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.

Therapeutic Success of Tiotropium/Olodaterol, Measured Using the Clinical COPD Questionnaire (CCQ), in Routine Clinical Practice: A Multinational Non-Interventional Study.

BACKGROUND: The Clinical COPD Questionnaire (CCQ) is a simple patient-reported tool to measure clinical control of chronic obstructive pulmonary disease (COPD). OBJECTIVE: This open-label, single-arm, non-interventional study (NCT03663569) investigated changes in CCQ score during treatment with tiotropium/olodaterol in clinical practice. METHODS: Data were included from consenting COPD patients, enrolled in Bulgaria, Czech Republic, Hungary, Israel, Lithuania, Poland, Romania, Russia, Slovenia, Switzerland and Ukraine, who were receiving a new prescription for tiotropium/olodaterol according to the treating physician in a real-world environment. The primary endpoint was the occurrence of therapeutic success, defined as a 0.4-point decrease in CCQ score after treatment with tiotropium/olodaterol for approximately 6 weeks. RESULTS: Overall, 4819 patients were treated; baseline and Week 6 CCQ scores were available for 4700 patients, mostly classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B (51.6%) or D (42.7%). After 6 weeks' treatment, 81.4% (95% confidence interval [95% CI] 80.24-82.49) of patients achieved therapeutic success; mean improvement in overall CCQ score was 1.02 points (95% CI 1.00-1.05). Improved CCQ score was seen in 92.2% of patients (95% CI 91.43-92.98), 2.5% had no change and 5.3% showed a worsening. When stratified by prior treatment, the greatest benefit was seen in treatment-naïve patients, with 85.7% achieving therapeutic success, compared with 79.5% of those pretreated with long-acting ß2-agonist (LABA)/inhaled corticosteroid (ICS) and 74.2% of those pretreated with LABA or long-acting muscarinic antagonist (LAMA) monotherapy. Overall, rescue medication decreased by 1.25 puffs/day (95% CI 1.19-1.31) versus baseline. In total, 29 patients (0.6%) reported drug-related adverse events and 7 patients reported serious adverse events (0.15%). CONCLUSION: In 4700 COPD patients, 6 weeks' treatment with tiotropium/olodaterol, as initial treatment or follow-up to LAMA or LABA monotherapy or LABA/ICS, improved CCQ and decreased rescue medication use. The adverse event profile was consistent with the known safety profile of tiotropium/olodaterol.

Determinants of CAT (COPD Assessment Test) scores in a population of patients with COPD in central and Eastern Europe: The POPE study.

BACKGROUND: The COPD Assessment Test (CAT) has been proposed to help guide therapy in chronic obstructive pulmonary disease (COPD). It is important to understand the distribution of scores in different COPD populations and their determinants. METHODS: The POPE study is an international, observational cross-sectional study of COPD subjects in 11 Central and Eastern European countries aimed at characterizing COPD phenotypes. Here we report the analysis of CAT scores with the objective of identifying their determinants, evaluating symptom load and investigating the distribution of scores among the participating countries. Additionally, we investigated the discrepancies between the CAT and modified Medical Research Council (mMRC) scores when used to classify patients according to the GOLD strategy. RESULTS: The study included 3452 patients (69.2% men, mean forced expiratory volume in 1 s (FEV1% predicted) 52.5%). The mean CAT score was 17.5 (SD = 7.8), ranging from 15.1 in Hungary to 21.2 in Bulgaria. Multiple linear regression analysis showed six variables significantly associated with CAT scores: depression, number of previous exacerbations, 6-min walking distance, FEV1(%), mMRC and country and explained 47.2% of the variance of CAT. According to either CAT or mMRC, up to 23.9% patients would be classified in different GOLD groups. CONCLUSIONS: The CAT score may be predicted by factors related to COPD severity, depression and exercise capacity, with significant differences in the distribution of CAT scores in different countries. According to our results CAT >10 is not equivalent to mMRC >2 for assessing symptom burden. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02119494.

Improvement In Self-Reported Physical Functioning With Tiotropium/Olodaterol In Central And Eastern European COPD Patients.

Background: Reduced physical activity is associated with increased morbidity and mortality in patients with COPD. Studies suggest that treatment with the long-acting muscarinic antagonist tiotropium and the long-acting ß2-agonist olodaterol increases exercise capacity. This study assessed the effects of a fixed-dose combination (FDC) of tiotropium/olodaterol (delivered via Respimat®) on physical functioning in patients with stable COPD in a "real-world setting". Methods: An international, open-label, single-arm, non-interventional study conducted in nine countries measuring changes in self-reported physical functioning in COPD patients treated with tiotropium/olodaterol 5/5 µg FDC for approximately 6 weeks. The primary endpoint was therapeutic success, defined as a minimum 10-point increase in the 10-question Physical Functioning Questionnaire (PF-10) score. Secondary endpoints included absolute change in PF-10 from Visit 1 to Visit 2, patient general condition (measured by Physician's Global Evaluation score) and patient satisfaction with the treatment and device (assessed by Patient Satisfaction Questionnaire at the end of the study period). Results: Therapeutic success was observed in 67.8% of 7218 patients (95% CI 66.7, 68.8) in the final analysis set after approximately 6 weeks of treatment with tiotropium/olodaterol. Mean change in PF-10 score between Visit 1 and Visit 2 was 16.6 points (95% CI 16.2, 17.0). Therapeutic success was 64.3% (95% CI 63.0-65.6%) in patients with infrequent (≤1) and 76.1% (95% CI 74.3-77.9%) in patients with frequent (≥2) exacerbations (p<0.0001). Patient general condition improved as indicated by an improvement in Physician's Global Evaluation scores between visits. Most patients were very satisfied or satisfied with tiotropium/olodaterol treatment in general (81%), reported inhalation satisfaction (85%), and satisfactory handling of the device (84%). 1.3% of patients reported an investigator-defined drug-related adverse event. Conclusion: Treatment with tiotropium/olodaterol led to an improvement in self-reported physical functioning in patients with COPD.

Comprehensive strategy to prevent nosocomial spread of methicillin-resistant Staphylococcus aureus in a highly endemic setting.

BACKGROUND: The effectiveness and feasibility of a comprehensive strategy to reduce nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) in a highly endemic setting have not yet been proved. Limited benefits and the high cost of such programs are the main concerns. METHODS: We prospectively evaluated the effect of an aggressive infection control program on transmission of MRSA in the University Clinic of Respiratory and Allergic Diseases. All patients with MRSA carriage during 5 years (January 1, 1998, through December 31, 2002) were included and categorized into imported or hospital-acquired cases. RESULTS: Methicillin-resistant S aureus was recovered from 223 hospitalized patients; 142 cases were imported and 81 were acquired at our institution. After introduction of the comprehensive infection control program in 1999, the annual incidence of MRSA carriage per 1000 admissions increased from 4.5 in 1998 to 8.0 in 1999 (P = .02), and remained stable thereafter. In this period, the proportion of MRSA cases acquired in our institution decreased from 50.0% in 1999 to 6.1% in 2002 (P<.001), whereas the proportion of MRSA cases transferred from other hospitals (P<.001) and nursing homes (P = .03) increased. All 19 MRSA carriers with 3 sets of follow-up cultures were successfully decolonized. CONCLUSIONS: With a comprehensive infection control program, it was possible to reduce nosocomial transmission of MRSA in a highly endemic setting. With good hand hygiene using alcohol handrub, early detection, isolation, and a decolonization strategy, containment of MRSA was achievable, despite a high rate of transferred patients with MRSA.

Molecular epidemiology of tuberculosis in Slovenia: results of a one-year (2001) nation-wide study.

Slovenia is a small Central European country with a population of 1.99 million and an incidence of tuberculosis (TB) of 18.6 per 100,000 inhabitants in 2001. In a prospective nation-wide, 1-y DNA fingerprinting study, the genetic diversity of 99.7% of all Mycobacterium tuberculosis isolates obtained from Slovenian patients with culture-verified TB in 2001 were assessed using a standardized IS6110 restriction fragment length polymorphism (RFLP) method. Among 306 M. tuberculosis isolates, 228 different IS6110 RFLP patterns were found. The number of IS6110 copies varied from 2 to 16 (9.2 copies per isolate on average). Only 2 isolates (0.7%) with less than 5 IS6110 copies were identified. Clustered M. tuberculosis isolates were detected in 116 (37.9%) patients. The degree of recent transmission in the 1-y period was 25%. The clustering rate decreased with age from 46.4% (age group under 35 y) to 19.5% (age group above 65 y). A history of alcohol abuse and homelessness was found to be associated with clustering of TB cases. In conclusion, a high clustering frequency was identified among Slovenian TB patients. The study increased our understanding of important risk factors and routes of TB transmission in Slovenia.

Complement factors c3a, c4a, and c5a in chronic obstructive pulmonary disease and asthma.

Studies of animal models have shown that the activation of the complement system could have a role in chronic obstructive pulmonary disease (COPD) and asthma by promoting inflammation and enhancing airway hyperresponsiveness. We sought to determine whether the levels of complement factors C3a, C4a, and C5a are elevated at the site of inflammation in patients with COPD and patients with asthma. We analyzed the induced sputum of seven patients with COPD, ten patients with asthma, and twelve healthy nonsmokers. The concentrations of anaphylatoxins in the induced sputum were measured by cytometric bead array. We found significantly increased C5a/C5a desArg concentrations in supernatants of the induced sputum of patients with COPD (P = 0.007) and those with asthma (P = 0.002) compared with the control group. In patients with COPD the C5a/C5a desArg concentrations were significantly negatively correlated with lung diffusion coefficient (r = -0.71, P = 0.035). There was no significant difference in C3a/C3a desArg or C4a/C4a desArg measurements between the three groups of subjects. These in vivo results propose the involvement of complement factor C5a in the pathogenesis of COPD and asthma.