Recently, investigation of asthma-COPD overlap syndrome (ACOS) is an actual topic due to difficulties in diagnosis and treatment. The aim of our study was to investigate HDAC2, PI3K-δ, GR-α, and GR-β relative expressions in order to found markers of steroid sensitivity in ACOS patients. Methods. We examined 31 ACOS patients and 32 control patients. Blood levels of HDAC2, PI3K-δ, GR-α, and GR-β mRNAs were measured by the real-time polymerase chain reaction. Results. Reduced expressions of HDAC2 and GR-α, as well as increased expressions of PI3K-δ and GR-β could result in lower steroid sensitivity and more severe ACOS course. Conclusion. Investigation of pharmacogenetic and epigenetic mechanisms of steroid sensitivity in patients with ACOS could predict the efficacy of steroids and personalize the choice of the targeted treatment.

 

Treatment of patients with chronic obstructive pulmonary disease (COPD) is one of the most important tasks of clinical medicine due to high prevalence of and high mortality from COPD. Treatment of COPD as a heterogeneous disease requires different approaches depending on the severity and the clinical course of COPD. Clinical guidelines have become the principal document that regulates different aspects of management of COPD patients. Algorithms of management and clinical decision making are the crucial part of guidelines because they help achieving a balance between making the decision in different clinical situations and simple graphics. The simplified approach is important for implementation the algorithm into clinical practice. Different evidence-based therapeutic schemes proposed by experts of Russian Respiratory Society and other countries have been enclosed into this article with discussion about their strengths and limitations and possibility of practical use. The Russian algorithm reflects a current view on differentiated management of COPD patients and fits the requirements of Healthcare Ministry of Russian Federation and needs of achieving the optimal balance between high informative significance and a simple graphics of the scheme.

 

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a poor prognosis. In recent years, the development of international diagnostic criteria based on clinical, physiological, radiological, and histopathological appearances, improved diagnosis of IPF. However, currently available clinical data do not accurately predict the course of the disease, which can vary from a slowly progressing to rapidly progressive, and, in 5% of cases, is punctuated by episodes of rapid acute exacerbation. These challenges highlight the need for the development and validation of diagnostic biomarkers specific to IPF and prognostic biomarkers of future disease behavior to guide treatment decisions, including referral for transplant. The recent approval of pirfenidone and nintedanib and the identification of new potential therapeutic targets have created an urgent need for theragnostic markers, i.e. biomarkers able to assess, ideally at an early stage, therapeutic response to a given drug. This will avoid the side effects and increase efficacy of treatment. In addition, the currently available methods are not able to identify the IPF in the early stage to predict the course of disease, and to assess response to antifibrotic therapy. Recent advances in understanding the multiple interrelated pathogenic pathways underlying IPF have identified various molecular phenotypes resulting from complex interactions among genetic, epigenetic, transcriptional, post-transcriptional, metabolic, and environmental factors. The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behavior.

The aim of this review was to analyze abilities of a novel diagnostic method intended to measure the lung function. Volumetric capnography is one of the most promising tools for assessing pulmonary function. This method reflects CO₂ elimination pattern at the exhaled air volume. Changes in CO₂ portion at the tidal volume are related to the integrated evaluation of the respiratory function and could be expressed as the following parameters: emphysema index, the dead space volume, phases 2 and 3 slopes, etc. Possible use of the volumetric capnography for diagnosis of chronic obstructive pulmonary disease, asthma, emphysema, and other respiratory diseases is discussed in the article. This method is simple, non-invasive, and safe. Diagnostic value of the volumetric capnography needs further investigation in order to implement this method in clinical practice.

Topographic and anatomical thoracic changes after pneumonectomy and lobectomy have been reviewed in this article including anatomic changes of the mediastinum, the diaphragm, the chest skeleton, operated and contralateral lungs. Results of Russian and foreign studies have been analyzed. This problem has been investigating more actively after wide implementation of computer tomography in the clinical practice. Certain trends in topographic and anatomical thoracic changes could be noted after pneumonectomy or lung resection. The most typical changes are the mediastinum displacement, diaphragm elevation and thoracic skeletal changes. A few data were published about quantitative postoperative changes. Current life-time imaging is able characterize postoperative changes quantitatively. 3D-modelling can comprehensively describe mechanisms of displacement of the heart, the tracheal bifurcation, the esophagus and large mediastinal vessels. Small number of studies precludes a detailed analysis of gender and constitutional differences and correlational analysis with post-operative ventilation changes. Thus, postoperative topographic and anatomical thoracic and abdominal changes after pulmonary surgery need further investigation.

Severe pulmonary disease in patients with cystic fibrosis (CF) is defined by the airway Pseudomonas aeruginosa infection. P.aeruginosa has still being the leading pathogen which causes progressive respiratory disease and poor prognosis in CF. Adequate and timely treatment of the initial Pseudomonas acquisition could prevent transformation to the chronic infection. This review was aimed at descripting the current antibacterial regimens for early eradication in cases of the initial and recurrent P.aeruginosa acquisition and at discussing factors affecting the treatment efficacy. The early eradication of P.aeruginosa is necessary and extremely important in CF patients. The aggressive pharmacological therapy together with early detection and subsequent microbiological control plays the leading role for the early eradication. The first-line therapy after the initial pathogen acquisition is inhaled tobramycin.

Prematurity and bronchopulmonary dysplasia (BPD), which is a complication of the neonatal respiratory distress-syndrome and respiratory therapy in neonates, are currently considered as possible risk factors of chronic obstructive pulmonary disease (COPD) in adults. Persisting reduction in the lung size in prematurely born children and pathological lesion typical for BPD can lead to ventilation disorders and clinical signs of chronic respiratory failure and / or bronchial obstruction in the children, adolescents and adults. Clinical, functional and morphological consequences of prematurity and BPD in preschool and school-aged children, adolescents and adults are discussed in this review considering the authors’ experience and the published data. The lung function abnormalities persist for lifetime. The lung tissue structural lesions, such as emphysema, fibrosis, the bronchial wall thickening, could be found on computed tomography. Therefore, patients with the history of BPD should be treated as risk group for early development of COPD.

The aim of the study was to investigate efficacy of specific prevention of pneumococcal infection in high-risk group patients living at Krasnoyarsk krai. Methods. The study involved 12,080 patients with a high risk of pneumococcal infection including patients with chronic lung diseases, chronic heart failure (CHF) and diabetes mellitus. A special questionnaire was developed which included medical history for the previous 1 year and for 1 year after the vaccination. Results. CHF was diagnosed in 41.08% of patients, diabetes was diagnosed in 28.44%, chronic lung diseases were diagnosed in 30.07%; 2.4% of patients had pneumonia. PCV13 vaccine (Prevenar 13) was used in 9,986 patients (82.67%) including 5,070 patients (41.97%) vaccinated against flu and pneumococcus simultaneously. PPV23 (Pneumo-23) vaccine was used in 1,967 patients (16.28%) including 1,181 patients (9.83%) vaccinated against flu and pneumococcus simultaneously. Due to the broad-scale vaccination against pneumococcal infection, exacerbation rate reduced trice, number of hospitalisations related to exacerbations reduced by 11.5 times, morbidity of pneumonia reduced by 4.8 times, morbidity of acute respiratory infections and flu reduced by 6.6 times. Conclusion. The results confirmed high efficacy and safety of 13-valent conjugate pneumococcal vaccine and 23-valent polysaccharide pneumococcal vaccine. The vaccination allowed reducing morbidity of respiratory infection and decrease number of hospitalisations due to exacerbations of chronic diseases.

The aim of this study was to investigate structural and functional changes of pulmonary vessels and cardiopulmonary blood flow in COPD patients with different alpha-1-antitrypsin (A1AT) phenotypes and endothelial dysfunction. Methods. Patients with COPD stage 2 to 3 (n = 113) with different A1AT phenotypes underwent clinical and radiological examination; endothelial dysfunction markers were measured. Results. More severe COPD was associated with more severe pulmonary microcirculation disorders and more significant perfusion defects. Patients with ZZ phenotype had worse pulmonary blood flow abnormalities compared to patients with MM phenotype. Pulmonary blood flow abnormalities were closely related to endothelial dysfunction (r = 0.75) and were more significant than structural abnormalities diagnosed on multi spiral computed tomography. Severe disorders of pulmonary blood flow were not accompanied by severe pulmonary hypertension. Conclusions: Blood levels of main endothelial dysfunction markers were directly related to COPD severity. Angiotensin-converting enzyme concentration was significantly below the normal level and was related to pulmonary artery pressure. The pulmonary blood flow differed in patients with different A1AT phenotypes and COPD stage 3 or higher. Perfusion defects were more severe in patients with ZZ phenotype.

The aim of the study was to investigate staging and time of onset of pulmonary inflammation in workers exposed to dust. Methods. This prospective study involved patients (n = 483) with occupational chronic bronchitis (OCB) and chronic obstructive pulmonary disease (COPD). We analyzed medical history, lung function, blood biochemistry, and sputum culturing. Additionally, medical recordts of died patients (n = 180) with occupational lung disease were also analyzed. Results. First symptoms of chronic lung disease occurred after 17.1 ± 1.1 years of occupational hazard exposure in women and after 20.1 ± 1.2 years in smoking men. Occupational etiology of the disease was recognized 5 – 6 years later. Occupational COPD occurred earlier that OCB; this could be explained by genetic predisposition to this disease. Occupational COPD developed independently of respiratory infection excepting patients with concurrent diabetes mellitus. Conclusion. The clinical course of COPD is gradual with initial sighs of OCB followed by bronchial obstruction, probably, in genetically predisposed subjects. The disease occurred earlier in women than in men; this could be related to higher susceptibility of females to inhalational pollutants. The cause of death was lung malignancy in > 50% of patients with occupational lung diseases. Lung tumors were diagnosed significantly later compared to non-pulmonary tumors.

The aim of this study was to compare three semi-quantification scales for prospective assessment of scleroderma-associated interstitial lung disease (SS-ILD) severity. Methods. From 110 prospectively followed patients with SS-ILD, we selected 12 patients (mean age, 42 ± 13 years, 11 females) with obvious improvement (n = 6) or worsening (n = 6) of lung lesions on high resolution computed tomography (HRCT) during a year. The patients had diffuse (n = 7) or limited (n = 7) SS with mean length of the disease of 8.5 ± 6.7 years (range, 1 to 23 years). HRCT was done at baseline (inclusion in the study) and in a year. CT scans were quantitatively assessed by four radiologists including one experienced radiologist. A blinded analysis of HRCT scans was done using three scales: J.H.Warrick et al. (1991), A.U.Wells et al. (1997), and E.A.Kazerooni et al. (1997). The intraclass correlation coefficient (ICC) was calculated to evaluate the assessment reliability. T-test for independent samples was used to evaluate reproducibility of the assessments. Agreement between independent experts' opinions was evaluated using Kendall's rank correlation coefficient. Results. The measurements were significantly divergent between the radiologists, both for the baseline and the follow-up HRCT scans. ICCs for investigated radiological parameters were 0.56 to 0.76. The highest ICC (0.76) was obtained for A.U.Wells' scale. All scales used to assess HRCT scans had lower interoperator reproducibility. Conclusion. Combined use of currently available semi-quantification methods for follow-up assessment of HRCT in SS-ILD patients allowed thorough qualitative evaluation of lung lesions, but the reliability of the radiological parameters in detecting 1-year fibrosis progression in SS patients was low. The risk of significant interoperator bias limited the use of the radiological parameters in clinical trials of SS-ILD patients.

The purpose of the study was to investigate effects of smoking on risk of pulmonary tuberculosis and clinical course of newly diagnosed tuberculosis. Methods. We questioned 342 patients with newly diagnosed pulmonary tuberculosis (of them, 296 active smokers; 86.5%) and 386 healthy individuals (115 smokers; 29.8%). To analyze an effect of smoking on occurrence of pulmonary tuberculosis, the odds ratio (OR), absolute and attributive risks and potential hazard index (number of subjects who should be exposed to a hazardous factor for development one case of a disease) were calculated. Results. Tobacco smoking was associated with 15-fold increase in the risk of tuberculosis (OR 15.16; 95%CI: 10.37; 22.16). This risk was directly related to number of cigarettes smoked per day and to smoking duration. The potential hazard index was less related to number of cigarettes smoked per day (3.87) or smoking duration (4.87) and more closely related to the smoking itself (1.74). Clinical course of pulmonary tuberculosis was analyzed in 296 active smokers with newly diagnosed disease. Conclusion. More severe course of newly diagnosed pulmonary tuberculosis was related to starting tobacco smoking at earlier age, smoking duration, and greater number of cigarettes smoked per day. Furthermore, heavier smoking was associated with more extending lung injury. Tobacco smoking was related to probability of development of pulmonary tuberculosis and to severity of the disease. There is a need of smoking control both in healthy population and in patients with tuberculosis.

This is a review of published data on pulmonary manifestations of ankylosing spondylitis (AS) and a case report of 49-year old male suffering from AS with pulmonary involvement. Lung lesions are frequent extra-articular manifestations of AS. There are a variety of pulmonary manifestations in AS, including lesions of the lung parenchyma, the pleura, the airways and ventilation disorders due to sclerosis of the costovertebral joints and ankylosis of the thoracic spine. An incidence of the lung injury in AS patients has increased significantly after implementation of high-resolution computed tomography (CT). Pulmonary apical fibro-bullous changes were found in CT scans. These lesions are common targets for Aspergillus infection. In the present case, bilateral upper lobe cavitating pneumonia was diagnosed in the patient after exclusion of pulmonary tuberculosis. The patient repeatedly received prolonged antibiotic therapy. His condition deteriorated with development of chronic bilateral pulmonary cavitary aspergillosis. This clinical case demonstrates insufficient knowledge of physicians and radiologists on pulmonary involvement in AS. This leads to therapeutic mistakes and the late diagnosis of pulmonary disease.

A case of recurrent sarcoidosis of intrathoracic lymth nodes and the lungs with development of tumor-like sarcoid granuloma narrowing the middle lobe bronchus and the right intermediate bronchus is reported in the article. The tumor-like sarcoid endobronchial mass was destructed using endoscopic Holmium YAG lazer. Combined treatment with endoscopic lazer ablation and systemic steroids resulted in successful reopening the bronchi.

Combination therapy with long-acting β2-agonists (LABA) and long-acting muscarinic antagonists (LAMA) can reduce symptoms of chronic obstructive pulmonary disease (COPD) and the risk of future exacerbations. To date, the only fixed combination of long-acting bronchodilators, indacaterol/glycopyrronium, has demonstrated a significant reduction in dyspnea and in the risk of moderate and severe exacerbations of COPD in clinical trials when compared with the combination of salmeterol/fluticasone. Addition of inhaled steroids (ICS) to long-acting bronchodilators is recommended for patients with recurrent COPD exacerbations, especially in those with asthma-COPD overlap syndrome or history of elevated blood or sputum eosinophil levels. It is recommended to consider phenotype-specific therapy including roflumilast, N-acetylcysteine, and macrolides, in patients who continue to exacerbate despite being treated with LABA/LAMA or LABA/LAMA/ICS combinations. Withdrawal of inhaled corticosteroids is possible in patients with the low risk of exacerbation and in those with severe adverse events during ICS treatment. ICS should be withdrawn in a single step in patients with no repeated exacerbations during 12 months and with moderate bronchial obstruction (FEV1 ≥ 50% predicted). Stepwise withdrawal of ICS during 3 month with continuous dual bronchodilator therapy is recommended in COPD patients with severe bronchial obstruction (FEV1 ˂ 50% predicted) without frequent exacerbations in the previous year.

Late diagnosis of chronic obstructive pulmonary disease (COPD) at advanced stage, high risk of exacerbations, low compliance of patients, and adverse effects of treatment have been still unresolved problems in the treatment of COPD despite the development of new drugs. The personalized medicine rneeds distinct indications and predictors of efficacy and safety of treatment. Budesonide/formoterol fixed combination is recommended for patients with asthma – COPD overlap syndrome and bronchitis phenotype, blood eosinophilia > 300 cells/mm³, if other causes were excluded, post-bronchodilator forced expiratory volume in 1 second (FEV₁) < 50% pred.; and ≥ 2 exacerbations or ≥ 1 hospitalization related to exacerbation during the previous year. Budesonide/formoterol fixed combination is not recommended for regular use in patients with emphysema phenotype of COPD and rare exacerbations (< 2 exacerbations and without hospitalizations in the previous year).

Inhalation therapy is a modern and preferable method of drug delivery which is currently used for treatment of majority of acute and chronic respiratory diseases in children and adults. Recently, inhalation devices have evolved significantly. Scientific researches are focused on interaction between drug molecules and aerosol-producing device. The efficacy of inhalation therapy is generally depends on the drug, its dose and technical parameters of the device. Inhalation devices that are able effectively produce drug aerosol have been used for treatment of most pediatric diseases. Advantages of this therapy are quick onset of the action, the possibility to reduce a drug dose due to higher drug concentration in the airways and to decrease the risk of adverse events, and independence of the liver metabolism. Nebulized therapy has been currently used for therapy of the majority of pediatric respiratory diseases. Drug formulation diversity and ability to combine > 2 drugs could enhance the treatment efficacy.