Increasing the life expectancy of patients with CF is an urgent healthcare task all over the world. According to the Register of patients with cystic fibrosis in the Russian Federation (2020), the number of patients over 18 years of age is 26.5%. Assumably, cystic fibrosis can be used as a model of accelerated aging to study the aging process in general.

Aim of the study was to analyze the number of rDNA copies in a sample of cystic fibrosis patients at different ages and with lethal outcome in relation to lung function, complications, and respiratory tract infections.

Methods. We studied DNA samples isolated by the standard method from peripheral blood leukocytes of 277 patients diagnosed with cystic fibrosis. 998 DNA samples from healthy volunteers were used as a control group.

Results. The study showed that the genomes of patients with CF contain more rDNA copies than those of control patients. The greatest number of copies of ribosomal genes was observed in DNA samples from deceased patients (p < 0.001) and was associated with more severe disease course. Among all CF patients, the largest number of rDNA copies in the genome was registered in patients with the lowest FEV1 values (less than 40%). It was found that patients with chronic Burkholderia cepacia complex infection had a significantly higher number of copies of ribosomal repeats than the total sample (p = 0.001) and the adults (p = 0.014). The number of ribosomal repeats did not differ between patients with other chronic respiratory tract infections.

Conclusion. In the group of deceased patients, the patients with low respiratory function and Burkholderia cepacia complex infection had the highest number of rDNA copies in the genome, and the differences were significant. It can be assumed that the number of rDNA copies in the genome of CF patients is an additional prognostic marker that is associated with the patient’s life expectancy.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases.

The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19.

Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed.

Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR.

Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.

The respiratory pump that provides pulmonary ventilation includes the respiratory center, peripheral nervous system, chest and respiratory muscles.

The aim of this study was to evaluate the activity of the respiratory center and the respiratory muscles strength after COVID-19 (COronaVIrus Disease 2019).

Methods. The observational retrospective cross-sectional study included 74 post-COVID-19 patients (56 (76%) men, median age – 48 years). Spirometry, body plethysmography, measurement of lung diffusing capacity (DLCO), maximal inspiratory and expiratory pressures (MIP and MEP), and airway occlusion pressure after 0.1 sec (P0.1) were performed. In addition, dyspnea was assessed in 31 patients using the mMRC scale and muscle strength was assessed in 27 of those patients using MRC Weakness scale.

Results. The median time from the COVID-19 onset to pulmonary function tests (PFTs) was 120 days. The total sample was divided into 2 subgroups: 1 – P0.1 ≤ 0.15 kPa (norm), 2 – > 0.15 kPa. The lung volumes, airway resistance, MIP, and MEP were within normal values in most patients, whereas DLCO was reduced in 59% of cases in both the total sample and the subgroups. Mild dyspnea and a slight decrease in muscle strength were also detected. Statistically significant differences between the subgroups were found in the lung volumes (lower) and airway resistance (higher) in subgroup 2. Correlation analysis revealed moderate negative correlations between P0.1 and ventilation parameters.

Conclusion. Measurement of P0.1 is a simple and non-invasive method for assessing pulmonary function. In our study, an increase in P0.1 was detected in 45% of post-COVID-19 cases, possibly due to impaired pulmonary mechanics despite the preserved pulmonary ventilation as well as normal MIP and MEP values.

According to the World Health Organization, chronic obstructive pulmonary disease is the third leading cause of death in 2020, accounting for approximately 6% of all deaths.

Aim. We studied how matrix metalloproteinases affect the likelihood and severity of chronic obstructive pulmonary disease.

Methods. The study included 60 patients aged 40 to 85 years with chronic obstructive pulmonary disease (7 women and 53 men). The average age of the patients was 63.2 ± 8.3 years. The smoker index ranged from 10 to 118 pack/years. We divided all examined patients into two groups by the severity of the disease, by age, by the duration of the disease, and by the clinical forms.

Results. Among the 60 examined patients, we did not identify a single patient with polymorphic variant C536T of TIMP-1 gene. All patients were homozygous and had the CC genotype. We found that only C-1562T polymorphism of MMP-9 gene is associated with severe COPD (p = 0.014), out of all studied variants of MMP-1, MMP-9, and MMP-12 genes. We did not find a reliable relationship between polymorphic variant C-1562T of MMP-9 gene and emphysematous changes in the lungs. We did not find a significant effect of polymorphic variants of MMP-1 and MMP-12 genes on the severity of COPD and the nature of structural changes in the lung tissue. As a result, we can assume that future studies should focus more on the relationship between the dominant pathogen and the level of matrix metalloproteinases. Understanding this relationship will allow us to influence the course and prognosis at an earlier stage of the disease. Our data on the leading role of polymorphism of MMP-1, MMP-9, and MMP-12 genes and other candidate genes are also confirmed by other recently published scientific papers.

Conclusion. This study established the presence of genetic markers for a poor prognosis of COPD. Smokers and people subject to occupational hazards are most susceptible to these factors.

The use of long-acting bronchodilators is central to the chronic obstructive pulmonary disease (COPD) therapy. One of the goals of bronchodilation is to reduce the morning COPD symptoms that are associated with a more severe disease and an increased risk of exacerbations.

The aim of the study was to evaluate the clinical efficacy of switching COPD patients with severe morning symptoms who received combinations of long-acting bronchodilators QD to a fixed-dose combination of aclidinium bromide (AB) and formoterol fumarate (FF) BID.

Methods. We examined COPD patients treated with combinations of long-acting β2-agonists and M-anticholinergics (but not AB and FF), who continued to complain of severe symptoms in the morning despite the treatment. After examination, the patients were switched to the fixed-dose combination of AB 0.4 mg and FF 0.012 mg (AB/FF) BID in the form of a metered-dose powder inhaler. The patients were examined at baseline and at 6-month follow-up.

Results. Of the 115 included COPD patients, 90 completed the study. After 6 months of treatment, they showed a significant decrease in the intensity of cough, sputum amount, severity of distant wheezing, and shortness of breath in the morning (–0.88, –0.38, –0.29, –0.58 on a 4-point scale, the mean score –0.44; p < 0.001). The result of the COPD Assessment test decreased from 28 (24; 34) to 24 (20; 28) (p = 0.011), the distance of a 6-minute walk increased from 319 ± 72 to 354 ± 67 m (p < 0.001). The fixed-dose combination of AB/FF did not cause serious adverse events.

Conclusion. The fixed-dose AB/FF combination in COPD patients resulted in a significant clinical improvement and was well tolerated. The AB/FF combination with twice daily dosing regimen is advisable for the patients with morning symptoms persisting despite therapy with other combinations of long-acting bronchodilators with once daily dosing regimen.

Post-COVID syndrome develops after COVID-19 (COronaVIrus Disease 2019) and leads to cumulative effects in the form of shortness of breath and impaired lung function. Notably, patients with airway inflammation and COVID-19 were found to have increased concentrations of hyaluronic acid (HA). Since bovhyaluronidase azoximer (Longidase®) catalyzes the hydrolysis of HA, this drug has the potential to reduce HA levels and improve lung function in patients with post-COVID syndrome.

The aim of the DISSOLVE trial, which was conducted early in the pandemic, was to investigate the efficacy and safety of bovhyaluronidase azoximer in patients with symptoms associated with post-COVID syndrome.

Methods. An open, prospective, controlled, comparative, multicenter clinical trial (NCT04645368) included adult patients (n = 160) who had post-COVID syndrome. Patients in the treatment group (n = 81) received bovhyaluronidase azoximer, and individuals in the control group (n = 79) were followed up without intervention. The study included physical examination, evaluation of forced vital capacity (FVC), assessment of dyspnea with the Modified Medical Research Council Dyspnea Scale (mMRC), 6-minute walking test, and pulse oximetry. These indicators were measured on 3 visits, at days 1 (baseline), 75, and 180. In addition, the number of patients who experienced adverse events and serious adverse events were recorded.

Results. Baseline patient characteristics in the treatment group and the control group were similar. In the treatment group, there was a statistically significant reduction in residual pulmonary abnormalities after visit 2 (day 75) and visit 3 (day 180). In addition, FVC, pulse oximetry values, and functional exercise tolerance increased statistically significantly at days 75 and 180 compared to baseline. The mMRC scores for dyspnea decreased statistically significantly in the treatment group over 75 days. The safety profile of the drug was reported to be favorable throughout the study.

Conclusion. Treatment with bovhyaluronidase azoximer in patients with post-COVID syndrome showed improvement in FVC, pulse oximetry, functional exercise tolerance, and mMRC dyspnea.

Deficiency of certain micronutrients interferes with the functioning of acquired immunity, which may negatively affect the efficacy and safety of vaccinations. The results of clinical and epidemiological studies have shown that micronutrient supplementation before vaccination increases its efficacy (antibody titers against viral/bacterial pathogens) and safety (prevention of malaise, reduction of disease severity and mortality in case of post-vaccination infection).

The aim of the study was to analyze the currently available studies on the relationship between micronutrient status and the results of vaccination against bacteria and viruses.

Conclusion. Micronutrient supplementation contributes to the formation of adequate immunity after vaccination and increases the safety of vaccination. Vitamin-mineral complexes represent a cost-effective method to reduce the risks of vaccination in patients with polyhypovitaminosis.

Chronic obstructive pulmonary disease (COPD) poses a significant burden on women’s health. Insufficient attention is paid to this problem in scientific research and in clinical practice, although more and more information surfaces about the gender-associated differences in the treatment, diagnostics, and management of COPD.

The aim of the review is to consider the most significant data currently available on the clinical signs, course, and outcomes of COPD in women and propose ways to achieve the best results in the diagnosis and treatment of this disease.

Conclusion. There are biological and cultural differences between the clinical manifestations, course and outcome of COPD in men and women, and these differences impact the clinical practice. It is advisable to apply individualized diagnostic, organizational, and pharmacotherapeutic approaches to COPD in women, based on the knowledge of female-specific variances in the symptoms of the disease and the health status.

Chronic obstructive pulmonary disease (COPD) is considered a typical model of accelerated aging due to the variability and systemic nature of its manifestations. The leading factor in tissue remodeling in COPD is a change or reprogramming of the cellular metabolism in response to external factors such as tobacco combustion products, biofuels, viruses, etc. Mitochondrial biology dominates the spectrum of mechanisms of tissue and cellular reprogramming in COPD. Being parasymbiotic organelles, mitochondria have a complex system of interaction with other cells of the human body and participate in both biogenesis, or formation of new organelles, and mitophagy, or elimination of defective mitochondria by the host cell. Both of these mechanisms are dysregulated in COPD.

The aim of this work is to combine the accumulated research experience in the field of cellular metabolism and the role of mitochondria for in-depth COPD phenotyping depending on the metabolic reprogramming variants and for development of new therapeutic possibilities to correct the reprogramming.

Conclusion. Mitochondria are key regulators of metabolism, redox homeostasis, cell survival and proliferation. These processes are controlled by various intra- and intercellular signaling pathways and reflect the COPD-associated imbalance at the level of various tissue lineages: alveolocytes, epithelial cells of the lung tissue, smooth myocytes of the respiratory tract, alveolar macrophages, striated muscle cells, mesenchymal stromal cells, progenitor cells, etc. The studies of metabolome and mitochondrial function pointed out where to look for new therapeutic options for COPD.

Community-acquired pneumonia is a potentially serious infection in children with high morbidity rate, risk of severe course and unfavorable outcomes. Specialists have noted the increased incidence of the destructive forms in the recent years.

Aim. To present a clinical case of destructive pneumonia in a 1 year 2 month old child, hospitalized in the State Budgetary Healthcare Institution “Children’s City Clinical Hospital of St. Vladimir Moscow Healthcare Department”, and analyze it in terms of current understanding on the disease pathogenesis.

Conclusion. During COVID-19 (COronaVIrus Disease 2019) pandemic, pulmonologists and pediatric surgeons encountered an unconventional course of destructive pneumonia. A large number of studies of pathophysiological processes in acute viral interstitial pneumonias have recently allowed to expand our understanding of the role of coagulation system. At the same time, new questions arose concerning the clinical course and development of the pathological infectious process.

According to the literature, exudative pleurisy and pericarditis are considered rare complications of the new coronavirus infection. This estimation can be explained by the fact that statistical studies cover mainly the hospital treatment of this disease. The true frequency of these complications and their consequences are not fully understood.

Aim. The study of late complications of the new coronavirus infection in the form of pleurisy and pericarditis.

Conclusion. In our case, a 62-year-old patient with the new coronavirus infection confirmed by polymerase chain reaction, severe bilateral polysegmental viral pneumonia, CT3, 60% on day 43 after the onset of clinical symptoms, was found to have manifestations of pleurisy and pericarditis during outpatient treatment. Cardiac MRI is the most informative method for detecting small pericardial and pleural effusions. The diagnostic capabilities of this method are superior to ultrasounography of the heart and pleural cavities and computed tomography of the lungs. Administration of colchicine 1.0 g per day for 1 month allowed not only to the elimination of pericarditis and pleurisy, but also the reduction of pressure in the right ventricle, probably by reducing the damage to the pulmonary parenchyma.

Chronic obstructive pulmonary disease (COPD) is a progressing disease. Each exacerbation impairs the patient’s prognosis and increases burden for the healthcare system. The most common maintenance treatment options for COPD include long-acting bronchodilators – β2-agonists (LABA) and long-acting antimuscarinic agents (LAMA), and inhaled glucocorticosteroids (ICS), in fixed/opened double and triple combinations. Triple therapy in subjects with exacerbation history is the most effective way to prevent negative outcomes of the disease. It can reduce the frequency of exacerbations, slow down the disease progression, improve quality of life, and reduce mortality in the long run. On the other hand, the response to triple therapy may change over the time depending on airways inflammation level, infection activity, and exacerbation frequency. Current COPD guidelines propose different indications for therapy escalation and de-escalation (ICS addition/withdrawal) for more personalized and safe treatment. At the same time, many practical issues of this process are still unclear, e.g. how often treatment regimens should be reviewed and what escalation/de-escalation criteria should be prioritized. The authors strongly believe that COPD therapy should adapt a holistic treatment approach (continuum) with quick responses to any changes in the patient’s condition.

The aim of our work was to create an algorithm for ICS administration/ withdrawal for COPD patients on long-acting dual bronchodilators maintenance therapy and to establish a therapeutic continuum that takes into account exacerbation history, symptoms severity, blood eosinophilia level, and concomitant asthma.

Conclusion. This instrument can be a useful and convenient tool for long-term patient management when access to specialized medical care might be restricted. It takes into account the main current recommendations for COPD management and is easy to apply in real clinical practice.

Patients with severe bronchial asthma, which remains uncontrolled despite the optimal basic therapy, carry a significant healthcare burden and require substantial financial investments. Severe asthma is a heterogeneous airway disease with complex pathophysiological mechanisms that can be broadly divided into inflammatory pathways with eosinophilic and non-eosinophilic inflammation.

Aim. This study aimed to analyze the literature data on the use of targeted genetic engineering therapy in patients with severe bronchial asthma, as well as to analyze the organization of immunobiological therapy in the Krasnoyarsk Territory. The addition of targeted drugs for severe eosinophilic bronchial asthma based on phenotyping has proven to be effective and is recommended by all current guidelines. Today, several biologics targeting specific endotypes and phenotypes has been approved for the treatment of severe eosinophilic asthma worldwide. These are antibodies binding immunoglobulin E (omalizumab), antagonists of interleukin-5 (mepolizumab, reslizumab) and its receptor (benralizumab), as well as antibodies selectively binding to the IL-4 and IL-13 receptors (dupilumab). Eosinophilic inflammation therapy is a relatively new direction of asthma treatment, and understanding its long-term efficacy and safety is important.

Conclusion. It is essential to differentiate patients with severe eosinophilic asthma from the general cohort of asthma patients, timely refer them to specialists who can prescribe this therapy and have experience with it, select the drug correctly, and monitor the patients during the treatment. This article describes organization of biological therapy for patients with severe eosinophilic bronchial asthma in the Krasnoyarsk Territory.