Aim . To study the effect of inhalation therapy with an active hydrogen (AH) on the protein composition of exhaled breath condensate (EBC) in patients with post-COVID syndrome (PCS). Material and methods . This randomized controlled parallel prospective study included 60 patients after coronavirus disease 2019 (COVID-19) with PCS during the recovery period and clinical manifestations of chronic fatigue syndrome who received standard therapy according to the protocol for managing patients with chronic fatigue syndrome (CFS). The patients were divided into 2 groups: group 1 (main) — 30 people who received standard therapy and AH inhalations (SUISONIA, Japan) for 10 days, and group 2 (control) — 30 medical workers who received only standard therapy. Patients in both groups were comparable in sex and mean age. All participants in the study were sampled with EBC on days 1 and 10. Samples were subjected to tryptic digestion and high-performance liquid chromatography combined with tandem mass spectrometry analysis using a nanoflow chromatograph (Dionex 3000) in tandem with a high-resolution time-of-flight mass spectrometer (timsTOF Pro). Results . A total of 478 proteins and 1350 peptides were identified using high resolution mass spectrometry. The number of proteins in samples after AH therapy, on average, is 12% more than before treatment. An analysis of the distribution of proteins in different groups of patients showed that only half of these proteins (112) are common for all groups of samples and are detected in EBC before, after, and regardless of hydrogen therapy. In addition to the qualitative difference in the EBC protein compositions in different groups, quantitative changes in the concentration of 36 proteins (mainly structural and protective) were also revealed, which together made it possible to reliably distinguish between subgroups before and after treatment. It is worth noting that among these proteins there are participants of blood coagulation (а-1-antitrypsin), chemokine- and cytokine-mediated inflammation, and a number of signaling pathways (cytoplasmic actin 2), response to oxidative stress (thioredoxin), glycolysis (glyceraldehyde-3- phosphate dehydrogenase), etc. Conclusion . The use of hydrogen therapy can contribute to the switching of a number of physiological processes, which may affect the success of recovery in PCS patients. In particular, the obtained results indicate the activation of aerobic synthesis of adenosine triphosphate in mitochondria by hydrogen therapy, which correlates well with the decrease in the blood lactate level detected by laboratory studies. At the same time, this therapy can inhibit pro-inflammatory activity, negatively affecting the coagulation and signaling pathways of integrins and apoptosis, and, in addition, activate protective pathways, tricarboxylic acid cycle, FAS signaling, and purine metabolism, which may be essential for effective recovery after COVID-19.

Therapy with inhaled nitric oxide (iNO) in patients with hypercapnic respiratory failure (RF) and pulmonary arterial hypertension (PAH) is currently of scientific interest. The aim of this study was to evaluate the effects of iNO therapy on COPD patients with hypercapnic RF and PAH during exacerbation of the disease. Methods. A randomized, prospective, controlled trial included 30 patients with COPD (age 65 (62; 75) years) with hypercapnic RF and pulmonary arterial hypertension (PAH) treated at the State Budgetary City Teaching Hospital “City Clinical Hospital named after D.D.Pletnev of Healthcare Moscow City Department” (2021). The inclusion criteria were: PaCO 2 ≥ 45 mm Hg and pulmonary artery systolic pressure PASP > 40 mm Hg as accessed by Doppler echocardiography. The patients were divided into two groups. Patients of the main group were administered iNO in the form of daily 90-minute sessons for two weeks using Tianoks device (Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics, State Corporation “Rosatom”, Russia). Patients of the control group received treatment that corresponded to the severity of their COPD exacerbation according to the guidelines by Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2020 – 2021. Hemodynamics and gas exchange, exercise tolerance, vascular stiffness, and obstructive disorders were assessed at baseline, on Days 7 and 14. Results. The main group demonstrated a decrease in PASP (38 (32; 43) mm Hg vs 47 (44; 54) mm Hg; p = 0.001), a decrease in stiffness index (SI) (7.03 m / s (5.3; 19.2) vs 12.2 m / s (5.7; 15.1); p = 0.01), decrease the pulmonary shunt fraction (Qs / Qt) (4.33% (3.7; 6.1) vs 9.12% (7.12; 11.3); p = 0.01), an increase in arterial vascular tone measured by reflective index (RI) (62.4% (51.2; 64.3) vs 58.5% (51.7; 63.8); p = 0.01), and increased exercise tolerance measured by 6-minute walking test (6MWT) (358.1 m (320.5; 368.2) vs 321.5 m (280.4; 329.1); p = 0.001) as compared to the control group. Conclusion. Our study indicates that iNO-therapy effectively reduces hypoxemia, endothelial dysfunction, improves hemodynamics, walking distance, and exercise tolerance during the exacerbation of COPD in patients with hypercapnic RF and PAH.

The proteome of exhaled breath condensate was analyzed by mass spectrometry before, immediately after the thermoheliox procedure and after a 3 h relaxation. The major part of the proteome remained unchanged and there was no extensive cell destruction

Active hydrogen inhalation (H(H2O)m) has powerful antioxidant and antiapoptotic effects. In recent years, it has been used in a number of experimental and clinical studies.Aim. To study the safety and effectiveness of inhalation of the “active form of hydrogen” (AFV;(H(H2O)m)) in the rehabilitation program of coronavirus disease 2019 (COVID-19) survivors during the recovery period.Material and methods. This randomized controlled parallel prospective study included 60 COVID-19 survivors with post-COVID-19 syndrome (ICD-10: U09.9) during the recovery period, with clinical manifestations of chronic fatigue syndrome (CFS), who received standard therapy in accordance with the management protocol of patients with CFS (ICD-10: G93.3): physiotherapy and medication therapy with drugs containing magnesium, B vitamins and L-carnitine. The patients were divided into 2 groups. The experimental group (n=30) included patients who received hydrogen inhalation for 90 minutes every day during 10 days (SUISONIA hydrogen inhalation device, Japan). The control group (n=30) consisted of patients who received standard therapy. In both groups, patients were comparable in sex and mean age: in the experimental group — 53 (22; 70) years, in the control group — 51 (25; 70) years. Biological markers of systemic inflammation, oxygen transport, lactate metabolism, intrapulmonary shunting, 6-minute walk test, and vascular endothelial function were determined in all patients on the 1st and 10th days of follow-up.Results. In the experimental group, a decrease in following parameters was revealed: stiffness index (SI), from 8,8±1,8 to 6,8±1,5 (p<0,0001); ALT, from 24,0±12,7 to 20,22±10,61 U/L (p<0,001); venous blood lactate, from 2,5±0,8 to 1,5±1,0 mmol/L (p<0,001); capillary blood lactate, from 2,9±0,8 to 2,0±0,8 mmol/L (p<0,0001); estimated pulmonary shunt fraction (Qs/Qt, Berggren equation, 1942) from 8,98±5,7 to 5,34±3,2 (p<0,01); white blood cells, from 6,64±1,57 to 5,92±1,32 109/L. In addition, we revealed an increase in the refractive index (RI) from 46,67±13,26% to 63,32±13,44% (p<0,0001), minimum blood oxygen saturation (SpO2) from 92,25±2,9 to 94,25±1, 56% (p<0,05), direct bilirubin from 2,99±1,41 to 3,39±1,34 pmol/L (p<0,01), partial oxygen tension (PvO2) from 26,9±5,0 to 34,8±5,6 mm Hg (p<0,0001), venous oxygen saturation (SvO2) from 51,8±020,6 to 61,1±018,1% (p<0,05), partial capillary oxygen tension (PcO2) from 48,7±15,4 to 63,8±21,2 mm Hg (p<0,01), capillary oxygen saturation (ScO2) from 82,2±4,2 to 86,2±4,8% (p<0,01), distance in 6 minute walk test from 429±45,0 to 569±60 m.Conclusion. Inhalation therapy with H(H2O)m in the rehabilitation program of COVID-19 survivors during the recovery period is a safe and highly effective method. Manifestations of silent hypoxemia and endothelial dysfunction decreased, while exercise tolerance increased. As for laboratory tests, a decrease in the white blood cell count, estimated pulmonary shunt fraction and lactate content parameters was revealed.

The high efficiency of using thermoheliox (inhalation with a high-temperature mixture of helium and oxygen) in the treatment of patients affected by COVID-19 was shown. The dynamics of accumulation of IgG, IgM, and C-reactive protein (CRP) in patients with coronavirus infection in the “working” and control groups was studied experimentally. It was shown that thermoheliox intensifies the synthesis of IgG, IgM, and CRP antibodies, while eliminating the induction period on the kinetic curves of the synthesis of specific antibodies in the IgG form and transfers the synthesis of CRP to a fast phase. The results of experiments confirm the previously obtained data based on the analysis of the kinetic model of the development of coronaviral infection in the human body.

Respiratory failure syndrome often develops due to the development of acute stroke but is not always diagnosed and treated. A new method of treating this syndrome improves the clinical course and prognosis of acute stroke.

A kinetic model of the development of acute viral infection is proposed and the dynamic behavior of key variables, including the concentrations of viral particles, infected cells, and pathogenic microorganisms, is described. The change in the hydrogen ion concentration in the lungs and pH dependence of the activity of carbonic anhydrase, a key respiration enzyme, are critical factors. An acute bifurcation transition determining either the life or collapse of the system is demonstrated. The transition is associated with exponential increase in the concentrations of participants in the process and with functioning of the key enzyme, carbonic anhydrase. A physicochemical interpretation is given for the therapeutic effect of temperature rise and potential therapeutic effect of "thermoheliox", that is, breathing by heated helium-oxygen mixture.

In this paper, we will discuss the use of t-Не/О 2 in the treatment of patients with the viral disease COVID-19. The aim of the study is to evaluate the effect of thermal helium-oxygen therapy on viral load, inflammatory markers, and antibody synthesis. Methods . A single-center, randomized, prospective study included 60 patients with COVID-19. Patients were divided into two groups: 1 ( n = 30; 17 male, 13 female) – t-Не/О 2 therapy was included in the standard COVID-19 treatment Protocol; 2 ( n = 30; 16 male, 14 female) – standard therapy in accordance with the clinical recommendations of Healthcare Ministry of Russia for patients with COVID-19. Of the 60 patients included in the study, 28 (46.7%) were medical professionals. The median age of patients in the study was 56.7 (45 – 61) years old. In the group 1 – 58 (45 – 59.5) years old, in the group 2 – 55 (46 – 66) years old. All patients had a positive test of SARS-CoV-2 coronavirus RNA, CT signs of “ground-glass opacity” type lung damage, and areas of air space consolidation. Patients were comparable by gender, age, body mass index (BMI), area of lesion of the pulmonary parenchyma, laboratory data. Results . As a result of the use of t-Не/О 2 , the elimination of the SARS-CoV-2 virus occurred within 48 – 72 hours from the start of inhalation and was confirmed by PCR test. The following changes were found in all patients: synthesis of IgM and IgG antibodies, increase in lymphocytes level, decrease of C-reactive protein, restoration of alanine aminotransferase and aspartate aminotransferase levels, D-dimer, and ferritin. These signs became more pronounced in the 1 st group within 72 – 168 hours, compared with the 2 nd group, where these results were achieved on the 10 th day of therapy. Conclusion . Тhe inclusion of thermal inhalation a gas mixture of helium and oxygen (t-Не/О 2 ) in the standard therapy of patients carrying infectious disease caused by SARS-CоV-2 with CT signs of COVID-19 pneumonia (СT1, CT2 grades) reduces the viral load by stimulating antibody synthesis, as the type of immunoglobulin G, and immunoglobulin M causing the effect of “termovaccination”; increases the effectiveness of treatment, reducing the markers of inflammation.

The proteome of exhaled breath condensate was analyzed by mass spectrometry before and immediately after the thermoheliox procedure and after a 3 h relaxation. The major part of the proteome remained unchanged and there was no extensive cell destruction.

Various degrees of pulmonary insufficiency (PI) (PaO2 ≤60 mm Hg, SaO2 ≤90%) are diagnosed in most of patients with severe acute stroke (AS). Frequency and severity of PI positively correlates with the severity of AS. PI worsens patient's condition, prolongs the hospitalization period, and increases the probability of fatal outcome. Early clinical signs of PI may be undiagnosed due to the severity of stroke and thus not treated. The initiating pathogenic mechanism of PI is stress-related activation of sympathetic nervous system (SNS) and systemic immunosuppression. In severe stroke with mass effect, the rapid and significant increase in intracranial pressure may additionally activate the SNS. Risk factors of PI include older age, previous pulmonary disease, prolonged supine position, respiratory muscle dysfunction, apnea, and concomitant somatic diseases. Decompensation of somatic diseases leads to multiple stage reactions with facilitation of functional and morphologic changes in the pulmonary system, hypoxemia and hypoxia, promotes infectious complications and multiple organ failure and worsens neurological outcome. Diagnosis and treatment of PI in AS decreases mortality and improves rehabilitation prognosis.

The aim of this study is to assessment of the rapid effects of t-He/O2 in comparison with the effective level of high-flow oxygen therapy (HPO) on the main indicators of oxygen transport, central and pulmonary hemodynamics in patients with chronic obstructive pulmonary disease (COPD) with hypercapnic acute respiratory failure.Methods. A total of 33 (29 male, 4 female) patients were included in a randomized, comparative study with exacerbation of COPD and acute respiratory failure, admitted to the department of anesthesiology and intensive care of D.D.Pletnev City Teaching Hospital, Moscow Healthcare Department, between March and May 2017. Patients were divided into two groups: the 1st group – 18 patients (15 male, 3 female) receiving t-He/O2 (He – 70%, O2 – 30% at a temperature of 70 °C; the 2nd group – 15 patients (14 male, 1 female) receiving high-flow oxygen therapy with FiO2 – 30% through a Venturi mask for the treatment of ODN against the background of basic therapy of the underlying disease, according to the recommendations of GOLD 2016. Assessment of oxygen transport, central and pulmonary hemodynamics was carried out through the definition of indicators: saturation of hemoglobin of arterial blood with oxygen (SaO2), saturation of venous blood hemoglobin with oxygen (SvO2), partial pressure of arterial blood oxygen (РaO2), partial pressure of arterial blood carbon dioxide (РaCO2), partial pressure of mixed venous blood oxygen (РvO2), partial pressure of mixed venous blood carbon dioxide (РvCO2),mean pulmonary artery pressure (MPAP), cardiac output (SV), heart index (CI), pulmonary vascular resistance (RVRI), impact volume index (SVI), pulmonary vascular resistance index (RVRI), left ventricular shock index (LVSW), right ventricular shock index (RVSW), system speed of oxygen delivery (DO2), the coeffiCIent of extraction of oxygen (ExO2), shunt fractions (venous mixing) (Qs / Qt)).Results. Short-term inhalation with a thermal helium-oxygen mixture in patients with COPD with hypercapnic acute respiratory failure is accompanied by an increase in SaO2 94,1 (92,8; 97,5) initially 86,1 (85,9; 88,1), РаО2 (78,1 (74,8; 80,1) initially 55,2 (52,5; 65,3)), decline РаСО2 (57,4 (54,2; 66.4) initially 65,4 (58,1; 67,2)). Thermal helium-oxygen mixture leads to stabilization of hemodynamics, improving the work of the right and left heart: decline MPAP 28,2 (24,3; 32,8) initially 43,3 (40,1; 49,5), RVRI (285,3 (258,4; 362,7) initially 592,1 (498,2; 623,5)), RVSW (16,2 (14,1; 21,4) initially 25,8 (21,8; 32)), HR 91,1 (86,4; 98,7) initially 115 ((105; 118) to increase LVSW (58,2 (49,8; 62,4) initially 35,5 (28,9; 42,1)), SVI 36,2 (31,8; 42,1) initially 31,5 (28,4; 36,2). Elimination of arterial hypoxemia and a positive effect on hemodynamics ensures adequate oxygen transport to tissues, which is expressed in the normalization of DO2 values DO2 (980,4 (858,45; 1208) initially 280,3 (270,34; 387,4)) и ExO2 (27,8 (25,6; 34,5) initially 32,1 (30,7; 39,8) and decline Qs/Qt. (28,7 (18,6; 35,4) initially 42,8 (39,2; 49,1).Conclusion. Short-term therapy of patients with COPD with hypercapnic acute respiratory failure using the t-He/O2 method, in comparison with high-flow oxygen therapy, improves blood oxygenation and hemodynamics. Elimination of arterial hypoxemia and a positive effect on hemodynamics made it possible to ensure adequate oxygen transport to tissues, which was expressed in the normalization of transport values, oxygen delivery, and a decrease in the shunt fraction.

AIM:Conducting a pilot study to assess the effect of thermal heliox on the state of the respiratory tract by studying of the exhaled breath condensate protein composition before the thermal heliox procedure, immediately after and after three hours of relaxation Materials and methods. A comparative study of the exhaled breath condensates (EBC) protein composition of five non-smoking healthy donors was carried out. The EBC was taken before the respiratory procedure, immediately after a 20-minute inhalation by mixture of He/O2 gases (70/30) heated to 70C and 3 hours later. The protein composition was determined by chromatography-mass spectrometric analysis after selective tryptic hydrolysis. The results were processed using the Mascot program and the UniProt database.RESULTS:After the heliox procedure, the volume of the collected condensate (11.5 ml) decreases by an average of 32% and is practically restored after three hours of relaxation. Most proteins were consistent for all samples, regardless of the thermal heliox procedure. These are keratins, several proteins of the immune system (immunoglobulins, compliment proteins), tubulin. In samples after thermal heliox, the appearance of small amounts of additional proteins is observed. These are proteins of muscle metabolism (actin and calmodulin), fibrinogen, traces of hemoglobin, apolipoprotein, type B creatine kinase. After three hours of relaxation, tubulin disappears in the EBC.CONCLUSION:Most exhaled proteins are the same before, after the procedure, and for three hours of relaxation. The results obtained demonstrate the relative safety of the use of high temperature heliox as a therapeutic agent.

Background. The paper discusses the use of a thermal helium-oxygen mixture (t-Не/О2 ), a novel technology, in treating patients with the 2019-nCoV acute respiratory disease (COVID-19) who develop life-threatening respiratory failure. Aim to evaluate the safety and efficacy of t-Не/О2 inhalation combined with standard therapy in the treatment of acute respiratory failure in patients with COVID-19. Materials and Methods. This was a single-center, randomized, prospective study of 70 patients with COVID-19. All patients were divided into two groups: in Group 1 (n = 38) patients received t-He/О2 in addition to the standard COVID-19 treatment; and in Group 2 (n = 32) patients were given the standard treatment in accordance with the Clinical Treatment Guidelines for patients with COVID-19, developed by the Ministry of Health of the Russian Federation. The male/female ratio was 18/20 in Group 1 and 18/14 in Group 2. The mean age of the patients in the study was 53.5 years (43; 62): 56 years (42; 64) in Group 1 and 52 years (43; 66) in Group 2. All patients had computed tomography (CT) signs of lung injury: ground-glass opacities and areas of consolidation. SARS-CoV-2 RNA was detected in 30 Group 1 patients and 28 Group 2 patients. The patients were matched by sex, age, body mass index (BMI), area of pulmonary involvement, and laboratory findings. All patients provided voluntary informed consent to participate in the study and signed a consent form. Results. Inhalation of thermal helium-oxygen mixture combined with standard therapy did not cause any procedure-related side effects in any of the patients. The following changes were observed in all patients: pO2 /FiO2 , SpO2 , and lymphocyte counts increased, C-reactive protein (CRP) levels decreased, and D-dimer and ferritin levels returned to normal. In Group 1 statistically significant changes in the above-mentioned parameters were seen within three days, while in Group 2 the same changes were observed between Days 7 and 10 of treatment. In Group 1 patients cleared SARS-CoV-2 within 4872 hours after initiation of inhalation, which was confirmed by polymerase chain reaction (PCR), and in Group 2 virus elimination was achieved within 72168 hours. Conclusion. The addition of inhalation of a thermal gas mixture of helium and oxygen (t-He/О2 ) to the standard therapy for patients with SARS-CoV-2 infection, CT signs of pneumonia (grades СT2 or CT3), and acute respiratory failure improves gas exchange, contributes to a more rapid virus elimination, and indirectly reduces inflammation.