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Oumouna M.,Sudan University of Science and Technology | Weitnauer M.,University of Heidelberg | Mijosek V.,University of Heidelberg | Schmidt L.M.,University of Heidelberg | And 3 more authors.
Immunobiology | Year: 2015

Airway epithelial cells (AEC) are the first line of defense against airborne infectious microbes and play an important role in regulating the local immune response. However, the interplay of epithelial cells and professional immune cells during both homeostasis and infection has only been partially studied. The present study was performed to determine how bronchial epithelial cells affect the activation of monocytes. Under healthy conditions, AECs were shown to inhibit reactivity of monocytes. We hypothesized that upon infection, monocytes might be released from inhibition by AECs. We report that direct contact of monocytes with unstimulated BEAS2B epithelial cells results in inhibition of TNF secretion by activated monocytes. In addition to the known soluble modulators, we show that cell contacts between epithelial cells and monocytes or macrophages also contribute to homeostatic inhibitory actions. We find AECs to express the inhibitory molecule PD-L1 and blockade of PD-L1 results in increased secretion of pro-inflammatory cytokines from monocytes. Contrary to the inhibitory activities during homeostasis, epithelial cells infected with Respiratory Syncitial Virus (RSV) induce a significant release of inhibition. However, release of inhibition was not due to modulation of PD-L1 expression in AECs. We conclude that airway epithelial cells control the reactivity of monocytes through direct and indirect interactions; however tonic inhibition can be reverted upon stimulation of AECs with RSV and thereof derived molecular patterns. The study confirms the important role of airway epithelial cells for local immune reactions. © 2015 Elsevier GmbH. Source


Shah P.L.,NIHR Respiratory Biomedical Research Unit | Shah P.L.,Imperial College London | Herth F.J.F.,University of Heidelberg | Herth F.J.F.,Translational Lung Research Center
Thorax | Year: 2014

Introduction: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Emphysema is a component of COPD characterised by hyperinflation resulting in reduced gas exchange and interference with breathing mechanics. Endoscopic lung volume reduction using one-way valves to induce atelectasis of the hyperinflated lobe has been developed and studied in clinical trials over the last decade. Methods: Searches for appropriate studies were undertaken on PubMed and Clinical Trials Databases using the search terms COPD, emphysema, lung volume reduction and endobronchial valves. Results: The evidence from the randomised clinical trials suggests that complete lobar occlusion in the absence of collateral ventilation or where there is an intact lobar fissure are the key predictors for clinical success. Other indicators are greater heterogeneity in disease distribution between upper and lower lobes. The proportion of patients that respond to treatment improves from 20% in the unselected population to 75% with appropriate patient selection. The safety profile for endobronchial valves in this severely affected group of patients with emphysema was acceptable and the main adverse events observed were an excess of pneumothoraces. Conclusion: Selected patients have the potential of significant benefit in terms of lung function, exercise capacity and possibly even survival. These considerations are essential in-order to maximise patient benefit in a resource-limited environment and also to ensure that beneficial treatments are available for the appropriate patient. Source


Triphan S.M.F.,Research Center Magnetic Resonance Bavaria e.V. | Triphan S.M.F.,Translational Lung Research Center | Triphan S.M.F.,University of Heidelberg | Breuer F.A.,Research Center Magnetic Resonance Bavaria e.V. | And 5 more authors.
Journal of Magnetic Resonance Imaging | Year: 2015

Purpose: To provide a robust method for the simultaneous quantification of T1 and T2∗ in the human lung during free breathing. Breathing pure oxygen accelerates T1 and T2∗ relaxation in the lung. While T1 shortening reflects an increased amount of dissolved molecular oxygen in lung tissue, T2∗ shortening shows an increased concentration of oxygen in the alveolar gas. Therefore, both parameters reflect different aspects of the oxygen uptake and provide complementary lung functional information. Materials and Methods: A segmented inversion recovery Look-Locker multiecho sequence based on a multiecho 2D ultrashort TE (UTE) was employed for simultaneous T1 and T2∗ quantification. The radial projections follow a modified golden angle ordering, allowing for respiratory self-gating and thus the reconstruction of a series of differently T1 and T2∗-weighted images in arbitrary breathing states. The method was evaluated in nine healthy volunteers while breathing room air and pure oxygen, with two volunteers examined at five oxygen concentrations. Results: Relative differences of ΔT1 between 7.9% and 12.7% and of ΔT2∗ between 13.2% and 6.0% were found. Conclusion: The proposed method provides inherently coregistered, quantitative T1 and T2∗ maps in both expiration and inspiration from a single measurement acquired during free breathing and is thus well suited for clinical application. © 2014 Wiley Periodicals, Inc. Source


Kauczor H.-U.,University of Heidelberg | Kauczor H.-U.,Translational Lung Research Center | Bonomo L.,melli University Hospital | Gaga M.,Athens Chest Hospital | And 7 more authors.
European Radiology | Year: 2015

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low-dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low-dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and a quality assurance plan. The establishment of a central registry, including a biobank and an image bank, and preferably on a European level, is strongly encouraged. Key points: • Lung cancer screening using low dose computed tomography reduces mortality. • Leading US medical societies recommend large scale screening for high-risk individuals. • There are no lung cancer screening recommendations or reimbursed screening programmes in Europe as of yet. • The European Society of Radiology and the European Respiratory Society recommend lung cancer screening within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. • High risk, eligible individuals should be enrolled in comprehensive, quality-controlled longitudinal programmes. © 2015, The Author(s). Source


Kauczor H.-U.,University of Heidelberg | Kauczor H.-U.,Translational Lung Research Center | Bonomo L.,melli University Hospital | Gaga M.,Asthma Center | And 7 more authors.
European Respiratory Journal | Year: 2015

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and quality assurance plan. The establishment of a central registry, including biobank and image bank, and preferably on a European level, is strongly encouraged. Copyright © ERS/ESR 2015. Source

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