Vol 94, No 3 (2022)

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Full Issue


Dyspnea: neurobiological and clinical aspects

Chuchalin A.G.


An analysis of the results of studies carried out by specialists of the Russian Respiratory Society over the past 15 years is given. The article also includes the main provisions set out in the III Guidelines for dyspnea. A significant part of the manual is devoted to the recent achievements in studying neurophysiological processes in the brain structures during the development of dyspnea. These achievements were driven by image-diagnosis methods. An important aspect of this series of works for the clinical practice was identifying dyspnea domains and developing the instruments to assess severity. Analysis of the data on dyspnea from the clinical practice showed a highly heterogenic clinical picture, which must be taken into account in the management of individual patients. A diagnostic algorithm for long-term follow-up of patients with dyspnea syndrome is also discussed. The attention of doctors is drawn to the features of dyspnea during COVID-19; the disproportion between the sensory perception of respiratory discomfort and the degree of oxygen desaturation is emphasized. It was concluded that in the Russian-speaking environment of patients, doctors should actively use a verbal characteristic of dyspnea – the “language of dyspnea”.

Terapevticheskii arkhiv. 2022;94(3):367-371
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Original articles

Hydrogen effect on the mechanisms of mucosal immunity in patients with COVID-19

Svitich O.A., Baranova I.A., Kryukova N.O., Poddubikov A.V., Vinnitskaya A.B., Abramova N.D., Zakharova V.V., Shogenova L.V., Kostinov M.P., Chuchalin A.G.


Aim. To study the inhalation of an active form of hydrogen effect to mucosal and system immunity in a rehabilitation program for health workers.

Materials and methods. The study involved patients that survived COVID-19 after therapy with inhaled hydrogen for 90 minutes (n=30), and a control group of patients treated according to standard protocol for managing patients that survived COVID-19 during the rehabilitation period (n=30). Biomaterial was carried out in 2 stages: on the first day of the study, before the accepted therapy and on the 10th day of the study. The indicators of humoral and cellular immunity were studied. The levels of secretory immunoglobulin A (sIgA) and IgG were investigated using the method of enzyme-linked immunosorbent assay. Phagocytosis was assessed on a Beckman Coulter FC-500 flow cytometer. Statistical data processing was carried out in the GraphPad Prism 7.00 software using nonparametric methods.

Results. It was shown that the phagocytic index (PI) of monocytes in nasal scrapings after inhaled hydrogen treatment did not significantly change relative to the first day of treatment and control, while the PI of granulocytes in nasal scrapings significantly increased relative to the first day by 2.5 times (p=0.000189), as well as relative to the control by 1.1 times (p=0.047410). PI of monocytes in pharyngeal scrapings showed a significant increase relative to the first day of treatment by 2.8 times (p=0.041103), however, did not differ relative to the control. PI of granulocytes of pharyngeal scraping did not differ significantly relative to the first day and control. PI of granulocytes and blood monocytes of the studied group did not change significantly. PI of granulocytes and monocytes of peripheral blood relative to control during therapy did not change. The sIgA level in nasal scrapings significantly increased by 2.9 times, while in pharyngeal scrapings the level of sIgA significantly decreased by 2 times.

Сonclusion. We have shown an increase in granulocytes PI in the nasal cavity and oral monocytes, as well as in the level of sIgA in the nasal cavity during therapy with active hydrogen. The data obtained indicate the effectiveness of therapy, which can be used both in the treatment of COVID-19, and in post-COVID syndrome as an additional therapy. The absence of changes in blood parameters, as well as individual links in nasal and pharyngeal scrapings, requires further study to develop ways to overcome treatment tolerance.

Terapevticheskii arkhiv. 2022;94(3):372-377
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Long-term follow-up study of post-COVID-19 patients

Karchevskaya N.A., Skorobogach I.M., Cherniak A.V., Migunova E.V., Leshchinskaya O.V., Kalmanova E.N., Bulanov A.I., Ostrovskaya E.A., Kostin A.I., Nikulina V.P., Kravchenko N.I., Belevskiy A.S., Petrikov S.S.


Aim. To evaluate dynamic changes in the lungs, hemostasis system, immune system in different terms after coronavirus pneumonia.

Materials and methods. Ventilation-perfusion single-photon emission computed tomography/computed tomography (CT), functional methods of lung investigation, evaluation of hemostasis system, immune status and specific humoral immune response were performed and evaluated in different terms after coronavirus pneumonia. A total of 71 patients were examined according to this protocol. We examined patients with the lesion volume not less than 50% according to chest CT. All patients were divided into 2 groups depending on the distance from the acute stage of coronavirus pneumonia. Group 1 included patients who were examined early (30–60 days after hospital discharge), group 2 included patients who were examined later (61–180 days after hospital discharge).

Results. We obtained gradual regression of pathologically-modified tissue from 67.3% during the inpatient phase to 30.9% during the early period and to 19.7% during the late period of examination, according to CT scan of the chest organs. The same tendency was demonstrated by diffusion capacity of the lungs. Perfusion scintigraphy data showed a decrease in perfusion deficit from 26.0±12.8% during the early period of examination to 19.4±6.2% during the late period of examination. On the contrary, ventilatory scintigraphy demonstrates the increase of isotope passage time through the alveolar-capillary membrane over time (from 48.2±31.3 minutes in the early period to 83.6±37.2 minutes in the late period). An increase in D-dimer was detected in 24% of patients in the early group. The levels of inflammatory markers, indices of immune status, and specific humoral immune response did not differ in the two described groups.

Conclusion. The results demonstrate gradual regression of pathological changes caused by coronavirus infection.

Terapevticheskii arkhiv. 2022;94(3):378-388
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Predictors of dysfunction of the small respiratory tract in patients with asthma

Yurenko A.V., Antonyuk M.V., Mineeva E.E., Gvozdenko T.A.


Aim. To identify predictors of development of small respiratory tract (SRT) dysfunction in patients with asthma of mild severity, partially controlled course.

Materials and methods. One hundred and fourteen patients with asthma of mild severity, partially controlled course, were examined. The control group consisted of 27 healthy volunteers. The main risk factors for the development of AD were revealed by questioning in all patients, an ACQ-5 test was used to determine the level of disease control, functional research was carried out using spirography and bodyplethysmography methods. To assess the relative risk, the odds ratio calculation was used.

Results. 55% of all examined patients with asthma indicated 3 or more risk factors. Bronchial obstruction occurred in 26.3% of cases. According to the functional examination, patients are divided into 2 groups: 94 patients without dysfunction of the SRT and 20 patients with dysfunction of the SRT (17.5% of cases). The significance of differences in the development of dysfunction of the SRT depending on the impact of the risk factor between groups of patients was assessed. Among the traditional risk factors for asthma, the most negatively affecting the development of dysfunction of the SRT in patients were identified. It has been established that the duration of asthma disease for more than 5 years, the symptoms of bronchial obstruction diagnosed in patients increase the risk of dysfunction of the SRT by 4.95 and 4.83 times, respectively, the presence of extrapulmonary allergic diseases, namely allergic rhinitis – by 4.31 times, urticaria – 3.58 times.

Conclusion. It has been shown that the most significant factors affecting the occurrence of dysfunction of the SRT in patients with asthma of mild severity are the duration of asthma for more than 5 years, the presence of extrapulmonary allergic diseases in patients (allergic rhinitis and urticaria) and bronchial obstruction in patients.

Terapevticheskii arkhiv. 2022;94(3):389-395
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Experience of using a triple fixed combination in the treatment of patients with chronic obstructive pulmonary disease

Bolotova E.V., Dudnikova A.V., Shulzhenko L.V.


Aim. To evaluate the effectiveness of a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate in the treatment of chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations.

Materials and methods. The study included 46 patients with severe and extremely severe COPD (GOLD 3–4) with frequent exacerbations. All patients were divided into 2 groups. The 1st group included 22 COPD patients with a content of eosinophils in the peripheral blood of ≥300 cells/ml, the 2nd group included 24 COPD patients with no signs of eosinophilic inflammation in the peripheral blood. Group 1 patients were recommended therapy with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate at a dose of 22/55/92 mcg 1 time per day, group 2 patients received vilanterol+umeclidinium bromide at a dose of 22/55 mcg 1 time per day. The duration of follow-up was 12 months.

Results. After 12 months of treatment with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate, a statistically significant decrease in peripheral blood eosinophilia was noted in patients with COPD with frequent exacerbations and peripheral blood eosinophilia (p=0.001), as well as a decrease in shortness of breath on the MMRs scale (p=0.001) and the frequency of exacerbations in patients with COPD with frequent exacerbations and eosinophilia (p=0.001).

Conclusion. The use of a fixed combination of vilanterol/umeclidinium bromide/fluticasone furoate for 12 months allowed to reduce the impact of the disease, improve respiratory function and quality of life in COPD patients with eosinophilia.

Terapevticheskii arkhiv. 2022;94(3):396-400
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Analysis of the dynamics of mortality from respiratory diseases in the Russian Federation for 2019–2020

Drapkina O.M., Samorodskaya I.V., Bolotova E.V., Dudnikova A.V.


Aim. To study the dynamics and contribution of mortality from Diseases of the respiratory system (DRS) in 2019 and 2020 to mortality from all causes with and without deaths from COVID-19 in 82 regions of the Russian Federation.

Materials and methods. The data provided by Rosstat for 2019 and 2020 on the average annual population and the number of deaths due to causes of DRS (class J00–J99) were used the standardised death rate (SDR) were calculated, the regional average value, standard deviation and coefficient of variation.

Results. The average increase in the SDR from DRS in 2020 was 22.19±13.22 per 100 thousand population (66.44±89.6% higher than in 2019). The average regional SDR from DRS + COVID-19 in 2020 was higher than the SDR from DRS in 2019 by 87.65±30.1 per 100 thousand population. The average regional share of SDR in the structure of mortality excluding COVID-19 increased from 3.66±1.44 to 5.06±2.49%; taking into account COVID-19, it increased to 10.96±3.13%. In 16 regions, the SDR from DRS + COVID-19 exceeded the increase in mortality from all causes. No correlation was found between SDR (2020) from all causes and SDR from COVID-19 (r=0.09; p=0.39); an inverse correlation was found between SDR from DRS and SDR from COVID-19 in 2020 (r=-0.42; p<0.0001).

Conclusion. Against the background of high interregional variability of SDR from DRS in most regions, an increase in the mortality rate from DRS and the contribution of DRS to total mortality in 2020 was registered.

Terapevticheskii arkhiv. 2022;94(3):401-408
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The role of artificial intelligence in assessing the progression of fibrosing lung diseases

Speranskaia A.A.


Introduction. The widespread use of artificial intelligence (AI) programs during the COVID-19 pandemic to assess the exact volume of lung tissue damage has allowed them to train a large number of radiologists. The simplicity of the program for determining the volume of the affected lung tissue in acute interstitial pneumonia, which has density indicators in the range from -200 HU to -730 HU, which includes the density indicators of "ground glass" and reticulation (the main radiation patterns in COVID-19) allows you to accurately determine the degree of prevalence process. The characteristics of chronic interstitial pneumonia, which are progressive in nature, fit into the same density framework.

Аim. To аssess AI's ability to assess the progression of fibrosing lung disease using lung volume counting programs used for COVID-19 and chronic obstructive pulmonary disease.

Results. Retrospective analysis of computed tomography data during follow-up of 75 patients with progressive fibrosing lung disease made it possible to assess the prevalence and growth of interstitial lesions.

Conclusion. Using the experience of using AI programs to assess acute interstitial pneumonia in COVID-19 can be applied to chronic interstitial pneumonia.

Terapevticheskii arkhiv. 2022;94(3):409-412
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Analysis of predictors of response to anti-IgE therapy in patients with severe atopic bronchial asthma in real clinical practice

Fomina D.S., Mukhina O.A., Lebedkina M.S., Gadzhieva M.K., Bobrikova E.N., Sinyavkin D.O., Parshin V.V., Chernov A.A., Belevskiy A.S.


Introduction. Guidelines on Biological Therapy for Bronchial Asthma of the European Academy of Allergy and Clinical Immunology (EAACI) identified a number of controversial issues for additional outcome analysis using randomized clinical trials and data from routine clinical practice. In particular, there is unmet need to clarify algorithms for prescribing biologicals using predictor’s of response and its timing, taking into account risk factors and multimorbidity. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody of IgG1 class used for the treatment of severe refractory atopic bronchial asthma (BA) and a variety of IgE-mediated diseases. Among biological agents, this "pioneer molecule" has the greatest experience in the "allergology and immunology" profile. Detailed description of the "nonresponders" portraits will allow to perform the therapy response assessment on time and facilitate rational planning of individual therapy, which is a prerequisite for biologicals era. Using only routine methods, it is possible to perform initial and dynamic screening to phenotype a heterogeneous cohort of patients with severe asthma and chose the optimal strategy.

Aim. To identify predictors of nonresponse to omalizumab anti-IgE therapy in patients with severe atopic BA and to establish optimal timing of efficacy assessment using retrospective analysis of data from the Biologic Therapy Registry of Allergology and Immunology in routine clinical practice.

Materials and methods. A retrospective single-center registry study was conducted at the Allergy and Immunology Reference Center from June 2017 to August 2021. 135 patients with severe BA, with confirmed perennial sensitization, who received omalizumab according to the recommendations of the current version of GINA, were selected from the clinical and dynamic observational system (registry). Dosing regimen and administration frequency of omalizumab were determined in accordance with the instructions for the drug. Assessment of therapy efficacy was performed at the time point 4, 6 and 12 months. Patients were subgrouped into "responders" and "non-responders" according to the following criteria: ACT score less than 19 and/or difference between initial ACT score in dynamics less than 3 points; forced expiratory volume in the first second less than 80%; combination of these two criteria. Nonparametric methods of descriptive statistics were used in data processing: median, interquartile range. Differences were considered significant at p<0.05. Mann–Whitney U-test, Kruskal–Wallis one-way analysis of variance, and Fisher's χ2 test were used to compare quantitative characteristics.

Results. Heterogeneous subgroups of patients differing in reaching the criteria of "non-responders" to treatment were identified; the informativity of modifiable and unmodifiable factors differed at time-points of dynamic observation. In the differential analysis, two profiles of "nonresponders" were defined in combination with the most significant predictors of "nonrsponse" to omalizumab. According to the data obtained, one of the clinical phenotypes, namely the combination of severe asthma with the Samter’s triad, corresponded to the characteristics of the patient "nonresponders": age of onset is about 30 years, females, severe exacerbations of BA while taking non-steroidal anti-inflammatory drugs, accompanied with high levels of eosinophilia.

Conclusion. The data obtained illustrates the hypothesis of pathogenetic heterogeneity of severe BA with the phenomenon of overlapping phenotypes and can serve as an additional orienteer for creating the individual plan of anti-IgE therapy in real clinical practice.

Terapevticheskii arkhiv. 2022;94(3):413-419
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Clinical notes

Differential diagnosis of pneumonia as a complication of nasal liquorrhea in the context of the COVID-19 pandemic: Case report

Chernikova N.A., Shelesko E.V., Sharipov O.I., Ershova O.N., Kalinin P.L., Kutin M.A., Fomichev D.V.


Nasal liquorrhea – the outflow of cerebrospinal fluid from the cerebrospinal fluid spaces of the cranial cavity into the nasal cavity or paranasal sinuses due to the presence of a congenital or acquired defect in the bones of the skull base and meninges of various etiologies. Nasal liquorrhea leads to potentially fatal complications: meningitis, meningoencephalitis, pneumocephalus, brain abscess. Also, with nasal liquorrhea, less dangerous complications may occur: aspiration bronchopneumonia and gastritis. The article presents a case of aspiration pneumonia in two patients with nasal liquorrhea treated at the Burdenko National Medical Research Center for Neurosurgery during the COVID-19 pandemic. Both patients noted the profuse nature of the nasal liquorrhea, complained of coughing in a horizontal position. In both cases, no RNA virus (SARS-CoV-2) was detected during the polymerase chain reaction. Antibodies (IgG, M) to coronavirus were not detected. Computed tomography of the chest organs in both cases revealed areas of frosted glass darkening. Since no data was obtained for coronavirus infection (negative tests for coronavirus, lack of antibodies), changes in the lungs were interpreted as a consequence of constant aspiration of CSF. The patients were admitted to a separate ward. Both patients underwent endoscopic endonasal plasty of the skull base defect. The postoperative period in both cases was uneventful. In both cases, the patients underwent computer tomography scan of the chest organs one month later. On the photographs, the signs of pneumonia completely regressed.

Terapevticheskii arkhiv. 2022;94(3):420-426
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Principles of modern diagnosis and treatment of atopic dermatitis and bronchial asthma: Clinical case

Shogenova M.S., Hutueva S.H., Shogenova L.S.


This article presents the experience of successful use of the drug dupilumab in a patient with severe atopic dermatitis and bronchial asthma. The effectiveness of biological therapy with dupilumab 300 mg subcutaneously for 52 weeks of T-2 associated diseases, including a combination of severe atopic dermatitis and bronchial asthma, uncontrolled course based on the case history of patient Ts., born in 2006 with the diagnosis "Main: atopic dermatitis, common form, severe course. Concomitant diagnosis: bronchial asthma, persistent course, uncontrolled, moderate severity". Dynamic monitoring of the total blood count with the calculation of the absolute number of eosinophils in peripheral blood was performed. The study showed high efficacy and safety of biological therapy with dupilumab 300 mg subcutaneously every 2 weeks for 52 weeks with a combination of severe atopic dermatitis and bronchial asthma, uncontrolled course in patient Ts (Born in 2006). The examination of the ALEX2 allergochip made it possible to establish the molecular components of the primary causal allergens, predict the course of an allergic disease, and carry out successful elimination measures against food allergens, preserving the maximum set of nutrients in the patient's diet. Dupilumab therapy in severe atopic dermatitis and uncontrolled bronchial asthma leads to clinically significant improvement in the course of diseases, control of disease symptoms. Atopic dermatitis shows a decrease in itching of the skin, normalization of sleep, improvement of quality of life. With bronchial asthma, a reduction in exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. The targeted biological drug dupilumab has a targeted effect on the key links in the pathogenesis of atopic dermatitis and bronchial asthma and reduces the burden of severe diseases. Therefore, the use of dupilumab in atopic dermatitis and bronchial asthma contributes to achieving disease control and improving the patient's quality of life.

Terapevticheskii arkhiv. 2022;94(3):427-433
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Human placenta hydrolysates: from V.P. Filatov to the present day: Review

Gromova O.A., Torshin I.Y., Chuchalin A.G., Maximov V.А.


Works of V.P. Filatov and his school laid the foundation for the study and clinical use of human placenta hydrolysates (HPH). To date, the PubMed database contains more than 5,000 publications on basic and clinical research on HPH. Studies of the peptide composition of HPH, carried out using the methods of modern proteomics, have made it possible to propose a complex of molecular mechanisms of the action of HPH in various pathologies. The article discusses the effects of HPH on the treatment of liver diseases, atopic dermatitis, viral infections (herpes, COVID-19, viral hepatitis), iron overload and chronic fatigue syndrome. Stimulation of HPH regenerative capabilities of the body is important for accelerating and improving the quality of wound healing, treatment of diseases of the joints and the reproductive system.

Terapevticheskii arkhiv. 2022;94(3):434-441
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Respiratory diseases and obesity: special phenotype or independent events: Review

Shchepikhin E.I., Shmelev E.I., Zaytseva A.S.


A combination of factors, including Western European eating habits, physical inactivity and genetic predisposition, lead to a dramatic increase in adipose tissue mass. A special place is occupied by abdominal obesity, in which there is an accumulation of adipose tissue in the mesentery of the small intestine and the omentum. Developing in conditions of visceral obesity, insulin resistance, dyslipidemia and systemic inflammation are one of the key components of the pathogenesis of type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver and pancreas disease, polycystic ovary disease, some forms of cancer (breast cancer, endometrial cancer, colonic and direct intestines). At the same time, the pathogenetic role of adipose tissue is not limited to its participation in the formation of the cardiometabolic continuum and oncogenesis. The most important role of metabolically active fat in the pathogenesis of many respiratory diseases is known, including bronchial asthma, obstructive sleep apnea and pulmonary hypertension. This paper presents an overview of current data on immunological, pathophysiological and clinical features of the phenotype of the combination of respiratory diseases with overweight and obesity.

Terapevticheskii arkhiv. 2022;94(3):442-447
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Risk of community acquired pneumonia in patients with diabetes mellitus: Review

Ignatova G.L., Blinova E.V., Struch S.V., Syrochkina M.A.


The article for the first time provides a relatively comprehensive overview of the main aspects of the epidemiology and clinical features of infectious pathology, i.e., community-acquired pneumonia, as comorbid and aggravating conditions in patients with type 1 and type 2 diabetes mellitus. Risk factors and pathogenetic patterns of infectious processes development, as well as the special etiological role of pneumococcal infection in this group of patients, are considered. Particular attention is paid to the possibilities of and approaches to the primary prevention of vaccine-preventable infections as the causes of the development of community-acquired pneumonia and invasive diseases in patients with diabetes mellitus with a review of international studies, guidelines, and local experience data in pneumococcal infection immunization.

Terapevticheskii arkhiv. 2022;94(3):448-453
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History of medicine

Comments on the article by Professor Dmitry D. Pletnev “Hypertension (the experience of analyzing its genesis)”

Baranova I.A.


The purpose of the comments is the analysis of Professor Dmitry D. Pletnev's article “Hypertension (experience in analyzing its genesis)” from the point of view of modern ideas about arterial hypertension. Currently, a small number of publications of Professor D.D. Pletnev, a Russian scientist and clinician, unjustly convicted in 1937, have been preserved. The small work includes not only a deep and critical analysis of the pathogenetic mechanisms of this disease, but also an assessment of diagnostic methods, as well as a detailed description of the clinical picture. The paper, published in 1935, remains relevant and of interest to clinicians and medical historians.

Terapevticheskii arkhiv. 2022;94(3):454-457
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