Publications by authors named "Claus F Vogelmeier"

116 Publications

Efficacy of indacaterol/glycopyrronium salmeterol/fluticasone in current and ex-smokers: a pooled analysis of IGNITE trials.

ERJ Open Res 2021 Jan 22;7(1). Epub 2021 Feb 22.

National Heart and Lung Institute, Imperial College London, London, UK.

Inhaled corticosteroids have proven to be less effective in asthmatic patients who smoke; however, there is limited information on the efficacy of inhaled corticosteroid-containing regimens in COPD patients who continue smoking. We evaluate the differential efficacy of once-daily indacaterol/glycopyrronium 110/50 µg compared with twice-daily salmeterol/fluticasone 50/500 µg in current smokers and ex-smokers with COPD. A pooled analysis of data from ILLUMINATE, LANTERN and FLAME studies was conducted to assess the efficacy of indacaterol/glycopyrronium compared with salmeterol/fluticasone in current smokers and ex-smokers with COPD. Efficacy was assessed in terms of improvements in trough forced expiratory volume in 1 s (FEV) transition dyspnoea index (TDI) focal score, St George's Respiratory Questionnaire (SGRQ) total score, reduced rescue medication use and exacerbation prevention at 26 weeks after the start of the therapy. In total, 1769 (38%) current smokers and 2848 (62%) ex-smokers were included. Patients treated with indacaterol/glycopyrronium experienced greater improvements in trough FEV salmeterol/fluticasone in both current and ex-smokers (least squares mean treatment difference, 105 mL and 78 mL, respectively). Improvements in TDI focal score, SGRQ total score and reduction in rescue medication use were also greater with indacaterol/glycopyrronium salmeterol/fluticasone in current and ex-smokers. Furthermore, indacaterol/glycopyrronium reduced all exacerbations (moderate/severe) compared with salmeterol/fluticasone, irrespective of smoking status. The difference in efficacy in favour of indacaterol/glycopyrronium was more prominent in current smokers in most cases. Indacaterol/glycopyrronium demonstrated greater efficacy salmeterol/fluticasone, and the differences were generally more prominent in current smokers suggesting smoking may reduce the effects of salmeterol/fluticasone.
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http://dx.doi.org/10.1183/23120541.00816-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897898PMC
January 2021

Improving lung health in low-income and middle-income countries: from challenges to solutions.

Lancet 2021 Feb 22. Epub 2021 Feb 22.

Global Asthma Network (GAN), Auckland, New Zealand; International Union Against Tuberculosis and Lung Diseases, Paris, France; Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; UNSW Medicine, Sydney, NSW, Australia.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.
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http://dx.doi.org/10.1016/S0140-6736(21)00458-XDOI Listing
February 2021

Artificial intelligence/machine learning in respiratory medicine and potential role in asthma and COPD diagnosis.

J Allergy Clin Immunol Pract 2021 Feb 19. Epub 2021 Feb 19.

Novartis Pharmaceuticals Corporation, East Hanover, USA.

Artificial intelligence (AI) and machine learning, a subset of AI, are increasingly utilized in medicine. AI excels at performing well-defined tasks, such as image recognition; for example, classifying skin biopsy lesions, determining diabetic retinopathy severity, and detecting brain tumors. This article provides an overview of the use of AI in medicine and particularly in respiratory medicine, where it is used to evaluate lung cancer images, diagnose fibrotic lung disease, and more recently is being developed to aid the interpretation of pulmonary function tests and the diagnosis of a range of obstructive and restrictive lung diseases. The development and validation of AI algorithms requires large volumes of well-structured data, and the algorithms must work with variable levels of data quality. It is important that clinicians understand how AI can function in the context of heterogeneous conditions such as asthma and COPD where diagnostic criteria overlap, how AI use fits into everyday clinical practice and how issues of patient safety should be addressed. AI has a clear role in providing support for doctors in the clinical workplace but its relatively recent introduction means that confidence in its use still has to be fully established. Overall, AI is expected to play a key role in aiding clinicians in the diagnosis and management of respiratory diseases in the future and it will be exciting to the see benefits that arise for patients and doctors from its use in everyday clinical practice.
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http://dx.doi.org/10.1016/j.jaip.2021.02.014DOI Listing
February 2021

Protocol for an observational study to identify potential predictors of an acute exacerbation in patients with chronic obstructive pulmonary disease (the PACE Study).

BMJ Open 2021 Feb 8;11(2):e043014. Epub 2021 Feb 8.

Department of Pulmonary Rehabilitation, Member of the German Center for Lung Research (DZL), Philipps University Marburg, Marburg, Germany.

Introduction: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are the most critical events for patients with COPD that have a negative impact on patients' quality of life, accelerate disease progression, and can result in hospital admissions and death. Although there is no distinct definition or detailed knowledge about AECOPD, it is commonly used as primary outcome in clinical studies. Furthermore, it may be difficult in clinical practice to differentiate the worsening of symptoms due to an AECOPD or to the development of heart failure. Therefore, it is of major clinical importance to investigate the underlying pathophysiology, and if possible, predictors of an AECOPD and thus to identify patients who are at high risk for developing an acute exacerbation.

Methods And Analysis: In total, 355 patients with COPD will be included prospectively to this study during a 3-week inpatient pulmonary rehabilitation programme at the Schoen Klinik Berchtesgadener Land, Schoenau am Koenigssee (Germany). All patients will be closely monitored from admission to discharge. Lung function, exercise tests, clinical parameters, quality of life, physical activity and symptoms will be recorded, and blood samples and exhaled air will be collected. If a patient develops an AECOPD, there will be additional comprehensive diagnostic assessments to differentiate between cardiac, pulmonary or cardiopulmonary causes of worsening. Follow-up measures will be performed at 6, 12 and 24 months.Exploratory data analyses methods will be used for the primary research question (screening and identification of possible factors to predict an AECOPD). Regression analyses and a generalised linear model with a binomial outcome (AECOPD) will be applied to test if predictors are significant.

Ethics And Dissemination: This study has been approved by the Ethical Committee of the Philipps University Marburg, Germany (No. 61/19). The results will be presented in conferences and published in a peer-reviewed journal.

Trial Registration Number: NCT04140097.
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http://dx.doi.org/10.1136/bmjopen-2020-043014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871687PMC
February 2021

COPD & COVID-19.

Arch Bronconeumol 2021 Jan 20. Epub 2021 Jan 20.

Respiratory Institute, Hospital Clinic, IDIBAPS, University of Barcelona and National Spanish Network for Respiratory Research (CIBERES), Barcelona, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.arbres.2021.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816617PMC
January 2021

Transcriptional analysis identifies potential biomarkers and molecular regulators in acute malaria infection.

Life Sci 2021 Apr 2;270:119158. Epub 2021 Feb 2.

Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-Universität Marburg, Marburg, Germany; Department of Internal Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, German Center for Lung Research (DZL), Marburg, Germany; German Center for Lung Research (DZL), German Center for infectious Disease Research (DZIF), Center for Synthetic Microbiology (Synmikro), Philipps-Universität Marburg, Germany. Electronic address:

Aims: Malaria is a serious health threat in tropical countries. The causative parasite of Malaria tropica, the severe form, is the protozoan Plasmodium falciparum. In humans, it infects red blood cells, compromising blood flow and tissue perfusion. This study aims to identify potential biomarkers and RNA networks in leukocyte transcriptomes from patients suffering from Malaria tropica.

Materials And Methods: We identified differentially regulated mRNAs and microRNAs in peripheral blood leukocytes of healthy donors and Malaria patients. Genes whose expression changes were not attributable to changes in leukocyte composition were used for bioinformatics analysis and network construction. Using a previously published cohort of community-acquired pneumonia (CAP) patients, we established discriminating transcriptomic features versus Malaria. We aimed to establish differences between the patient groups by principal component (PCA) and receiving operator characteristic (ROC) analyses and in silico cell type deconvolution.

Key Findings: We found 870 genes that were significantly differentially expressed between healthy donors and Malaria patients. E2F1, BIRC5 and CCNB1 were identified to be primarily responsible for PCA separation of these two groups. We searched for biological function and found that cell cycle processes were strongly activated. By in silico cell type deconvolution, we attribute this to an expansion of γδ T cells. Additional discrimination between CAP and Malaria yielded 445 differentially expressed genes, among which immune proteasome transcripts PSMB8, PSMB9 and PSMB10 were significantly induced in Malaria.

Significance: We identified transcripts from patient leukocytes that differentiate between healthy, Malaria and CAP, and indicate a biological context with potential pathophysiological relevance.
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http://dx.doi.org/10.1016/j.lfs.2021.119158DOI Listing
April 2021

Deterioration and Mortality Risk of COPD Patients Not Fitting into Standard GOLD Categories: Results of the COSYCONET Cohort.

Respiration 2021 Jan 22:1-10. Epub 2021 Jan 22.

Department of Internal Medicine V, Comprehensive Pneumology Center (CPC), Member of the German Center for Lung Research (DZL), University of Munich (LMU), Munich, Germany,

Background: Patients with COPD-specific symptoms and history but FEV1/FVC ratio ≥0.7 are a heterogeneous group (former GOLD grade 0) with uncertainties regarding natural history.

Objective: We investigated which lung function measures and cutoff values are predictive for deterioration according to GOLD grades and all-cause mortality.

Methods: We used visit 1-4 data of the COSYCONET cohort. Logistic and Cox regression analyses were used to identify relevant parameters. GOLD 0 patients were categorized according to whether they maintained grade 0 over the following 2 visits or deteriorated persistently into grades 1 or 2. Their clinical characteristics were compared with those of GOLD 1 and 2 patients.

Results: Among 2,741 patients, 374 GOLD 0, 206 grade 1, and 962 grade 2 patients were identified. GOLD 0 patients were characterized by high symptom burden, comparable to grade 2, and a restrictive lung function pattern; those with FEV1/FVC above 0.75 were unlikely to deteriorate over time into grades 1 and 2, in contrast to those with values between 0.70 and 0.75. Regarding mortality risk in GOLD 0, FEV1%predicted and age were the relevant determinants, whereby a cutoff value of 65% was superior to that of 80% as proposed previously.

Conclusions: Regarding patients of the former GOLD grade 0, we identified simple criteria for FEV1/FVC and FEV1% predicted that were relevant for the outcome in terms of deterioration over time and mortality. These criteria might help to identify patients with the typical risk profile of COPD among those not fulfilling spirometric COPD criteria.
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http://dx.doi.org/10.1159/000513010DOI Listing
January 2021

From GOLD 0 to Pre-COPD.

Am J Respir Crit Care Med 2021 02;203(4):414-423

Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, member of the German Center for Lung Research (DZL), Philipps-University, Marburg, Germany.

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http://dx.doi.org/10.1164/rccm.202008-3328PPDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885837PMC
February 2021

Impact of Education on COPD Severity and All-Cause Mortality in Lifetime Never-Smokers and Longtime Ex-Smokers: Results of the COSYCONET Cohort.

Int J Chron Obstruct Pulmon Dis 2020 5;15:2787-2798. Epub 2020 Nov 5.

Department of Internal Medicine V, University of Munich (LMU), Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Munich, 80336, Germany.

Background: Beyond smoking, several risk factors for the development of chronic obstructive pulmonary disease (COPD) have been described, among which socioeconomic status including education is of particular interest. We studied the contribution of education to lung function and symptoms relative to smoking in a group of never-smokers with COPD compared to a group of long-time ex-smokers with COPD.

Methods: We used baseline data of the COSYCONET cohort, including patients of GOLD grades 1-4 who were either never-smokers (n=150, age 68.5y, 53.3% female) or ex-smokers (≥10 packyears) for at least 10 years (n=616, 68.3y, 29.9% female). Socioeconomic status was analyzed using education level and mortality was assessed over a follow-up period of 4.5 years. Analyses were performed using ANOVA and regression models.

Results: Spirometric lung function did not differ between groups, whereas CO diffusing capacity and indicators of lung hyperinflation/air-trapping showed better values in the never-smoker group. In both groups, spirometric lung function depended on the education level, with better values for higher education. Quality of life and 6-MWD were significantly different in never-smokers as well as patients with higher education. Asthma, alpha-1-antitrypsin deficiency, and bronchiectasis were more often reported in never-smokers, and asthma was more often reported in patients with higher education. Higher education was also associated with reduced mortality (hazard ratio 0.46; 95% CI 0.22-0.98).

Conclusion: Overall, in the COSYCONET COPD cohort, differences in functional status between never-smokers and long-time ex-smokers were not large. Compared to that, the dependence on education level was more prominent, with higher education associated with better outcomes, including mortality. These data indicate that non-smoking COPD patients' socioeconomic factors are relevant and should be taken into account by clinicians.
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http://dx.doi.org/10.2147/COPD.S273839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652228PMC
November 2020

Impact of baseline COPD symptom severity on the benefit from dual mono-bronchodilators: an analysis of the EMAX randomised controlled trial.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620968500

Centre de Pneumologie, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Québec, Canada.

Rationale: Symptom relief is a key treatment goal in patients with chronic obstructive pulmonary disease (COPD). However, there are limited data available on the response to bronchodilator therapy in patients at low risk of exacerbations with different levels of symptom severity. This study compared treatment responses in patients with a range of symptom severities as indicated by baseline COPD assessment test (CAT) scores.

Methods: The 24-week EMAX trial evaluated the benefits of umeclidinium/vilanterol umeclidinium or salmeterol in symptomatic patients at low exacerbation risk who were not receiving inhaled corticosteroids. This analysis assessed lung function, symptoms, health status, and short-term deterioration outcomes in subgroups defined by a baseline CAT score [<20 () and ⩾20 (pre-specified)]. Outcomes were also assessed using fractional polynomial modelling with continuous transformations of baseline CAT score covariates.

Results: Of the intent-to-treat population ( = 2425), 56% and 44% had baseline CAT scores of <20 and ⩾20, respectively. Umeclidinium/vilanterol demonstrated favourable improvements compared with umeclidinium and salmeterol for the majority of outcomes irrespective of the baseline CAT score, with the greatest improvements generally observed in patients with CAT scores <20. Fractional polynomial analyses revealed consistent improvements in lung function, symptoms and reduction in rescue medication use with umeclidinium/vilanterol umeclidinium and salmeterol across a range of CAT scores, with the largest benefits seen in patients with CAT scores of approximately 10-21.

Conclusions: Patients with symptomatic COPD benefit similarly from dual bronchodilator treatment with umeclidinium/vilanterol. Fractional polynomial analyses demonstrated the greatest treatment differences favouring dual therapy in patients with a CAT score <20, although benefits were seen up to scores of 30. This suggests that dual bronchodilation may be considered as initial therapy for patients across a broad range of symptom severities, not only those with severe symptoms (CAT ⩾20). NCT03034915, 2016-002513-22 (EudraCT number).
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http://dx.doi.org/10.1177/1753466620968500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659027PMC
November 2020

Extrafine Beclometasone Dipropionate/Formoterol Fumarate vs Double Bronchodilation Therapy in Patients with COPD: A Historical Real-World Non-Inferiority Study.

Int J Chron Obstruct Pulmon Dis 2020 29;15:2739-2750. Epub 2020 Oct 29.

Observational & Pragmatic Research Institute Pte Ltd, Singapore, Singapore.

Purpose: This study aimed to evaluate the non-inferiority of initiating extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF) versus double bronchodilation (long-acting beta-agonists [LABA]/long-acting muscarinic antagonists [LAMA]) among patients with a history of chronic obstructive pulmonary disease (COPD) exacerbations.

Patients And Methods: A historical cohort study was conducted using data from the UK's Optimum Patient Care Research Database. Patients with COPD ≥40 years at diagnosis were included if they initiated extrafine BDP/FF or any LABA/LAMA double therapy as a step-up from no maintenance therapy or monotherapy with inhaled corticosteroids (ICS), LAMA, or LABA and a history of ≥2 moderate/severe exacerbations in the previous two years. The primary outcome was exacerbation rate from therapy initiation until a relevant therapy change or end of follow-up. Secondary outcomes included rate of acute respiratory events, acute oral corticosteroids (OCS) courses, and antibiotic prescriptions with lower respiratory indication, modified Medical Research Council score (mMRC) ≥2, and time to first pneumonia diagnosis. The non-inferiority boundary was set at a relative difference of 15% on the ratio scale. Five potential treatment effect modifiers were investigated.

Results: A total of 1735 patients initiated extrafine BDP/FF and 2450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV <80% predicted. Extrafine BDP/FF showed non-inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 1.01 [95% CI 0.94-1.09]), acute respiratory events (IRR = 0.98 [0.92-1.04]), acute OCS courses (IRR = 1.01 [0.91-1.11]), and antibiotic prescriptions (IRR = 0.99 [0.90-1.09]), but not for mMRC (OR = 0.93 [0.69-1.27]) or risk of pneumonia (HR = 0.50 [0.14-1.73]). None of the a priori defined effect modifier candidates affected the comparative effectiveness.

Conclusion: This study found that stepping up to extrafine BDP/FF from no maintenance or monotherapy was not inferior to stepping up to double bronchodilation therapy in patients with a history of exacerbations.
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http://dx.doi.org/10.2147/COPD.S269287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605609PMC
October 2020

Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med 2021 01;203(1):24-36

Department of Medicine, Pulmonary, and Critical Care Medicine, the German Center for Lung Research, University Medical Center Giessen and Marburg, Philipps-University Marburg, Marburg, Germany.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised many questions about the management of patients with chronic obstructive pulmonary disease (COPD) and whether modifications of their therapy are required. It has raised questions about recognizing and differentiating coronavirus disease (COVID-19) from COPD given the similarity of the symptoms. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee used established methods for literature review to present an overview of the management of patients with COPD during the COVID-19 pandemic. It is unclear whether patients with COPD are at increased risk of becoming infected with SARS-CoV-2. During periods of high community prevalence of COVID-19, spirometry should only be used when it is essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. Patients with COPD should follow basic infection control measures, including social distancing, hand washing, and wearing a mask or face covering. Patients should remain up to date with appropriate vaccinations, particularly annual influenza vaccination. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an acute COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate-to-severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung strategy in patients with COPD and severe acute respiratory distress syndrome. Patients who developed asymptomatic or mild COVID-19 should be followed with the usual COPD protocols. Patients who developed moderate or worse COVID-19 should be monitored more frequently and accurately than the usual patients with COPD, with particular attention to the need for oxygen therapy.
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http://dx.doi.org/10.1164/rccm.202009-3533SODOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781116PMC
January 2021

A Non-Interventional Study of Tiotropium/Olodaterol versus Any Triple Combination Therapy for Chronic Obstructive Pulmonary Disease: The EVELUT Study Protocol.

Int J Chron Obstruct Pulmon Dis 2020 22;15:2601-2608. Epub 2020 Oct 22.

Department of Pneumology, University Hospital of Giessen and Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany.

Background: The Global Initiative for Chronic Obstructive Lung Disease 2020 report recommends that patients with chronic obstructive pulmonary disease (COPD) suffering from persistent dyspnea, despite long-acting β-agonist (LABA)/inhaled corticosteroid (ICS) maintenance therapy, are switched to either a long-acting muscarinic antagonist (LAMA)/LABA combination regimen or LAMA/LABA/ICS triple therapy. However, to date, no studies have investigated the direct switch from LABA/ICS to LAMA/LABA therapy-instead of switching to triple therapy-in a prospective, real-world, non-interventional setting.

Methods: EVELUT (NCT03954132) is an ongoing, prospective, open-label, multicenter, non-interventional study comparing the once-daily fixed-dose combination of tiotropium and olodaterol (tio/olo) versus any triple therapy (LAMA/LABA/ICS) in patients with COPD who are symptomatic despite LABA/ICS maintenance therapy. Patients with acute or frequent COPD exacerbations are excluded from the study. Participants will receive LABA/ICS maintenance treatment until Visit 1, followed by switching of treatment to tio/olo or LAMA/LABA/ICS. The primary endpoints are changes in modified Medical Research Council (mMRC) and COPD Assessment Test (CAT) scores after approximately 12 weeks of treatment. Secondary endpoints are change in the patients' general condition according to the Physician's Global Evaluation score, the proportion of responders with a change in mMRC score of ≥1 and in CAT score of ≥2, and patient satisfaction with the inhaler and therapy. The study is expected to enroll approximately 900 patients.

Conclusion: EVELUT results are expected to add to the current real-world evidence informing therapeutic decisions for COPD in everyday clinical practice.

Trial Registration: The European Union electronic Register of Post-authorisation Studies (EU PAS Register): EUPAS29784; the Federal Institute for Drugs and Medical Devices (BfArM): NIS Study No 7305; Clinicaltrials.gov: NCT03954132.
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http://dx.doi.org/10.2147/COPD.S262746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591229PMC
October 2020

COPDCompEx: A novel composite endpoint for COPD exacerbations to enable faster clinical development.

Respir Med 2020 11 28;173:106175. Epub 2020 Sep 28.

AstraZeneca, Early Respiratory & Immunology (R&I) Clinical Development, BioPharmaceuticals R&D, Gothenburg, Sweden. Electronic address:

Background: Frequency of moderate and severe chronic obstructive pulmonary disease exacerbations is an important endpoint in clinical trials, but makes them large and lengthy when powered to evaluate it. We aimed to develop a composite endpoint (COPDCompEx) that could predict treatment effect on exacerbations, enabling the design of shorter early phase clinical trials requiring fewer patients.

Methods: In this post hoc analysis, data from 20 randomized controlled trials were used to develop and test COPDCompEx. Diary events were tested against predefined threshold values for peak expiratory flow, reliever medication use, and symptoms. A COPDCompEx event was defined as first occurrence of a diary event, a moderate or severe exacerbation, or a study dropout. Ratios of event frequency, treatment effect and future trial sample size were compared between COPDCompEx and moderate and severe exacerbations.

Findings: At 3 months, the proportion of patients experiencing COPDCompEx events increased over 3-fold versus exacerbations alone. All components contributed to COPDCompEx event rate. Treatment effects at 3 months were closely matched between COPDCompEx and exacerbations, and the large net gain in power substantially reduced the required sample size.

Interpretation: COPDCompEx may be used to predict treatment effect on moderate and severe exacerbations of chronic obstructive pulmonary disease. This may enable the design of shorter Phase 2 clinical trials requiring fewer patients when compared with current exacerbation studies, with exacerbations as a key Phase 3 endpoint. This would, therefore, allow more efficient decision-making with reduced burden and risk to study participants.
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http://dx.doi.org/10.1016/j.rmed.2020.106175DOI Listing
November 2020

Utilization and determinants of use of non-pharmacological interventions in COPD: Results of the COSYCONET cohort.

Respir Med 2020 09 12;171:106087. Epub 2020 Jul 12.

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, GmbH - German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany; Institute for Medical Information Processing, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University Munich (LMU), Marchioninistr. 15, 81377, Munich, Germany.

Background: Guidelines for chronic obstructive pulmonary disease (COPD) recommend supplementing pharmacotherapy with non-pharmacological interventions. Little is known about the use of such interventions by patients. We analyzed the utilization of a number of non-pharmacological interventions and identified potential determinants of use.

Methods: Based on self-reports, use of interventions (smoking cessation, influenza vaccination, physiotherapy, sports program, patient education, pulmonary rehabilitation) and recommendation to use were assessed in 1410 patients with COPD. The utilization was analyzed according to sex and severity of disease. Potential determinants of utilization included demographic variables and disease characteristics and were analyzed using logistic regression models.

Results: Influenza vaccination in the previous autumn/winter was reported by 73% of patients. About 19% were currently participating in a reimbursed sports program, 10% received physiotherapy, 38% were ever enrolled in an educational program, and 34% had ever participated in an outpatient or inpatient pulmonary rehabilitation program. Out of 553 current or former smokers, 24% had participated in a smoking cessation program. While reports of having received a recommendation to use mainly did not differ according to sex, women showed significantly (p < 0.05) higher utilization rates than men for all interventions except influenza vaccination. Smoking was a predictor for not having received a recommendation for utilization and also significantly associated with a reduced odds of utilization. We found a correlation between recommendation to use and utilization.

Conclusions: Utilization of non-pharmacological interventions was lower in men and smokers. A recommendation or offer to use by the physician could help to increase uptake.
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http://dx.doi.org/10.1016/j.rmed.2020.106087DOI Listing
September 2020

Relationship between clinical and radiological signs of bronchiectasis in COPD patients: Results from COSYCONET.

Respir Med 2020 10 22;172:106117. Epub 2020 Aug 22.

Department of Pneumology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.
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http://dx.doi.org/10.1016/j.rmed.2020.106117DOI Listing
October 2020

Early Clinically Important Improvement (ECII) and Exacerbation Outcomes in COPD Patients.

Int J Chron Obstruct Pulmon Dis 2020 28;15:1831-1838. Epub 2020 Jul 28.

Respiratory Clinical Science Section, National Heart and Lung Institute, Imperial College London, London, UK.

Background: Chronic obstructive pulmonary disease (COPD) exacerbations are difficult outcomes to measure in clinical trials. It would be valuable to be able to predict which patients are likely to benefit in terms of exacerbation prevention based on their early response in lung function and symptoms.

Methods: This was a post-hoc analysis from the 52-week, randomized, double-blind, double-dummy, non-inferiority FLAME trial. Early clinically important improvement (ECII) was defined as achievement of minimal clinically important difference in trough forced expiratory volume in 1 second (FEV; ≥100 mL increase) and one patient-reported outcome (PRO): either St. George's Respiratory Questionnaire for COPD (≥4-unit reduction; D1), or COPD assessment test (≥2-point reduction; D2) at Week 4 or 12.

Results: Approximately 18-20% of patients achieved ECII at Week 4 or 12 post-randomization according to any of the two definitions. The rate of subsequent exacerbations was lower in patients who achieved ECII at Week 4 (D1: ratio of rates [95% CI], 0.85 [0.74 to 0.98]; D2, 0.88 [0.77 to 1.00]) or at Week 12 (D1, 0.85 [0.74 to 0.98]; D2, 0.86 [0.75 to 1.00]) versus patients not achieving ECII. Patients who achieved ECII experienced longer time-to-first exacerbation between Week 4 or 12 to end of study. More patients achieved ECII with indacaterol/glycopyrronium versus salmeterol/fluticasone according to both definitions at Week 4 (D1, odds ratio [95% CI], 1.69 [1.40 to 2.04]; D2, 1.61 [1.34 to 1.93]), and 12 (D1, 2.01 [1.66 to 2.44]; D2, 1.80 [1.48 to 2.18]).

Conclusion: ECII is a novel composite endpoint, based on clinically relevant improvement in lung function and PROs in the early phase of treatment intervention that may predict subsequent exacerbation risk and may be used in clinical trials.
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http://dx.doi.org/10.2147/COPD.S247966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435751PMC
July 2020

Effects of Vibration Training in Interstitial Lung Diseases: A Randomized Controlled Trial.

Respiration 2020;99(8):658-666. Epub 2020 Aug 19.

Center for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik University of Heidelberg, Heidelberg, Germany.

Background: Numerous studies have reported positive effects of exercise training in patients with interstitial lung disease (ILD) on physical capacity and quality of life. However, evidence is rare on the effects of specific forms of training and further pathophysiological mechanisms in these patients.

Objectives: In this multicenter study we aimed to explore the clinical effects of whole-body vibration training (WBVT) in patients with ILD on various outcome measures, including proinflammatory cytokines and myostatin.

Methods: We randomly assigned 26 patients with different forms of multidisciplinary confirmed fibrotic ILDs either to the WBVT group (n = 11; 55% male, 61 ± 14 years old, forced vital capacity 83.2 ± 29.3% predicted, 6-min walking distance [6MWD] 478 ± 79 m) performing 3 months of a standardized training (3 times per week), or to a control training group (CTG, n = 15; 60% male, 63 ± 9 years old, FVC 74.6 ± 20.5% predicted, 6MWD 455 ± 85 m) performing sham WBV training. Training in the two groups was performed on a GalileoTM vibration plate (6-20 vs. 5 Hz). The functional assessments before and after the intervention period included pulmonary function, 6MWD test, chair rise test, ultrasonographic measurement of quadriceps muscle thickness (cross-sectional area), quality of life questionnaires, and serum samples.

Results: We observed a significant increase in 6MWD (∆Training = 30 m [12-67], p = 0.024) and a decrease of myostatin (∆Training = -465 pg/mL [-713 to -166], p = 0.008) in the WBVT group. In contrast, no significant differences were observed in the CTG.

Conclusions: The present study demonstrates that WBVT is able to significantly increase 6MWD and decrease myostatin in patients with fibrotic ILDs. Therefore, WBVT seems to be a beneficial and feasible training modality in ILD patients. Clinical Trial Registry: German Clinical Trials Registry (DRKS00012930).
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http://dx.doi.org/10.1159/000508977DOI Listing
August 2020

Assessing Symptom Burden.

Clin Chest Med 2020 09;41(3):367-373

Department of Internal Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg (UMR), Baldingerstrasse, Marburg 35043, Germany.

Evaluating symptoms is a central part of the chronic obstructive pulmonary disease (COPD) assessment system as suggested by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Considering the pros and cons of all currently available tests, GOLD suggests using primarily the modified Medical Research Council dyspnea scale or the COPD Assessment Test. Based on the test results, patients are categorized as having a low or high level of symptoms. This level then becomes one of the 2 dimensions of the ABCD grading system, which was designed to match the best initial treatment option to the individual patient's needs.
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http://dx.doi.org/10.1016/j.ccm.2020.06.005DOI Listing
September 2020

Tiotropium/Olodaterol Decreases Exacerbation Rates Compared with Tiotropium in a Range of Patients with COPD: Pooled Analysis of the TONADO/DYNAGITO Trials.

Adv Ther 2020 10 10;37(10):4266-4279. Epub 2020 Aug 10.

Clinical Science Centre, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Introduction: Previous studies demonstrated that tiotropium/olodaterol reduced rates of exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this should be examined in a wider population.

Methods: This post hoc analysis pooled data from TONADO 1 + 2 and DYNAGITO, three 52-week, parallel-group, randomised, double-blind, phase III trials investigating patients with moderate-to-very severe COPD, with and without previous exacerbations, who received tiotropium/olodaterol 5/5 µg or tiotropium 5 µg. Subgroup analyses were conducted on patients stratified by exacerbation history, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 disease severity and baseline inhaled corticosteroid (ICS) use.

Results: In 9942 patients, tiotropium/olodaterol was associated with lower rates of moderate/severe exacerbations (0.68 vs. 0.77 per patient-year; rate ratio (RR) vs. tiotropium 0.89, 95% confidence interval (CI) 0.84, 0.95; P = 0.0003) and exacerbations requiring hospitalisation (0.11 vs. 0.13 per patient-year; RR 0.86, 95% CI 0.75, 0.99; P = 0.0380) versus tiotropium. Lower rates of moderate/severe exacerbations with tiotropium/olodaterol versus tiotropium were evident in patients with 0-1 moderate exacerbation in the previous year (0.54 vs. 0.60 per patient-year; RR 0.90, 95% CI 0.82, 0.98; P = 0.0187) and at least two moderate or at least one severe exacerbation(s) in the previous year (0.97 vs. 1.09 per patient-year; RR 0.89, 95% CI 0.82, 0.97; P = 0.0096). In patients with GOLD 2 and GOLD 3 COPD, moderate/severe exacerbation rates were lower with tiotropium/olodaterol versus tiotropium; GOLD 4 patients showed negligible difference between treatments. When evaluating patients by baseline ICS use, there was a significantly lower rate of moderate/severe exacerbations with tiotropium/olodaterol versus tiotropium in patients receiving ICS.

Conclusions: Tiotropium/olodaterol decreased the rate of moderate/severe exacerbations and exacerbations leading to hospitalisation versus tiotropium. Results from this large, pooled, post hoc analysis support the use of dual bronchodilation with tiotropium/olodaterol in a broad range of patients, reflective of patients with COPD in clinical practice.

Trial Registration: TONADO 1 (ClinicalTrials.gov: NCT01431274); TONADO 2 (ClinicalTrials.gov: NCT01431287); DYNAGITO (ClinicalTrials.gov: NCT02296138). People with chronic obstructive pulmonary disease (COPD) may have times when their symptoms worsen, known as exacerbations. This may mean that they need to take additional medications, such as antibiotics or oral steroids. Studies have shown that a combination of two types of inhaled medicine-tiotropium and olodaterol-can help to reduce exacerbations in some people. To see if this is also the case across a larger and more diverse range of people, we combined the results from three studies (TONADO 1 + 2 and DYNAGITO) that looked at people who were taking tiotropium and olodaterol together and people who were taking tiotropium alone. We showed that, across a wide range of people, treatment with tiotropium/olodaterol was generally better at reducing exacerbations than tiotropium. Tiotropium/olodaterol also decreased the number of exacerbations that led to hospitalisation compared with tiotropium. Overall, our results support the use of combined tiotropium/olodaterol in people at different stages of COPD.
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http://dx.doi.org/10.1007/s12325-020-01438-3DOI Listing
October 2020

Prediction of air trapping or pulmonary hyperinflation by forced spirometry in COPD patients: results from COSYCONET.

ERJ Open Res 2020 Jul 27;6(3). Epub 2020 Jul 27.

Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Comprehensive Pneumology Center Munich (CPC-M), member of the DZL, Munich, Germany.

Background: Air trapping and lung hyperinflation are major determinants of prognosis and response to therapy in chronic obstructive pulmonary disease (COPD). They are often determined by body plethysmography, which has limited availability, and so the question arises as to what extent they can be estimated spirometry.

Methods: We used data from visits 1-5 of the COPD cohort COSYCONET. Predictive parameters were derived from visit 1 data, while visit 2-5 data was used to assess reproducibility. Pooled data then yielded prediction models including sex, age, height, and body mass index as covariates. Hyperinflation was defined as ratio of residual volume (RV) to total lung capacity (TLC) above the upper limit of normal. (ClinicalTrials.gov identifier: NCT01245933).

Results: Visit 1 data from 1988 patients (Global Initiative for Chronic Obstructive Lung Disease grades 1-4, n=187, 847, 766, 188, respectively) were available for analysis (n=1231 males, 757 females; mean±sd age 65.1±8.4 years; forced expiratory volume in 1 s (FEV) 53.1±18.4 % predicted (% pred); forced vital capacity (FVC) 78.8±18.8 % pred; RV/TLC 0.547±0.107). In total, 7157 datasets were analysed. Among measures of hyperinflation, RV/TLC showed the closest relationship to FEV % pred and FVC % pred, which were sufficient for prediction. Their relationship to RV/TLC could be depicted in nomograms. Even when neglecting covariates, hyperinflation was predicted by FEV % pred, FVC % pred or their combination with an area under the curve of 0.870, 0.864 and 0.889, respectively.

Conclusions: The degree of air trapping/hyperinflation in terms of RV/TLC can be estimated in a simple manner from forced spirometry, with an accuracy sufficient for inferring the presence of hyperinflation. This may be useful for clinical settings, where body plethysmography is not available.
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http://dx.doi.org/10.1183/23120541.00092-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383055PMC
July 2020

NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD.

Nat Metab 2020 06 8;2(6):532-546. Epub 2020 Jun 8.

Justus-Liebig University, Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the superoxide source and an essential driver of smoke-induced emphysema and pulmonary hypertension development in mice. NOXO1 is consistently upregulated in two models of lung emphysema, Cybb (also known as NADPH oxidase 2, Nox2)-knockout mice and wild-type mice with tobacco-smoke-induced emphysema, and in human COPD. Noxo1-knockout mice are protected against tobacco-smoke-induced pulmonary hypertension and emphysema. Quantification of superoxide, nitrotyrosine and multiple NOXO1-dependent signalling pathways confirm that peroxynitrite formation from nitric oxide and superoxide is a driver of lung emphysema. Our results suggest that NOXO1 may have potential as a therapeutic target in emphysema.
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http://dx.doi.org/10.1038/s42255-020-0215-8DOI Listing
June 2020

Ruxolitinib for the treatment of SARS-CoV-2 induced acute respiratory distress syndrome (ARDS).

Leukemia 2020 08 17;34(8):2276-2278. Epub 2020 Jun 17.

Department of Medicine, Hematology, Oncology, Immunology, University Hospital Giessen and Marburg, and Philipps University Marburg, Baldinger Strasse 1, Marburg, Germany.

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http://dx.doi.org/10.1038/s41375-020-0907-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298698PMC
August 2020

Health-related quality of life associates with change in FEV in COPD: results from the COSYCONET cohort.

BMC Pulm Med 2020 May 29;20(1):148. Epub 2020 May 29.

Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, GmbH - German Research Center for Environmental Health, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.

Background: Forced expiratory volume in one second (FEV) characterizes the pathophysiology of COPD and different trajectories of FEV decline have been observed in patients with COPD (e.g. gradual or episodic). There is limited information about the development of patient-reported health-related quality of life (HRQL) over the full range of the natural history of COPD. We examined the longitudinal association between change in FEV and change in disease-specific and generic HRQL.

Methods: We analysed data of 1734 patients with COPD participating in the COSYCONET cohort with up to 3 years of follow-up. Patients completed the Saint George's Respiratory Questionnaire (SGRQ) and the EQ-5D Visual Analog Scale (EQ VAS). Change score models were used to investigate the relationship between HRQL and FEV and to calculate mean changes in HRQL per FEV change categories [decrease (≤ - 100 ml), no change, increase (≥ 100 ml)] after 3 years. Applying hierarchical linear models (HLM), we estimated the cross-sectional between-subject difference and the longitudinal within-subject change of HRQL as related to a FEV difference or change.

Results: We observed a statistically significant deterioration in SGRQ (total score + 1.3 units) after 3 years, which was completely driven by the activity component (+ 4 units). No significant change was found for the generic EQ VAS. Over the same period, 58% of patients experienced a decrease in FEV, 28% were recorded as no change in FEV, and 13% experienced an increase. The relationship between HRQL and FEV was found to be approximately linear with decrease in FEV being statistically significantly associated with a deterioration in SGRQ (+ 3.20 units). Increase in FEV was associated with improvements in SGRQ (- 3.81 units). The associations between change in FEV and the EQ VAS were similar. Results of the HLMs were consistent and highly statistically significant, indicating cross-sectional and longitudinal associations. The largest estimates were found for the association between FEV and the SGRQ activity domain.

Conclusions: Difference and change in FEV over time correlate with difference and change in disease-specific and generic HRQL. We conclude, that deterioration of HRQL should induce timely re-examination of physical status and lung function and possibly reassessment of therapeutic regimes.

Trial Registration: NCT01245933. Date of registration: 18 November 2010.
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http://dx.doi.org/10.1186/s12890-020-1147-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257512PMC
May 2020

Early and sustained symptom improvement with umeclidinium/vilanterol monotherapy in COPD: a analysis of the EMAX randomised controlled trial.

Ther Adv Respir Dis 2020 Jan-Dec;14:1753466620926949

Respiratory Medicine and Allergology, Lund University, Lund, Sweden.

Background: In chronic obstructive pulmonary disease (COPD), both the time needed for patients to gain symptom improvement with long-acting bronchodilator therapy and whether an early response is predictive of a sustained response is unknown. This study aimed to investigate how quickly meaningful symptom responses are seen in patients with COPD with bronchodilator therapy and whether these responses are sustained.

Methods: Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a 24-week, double-blind, double-dummy, parallel-group trial that randomised patients to umeclidinium/vilanterol (UMEC/VI), umeclidinium or salmeterol. Daily Evaluating Respiratory Symptoms in COPD (E-RS:COPD) score and rescue salbutamol use were captured an electronic diary and analysed initially in 4-weekly periods. analyses assessed change from baseline in daily E-RS:COPD score and rescue medication use weekly (Weeks 1-8), and association between E-RS:COPD responder status at Weeks 1-4 and later time points.

Results: In the intent-to-treat population ( = 2425), reductions from baseline in E-RS:COPD scores and rescue medication use were apparent from Day 2 with all treatments. Treatment differences for UMEC/VI either monotherapy plateaued by Week 4-8 and were sustained at Weeks 21-24; improvements were consistently greater with UMEC/VI. For all treatments, most patients (60-85%) retained their Weeks 1-4 E-RS:COPD responder/non-responder status at Weeks 21-24. Among patients receiving UMEC/VI who were E-RS:COPD responders at Weeks 1-4, 70% were responders at Weeks 21-24.

Conclusion: Patients with symptomatic COPD had greater potential for early symptom improvements with UMEC/VI either monotherapy. This benefit was generally maintained for 24 weeks. Early monitoring of treatment response can provide clinicians with an early indication of a patient's likely longer-term response to prescribed bronchodilator treatment and will facilitate appropriate early adjustments in care.

Clinical Trial Registration: NCT03034915, 2016-002513-22 (EudraCT Number).
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http://dx.doi.org/10.1177/1753466620926949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278094PMC
May 2020

Update in Chronic Obstructive Pulmonary Disease 2019.

Am J Respir Crit Care Med 2020 08;202(3):348-355

Department of Medicine, Pulmonary and Critical Care Medicine, Member of the German Center for Lung Research (DZL).

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http://dx.doi.org/10.1164/rccm.202002-0370UPDOI Listing
August 2020

High eosinophil blood counts are associated with a shorter length of hospital stay in exacerbated COPD patients - a retrospective analysis.

Respir Res 2020 May 6;21(1):106. Epub 2020 May 6.

Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Centre Giessen and Marburg, Philipps-University, Centre for Lung Research (DZL), 35043, Marburg, Germany.

Background: In COPD, the course of the disease including morbidity and mortality is strongly associated with severe exacerbations. The current GOLD recommendations emphasize blood eosinophil counts as a marker for responsiveness to inhaled corticosteroids (ICS). Retrospective analyses from randomized clinical trials indicate a favorable response to systemic corticosteroids in exacerbated COPD patients with blood eosinophils > 2%, however data outside clinical trials are scarce.

Patients And Methods: We retrospectively evaluated data from 1007 cases of patients who were admitted to the University Medical Center Marburg between 01/2013 and 12/2018. All patients had been diagnosed with an acute exacerbation of COPD (ICD-10 J44.0/J44.1). Our analysis was based on a subgroup of 417 patients in whom a full blood cell count was obtained at the day of admission. Patients were predominantly male (63.3%), had a median age of 74 years (IQR 65 years - 83 years) and a median FEV1 of 1.03 l (42.6% predicted). We compared the hospital length of stay and other outcome parameters using established thresholds for the eosinophil blood cell count (100 and 300 eosinophils/μl and 2%).

Results: Patients with low eosinophils (< 2%, <100 cells/μl) had a longer median time in hospital (length of hospital stay - LOS) as compared to patients with high eosinophils (< 2%: 9.31 vs. ≥2%:7 days, and < 100/μl: 10 vs. 100-300/μl: 8 vs. > 300/μl: 7 days). The median CRP was higher in patients with low eosinophils as compared to the other groups (< 2%: 22.7 vs. ≥2%: 9 mg/dl and < 100: 25 vs. 100-300: 13.5 vs. > 300: 7.1 mg/dl). Time to re-hospitalization or time to death did not differ between strata of eosinophils. Sensitivity analysis in a subgroup of patients in which pneumonia was excluded by chest x-ray did not significantly alter the results.

Conclusion: The results support the hypothesis that patients with severe COPD exacerbations and elevated blood eosinophil counts respond better to systemic corticosteroid treatment than patients with a non-eosinophilic exacerbation.
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http://dx.doi.org/10.1186/s12931-020-01365-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204070PMC
May 2020

COPD Assessment Test Changes from Baseline Correlate with COPD Exacerbations: A Longitudinal Analysis of the DACCORD Observational Study.

Lung 2020 06 4;198(3):507-514. Epub 2020 May 4.

Department of Sleep and Respiratory Medicine, Evangelical Hospital Goettingen-Weende, 37120, Bovenden, Germany.

Purpose: A number of analyses have shown the immediate impact of COPD exacerbations on health status. However, none evaluated the long-term correlation between health status and the occurrence of exacerbations.

Methods: DACCORD is an observational study in patients with COPD recruited across Germany following initiation or change in COPD maintenance medication. Data collected include COPD Assessment Test (CAT) total score on entry and after 1 and 2 years, and the occurrence of exacerbations. We analysed the correlation between change from baseline in CAT total score and exacerbations, after excluding patients who exacerbated during the quarter immediately prior to the CAT assessment of interest.

Results: The initial correlation analysis was performed in 6075 patients, 28% with ≥ 1 exacerbation over the 2-year follow-up, and 58% with a clinically relevant CAT improvement. There was a significant correlation between exacerbations over 2 years and CAT change from baseline at Year 2 (p = 0.0041). The Spearman's correlation coefficient was 0.03711, indicating very weak correlation-potentially driven by the high proportion of non-exacerbating patients. In a subsequent logistic regression, the probability of experiencing frequent (≥ 2 per year) or severe exacerbations was higher in patients with worsening in CAT total score (p < 0.001). However, the probability of a patient exacerbating in Year 1 or Year 2 did not correlate with CAT change.

Conclusions: In this population (initiating or changing maintenance COPD medication), patients with frequent or severe exacerbations had a long-term worsening in health status (beyond the acute effect of an exacerbation) compared with patients who do not exacerbate.
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http://dx.doi.org/10.1007/s00408-020-00357-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242247PMC
June 2020

Goals of COPD treatment: Focus on symptoms and exacerbations.

Respir Med 2020 05 21;166:105938. Epub 2020 Mar 21.

Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA.

Chronic obstructive pulmonary disease (COPD) is currently a leading cause of death worldwide, and its burden is expected to rise in the coming years. Common COPD symptoms include dyspnea, cough and/or sputum production. Some patients may experience acute worsening of symptoms (known as an exacerbation), and therefore require additional therapy. Exacerbations are mainly triggered by respiratory infections and environmental factors. Healthcare professionals face many challenges in COPD management, including the heterogeneity of the disease and under-reporting of symptoms. The authors review these challenges and provide recommendations for the best methods to assess COPD. The goals of COPD treatment include recognising the impact that both symptoms and exacerbations have on patients' lives when considering optimal patient-focused management. The review discusses the need for COPD management strategies to include both pharmacologic and non-pharmacologic approaches and provides recommendations for monitoring treatment outcomes and adjusting management strategies accordingly. Novel treatment strategies including precision medicine and point-of-care testing are also discussed.
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http://dx.doi.org/10.1016/j.rmed.2020.105938DOI Listing
May 2020