Vol 89, No 3 (2017)

The paper presents information on possible approaches to the classification, pathogenesis, and determination of the etiological causes of bronchiectasis. It discusses a group of bronchiectasis-associated diseases. It gives a detailed diagnostic algorithm aimed to establish the etiology of bronchiectasis and the markers of the efficiency of different treatment options. Much attention is paid to genetically predetermined bronchiectasis. Universal approaches to treating patients with bronchiectasis as a whole, as well as treatments for certain entities of bronchiectasis are discussed.

Aim. To determine plasma extracellular low-molecular-weight DNA (elmwDNA) as an indicator of apoptosis in patients with chronic obstructive pulmonary disease (COPD) in remission versus healthy donors, patients with chronic non-obstructive bronchitis (CNOB), and their first-degree relatives (FDRs). Subjects and methods. The investigation recruited 110 participants, including 17 healthy donors, 31 patients with COPD, and 20 patients with CNOB in remission, 19 healthy FDRs of patients with COPD, and 23 healthy FDRs of those with SNOB. The plasma levels of elmwDNA were determined in the study participants. Nucleic acids were isolated by phenol/chloroform extraction, precipitated with ethanol, and treated with RNase; elmwDNA was analyzed by electrophoresis. Results. In patients with COPD, the mean level of elmwDNA was 7.8±2.0 ng/ml, which was 3.9 and 3.0 times statistically significantly lower than that in healthy donors and patients with SNOB, respectively; while the level of elmwDNA in the latter did not differ statistically significantly from that in healthy donors. In both the blood relatives of patients with COPD and FDRs of those with SNOB, the mean level of elmwDNA was not significantly different from that in healthy donors. The content of elmwDNA tended to increase in COPD patients aged 60—80 years as compared to those aged 45—59 years; that in both age groups was, however, significantly lower than in healthy donors of the same age. Conclusion. The level of elmwDNA in plasma and, accordingly, apoptosis in the lung are reduced in patients with COPD in remission, whereas that is unchanged in those with SNOB. In patients with COPD, blood elmwDNA release is unrelated to heredity and varies little with age. The determination of elmwDNA is recommended for use in patients with COPD to assess apoptosis.

Aim. To investigate the impact of smoking on the air exhaled by patients with chronic obstructive pulmonary disease (COPD) and asthmatics, by applying photoacoustic spectroscopy. Subjects and methods. The exhaled air absorption spectra (EAAS) were analyzed in healthy volunteers and patients with COPD and asthmatics, by applying an ILPA-1 CO2 laser photoacoustic gas analyzer. The procedure based on the calculation of an integrated estimate (IE) of the state of the object was used to assess the findings. Results. Comparison of the IE of EAAS in COPD patients and non-smoking healthy individuals showed that spectra of the compounds, the formation of which was associated with smoking, were recorded in the range of wavelengths corresponding to the 10R branch of CO2 laser generation. This also provided evidence indicating that the exhaled air of asthmatics differed from that of both smoking and non-smoking healthy individuals. The calculations yielded the threshold values of EAAS IE in the range of wavelengths corresponding to the 10P branche of CO2 laser generation, which made it possible to distinguish non-smoking healthy individuals from asthmatics and COPD patients in 94 and 89% of cases, respectively. Conclusion. The investigation has confirmed that smoking substantially impacts the composition of the air exhaled by healthy individuals. It has been shown that the use of reference groups formed from non-smoking healthy individuals can improve the accuracy of photoacoustic spectroscopy in detecting COPD and asthma. A further development in this direction will open up new prospects for a new method to diagnose COPD and asthma.

Aim. To conduct a comprehensive study of the components of negative cell signaling regulation in different types of asthma. Subjects and methods. A total of 171 people, including 80 patients with allergic asthma (AA), 60 patients with non-allergic asthma (NAA), and 31 apparently healthy individuals, were examined. SOCS5 mRNA expression was assessed by reverse-transcription polymerase chain reaction. The expression of SOCS1 and SOCS3 proteins was investigated by immunoblotting. The concentration of total serum IgE was determined by enzyme immunoassay; the level of cytokines was measured according to the standard protocol using a Bio-Plex fluorometer. Results. The findings show that the patients with AA generally display more marked changes in the expression of all three investigated SOCSes (SOCS1, SOCS3, and SOCS5) at baseline and when interleukin 4 (IL-4) acts. In NAA, there are pronounced changes in the expression of SOCS3 only and, to a lesser extent, SOCS5. The results of investigating the concentrations of IL-4 in the examined groups demonstrate its significant decrease in the AA group, whereas in the NAA group, it is similar to those in healthy individuals. On the contrary, IL-10 concentrations in AA tend towards those in the control group, but much exceed in NAA. Conclusion. The findings allow one to consider the complexity of regulatory disorders arising at various levels of cell signaling in the context of the multifunctional nature of the molecules from the family of negative regulators of transcription of the SOCS1, SOCS3, and SOCS5 genes, which provide the comprehensive control of cytokine signaling simultaneously in different signal pathways.

Aim. To investigate the indicators of filling of the right ventricle (RV) in patients with chronic lung diseases with and without pulmonary hypertension (PH) compared to healthy individuals. Subjects and methods. 365 people (198 men); mean age 64.6±8.0 years) were examined and divided into a group of patients with respiratory pathology without and with PH (n=124 and n=138, respectively) and a comparison group that included individuals without cardiovascular and respiratory diseases (n=103). All underwent echocardiography with examination of RV filling flows (Et, At, Et/At), data of the spectral tissue Doppler imaging of the fibrous ring of the tricuspid valve (e’t, a’t, e’t/a’t), and early tricuspid flow propagation velocity (ETFPV). Results. All the groups were found to have an e’t/a’t decrease to 0.75 (0.63—0.90) — 0.8 (0.63—1.0; p=0.26). The groups showed no noticeable differences in indicators, such as Еt/Аt, e’t/a’t, and Еt/e’t ratios, although the increased size of the right heart was noted in patients without PH along with the ETFPV decrease from 33.5 (28—39) to 31.5 (24.5—36) cm/sec, which continued to substantially decline to 27.1 (24—35) cm/sec in patients with PH (p<0.0001). Conclusion. Patients with chronic lung disease even without the development of PH exhibited a decreased ETFPV along with the increased size of the right heart. Another indicator of RV diastolic function is a tricuspid valve annular velocity ratio in early and late diastole; the e’t/a’t ratio was not considerably different in the groups, although its decline was observed in all the groups probably due to age-related changes. Thus, RV diastolic function should be comprehensively evaluated in patients with lung disease regardless of the presence of PH.

Aim. To investigate factors that influence annual prognosis in patients with non-ST-segment elevation acute coronary syndrome ((NSTEACS) concurrent with type 2 diabetes mellitus (DM2). Subjects and methods. The registry of patients with NSTEACS (non-ST-segment elevation myocardial infarction (NSTEMI), unstable angina) included 415 patients, of them 335 had no carbohydrate metabolic disorders, 80 had DM2. The follow-up period, during which the prognosis was evaluated in the patients, was one year after hospital discharge following the index NSTEACS event. Lipidogram readings and the serum levels of endothelin-1 (ET-1), sP-selectin, sE-selectin, and sPECAM were determined on day 10 after admission to hospital. All the patients underwent coronary angiography (CA), Doppler ultrasound of peripheral arteries during their hospital stay. Results. The patients with DM2 versus those without diabetes proved to be significantly older and to have a higher body mass index; among them there were more women, they were noted to have more frequently hypertension and less frequently smoked. The presence of DM2 was associated with significantly increased intima-media thickness and higher GRACE scores (p=0.013) as compared to those in the patients with normal carbohydrate metabolism. There were significant differences in high-density lipoprotein levels that were lower, as well as in triglyceride levels and atherogenic index, which were higher in patients with DM2 than in those without this condition. In addition, there were significant differences in ET-1, sP-selectin, sE-selectin, and sPECAM levels that were significantly higher in the DM2 group. Moreover, the levels of ET-1 and sPECAM were above normal in both the DM and non-DM2 groups. Assessment of poor outcomes at one year of the observation established that cardiovascular mortality rates were significantly higher and coronary angiography was performed much less frequently in the DM2 group. The most significant prognostic factors associated with a poor prognosis were as follows: multifocal atherosclerosis, reduced left ventricular ejection fraction (LVEF) less than 51%, and increased ET-1 levels more than 0.87 fmol/ml. Conclusion. The register-based study has shown that the presence of DM2 statistically significantly increases cardiovascular mortality rates during a year after the index ACS event; the patients of this category are less commonly referred for CA for the estimation of the degree of coronary bed lesion. The most important factors of recurrent cardiovascular events in patients with DM2 within a year after prior ACS are multifocal atherosclerosis, reduced myocardial contractility (LVEF less than 51%), and increased vasospastic endothelial function (an increase in ET-1 levels more than 0.87 fmol/ml).

Aim. To investigate the prognostic value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in the development of acute kidney injury (AKI) in patients with acute decompensated chronic heart failure (ADCHF). Subjects and methods. Eighty-three patients (55 (66%) men and 28 (34%) women; mean age, 65±11 years) with ADCHF were examined. AKI was diagnosed and classified according to the 2012 Kidney Disease Improving Global Outcomes Clinical Practice guidelines. To rule out contrast-induced AKI, the investigation enrolled only patients in whom radiopague agents had not been injected 7 days before and during hospitalization. Enzyme immunoassay was used to determine serum NT-proBNP concentrations in all the patients upon hospital admission. Results. AKI was diagnosed in 18 (22%) patients, 13 (16%) had Stage I, 4 (5%) had Stage II, and 1 (1%) had Stage III. The serum concentration of NT-proBNP was significantly higher in patients with AKI than that in the other patients [1512.1 (981.0; 2246.2) and 861.8 (499.0; 1383.6) pg/ml (p=0.008). The rise in NT-proBNP concentrations of more than 942 pg/ml was established to be associated with a considerable increase in the risk of AKI (relative risk (RR) was 4.3; 95% confidence interval (CI), 1.27—14.90; p=0.02). RОС analysis indicated that a NT-proBNP level of >942 pg/ml allows prediction of AKI with a sensitivity of 78% (52; 94) and a specificity of 55% (44; 69) (AUC=0.70; p=0.006). Four (5%) patients died in hospital. NT-proBNP levels in all the dead were greater than 942 pg/ml. Two of the 4 deceased patients had AKI. Conclusion. A high level of NT-proBNP in a patient with ADCHF during hospitalization can serve as a biomarker for high risk of AKI and for high mortality rates.

1Moscow Clinical Research-and-Practical Center, Moscow Healthcare Department, Moscow; 2A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow; 3Children’s Health Research Center, Ministry of Health of Russia, Moscow; 4I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg; 5M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow; 6Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow; 7Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk; 8Russian Children’s Clinical Hospital, Moscow; 9Department of Pediatrics, Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow; 10I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia, Saint Petersburg; 11Acad. Yu.E. Veltishchev Research Clinical Institute of Pediatrics, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow; 12Clinic Four, Department of Pediatrics, I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia, Saint Petersburg; 13Childhood Diseases Department Two, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow; 14Research Laboratory of Surgical Gastroenterology and Endoscopy, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow; 15Department of Endoscopic Surgery, City Clinical Hospital Thirty-One, Moscow Healthcare Department, Moscow; 16A.N. Ryzhikh State Research Center of Coloproctology, Ministry of Health of Russia, Moscow; 17Department of Intermediate-Level Therapy, Tver State Medical University, Ministry of Health of Russia, Tver; 18Laboratory of Medical Genetics, Diagnostic Center of Medical Genetics, Saint Petersburg; 19HLA Typing Laboratory, Blood Transfusion Station, Moscow Healthcare Department, Moscow; 20S.P. Botkin City Clinical Hospital, Moscow Healthcare Department, Moscow; 21Department of Nervous System Diseases, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow; 22Department of Endocrinology and Diabetology, A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow; 23Acad. V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, Moscow; 24Department of Therapy, Kazan State Medical Academy, Ministry of Health of Russia, Kazan; 25Department of Intermediate-Level Therapy with Course of Occupational Diseases, Faculty of General Medicine, Omsk State Medical University, Ministry of Health of Russia, Omsk; 26Dmitry Rogachev Federal Research Clinical Center of Pediatric Hematology, Oncology, and Immunology, Ministry of Health of Russia, Moscow The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2—3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

Asthma is a serious health problem affecting all age groups. Melatonin or its agonists are commonly used to treat many diseases, but there are conflicting data on asthma therapy. This paper analyzes researches on the possible use of melatonin in the therapy of asthma. Melatonin is a potent antioxidant and a vasodilator, but in some experiments, it can act as a pro-oxidant and a vasoconstrictor, which may depend on the duration of use. It has been suggested that circadian rhythms should be corrected in asthmatics to optimize the desired effects of drugs and to reduce the severity of their adverse reactions. Disordered diurnal variations in the salivary levels of melatonin and cortisol are detectable in patients with asthma and may be implicated in its pathogenesis. In addition, the conflicting data on the effect of melatonin on the development of asthma are associated with an incomplete view of the factors influencing the level of melatonin. Thus, to study the effects of melatonin, it is necessary to take into account the greatest possible factors that may influence the level of melatonin and the course of asthma: a daily diet in terms of the use of caffeine, alcohol, sleep-wakefulness pattern, sleep quality proper, and drowsiness during the daytime, social burden, the level of anxiety and stress resistance, and to investigate the levels of endogenous melatonin or its derivatives, immune status, oxidative stress intensity, etc. Obviously, the use of melatonin in the therapy of asthma can be considered, by applying a personalized approach.