CAT score single item analysis in patients with COPD: results from COSYCONET

Abstract The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and Systemic Consequences - Comorbidities Network) with complete CAT data were included (n = 2270), of whom 493 had chest CT evaluated for the presence of emphysema. Comorbidities and lung function were assessed following standardised procedures. Cross-sectional data analysis was based on multiple regression analysis of the single CAT items ag…

Anticholinergika in der Therapie der chronisch-obstruktiven Lungenerkrankung (COPD)

Die chronisch-obstruktive Lungenerkrankung (COPD) stellt weltweit einen der wichtigsten Morbiditats- und Mortalitatsfaktoren dar. Der Erkrankung liegt in der uberwiegenden Mehrzahl der Falle ein jahrelanger Nikotinabusus zugrunde. Anders als beim Asthma bronchiale ist bei den Patienten mit COPD neben der Hypersekretion submuskuloser Drusen insbesondere die Erhohung des Bronchialmuskeltonus durch cholinerge Mechanismen eine dominierende Komponente der Bronchialobstruktion. Anticholinergika sind daher Mittel der ersten Wahl fur die Therapie der Bronchialobstruktion bei COPD. Anticholinergika verbessern neben der Lungenfunktion gleichermasen die Belastungstoleranz sowie Lebens- und Schlafquali…

Tiotropium - ein langwirksames, inhalatives Anticholinergikum zur Therapie der chronisch-obstruktiven Lungenerkrankung (COPD)

Anticholinergics are agents of first choice for the symptomatic treatment of patients with COPD. Tiotropium (Ba 679 BR, Spiriva) is a long-acting inhaled anticholinergic designed for once-daily bronchodilator treatment of COPD. Tiotropium is a selective antagonist of pulmonary M1 and M3 muscarinic receptor subtypes, that produces a long-lasting (24 hours), dose-dependent bronchodilation and bronchoprotection against constrictive stimuli, e. g. methacholine, following inhalation of single doses. Clinical trials with tiotropium in COPD patients over a maximum treatment duration of one year have confirmed a persisting bronchodilator effect of tiotropium compared with placebo and ipratropium, a…

The German COPD cohort COSYCONET: Aims, methods and descriptive analysis of the study population at baseline

Abstract Background The German COPD cohort study COSYCONET (" CO PD and SY stemic consequences- CO morbidities NET work") investigates the interaction of lung disease, comorbidities and systemic inflammation. Recruitment took place from 2010 to 2013 in 31 study centers. In addition to the baseline visit, follow-up visits are scheduled at 6, 18, 36 and 54 months after baseline. The study also comprises a biobank, image bank, and includes health economic data. Here we describe the study design of COSYCONET and present baseline data of our COPD cohort. Methods Inclusion criteria were broad in order to cover a wide range of patterns of the disease. In each visit, patients undergo a large panel …

Lung Preservation With Perfadex or Celsior in Clinical Transplantation: A Retrospective Single-Center Analysis of Outcomes.

BACKGROUND Despite improvement of lung preservation by the introduction of low-potassium dextran (LPD) solution, ischemia-reperfusion injury remains a major contributor to early post-lung transplant graft dysfunction and mortality. After favorable experimental data, Celsior solution was used in our clinical lung transplant program. Data were compared with our historic LPD cohort. METHODS Between January 2002 and January 2005, 209 consecutive lung transplantations were performed with LPD. These were compared to 208 transplants between February 2005 and September 2007 with Celsior. Endpoints included posttransplant PaO2/FiO2 ratio at different timepoints after intensive care unit (ICU) admiss…

New horizons in early stage COPD--improving knowledge, detection and treatment.

SummaryEarly stage COPD carries a significant healthcare burden that is currently underrecognised, underdiagnosed and undertreated. Furthermore, patients at this stage can rapidly decline to advanced disease, especially if they continue to smoke. The natural history of the disease in early stages remains largely unknown, and emerging evidence indicates that we are able to reduce lung function decline and exacerbations, and improve quality of life, in early stage COPD, mainly through smoking cessation. But new evidence from randomised clinical trials also suggests an impact of pharmacotherapy on clinical outcomes in early disease. Guidelines need to be updated to reflect this greater underst…

In human and rat lung membranes [35s]GTPγS binding is a tool for pharmacological characterization of G protein-coupled devucleotide receptors

The P2Y receptor family is activated by extracellular nucleotides such as ATP and UTP. P2Y receptors regulate physiological functions in numerous cell types. In lung, the P2Y2 receptor subtype plays a role in controlling Cl- and fluid transport. Besides ATP or UTP, also diadenosine tetraphosphate (Ap4A), a stable nucleotide, seems to be of physiological importance. In membrane preparations from human and rat lung we applied several diadenosine polyphosphates to investigate whether they act as agonists for G protein-coupled receptors. We assessed this by determining the stimulation of [35S]GTPgammaS binding. Stimulation of [35S]GTPgammaS binding to G proteins has already been successfully ap…

Reductions in Inflammatory Biomarkers in Patients with Oral Corticosteroid-Dependent Asthma Treated with Tezepelumab

Alternative mechanisms for tiotropium

Tiotropium is commonly used in the treatment of chronic obstructive pulmonary disease. Although largely considered to be a long-acting bronchodilator, its demonstrated efficacy in reducing the frequency of exacerbations and preliminary evidence from early studies indicating that it might slow the rate of decline in lung function suggested mechanisms of action in addition to simple bronchodilation. This hypothesis was examined in the recently published UPLIFT study and, although spirometric and other clinical benefits of tiotropium treatment extended to four years, the rate of decline in lung function did not appear to be reduced by the addition of tiotropium in this study. This article summ…

Primary ciliary dyskinesia in adults with bronchiectasis: Data from the Embarc registry

Introduction: Primary ciliary dyskinesia (PCD) is an inherited cause of bronchiectasis where defects in motile cilia result in failure to clear mucus. Individuals have life-long productive cough and recurrent infections Methods: The embarc registry is a prospective pan-European observational study of adults with bronchiectasis. Data entered into the registry between March 2015 and Jan 2018 was assessed. Disease severity in PCD was compared to two age and gender matched cohorts, the first consisting of individuals with immune deficiency and a second with idiopathic disease. Results: 287/11204 individuals (2.6%) were reported to have PCD. 65% were female, reflecting the female predominance in…

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

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 sign…

Real-World Multicenter Experience with Mepolizumab and Benralizumab in the Treatment of Uncontrolled Severe Eosinophilic Asthma Over 12 Months

Moritz Z Kayser,1 Nora Drick,1 Katrin Milger,2,3 Jan Fuge,1,4 Nikolaus Kneidinger,2,3 Stephanie Korn,5 Roland Buhl,6 Jürgen Behr,2,3 Tobias Welte,1,4 Hendrik Suhling1 1Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 2Department of Medicine V, University Hospital, LMU, Munich, Germany; 3Comprehensive Pneumology Center-Munich (CPC‐M), Member of the German Center for Lung Research (DZL), Munich, Germany; 4Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; 5Clinical Research Centre for Respiratory Medicine, Mainz, Germany; 6Pulmonary Department, Mainz Universit…

Evidenz für eine frühzeitige Therapie der COPD mit Tiotropium

Hintergrund: Die Wirksamkeit von Tiotropium versus Kontrolle wurde in einer praspezifizierten Subgruppenanalyse der 4-Jahres-Studie „Understanding Potential Long-term Impacts on Function with Tiotropium“ bei Patienten mit chronisch obstruktiver Lungenerkrankung (COPD) mittleren Schweregrades (GOLD II) untersucht und erstmals den gepoolten Ergebnissen aus den schwereren Krankheitsstadien (GOLD III/IV) gegenubergestellt. Methode: Randomisierte multizentrische, doppelblinde, kontrollierte Studie mit parallelem Gruppenvergleich bei 5993 Patienten uber 4 Jahre. Die Patienten erhielten entweder Tiotropium 18 µg einmal taglich oder Plazebo. Als Endpunkte wurden der jahrliche FEV1-Abfall und weiter…

Morphomolecular motifs of pulmonary neoangiogenesis in interstitial lung diseases

The pathogenetic role of angiogenesis in interstitial lung diseases (ILDs) is controversial. This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD. The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD.We performed comprehensive and compartment-specific analysis of 24 human lung explants with usual intersitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and alveolar fibroelastosis (AFE) using histopathology, microvascular corrosion casting, micro-comupted tomography based volumetry and gene expression…

Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD)

ZusammenfassungDas vorliegende Dokument ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit COPD, die die bisherige Version aus dem Jahr 2007 ablöst. Die Fülle an neuen Erkenntnissen zu Risikofaktoren, Diagnostik, Schweregradeinschätzung, Prävention und medikamentösen sowie nicht medikamentösen Therapiemaßnahmen machten eine umfassende Überarbeitung erforderlich. Die neue Leitlinie baut auf das GOLD-Dokument unter Berücksichtigung von Besonderheiten in Deutschland und Österreich auf.

Angiogenesis Patterns in Interstitial Lung Disease

Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (…

Onset of Effect, Changes in Airflow Obstruction and Lung Volume, and Health-Related Quality of Life Improvements with Benralizumab for Patients with Severe Eosinophilic Asthma: Phase IIIb Randomized, Controlled Trial (SOLANA)

Reynold A Panettieri Jr,1 Tobias Welte,2 Kartik V Shenoy,3 Stephanie Korn,4 Margret Jandl,5 Edward M Kerwin,6 Rosa Feijoo,7 Peter Barker,8 Richard F Olsson,9 Ubaldo J Martin8 On behalf of the SOLANA Study Investigators1Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA; 2Department of Respiratory Medicine, Member of the German Center of Lung Research, Medizinische Hochschule Hannover, Hannover, Germany; 3Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; 4Pulmonary Department, Universitätsmedizin Mainz, Langenbeckstr, Mainz, Germany; 5Hamburger Institut Für Th…

Studienendpunkte bei der chronisch-obstruktiven Lungenerkrankung (COPD): „Minimal Clinically Important Difference”

The concept of the minimal clinically important difference (MCID) is intended to provide a measure of relevance for a statistically applied in patients with COPD. Clinically important differences are those differences relevant to the individual patient and important to the patient's life. However, people's difference in a diagnostic parameter perception of what is important vary. Furthermore, physicians may rate the significance of a particular marker and its difference which can be achieved by a pharmacological intervention differently from the patient. Thus, the major problem with defining an MCID for any measure is that the most important differences, which require the most subtle measur…

Evolving Risk Factors for Mortality after Lung Transplantation over the Last 10 Years: Insights from a Single-Centre Database

s S233 218 (82%) patients received pooled platelet transfusion -median (IQR) 1(1-2) U. 209 (79%) and 129 (49%) patients received fresh frozen plasma (FFP) and cryoprecipitate with a median (IQR) of 3(2-4) and 0(0-0) U respectively. Conclusion: Rate and volume of transfusion of blood products compare favourably with centres performing surgery off CPB or on ECMO. Requirement for ECMO particularly for BTT, but also PGD is associated with high transfusion requirements.

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Abstract: BackgroundProgressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. MethodsWe examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immun…

<p>Switch from IL-5 to IL-5-Receptor α Antibody Treatment in Severe Eosinophilic Asthma</p>

Background Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy. Methods In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under …