Kirill Zykov

Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region. Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment. 3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma–COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma–COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes. The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes. Distinct phenotypes of COPD in Central and Eastern Europe have differences in symptoms, comorbidities and treatment http://ow.ly/oMZI307ndr5

POPE study: rationale and methodology of a study to phenotype patients with COPD in Central and Eastern Europe

Introduction Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries. However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown. This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE. Methods/design The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE. Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks. Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded. The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494. Outcomes The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications. Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries. Conclusion There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD. The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE.

GOLD 2017 on the way to a phenotypic approach? Analysis from the Phenotypes of COPD in Central and Eastern Europe (POPE) Cohort

Recently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) released a revised consensus report (2017 GOLD Report) [1] in which the formerly defined ABCD classification of patients with COPD has been refined. The 2011 GOLD Report and its 2016 Update classified patients on the basis of three variables, i.e. the symptom burden, lung function impairment and exacerbations [2], now the A–D groups are defined solely on the basis of symptoms and history of exacerbations – thus recognising the limitations of the forced expiratory volume in 1 s (FEV1) in influencing therapeutic decisions in COPD [1]. The obvious consequence of the new classification is a shift of a proportion of patients from the C to the A group, and from the D to the B group. Nevertheless, the magnitude of such redistribution remains unknown. The distribution of patients based on exacerbations solely is the most profound consequence of the 2017 GOLD Report http://ow.ly/4UJa309fLbM

Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects

ABSTRACT Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD. Methods: Approximately 100 subjects from the Russian Federation who were either 2 to 49 y of age with increased risk for PD or ≥50 years of age were enrolled into the study (NCT01734239) to receive a single dose of PPV23 administered intramuscularly. Each subject was followed for local and systemic adverse events (AEs) for 5 and 14 days, respectively. Serious AEs were collected for 28 d postvaccination. Blood samples were collected immediately prior to vaccination and 28 d postvaccination for the measurement of IgG to serotypes 1, 6B, 14, 19F, and 23F. Results: High proportion of subjects had ≥2 -fold increase in IgG following receipt of PPV23. Rates were 92.0%, 83.0%, 89.0%, 81%, 84% for serotypes 1, 6B, 14, 19F, and 23F, respectively. Similar rates of responders and increases in the magnitude of immune responses were observed in both age groups (2–49, ≥50 ). PPV23 was generally safe and well tolerated. Injection site and systemic AEs were reported by 14.7% and 18.6% of study subjects, respectively. Conclusions: PPV23 is generally safe, well tolerated, and highly immunogenic when given as a single dose to Russian individuals 50 y of age and older, as well as Russian individuals 2 to 49 y of age who are at high risk for PD.

Radioligand method of assessment of human T-lymphocytes’ β-adrenoceptors activity

A new method of evaluation of beta-receptor’s activity on the surface of human T-lymphocytes has been proposed based on the radioligand method. Optimal conditions for evaluation of specific binding to β2-adrenoceptors of 0.5 fmol ligand per 1 million cells using [125I] -cyanopindolol were found. The possibility of using β2-adrenoceptor’s activity assessment in clinical settings was demonstrated on human T-lymphocytes.

Approaches to drug therapy for COPD in Russia: a proposed therapeutic algorithm

Until recently, there have been few clinical algorithms for the management of patients with COPD. Current evidence-based clinical management guidelines can appear to be complex, and they lack clear step-by-step instructions. For these reasons, we chose to create a simple and practical clinical algorithm for the management of patients with COPD, which would be applicable to real-world clinical practice, and which was based on clinical symptoms and spirometric parameters that would take into account the pathophysiological heterogeneity of COPD. This optimized algorithm has two main fields, one for nonspecialist treatment by primary care and general physicians and the other for treatment by specialized pulmonologists. Patients with COPD are treated with long-acting bronchodilators and short-acting drugs on a demand basis. If the forced expiratory volume in one second (FEV1) is ≥50% of predicted and symptoms are mild, treatment with a single long-acting muscarinic antagonist or long-acting beta-agonist is proposed. When FEV1 is <50% of predicted and/or the COPD assessment test score is ≥10, the use of combined bronchodilators is advised. If there is no response to treatment after three months, referral to a pulmonary specialist is recommended for pathophysiological endotyping: 1) eosinophilic endotype with peripheral blood or sputum eosinophilia >3%; 2) neutrophilic endotype with peripheral blood neutrophilia >60% or green sputum; or 3) pauci-granulocytic endotype. It is hoped that this simple, optimized, step-by-step algorithm will help to individualize the treatment of COPD in real-world clinical practice. This algorithm has yet to be evaluated prospectively or by comparison with other COPD management algorithms, including its effects on patient treatment outcomes. However, it is hoped that this algorithm may be useful in daily clinical practice for physicians treating patients with COPD in Russia.

[PP.34.08] PECULIARITIES OF INFLAMMATORY MARKERS IN MIDDLE-AGED MALE PATIENTS WITH ARTERIAL HYPERTENSION, OBESITY AND OBSTRUCTIVE SLEEP APNEA SYNDROME

Objective: Obesity and obstructive sleep apnea syndrome (OSAS) are the conditions associated with inflammation. The aim of this study was to explore peculiarities in serum levels of inflammation markers in patients with arterial hypertension (AH) with or without obesity and OSAS. Design and method: In the study we included 10 healthy volunteers (group 1) and 52 middle-aged male patients with AH. According to BMI and AHI (apnea/hypopnea index) patients were divided into 3 groups: group 2 patients solely with AH (n = 17), group 3 (n = 15) patients with AH and obesity, without OSAS and group 4 (n = 20) patients with AH, obesity and severe OSAS. Patients were healthy in terms of chronic heart disease, diabetes mellitus, chronic kidney disease, manifested autoimmune or inflammatory disease. All blood samples were obtained after initial diagnostics, in the morning, in fasting condition; initially patients were not on any medication. Results: Patients were examined for levels of fibrinogen, CRP, hsCRP, IL 6, sCD40L, IL 1b, IL 2R &agr;, IL 6, TNF &agr;, ICAM and VCAM. Levels of fibrinogen were higher in group 2 and group 4 vs control group 1. The highest levels of CRP and hsCRP were detected in group 4: CRP 0,55 (0,26–0,83), hsCRP 4,52 (2,47–6,56), but statistically significant difference was obtained between group 1 and group 2 vs group 4. IL 2R &agr; was the highest in group 3 with high diversity in levels, and statistically higher in comparison with group 2. Figure. No caption available. Conclusions: Obese patients with AH and severe OSAS have elevated levels of CRP and hsCRP compared to age and BP matched patients with solely AH, but not with patients with concomitant obesity, suggesting a confounding role of OSAS together with obesity in promoting inflammation.

464 THE INFLUENCE OF A SINGLE LOW DOSE OF CARDIOSELECTIVE BETA-BLOCKER ON PULMONARY FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSION AND BRONCHIAL ASTHMA

Objective: the patients with arterial hypertension (AH) and bronchial asthma (BA) often need beta-blockers (BB), which can degrade the pulmonary function [1]. But certain researches show the possibility of the use of selective BB in the given group of patients [2,3]. To determine the effects of single dose cardio-selective BB on FEV1, FVC and acute bronchodilator response to salbutamol in patients with AH and BA. Methods: 12 patients (mean age 63.9 ± 10.9 years) were included in the study and received single dose bisoprolol 1.25 mg. The FEV1 and FVC were assessed initially, after 30, 90, 150, 240 min and after up to 30 min salbutamol 400 mkg. In case when sharp sample with the single dose of bisoprolol doesn’t cause significant reduction of FEV1 the patients can be given with the titration of bisoprolol dose from minimun to effective. The titration of bisoprolol is necessary to reduce the possibility of bronchospasm. Results: At baseline the FEV1 was 75.1 ± 19.7%, FVC 88.5 ± 22.4% and significantly didn’t change after 30, 90, 150 and 240 min (FEV1 was 75.5 ± 20.1%; 76.4 ± 20.5; 76.9 ± 19.6% and 74.7 ± 18.4% respectively). After use of salbutamol a considerable increase of FEV1 up to 81.8 ± 19.7 was registered. The bronchodilating effect of salbutamol on &Dgr;FEV1 was +9.8 ± 4.9% (p = 0.004). Conclusion: The single dose of bisoprolol 1.25 mg was not altered to FEV1 and bronchodilating effect of salbutamol in patients with AH and BA. This allows recommending the choice of individual effective dose of bisoprolol for long-term dose starting with 1.25 mg a day, which needs further investigations. References:BabuKS, Marshall BG. Drug-induced airway diseases. Clin Chest Med. 2004 Mar;25(1):113-22.SalpeterSR,Ormiston TM,SalpeterEE. Cardioselectivebeta-blockers in patients withreactiveairwaydisease: a meta-analysis. Ann Intern Med.2002 Nov5;137(9):715-25.Chatterjee SS. The cardioselective and hypotensive effects ofbisoprololin hypertensive asthmatics.J Cardiovasc Pharmacol.1986;8 Suppl 11:S74-7.

608 HOW CHRONIC OBSTRUCTIVE PULMONARY DISEASE OR ASTHMA AFFECTS TARGET ORGAN DAMAGE IN PATIENTS WITH HYPERTENSION

Background: Broncho-obstructive disease in combination with cardiovascular disease decline the clinical course of each of them and affects the prognosis [1,2]. The aim of our study is to compare the frequency of the target organ damage in arterial hypertension (AH) patients to AH patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA) comorbidity, included in AH clinical trials. Methods: Retrospective analysis of 5 clinical trials, conducted in Russia with AH patients from 2005 to 2010 [3]. Results are presented as Mean±std. Results: 3409 patients aged 40-80 years were included in 5 studies. Patients with COPD (as compared to BA and AH patients) have most often left ventricular hypertrophy (76.1%, 69.2%, 67.6%, p <0.001), carotid plaque (25.7%, 22.0%, 20.2%, p <0.04), renal damage (45.5%, 44.0%, 31.2%, p <0.001). Table. No title available. Conclusion: Patients with AH and COPD have a higher frequency of target organ damage (heart, blood vessels, kidneys) as compared to patients with hypertension and bronchial asthma and patients with hypertension without a bronchial disease that may require a specific tactics approach. References:WHO World Health Survey. WHO 20 December 2010 Retrieved 9 February 2012.World Health Organization 2011 Reprinted 2011WHO Library Cataloguing-in-Publication Data Global status report on noncommunicable diseases 2010.Ratova L.G., Zykov K.A., Dolgusheva Yu.A., Agapova O.Yu., Nazarov B.M., Chazova I.E. Arterial hypertension and obstructive lung disease – features of clinical picture. System Hypertension 2012; 9(1):54-8.