Thomas O Wagner

• Goethe University Frankfurt

Background Lung disease phenotype varies widely even in the F508del (homozygous) genotype. Leukocyte-driven inflammation is important for pulmonary disease pathogenesis in cystic fibrosis (CF). Blood cytokines correlate negatively with pulmonary function in F508del homozygous patients, and gap junction proteins (GJA) might be related to the influx...

Developments in managing CF continue to drive dramatic improvements in survival. As newborn screening rolls-out across Europe, CF centres are increasingly caring for cohorts of patients who have minimal lung disease on diagnosis. With the introduction of mutation-specific therapies and the prospect of truly personalised medicine, patients have the...

Background: The European Union considers diseases to be rare when they affect less than 5 in 10,000 people. It is estimated that there are between 5000 and 8000 different rare diseases. Consistent with this diversity, the quality of information available on the Web varies considerably. Thus, quality criteria for websites about rare diseases are nee...

Die Mukoviszidose (syn. zystische Fibrose, CF) ist eine autosomal rezessiv vererbte Stoffwechselkrankheit. Durch Mutationen des „Cystic Fibrosis Transmembrane Conductance Regulator“-Gens, das einen defekten Chloridkanal kodiert, entsteht zähes Sekret in allen exokrinen Drüsen. Die Therapie beruht auf den drei Säulen Physiotherapie und Sport, Ernähr...

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering m...

Background. Cystic fibrosis (CF) is one of the most frequent autosomal recessive inherited diseases in the Caucasian population. A genetic defect in the CFTR gene leads to a reduction in chloride ion transport in cell membranes. The resulting dehydration of the wet epithelial film causes a reduction in secretion clearance. The consequence is a mult...

Hintergrund In Deutschland leben schätzungsweise 4 Mio. Patienten mit einer seltenen Erkrankung. Ihre Versorgung ist aufgrund der Seltenheit und Heterogenität der unterschiedlichen Erkrankungsbilder problematisch. Das Bundesministerium für Gesundheit hat deshalb im Jahr 2009 einen Forschungsbericht zum Thema „Maßnahmen zur Verbesserung der gesundhe...

Background: Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients recei...

BACKGROUND: Approximately 4 million patients with a rare disease live in Germany. The medical care of these patients is problematic because of the rarity and heterogeneity of different clinical pictures. The Federal Ministry of Health has therefore published a research report on "Measures to improve the health situation of people with rare diseases...

Aim: Mediastinal lymphadenopathy is a typical feature of pulmonary sarcoidosis and an important parameter for diagnosis and follow-up. The present feasibility study is the first to elucidate the role of transthoracic mediastinal ultrasonography (US) for evaluation and staging of lymphadenopathy in patients with sarcoidosis. Material and method:...

In Germany, many highly specialized facilities for the diagnosis and treatment of rare diseases exist. However it is quite difficult for patients to find the required specialists because of the fact that information on the internet is scattered and of variable quality. The German Federal Ministry of Health initiated several activities to address th...

There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplan...

A clinical study to investigate the leukotriene B4 (LTB4)-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better underst...

Rationale: Glutathione is the major antioxidant in the extracellular lining fluid of the lungs and depleted in patients with cystic fibrosis (CF). Objectives: We aimed to assess glutathione delivered by inhalation as a potential treatment for CF lung disease. Methods: This randomized, double-blind, placebo-controlled trial evaluated inhaled gl...

Die Entdeckung des Zystische-Fibrose-Transmembran-Regulator-(CFTR-)Gens im Jahr 1989 gab Grund zur Hoffnung, dass eine kausale Therapie der Mukoviszidose (CF) in Kürze verfügbar sein würde. Obwohl Wissenschaftler Fortschritte in Bezug auf die Korrektur des zugrundeliegenden Defekts auf Genebene erreicht haben, gibt es bislang keine verfügbare Thera...

Background: Patients with cystic fibrosis (CF) have a relevant morbidity and mortality caused by CF-related liver-disease. While transient elastography (TE) is an established elastography method in hepatology centers, Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is a novel ultrasound-based elastography method which is integrated in a convention...

Die Mukoviszidose ist eine autosomal-rezessiv vererbte Stoffwechselerkrankung. Sie beruht auf einer Störung des CFTR-Gens, die zu einem Defekt der Chloridkanäle auf Epithelzellmembranen führt und vielfältige Störungen im Respirations-, Gastrointestinal- und Urogenitaltrakt zur Folge hat. In allen exokrinen Drüsen kommt es zur Bildung von zähem Sekr...

Cystic fibrosis is an inherited autosomal recessive metabolic disease caused by mutations on the CFTR gene. This leads to defective chloride channels on epithelial cell membranes and causes various disorders of the respiratory, gastrointestinal, and urogenital tracts.As a result, all exocrine glands produce a viscous secretion, leading to pulmonary...

Unter dem Oberbegriff Hoch-Frequenz-Ventilation (HFV) werden heterogene Beatmungstechniken zusammengefasst, denen allen gemeinsam ist, dass sie mit einer Beatmungsfrequenz im Hertz-Bereich (>60/min) arbeiten. Wahrend vor allem die Hochfrequenz-Jet-Ventilation (HFJV) im Rahmen von Operationen im Bereich der Trachea und Glottis etabliert ist, bestehe...

The European Centres of Reference Network for Cystic Fibrosis (ECORN-CF) established an Internet forum which provides the opportunity for CF patients and other interested people to ask experts questions about CF in their mother language. The objectives of this study were to: 1) develop a detailed quality assessment tool to analyze quality of expert...

Training manual for quality assessment of expert answers according to the newly developed scoring system. This guide gives a detailed description with examples how to assess the content and formal quality of an expert answer. The scoring system is introduced which comprises points given to each aspect of content and formal quality and the calculati...

In Deutschland leben derzeit etwa 8000 Menschen mit Mukoviszidose (zystischer Fibrose, CF), der häufigsten erblich letal verlaufenden Stoffwechselerkrankung in der weißen Population. Inzwischen steht für CF-Patienten mit der Mutation G551D eine erste kausale Therapie zur Verfügung. Die sich rasch entwickelnden Diagnostik- und Therapiemöglichkeiten...

The prevalence of Crohn's disease (CD) is increased in patients with cystic fibrosis (CF). Anti-Saccharomyces cerevisiae antibodies (ASCA) have been suggested as a screening tool to detect CD in CF. Recently, several new anti-glycan antibodies have been reported in CD. - The sera of 119 CF patients of various age groups were prospectively screened...

We describe the rationale for disease specific research networks in general as well as the aims and function of the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) specifically. The ECFS-CTN was founded in 2009 with the aim of improving the quality and quantity of clinical research in the area of cystic fibrosis (CF) in Europe....

Objective Objective of this study is to assess and evaluate resource use in outpatient treatment in Germany and to compare it with remuneration.Methods Outpatient treatment was evaluated in seven different centers for pediatric and adult CF patients. Data were recorded during one representative month in 2006. A micro-costing approach was used to va...

Einfuhrung: Erlotinib (Tarceva®) ist ein oral wirksamer Tyrosinkinaseinhibitor, der den epidermalen Wachstumsfaktor (EGFR) hemmt. Ziel der vorliegenden Studie war die Beurteilung der Vertraglichkeit und Wirksamkeit einer Behandlung mit Erlotinib im klinischen Routinealltag bei Patienten mit fortgeschrittenem nicht-kleinzelligen Lungenkarzinom (NSCL...

Background and Purpose: Drug treatment of cystic fibrosis (CF) is associated with significant costs. To help ensure sustainable care, this study assesses the costs associated with outpatient treatment of adult CF patients in Germany. It identifies main cost drivers, evaluates the potential for cost savings from “aut idem” substitution and presents...

There are no European Guidelines on issues specifically related to travel for people with cystic fibrosis (CF). The contributors to these recommendations included 30 members of the ECORN-CF project. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Executive Agency of Health and Consumers of the European Union an...

Drug treatment of cystic fibrosis (CF) is associated with significant costs. To help ensure sustainable care, this study assesses the costs associated with outpatient treatment of adult CF patients in Germany. It identifies main cost drivers, evaluates the potential for cost savings from "aut idem" substitution and presents a projection of lifelong...

Cystic fibrosis (CF) patients need specialized long-term treatment. In order to support lung function, pharmaceuticals such as bronchodilators, mucolytic agents or anti-inflammatory drugs have to be used. Oral, inhaled or intravenous antibacterial therapy is of special importance for patients who have problems with chronic bacterial colonization of...

The currently available immunosuppressive agents applied in human transplantation medicine are highly potent in the protection from acute allograft rejection. However, long-term allograft survival is still poor as these drugs fail to sufficiently prevent chronic allograft rejection. Naturally occurring regulatory T cells have been postulated as the...

Low-pressure membranes suffer from particulate, organic and biological fouling during operation. In order to elucidate the impact of nanoparticles on membrane fouling, experiments were carried out with a small membrane test unit operated with artifi cial and natural waters. Both microfi ltration (MF) and ultrafi ltration (UF) membranes were used. A...

We conducted a single-centre, randomised, double-blinded, placebo-controlled phase II clinical study to test safety and efficacy of a 12-week therapy with low-dose (700 mg/daily) or high-dose (2800 mg/daily) of NAC. Twenty-one patients (DeltaF508 homo/heterozygous, FEV1>40% pred.) were included in the study. After a 3-weeks placebo run-in phase, 11...

Lung transplantation in cystic fibrosis is an established therapy, due to the fact that vast majority of adult CF patients will develop respiratory failure. Even adolescents and children can be transplanted successfully today. Lung transplantation in cystic fibrosis requires special consideration concerning candidate selection, surgery and postoper...

Die Lungentransplantation bei Mukoviszidose ist eine inzwischen etablierte Therapieoption, da die große Mehrzahl der Erwachsenen mit cystischer Fibrose eine respiratorische Insuffizienz entwickelt. Auch Jugendliche und Kinder können erfolgreich transplantiert werden. Allerdings hat die Lungentransplantation bei Mukoviszidose Besonderheiten bei der...

Main objective of this study is to assess and evaluate resource use in outpatient treatment of cystic fibrosis (CF) in Germany and to compare this with current reimbursement. Outpatient treatment was evaluated in seven different CF centers.Clinical patient data, resource use, and time consumption were recorded in 2006. A micro-costing approach was...

Purpose: Main objective of this study is to assess and evaluate resource use in outpatient treatment of cystic fibrosis (CF) in Germany and to compare this with current reimbursement. Methods: Results: Conclusion: Key Words: Med Klin 2009;104:529–35. Methods: Outpatient treatment was evaluated in seven different CF centers.Clinical patient data, re...

For the past decade, percentage of ideal body weight (%IBW) was recommended by European and US nutrition consensus reports as preferred clinical measure of nutritional status in children with cystic fibrosis (CF). We and others have demonstrated that the %IBW method underestimates the prevalence of nutritional failure in CF, but the underlying mech...

Oxy-Gen lite, a recently developed combined electrolysis and fuel cell technology, de-novo generates oxygen with high purity for medical use from distilled water and room air. However, its use in patients with chronic respiratory failure has never been evaluated. To test the clinical applicability and safety of Oxy-Gen lite technology, we enrolled...

The efficacy of high-dose nifedipine in the treatment of primary pulmonary hypertension was determined in a nonrandomized, uncontrolled trial at a single referral center. Sixteen consecutive patients with primary pulmonary hypertension referred for evaluation of lung transplantation, were assessed for acute hemodynamic response to oral nifedipine (...

The influence of various variables on the rate of pneumothorax and intrapulmonal hemorrhage associated with computed tomography (CT)-guided transthoracic needle biopsy of the lung were evaluated retrospectively. One hundred and thirty-three patients underwent CT guided biopsy of a pulmonary lesion. Two patients were biopsied twice. Variables analyz...

In this paper we comprehensively characterized particles in drinking water originating from a lake water source. We focused on particles smaller than a few hundred nm. Several analytical techniques were applied to obtain information on number concentration, size distribution, morphology and chemical composition of the particles. Morphological infor...

Asthma hat viele Gesichter. Hierzu zählt zunächst die Häufigkeit der Erkrankung, die Asthma im wahrsten Sinne des Wortes zu einer »Volkskrankheit« macht. Hierher gehört die Einschränkung der Lebensqualität ebenso wie die Beeinträchtigung des sozialen Umfelds. Asthma bedingt aber auch Behinderungen im Berufsleben, sei es in Form einer verminderten k...

We describe the rare case of a high-grade chemical irritating-toxic damage to the larynx, the trachea and the bronchial system due to the aspiration of the bisphosphonate alendronate. The aspiration of alendronate was caused by oropharyngeal dysphagia. The 68-year-old female patient was sent to hospital with increasing hoarseness and a tormenting c...

Wir beschreiben den seltenen Fall einer schwergradigen chemisch irritativ-toxischen Schädigung des Kehlkopfes und der Trachea mit Beteiligung der Bronchien infolge der Aspiration des Bisphosphonats Alendronsäure. Der Aspiration des Alendronats lag eine Schluckstörung zugrunde. Die 68-jährige Patientin stellte sich mit progredienter Heiserkeit und e...

To compare the performance of recently released body mass index percentiles (BMIp) with standard anthropometric indexes, including height-for-age percentile (HAP), weight-for-age percentile (WAP) and percent ideal body weight (%IBW), as measures for nutritional failure in children with cystic fibrosis (CF). Cross-sectional analysis of growth and lu...

Die Mukoviszidose (syn. zystische Fibrose, engl.: cystic fibrosis: [CF]) ist die häufigste tödlich verlaufende genetisch bedingte Erkrankung in der europiden Bevölkerung. Sie wird autosomalrezessiv vererbt, wobei etwa jeder 25. Erwachsene ein klinisch asymptomatischer Träger des defekten Gens ist, und auf 2000–2500 Neugeborene je ein Kind mit zysti...

For staging, follow-up and even screening (www.screening.info) an "all-in-one" imaging examination is desirable. In the concept of whole body MRI, lung imaging prevails as the weakest link. The purpose of our study was to determine the optimal MRI sequences for the detection of malignant lung nodules. On the basis of 6 lung cancer, 46 metastases an...

Leptin plays an important role in the energy balance and may be affected by hormonal and metabolic derangement associated with chronic disease. The aim of this study was to assess the correlation between leptin, proinflammatory cytokines and nutritional status with regard to clinical status in homozygous delta F 508 cystic fibrosis patients. Patien...

PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. PPARalpha, beta and gamma mRNA levels were measured in peripheral blood cells of CF p...

Until recently "mechanical ventilation" meant "intensive care unit (ICU)". Important arguments for more flexibility concerning the locality where patients are mechanically ventilated are the increase in number of patients, costs and reduced resources. The pulmonary centre for mechanical ventilation, where ICU, respiratory intermediate care unit (RI...

Oft sind die beiden Begriffe „Beatmung” und „Intensivstation” auch heute noch fest miteinander verknüpft. Die kontinuierlich steigende Anzahl von Beatmungsfällen, der wachsende Kostendruck und die eingeschränkten Ressourcen sind wesentliche Argumente für einen flexiblen Umgang bei der Wahl des Bereiches, in dem beatmet wird. Das pneumologische Beat...

Bronchial obstruction due to one of the major pulmonary diseases asthma, COPD, or emphysema are a common problem in intensive care medicine as the leading cause or as comorbidity. While in pharmacological therapy no major changes have occurred during the last few years, two major advances have been reached in ventilation therapy which are in the fo...

The severity of lung disease in cystic fibrosis may be related to the genetic propensity of the host to produce tumor necrosis fector alpha (TNF-alpha). A polymorphism in the promoter region of the TNF-alpha gene at nucleotide 308 relative to the transcription start site may be important in determing the host's TNF-alpha response. The aim of this s...

Die zystische Fibrose (CF, syn.: Mukoviszidose) ist ein Musterbeispiel dafr, wie neue Erkenntnisse ber ein Krankheitsbild zu einer kontinuierlichen Verbesserung der Therapie und Prognose genutzt wurden. Dennoch liegt der klinische Schwerpunkt bisher auf einer symptomatischen Behandlung, und weiterhin versterben 80% der CF-Patienten an den Folgen re...

Bronchial obstruction due to one of the major pulmonary diseases asthma, COPD, or emphysema are a common problem in intensive care medicine as the leading cause or as comorbidity. While in pharmacological therapy no major changes have occurred during the last few years, two major advances have been reached in ventilation therapy which are in the fo...

Today, the majority of cystic fibrosis (CF) patients treated in Germany have reached adulthood. However, with increasing age the morbidity and frequency of severe pulmonary complications continues to rise. Further optimization of conventional therapy alone will be insufficient to compensate for this development. In recent years, there has been impr...

According to the endotoxin lipoprotein hypothesis, lipoproteins may down-regulate cytokine production by neutralizing lipopolysaccharide (LPS) binding protein (LBP) complexes. We investigated the correlation between lipoproteins, LBP, cytokine production, and clinical status in Delta F 508 (homozygous) individuals. Cystic fibrosis patients with mil...

Inzwischen hat die Mehrheit der an Mukoviszidose (syn.: Cystische Fibrose, CF) leidenden Patienten in Deutschland die Volljährigkeit erreicht. Mit zunehmendem Lebensalter steigt jedoch die Morbidität und der Anteil pulmonaler Komplikationen überproportional an. Auch durch weitere Optimierung der bestehenden symptomatischen Maßnahmen kann diese Entw...

Oxidative stress is a likely contributor to the pathogenesis of cystic fibrosis (CF) lung disease. However, hydrogen peroxide (H(2)O(2)), a physiological oxidant, is not elevated in CF exhalates. H(2)O(2) may be neutralized by antioxidants in CF airway secretions. The H(2)O(2)-detoxifying capacity of CF airway secretions, obtained via sputum induct...

Lung transplantation (LTx) requires a delicate post-surgical care due to the complex intervention and the necessary high-level immunsuppression therapy. The post-LTx care encompasses the management of immunsuppression therapy and numerous necessary medications, bacterial and viral infection and exacerbations, transplant rejection and of the likely...

Cystic fibrosis (CF) is one of the most frequent and most successful indications for lung transplantation. Bilateral lung transplantation (BLTx) is an option for all CF patients with pulmonary insufficiency where conservative means have come to a limit. Absolute contraindications are a rare situation due to the relatively young age of the patients....

Cytokines and polymorphonuclear leukocytes play a key role in immune mediated inflammation in progressive pulmonary damage due to cystic fibrosis. The aim of this study is to establish a simple measure of the host's propensity to secrete inflammatory cytokines and to correlate this with clinical status. Patients (n=44, median age 16 years) with the...

The purpose of this study was to evaluate the scope of sub-millimeter collimation reconstruction parameters using 16-row computer tomography and ECG triggering on image quality in virtual bronchoscopy. Thirty-two patients (5 women, 27 men, mean age 66.6+/-1.4) who had been admitted for coronary artery bypass graft surgery underwent CT examination o...

Virtual endoscopy of the tracheo-bronchial system: sub-millimeter collimation with the 16-row multidetector scanner.

Autoimmune paraneoplastic processes are investigated in detail concerning the Lambert-Eaton-Myasthenic-Syndrome for bronchial carcinomas. For the cutaneous leukocytoclastic vasculitis as a non-ANCA-associated vasculitis the paraneoplastic genesis is described. Litttle is known about ANCA-associated vasculitis as a paraneoplastic autoimmune phenomen...

Autoimmunologische, paraneoplastische Prozesse sind für das Lambert-Eaton-Syndrom im Bereich der Bronchialkarzinome detailliert untersucht. Auch für Vaskulitiden wie die Nicht-ANCA-assoziierte leukozytoklastische Vaskulitis ist die paraneoplastische Genese beschrieben. Wenig ist bisher über ANCA-assoziierte Vaskulitiden im Rahmen von paraneoplastis...

Reduced glutathione (GSH) is a major antioxidant in the lung. In cystic fibrosis (CF) patients, extracellular GSH levels of lower airways, obtained by bronchoalveolar lavage (BAL), were reported to be lower than non-CF individuals. Upper airway secretions of stable adult CF patients (29 spontaneous and 13 induced sputum) and non-CF individuals (14...

Nanoparticles are able to enhance drug or DNA stability for purposes of optimised deposition to targeted tissues. Surface modifications can mediate drug targeting. The suitability of nanoparticles synthesised out of porcine gelatin, human serum albumin, and polyalkylcyanoacrylate as drug and gene carriers for pulmonary application was investigated...

The authors report on a fatal case of hemolytic disease of the newborn (HDN) due to anti-K antibodies with subsequent trilineage pancytopenia in a preterm infant of 28 weeks gestational age, with pronounced leukopenia and neutropenia. In addition, molecular typing of the Kk polymorphism was necessary to confirm HDN. This case of HDN associated with...

The value of ultrasound examination of the pleura and lungs remains highly underestimated to this day. While the ventilated lungs and the osseous skeleton of the thorax represent potent obstacles for ultrasound, a multitude of pathological processes of the chest wall, pleura, and lungs results in altered tissue composition, providing markedly incre...

The value of ultrasound examination of the pleura and lungs remains highly underestimated to this day. While the ventilated lungs and the osseous skeleton of the thorax represent potent obstacles for ultrasound, a multitude of pathological processes of the chest wall, pleura, and lungs results in altered tissue composition, providing markedly incre...