RETRO-POPE: A Retrospective, Multicenter, Real-World Study of All-Cause Mortality in COPD

Abstract

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 [email protected]: 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

Keywords

• copd
• survival
• mortality
• central and eastern europe
• respiratory
• clinical phenotype
• cluster.