Terapevticheskii arkhiv



Therapeutic archive journal (ISSN key title is "Terapevticheskiy arkhiv") was founded by the prominent Russian therapists M.P. Konchalovsky and G.F. Lang in 1923. Then its editors-in-chief were Professors V.N. Vinogradov and A.G. Gukasyan. Since 1972, E.I. Chazov, Academician of the Russian Academy of Sciences, has been heading the editorial board of the journal.

Over 90 years, there have been more than 1000 issues where the authors and editorial staff have done their best for readers to keep abreast of current advances in medical science and practice and for physicians to master the advanced principles of recognition and treatment of a wide spectrum of visceral diseases.

The papers published in the journal (editorials, original articles, lectures, reviews, etc.) cover both current scientific achievements and practical experience in diagnosing, treating, and preventing visceral diseases. The authors of publications are not only Russian, but also foreign scientists and physicians. All papers are peer-reviewed by highly qualified Russian specialists.

The journal is published monthly. Traditionally, each issue has predominantly certain thematic areas covering individual therapy specializations. Every year, one of the issues is devoted to related problems in practical medicine (allergology and immunology, neurology and psychiatry, obstetrics, oncology, etc.). This all draws the attention of the reading public to the journal.



Irina Chazova
MD, PhD, Professor, Academician of the Russian academy of Sciences
ORCID: http://orcid.org/0000-0002-1576-4877



Monthly issues publish in print and online in Open Access under the Creative Commons NC-ND 4.0 International Licensee.



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Current Issue

Vol 95, No 3 (2023)

Cover Page

Full Issue


Respiratory disorders of post-COVID-19 syndrome
Leshchenko I.V., Esaulova N.A., Glushkova T.V., Skornyakov S.N.

Aim. Assess the functional state of trespiratory system and effectiveness of therapeutic tactics for broncho-obstructive syndrome (BOS) in patients in the post-COVID period.

Materials and methods. A two-center cohort prospective study included 10 456 and 89 patients, respectively. A comprehensive assessment of the respiratory system included clinical, laboratory and functional data, spirometry, body plethysmography, and a study of diffusive capacity of the lungs (DLCO). Therapy consisted of budesonide suspension or fixed combination beclomethasone dipropionate/formoterol (EMD BDP/FORM).

Results. The frequency of BOS in the cohort was 72% (7497 patients). In 13% (n=974) of cases, bronchial asthma was diagnosed for the first time, in 4.4% (n=328) – chronic obstructive pulmonary disease. Risk factors for the development and decrease in DLCO in the post-COVID period were identified. In the group of complex instrumental examination of lung function, the absence of violations of spirometric data and indicators determined by body plethysmography was determined.

Conclusion. Risk factors for BOS in post-COVID period are atopy, a history of frequent acute respiratory infections, smoking, blood eosinophilia, moderate and severe forms of COVID-19. The advantage of a fixed combination of EMD BDP/FORM in MART mode compared with nebulized suspension budesonide + solution of salbutamol in treatment of BOS was shown. Risk factors for DLCO disorders were established: severe COVID-19, hospitalization in the intensive care unit, the need for additional oxygen therapy.

Terapevticheskii arkhiv. 2023;95(3):203-209
pages 203-209 views

Original articles

Assessment of inhalation technique in patients with bronchial asthma and chronic obstructive pulmonary disease
Trushenko N.V., Stoliarevich A.A., Andriukov B.G., Nuralieva G.S., Tsareva N.A., Lavginova B.B., Avdeev S.N.

Aim. Investigate inhalation techniques using different inhalers types and their effect on the course of disease.

Materials and methods. This cross-sectional study included 110 patients with asthma, chronic obstructive pulmonary disease using the inhaler at least one month. Inhaler errors performed during demonstration were evaluated for each patient and entered in the check-lists. We also collected information about co-morbidities, education, mMRC dyspnea score, rate of exacerbations, and performed spirometry.

Results. 80.9% of patients used metered-dose inhaler, 20.9% – single-dose and 21.8% – multiple-dose dry powder inhaler, 22.7% – soft-mist inhaler. Inhaler errors were made by 80.9% patients. The mean number of mistakes in metered-dose inhaler use was 2±1.6, single-dose powder inhaler –1.5±1.3, multiple-dose dry powder inhaler – 1.25±1.4, soft-mist inhaler – 0.68±0.7 (р=0.003). Age, diagnosis, duration of disease, education level, inhalers usage by relatives have no influence on the inhalation technique. A number of errors was related to female gender (р=0.007) and usage of more than 2 inhalers (r=0.3, p=0.002), previous instruction about inhalation technique (r=0.3, p=0.001). On the other hand, there were correlations between the number of errors and degree of bronchial obstruction, asthma control, severity of dyspnea by mMRC score, exacerbation rate.

Conclusion. Patients with bronchoobstructive diseases perform many inhaler errors, that substantially influences the severity and course of asthma and chronic obstructive pulmonary disease.

Terapevticheskii arkhiv. 2023;95(3):210-216
pages 210-216 views
Clinic and functional features of chronic obstructive pulmonary disease after virus-induced acute exacerbations.
Shpagina L.A., Kotova O.S., Shpagin I.S., Karmanovskaya S.A., Loktin E.M., Rukavitsyna A.A., Kuznetsova G.V., Gerasimenko D.A., Anikina E.V.

Aim. To establish symptoms, lung function and to evaluate subsequent exacerbations of chronic obstructive pulmonary disease (COPD) during a year after virus-induced COPD exacerbations.

Materials and methods. Patients hospitalized with viral (n=60), bacterial (n=60) and viral-bacterial (n=60) COPD exacerbations were enrolled to single-center prospective observational study. COPD was diagnosed according spirography criteria. Viral infection was established in bronchoalveolar lavage fluid or sputum by real-time reverse transcription-polymerase chain reaction for RNA of influenza A and B virus, rhinovirus, respiratory syncytial virus and SARS-CoV-2. Symptoms, lung function, COPD exacerbations were assessed. Patients were investigated at the hospitalization onset and then 4 and 52 weeks following the discharge from the hospital.

Results. After 52 weeks in viral and viral-bacterial COPD exacerbations groups the rate of forced expiratory volume in one second (FEV1) decline were maximal – 71 (68; 73) ml/year and 69 (67; 72) ml/year versus 59 (55; 62) ml/year after bacterial exacerbations. Low levels of diffusion lung capacity for carbon monoxide (DLco/Va) – 52.5% (45.1%; 55.8%), 50.2% (44.9%; 56.0%) and 75.3% (72.2%; 80.1%) respectively, of 6-minute walk distance; p<0.001 in relation to bacterial exacerbations. In Cox proportional hazards regression analyses viral and viral-bacterial exacerbations were associated with increased risk of subsequent COPD exacerbations by 2.4 times independent of exacerbations rate before index event and FEV1. In linear regression models the relationships between airflow limitation and respiratory syncytial virus, rhinovirus and influenza virus infection, between low DLco/Va and rhinovirus, influenza virus and SARS-CoV-2 infection.

Conclusion. COPD after virus-induced exacerbations were characterized by progression of airflow limitation, low DLco/Va, low 6-minute walking test distance, subsequent COPD exacerbations risk.

Terapevticheskii arkhiv. 2023;95(3):217-222
pages 217-222 views
Interstitial pneumonia with autoimmune features: monocentric prospective study
Akulkina L.A., Shchepalina A.A., Moiseev A.S., Brovko M.Y., Sholomova V.I., Moiseev S.V.

Aim. To study demographic, clinical, serological and morphological features of interstitial pneumonia with autoimmune features (IPAF), compare survival in IPAF and interstitial lung disease in connective tissue diseases (CTD-ILD), and identify predictors of mortality and transformation to CTD in the IPAF group.

Materials and methods. The IPAF group included 48 patients (75.0% women, median age 57.5 years), CTD-ILD – 49 patients (79.6% women, median age 60.0 years). The analysis of demographic, clinical, laboratory and instrumental data was performed, as well as comparison of survival with the Kaplan–Meier method and the log-rank test in the IPAF and CTD-ILD groups. In the IPAF group, predictors of mortality and the development of CTD were studied with multivariate regression analysis.

Results. Duration of observation period did not differ significantly in the IPAF and CTD-ILD groups (40.0 and 37.0 months, respectively). Clinical criteria of IPAF were observed in 25 (52.1%) patients, serological – in 44 (91.7%), morphological – in 44 (91.7%). Mortality in the IPAF group was significantly higher than in the CTD-ILD group (29.2 and 6.1%, respectively; p=0.023). The presence of diabetes mellitus, CT-pattern of usual interstitial pneumonia, and an initial low forced vital capacity value were independent predictors of mortality in the IPAF group. During the observation period, the development of CTD was noted in 4 (8.3%) patients with IPAF. The independent predictor of the CTD development was the increased C-reactive protein level.

Conclusion. IPAF is characterized by a lower survival rate compared to CTD-ILD, and a relatively low risk of CTD transformation.

Terapevticheskii arkhiv. 2023;95(3):224-229
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Possibilities of non-invasive diagnosis of fibrotic phenotype of interstitial lung diseases
Shchepikhin E.I., Shmelev E.I., Ergeshov A.E., Zaytseva A.S., Shergina E.A., Adamovskaya E. .

Progressive pulmonary fibrosis is a major problem in respiratory medicine. Currently, there are no reliable biomarkers for early diagnosis of progressive pulmonary fibrosis, which leads to delayed diagnosis.

Aim. To determine the role of serum biomarkers CA-19-9 and CA-125 and the possibilities of capillaroscopy of the nail fold in the diagnosis of progressive pulmonary fibrosis.

Materials and methods. The study included 43 patients with interstitial changes in the lungs. Based on the presence/absence of signs of progression over the previous 12 months, patients were divided into 2 groups. All patients underwent forced spirometry, body plethysmography, diffusion test, CT, lung ultrasound, capillaroscopy of the nail fold, study of serum concentrations of CA-19-9 and CA-125.

Results. In the group of patients with a progressive fibrotic phenotype of Interstitial lung diseases, a greater severity of capillaroscopic changes and a higher level of CA-19-9 were revealed. Correlation of these parameters with changes according to CT scan data (Warrick test) and lung ultrasound was shown.

Conclusion. The data obtained demonstrate the possibilities of non-invasive diagnosis of progressive fibrosing interstitial lung diseases and require further research and prospective follow-up to assess the diagnostic and prognostic role of the studied biomarkers, as well as to determine their place in clinical practice.

Terapevticheskii arkhiv. 2023;95(3):230-235
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Evaluation of the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol versus a fixed-dose combination of bromhexine/guaifenesin/salbutamol in the treatment of productive cough in adult patients with acute bronchitis
Zaitsev A.A., Leshchenko I.V., Esaulova N.A., Viktorova I.A.

Aim. To evaluate the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol, oral solution, versus Ascoril Expectorant, syrup (combination of bromhexine, guaifenesin, and salbutamol) in the treatment of productive cough in adult patients with acute bronchitis.

Materials and methods. This open-label, randomized, phase III study included patients with acute bronchitis who had a productive cough with difficulty in sputum expectoration. 244 patients were randomized in a 1:1 ratio and received 10 mL of the study drug or reference drug 3 times daily for 2 weeks. After 7 and 14 days of treatment, the physician evaluated patient’s subjective complaints and the efficacy of therapy. The primary endpoint was the proportion of patients with high and very high efficacy.

Results. The primary endpoint was reached by 70 (0.5738) patients in the study drug group and 54 (0.4426) in the reference drug group (p=0.04). The intergroup difference was 0.1311 [95% confidence interval: 0.0057; 0.2566]. The lower limit of the 95% confidence interval was above zero, which confirms the superiority of therapy with the study drug over therapy with Ascoril Expectorant. The proportion of patients with a 1-point total score reduction and with complete resolution of all symptoms according to the Modified Cough Relief and Sputum Expectoration Questionnaire after 7 and 14 days was numerically higher in the study drug group versus the reference drug group. There were no statistically significant differences between the groups in the incidence of adverse events.

Conclusion. The efficacy of a new combination drug containing ambroxol, guaifenesin, and levosalbutamol in the treatment of productive cough in adult patients with acute bronchitis is superior to the efficacy of Ascoril Expectorant. The safety profiles of the study drug and the reference drug were comparable.

Terapevticheskii arkhiv. 2023;95(3):236-242
pages 236-242 views
Efficacy and safety of patients immunization with chronic obstructive pulmonary disease with monoclonal antibodies
Antonov V.N., Ignatova G.L.

Background. Chronic obstructive pulmonary disease (COPD) is characterized by a high level of morbidity and mortality and is associated with significant social and economic damage to the health system and society. COPD and COVID-19 have many potentially negative relationships that can lead to worse outcomes of COVID-19, including impaired lung function, old age and the presence of concomitant diseases

Aim. To assess efficacy and safety of the drug Tixagevimab + Cilgavimab for the pre-contact prevention of COVID-19 infection in patients with COPD.

Material and methods. A total of 324 male patients were included in the study, who were treated or monitored at the Regional Clinic Hospital №3 and the Regional Pulmonological Center of Chelyabinsk in April–May 2022. The main endpoints of observation, for 3 and 6 months, to assess the effectiveness were the dynamics of shortness of breath according to The Modified Medical Research Council Dyspnea Scale – mMRC, the The forced expiratory volume in 1 second, the number of exacerbations, emergency calls, hospitalizations, polymerase chain reaction for SARS-CoV-2. Local and general reactions after immunization were evaluated. The drug Evusheld (150 mg Tixsagevimab +150 mg Cilgavimab, AstraZeneca) was used for immunization.

Results and conclusion. The effectiveness of pre-contact prevention of COVID-19 was 88.8%. The administration of the drug does not provoke an exacerbation of the underlying disease. The main clinical and functional indicators have positive dynamics by the 6th month of follow-up. The drug is well tolerated and has no significant both early and late complications.

Terapevticheskii arkhiv. 2023;95(3):243-247
pages 243-247 views

Clinical notes

Difficult case of differential diagnosis of partial lung atelectasis. Case report
Gordeeva O.M., Egorova A.D., Chesalina Y.O., Gretcov E.M., Semenova L.A., Karpina N.L., Sivokozov I.V.

In December 2018 the patient over 60 years old sought medical help with complaints of persistent cough. Based on computed tomography data there were identified the sings (symptoms) of right lung lower lobe atelectasis. To run this patient diagnostics there were performed 6 bronchoscopies narrowed down by bronchi checks up only and described the right lung central cancer picture. At the same time the biopsy taken during one of the bronchoscopies appeared non informative. Fine needle biopsy of mediastinal lymph nodes and bronchial wall was performed twice: at Tomsk Cancer Research Institute (it was suspected B-cell lymphoma based on biopsy examination) and at The Loginov Moscow Clinical Scientific Center (signs of inflammation based on biopsy examination). The video-assisted thoracoscopy with lymph node dissection of the right lung root was performed in January 2020. As a surgical material analysis result reactive adenopathy was determined. Therefore, during more than 1 year of diagnostic research the genesis of right lung lower lobe atelectasis was not established. The patient was directed to Central Tuberculosis Research Institute for diagnosis verification. Based on clinical and radiological picture Central Tuberculosis Research Institute colleagues suspected a foreign body in the intermediate bronchus. During an endoscopic examination it was revealed stenosis, biopsies were performed, but the foreign body could not be identified. In the pathomorphological laboratory of Central Tuberculosis Research Institute there were conducted histological examination of the material after endobronchial cryobiopsy and rigid needle biopsy. Both gave an unexpected result: invasive mycosis of the bronchial wall. As a conclusion the decision was taken to apply antimycotic therapy on an outpatient basis. As a result, clear clinical and radiological positive dynamics was obtained. In these favorable conditions for endoscopic examination, it was performed vitally essential cryoextraction of foreign body. The foreign body turned out to be a fragment of a spongy bone of a centimeter size. These actions have let to unlock the right lung lower lobe.

Terapevticheskii arkhiv. 2023;95(3):248-254
pages 248-254 views


Progressive fibrosing lung disease. Discussion aspects of the problem: A review
Ilkovich M.M., Novikova L.N., Speranskaya A.A., Dvorakovskaya I.V.

The authors of the article prove the need to include a new name for the disease – "Progressive Fibrosing Lung Disease" into clinical practice. Recognition of the fact that some lung diseases end in a fibrosing process, which does not have any significant differences depending on the initial disease that led to fibrosis, will expand the indications for earlier prescription of antifibrotic drugs, which will undoubtedly improve the prognosis in this extremely severe category of patients.

Terapevticheskii arkhiv. 2023;95(3):255-259
pages 255-259 views
Finerenone cardiorenal effects and its placement in treatment of chronic kidney disease in patients with type 2 diabetes mellitus: A review
Salukhov V.V., Shamkhalova M.S., Duganova A.V.

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high. To date, current medications for CKD haven’t reduced enough the residual risk associated with inflammation and fibrosis in patients with type 2 diabetes. Here, in this review we present the results of FIDELIO-DKD, FIGARO-DKD trials and their pooled analysis FIDELITY, aimed to evaluate the effectiveness and safety of selective non-steroidal mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes with wide range stages of CKD. Modern pathophysiological aspects of mineralocorticoid receptor hyperactivation and features of their blockade by steroidal and nonsteroidal mineralocorticoid receptor antagonists are considered, differences in pharmacological effects between them are also discussed, finerenone benefits and its adverse events, demonstrated in randomized clinical trials are considered here. The probable mechanisms of early and delayed action of finerenone, which were realized in beneficial cardiovascular and renal outcomes in patients with type 2 diabetes with CKD, are presented here. Practical points for finerenone initiation and titration are indicated, aimed to minimize the hyperkalemia risk. Current guidelines for CKD treatment in patients with type 2 diabetes are analyzed, the finerenone placement in combined nephroprotective therapy is determined.

Terapevticheskii arkhiv. 2023;95(3):261-273
pages 261-273 views
Genetic aspects of type 1 glucagon peptide agonists clinical efficacy: A review
Golovina E.L., Grishkevich I.R., Vaizova O.E., Samoilova I.G., Podchinenova D.V., Matveeva M.V., Kudlay D.A.

A review of publications devoted to the analysis of genetic polymorphisms of the gene encoding the glucagon-like peptide type 1 receptor and some other genes directly and indirectly involved in the implementation of its physiological action is presented. The aim of the study: to search for information on genes polymorphism that can affect the effectiveness of glucagon-like peptide type 1 agonists. The review was carried out in accordance with the PRISMA 2020 recommendations, the search for publications was based on PubMed databases (including Medline), Web of Science, as well as Russian scientific electronic source eLIBRARY.RU from 1993 to 2022. The several genes polymorphisms (GLP1R, TCF7L2, CNR1, SORCS1, WFS1, PPARD, CTRB1/2) that may affect the course and therapy of type 2 diabetes mellitus, metabolic syndrome and obesity, was described. Single nucleotide substitutions in some regions of these genes can both decrease and increase the clinical efficacy of the treatment of diabetes mellitus and metabolic syndrome with the help of type 1 glucagon-like peptide agonists: exenatide, liraglutide. Data on the role of genetic variations in the structure of the products of these genes in the effectiveness of other type 1 glucacone-like peptide agonists have not been found.

Terapevticheskii arkhiv. 2023;95(3):274-278
pages 274-278 views

History of medicine

Heart Diseases by Professor Dmitry D. Pletnev (for the reprint of D.D. Pletnev's monograph “Heart Diseases”, 1936)
Chuchalin A.G., Bobkov E.V.

The article presents a brief review of Heart Diseases (1936), the monograph by one of the founders of domestic and world cardiology Dmitry Dmitrievich Pletnev. In the monograph, he summarized his clinical and experimental approach to the issues of heart diseases, addressed several fundamental problems of modern physiology and healthcare, introduced the concept of “functional unit” and “functional unity of the whole body”, the concept of the extracardiac genesis of the chest frog, differential diagnosis of left and right ventricle myocardial infarction, semiotics and treatment of chronic heart failure, functional diagnosis of heart arrhythmias. All these approaches and concepts have long been included in the classics of world cardiology.

Terapevticheskii arkhiv. 2023;95(3):279-284
pages 279-284 views

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