Ulrich Wahn

Publications (148)813.5 Total impact

• Article: Clinically Relevant Effect of a New Intranasal Therapy (MP29-02) in Allergic Rhinitis Assessed by Responder Analysis.

  Eli Meltzer, Paul Ratner, Claus Bachert, Warner Carr, William Berger, G Walter Canonica, James Hadley, Phil Lieberman, Frank C Hampel, Joaquim Mullol, Ullrich Munzel, David Price, Glenis Scadding, J Christian Virchow, Ulrich Wahn, Ruth Murray, Jean Bousquet
  [show abstract] [hide abstract]
  ABSTRACT: Background: It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses. Methods: 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses. Results: MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom. Conclusions: MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.
  International Archives of Allergy and Immunology 05/2013; 161(4):369-377. · 2.40 Impact Factor
• Article: Body mass index trajectory classes and incident asthma in childhood: Results from 8 European Birth Cohorts-a Global Allergy and Asthma European Network initiative.

  Peter Rzehak, Alet H Wijga, Thomas Keil, Esben Eller, Carsten Bindslev-Jensen, Henriette A Smit, Joost Weyler, Sandra Dom, Jordi Sunyer, Michelle Mendez, [......], Carl-Peter Bauer, Dietrich Berdel, Beate Schaaf, Chih-Mei Chen, Anna Bergström, Maria P Fantini, Monique Mommers, Ulrich Wahn, Susanne Lau, Joachim Heinrich
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: The causal link between body mass index (BMI) or obesity and asthma in children is still being debated. Analyses of large longitudinal studies with a sufficient number of incident cases and in which the time-dependent processes of both excess weight and asthma development can be validly analyzed are lacking. OBJECTIVE: We sought to investigate whether the course of BMI predicts incident asthma in childhood. METHODS: Data from 12,050 subjects of 8 European birth cohorts on asthma and allergies were combined. BMI and doctor-diagnosed asthma were modeled during the first 6 years of life with latent growth mixture modeling and discrete time hazard models. Subpopulations of children were identified with similar standardized BMI trajectories according to age- and sex-specific "World Health Organization (WHO) child growth standards" and "WHO growth standards for school aged children and adolescents" for children up to age 5 years and older than 5 years, respectively (BMI-SDS). These types of growth profiles were analyzed as predictors for incident asthma. RESULTS: Children with a rapid BMI-SDS gain in the first 2 years of life had a higher risk for incident asthma up to age 6 years than children with a less pronounced weight gain slope in early childhood. The hazard ratio was 1.3 (95% CI, 1.1-1.5) after adjustment for birth weight, weight-for-length at birth, gestational age, sex, maternal smoking in pregnancy, breast-feeding, and family history of asthma or allergies. A rapid BMI gain at 2 to 6 years of age in addition to rapid gain in the first 2 years of life did not significantly enhance the risk of asthma. CONCLUSION: Rapid growth in BMI during the first 2 years of life increases the risk of asthma up to age 6 years.
  The Journal of allergy and clinical immunology 02/2013; · 9.17 Impact Factor
• Source

  Available from: Nelson A Rosário

  Dataset: children's asthma charter PAI 2010

  John O. Warner, Nelson Rosario, Paul Potter, Ulrich Wahn, Carlos E. Baena-Cagnani
• Source

  Available from: Victòria Cardona

  Article: EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy.

  Moises A Calderon, Pascal Demoly, Roy Gerth van Wijk, Jean Bousquet, Aziz Sheikh, Anthony Frew, Glenis Scadding, Claus Bachert, Hans J Malling, Rudolph Valenta, [......], Giovanni Passalacqua, Oliver Pfaar, Sabina Rak, Gianenrico Senna, Gabriela Senti, Erkka Valovirta, Marianne van Hage, Johannes C Virchow, Ulrich Wahn, Nikolaos G Papadopoulos
  [show abstract] [hide abstract]
  ABSTRACT: Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy. Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals' quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits. We call upon Europe's policy-makers to coordinate actions and improve individual and public health in allergy by: * Promoting awareness of the effectiveness of allergen specific immunotherapy * Updating national healthcare policies to support allergen specific immunotherapy * Prioritising funding for allergen specific immunotherapy research * Monitoring the macroeconomic and health economic parameters of allergy * Reinforcing allergy teaching in medical disciplines and specialties The effective implementation of the above policies has the potential for a major positive impact on European Health and Well-Being in the next decade.
  Clinical and translational allergy. 10/2012; 2(1):20.
• Article: Organ-specific symptoms during oral food challenge in children with food allergy.

  Birgit Ahrens, Bodo Niggemann, Ulrich Wahn, Kirsten Beyer
  The Journal of allergy and clinical immunology 08/2012; 130(2):549-51. · 9.17 Impact Factor
• Article: Molecular spreading and predictive value of preclinical IgE response to Phleum pratense in children with hay fever.

  Laura Hatzler, Valentina Panetta, Susanne Lau, Petra Wagner, Renate L Bergmann, Sabina Illi, Karl E Bergmann, Thomas Keil, Stephanie Hofmaier, Alexander Rohrbach, Carl Peter Bauer, Ute Hoffman, Johannes Forster, Fred Zepp, Antje Schuster, Ulrich Wahn, Paolo Maria Matricardi
  [show abstract] [hide abstract]
  ABSTRACT: IgE sensitization against grass pollen is a cause of seasonal allergic rhinitis. We sought to investigate the evolution at the molecular level and the preclinical predictive value of IgE responses against grass pollen. The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was administered yearly, and blood samples were collected at 1, 2, 3, 5, 6, 7, 10, and 13 years of age. Grass pollen-related seasonal allergic rhinitis (SARg) was diagnosed according to nasal symptoms in June/July. Serum IgE antibodies to Phleum pratense extract and 8 P pratense molecules were tested with immune-enzymatic singleplex and multiplex assays, respectively. One hundred seventy-seven of the 820 examined children had SARg. A weak monomolecular/oligomolecular IgE response to P pratense was observed very frequently before SARg onset. These initial IgE responses increased in concentration and molecular complexity during the preclinical and clinical process. A typical progression of IgE sensitization was observed: Phl p 1 (initiator in >75% of cases); then Phl p 4 and Phl p 5; then Phl p 2, Phl p 6, and Phl p 11; and then Phl p 12 and Phl p 7. At age 3 years, IgE sensitization predicted SARg by age 12 years (positive predictive value, 68% [95% CI, 50% to 82%]; negative predictive value, 84% [95% CI, 80% to 87%]). At this preclinical prediction time, the number of recognized molecules and the serum levels of IgE to P pratense were significantly lower than at 3 or more years after SARg onset. The IgE response against grass pollen molecules can start years before disease onset as a weak monosensitization or oligosensitization phenomenon. It can increase in serum concentration and complexity through a "molecular spreading" process during preclinical and early clinical disease stages. Testing IgE sensitization at a preclinical stage facilitates prediction of seasonal allergic rhinitis at its molecular monosensitization or oligosensitization stage.
  The Journal of allergy and clinical immunology 07/2012; 130(4):894-901.e5. · 9.17 Impact Factor
• Article: Toward a definition of asthma phenotypes in childhood: making a long way shorter?

  Ulrich Wahn, Paolo M Matricardi
  The Journal of allergy and clinical immunology 07/2012; 130(1):111-2. · 9.17 Impact Factor
• Article: Allergieprävention und alimentäre Allergenexposition

  Birgit Ahrens, Ulrich Wahn, Kirsten Beyer
  [show abstract] [hide abstract]
  ABSTRACT: Die Inzidenz allergischer Erkrankungen ist in den letzten Jahrzehnten deutlich gestiegen. Neben der Verbesserung therapeutischer Behandlungsmöglichkeiten steht die Suche nach geeigneten präventiven Instrumenten. Als ein wichtiger Faktor zur Ausprägung eines allergischen Phänotyps gilt unter anderem der Einfluss der frühkindlichen Ernährung. Gerade in diesem Bereich haben sich in den letzten Jahren die Hypothesen hinsichtlich einer Allergie-Prävention gravierend geändert. Ging man bislang eher von einer Allergenvermeidung im Sinne einer diätetischen Restriktion aus, wird jetzt eher eine Prävention durch Exposition mit Allergenen im Sinne einer potentiellen Toleranzinduktion diskutiert. Diese Übersicht, die sich an den neuen S3-Leitlinien zur Allergieprävention vom Frühjahr 2009 orientiert, soll die aktuellsten Empfehlungen hinsichtlich der Ernährungsoptionen während Schwangerschaft, Stillzeit und des ersten Lebensjahrs darstellen. Zusammenfassend wird ein ausschließliches Stillen in den ersten vier Monaten empfohlen. Für einen präventiven Effekt durch eine Verzögerung der Beikosteinführung über den 4. Lebensmonat hinaus können keine Empfehlung mehr ausgesprochen werden. Auch für einen präventiven Effekt einer diätetischen Restriktion durch Meidung potenter Nahrungsmittelallergene gibt es keine Belege. Eine allgemeine (restriktive) Diät für Mutter und Kind kann nicht empfohlen werden. Hinweise jedoch gibt es darauf, dass Fischkonsum im 1. Lebensjahr bzw. in Schwangerschaft und Stillzeit einen protektiven Effekt auf die Entwicklung atopischer Erkrankungen hat.
  Journal für Verbraucherschutz und Lebensmittelsicherheit 04/2012; 4:21-23. · 0.63 Impact Factor
• Source

  Available from: PubMed Central

  Article: Allergen-specific immunotherapy provides immediate, long-term and preventive clinical effects in children and adults: the effects of immunotherapy can be categorised by level of benefit -the centenary of allergen specific subcutaneous immunotherapy.

  Lars Jacobsen, Ulrich Wahn, M Beatrice Bilo
  [show abstract] [hide abstract]
  ABSTRACT: Allergen Specific Immunotherapy (SIT) for respiratory allergic diseases is able to significantly improve symptoms as well as reduce the need for symptomatic medication, but SIT also has the capacity for long-term clinical effects and plays a protective role against the development of further allergies and symptoms. The treatment acts on basic immunological mechanisms, and has the potential to change the pathological allergic immune response. In this paper we discuss some of the most important achievements in the documentation of the benefits of immunotherapy, over the last 2 decades, which have marked a period of extensive research on the clinical effects and immunological background of the mechanisms involved. The outcome of immunotherapy is described as different levels of benefit from early reduction in symptoms over progressive clinical effects during treatment to long-term effects after discontinuation of the treatment and prevention of asthma. The efficacy of SIT increases the longer it is continued and immunological changes lead to potential long-term benefits. SIT alone and not the symptomatic treatment nor other avoidance measures has so far been documented as the therapy with long-term or preventive potential. The allergic condition is driven by a subset of T-helper lymphocytes (Th2), which are characterised by the production of cytokines like IL-4, and IL-5. Immunological changes following SIT lead to potential curative effects. One mechanism whereby immunotherapy suppresses the allergic response is through increased production of IgG4 antibodies. Induction of specific IgG4 is able to influence the allergic response in different ways and is related to immunological effector mechanisms, also responsible for the reduced late phase hyperreactivity and ongoing allergic inflammation. SIT is the only treatment which interferes with the basic pathophysiological mechanisms of the allergic disease, thereby creating the potential for changes in the long-term prognosis of respiratory allergy. SIT should not only be recognised as first-line therapeutic treatment for allergic rhinoconjunctivitis but also as secondary preventive treatment for respiratory allergic diseases.
  Clinical and translational allergy. 04/2012; 2:8.
• Article: Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with 1 atopic parent in a randomized, placebo-controlled trial.

  Susanne Lau, Kerstin Gerhold, Kurt Zimmermann, Charlotte W Ockeloen, Siri Rossberg, Petra Wagner, Claudia Sulser, Rita Bunikowski, Imke Witt, Juliane Wauer, John Beschorner, Georg Menke, Eckard Hamelmann, Ulrich Wahn
  [show abstract] [hide abstract]
  ABSTRACT: Lower prevalence of atopy was found in children with continuous exposure to livestock and thus to microbial compounds. In animal models exposure to endotoxin (LPS) decreases allergic sensitization and airway inflammation. We sought to evaluate the effect of orally applied bacterial lysate in infancy on the prevalence of atopic dermatitis (AD) after the treatment phase at 7 months of age. This randomized, placebo-controlled trial included 606 newborns with at least single heredity for atopy. From week 5 until the end of month 7, infants were treated orally with bacterial lysate containing heat-killed gram-negative Escherichia coli Symbio and gram-positive Enterococcus faecalis Symbio or its placebo. Children were followed until 3 years of age. There was no difference in the primary outcome between the active and placebo groups in the total study group. AD prevalence was significantly reduced at the end of the intervention phase (31 weeks of age) in the subgroup of infants with single heredity for atopy (relative risk, 0.52; 95% CI, 0.3-0.9). Ten percent (15/154) of infants in the active group had AD compared with 19% (27/145, P = .030) in the placebo group. This was more pronounced in the group of infants with paternal heredity for atopy (11% vs 32%, P = .004; relative risk, 0.34; 95% CI, 0.2-0.7). Feeding of bacterial lysate might have prevented the development of AD, especially in children with paternal atopy, possibly indicating a preventive property only in subjects with a limited risk for atopy.
  The Journal of allergy and clinical immunology 04/2012; 129(4):1040-7. · 9.17 Impact Factor
• Article: Miliary Tuberculosis Complicated by Pulmonary Cavitations and Pneumothorax in a 14-Month Old Boy.

  Quentin Ballouhey, Susanne Lau, Franck Accadbled, Ulrich Wahn, Dirk Kaiser, Karin Rothe, Klaus Magdorf
  [show abstract] [hide abstract]
  ABSTRACT: Surgical management of tuberculosis is uncommon in children. We report a case of a 14-month-old boy with miliary tuberculosis and recurrent pneumothorax due to cavities in the left lung. This boy had no previous medical history and was referred to our hospital for a severe pneumonia. Initial chest radiograph showed bilateral miliary pattern. Direct microscopy of gastric lavage showed the presence of tubercle bacilli, providing definitive diagnosis. In spite of effective medication, his status rapidly worsened. A cardiac resuscitation was followed by intubation, and he required high-pressure ventilation for four weeks. He developed left pneumothorax, for which several drainages were performed. Computed tomography revealed a huge cavern system involving the entire lingula and surrounded by the left pneumothorax. Eventually, a massive enlargement of the initial cavity necessitated a thoracotomy and wedge resection.
  Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 01/2012;
• Source

  Available from: Ben D Spycher

  Article: Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts.

  Karin C Lødrup Carlsen, Stephanie Roll, Kai-Håkon Carlsen, Petter Mowinckel, Alet H Wijga, Bert Brunekreef, Maties Torrent, Graham Roberts, S Hasan Arshad, Inger Kull, [......], Andreas Reich, Anna Asarnoj, Carmen Puig, Olf Herbarth, Jestinah M Mahachie John, Kristel Van Steen, Stefan N Willich, Ulrich Wahn, Susanne Lau, Thomas Keil
  [show abstract] [hide abstract]
  ABSTRACT: To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6-10 years. Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. EXPOSURE DEFINITION: Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. OUTCOME DEFINITION: Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6-10 years of age. Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with "no pets" (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I(2) = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with "no pets" (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I(2) = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to "no pets" resulted in an odds ratio of 1.04 (0.59 to 1.84) (I(2) = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6-10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.
  PLoS ONE 01/2012; 7(8):e43214. · 4.09 Impact Factor
• Article: Walnut allergy in peanut-allergic patients: significance of sequential epitopes of walnut homologous to linear epitopes of Ara h 1, 2 and 3 in relation to clinical reactivity.

  Leonard Rosenfeld, Wayne Shreffler, Ludmilla Bardina, Bodo Niggemann, Ulrich Wahn, Hugh A Sampson, Kirsten Beyer
  [show abstract] [hide abstract]
  ABSTRACT: Peanut allergy is a frequent and potentially life-threatening food allergy. Despite the large taxonomic distance between the plants, peanut-allergic patients often react to tree nuts such as walnuts. While the allergens of peanut and walnut have a high degree of homology in their amino-acid sequences, it is unknown whether this similarity is responsible for the observed co-reactivity. Therefore, we analyzed the binding of specific IgE antibodies to sequential epitopes of peanut and walnut in peanut-allergic patients with and without walnut allergy. The IgE binding to previously described sequential epitopes of peanut and the homologous regions of walnut was assessed in 32 peanut-allergic patients using a peptide microarray technology. Twelve patients had a clinically relevant walnut allergy and 20 were tolerant to walnut. Inhibition assays with peanut peptides and corresponding walnut sequences were performed to show specific binding to sequential epitopes. No differences in the recognition of sequential epitopes could be found between peanut-allergic patients with or without walnut allergy. Only a few patients showed IgE binding to walnut sequences that corresponded to sequential epitopes of peanut. In the inhibition assays, no relevant cross-reacting IgE antibodies could be detected for the peptides analyzed. Our results indicate that although they share a rather high degree of homology with the corresponding regions of walnut allergens, the sequence stretches previously identified as sequential IgE binding epitopes of Ara h 1, Ara h 2 and Ara h 3 have no IgE binding equivalents in walnut allergens.
  International Archives of Allergy and Immunology 01/2012; 157(3):238-45. · 2.40 Impact Factor
• Article: Serum retinoic acid and atopy among children of different ethnic origin living in Germany.

  Christoph Grüber, Ceylan Taner, Johanna Mihály, Paolo M Matricardi, Ulrich Wahn, Ralph Rühl
  [show abstract] [hide abstract]
  ABSTRACT: We hypothesized that higher provitamin A carotenoid serum levels may be associated with higher concentrations of all-trans retinoic acid (ATRA) and atopy. Concentration of ATRA was measured by high-performance liquid chromatography in sera from German domestic and Turkish migrants' children. ATRA serum levels were significantly higher in German children if compared with Turkish children and correlated with those of β-carotene (rs = 0.692) and other provitamin A carotenoids. They did not differ significantly between atopic and nonatopic individuals. Serum levels of ATRA are related to those of provitamin A carotenoids but are not directly related to atopy in the present study.
  Journal of pediatric gastroenterology and nutrition 12/2011; 54(4):558-60. · 2.18 Impact Factor
• Article: Interferon-gamma inducible protein 10 as a biomarker for active tuberculosis and latent tuberculosis infection in children: a case-control study.

  Neele Alsleben, Morten Ruhwald, Holger Rüssmann, Florian M Marx, Ulrich Wahn, Klaus Magdorf
  [show abstract] [hide abstract]
  ABSTRACT: Interferon-gamma (IFN-γ) release assays (IGRAs) are suboptimally sensitive to diagnose tuberculosis (TB) and latent TB infection (LTBI) in young children. In this study we compared Mycobacterium tuberculosis antigen-stimulated IFN-γ inducible protein 10 (IP-10) responses in children with active TB and LTBI to responses from children with non-tuberculous mycobacterial (NTM) lymphadenopathy and respiratory tract infection (RTI). We also assessed test agreement between IP-10 and the QuantiFERON(®)-TB Gold In-Tube (QFT-IT) test results, and investigated whether IP-10 release upon mitogen stimulation is associated with age. We recruited 48 children (median age 54 months) diagnosed in Germany with either active TB (n = 11), LTBI (n = 14), NTM lymphadenopathy (n = 8), or common RTI (n = 15). IFN-γ levels were measured using the QFT-IT. These plasma supernatants were used to determine IP-10 concentrations using an in-house enzyme-linked immunosorbent assay (ELISA). The median antigen-stimulated IP-10 levels in children with active TB, LTBI, NTM lymphadenopathy, and RTI were 12,702 pg/ml, 9109 pg/ml, 97 pg/ml, and 84 pg/ml, respectively. We observed a strong correlation between IP-10 and IFN-γ plasma concentration in children with active TB and LTBI (r(2) = 0.69). Overall agreement between IP-10 and QFT-IT assays was high (kappa = 0.95). IP-10 levels after mitogen stimulation showed no association with age. IP-10 and IFN-γ were both induced with antigen stimulation in blood from children in the TB and LTBI groups, in contrast to the NTM and RTI groups. Compared to IFN-γ the IP-10 levels were higher and IP-10 was released independently of age. IP-10 therefore may represent an additional biomarker in the paediatric population.
  Scandinavian Journal of Infectious Diseases 11/2011; 44(4):256-62. · 1.72 Impact Factor
• Article: Effects of systemic versus local administration of corticosteroids on mucosal tolerance.

  Jerome Kerzerho, Daniela Wunsch, Natacha Szely, Hellmuth-Alexander Meyer, Lisa Lurz, Lars Röse, Ulrich Wahn, Omid Akbari, Philippe Stock
  [show abstract] [hide abstract]
  ABSTRACT: Respiratory exposure to allergen induces T cell tolerance and protection against the development of airway hyperactivity in animal models of asthma. Whereas systemic administration of dexamethasone during the delivery of respiratory Ag has been suggested to prevent the development of mucosal tolerance, the effects of local administration of corticosteroids, first-line treatment for patients with bronchial asthma, on mucosal tolerance remain unknown. To analyze the effects of systemic versus local administration of different types of corticosteroids on the development of mucosal tolerance, mice were exposed to respiratory allergen to induce mucosal tolerance with or without systemic or intranasal application of different doses of dexamethasone or prednisolone. After the induction of mucosal tolerance, proliferation of T cells was inhibited in tolerized mice, whereas systemic applications of corticosteroids restored T cell proliferation and secretion of Th2 cytokines. In contrast, inhaled corticosteroids showed no effect on both T cell proliferation and cytokine secretion. In addition, mice systemically treated with corticosteroids showed an increased airway hyperactivity with a significant lung inflammation, but also an increased T effector cells/regulatory T cells ratio in the second lymphoid organs when compared with mice that receive corticosteroids by inhalation. These results demonstrate that local administration of corticosteroids has no effect on the development of immune tolerance in contrast to systemically applied corticosteroids. Furthermore, although different concentrations of corticosteroids are administered to patients, our results demonstrated that the route of administration rather than the doses affects the effect of corticosteroids on respiratory tolerance induction. Considering the broad application of corticosteroids in patients with allergic disease and asthma, the route of administration of steroid substances seems crucial in terms of treatment and potential side effects. These findings may help elucidate the apparently contradicting results of corticosteroid treatment in allergic diseases.
  The Journal of Immunology 11/2011; 188(1):470-6. · 5.79 Impact Factor
• Article: Subcutaneous immunotherapy and pharmacotherapy in seasonal allergic rhinitis: a comparison based on meta-analyses.

  Paolo Maria Matricardi, Piotr Kuna, Valentina Panetta, Ulrich Wahn, Annemie Narkus
  [show abstract] [hide abstract]
  ABSTRACT: Allergen-specific subcutaneous immunotherapy (SCIT) of seasonal allergic rhinitis (SAR) is usually considered a "second-line," slow-acting, disease-modifying treatment. We sought to test whether SCIT is as effective as antisymptomatic treatment in the control of symptoms in patients with SAR in the first year of treatment. We reviewed meta-analyses with 5 or more randomized, double-blind, placebo-controlled trials of SCIT or antisymptomatic treatment in patients with SAR. We then selected trials measuring the total nasal symptom score (TNSS), the total symptom score (TSS), or both during the first pollen season after treatment initiation. Efficacy was determined as the percentage reduction in TSSs and TNSSs obtained with active treatment compared with placebo (relative clinical impact [RCI]) and the standardized mean difference (SMD) of treatment verses placebo (effect size [ES]). The weighted mean RCI of SCIT on TNSSs (-34.7% ± 6.8%) was higher than those of mometasone (-31.7% ± 16.7%, P < .00001) and montelukast (-6.3% ± 3.0%, P < .00001). The weighted mean RCI of SCIT on TSSs (-32.9% ± 12.7%) was higher than that of desloratadine (-12.0% ± 5.1%, P < .00001). The overall ES of SCIT in terms of TNSSs (SMD, -0.94; 95% CI, -1.45 to -0.43) was similar to that of mometasone (SMD, -0.47; 95% CI, -0.63 to -0.32; P > .05) and higher than that of montelukast (SMD, -0.24; 95% CI, -0.33 to -0.16; P < .05). The overall ES of SCIT in terms of TSSs (SMD, -0.86; 95% CI, -1.17 to -0.55) was comparable with that of desloratadine (SMD, -1.00; 95% CI, -1.68 to -0.32; P > .05). Our data provide indirect but consistent evidence that SCIT is at least as potent as pharmacotherapy in controlling the symptoms of SAR as early as the first season of treatment.
  The Journal of allergy and clinical immunology 05/2011; 128(4):791-799.e6. · 9.17 Impact Factor
• Source

  Available from: Christian A Ganoza

  Article: Granulysin-expressing CD4+ T cells as candidate immune marker for tuberculosis during childhood and adolescence.

  Henrik Mueller, Kellen C Faé, Klaus Magdorf, Christian A Ganoza, Ulrich Wahn, Ute Guhlich, Cornelia Feiterna-Sperling, Stefan H E Kaufmann
  [show abstract] [hide abstract]
  ABSTRACT: Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB. Peripheral blood mononuclear cells (PBMC) from children and adolescents (1-17 years) with active TB, latent TB infection (LTBI), nontuberculous mycobacteria (NTM) infection and from uninfected controls were isolated and restimulated in a 7-day restimulation assay. Intracellular staining was then performed to analyze antigen-specific induction of activation markers and cytotoxic proteins, notably, granulysin in CD4(+) CD45RO(+) memory T cells. CD4(+) CD45RO(+) T cells co-expressing granulysin with specificity for Mycobacterium tuberculosis (Mtb) were present in high frequency in TB-experienced children and adolescents. Proliferating memory T cells (CFSE(low)CD4(+)CD45RO(+)) were identified as main source of granulysin and these cells expressed both central and effector memory phenotype. PBMC from study participants after TB drug therapy revealed that granulysin-expressing CD4(+) T cells are long-lived, and express several activation and cytotoxicity markers with a proportion of cells being interferon-gamma-positive. In addition, granulysin-expressing T cell lines showed cytolytic activity against Mtb-infected target cells. Our data suggest granulysin expression by CD4(+) memory T cells as candidate immune marker for TB infection, notably, in childhood and adolescence.
  PLoS ONE 01/2011; 6(12):e29367. · 4.09 Impact Factor
• Article: The Consolidated Standards of Reporting Trials (CONSORT) Statement applied to allergen-specific immunotherapy with inhalant allergens: a Global Allergy and Asthma European Network (GA(2)LEN) article.

  Philippe J Bousquet, Moisés A Calderón, Pascal Demoly, Désirée Larenas, Giovanni Passalacqua, Claus Bachert, Jan Brozek, G Walter Canonica, Thomas Casale, Joao Fonseca, Ronald Dahl, Stephen R Durham, Hans Merk, Margitta Worm, Ulrich Wahn, Torsten Zuberbier, Holger J Schünemann, Jean Bousquet
  [show abstract] [hide abstract]
  ABSTRACT: Randomized trials provide evidence to inform treatment decisions. The Consolidated Standards of Reporting Trials (CONSORT) Statement is a set of recommendations for the reporting of trials. We sought to assess the quality of reporting allergen-specific immunotherapy trials according to CONSORT criteria. The reporting of the procedure, randomization, dropouts, strict conduct of intention-to-treat (ITT) analysis, and sample size calculation according to CONSORT were assessed in the 46 subcutaneous and 48 sublingual immunotherapy (SLIT) blind, placebo-controlled randomized trials published between 1996 and 2009 in English. One subcutaneous immunotherapy (2.2%) and 3 SLIT (6.6%) trials met CONSORT Statement criteria. These were used for the registration of sublingual tablets to the European Medicines Agency. In subcutaneous immunotherapy, 16 (35%) studies reported a CONSORT flow chart, and 12 (26%) provided a description of dropouts. Adequate randomization was reported in 9 (35%) studies, and incomplete randomization was reported in 15 (33%). Power analysis was reported in 15 (33%) studies. In SLIT, 20 (42%) studies reported a CONSORT flow chart, and 16 (32%) a description of dropouts. ITT analysis was carried out in 1 (2.2%) SLIT study, and a modified ITT analysis was used in 1 (2.2%) subcutaneous immunotherapy study and 2 (4.4%) SLIT studies. Adequate randomization was reported in 6 (12%) studies, and incomplete randomization was reported in 16 (32%). Power analysis was reported in 15 (27%) studies. As in other areas of medicine, the quality of reporting of most immunotherapy trials is low, and only 4.2% of SLIT randomized controlled trials met all of the criteria of the CONSORT Statement. Use of the CONSORT criteria should be encouraged.
  The Journal of allergy and clinical immunology 01/2011; 127(1):49-56, 56.e1-11. · 9.17 Impact Factor
• Source

  Available from: healtheconomicsreview.com

  Article: Staff costs of hospital-based outpatient care of patients with cystic fibrosis.

  Helge Hollmeyer, Jonas Schreyögg, Ulrich Wahn, Doris Staab
  [show abstract] [hide abstract]
  ABSTRACT: This study identified per patient resource use and staff costs at a cystic fibrosis (CF) outpatient unit from the health care provider's perspective. Personnel cost data were prospectively collected for all CF outpatients (n = 126) under routine conditions at the Charité Medical School Berlin in Germany over a six month study period. Patients were grouped according to age, sex and two severity categories. Ordinary least squares regression analysis was performed to determine the impact of various independent variables on personnel costs. The mean staff costs were €142.3 per patient over six months of outpatient service. Services provided by physicians were the biggest contributor to staff costs. Patient age correlated significantly and negatively with mean total costs per patient. Age of patient is a significant determinant of staff costs for CF outpatient care. For a cost-covering remuneration of outpatient treatment it seems plausible to create separate reimbursement rates for two or three age groups and to consider additional costs due to tasks carried out by physicians without direct patient contact. The relatively low staff costs identified by our study reflect a staffing level not sufficient for specialist CF outpatient care.
  Health economics review. 01/2011; 1(1):10.