Translational Lung Research Center

Heidelberg, Germany

Translational Lung Research Center

Heidelberg, Germany
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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).


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 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.


Herth F.J.F.,University of Heidelberg | Herth F.J.F.,Translational Lung Research Center | Eberhardt R.,University of Heidelberg | Eberhardt R.,Translational Lung Research Center | And 5 more authors.
Thorax | Year: 2015

Introduction The promise of benefits from lung cancer screening is tempered by the false positive rate and the need to perform diagnostic procedures to determine the aetiology of the solitary pulmonary nodules (SPN) identified. We have developed a novel procedure which allows sampling of SPNs via a transparenchymal approach, and report the results from this as a first in human trial. Methods This study was a prospective single-arm interventional study. We recruited patients with a SPN detected on CT imaging, which was suspicious for lung cancer, who were suitable for surgical resection. Using the subject's CT, an optimal airway wall point of entry (POE), and an avascular path through lung tissue from the POE to the SPN was calculated. A tunnel tract was created from the POE to the nodule using a set of catheter-based tools under fused fluoroscopy guidance. The patients proceeded to surgical resection immediately after the biopsy. The participants were followed-up for 6 months after the procedure. The primary endpoint of the study was to evaluate the feasibility to access and biopsy the nodule. Results Twelve patients were recruited, and a tunnel pathway created in 10 patients. There were no adverse events during the procedures. Adequate biopsies were obtained from 10 patients (83%), which correlated with the histological findings from the surgical resection. Inspection of the resected lobes did not raise any safety concerns and indicated appropriately tunnelled pathways to the nodule. Conclusions This first in human study demonstrates that bronchoscopic transparenchymal access of SPNs is feasible.


Weitnauer M.,University of Heidelberg | Mijosek V.,University of Heidelberg | Dalpke A.H.,University of Heidelberg | Dalpke A.H.,Translational Lung Research Center
Mucosal Immunology | Year: 2016

The lung is ventilated by thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbial compounds, most of them harmless contaminants. Airway epithelial cells are known to have innate sensor functions, thus being able to detect microbial danger. To avoid chronic inflammation, the pulmonary system has developed specific means to control local immune responses. Even though airway epithelial cells can act as proinflammatory promoters, we propose that under homeostatic conditions airway epithelial cells are important modulators of immune responses in the lung. In this review, we discuss epithelial cell regulatory functions that control reactivity of professional immune cells within the microenvironment of the airways and how these mechanisms are altered in pulmonary diseases. Regulation by epithelial cells can be divided into two mechanisms: (1) mediators regulate epithelial cells' innate sensitivity in cis and (2) factors are produced that limit reactivity of immune cells in trans.


Shah P.L.,Royal Brompton Hospital | Shah P.L.,Chelsea and Westminster Hospital | 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.


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.


Gompelmann D.,University of Heidelberg | Gompelmann D.,Translational Lung Research Center | Eberhardt R.,University of Heidelberg | Eberhardt R.,Translational Lung Research Center | And 2 more authors.
Annals of the American Thoracic Society | Year: 2013

Endoscopic lung volume reduction (ELVR) offers a novel therapeutic approach for patients with severe pulmonary emphysema. In Europe, several types of ELVR are available. The choice of ELVR technique depends both on the distribution of emphysema and the presence or absence of interlobar collateral ventilation (CV). For this reason, accurate patient selection is crucial. Bronchial valve implantation is the technique that has been most widely studied and represents an effective treatment option for patients with severe heterogeneous upper- or lower-lobe-predominant emphysema. Lobar occlusion and low interlobar CV are predictive factors for positive outcomes. Lung volume reduction coil implantation is an effective option for patients with upper- and lower-lobe-predominant emphysema, and the efficacy is not influenced by CV; however, the technique should be regarded as mainly irreversible. Polymeric lung volume reduction relies on irreversible scarring and fibrosis and is especially effective in patients with chronic obstructive pulmonary disease classified as Global Initiative for Chronic Obstructive Lung Disease stage III; it also offers benefits to patients with upper-lobe-predominant emphysema and those with homogeneous emphysema. Like polymeric lung volume reduction, bronchoscopic thermal vapor ablation is also not influenced by CV and represents a good option for patients with upper-lobe-predominant emphysema. Exhale airway stents for emphysema-''airway bypass''-Appeared to be a promising technique but proved ineffective in randomized clinical trials, likely in part due to long-term occlusion of the drug-eluting stents. Although European physicians are able to choose from a host of approved bronchoscopic interventions for emphysema, future studies for techniques in use are needed to further clarify patient selection criteria. © 2013 by the American Thoracic Society.


Balint B.,Translational Lung Research Center | Haas J.,Translational Lung Research Center | Schwarz A.,Translational Lung Research Center | Jarius S.,Translational Lung Research Center | And 11 more authors.
Neurology | Year: 2013

Objective: To assess pediatric patients with multiple sclerosis (MS) for early signs of homeostatic and functional abnormalities in conventional (Tcon) and regulatory T cells (Treg). Methods: We studied the composition of the peripheral T-cell compartment and Treg function in a cross-sectional study with 30 pediatric MS (pMS) patients by multicolor flow cytometry and proliferation assays. Data were compared to those obtained from adult patients (n 5 26) and age-matched control donors (n 5 67). Results: Proportions of naive T cells were 10%-20% higher in children than in adults, reflecting the age-related decline. pMS patients, however, had clearly lower numbers of naive T cells, among them recent thymic emigrants (RTE), whereas percentages of memory T cells were increased. In the Treg compartment, reduced RTE numbers coincided with markedly dampened suppressive capacities of total Treg. These homeostatic changes in circulating T cells precisely paralleled the pattern seen in adult MS. As in adults, treatment with immunomodulatory drugs attenuated these alterations. Conclusion: The homeostatic changes detected in the T-cell compartment in pMS are similar to those in adult-onset disease. With ratios between naive and memory T-cell subsets matching those of 20- to 30-years-older controls, signs of early thymic involution are already found in pMS, suggesting that an intrinsic compromise in thymic-dependent T-cell neogenesis might contribute to MS pathogenesis. © 2013 American Academy of Neurology.


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.


Dalpke A.,University of Heidelberg | Dalpke A.,Translational Lung Research Center | Zimmermann S.,University of Heidelberg | Schnitzler P.,University of Heidelberg
Diagnostic Microbiology and Infectious Disease | Year: 2016

We compared a multiplex PCR diagnostic approach against specific PCR diagnosis for detection of Mycoplasma pneumoniae infection. Seventy-five percent of all M. pneumoniae infections were only detected “unintentionally” by the use of the multiplex PCR indicating underdiagnosing of M. pneumoniae due to absence of clinical suspicion. © 2016 Elsevier Inc.

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