Tobias Welte

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Papers by Tobias Welte

Sepsistherapie 2007 - zurück auf dem Boden der Tatsachen

Intensivmedizin up2date, 2008

chwere Infektionskrankheiten sind zu einem Großteil die Erkrankungen des alten Men− schen. Die si... more chwere Infektionskrankheiten sind zu einem Großteil die Erkrankungen des alten Men− schen. Die sich schnell verändernde Demo− grafie und die Intensivierung der Therapie bei früher schnell zum Tode führenden Erkrankungen hat weltweit zu einem dramatischen Anstieg der Sep− sisprävalenz beigetragen. Ein Ende dieser Entwicklung ist nicht absehbar. Schwere Sepsis (also Sepsis mit Or− ganversagen) und septischer Schock (also Sepsis mit katecholaminbedürftigem Kreislaufversagen) sind da− bei immer noch mit einer Sterblichkeit von mehr als 50 % belastet und stellen hierdurch eines der wesent− lichen medizinischen und ökonomischen Probleme der Intensivmedizin dar.

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Die ambulant erworbene Pneumonie: Weiterhin eine gefährliche Krankheit? - Neue S3-Leitlinie orientiert sich an Risiko- und Schweregrad

Notfall & Hausarztmedizin, 2007

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography

The European respiratory journal, Jul 26, 2016

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify b... more EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and…

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Fixed Combination of a Long-Acting ?2-Agonist and an Inhaled Steroid. A Therapeutic Option for COPD?

Med Klin, 2003

Pneumococcal conjugate vaccine for adults: "It's tough to make predictions,

The European respiratory journal, 2015

Do the results of the CAPITA study justify the general vaccination of adults with PCV13? http://o... more Do the results of the CAPITA study justify the general vaccination of adults with PCV13? http://ow.ly/RW74T "… especially about the future." This frequently used Yogi Berra quote also holds true for the paper by MANGEN et al. [1] from the Netherlands, which modelled the cost-effectiveness of a potential vaccination programme for elderly adults using the 13-valent pneumococcal conjugate vaccine. The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed for adults in 2011. Data from the largest randomised controlled trial (RCT) on a pneumococcal vaccine published to date (the CAPITA study) show a vaccine efficacy of 45.6% for pneumonia caused by the 13 vaccine serotypes, including 45.0% for non-bacteraemic pneumonia [2]. Do these data justify the general use of PCV13 in adults? MANGEN et al. [1] conducted economic modelling mainly based on the data of the CAPITA study that showed that PCV13 in adults is highly cost-effective. However, vaccination of infants, the main reservoir of pneumococci, with conjugate vaccines has resulted in herd protection effects, i.e. also decreased prevalence of the serotypes contained in vaccine in adults. So the question remains, are the results of MANGEN et al. [1] are transferable to countries that have implemented PCV13 in infants? Undoubtedly, community-acquired pneumonia (CAP) is a major public health topic, including in developed countries. Its morbidity and mortality increase with age [3]. Most studies have found Streptococcus pneumoniae to be the most frequent pathogen in CAP [4]. Therefore, an effective vaccine against S. pneumoniae for elderly adults would be a breakthrough for CAP prevention. However, S. pneumoniae is a smart pathogen: its main virulence factor is a polysaccharide capsule that prevents recognition by phagocytes. Not only are polysaccharides are of limited immunogenicity when used as vaccine antigens, there are also 94 known different capsular types with no or very limited cross-immunity [5]. Earlier vaccination strategies against S. pneumoniae involved administering large amounts of pure polysaccharide. The 23-valent polysaccharide (PPV23) vaccine contains the polysaccharides of 23 out of the 94 serotypes. However, its efficacy was not convincing, probably because polysaccharides are primary B-cell antigens and therefore vaccination does not induce a T-cell response, resulting in a lack of both memory cells and mucosal immunity [6, 7]. In addition, this vaccine could not be used in younger infants, because their immature immune system did not properly respond to this vaccine. However, several meta-analyses of RCTs have shown that PPV23 has a efficacy of up to 75% against pneumococcal bacteraemia [8, 9]. Interestingly, we found the same efficacy in our CAPNETZ (German Network for community-acquired pneumonia) cohort, which was not included in these meta-analyses [10].

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[CAPNETZ : The competence network for community-acquired pneumonia (CAP)]

Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 2016

CAPNETZ is a medical competence network for community-acquired pneumonia (CAP), which was funded ... more CAPNETZ is a medical competence network for community-acquired pneumonia (CAP), which was funded by the German Ministry for Education and Research. It has accomplished seminal work on pneumonia over the last 15 years. A unique infrastructure was established which has so far allowed us to recruit and analyze more than 11,000 patients. The CAPNETZ cohort is the largest cohort worldwide and the results obtained relate to all relevant aspects of CAP management (epidemiology, risk stratification via biomarkers or clinical scores, pathogen spectrum, pathogen resistance, antibiotic management, prevention and health care research). Results were published in more than 150 journals and informed the preparation and update of the national S3-guideline. CAPNETZ was also the foundation for further networks like the Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) (PROGRESS), the Systems Medicine of Community Acquired Pneumonia Network (CAPSyS...

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Prognostic assessment in COPD without lung function: the B-AE-D indices

The European respiratory journal, Jun 21, 2016

Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary... more Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our aim was to provide and validate a simplified COPD risk index independent of lung function.The PROMISE study (n=530) was used to develop a novel prognostic index. Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality. External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C. It was observed that B-AE-D and B-AE-D-C were at least as good ...

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Topical Nasal Anesthesia in Flexible Bronchoscopy – A Cross-Over Comparison between Two Devices

PLOS ONE, 2016

Introduction Topical airway anesthesia is known to improve tolerance and patient satisfaction dur... more Introduction Topical airway anesthesia is known to improve tolerance and patient satisfaction during flexible bronchoscopy (FB). Lidocaine is commonly used, delivered as an atomized spray. The current study assesses safety and patient satisfaction for nasal anesthesia of a new atomization device during outpatient bronchoscopy in lung transplant recipients. Methods Using a prospective, non-blinded, cross-over design, patients enrolled between 01-10-2014 and 24-11-2014 received 2% lidocaine using the standard reusable nasal atomizer (CRNA). Those enrolled between 25-11-2014 and 30-01-2015, received a disposable intranasal mucosal atomization device (DIMAD). After each procedure, the treating physician, their assistant and the patient independently rated side-effects and satisfaction, basing their responses on visual analogue scales (VAS). At their next scheduled bronchoscopy during the study period, patients then received the alternative atomizer. Written consent was obtained prior to the first bronchoscopy, and the study approved by the institutional ethics committee. Results Of the 252 patients enrolled between 01-10-2014 and 30-01-2015, 80 (32%) received both atomizers. Physicians reported better efficacy (p = 0.001) and fewer side effects (p< = 0.001) for DIMAD in patients exposed to both procedures. Among patients with one visit, physicians and their assistants reported improved efficacy (p = 0.018, p = 0.002) and fewer side effects (p< = 0.001, p = 0.029) for the disposable atomizer, whereas patients reported no difference in efficacy or side effects (p = 0.72 and p = 0.20). No severe adverse events were noted. The cost of the reusable device was 4.08€ per procedure, compared to 3.70€ for the disposable device. Discussion Topical nasal anesthesia via a disposable intranasal mucosal atomization device (DIMAD) offers comparable safety and patient comfort, compared to conventional reusable nasal PLOS ONE |

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Infektionskontrolle � der Weg zur �berwindung der Resistenzproblematik auf Intensivstationen?

Intensivmedizin Up2date, 2009

α1-Antitrypsin Combines with Plasma Fatty Acids and Induces Angiopoietin-like Protein 4 Expression

Journal of immunology (Baltimore, Md. : 1950), Jan 15, 2015

α1-Antitrypsin (A1AT) purified from human plasma upregulates expression and release of angiopoiet... more α1-Antitrypsin (A1AT) purified from human plasma upregulates expression and release of angiopoietin-like protein 4 (Angptl4) in adherent human blood monocytes and in human lung microvascular endothelial cells, providing a mechanism for the broad immune-regulatory properties of A1AT independent of its antiprotease activity. In this study, we demonstrate that A1AT (Prolastin), a potent inducer of Angptl4, contains significant quantities of the fatty acids (FA) linoleic acid (C18:2) and oleic acid (C18:1). However, only trace amounts of FAs were present in preparations that failed to increase Angplt4 expression, for example, A1AT (Zemaira) or M-type A1AT purified by affinity chromatography. FA pull-down assays with Western blot analysis revealed a FA-binding ability of A1AT. In human blood-adherent monocytes, A1AT-FA conjugates upregulated expression of Angptl4 (54.9-fold, p < 0.001), FA-binding protein 4 (FABP4) (11.4-fold, p < 0.001), and, to a lesser degree, FA translocase (CD...

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How Can We Improve the Detection of Alpha1-Antitrypsin Deficiency?

PloS one, 2015

The Z deficiency in α1-antitrypsin (A1ATD) is an under-recognized condition. Alpha1-antitrypsin (... more The Z deficiency in α1-antitrypsin (A1ATD) is an under-recognized condition. Alpha1-antitrypsin (A1AT) is the main protein in the α1-globulin fraction of serum protein electrophoresis (SPE); however, evaluation of the α1-globulin protein fraction has received very little attention. Serum Z-type A1AT manifests in polymeric forms, but their interference with quantitative immunoassays has not been reported. Here, 214 894 samples were evaluated by SPE at the G. Fracastoro Hospital of Verona, Italy. Patients with an A1AT level ≤ 0.92 g/L were recalled to complete A1ATD diagnosis. In parallel, to qualitatively and quantitatively characterize A1AT, sera samples from 10 PiZZ and 10 PiMM subjects obtained at the National Institute of Tuberculosis and Lung Diseases in Warsaw, Poland, were subjected to non-denaturing 7.5% PAGE and 7.5% SDS-PAGE followed by Western blot. Moreover, purified A1AT was heated at 60°C and analyzed by a non-denaturing PAGE and 4-15% gradient SDS-PAGE followed by West...

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A cohort study of the airway mycobiome in adult cystic fibrosis patients: differences in community structure of fungi compared to bacteria reveal predominance of transient fungal elements

Journal of clinical microbiology, 2015

The respiratory mycobiome is an important but understudied component of the human microbiota. Lik... more The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases but infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult cystic fibrosis (CF) patients during non-exacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and ITS) and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were only detected at low frequencies. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed sat...

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Concept for a study design in patients with severe community-acquired pneumonia: A randomised controlled trial with a novel IGM-enriched immunoglobulin preparation - The CIGMA study

Respiratory medicine, Jan 2, 2015

Severe community-acquired pneumonia is defined as community-acquired pneumonia that requires inte... more Severe community-acquired pneumonia is defined as community-acquired pneumonia that requires intensive medical care. Mortality in these patients is still high depending on time and admission. Since bad outcomes may occur despite antibiotic therapy to treat severe community-acquired pneumonia, the focus has shifted to targeting the host response. The CIGMA Study examines the safety and efficacy of the novel IgM-enriched immunoglobulin preparation BT086 when added to standard of care treatment. The aim of this multicentre, randomised, placebo-controlled, double-blind, parallel-group, adaptive group-sequential phase II study is to determine the efficacy and safety of BT086, an IgM-enriched immunoglobulin preparation, as an adjunctive treatment in mechanically-ventilated patients with severe community-acquired pneumonia. The increase of ventilator-free days is the primary endpoint in this study. For this trial, ventilator-free days are defined as the number of days between successful ex...

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Anschriften der Herausgeber und Autoren

Differenzialdiagnostik und Differenzialtherapieb, 2010

Imaging in the diagnosis of lung disease: more sophisticated methods require greater interdisciplinary collaboration

Deutsches Ärzteblatt international, Jan 14, 2014

Editorial to accompany the article "Radiological diagnosis in lung disease-factoring treatment op... more

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Nosocomial infections - a present and future challenge

Deutsches Ärzteblatt international, 2013

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[Treatment of community acquired pneumonia]

Der Internist, 2007

The S3 guidelines for diagnosis and therapy use German epidemiological data to set the standards ... more The S3 guidelines for diagnosis and therapy use German epidemiological data to set the standards for a risk and degree of severity based treatment of community acquired pneumonia (CAP). Over the last few years, a change in pathogen epidemiology has been recognized with the significance of staphylococci and enterobacteria increasing. CAP is becoming increasingly a disease of the elderly, for whom a more broadly effective initial therapy appears to be needed. Resistant pathogens play an important role in the course of the disease. For patients with a low risk of mortality, a reduction in the length of therapy seems possible. On the other hand, the early identification of critically ill patients who require treatment with high dose, broad spectrum antibiotics is necessary. Antibiotic associated diarrhoea, caused by Clostridium difficile, is a significant complication in antibiotic therapy. With the introduction of vaccination against Streptococcus pneumoniae for children, a change in t...

The Prevalence Of Reported Cardiovascular Disease In Subjects With Non-Reversible Airways Obstruction - Findings From The Multi-Center Population-Based Burden Of Obstructive Lung Disease (BOLD) Study

D18. AIR POLLUTION AND CARDIOVASCULAR DISEASE, 2011

Respiratorische Notfälle

Notarzt-Leitfaden, 2007

High Individuality of Respiratory Bacterial Communities in a Large Cohort of Adult Cystic Fibrosis Patients under Continuous Antibiotic Treatment

PLOS ONE, 2015

Background Routine clinical diagnostics of CF patients focus only on a restricted set of well-kno... more Background Routine clinical diagnostics of CF patients focus only on a restricted set of well-known pathogenic species. Recent molecular studies suggest that infections could be polymicrobial with many bacteria not detected by culture-based diagnostics. Methodology and Principal Findings A large cohort of 56 adults with continuous antibiotic treatment was studied and different microbial diagnostic methods were compared, including culture-independent and culturebased bacterial diagnostics. A total of 72 sputum samples including longitudinal observations was analysed by 16S rRNA gene sequence comparison. Prevalence of known pathogens was highly similar among all methods but the vast spectrum of bacteria associated with CF was only revealed by culture-independent techniques. The sequence comparison enabled confident determination of the bacterial community composition and revealed a high diversity and individuality in the communities across the cohort. Results of microbiological analyses were further compared with individual host factors, such as age, lung function and CFTR genotype. No statistical relationship between these factors and the diversity of the entire community or single bacterial species could be identified. However, patients with non-ΔF508 mutations in the CFTR gene often had low abundances of Pseudomonas aeruginosa. Persistence of specific bacteria in some communities was demonstrated by longitudinal analyses of 13 patients indicating a potential clinical relevance of anaerobic bacteria, such as Fusobacterium nucleatum and Streptococcus millerii.

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