0000000000135693

AUTHOR

Klaus F. Rabe

0000-0002-7020-1401

Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study

BACKGROUND: Small airways dysfunction (SAD) is well recognised in asthma, yet its role in the severity and control of asthma is unclear. This study aimed to assess which combination of biomarkers, physiological tests, and imaging markers best measure the presence and extent of SAD in patients with asthma.METHODS: In this baseline assessment of a multinational prospective cohort study (the Assessment of Small Airways Involvement in Asthma [ATLANTIS] study), we recruited participants with and without asthma (defined as Global Initiative for Asthma severity stages 1-5) from general practices, the databases of chest physicians, and advertisements at 29 centres across nine countries (Brazil, Chi…

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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 …

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WITHDRAWN: Scaling up strategies of the Chronic Respiratory Disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 – Area 5)

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Lumican and biglycan expression in lungs of COPD patients

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S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma

ZusammenfassungDie vorliegende Leitlinie ist eine Neufassung und Aktualisierung der Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma, welche die bisher für den deutschen Sprachraum gültige Version aus dem Jahr 2006 ablöst. Die Fülle an neuen Erkenntnissen zur Pathophysiologie und zu den Phänotypen von Asthma und das erweiterte Spektrum an diagnostischen und therapeutischen Möglichkeiten bei dieser Erkrankung machte eine Neufassung und Aktualisierung notwendig. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

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Roflumilast for asthma: Weighing the evidence

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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…

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Abstract 13257: FEV1 and FVC predict Mortality in Individuals Without Manifest Lung Disease Independent of Cardiac Performance - Results From the Population-based Gutenberg Health Study

Background: Pulmonary disease has consistently been related to increased mortality. We investigated central spirometry variables in relation to total mortality in individuals from the general population without diagnosed lung disease also accounting for cardiac function. Methods: In 15,010 individuals from the general population (mean age 55±11 years, age range 35-74 years, 50.5% men) in the Gutenberg Health Study we performed spirometry and multimodal transthoracic echocardiography. The biomarkers N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (TnI) were measured in the first 5000 individuals using commercially available assays. Multivariable Cox regre…

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Subclinical impairment of lung function is related to mild cardiac dysfunction and manifest heart failure in the general population.

Lung function impairment has previously been related to heart failure, although no overt cardiovascular or structural heart disease is present. The extent to which pulmonary function is related to subclinical left ventricular impairment in the general population remains to be investigated.15010 individuals from the general population (mean age 55±11years, 50.5% men) in the Gutenberg Health Study underwent spirometry, transthoracic echocardiography and biomarker measurement. Forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) in percent of the predicted value and FEV1/FVC ratio were associated with echocardiographic measures of cardiac structure, systolic and diastolic func…

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Seasonal Distribution Of Exacerbations In The Poet-COPD; Study

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Tiotropium Reduces Exacerbations Versus Salmeterol Irrespective Of Baseline ICS Treatment In The Poet-COPD; Study

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Differential distribution of inflammatory cells in large and small airways in smokers

BACKGROUND: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell distribution between large airways (LA) and small airways (SA) have not been systematically explored in smokers. Hypothesis: The content of cells infiltrating the airway wall differs between LA and SA. AIMS: To compare the content of neutrophils, macrophages, lymphocytes and mast cells infiltrating LA and SA in smokers who underwent surgery for lung cancer. METHODS: Lung tissue from 15 smokers was analysed. Inflammatory cells in the lamina propria were identified by immuno…

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S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma – Addendum 2020

ZusammenfassungDas vorliegende Addendum zur Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma (2017) ergänzt wichtige neue Erkenntnisse zur Diagnostik und Therapie von Asthma sowie zu neu für die Therapie des Asthmas zugelassenen Medikamenten. Es werden sowohl für Kinder und Jugendliche als auch für Erwachsene mit Asthma die aktuellen, Evidenz-basierten diagnostischen und therapeutischen Empfehlungen dargelegt.

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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.

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Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA<sup>2</sup>LEN – ARIA Position Paper

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in …

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Benefits of Tiotropium + Olodaterol Over Tiotropium at Delaying Clinically Significant Events in Patients with COPD Classified as GOLD B

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Versican and collagen-III expression in bronchial and pulmonary muscular arteries in COPD patients

Background: We demonstrated that COPD patients have thicker bronchial and pulmonary muscular arteries (MA) compared with never and non-obstructed smokers. The composition of the extracellular matrix of these altered MA has been not fully described. Objectives: To investigate the expression of versican and collagen-III in bronchial and pulmonary MA in the lungs of mild/moderate COPD patients. Methods: Eighteen mild/moderate COPD subjects (67±8y, FEV 1 : 67±15%pred), 14 non-obstructed smokers (64±8y, FEV 1 : 95±10%pred) and 11 never-smoking controls (CTRL) (51±12y, FEV 1 : 108±15%pred) were studied. Lung tissue obtained during surgery (ethical approval obtained) was used to analyze the expres…

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Extracellular matrix composition in COPD

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls…

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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…

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FEV1 and FVC predict all-cause mortality independent of cardiac function - Results from the population-based Gutenberg Health Study.

Abstract Background Lung function has previously been related to increased mortality. Whether pulmonary impairment is associated with an increased mortality independent of cardiac dysfunction remains unclear. Methods In 15010 individuals from the general population (age range 35–74years, 51% men) in the Gutenberg Health Study we performed spirometry and transthoracic echocardiography. N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (hsTnI) were measured in all individuals. 1819 individuals with pulmonary diseases were excluded from further analysis. Results The median for forced expiratory volume in 1s (FEV1) was 94.2% and for forced vital capacity (FVC) …

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Glycoproteins In Large And Small Airways And In Lung Parenchyma Of COPD Patients

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The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy.

Abstract Background Divergent strategies have emerged for the management of severe asthma. One strategy utilises high and fixed doses of maintenance treatment, usually inhaled corticosteroid/long-acting β2-agonist (ICS/LABA), supplemented by a short-acting β2-agonist (SABA) as needed. Alternatively, budesonide/formoterol is used as both maintenance and reliever therapy. The latter is superior to fixed-dose treatment in reducing severe exacerbations while achieving similar or better asthma control in other regards. Exacerbations may be reduced by the use of budesonide/formoterol as reliever medication during periods of unstable asthma. We examined the risk of a severe exacerbation in the per…

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Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

International audience; Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance …

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P294 Benefits of tiotropium/olodaterol over tiotropium at delaying clinically significant events in patients with copd classified as gold B

Rationale The once-daily combination of tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, has demonstrated efficacy and safety in COPD. Two large clinical studies (TONADO ® 1 + 2) have also demonstrated the benefits of T/O compared to the monocomponents in patients with moderate to very severe COPD. This post hoc analysis investigated whether T/O is more effective than T at delaying clinically significant events in patients with GOLD stage B COPD. Methods A total of 5162 patients were randomised to O 5 µg, T 2.5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg (delivered via Respimat ® inhaler) in two 52-week, parallel-group, double-blind studies (NC…

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Remodeling of bronchial and pulmonary muscular arteries in mild/moderate COPD

Pulmonary hypertension is well documented in severe COPD but little is known about vascular remodeling in mild/moderate patients. Aim:To investigate bronchial and pulmonary muscular arteries morphology and the expression of elastic fibers (EF) and collagen I in the lungs of mild/moderate COPD patients. Methods:Lung tissue of 18 COPD subject (FEV1:67±15%pred), 14 non-obstructed smokers(NOS) (FEV1:95±10%pred) and 11 never-smoking controls(CTRL) (FEV1:108±15%pred) was used to analyze the morphology of bronchial and pulmonary muscular arteries and the expression of EF and collagen I in the tunica intima, media and adventitia, using immune- and histochemistry and image analysis. Values (mean±SD)…

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