[Pulmonary fibrosis after a new coronavirus infection - versions and controversies: A review].

Fibrosis is a dynamic process characterized by a typical cascade of events as a result of overexpressed repair of connective tissue in response to injury, and manifested by excessive accumulation of extracellular matrix. The development of fibrosis is a determining factor in the pathogenesis, clinical course and prognosis of many diseases, among which interstitial lung diseases occupy a special place. According to a large Russian registry (ClinicalTrials.gov: NCT04492384), in a third of patients with COVID-19, the volume of lung parenchyma involvement exceeds 50% (CT 3-4). The rapid growth in the number of patients who have had a coronavirus infection with lung damage has raised the issues of its long-term consequences to the number of the most relevant in internal medicine of the current time. Often, in the outcome of a coronavirus infection, patients retain clinical and functional changes that are similar to interstitial lung diseases of a different origin, the prognosis of which is determined by the development of interstitial fibrosis and the rate of its progression. This article is an attempt to consider topical issues of fibrogenesis in patients who have undergone a new coronavirus infection through the prism of polar data on immunobiology, clinical course and prognosis.

Possibilities of non-invasive diagnosis of fibrotic phenotype of interstitial lung diseases.

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.

[Miocarditis in Patients with COVID-19 Confirmed by Immunohistochemical].

Aim      Despite the regular heart damage in patients with coronavirus pneumonia caused by SARS-Cov-2, a possibility of developing lymphocytic myocarditis as a part of COVID-19 remains unsubstantiated. The aim of this study was to demonstrate a possibility of lymphocytic myocarditis and to study its morphological features in patients with the novel coronavirus infection (COVID-19) with a severe course.Material and methods   Postmortem data were studied for 5 elderly patients (74.8±4.4 years; 3 men and 2 women) with the novel coronavirus infection and bilateral, severe polysegmental pneumonia (stage 3-4 by computed tomography). COVID-19 was diagnosed based on the typical clinical presentation and positive polymerase chain reaction test in nasopharyngeal swabs. All patients were treated in different hospitals repurposed for the treatment of patients with COVID-19. A standard histological study was performed with hematoxylin and eosin, toluidine blue, and van Gieson staining. Serial paraffin slices were studied immunohistochemically with antibodies to CD3, СD68, CD20, perforin, and toll-like receptors (TLR) 4 and 9.Results In none of the cases, myocarditis was suspected clinically, added to the diagnosis or indicated as a possible cause of death. IHD and acute myocardial infarction were mentioned as error diagnoses not confirmed by the postmortem examination. The morphological examination of the heart identified signs of lymphocytic myocarditis consistent with Dallas criteria for this diagnosis. Myocardial infiltrate was characterized in detail, and a combined inflammatory damage of endocardium and pericardium was described. The immunohistochemical study with cell infiltrate typing confirmed the presence of CD3-positive Т lymphocytes and the increased expression of TLR-4. A picture of coronaritis, including that with microvascular thrombosis, was found in all cases.Conclusion      A possibility for development of lymphocytic viral myocarditis in COVID-19 was confirmed morphologically and immunohistochemically. Specific features of myocarditis in COVID-19 include the presence of coronaritis and a possible combination of myocarditis with lymphocytic endo- and pericarditis.

[Differential diagnosis of idiopathic pulmonary fibrosis].

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.

Changes in Microbiota and Development of Nonspecific Inflammation of Genitals in Female C57Bl/6 Mice after Aerosol Infection with Mycobacterium tuberculosis.

Infectious process even at the initial stage after aerosol infection with Mycobacterium tuberculosis induced rapid changes in vaginal microbiota in mice. Rapid decrease in both the quantity and diversity of microbiota was noted, and then, partial recovery of normal flora was observed. Changes in vaginal microbiota was detected as soon as in 3-7 days after lung infection, while inflammatory changes appeared by day 35. At the early stage of infection, no signs of inflammation were observed, neither M. tuberculosis nor its DNA were detected in mouse genital organs.

[Non - tuberculous mycobacteriosis of the lungs - diagnostic possibilities in the practice of the pulmonologist].

AIM OF THE STUDY: Show the possibilities of diagnosing non - tuberculous mycobacteriosis of the lungs (NTML) in the practice of the pulmonologist. MATERIALS AND METHODS: A survey of 90 patients with a confirmed diagnosis of non - tuberculous mycobacteriosis of the lungs (NTML) was presented. The diagnosis of pulmonary mycobacteriosis was established in accordance with the criteria proposed in 2007 by the American Thoracic Society and the American Society of Infectious Diseases (ATS/IDRS). Among the patients, 55 (61.1%) women prevailed, the average age was 51.2±15.3 years. Patients were evaluated complaints, the presence of concomitant diseases of the lungs, was carried out computed tomography of the chest high - resolution (HRCT), a culture study of sputum, in the absence of sputum or a single determination of the NTM culture in it, a study was conducted on materials of bronchoalveolar washout (ALS/BAL), or lung biopsies. Statistical processing of the research results was performed using descriptive statistics using Microsoft® Excel for Windows xp® on a personal computer. RESULTS AND CONCLUSION: As a result of the study, it was revealed that before the diagnosis of NTML was established, 66.7% of patients were long observed for chronic lung diseases (chronic obstructive pulmonary disease, chronic bronchitis), and in 55.6% of cases (50 people) were registered with a phthisiologist about pulmonary tuberculosis. According to the CT scan of OGK, dissemination was determined in 66.7% of cases, in 48.9% - bronchiectasis, single or multiple destruction cavities - 46.7% of cases. In 72.2% of cases, non - tuberculous mycobacteria (NTM) were found in sputum, in 33.3% - in ALS and in 22.2% of NTMs were found in the surgical material. In 14.4% of cases, only surgery allowed to establish the diagnosis of mycobacteriosis.

[Immunological aspects of tuberculosis pathogenesis].

The morphological aspects of TB pathogenesis are well described in the publications. Much is also known about the main stages of development and formation of specific adaptive immunity. However, from our point of view, not enough attention is being paid to the involvement of the immune system in the pathogenesis of clinically relevant TB abnormalities, as well as various forms of the disease. Nevertheless, there is no doubt that the variety of clinical manifestations of any disease associated with the penetration of a foreign agent into the body, and Mycobacterium tuberculosis (MTB) in particular, is due to the collective interaction of the infectious agent and the individual response of the macroorganism to this infectious agent. The mosaic of such interactions usually imposes its own adjustments on the development of different forms of the process, its speed and direction, as well as the outcomes. Certainly, the response of a macroorganism to MTB is an integral part of pathogenesis and consists of many general components including the responses associated with the mechanisms of natural and acquired immunity. Intensity of these reactions depends on the characteristics of an agent (MTB) and a macroorganism. For the development of TB disease, massiveness of TB infection, dose and duration of MTB exposure to the human body, as well as virulence of MTB and the level of body's protection during the exposure play a very important role. TB pathogenesis is somewhat different in primary MTB infection and re - infection. With primary infection, 88-90% of individuals do not have clinical manifestations, and only the tuberculin skin test conversion signals the onset of infection. In some cases, without any use of anti-TB drugs limited abnormalities may result in spontaneous cure with the minimal residual changes in the lungs, intrathoracic lymph nodes and tissues of other organs, often in the form of calcifications and limited areas of fibrosis in more advanced cases. Only 10-12% of newly infected individuals develop TB with severe clinical manifestations requiring TB therapy. The absence of clinical manifestations of primary TB infection can be explained by a high level of natural resistance of the human body to tuberculosis, and sometimes can be an effect of acquired protection due to BCG vaccination. This review attempts to discuss the role of immune mechanisms in the pathogenesis both at the beginning of disease development, and in the process of its various manifestations. Issues of genetically determined resistance or susceptibility to TB are not being covered in detail in this manuscript.

[Comparative analysis of the semiotics of disseminated pulmonary tuberculosis and exogenous allergic alveolitis in accordance with the data of computed tomography].

OBJECTIVE: to improve the differential diagnosis of disseminated pulmonary tuberculosis (DPT) and exogenous allergic alveolitis (EAA) via comparative investigation of their computed tomography (CT) semiotics and identification of the most informative diagnostic criteria. MATERIAL AND METHODS: 70 patients, including 40 patients with DPT in a phase of infiltration and 30 patients with acute EAA, were studied using a Somatom Emotion 16 multi-slice spiral CT scanner (Siemens). All the patients underwent spiral scanning from the upper chest aperture to the costodiaphragmatic recesses with a high CT algorithm at 0.8-mm slice thickness and a 1.5-mm step. RESULTS: Analysis of the spread of dissemination foci established that pathological changes were peribronchovascularly located in both nosological entities and characterized by a preponderance of septal and intrabronchial locations in DPT and by a centrilobular distribution in EAA. Centrilobular foci were more commonly poorly defined in EAA and mixed foci were observed in DPT. In the latter, peribronchovascular, centrilobular foci were revealed at a distance from the visceral pleura (the boundary of the deep and superficial lymphatic network, respectively) in 38% and more than half of the cases (62%) with the involvement of the visceral and parietal pleura; in EAA, the centrilobular foci were more often combined with the involvement of the visceral pleura in more than 92% of cases. The tree-in-bud sign was significantly more common in DPT. The latter was mostly characterized by apicocaudal regression of dissemination. In EAA, the foci were more frequently located asymmetrically. Monomorphic foci with destruction, as well as their polymorphism were seen in DPT; those without destruction were predominantly observed in EAA. CT ground glass and mosaic perfusion syndromes were significantly more often in EAA. In DPT, the visceral and parietal pleuras were involved in the process in 62% of cases and changes were also more common in the extrapleural fat. CONCLUSION: In addition to the peribronchovascular location of foci, the characteristic CT signs for DPT are a preponderance of intrabronchial and septal locations of foci, their apicocaudal regression, the presence of the CT tree-in-bud sign, and thickened extrapleural fat. EAA showed a prevalence of asymmetrical foci with centrilobular location with the involvement of the visceral pleura into the process, with the presence of CT ground glass and mosaic perfusion syndromes, as well as the bronchial lumen visualized in the peripheral segments of the lung.

[Difficulties in the radiodiagnosis of lung injuries in phthisiatric practice].

The paper describes clinical cases of concomitant lung and intrathoracic lymph node involvements as evidenced by conventional radiography and computed tomography (CT). It shows difficulties in the differential diagnosis of different nosological entities in pulmonary tuberculosis. The x-ray semiotics of concomitant lung injuries is also depicted.

[Chemotherapy of tuberculosis: problems and perspectives].

Challenges of tuberculosis chemotherapy under conditions of high drug resistant (DR) tuberculosis burden are discussed. Ultimate results of treatment by standard regimens of 1658 patients with new tuberculosis cases and relapses were analyzed. Favorable ultimate results were observed among both patients with new tuberculosis cases and relapses having drugs sensitivity. Efficacy of tuberculosis treatment by standard regimens of chemotherapy is decreasing as a result of DR amplification. Risk factors of unfavorable ultimate result among pulmonary tuberculosis patients are primary resistance to isoniazid (OR = 2.1) and multiple drug resistance of M. tuberculosis (OR = 8.0). Earlier onset of treatment and correct individual therapy with second line drugs as a result of rapid methods of DR tuberculosis diagnostics are those approaches which provide the best therapeutic effect among multiple drug resistant tuberculosis patients both in culture conversion (97.7%) and cavity closure rate (82.7%).

[Psychoemotional changes in patients with pulmonary tuberculosis during therapy using psychological and neuropsychological methods].

Therapy for pulmonary tuberculosis in patients is complicated by their negative psychoemotional state frequently deteriorated by long inpatient stay. Enhancing the efficiency of rehabilitative measures in phthisiology requires active optimization of the patients' mental state. This problem can be solved by a package of correction measures involving psychological correction with reflex therapeutic normalization of the functional state of the cortical regions of the central nervous system in patients with pulmonary tuberculosis. One hundred tuberculosis patients with decompensated mind, including 60 with OG and 40 with KG, were examined. A noticeable psychoemotional improvement was reliably detected 5 months after complex correction psychological and neuropsychological accompaniments of standard chemotherapy in the OG study.

[Digital X-ray study in the monitoring of collapse therapy in patients with destructive pulmonary tuberculosis].

Digital versus analogue X-ray studies in identifying different X-ray symptoms are analyzed; their accuracy, sensitivity, and radiation load on a patient were established. The costs of consumables used at digital and analogue X-ray studies have been calculated. An algorithm for monitoring artificial pneumothorax and pneumoperitoneum has been proposed for patients with destructive pulmonary tuberculosis. A procedure has been developed to determine a commissural process in the pleural cavity by digital X-ray study and X-ray computed tomography. The findings are indicative of the expediency and medicoeconomic effectiveness of digital X-ray study used in the monitoring collapse therapy in patients with destructive pulmonary tuberculosis.

[Mycobacterial antigens and tuberculosis antibodies in the blood and pleural exudate of patients with tuberculous pleurisy]. / Antigeny mikobakterii i protivotuberkuleznye antitela v krovi i plevral'nom ékssudate u bol'nykh tuberkuleznym plevritom.

To enhance the efficiency of treating tuberculous pleurisy, a complex of therapeutical measures was supplemented by the immunomodulator licopid in 51 patients. The control group included 52 patients with pleurisy who received the same treatment regimen without licopid. Comparing the outcomes of treatment has revealed that licopid reduced the time of treatment, promotes the substantial diminution of antigenemia and the production of tuberculosis antigens, improves cell immunity and natural resistance.

[Detection of Mycobacterial antigens in tuberculous pleuritis, empyema and meningitis]. / Opredelenie mikobakterialnykh antigenov pri tuberkulëznykh plevrite, émpieme i meningite.

Mycobacterial antigens were identified by inhibition solid-phase enzyme immunoassay specific antibodies to M.H37Rv labelled with horse radish peroxidase in 20, 27, 24, 47 and 21 patients with tuberculous pleurisy, tuberculous empyema, meningitis, pleurisy and nontuberculous empyema, respectively. Mycobacterial antigens were found more frequently and in greater quantities in pleural and cerebrospinal fluids in tuberculosis than in the above nontuberculous affections. These differences were less pronounced in serum assays.

[New methods of prevention, diagnosis and treatment of tuberculosis in children]. / Novye metody profilaktiki, diagnostiki i lecheniia tuberkuleza u detei.

The follow-up included two groups of schoolchildren: 862 were repeatedly given BCG and 725, BCG-M vaccines. It was demonstrated that both vaccines had the same effectiveness and the latter could also be used. Upright tomographic findings in 70 children showed that it was highly informative for the diagnosis of intrathoracic tuberculosis in children, especially for that of bronchoadenitis. Monitoring of 315 children with destructive pulmonary processes (157 of them had lesions of tuberculous etiology) made it possible to define risk factors of destructive tuberculosis contamination (in particular, genetical predisposition), the diagnostic criteria and high diagnostic value of the enzyme-linked immunoassay (96%). Ultrasound examination of the liver in 121 tuberculosis children enabled one to diagnose the type and etiology of liver affection, to control its state during treatment, to specify the side effects of the drugs and to modulate the therapy. The course and outcomes of tuberculosis were found to be affected by liver affections. The parenteral administration of isoniazid in combination with other drugs was shown to be highly beneficial in disseminated form of tuberculosis in children.