Vol 92, No 3 (2020)

The Universal Declaration on Bioethics and Human Rights was adopted at the UNESCO General Conference on October 19, 2005. From today's perspective, it must be recognized that it was adopted at a historically important period in the development of civilization; It has always been seen as a document that significantly expanded the declaration on human rights, as it gave a new interpretation of human activity in modern society. Next year marks 25 years of active implementation of the main provisions of the declaration in the field of education, research and cultural heritage. Scientific ideas about the world were changing dynamically, new pedagogical technologies developed, society more than ever began to perceive cultural heritage more acutely. Under the influence of these processes, our ideas about moral values ​​and ethical principles changed. An idea of ​​bioethics has formed; The term implies versatile human activities, including not only the doctor-patient relationship, but also the active participation of a person in the field of industry, climate change, as well as new areas such as editing the human genome, transplantology and much more.

Chronic obstructive pulmonary disease (COPD) is an important public health problem. According to various studies, the prevalence of obesity in patients with COPD is as high as 50%.

Aim. To evaluate pro- and anti-inflammatory cytokine profile, lung diseases biomarkers levels and adipokines levels in patients with COPD and obesity.

Materials and methods. The study included 88 patients with COPD (GOLD 2–4, group D). Patients were divided into two groups. The first group consisted of 44 patients with COPD and normal body weight: 35 men and 9 women. The second group – 44 patients with obesity and COPD: 34 men and 10 women. The levels of pro- and anti-inflammatory cytokines were determined – interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor  (TNF-), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as the concentration of highly sensitive C-reactive protein (CRP), surfactant protein D, elastase, leptin, adiponectin, 1-antitrypsin, receptors of tumor necrosis factor 1 and 2 (TNF-R1, TNF-R2).

Results. In patients with COPD and obesity, compared with patients with COPD and normal body weight, the levels of CRP, interferon-, TNF-, TNF-R1, TNF-R2 were significantly higher. At the same time, the levels of IL-4, IL-6, IL-8, IL-10 did not differ significantly. The level of leptin in patients with COPD and obesity was significantly higher than in patients with COPD and normal body weight.

Conclusion. In patients with COPD and obesity, in contrast to patients with COPD with normal body weight, the severity of systemic inflammation is significantly higher. However, further research is needed in this area.

Aim. To assess the risk of exacerbations of bronchial asthma (BA) in smoking patients with the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) after inpatient treatment.

Materials and methods. 36 smokers with ACO (main group) and 36 non-smoking patients (control group) with severe or moderate exacerbation of bronchial asthma were examined. Assessment of the severity of exacerbation of BA before treatment, levels of control and risk of exacerbations of BA after treatment was determined according to the Federal clinical guidelines for the diagnosis and treatment of BA (2016). Spirometry, monitoring of blood oxygenation using transcutaneous spectral pulse oximetry and enzyme immunoassay for determination of matrix metalloproteinases 9 were performed. Smoking experience, smoking index and pack/years index were taken into account in patients with ACO. The carboxyhaemoglobin level was analyzed by the carbon monoxide fraction in the exhaled air.

Results. For the first time in patients with the ACO, the ability of «heavy» tobacco smoking and associated decrease in blood oxygenation to potentiate the negative impact of other predictors on the risk of exacerbations of the underlying disease was revealed. In smoking patients with the ACO, for the first time, a direct association of higher levels of matrix metalloproteinases 9 (measured before inpatient treatment) with such a predictor of the risk of further exacerbations of the disease as more frequent detection of symptoms of uncontrolled BA was revealed. In non-smoking patients with BA, a direct relationship between increased sputum secretion and eosinophilia of blood and/or sputum (a predictor of exacerbation of BA) and the relative duration of episodes of decreased blood oxygenation was established.

Conclusion. It was found that intensive and prolonged smoking increases the duration and reduces the effectiveness of inpatient treatment of patients with ACO, contributing to the preservation of air traps and low (forced expiratory volume in 1 second <60%) ventilation capacity of the lungs with the persistence of moderately reduced blood oxygenation; the risk of further exacerbations of BA in this phenotype of patients is significantly higher than in non-smoking patients with BA without combination with COPD.

Chronic obstructive pulmonary disease (COPD) is a group of diseases with high levels of comorbidity. Pathological changes of peripheral skeletal and respiratory muscles in COPD patients, which are often underestimated, occupy a special place.

Aim. To study the relationship between functional and quantitative parameters of the peripheral (limb muscle) and respiratory muscles in COPD patients.

Materials and methods. 127 patients (98 men/29 women, mean age 67.6±8.2 years) were under observation without acute COPD. All COPD patients were classified according to GOLD (2019) into groups A, B, C, D. The algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP2) was used to diagnose sarcopenia. The muscle mass was measured using dual energy X-ray absorptiometry (DXA) and the appendicular lean mass index (ASM) was estimated. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured by body plethysmograph MasterScreen Body. Quantitative assessment of thoracic muscle cross-sectional areas were performed using the CT scan using Vidar Dicom Viewer software.

Results. Sarcopenia was diagnosed in 43.3% of COPD patients. Respiratory muscle dysfunction was determined in 66.1% of patients with COPD, its probability increased in groups C and D in comparison with groups A and B [chance ratio 6.6 (95% confidence interval 2.9–15.0); p<0.0001]. Correlations between the functional parameters of sarcopenia and respiratory muscle strength as well as between the mass of peripheral skeletal muscles and respiratory muscle area have been established according to the data of computerized tomography (р<0.01). Sarcopenia as well as respiratory muscle dysfunction was observed more frequently in persons with severe and extremely severe airway obstruction and in patients with predominantly emphysematic COPD phenotype (p<0.01).

Conclusion. Sarcopenia is a frequent comorbidity in COPD and its development is connected with the severity of the course of the main disease. Correlation between parameters of peripheral (limb muscle) and respiratory muscles in patients with COPD has been determined.

Aim. To assess the effectiveness of the use of the antiviral drug enisamium iodide in the complex treatment of acute respiratory viral infections (ARVI) caused by various pathogens in routine clinical practice.

Materials and methods. А prospective randomized study included 134 patients who were treated in the epidemic season of influenza and ARVI in 2018–2019. All patients were examined for the presence of influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, rhinoviruses, adenoviruses in nasopharyngeal swabs by PCR. Patients of the main group received enisamium iodide along with symptomatic therapy, the control group received only symptomatic therapy. The primary parameter of the effectiveness of therapy was evaluated on the scale of the general severity of the manifestations of ARVI (Total Symptom Score – TSS) from the 2nd to the 4th day and by the secondary criteria of effectiveness: assessment of the duration of ARVI, the severity of fever, the proportion of patients with normal body temperature, the duration of the main clinical symptoms of acute respiratory viral infections, the proportion of patients in whom complications requiring antibiotics were noted, the dynamics of interferon status on the 6th day. To conduct a statistical analysis, depending on the efficiency parameter, the ANCOVA method with a fixed group factor and an initial score on the TSS severity scale was used as covariates, a criterion for comparing quantitative indicators in two independent groups.

Results. According to the results of the analysis of the primary efficacy parameter, the median (interquartile range) of the average score on the scale of the general severity of ARVI manifestations in the main group was 4.33 (3.67–5.83), in the comparison group – 6.00 (4.67–7.25; p<0.001). The duration of systemic and local manifestations of acute respiratory viral infections was statistically significantly less in the main group (p=0.002 and p=0.019, respectively). Prescription of additional therapy was required in 2 (2.9%) patients of the main group (patients taking enisamium iodide), compared with 8 (11.9%) patients in the control group. Serum levels of interferon  and interferon  on the last day of treatment were statistically significantly higher in patients of the main group compared with the control group (p<0.001). Treatment (excellent) was evaluated by 42 (62.7%) patients, while in the control group only 17 (25.8%) patients gave similar ratings. Both patients (p<0.001) and doctors (p<0.002) rated therapy tolerance better in the study group.

Conclusion. The results confirmed the safety and effectiveness of enisamium iodide as a treatment for ARVI and influenza. The antiviral, interferonogenic and anti-inflammatory properties of the drug are involved in the formation of an antiviral response and reduce the risk of complications, which makes it possible to reduce the number of symptomatic agents used.

Tuberculosis is a chronic infectious disease, usually localized in the respiratory system and representing one of the most important global social and biomedical health problems associated with the spread of therapy-resistant forms (multidrug-resistant and extensively drug-resistant tuberculosis). One of the most promising targets for the development of antimycobacterial drugs is the enzyme DprE1, which is involved in the synthesis of the cell wall of mycobacteria. In the series of DprE1 inhibitor drugs, the most advanced drug is PBTZ169 (INN maсozinone). Clinical trials (CT) of the efficacy and safety of macozinone are conducted by the pharmaceutical company LLC NEARMEDIC PLUS in the Russian Federation, and in other countries (Sponsors: Innovative Medicines for Tuberculosis Foundation, École polytechnique fédérale de Lausanne and Bill and Melinda Gates Foundation). The publication describes results of completed I, IIa and Ib phases CT, conducted in the Russian Federation.

Aim. The goal of phase I CT was to assess the safety, tolerability and pharmacokinetics (PK) of PBTZ169, 40 mg capsule, after single and multiple administration under fasting conditions in increasing doses in healthy volunteers. The goal of phase IIa CT was to study the efficacy (in terms of early bactericidal activity – EBA), safety and PK of the drug PBTZ169, 80 mg capsules, in various doses, when used as monotherapy in patients with newly diagnosed respiratory tuberculosis with bacterial excretion and retained sensitivity to isoniazid and rifampicin. The purpose of phase Ib CT was to evaluate the safety, tolerability, PK of PBTZ169, 80 mg capsule, after single, double and multiple administration under fasting conditions in increasing doses, as well as the effect of food on its bioavailability in healthy volunteers.

Materials and methods. The data of 100 healthy volunteers and 15 patients with newly diagnosed pulmonary tuberculosis, who received the study medication PBTZ169, capsules 40 mg and 80 mg, in the dose range 40 mg – 1280 mg of PBTZ169, obtained during phase I, IIa and Ib CTs were analyzed. During I phases CTs, safety, tolerability, and PK of the drug after a single and multiple administration under fasting condition and after meals at rising doses were evaluated. The safety assessment included evaluation of AE/SAE, vital signs, ECG results, and laboratory tests results in the safety population. In the course of phase IIa CT, in addition to safety, tolerance, and PK evaluation, the efficacy of the drug (in terms of EBA) using sputum culture on agar with CFU/ml counting (main method) and quantitative PCR method (auxiliary method) was evaluated.

Results. During all CTs, a high safety and tolerability profile was shown, the main PK parameters of the drug and the efficacy were described. PBTZ169 demonstrated linear PK in the dosage range up to 640 mg after single and multiple administration, a statistically significant of EBA of the drug after monotherapy at the dose of 640 mg/day was demonstrate, and it was concluded that the preferred regimen of the drug PBTZ169 intake is administration after meals. Good tolerability and a favorable safety profile of the drug in the studied doses range were demonstrate during all the CTs.

Conclusion. One of the most promising and currently studied drugs-inhibitors of DprE1, a new target for the cell wall of mycobacteria, is PBTZ169 or macozinone, which is being develop by the Russian pharmaceutical company NEARMEDIC PLUS ltd.

Due to the global aging of the population, the deteriorating ecology and lifestyle changes, patients with isolated cardiovascular diseases (CVD) are becoming less common, and the portrait of a comorbid patient comes first in the structure of patients with CVD. Among a number of diseases complicating and concomitant with cardiovascular, a special place is occupied by chronic obstructive pulmonary disease (COPD). The prevalence of COPD among CVD patients can reach 60%. Many of the pathophysiological mechanisms underlying COPD can increase the risk of cardiovascular disease and vice versa. The most common cases of COPD are arterial hypertension, coronary heart disease, heart failure, and atrial fibrillation. Given the close relationship between COPD and CVD, it is clear that treatment for one condition can affect another. This review discusses current positions about the influence of both groups of diseases on each other, and also observes the effects of drug therapy of both diseases.

The article presents modern data on the causes of platypnea, methods of its diagnosis and treatment. The data on the development of platypnea syndrome are given not only in cardiac pathology, but also in severe liver diseases with the development of hepatopulmonary syndrome and chronic obstructive pulmonary disease of a severe course.

The review is devoted to the urgent problem of modern pulmonology: the differential diagnosis of idiopathic pulmonary fibrosis (ILF). ILF occupies a special place among many interstitial lung diseases for a number of reasons: 1) it is a deadly disease; 2) early diagnosis and adequate antifibrotic therapy significantly extend the life expectancy of patients; 3) anti-inflammatory drugs (corticosteroids) and cytostatics with ILF that are widely used in other forms of interstitial lung diseases are ineffective and accelerate the progression of the process; 4) the commonality of the main clinical signs (increasing respiratory failure) of various interstitial lung diseases. The list of respiratory diseases with which ILF should be differentiated is huge, and if with diffuse lung lesions of a known nature (disseminated pulmonary tuberculosis, pneumoconiosis, etc.) with a certain experience/qualification, the diagnosis is relatively simple, then the isolation of ILF from the group of idiopathic interstitial pneumonias always represents certain difficulties. The main methods used in the diagnosis of ILF are summarized taking into account current international and national recommendations.

Emphysema is one of the main manifestations of chronic obstructive pulmonary disease (COPD), and smoking is one of the most significant risk factors. The results of studies in humans and animals show the vascular endothelium initiates and modulates the main pathological processes in COPD and smoking is an important factor initiating, developing and persisting inflammation and remodeling of blood vessels and tissues, including the destruction of small respiratory tracts with the development of lung tissue destruction and emphysema. The latest studies describe mechanisms not just associated with the endothelium, but specific neuro-mediated mechanisms. There is reason to believe that neuro-mediated and neuro-similar mechanisms associated and not related to endothelial dysfunction may play the significant role in the pathogenesis of COPD and emphysema formation. Information about components and mechanisms of neurogenic inflammation in emphysema development is fragmentary and not systematized in the literature. It is described that long-term tobacco smoking can initiate processes not only of cells and tissues damage, but also become a trigger for excessive release of neurotransmitters, which entails whole cascades of adverse reactions that have an effect on emphysema formation. With prolonged and/or intensive stimulation of sensor fibers, excessive release of neuropeptides is accompanied by a number of plastic and destructive processes due to a cascade of pathological reactions of neurogenic inflammation, the main participants of which are classical neuropeptides and their receptors. The most important consequences can be the maintenance and stagnation of chronic inflammation, activation of the mechanisms of destruction and remodeling, inadequate repair processes in response to damage, resulting in irreversible loss of lung tissue. For future research, there is interest to evaluate the possibilities of therapeutic and prophylactic effects on neuro-mediated mechanisms of endothelial dysfunction and damage emphysema in COPD and smoking development.

Alexander Grigorievich Chuchalin is a world-famous scientist, an outstanding representative of modern Russian medical science and practical health care, the founder of a whole area in Russian medicine - pulmonology. Thanks to his activities, his unique developments in Russia and abroad, millions of people with lung diseases have been saved. The whole domestic and world medical community congratulates Alexander Grigoryevich on his eightieth birthday!

Idiopathic pulmonary fibrosis (IPF) is usually characterized by a chronic and slowly progressive course. According to several studies, a small number of patients with IPF (about 5–15%) develops an acute deterioration of deasese – exacerbation of IPF. Exacerbations of IPF can occur at any time of the disease and sometimes becomes the first manifestation of IPF. Pulmonary hypertension in IPF is a fairly frequent complication, which leads to severe violations of gas exchange and reduced tolerance to physical stress. Currently, proven effective treatments for exacerbations of IPF do not exist, the management of this condition is based on supportive therapy (oxygen, respiratory support) and interventions with inadequate evidences (corticosteroids, immunosuppressant). During exacerbation of IPF a careful search of all the possible triggers is justified. In the presented clinical case of exacerbation of IPF there was demonstrated the efficacy of complex therapy including antifibrotic therapy, PAH-specific medicines and enhanced oxygen therapy.