The purpose of this overview was to present historical data on the discovery of hydrogen and a brief summary of its physical properties that form the basis for its use in aeronautics. Information is provided on the use of hydrogen, a biologically neutral molecule, in medicine as a diagnostic indicator for penetrating wounds of the gastrointestinal tract, the determination of local blood flow using the hydrogen clearance method, the use of the hydrogen breath test for the diagnosis of malabsorption and carbohydrate intolerance, achlorhydria, the diagnosis of bacterial overgrowth syndrome, the assessment of biodegradation of magnesium-containing implants, the orocecal transit time, and during deep-sea diving. The reasons for the sharp increase in the doctors’ interest in studying the biological role of hydrogen after the discovery of its antioxidant properties by a group of Japanese scientists (2007) are analyzed. In order to increase antioxidant protection of the body, data from recent research on ways to increase its concentration in the body through the supply of exogenous gas by inhalation or by administering hydrogen-rich water or saline solution is presented. Particular attention is paid to a critical analysis of studies on the kinetics of hydrogen by different routes, its concentration in blood and tissues, inhalation, and the use of hydrogen-rich water. Based on an analysis of publications, that the use of molecular hydrogen to relieve oxidative stress in the tissues of the intestines, liver and lungs is most promising, since its highest concentration is found in these tissues. Fermentation of carbohydrates has also been shown to increase the production of hydrogen by the intestinal  microbiota. Considering that a large number of molecular hydrogen generators appeared on the market, the data on the requirements for their safety are summarized. Considerations on the use of molecular hydrogen for the purpose of antioxidant protection of the body in cardiology, gastroenterology, pulmonology, and other areas of medicine are based on modern views on the mechanisms of antioxidant, anti-apoptotic, cytoprotective, and anti-inflammatory effects of hydrogen. Particular attention is paid to the analysis of experimental and clinical research on the use of hydrogen in acute and chronic lung lesions, therapy of acute and chronic COVID-19 infection.

Conclusion. Based on an analysis of the literature and our own data, a conclusion was drawn on the safety and prospects of the clinical use of molecular hydrogen in a wide range of concentrations in many diseases with the pathogenesis based on oxidative stress. In particular, the need for additional research was highlighted to clarify the regimen, frequency, duration and concentrations of hydrogen used, and a personalized approach to the combination of endogenous (from the intestinal microbiota) and exogenous hydrogen in various diseases.

Hydrogen is known to have selective antioxidant properties. It binds highly reactive hydroxyl radicals. The pathogenesis of the monocrotaline animal model of pulmonary hypertension is associated with oxidative stress and leads to all the symptoms of pulmonary hypertension (PH) and interstitial lung disease (ILD) associated with hypertension.

The aim of this work was to study the effect of 4% hydrogen inhalations on the symptoms of PH and ILD in rats.

Methods. To model monocrotaline-induced pulmonary hypertension (MCT-PH), two groups of animals received a single subcutaneous injection of monocrotaline (MCT) on day 1. The control group was injected subcutaneously with MCT solvent only. The animals receiving MCT were further divided into 2 subgroups. Subgroup 1 rats breathed room air and subgroup 2 rats breathed a mixture of room air and 4% hydrogen. The regular inhalations continued until day 21. On day 21, hemodynamic parameters were measured under urethane anesthesia, the heart and its components and the lungs were weighed, and lung tissue was preserved for morphological study.

Results. The inhalation had no effect on the main cardiovascular symptoms of PH, but a positive effect on the state of the connective tissue of the lungs affected by PH was shown. The mast cell response was reduced both quantitatively and functionally. There was a decrease in tryptase expression by mast cells, with predominance of the forms without signs of degranulation. TGF-β secretion was also significantly reduced and visualized by immunopositive cells in alveolar cellular structures and vessel walls.

Conclusion. Inhalation of 4% hydrogen reduces inflammation and fibrosis of lung tissue during the development of MCT-PH. 

The purpose of the study was to evaluate the effectiveness of myocardial protection with a combined supply of nitric oxide (NO) (40 ppm) and hydrogen (1.2 ppm) into the gas-air mixture delivery line of the cardiopulmonary bypass (CPB) machine during the entire period of CPB.

Methods. The study included patients (n = 91) who had cardiac surgery under cardiopulmonary bypass and pharmacological cold cardioplegia. Patients were randomized into 3 groups. The Group 1 (n = 30) was control. Groups 2 (n = 28) and 3 (n = 33) received an isolated supply of NO (40 ppm) and a combined supply of NO (40 ppm) and hydrogen (1.2 ppm) into the extracorporeal IR circuit, respectively. During the postoperative period, clinical and functional indicators were studied (dynamics of myocardial contractile function according to ultrasound data); duration of artificial pulmonary ventilation (ALV); stay in the intensive care unit; hospital stay; mortality; level of marker of myocardial injury – troponin I (cTnI). Myocardial injury index (MII) was calculated to assess the degree of injury.

Results. It was found that the level of cTnI in the postoperative period increased statistically significantly in all groups but was statistically significantly lower in Groups 2 and 3 compared to Group 1 at the end of the surgery and 12 and 24 hours after the surgery. Also, level of cTnI was statistically significantly lower in Group 3 at all stages of the study compared to Group 1 and after 12, 24 and 48 hours compared to Group 2. Statistically significantly lower MII values were revealed at all stages of the postoperative period in Group 3 compared with Groups 1 and 2. Changes in indicators of myocardial contractile function suggest an earlier and more complete recovery in Groups 2 and 3 (the changes were statistically significantly higher than that in Group 1). In Groups 2 and 3, the incidence of acute heart failure was statistically significantly lower (p = 0.046) compared to Group 1, according to Fisher’s exact test. There were no statistically significant differences in the incidence of acute respiratory and multiple organ failure in Groups 2 and 3 compared to Group 1. Also, patients of Groups 2 and 3 did not experience any complications in the early postoperative period. In Group 3, there was a statistically significant decrease in the duration of mechanical ventilation and stay in the intensive care unit after surgery compared to Group 2.

Conclusion. Isolated supply of NO into the IR circuit has an additional cardioprotective effect, which is confirmed by statistically lower levels of troponin I and smaller changes in the indicators of myocardial contractile function during the postoperative period compared to standard technology. A more pronounced protective effect on the myocardium was shown with the combined supply of NO and molecular hydrogen to the IR circuit as seen by statistically lower levels of troponin I and MII in the postoperative period compared with the isolated supply of NO.

Inhaled nitric oxide (NO) and molecular hydrogen (iH₂) are actively studied nowadays. The therapeutic algorithms for their use in the various conditions are being developed, but the combined use of these medical gases (MG) has not been studied well enough.

The aim of the study was to assess the safety of iNO and iH₂ combination in healthy volunteers.

Methods. 10 healthy volunteers (4 males and 6 females), mean age 24.0 ± 1.3 years, were included in the open non-comparative prospective study. All volunteers received a single combined inhalation of NO and H₂ for 90 minutes. The NO concentration was 60 ppm and the H₂ concentration did not exceed 4% in the gas mixture. Changes in the vital signs, arterial blood gases, and hemodynamic parameters were evaluated. The hemodynamic parameters were investigated before and after inhalation using echocardiography (Vivid E9 General Electric, USA). We also assessed the microcirculation of the bulbar conjunctiva (“OKO” capillaroscope), the main functional lung parameters, and the diffusion lung capacity (GANSHORN PowerCube Body apparatus). The clinical side effects were recorded. After inhalation, the serum concentration of methemoglobin was evaluated.

Results. When comparing the results before and after MG inhalation, there was no negative impact on the vital signs, arterial blood gases (РaO₂, РaСO₂, SаO₂), the functional lung volumes (FEV₁, FVC, FEV₁ / FVC), the diffusion test parameters, main EchoCG hemodynamic data (ejection fraction, tricuspid annular plane systolic excursion (TAPSE), mean pulmonary artery pressure, left and right ventricular sizes) (p > 0,05). After inhalation, the microcirculatory parameters (the volume velocity in arterioles and venules and the arteriolar diameter) increased significantly (p < 0.05). We did not observe the increase in serum methemoglobin concentration (0.59 ± 0.11%). No clinical side effects were reported during the study.

Conclusions. Combined use of inhaled NO / H₂ is clinically safe, does not have any negative impact on hemodynamic parameters, functional lung volumes, and arterial blood gases. The improvement of the microcirculation was noted after a single inhalation. This new method can be recommended for further studies of the therapeutic effect in various conditions.

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressing disease characterized by a tumor-like overgrowth of smooth muscle fibers in the interstitial lung tissue, around blood and lymph vessels, bronchi, bronchioles, in lymph nodes. The disease has mainly been described in women of childbearing age, with a mean age of diagnosis of about 35 years.

Methods. This retrospective, cohort study included 16 patients who were diagnosed with LAM at the age of 17 – 53 years (Me – 39, HQ – 42.5, LQ – 30.5). The calculation of the volumetric area of cystic lesion in the entire volume of the lungs was carried out using the GE aws 3.2 Thoracic VCAR software. To assess the area of cystic lesion on histological sections, we calculated area of cystic formations, in the walls of which smooth muscle nodules were found. For statistical analysis, the Kolmogorov–Smirnov test, the Mann – Whitney U-test (p < 0.05), and the Spearman correlation analysis were used.

Results. Morphometric analysis of histological preparations of the lungs showed no statistically significant difference between women of young age and older age. A correlation was found between the volumetric area of cystic lesion on CT and FEV₁ (correlation coefficient = –0.886). Baseline median area of cysts was larger in patients who later deteriorated, while condition of patients with a smaller area of cysts remained stable (2.677 vs 1.119 mm2  correspondingly).

Conclusion. The volumetric area of cystic lesions in LAM correlates with functional parameters. The size of cysts in LAM may determine the prognosis of the course of the disease, because the formation of larger cysts is an unfavorable prognostic factor that increases the risk of developing pneumothorax. 

The aim of the work was to systematize the data on the biologically significant effects of molecular hydrogen to uncover the mechanisms of its effect on the human body. The paper analyzes the literature on the effect of molecular hydrogen administered in the form of inhalation and hydrogenenriched water on the human body, on laboratory mammals (rats, mice), and on model cell systems in vitro. As a result, a mechanism has been proposed according to which, in addition to the already known effect of hydrogen in neutralizing highly reactive oxygen species, there is at least one other group of molecules that are the target of molecular hydrogen in the body. These are the porphyrins, which are part of the hemoproteins, in particularly the cytochromes of the mitochondrial respiratory chain. In the presence of high concentrations of carbon dioxide, which is formed in the tricarboxylic acid cycle in the mitochondrial matrix, hydrogen damages some of the hemes as a result of covalent binding of the CO group to them. At low doses of hydrogen, this causes a moderate decrease in mitochondrial potential and stimulates the adaptive response of the body, including activation of the transcription factor Nrf2, expression of the heme oxygenase and antioxidant defense enzymes, mitophagy, and renewal of the mitochondrial population in the cell.

Conclusion. Molecular hydrogen is an adaptogen that causes mitochondrial hormesis – the renewal and strengthening of the body’s bioenergetic and antioxidant systems.

Chronic obstructive pulmonary disease (COPD) is one of major causes of chronic noncommunicable diseases and mortality worldwide. The roles of macrophages, T-lymphocytes, neutrophils, and other cells in the development of chronic inflammation in this disease are well studied, but more and more researchers have focused on mast cells (MC) in recent years.

The aim of this work is to summarize the data of experimental and clinical studies on the possible role of MCs in the pathogenesis of COPD. To this end, the review analyzed data on the relationship between MCs and respiratory function parameters in COPD, as well as the distribution of MCs subpopulations in different parts of the respiratory tract. The involvement of proteases (chymase and tryptase) in the development of inflammatory and fibrotic changes in COPD is discussed. The review presents research findings that indicate the possible involvement of chymase in pulmonary artery remodeling, increased secretion of mucins, and slowing down the airway epithelial repair. The role of MC tryptase in the development of fibrotic changes in the lungs and airways in COPD is also highlighted. A separate section of the review is devoted to chemokines that promote MC migration and their specific receptor. Chemokines play a special role in the development of inflammation in COPD.

Conclusion. The available data suggest that MCs play a major role in the pathogenesis of COPD. Because of the inconsistency of some results, further clinical studies in larger cohorts of patients are needed.

Pathogenesis of chronic lung diseases is assumed to involve systemic inflammation factors, as well as hormone-like substances adipokines produced by adipose tissue, which is an independent endocrine organ. Adipokines cause systemic inflammation under the influence of hypoxemia due to obesity and associated respiratory disorders such as obstructive sleep apnea syndrome, chronic obstructive pulmonary disease, hypoventilation syndrome, etc. However, the influence of specific adipocytes on the development and course of bronchopulmonary diseases remains unclear.

Purpose of this review was to evaluate the contribution of some adipocytokines to the development of bronchopulmonary conditions against abdominal obesity. We collected data on adiponectin, adipsin, lipocalin-2, interleukin 6, insulin, glucagon, leptin, monocyte-chemoattractant protein type 1, tumor necrosis factor-α, amylin, glucose-dependent insulinotropic polypeptide, ghrelin, and pancreatic polypeptide in patients with abdominal obesity and bronchopulmonary disorders.

Conclusion. The presented data confirm that hormone-like substances produced by adipose tissue make a significant contribution to the severity of respiratory disorders.

Tuberculosis (TB) remains a global problem up to this day. Against the background of the successes achieved in the fight against this infection, many problems have not yet been fully solved. These problems include drug resistance of the pathogen, comorbidity and multimorbidity of TB, the search for new types of drugs, the management and prevention of undesirable side effects of long-term chemotherapy, etc. These problems can only be solved through collaboration between health care professionals and patients. Timely abacillation, closing of decay cavities and stabilization of the clinical condition are practically impossible without such cooperation. Therefore, an important task of phthisiology is to stabilize the patient’s adherence to anti-TB therapy throughout the course of treatment.

The aim of the review is to describe existing and innovative ways to improve the level of adherence of TB patients to anti-TB therapy.

Conclusion. Current methods to improve adherence of TB patients, both in Russia and other countries, need to be improved and adequately funded. Additive technologies that more effectively reduce the risks of unmotivated discontinuation of polychemotherapy may be the solution.

“Ground glass opacity” (GGO) sign is one of the most common radiological symptoms of lung diseases that has become the focus of discussion by the general medical community during the pandemic of COVID-19. Non-specificity of GGO and the variety of diseases accompanied by this sign hinder the correct interpretation and differential diagnosis.

The purpose of this review is to study the differential diagnostic features of GGO detected by multispiral computed tomography in various lung diseases.

Conclusion. Knowledge of the features of GGO CT-pattern in various lung diseases significantly facilitates the interpretation of the imaging results and speeds up the differential diagnosis.

Currently, despite the accumulated experience with the use of N-acetylcysteine (NAC) in scientific and real clinical practice, there are a number of questions about its potential and the future prospects for its use.

The aim of this work was to summarize new data on the use of NAC in patients with various conditions, based on publications in domestic and foreign medical journals.

Results. The article presents an overview of publications in domestic and foreign medical journals devoted to the use of N-acetylcysteine (NAC) in pulmonology practice. The experience with the use of NAC in chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), bronchial asthma, community-acquired pneumonia, idiopathic pulmonary fibrosis, postinfectious bronchiectasis, and acute respiratory distress syndrome associated with COVID-19 (COronaVIrus Disease 2019) is summarized. The aspects of dose-dependent clinical effects and long-term administration of NAC in CB and COPD are analyzed. In addition, there are controversial and contradictory data on the possibility of prescribing NAC for idiopathic pulmonary fibrosis.

Conclusion. NAC is a drug with a broad spectrum of action. Due to its antioxidant and anti-inflammatory properties, minor side effects compared to other anti-inflammatory drugs even at high doses, and low price, NAC can be prescribed for many respiratory diseases. Although it has been used for more than half a century, interest in both its practical application and clinical research has not waned to this day.

The issues of organization of medical care and early administration of antifibrotic therapy in patients with progressive fibrotic phenotype require in-depth study and implementation in real clinical practice.

The aim of this paper is to provide a rationale for the early administration of antifibrotic drugs in patients with various forms of interstitial lung disease.

Results. The article addresses organizational issues in the medical care for interstitial lung disease with a progressive fibrotic phenotype. Topical epidemiological problems are also addressed, in particular the high mortality rate in this disease. The main risk factors of the disease are considered. Diagnostic markers for the fibrosis progression are analyzed. Data from large-scale studies on the early initiation of antifibrotic therapy and its effect on disease outcomes are presented.

Conclusion. The main reasons for early initiation of therapy in a progressive fibrotic phenotype are presented: an unfavorable prognosis, an unpredictable course, a progressive decrease in forced vital capacity, and the association of changes in FVC with an increase in mortality. Using the Chelyabinsk region as an example, a model of care for patients with interstitial lung diseases is considered, with a brief analysis of the effectiveness of antifibrotic therapy, its early initiation and the impact on mortality in patients with this disease.

Sepsis with acute organ dysfunction is an urgent problem of modern healthcare. A clinical case of a 38-year-old young woman with communityacquired severe viral-bacterial pneumonia complicated by sepsis, endocarditis, and multiple organ failure is presented. On the 68th day of her stay in the intensive care unit (ICU), the patient was brought out of comatose state and transferred to the pulmonology department for rehabilitation.

The purpose of the work was to demonstrate the significance of this clinical case because of the urgent need to increase the effectiveness of treatment and long-term rehabilitation of patients with this severe comorbid pathology.

Conclusion. Early diagnosis is extremely important to select effective treatment. The Quick SOFA (Sepsis-related sequential Organ Failure Assessment) score should be used to identify patients with suspected sepsis outside the ICU. This score is based on simple and accessible clinical characteristics that do not require laboratory analysis of homeostatic parameters. The patient was discharged in satisfactory condition to continue rehabilitation in outpatient settings.

Plastic bronchitis (PB) is a recurrent inflammation of the bronchi, characterized by the formation of fibrin-rich rubber-like secretions that obstruct the airways.

Aim. The authors present a rare case of PB in a 67-year-old woman who had been receiving treatment for bronchial asthma for 20 years. This case was complicated by the development of persistent atelectasis and saccular bronchiectasis of the left lower lobe requiring surgical treatment.

Conclusion. Removal of the rubbery contents of the bronchi by bronchoscopy provides a temporary effect only. Surgical treatment is advisable with a progressive course of the disease.