female patient of 43 years old is reported in the article. The diagnostic difficulty of this case was due to absolute lack of both respiratory and gastrointestinal clinical symptoms and signs. Timely scheduled chest fluorographic examination was the starting point of the diagnostic work-up resulted in diagnosis of colon cancer with metastasis to the lungs.