[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.

[Problems and opportunities to improve diagnosis of asthma and chronic obstructive pulmonary disease in Russia: resolution of advisory board].

Asthma and chronic obstructive pulmonary disease remain major problems of medicine, and still there is need to improve the level and quality of diagnosis of these diseases. Primary care physicians (general practitioners, therapists) should be involved widely and actively in this process. To simplify the diagnosis, special questionnaires have been developed, they can be used in a real clinical practice. Only this approach will bring statistical data closer to the true prevalence of these diseases and improve quality of their treatment.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

[Case of lifetime diagnosis of isolated primary amyloidosis of the heart].

The article presents a case of intravital diagnosis of a rare heart disease, isolated primary amyloidosis. The clinical onset of the disease was heart failure (HF) that was resistant to treatment; chemotherapy was ineffective and was poorly tolerated by the patient. The diagnostics was based on a combination of refractory HF and changes in echocardiography data (atrial dilatation, small size of the left ventricular cavity, interventricular septal hypertrophy with the presence of hyperechoic inclusions of the "granular fluorescence" type), and changes detected by contrast-enhanced cardiac magnetic resonance imaging. The diagnosis of amyloidosis was confirmed by results of pathohistological examination of the material obtained during autopsy.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

[International register "Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients (ACTIV SARS-CoV-2)"].

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[Modern understanding of bronchial asthma with fixed airflow obstruction].

The review provides data on one of the phenotypes of severe bronchial asthma it is asthma with fixed airway obstruction. According to data published today, there is no single pathway for the formation of fixed airway obstruction in patients with severe asthma. Increasing knowledge of the pathophysiology of fixed airway obstruction, as well as identifying the most significant risk factors, is essential for the successful treatment of such patients. In addition, the development of fixed obstruction is associated with a worse and sometimes fatal prognosis. Expanding the existing views is also necessary to overcome the difficulties of differential diagnosis between bronchial asthma with fixed airway obstruction and bronchial asthma in combination with COPD. All this will optimize the approach to the management of patients with bronchial asthma to prevent the formation of fixed airway obstruction.

[Severe bronchial asthma patient care organization in various regions of the Russian Federation. From endotypes and phenotypes of bronchial asthma to personalized choice of therapy].

The meeting of the Expert board was held in Moscow on June 24, 2019, at which the following issues were considered: the applicability of a new terminology characterizing asthma endotypes and phenotypes in real clinical practice, the effect of phenotypes and biomarkers in patients with bronchial asthma on the choice of biological drug, as well as the optimal clinical profiles of patients for whom dupilumab is most effective, taking into account the data of the III phase clinical trials, regional features of medical care and changes in updated international clinical guidelines for the diagnosis and treatment of asthma. The Expert board included members of leading Russian scientific and educational medical institutions: S.N. Avdeev, corresponding member of the Russian Academy of Sciences, prof., MD; O.A. Volkova, Ph.D.; I.V. Demko, prof., MD; G.L. Ignatova, prof., MD; I.V. Leshchenko, prof., MD; Kanukova N.A.; Kudelya L.M., prof., MD; V.A. Nevzorova, prof., MD; N.G. Nedashkovskaya; O.P. Ukhanova, prof., MD; L.V. Shulzhenko, prof., MD; R.S. Fassakhov, prof., MD.

Features of cellular structure of the induced sputum and profile of cytokines at sintropiya of bronchial asthma and obesity at young patients.

AIM: To estimate changes of cellular structure of the induced sputum at young patients with bronchial asthma at interrelations with BMI and level of cytokines in blood plasma. MATERIALS AND METHODS: 164 patients with bronchial asthma were divided into 2 groups taking into BMI: the 1st group included patients with bronchial asthma and BMI from 18 to 25 kg/m2, patients with bronchial asthma and BMI from 30 to 40 kg/m2 entered into the 2nd group. The group of control was made by 40 almost healthy volunteers. Estimated existence of excess weight and defined obesity degree according to recommendations of World Health Organization. Studied the level of control of bronchial asthma, cellular structure of the induced sputum, the IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, INF-γ levels in plasma of peripheral blood. RESULTS: There are presented the results of the research of cellular profile of the induced sputum and profile of cytokines at patients with bronchial asthma depending on BMI and severity of the disease. The received results testify to prevalence of eosinophilic type of an inflammation in the group of patients with BMI less than 25 kg/m2 whereas at patients mainly paucigranulation inflammation decided on obesity. The highest content of the Il-17 was registered at patients with bronchial asthma and obesity as in comparison with indicators of patients with normal BMI, and with almost healthy that, perhaps, is the reason of low effect of steroid therapy at these patients. CONCLUSION: Endotype assessment before basic antiinflammatory therapy at patients with the first time diagnosed bronchial asthma, will be able to help with selection of the most optimum treatment to each specific patient.

[ACOS: Clinical and functional features The Russian formulation mesalazine (kansalazine) in the therapy of ulcerative colitis]. / ACOS-sindrom: kliniko-funktsional'nye osobennosti.

AIM: To investigate the clinical and functional parameters in patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) versus those with chronic obstructive pulmonary disease (COPD) and asthma. SUBJECTS AND METHODS: A total of 129 people were examined. 51 patients with ACOS were followed up in Group 1; Group 2 included 38 patients with severe asthma; Group 3 consisted of 40 patients with severe COPD. All the patients underwent clinical examination: history data collection, physical examination, evaluation of disease symptoms, and study of respiratory function (spirometry, body plethysmography). RESULTS: ACOS is clinically characterized by considerable demands for emergency drugs and by more frequent asthmatic fits and exacerbations, which require hospitalization. The parameters of bronchial resistance in ACOS were established to be increased throughout the follow-up period and to be comparable with those in patients with COPD. In the patients with ACOS, the severity of pulmonary hyperinflation was associated with increased demands for emergency drugs (r=0.59; p=0.015). Fixed bronchial obstruction in ACOS can be caused by smoking intensity and duration associated with increased bronchial resistance in expiration (r=0.51; p=0.003) and intrathoracic volume (r=0.71; p=0.0001); as well as increased body mass index (p<0.001) and disease duration, which were interrelated with a reduction in the forced expiratory volume in one second/forced vital capacity ratio (r=-0.63; p=0.001 and r=-0.71; p=0.0034, respectively). CONCLUSION: Patients with ACOS show more severe clinical manifestations and a substantial increase in functional residual capacity and intrathoracic volume throughout the follow-up period, suggesting that the distal bronchi are impaired and pulmonary hyperinflation develops.

[CLINICAL AND PATHOGENETIC PECULIARITIES OF DEVELOPMENT OF ENDOTHELIAL DYSFUNCTION].

The purpose of the study was to examine the relationship between functional parameters, arterial rigidity, lipid profile, markers of systemic inflammation and endothelial dysfunction in patients with COPD and COPD + coronary heart disease. We examined 110 subjects divided into 3 groups. G group 1 included 40 patients with severe and very severe COPD, group 2 consisted of 40 patients with severe and very severe COPD + coronary artery disease, the control group was comprised of 30 healthy volunteers. We studied parameters of respiratory function, the level of blood oxygenation, the main characteristics of arterial rigidity plasma lipid, TNF-α, CRP, fibrinogen, sPECAM-1 levels and the expression of CD38/ADP-ribosylcyclase in peripheral blood lymphocytes. The study revealed increased rigidity of the central arteries in the patients of groups 1and 2 regardless of the duration of observation and the presence of coronary artery disease, as evidenced by the increase of the pulse wave velocity in the aorta. Patients of both groups had elevated levels of TNF-α, CRP and fibrinogen indicating systemic inflammatory response. Taken together, the enhanced expression of CD38 in peripheral blood lymphocytes, elevated concentration of soluble CD31 (sPECAM-1) in both groups related to bronchial obstruction and neutrophil elastase activity as well as increased rigidity of the vascular bed gives evidence that the CD38 and sCD31 relationship plays a role in the formation of endothelial dysfunction, and dysregulation of vascular tone in COPD patients. Disorders of lipid metabolism combined with increased rigidity of the vascular wall, elevated levels of markers of systemic inflammation and endothelia dysfunction, suggest that patients with COPD are at risk of cardiovascular events.

[Functional and laboratory characteristics in the concomitance of asthma and obesity at a young age].

AIM: To study the peripheral blood level of leptin and adiponectin and their possible effect on the functional status of the respiratory system in young asthmatic patients in relation to body mass index (BMI) for the optimization of asthma therapy. MATERIALS AND METHODS: Examinations were made in 133 people, including a study group of 93 patients with asthma who were divided into 2 groups according to BMI: 1) those with a BMI of less 25 kg/m2 and 2) those with a BMI of 30 kg/m2 or more, as well as a control group of 40 apparently healthy patients. The investigators studied external respiratory function (ERF), the peripheral blood levels of leptin and adiponectin, the biochemical composition of plasma, by determining total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. RESULTS: Lipid metabolic disorders as dyslipidemia and hypercholesterolemia, increased severity of disease, and decreased ERF were recorded in the concomitance of obesity and asthma. The peripheral blood level of leptin in young asthmatic patients with obesity was found to be associated with higher BMI. CONCLUSION: A more severe course of disease presenting with decreased ERF, impaired lipid metabolism, and elevated peripheral blood leptin levels were noted in the concomitance of asthma and obesity at a young age.

[A case of mucoviscidosis in practical work of a pulmonologist].

A case of late manifestation ofmucoviscidosis is reported. In the past, this pathology was dealt with by pediatricians, but to-day the management of this problem involves a number of different specialists. The progress in clinical practice makes it possible to significantly prolong the life span of patients with this condition. The present case shows that its clinical manifestations may appear at any age.

[Impact of tobacco smoking on the clinical and functional indicators and markers of systemic inflammation in patients with severe asthma].

AIM: To study cytokine status and to reveal a possible relationship of clinical and functional indicators and systemic inflammation in patients with severe asthma to tobacco smoking. Subjects and methods. Examinations were made in 139 patients with severe asthma during its exacerbation and without the latter after 12 months. Groups 1 and 2 included 98 nonsmoking and 41 smoking patients with severe asthma, respectively. A control group consisted of 40 apparently healthy volunteers. External respiratory function, plasma TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, C-reactive protein, and neutrophil elastase levels, and integral cytokine index were studied. RESULTS: Systemic inflammation that was more marked on a disease exacerbation and mediated by elevated TNF-α, IL-2, and C-reactive protein levels was detected in severe asthma in both groups. The smoking patient group showed a statistically significant increase in IL-8 and neutrophil elastase levels, which may be indirectly indicative of the active participation of neutrophils in the development of chronic persistent inflammation. CONCLUSION: Tobacco smoking is a clinically significant risk factor that aggravates both the course of asthma and the magnitude of inflammation during a disease exacerbation.

[THE RELATIONSHIP BETWEEN DISORDERS-OF EXTERNAL RESPIRATION AND RIGHT HEART REMODELING IN PATIENTS WITH ATOPIC BRONCHIAL ASTHMA].

This study aimed at the evaluation of the state of the respiratory system and its possible influence on the structural and functional characteristics of the right heart in patients with atopic bronchial asthma (BA) with a view to optimizing diagnostics and prevention of cardiovascular complications. The study included 189 subjects of whom 148 with BA were divided into 3 groups depending on the severity of the disease. Forty practically healthy volunteers comprised the control group. The external respiration function and right ventricle functional parameters were the main variables measured in all the participants of the study. It was shown that disorders of external respiration and pulmonary hyperinflation progressed with severity of BA and thereby promoted right ventricular myocardium remodeling and dysfunction that in turn led to chronic cardiac insufficiency. It is concluded that functional changes in the right heart in of patients with BA of different severity are associated with remodeling of the respiratory tract.

[Organization and character of measures to realize and conduct medical examinations of workers in Krasnoyarsk area according to Russian Health and Social Development Ministry Order No. 302n (12/04/2011)].

The article presents organizational, informational, educational and methodic measures accomplished in Krasnoyarsk area, aimed to timely and high-quality fulfil the Russian Health and Social Development Ministry Order No 302n (12/04/2011) in its part concerning procedure of mandatory preliminary and periodic medical examinations of workers.

[CD38/ADP-ribosyl cyclase, a marker of endothelial dysfunction in bronchial asthma].

The study was aimed at measuring the number of CD38+ lymphocytes in peripheral blood and its relationship with a marker of endothelial dysfunction CD31/PECAM-1 in patients with moderate or severe bronchial asthma (BA) during exacerbation and 12 months after it. The study groups included 153 patients, the control one consisted of 40 subjects. Group 1 comprised 106 patients with moderate BA, group 2 patients with severe steroid-independent BA (n=61), group 3 patients with steroid-dependent BA (n=53). CD38+ lymphocytes were detected by immunocytochemical methods, IL-6, IL-4, IL-2, and TNF-α by solid-phase immunoenzyme assay. BA patients exhibited signs of systemic inflammation reflected in the two-fold and 2.5-fold increase of serum TNF-α and IL-6 levels respectively in the patients of group 1. TNF-α, IL-6 and C-reactive peptide levels increased by 3, 2 and 2.5-4 times in groups 2 and 3. Exacerbation of BA resulted in a 5-fold rise in the number of DC38 lymphocytes that persisted during the next 12 months suggesting a 15% increase in the level of sPECAM-1/sCD31 (a non-substrate ligand of CD38) associated with endothelial dysfunction. The study revealed positive correlation between elevated sPECAM-1/sCD31 levels and the number of CD38+ lymphocytes in all groups (r=0.456; p<0.05).

[Clinical picture and treatment of bronchial asthma comorbid with cardiovascular diseases].

AIM: To evaluate prevalence of cardiovascular diseases (CVD) in bronchial asthma (BA) patients and effects of CVD on BA course. MATERIAL AND METHODS: Register data for 2005 have been analysed for 5104 BA outpatients living in Krasnoyarsk city (pulmonary ventilation, ECG, echocardiography, duration of BA, number of exacerbations for the last 12 months, number of hospitalizations, disability, BA complications, BA and CVD treatment). RESULTS: Combination of BA with CVD was observed in 88.3% patients. Severe and moderate BA was in 55 and 44% patients, respectively. 64% BA patients were invalids. CVD were diagnosed more often in patients with detected BA. CVD were treated without allowances for BA. The latter was treated without consideration of its severity and GYNA recommendations. CONCLUSION. To control BA, it is necessary to check up pulmonary function regularly, to diagnose comorbid cardiovascular diseases early, prescrive adequate treatment and teach patients to comply with recommendations.