Search

Andreas Horner,1 Horst Olschewski,2 Sylvia Hartl,3 Arschang Valipour,4 Georg-Christian Funk,5 Michael Studnicka,6 Monika Merkle,7 Bernhard Kaiser,1 Eva Maria Wallner,8 Stephan Brecht,8 Bernd Lamprecht1 1Johannes Kepler University Linz, Kepler University Hospital, Department of Pulmonology, Linz, Austria; 2Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, and Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria; 3Department of Respiratory and Critical Care Medicine, Klinik Penzing and Sigmund Freud University, Medical School, Vienna, Austria; 4Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria; 5Department of Internal and Respiratory Medicine, Klinik Ottakring, Vienna, Austria; 6Department of Pulmonary Medicine, Paracelsus Medical University, Salzburg, Austria; 7Specialist Office for Pulmonology Dr. Merkle, Vienna, Austria; 8A. Menarini Pharma GmbH, Vienna, AustriaCorrespondence: Andreas Horner, Johannes Kepler University Linz, Kepler University Hospital, Department of Pulmonology, Altenberger Strasse, 69, 4040 Linz and Krankenhausstrasse 9, 4020 Linz, Austria, Email Andreas.Horner@kepleruniklinikum.atBackground: Symptoms of depression, pain and limitations in physical activity may affect quality of life in COPD patients independent from their respiratory burden. We aimed to analyze the associations of these factors in outpatients with COPD in Austria in a stable phase of disease.Methods: We conducted a national, cross-sectional study among patients with COPD. For depression, the Patient Health Questionnaire-9 (PHQ-9) and for respiratory symptoms the St. George’s Respiratory Questionnaire for COPD patients (SGRQ-C) were used along with 10-point scales for physical activity and pain.Results: After exclusion of 211 patients due to non-obstructive spirometry or missing data, 630 patients (62.5% men; mean age 66.8 ± 8.6 (SD) years; mean FEV1%pred. 54.3 ± 16.5 (SD)) were analyzed. Of these, 47% reported one or more exacerbations in the previous year, 10.4% with hospitalization. A negative depression score was found in 54% and a score suggesting severe depression (PHQ-9 score ≥ 15) in 4.7%. In a multivariate linear regression model, self-reported pain, dyspnea, and number of exacerbations were predictors for higher PHQ-9-scores. A negative pain score was found in 43.8%, and a score suggesting severe pain in 2.9% (8– 10 points of 10-point scale). Patients reporting severe pain were more often female, had more exacerbations, and reported more respiratory and depressive symptoms, a lower quality of life, and less physical activity. About 46% of patients rated their physical activity as severely impaired. These patients were significantly older, had more exacerbations, concomitant heart disease, a higher pain and depression score, and a lower quality of life (SGRQ-C – total score and all subscores).Conclusions: In Austria, nearly half of stable COPD outpatients reported symptoms of depression, which were associated with lower levels of self-reported physical activity, more pain, and respiratory symptoms. The associations were particularly strong for depression with SGRQ-C.Keywords: chronic obstructive pulmonary disease, depression, PHQ-9, pain, quality of life, St. George’s Respiratory Questionnaire, physical activity

Vladimir Koblizek,1,2 Branislava Milenkovic,3,4 Michal Svoboda,5,6 Jana Kocianova,7 Stanislav Holub,8 Vladimir Zindr,9 Miroslav Ilic,10,11 Jelena Jankovic,3,4 Vojislav Cupurdija,12,13 Jiri Jarkovsky,6 Boris Popov,14 Arschang Valipour15 1Department of Pneumology, University Hospital, Hradec Kralove, Czech Republic; 2Faculty of Medicine Hradec Kralove, Charles University, Hradec Kralove, Czech Republic; 3Clinic for Pulmonary Diseases, Clinical Center of Serbia, Belgrade, Serbia; 4Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 5Institute of Biostatistics and Analyses Ltd., Brno, Czech Republic; 6Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic; 7Outpatient Department of Pneumology Alveolus, APRO MED, Ostrava, Czech Republic; 8Outpatient Chest Clinic, Plicni Stredisko Teplice Ltd., Teplice, Czech Republic; 9Outpatient Chest Clinic, PNEUMO KV Ltd., Karlovy Vary, Czech Republic; 10Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia; 11Clinic for Tuberculosis and Interstitial Lung Diseases, PolyClinic Department, Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia; 12Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; 13Clinic for Pulmonology, University Clinical Center Kragujevac, Kragujevac, Serbia; 14Medicine Department, Boehringer Ingelheim Serbia d.o.o. Beograd, Belgrade, Serbia; 15Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna Health Care Group, Vienna, AustriaCorrespondence: Vladimir Koblizek, Email vladimir.koblizek@fnhk.czPurpose: The Phenotypes of COPD in Central and Eastern Europe (POPE) study assessed the prevalence and clinical characteristics of four clinical COPD phenotypes, but not mortality. This retrospective analysis of the POPE study (RETRO-POPE) investigated the relationship between all-cause mortality and patient characteristics using two grouping methods: clinical phenotyping (as in POPE) and Burgel clustering, to better identify high-risk patients.Patients and Methods: The two largest POPE study patient cohorts (Czech Republic and Serbia) were categorized into one of four clinical phenotypes (acute exacerbators [with/without chronic bronchitis], non-exacerbators, asthma–COPD overlap), and one of five Burgel clusters based on comorbidities, lung function, age, body mass index (BMI) and dyspnea (very severe comorbid, very severe respiratory, moderate-to-severe respiratory, moderate-to-severe comorbid/obese, and mild respiratory). Patients were followed-up for approximately 7 years for survival status.Results: Overall, 801 of 1,003 screened patients had sufficient data for analysis. Of these, 440 patients (54.9%) were alive and 361 (45.1%) had died at the end of follow-up. Analysis of survival by clinical phenotype showed no significant differences between the phenotypes (P=0.211). However, Burgel clustering demonstrated significant differences in survival between clusters (P< 0.001), with patients in the “very severe comorbid” and “very severe respiratory” clusters most likely to die. Overall survival was not significantly different between Serbia and the Czech Republic after adjustment for age, BMI, comorbidities and forced expiratory volume in 1 second (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.65– 0.99; P=0.036 [unadjusted]; HR 0.88, 95% CI 0.7– 1.1; P=0.257 [adjusted]). The most common causes of death were respiratory-related (36.8%), followed by cardiovascular (25.2%) then neoplasm (15.2%).Conclusion: Patient clusters based on comorbidities, lung function, age, BMI and dyspnea were more likely to show differences in COPD mortality risk than phenotypes defined by exacerbation history and presence/absence of chronic bronchitis and/or asthmatic features.Plain language summary: People with COPD have difficulty breathing and can have a greater risk of death (mortality) than people without COPD. However, the mortality risk of a person with COPD depends on their individual clinical profile. Previous studies have shown that grouping patients into different “phenotypes” based on their respiratory symptoms or into “clusters” based on additional characteristics, including their age, body mass index and illnesses they have alongside COPD, can help to predict mortality.There is limited data on COPD-related mortality in Central and Eastern Europe (CEE). In 2014– 2015, a large, cross-sectional study conducted across 11 countries in CEE (the POPE study) analyzed the prevalence of different patient phenotypes but did not assess mortality. In this retrospective analysis of the POPE study, we assessed mortality in 801 patients with COPD in two countries (the Czech Republic and Serbia) over a 7-year follow-up period. We grouped patients by clinical phenotypes and clusters to see which method provided significant differences between the groupings when it came to patient survival.We found that most patients with COPD died due to diseases related to their airways and lungs. However, when grouping patients into clinical phenotypes based on respiratory symptoms alone, differences in risk of death between groups were only seen in one country. Grouping patients into clusters showed differences in risk of death between clusters for both countries. Patients with worse lung function and who were more breathless had a higher risk of death, along with those with other severe diseases alongside their COPD.Keywords: COPD, survival, mortality, Central and Eastern Europe, respiratory, clinical phenotype, cluster

Arschang Valipour,1 Sergey Avdeev,2 Adam Barczyk,3 Valentina Bayer,4 Zvi Fridlender,5 Mariela Georgieva,6 Ondřej Kudela,7 Alexey Medvedchikov,8 Ramona Miron,9 Maria Sanzharovskaya,8 Virginija Šileikienė,10 Jurij Šorli,11 Marc Spielmanns,12 Zsuzsanna Szalai13 1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Vienna Health Care Group, Klinik Floridsdorf, Vienna, Austria; 2I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 3Wydział Nauk Medycznych Śląskiego Uniwersytetu Medycznego, Katowice, Poland; 4Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 6Medical Center “Sv.ivan Rilski” OOD, Vidin, Bulgaria; 7Department of Pneumology, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic; 8Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 9Clinical Pneumophtysiology Hospital Iasi, Iasi, Romania; 10Faculty of Medicine, Clinic of Chest Diseases, Immunology and Allergology, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania; 11Bolnišnica Topolšica, Topolšica, Slovenia; 12Zürcher RehaZentrum Wald, Wald, Switzerland; 13Petz Aladar County Teaching Hospital, Gyor, HungaryCorrespondence: Arschang ValipourDepartment of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Vienna Health Care Group, Klinik Floridsdorf, Brünner Straße 68, 1210 Vienna, AustriaTel +43 1 277 00-72201Fax +43 1 277 00 99 2208Email arschang.valipour@gesundheitsverbund.atBackground: 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 β2-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.Keywords: tiotropium, olodaterol, COPD, CCQ, Clinical COPD Questionnaire, non-interventional study

Abstract Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. Methods TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV1, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

Arschang Valipour,1 Pallav L Shah,2 Felix J Herth,3 Christophe Pison,4 Christian Schumann,5 Ralf-Harto Hübner,6 Peter I Bonta,7 Romain Kessler,8 Wolfgang Gesierich,9 Kaid Darwiche,10 Bernd Lamprecht,11 Thierry Perez,12 Dirk Skowasch,13 Gaetan Deslee,14 Armelle Marceau,15 Frank C Sciurba,16 Reinoud Gosens,17 Jorine E Hartman,18 Francesca Conway,2 Marina Duller,1 Martin Mayse,19 Holly S Norman,19 Dirk-Jan Slebos18 On behalf of the AIRFLOW-2 Trial Study Group1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord-Klinik Floridsdorf, Vienna, Austria; 2Royal Brompton & Harefield NHS Trust, Chelsea & Westminster Hospital and Imperial College, London, UK; 3Thoraxklinik, Department of Pneumology and Critical Care Medicine and Translational Lung Research Center Heidelberg (TLRCH), University of Heidelberg, Heidelberg, Germany; 4CHU Grenoble Alpes, Service Hospitalier Universitaire Pneumologie Physiologie; Université Grenoble Alpes, Grenoble, France; 5Clinic of Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care, Klinikverbund Allgaeu, Kempten and Immenstadt, Germany; 6Charité Universitätsmedizin Berlin, Medizinische Klinik m. Schw. Infektiologie und Pneumologie, Campus Virchow, Berlin, Germany; 7Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 8Service de Pneumologie, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, France; 9Asklepios-Fachkliniken Munich-Gauting, Comprehensive Pneumology Center Munich, Gauting, Germany; 10Department of Pulmonary Medicine, Section of Interventional Pneumology, Ruhrlandklinik - University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 11Department of Pulmonary Medicine, Kepler Universitatsklinikum GmbH, Linz, Austria; 12CHU de Lille – Hôpital Calmette, Lille, France; 13Department of Internal Medicine II - Cardiology/Pneumology, University of Bonn, Bonn, Germany; 14CHU de Reims, Hôpital Maison Blanche, Service de Pneumologie, Reims, France; 15Service de Pneumologie, Hôpital Universitaire Bichat, Paris, France; 16University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 17Department of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; 18Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 19Nuvaira, Inc., Minneapolis, MN, USACorrespondence: Dirk-Jan SlebosDepartment of Pulmonary Diseases/Interventional Bronchoscopy AA11, University Medical Center Groningen, PO Box 30001, Groningen, the NetherlandsTel +31 503612357Fax +31503619320Email d.j.slebos@umcg.nlPurpose: COPD exacerbations are associated with worsening clinical outcomes and increased healthcare costs, despite use of optimal medical therapy. A novel bronchoscopic therapy, targeted lung denervation (TLD), which disrupts parasympathetic pulmonary innervation of the lung, has been developed to reduce clinical consequences of cholinergic hyperactivity and its impact on COPD exacerbations. The AIRFLOW-2 study assessed the durability of safety and efficacy of TLD additive to optimal drug therapy compared to sham bronchoscopy and optimal drug therapy alone in subjects with moderate-to-severe, symptomatic COPD two years post randomization.Patients and Methods: TLD was performed in COPD patients (FEV1 30– 60% predicted, CAT≥ 10 or mMRC≥ 2) in a 1:1 randomized, sham-controlled, double-blinded multicenter study (AIRFLOW-2) using a novel lung denervation system (Nuvaira, Inc., USA). Subjects remained blinded until their 12.5-month follow-up visit when control subjects were offered the opportunity to undergo TLD. A time-to-first-event analysis on moderate and severe and severe exacerbations of COPD was performed.Results: Eighty-two subjects (FEV1 41.6± 7.4% predicted, 50.0% male, age 63.7± 6.8 yrs, 24% with prior year respiratory hospitalization) were randomized. Time-to-first severe COPD exacerbation was significantly lengthened in the TLD arm (p=0.04, HR=0.38) at 2 years post-TLD therapy and trended towards similar attenuation for moderate and severe COPD exacerbations (p=0.18, HR=0.71). No significant changes in lung function or SGRQ-C were found 2 years post randomization between groups.Conclusion: In a randomized trial, TLD demonstrated a durable effect of significantly lower risk of severe AECOPD over 2 years. Further, lung function and quality of life remained stable following TLD.Clinical Trial Registration: NCT02058459.Keywords: COPD exacerbation, targeted lung denervation, bronchoscopy, COPD

Arschang Valipour,1 Michael Tamm,2 Jana Kociánová,3 Valentina Bayer,4 Maria Sanzharovskaya,5 Alexey Medvedchikov,6 Monika Haaksma-Herczegh,6 János Mucsi,7 Zvi Fridlender,8 Claudia Toma,9,10 Andrey Belevskiy,11 Bohumil Matula,12 Jurij Šorli13 1Department of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord – Klinik Floridsdorf, Vienna, Austria; 2Lung Centre/Pneumology Department, University Hospital Basel, Basel, Switzerland; 3Pneumological Outpatient Department, MephaCentrum, a.s., Ostrava-Poruba, Czech Republic; 4Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5Respiratory TA, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 6Medical Affairs Regional Center, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna, Austria; 7Elizabeth Nursing Home, Gödöllő, Hungary; 8Department of Internal Medicine, Hebrew University Hadassah Medical School, Jerusalem, Israel; 9Department of Pneumology, Institute of Pneumatology “Marius Nasta”, Bucharest, Romania; 10Department Of Pneumology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 11Department of Pulmonology, Pirogov Russian National Research Medical University, Pletnev Hospital, Moscow, Russian Federation; 12Department of Functional Diagnostics, Specialized Hospital of Saint Zoerardus, Teaching Facility of the Slovak Medical University, Nitra, Slovakia; 13Topolšica Hospital, Topolšica, SloveniaCorrespondence: Arschang ValipourDepartment of Respiratory and Critical Care Medicine, Karl-Landsteiner-Institute for Lung Research and Pulmonary Oncology, Krankenhaus Nord-Klinik, Floridsdorf Brünnerstrasse 68, Wien, Vienna 1210, AustriaTel +43 1 910 600Email arschang.valipour@wienkav.atBackground: 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 β2-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

Arschang Valipour,1 Sherwin Asadi,1 Christophe Pison,2 Marie Jondot,2 Romain Kessler,3 Khaled Benneddif,3 Gaetan Deslee,4 Margaux Verdier,4 Dirk-Jan Slebos,5 Martin Mayse6 1Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Otto-Wagner-Spital, Vienna, Austria; 2CHU Grenoble Alpes, Clinique Universitaire de Pneumologie, Université Grenoble Alpes, Grenoble, France; 3Service de Pneumologie, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, France; 4CHU de Reims, Hôpital Maison Blanche, Service de Pneumologie, INSERM UMRS903, Reims, France; 5Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 6Nuvaira, Inc., Minneapolis, MN, USA Background: Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD which ablates parasympathetic pulmonary nerves running along the outside of the two main bronchi with the intent of inducing permanent bronchodilation. The goal of this study was to evaluate the feasibility and long-term safety of bilateral TLD during a single procedure. Patients and methods: This prospective, multicenter study evaluated 15 patients with moderate-to-severe COPD (forced expiratory volume in 1 s [FEV1] 30%–60%) who underwent bilateral TLD treatment following baseline assessment without bronchodilators. The primary safety end point was freedom from documented and sustained worsening of COPD directly attributable to TLD up to 1 year. Secondary end points included technical feasibility, change in pulmonary function tests, exercise capacity, and health-related quality of life. Follow-up continued up to 3 years for subjects who reconsented for longer-term follow-up. Results: A total of 15 patients (47% male, age 63.2±4.0 years) underwent TLD with a total procedure time of 89±16 min, and the total fluoroscopy time was 2.5±2.7 min. Primary safety end point of freedom from worsening of COPD was 100%. There were no procedural complications reported. Results of lung function analysis and exercise capacity demonstrated similar beneficial effects of TLD without bronchodilators, when compared with long-acting anticholinergic therapy at 30 days, 180 days, 365 days, 2 years, and 3 years post-TLD. Five of the 12 serious adverse events that were reported through 3 years of follow-up were respiratory related with no events being related to TLD therapy. Conclusion: TLD delivered to both lungs in a single procedure is feasible and safe with few respiratory-related adverse events through 3 years. Keywords: COPD, bronchoscopy, radiofrequency ablation, denervation, device

In the present study, lysozyme, immunoglobulin M (IgM), and complement component 3 (C3) were measured in unfertilized and fertilized eggs, two week post fertilization (WPF) larvae and 1, 2, 4, 6, and 12 month post fertilization (MPF) juveniles and the female broodstock of Siberian sturgeon, Acipenser baerii Brandt. The lysozyme level was measured with the turbidimetric method and IgM and C3 levels were measured with the ELISA method. The results showed that the lysozyme level decreased significantly from the unfertilized eggs to the 2-week-old larvae, and then it increased until 2 MPF. Significant changes in lysozyme levels were not observed from the 2 MPF juveniles to the broodstock. The IgM level decreased significantly from the unfertilized eggs to the 2 WPF larvae, then it increased until the 2 MPF, and, finally, it revealed a significant decrease in 4 MPF juveniles. Significant variations of C3 were found from the unfertilized eggs to the 2 MPF juveniles. Additionally, there were no significant variations in IgM or C3 in 4 to 12 MPF juveniles or in the female broodstock. The results indicate that two weeks post fertilization can be an immunologically sensitive period in early life stages of Siberian sturgeon.

Amnon Ariel,1 Alan Altraja,2,3 Andrey Belevskiy,4 Piotr W Boros,5 Edvardas Danila,6 Matjaz Fležar,7 Vladimir Koblizek,8 Zvi G Fridlender,9 Kosta Kostov,10 Alvils Krams,11 Branislava Milenkovic,12 Attila Somfay,13 Ruzena Tkacova,14 Neven Tudoric,15 Ruxandra Ulmeanu,16 Arschang Valipour17 1Emek Medical Center, Clalit Healthcare Services, Afula, Israel; 2Department of Pulmonary Medicine, University of Tartu, 3Lung Clinic, Tartu University Hospital, Tartu, Estonia; 4Department of Pulmonology, Russian National Research Medical University, Moscow, Russia; 5Lung Pathophysiology Department, National TB and Lung Diseases Research Institute, Warsaw, Poland; 6Clinic of Infectious Chest Diseases, Dermatovenereology, and Allergology, Vilnius University, Centre of Pulmonology and Allergology, Vilnius University Hospital, Vilnius, Lithuania; 7University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; 8Department of Pneumology, University Hospital, Hradec Králové, Czech Republic; 9Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem, Israel; 10Clinic of Pulmonary Diseases, Military Medical Academy, Sofia, Bulgaria; 11Medical Faculty of Latvian University, Riga East University Hospital, Riga, Latvia; 12Clinic for Pulmonary Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 13Department of Pulmonology, University of Szeged, Deszk, Hungary; 14Department of Respiratory Medicine and Tuberculosis, Faculty of Medicine, PJ Safarik University, Košice, Slovakia; 15School of Medicine, Dubrava University Hospital, Zagreb, Croatia; 16Marius Nasta Institute of Pneumology, Bucharest, Romania; 17Department of Respiratory and Critical Care Medicine, Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna, Austria Abstract: COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups. Keywords: dual bronchodilation, inhaled corticosteroid, LAMA, LABA, tiotropium, anticholinergic

Matthias Helmut Urban,1 Philipp Eickhoff,2 Georg-Christian Funk,1 Otto Chris Burghuber,1 Michael Wolzt,3 Arschang Valipour1 1Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria; 2Department of Obstetrics and Gynecology, St. Josef Hospital, Vienna, Austria; 3Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. Methods: The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. Results: Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. Conclusion: B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels. Keywords: cardiovascular risk, chronic obstructive pulmonary disease, comorbidity, subclinical atherosclerosis, biomarker

Abstract Background Acute coronary syndrome (ACS) is frequently reported in patients with coronavirus disease 2019 (COVID-19). Cytokine storm induced by interleukin-6 (IL-6) has been suggested to potentially cause myocardial injury in COVID-19. We investigated the association between baseline level of IL-6 and development of ACS in COVID-19 patients. Methods Demographic and clinical data of hospitalized COVID-19 patients from 2020 to 2022 were reviewed. Extracted data including patient characteristics, laboratory biomarkers, and systemic inflammation indexes in patients with or without ACS were reviewed and analyzed. Logistic regression models were applied to analyze predictors of ACS development and receiver-operating characteristic (ROC) curves were used to assess discriminatory power of IL-6 and other risk factors for predicting ACS development. Results Among 1,753 COVID-19 patients, 37 cases experienced ACS and 159 patients without main COVID-19 complications were randomly selected as controls. ACS patients were older (p = 0.001) and suffered from more comorbidities including diabetes (43% vs. 18%, p = 0.001), hypertension (40.5% vs. 24.5%, p = 0.050), ischemic heart disease (49% vs. 9%, p = 0.001), and hyperlipidemia (19% vs. 5%, p = 0.010). Also, decreased level of consciousness (31.6% vs. 2.5%, p = 0.001), ICU admission (65% vs. 2%, p = 0.001), and mortality events (70% vs. 0.6%, p = 0.001) were more prevalent in the ACS group. Baseline levels of IL-6 (p = 0.001), D-dimer (p = 0.026), troponin (p = 0.001), blood urea nitrogen (p = 0.002), and creatinine (p = 0.008) were higher in ACS patients but erythrocyte sedimentation rate (p = 0.013), hemoglobin (p = 0.033), and red blood cells (p = 0.028) were lower compared with controls. Also, age (OR: 1.06, p = 0.019), IL-6 (OR: 1.44, p = 0.047), and cardiovascular disease (CVD) (OR: 3.66, p = 0.043) were associated with ACS development. The area under the curve (AUC) of IL-6 and combined predictors respectively was 0.661 (p = 0.002) and 0.829 (p = 0.001). Conclusions High IL-6 concentration at baseline is a strong predictor for ACS development in COVID-19 patients. Also, elderly and concurrent CVD are significantly associated with ACS development.

Objective Work-related musculoskeletal disorders are one of dentists’ most common occupational health problems. Human error is considered one of the critical factors of medical error. Musculoskeletal abnormality due to inappropriate work postures and mental workload are two important causes of human error in dental operations. Hence, this study investigates dentists’ mental workload and the incidence of skeletal-muscular disorders. Materials & Methods A cross-sectional descriptive study was conducted in Shahid Shukri Dental Hospital in 2021. The sampling was done via the targeted sampling method and 42 individuals were included in the study. The NASA task load index and the Nordic questionnaire were used to collect the data. Data analysis was done using the SPSS software, version 26, at the significance level of 0.05. Results The average percentage of disorders were as follows: Neck area=30.1%, left shoulder=11.76%, right shoulder=13.74%, right elbow=9.23%, left elbow=6.56%, right wrist=28%, left-hand wrist=25.06%, upper back area=20.1%, waist=13.8%, hip and thigh=17.1%, knee=26% and ankle=23.46%. Age and work experience had a significant relationship with the prevalence of musculoskeletal disorders (P

Zuzana Zbozinkova,1 Adam Barczyk,2 Ruzena Tkacova,3 Arschang Valipour,4 Neven Tudoric,5 Kirill Zykov,6 Attila Somfay,7 Marc Miravitlles,8 Vladimir Koblizek91Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2Department of Pneumology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland; 3Department of Respiratory Medicine, Faculty of Medicine, P.J. Safarik University, Kosice, Slovakia; 4Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann-Institute for COPD and Respiratory Epidemiology, Otto-Wagner-Spital, Wien, Austria; 5School of Medicine Zagreb, University Hospital Dubrava, Zagreb, Croatia; 6Laboratory of Pulmonology, Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Moscow, Russia; 7Department of Pulmonology, University of Szeged, Deszk, Hungary; 8Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 9Department of Pneumology, Faculty of Medicine in Hradec Kralove, University Hospital Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech RepublicIntroduction: 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.Keywords: COPD, phenotypes, Central Europe, Eastern Europe, study, GOLD, comorbidity

Background: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, Alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population. Methods: The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P> 0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P= 0.037). Furthermore, the distribution of AA+ AG /G G genotypes was found to be statistically significant between the two groups (P= 0.011). Conclusions: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.