The objective: to compare the correct use of different types of inhalers in patients with COPD and bronchial asthma.

Subjects and Methods. 100 patients with COPD and 108 patients with BA were examined. Nine devices were evaluated – a metered dose inhaler (MDI), Rapihaler, Respimat, Breezhaler, CDM, Turbuhaler, Genuair, Spiromax, and Ellipta. The application technique was assessed before the patient read the use instructions and was governed by his intuition, after reading the use instructions, and after training in the inhalation technique by the investigating physician.

Results. When COPD patients used inhalers by intuition, they managed to use them successfully in more than 30% of cases with Ellipta, Breezhaler, and Spiromax. After reading the use instructions, the correct use was achieved in 80% of cases when using CDM inhaler, Spiromax, Genuair, and Ellipta. Training conducted by the physician resulted in 100% success rate for Spiromax, Genuair, Ellipta, Breezhaler, and CDM inhaler. With asthma patients using inhalers by intuition, the correct use was observed in more than 50% of cases with Spiromax, Ellipta, Rapihaler, and MDI. After reading the instructions, the correct use was achieved in 80% of cases with CDM inhaler, Spiromax, Ellipta, CDM inhaler, Breezhaler, and Genuair. Training conducted by the physician allowed achieving 100% success rate for Spiromax, Ellipta, Breezhaler, and CDM inhaler.

Conclusion. Inhalers vary significantly by the patients’ ability to use them correctly. Asthma patients master the correct inhalation technique better versus COPD patients. Liquid inhalers were more difficult to be used correctly, and the best results were observed with multi-dose powder inhalers. The patient’s training by a healthcare professional is critical to assure the correct use of inhalers.

The objective: to analyze results of TBNA for diagnosis of mediastinal lymphadenopathy performed with flexible and rigid tracheobronchoscopy with needles of different diameters.

Subjects and Methods. We analyzed data of 194 patients who underwent TBNA with fibrobronchoscopy (Group 1) or rigid bronchoscopy (Group 2) for mediastinal lymphadenopathy of uncertain etiology.

Results. The overall diagnostic efficacy of the biopsy was 90,7%, while in case of tumors, the sensitivity was 89,5% and specificity was 97,5%, in case of respiratory sarcoidosis, they were 92,5% and 85,9%, respectively. Better diagnostic efficacy rates were observed in Group 1 (flexible bronchoscopy with 19G puncture needles) versus Group 2 (rigid bronchoscopy with 16G puncture needles) which may be due to the small number of biopsies in Group 2.

The objective: to determine the potential impact of particular nosologies and their groups on the risk of developing tuberculosis.

Subjects and Methods. The incidence of particular nosologies and their groups standardized by gender and age in new tuberculosis cases detected in 2020 was compared to the general incidence of those nosologies among population of RNO-Alania. Relative risk (RR) and statistical significance of differences (p) were determined.

Results. RR of type I diabetes mellitus (DM) in tuberculosis patients to the overall incidence of the entire population was 9,5 (p<0,001); RR of viral hepatitis – 6,4 (p<0,001); mental disorders – 3.2 (p<0,001); type II DM – 2,6 (p<0,001); chronic nonspecific lung diseases (CNLD) – 2,3 (p=0,005). There was no excess of RR for digestive diseases (RR=0,9; p=0,9). The role of genitourinary diseases could not be verified due to the lack of observations.

The objective: to evaluate changes in detection frequency of Mycobacterium tuberculosis of the main phylogenetic lines with various genetic determinants of resistance to rifampicin, isoniazid and fluoroquinolones in 1998–2003 and 2016–2021.

Subjects and Methods. 965 mycobacterial cultures were studied, those cultures were isolated from pulmonary tuberculosis patients in 1998–2003 and 2016–2021. The spoligotypes of isolated Mycobacterium tuberculosis cultures and presence of gene mutations associated with resistance to isoniazid, rifampicin, and fluoroquinolones were determined.

Results. In 2016–2021 versus 1998–2003, the incidence of Beijing subline increased from 50,72% to 64,60%. Within Euro-American line, the detection frequency of subline LAM9 decreased (from 40,00% to 14,81%), while the detection frequency of subline

T1 increased (from 27,11% to 41,36%). Mycobacterium tuberculosis with MDR genotype rpoB531_Ser->Leu + katG315_Ser-> Thr [1] was selected. Mycobacterium tuberculosis with genotypic resistance to fluoroquinolones was detected only in cultures of 2016–2021, and Mycobacterium tuberculosis with preXDR genotype was significantly more common in Beijing subline compared to Euro-American line (21,67% vs. 3,73%, p <0,05).

The objective: to study the incidence of relapses over a two-year period after successful completion of chemotherapy in patients with isoniazid-resistant tuberculosis (Hr TB), to determine the risk factors for relapses in this cohort.

Subjects and Methods. The medical records of 1860 Hr-TB patients who started treatment in 2015 in TB hospitals in 18 regions of the Russian Federation were retrospectively studied. Of these, 1271 (68.3 ± 1.08%) patients successfully completed a full course of chemotherapy, which were divided into two groups depending on the presence/absence of relapse in the next two years.

Results. Tuberculosis relapse was observed in 131/1271 (10.31%; CI 8,75–12,10%) (R+ Group) patients, the remaining 1140 patients

(R– Group) developed no relapse. For R+ and R– Groups, the first episode of the disease (FED) was analyzed, for R+ Group, the episode of the disease recurrence detection (DRD) was also analyzed. The risk factors for relapse development include the following parameters that were available in patients during first episode of the disease: unemployment at working age (OR=1,98; 95% CI [1,36–2,88]), diabetes mellitus or chronic alcohol addiction (OR=3,93; 95% CI [2,13–7,26%] and OR=2,25; 95% CI [1,02–5,01]), lung tissue decay OR=2,01; 95% CI [1,31–3,07], and drug resistance of Mycobacterium tuberculosis (H+Ag+Fq) (OR=7,26; 95% CI [3,90–10,62]).

With the disease recurrence detection, out of 131 patients of R+ Group, the positive results of the sputum test was recorded only in 117 (89,3%) patients, 41/131 (31,3%) patients developed a different clinical form of tuberculosis versus the first episode of the disease, and in 12/41 ( 29,3%) or 12/131 (9,2%) patients, the disease was more severe. 44/117 (37,6%) patients had been already resistant to rifampicin. It means they had developed MDR TB before the relapse was detected.

The objective: to evaluate functional and radiological data of the respiratory system assessment in patients with impaired lung diffusion capacity in the post-COVID period.

Subjects and Methods. Clinical, functional and radiological data were analyzed and compared in the patients divided into two groups according to the degree of lung diffusion capacity (LDC) impairment measured by carbon monoxide (Dlco) after 180 (135–196) days from the onset of acute symptoms of COVID-19: Group 1 included patients with Dlco of 80–60%, and Group 2 included patients with Dlco less than 60%. The lung functions were assessed by spirometry, body plethysmography and the Dlco level measurement. The data of CT scans of patients performed in the acute period of COVID-19, after 93 (89–103) days and 180 (135–196) days from the onset of acute symptoms were analyzed.

Results. The patients of Group 2 developed a severe form of COVID-19 statistically significantly more often, they required high-flow oxygen therapy (HFO) and stayed in the intensive care unit (ICU): 13/20 (65%), 11/20 (55%), 10/20 (50%) versus 8/24

(33,3%), 2/24 (8,3%) and 3/24 (13,5%) in the patients of Group 2, respectively. The level of Dlco (%) after 93 (89–103) days and 180 (135–196) days in Groups 1 and 2 made 66 (64–71) and 71 (67–73) versus 45 (41–53) and 51(47–58), respectively (p<0,05). Honeycombing changes in the lungs were detected by chest CT only in the patients of Group 2 – 16.7% on 93 (89–103) and 180 (135–196) days of observation, respectively.

Conclusion. A severe form of COVID-19, stay in the ICU and additional oxygen support are the factors indicating an unfavorable functional state of the respiratory system and presence of irreversible changes in the lung tissue in the post-COVID period.

The objective: to determine the rate of treatment success in MDR and XDR pulmonary tuberculosis patients when treated with chemotherapy regimens containing bedaquiline based on a meta-analysis using mathematical modeling.

Subjects and Methods. We searched and analyzed published studies of bedaquiline conducted from 2014 to 2022 in the Russian Federation. A total of 41 publications were found, of which 15 were included in the meta-analysis since they contained data eligible for analysis. They presented treatment results of 1,356 TB patients, 886 (65,3%) patients had MDR TB, and 470 (34,7%) had XDR TB (according to the definition as of 2020). All of them received bedaquiline within the standard regimen for 24–26 weeks.

Results. According to the meta-analysis results, when using treatment regimens containing bedaquiline in MDR/XDR TB patients, sputum conversion was achieved in 79,6% (95% CI 75,1–83,4) of cases, and effective treatment was observed in 82,0% (95% CI 78,6–84.9) of cases. Treatment default was noted in 8,7% (95% CI 5,7–13,1) of cases. At the same time, there is a statistically significant relationship (p<0,01) between the proportion of patients with comorbidities and the proportion of patients with incomplete treatment. Lethal outcomes were recorded in 5,8% (95% CI 3,6–9,2), which were associated with the severe course of tuberculosis and concomitant pathology. Bedaquiline was canceled in 7,8% (95% CI 4,0–13,5) of cases. When analyzing the data of patients with MDR TB and XDR TB separately, treatment efficacy differed and amounted to 89,9% (95% CI 85,9–92,9) versus 71,9% (95% CI 66,3–76,8), respectively.

The objective: to evaluate the efficacy and safety of delamanid in a short-course treatment regimen for patients with MDR/pre-XDR pulmonary tuberculosis in Arkhangelsk Region from 2019 to 2021.

Subjects and Methods. 32 patients (4 with MDR TB and 28 with pre-XDR TB) started treatment with delamanid within the combination chemotherapy with new drugs, treatment lasted for 12 months. All patients with pre-XDR TB received delamanid, bedaquiline, linezolid, and clofazimine, then the chemotherapy regimen was compiled depending on the clinical situation.

Results. Effective treatment was registered in 21/32 patients (65,6%). 4/32 (12,5%) patients interrupted the treatment. Treatment failure was registered in 2/32 (6,25%). During the study, 5 (15,6%) patients died, in none of them tuberculosis was the cause of death. 106 adverse events (AEs) were reported, they included electrolyte imbalance (18,9%), hepatotoxic (16,0%), nephrotoxic (10,4%) and cardiotoxic (10,4%) reactions.

The objective: to study the genetic determinants of rifampicin resistance of Mycobacterium tuberculosis by sequencing the RRDR rpoB gene.

Subjects and Methods. The study included 651 M. tuberculosis isolates that were tested for drug suceptibility (DST) by genotypic methods (gDST) TB-TEST (BIOCHIP-IMB, Russia), and Amplitube-MDR-RV (NPK Sintol, Russia) and phenotypic methods (phDST): the absolute concentration method, BACTEC MGIT 960 system, and Sensititre Myco TB kit. Sanger RRDR sequencing of the rpoB gene was performed for 20 isolates with discrepancies in the results of phDST and gDST.

Results. As a result of sequencing, two variants of mutations in the RRDR region of the rpoB gene were found, which were not detected by TB-TEST and Amblitub MDR-RV test systems, however were strongly associated with rifampicin resistance of Mycobacterium tuberculosis. The most common variant was the insertion of three nucleotides (TTC) encoding the amino acid phenylalanine at position 434 of the codon (1296-1300insTTC).

The objective: to assess NETosis-forming ability of neutrophils in patients with limited and disseminated tuberculous lesions.

Subjects and Methods. 44 new cases of respiratory tuberculosis were included in the study. Group 1 consisted of 22 patients with limited focal or infiltrative tuberculosis with no lung tissue destruction, Group 2 included 22 patients with disseminated tuberculosis with destruction of the lung tissue. Control Group (Group 0) included 22 healthy volunteers. NETosis-forming ability was assessed in vitro in the isolated fraction of neutrophils from peripheral venous blood. The ratio (%) of neutrophils of different degrees of activation and the ratio (%) of various forms of neutrophil extracellular traps (NET), the bacterial capture coefficient of NEL were calculated.

Results. NETosis-forming ability of neutrophils in the patients from Groups 1 and 2 was more pronounced versus Group 0, and in Group 2 it was maximum. In Group 2, the bacterial capture rate by NET was statistically significantly lower versus Group 1 (p=0,0147), which may indicate some degree of «inferiority» of NET formed in Group 2.

Contemporary publications on possible pharmaceutical treatment of ototoxic effect of aminoglycosides have been analyzed. In this respect, substances with the antioxidant effect seem to be the most promising. Their use in therapeutic doses is not accompanied by adverse reactions, and they do not interfere with the antibacterial effect of anti-tuberculosis drugs. Currently, the mechanisms of the otoprotective action of various antioxidants are being studied.