B Niggemann

Charité Universitätsmedizin Berlin, Berlín, Berlin, Germany

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Publications (322)1710.19 Total impact

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    ABSTRACT: The identification of B-cell epitopes of food allergens can possibly lead to novel diagnostic tools and therapeutic reagents for food allergy. We sought to develop a flexible, low-tech, cost-effective and reproducible multipeptide microarray for the research environment to enable large-scale screening of IgE epitopes of food allergens. Overlapping peptides (15-mer, 4 amino acid offset) covering the primary sequence of either peanut allergen Ara h 1 or all 3 subunits of the soybean allergen Gly m 5 were simultaneously synthesized in-house on a porous cellulose matrix. Identical peptide microarrays created with up to 384 duplicate peptide-cellulose microspots each were investigated for specificity and sensitivity in IgE immunodetection and in direct experimental comparison to the formerly established SPOT™ membrane technique. The in-house microarray identified with 98% reproducibility the same IgE-binding peptides as the SPOT™ membrane technique. Additional IgE-binding peptides were identified using the microarray. While the sensitivity was increased between 2- and 20-fold, the amount of human serum required was reduced by at least two thirds over the SPOT™ membrane technique using the microarray. After subtraction of the potential background, we did not observe non-specific binding to the presented peptides on microarray. The novel peptide microarray allows simple and cost-effective screening for potential epitopes of large allergenic legume seed storage proteins, and it could be adapted for other food allergens as well, to study allergenic epitopes at the individual subject level in large paediatric and adult study groups of food allergic subjects. © 2015 S. Karger AG, Basel.
    International Archives of Allergy and Immunology 04/2015; 166(3):213-224. DOI:10.1159/000381344 · 2.43 Impact Factor
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    ABSTRACT: Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent of origin effects. Beyond the known role of FLG inheritance in AD (R1 meta-analysis = 2.4, P = 1.0 x 10 −36), we observed a strong maternal FLG genotype effect that was consistent in
    PLoS Genetics 03/2015; · 8.52 Impact Factor
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    ABSTRACT: Epidemiological studies suggest that allergy risk is preferentially transmitted through mothers. This can be due to genomic imprinting, where the phenotype effect of an allele depends on its parental origin, or due to maternal effects reflecting the maternal genome's influence on the child during prenatal development. Loss-of-function mutations in the filaggrin gene (FLG) cause skin barrier deficiency and strongly predispose to atopic dermatitis (AD). We investigated the 4 most prevalent European FLG mutations (c.2282del4, p.R501X, p.R2447X, and p.S3247X) in two samples including 759 and 450 AD families. We used the multinomial and maximum-likelihood approach implemented in the PREMIM/EMIM tool to model parent-of-origin effects. Beyond the known role of FLG inheritance in AD (R1meta-analysis = 2.4, P = 1.0 x 10-36), we observed a strong maternal FLG genotype effect that was consistent in both independent family sets and for all 4 mutations analysed. Overall, children of FLG-carrier mothers had a 1.5-fold increased AD risk (S1 = 1.50, Pmeta-analysis = 8.4 x 10-8). Our data point to two independent and additive effects of FLG mutations: i) carrying a mutation and ii) having a mutation carrier mother. The maternal genotype effect was independent of mutation inheritance and can be seen as a non-genetic transmission of a genetic effect. The FLG maternal effect was observed only when mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels), suggesting that FLG mutation-induced systemic immune responses in the mother may influence AD risk in the child. Notably, the maternal effect reported here was stronger than most common genetic risk factors for AD recently identified through genome-wide association studies (GWAS). Our study highlights the power of family-based studies in the identification of new etiological mechanisms and reveals, for the first time, a direct influence of the maternal genotype on the offspring's susceptibility to a common human disease.
    PLoS Genetics 03/2015; 11(3):e1005076. DOI:10.1371/journal.pgen.1005076 · 8.17 Impact Factor
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    ABSTRACT: Background Currently there is no mandatory labelling of allergens for non-pre-packed foods in the EU. Therefore, consumers with food allergy rely on voluntary information provided by the staff. The aim of this study was to characterise allergic reactions to non-pre-packed foods and to investigate whether staff in baker's shops were able to give advice regarding a safe product choice.Methods Questionnaires were sent to 200 parents of children with a food allergy. Staff of 50 baker's shops were interviewed regarding selling non-pre-packed foods to food-allergic customers. Bakery products being recommended as “cow's milk free” were bought and cow's milk protein levels were measured using ELISA.Results104/200 questionnaires were returned. 25% of the children experienced an allergic reaction due to a non-pre-packed food from baker's shops and 20% from ice cream parlours. 60% of the bakery staff reported serving food-allergic customers at least once a month, 24% once a week. 84% of the staff felt able to advise food allergic consumers regarding a safe product choice. 73 “cow's milk free” products were sold in 44 baker's shops. Cow's milk could be detected in 43% of the bakery products, 21% contained >3 mg cow's milk protein per serving.Conclusion Staff in baker's shops felt confident about advising customers with food allergy. However, cow's milk was detectable in almost half of bakery products being sold as “cow's milk free”. Every fifth product contained quantities of cow's milk exceeding an amount where approximately 10% of cow's milk allergic children will show clinical relevant symptoms.This article is protected by copyright. All rights reserved.
    Allergy 02/2015; 70(5). DOI:10.1111/all.12588 · 6.00 Impact Factor
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    ABSTRACT: Background Oral challenges are the gold standard in food allergy diagnostic, but time consuming. Aim of the study was to investigate the role of peanut- and hazelnut-component-specific IgE in the diagnostics of peanut and hazelnut allergy and to identify cut-off levels to make some challenges superfluous.Methods In a prospective and multicenter study, children with suspected peanut or hazelnut allergy underwent oral challenges. Specific IgE to peanut, hazelnut and their components (Ara h 1, Ara h 2, Ara h 3, and Ara h 8, Cor a 1, Cor a 8, Cor a 9, and Cor a 14) were determined by ImmunoCAP-FEIA.Results210 children were challenged orally with peanut and 143 with hazelnut. 43% of the patients had a positive peanut and 31% a positive hazelnut challenge. With an area under the curve of 0.92 and 0.89 respectively, Ara h 2 and Cor a 14-specific IgE discriminated between allergic and tolerant children better than peanut or hazelnut-specific IgE. For the first time, probability curves for peanut and hazelnut components have been calculated. A 90% probability for a positive peanut or hazelnut challenge was estimated for Ara h 2-specific IgE at 14.4 kU/L and for Cor a 14-specific IgE at 47.8 kU/L. A 95% probability could only be estimated for Ara h 2 at 42.2 kU/L.Conclusions Ara h 2- and Cor a 14-specific IgE are useful to estimate the probability for a positive challenge outcome in the diagnostic workup of peanut or hazelnut allergy making some food challenges superfluous.This article is protected by copyright. All rights reserved.
    Allergy 10/2014; 70(1). DOI:10.1111/all.12530 · 6.00 Impact Factor
  • B. Niggemann, K. Beyer
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    ABSTRACT: Elicitors of anaphylactic reactions are any sources of protein with allergenic capacity, such as foods, drugs, insect venoms, pollen, animal dander, occupational allergens, or seminal fluid. However, not all allergic reactions end up in the most severe form of anaphylaxis. Accompanying factors may explain, why some conditions lead to anaphylaxis while in other cases the allergen is tolerated.This article is protected by copyright. All rights reserved.
    Allergy 10/2014; DOI:10.1111/all.12532 · 6.00 Impact Factor
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    ABSTRACT: Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence-based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non-life-threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.
    Allergy 06/2014; DOI:10.1111/all.12429 · 6.00 Impact Factor
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    ABSTRACT: Anaphylaxis is a clinical emergency, and all healthcare professionals should be familiar with its recognition and acute and ongoing management. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Taskforce on Anaphylaxis. They aim to provide evidence-based recommendations for the recognition, risk factor assessment, and the management of patients who are at risk of, are experiencing, or have experienced anaphylaxis. While the primary audience is allergists, these guidelines are also relevant to all other healthcare professionals. The development of these guidelines has been underpinned by two systematic reviews of the literature, both on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a potentially life-threatening condition whose clinical diagnosis is based on recognition of a constellation of presenting features. First-line treatment for anaphylaxis is intramuscular adrenaline. Useful second-line interventions may include removing the trigger where possible, calling for help, correct positioning of the patient, high-flow oxygen, intravenous fluids, inhaled short-acting bronchodilators, and nebulized adrenaline. Discharge arrangements should involve an assessment of the risk of further reactions, a management plan with an anaphylaxis emergency action plan, and, where appropriate, prescribing an adrenaline auto-injector. If an adrenaline auto-injector is prescribed, education on when and how to use the device should be provided. Specialist follow-up is essential to investigate possible triggers, to perform a comprehensive risk assessment, and to prevent future episodes by developing personalized risk reduction strategies including, where possible, commencing allergen immunotherapy. Training for the patient and all caregivers is essential. There are still many gaps in the evidence base for anaphylaxis.
    Allergy 06/2014; 69(8). DOI:10.1111/all.12437 · 6.00 Impact Factor
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    ABSTRACT: Threshold levels for peanut allergy determined by using oral challenges are important for the food industry with regard to allergen labeling. Moreover, the utility of biological markers in predicting threshold levels is uncertain. We sought to use a modified oral food challenge regimen that might determine threshold levels for peanut allergy mimicking a more real-life exposure and to correlate the eliciting dose (ED) and severity of clinical reaction in children with peanut allergy with B-cell, T-cell, and effector cell markers. A modified food challenge procedure with doses scheduled 2 hours apart was used in 63 children with peanut allergy. All children received a maximum of 8 semi-log increasing titration steps of roasted peanuts ranging from 3 to 4500 mg of peanut protein until objective allergic reactions occurred. Severity of symptoms was graded from I to V. Biological markers were measured before challenge. Forty-five of 63 patients showed objective symptoms after greater than 30 minutes, with a median latency of clinical reaction of 55 minutes. By using a log-normal dose-distribution model, the ED5 was calculated to be 1.95 mg of peanut protein. The ED was significantly and inversely correlated with peanut- and Ara h 2-specific IgE levels, skin prick test responses, basophil activation, and TH2 cytokine production by PBMCs. Symptom severity did not correlate with any of the markers or the ED. This modified food challenge procedure might better reflect threshold levels for peanut allergy than the standard procedure because most of the patients reacted at a time interval of greater than 30 minutes. By using this model, threshold levels, but not severity, could be correlated with biological markers.
    The Journal of allergy and clinical immunology 05/2014; 134(2). DOI:10.1016/j.jaci.2014.03.035 · 11.25 Impact Factor
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    ABSTRACT: ProblemstellungUnter Anaphylaxie versteht man eine akute systemische Reaktion mit Symptomen einer allergischen Sofortreaktion, die den ganzen Organismus erfassen kann und potenziell lebensbedrohlich ist [1–3].Die Definition der Anaphylaxie ist weltweit nicht einheitlich. Derzeit werden verschiedene Klassifikationssysteme verwendet. Im deutschen Sprachraum ist bislang überwiegend die hier verwendete Klassifikation eingesetzt worden.Anaphylaktische Reaktionen gehören zu den schwersten und potenziell lebensbedrohlichen, dramatischen Ereignissen in der Allergologie. Die Akutbehandlung wird auf der Grundlage internationaler Leitlinien und Empfehlungen von Lehrbüchern durchgeführt. 1994 erschien das Ergebnis einer interdisziplinären Konsensuskonferenz als Positionspapier der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI) im Allergo Journal [4], welches im Jahr 2007 aktualisiert als Leitlinie veröffentlicht wurde [5].Auf Vorstandsbeschluss der DGAKI von 2009 wurde d ...
    Allergo Journal: interdisziplinäre Zeitschrift für Allergologie und Umweltmedizin: Organ der Deutschen Gesellschaft für Allergie- und Immunitätsforschung 05/2014; 23(3):36-54. DOI:10.1007/s15007-014-0542-8
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    ABSTRACT: In a large randomised trial in patients with seasonal allergic rhinitis (SAR), acupuncture was superior compared to sham acupuncture and rescue medication. The aim of this paper is to describe the characteristics of the trial's participating physicians and to describe the trial intervention in accordance with the STRICTA (Standards for Reporting Interventions in Controlled Trials of Acupuncture) guidelines, to make details of the trial intervention more transparent to researchers and physicians. ACUSAR (Acupuncture in Seasonal Allergic Rhinitis) was a three-armed, randomised, controlled multicentre trial. 422 SAR patients were randomised to semi-standardised acupuncture plus rescue medication (RM, cetirizine), sham acupuncture plus RM or RM alone. We sent a questionnaire to trial physicians in order to evaluate their characteristics regarding their education about and experience in providing acupuncture. During the trial, acupuncturists were asked to diagnose all of their patients according to Chinese Medicine (CM) as a basis for the semi-standardised, individualized intervention in the acupuncture group. Every acupuncture point used in this trial had to be documented after each session RESULTS: Acupuncture was administered in outpatient clinics by 46 (mean age 47 +/- 10 years; 24 female/ 22 male) conventionally-trained medical doctors (67% with postgraduate specialization such as internal or family medicine) with additional extensive acupuncture training (median 500 hours (1st quartile 350, 3rd quartile 1000 hours with 73% presenting a B-diploma in acupuncture training (350 hours)) and experience (mean 14 years in practice). The most reported traditional CM diagnosis was 'wind-cold invading the lung' (37%) and 'wind-heat invading the lung' (37%), followed by 'lung and spleen qi deficiency' (9%). The total number of needles used was higher in the acupuncture group compared to the sham acupuncture group (15.7 +/- 2.5 vs. 10.0 +/- 1.6). The trial interventions were provided by well educated and experienced acupuncturists. The different number of needles in both intervention groups could be possibly a reason for the better clinical effect in SAR patients. For future trials it might be more appropriate to ensure that acupuncture and sham acupuncture groups should each be treated by a similar number of needles.Trial registration: ClinicalTrials.gov: NCT00610584.
    BMC Complementary and Alternative Medicine 04/2014; 14(1):128. DOI:10.1186/1472-6882-14-128 · 1.88 Impact Factor
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    ABSTRACT: Reported food-related symptoms of patients may sometimes be misleading. A correct delineation of food-induced symptoms is often difficult and various differential diagnoses have to be considered. We report on two cases of food-induced, predominantly respiratory symptoms (in one case life-threatening) in children with food allergy. First, a two-year-old boy with no history of allergies and suspected foreign body aspiration which was finally diagnosed as an anaphylactic reaction to fish, and secondly a six-year-old girl with multiple food allergies and allergic asthma who during an electively performed oral food challenge developed severe respiratory distress, drop in blood pressure, and asphyxia not due to an anaphylactic reaction but due to choking on an unnoticed sweet. These two cases represent challenging, life-threatening symptom constellations involving food-induced reactions in food allergic children, reminding us to question first impressions. Pediatr Pulmonol. 2013 9999:XX-XX. © 2013 Wiley Periodicals, Inc.
    Pediatric Pulmonology 03/2014; 49(3). DOI:10.1002/ppul.22816 · 2.30 Impact Factor
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    ABSTRACT: Darf ich das essen? Die Lebensmittelinformationsverordnung soll mehr Sicherheit für Allergiker bringen, es gibt jedoch noch Verbesserungspotenzial.© Art Allianz / fotolia.com Wir begrüßen, dass über die Lebensmittelinformationsverordnung (LMIV) mehr Sicherheit für Allergiker geschaffen wird. Die Einbeziehung loser Ware in die verpflichtende Deklaration häufiger Auslöser von Unverträglichkeitsreaktionen stellt einen wichtigen Schritt in Richtung Sicherheit und damit Lebensqualität für Personen mit Allergien und anderen Unverträglichkeiten dar.Problematisch ist aus unserer Sicht, dass es sich bei einigen der in Anhang II der LMIV aufgeführten Liste von Stoffen oder Erzeugnissen, die Allergien oder andere Unverträglichkeiten auslösen können, um Gruppenbezeichnungen (glutenhaltiges Getreide, Krebstiere, Fische, Milchprodukte, Schalenfrüchte, Weichtiere) handelt, die allergologisch unbedingt zu differenzieren sind. Die fehlende Differenzierung kann schwerwiegende gesundhei ...
    Allergo Journal: interdisziplinäre Zeitschrift für Allergologie und Umweltmedizin: Organ der Deutschen Gesellschaft für Allergie- und Immunitätsforschung 02/2014; 23(1):78-79. DOI:10.1007/s15007-014-0491-2
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    ABSTRACT: Bei älteren Kindern, Jugendlichen und Erwachsenen wird ein großer Teil Immunglobulin-E(IgE)-vermittelter Nahrungsmittelallergien durch kreuzreaktive allergene Strukturen ausgelöst. Die primäre Sensibilisierung ist vorrangig gegen Inhalationsallergene gerichtet (z. B. Bet v 1 als Hauptallergen der Birkenpollen). IgE kann über verschiedene kreuzreaktive Allergene aktiviert werden und zu unterschiedlichen klinischen Manifestationen führen. In der Regel treten lokale und milde, selten auch schwere systemische Reaktionen direkt nach Verzehr des Nahrungsmittels auf, welches das kreuzreaktive Allergen enthält (z. B. pflanzliche Nahrungsmittel mit Proteinanteil aus der Bet-v-1-Familie). In der klinischen Praxis können Sensibilisierungen gegen die primär verantwortlichen Inhalations- und/oder Nahrungsmittelallergene mit dem Pricktest und/oder der Bestimmung von spezifischem IgE in vitro erfasst werden. Die komponentenbasierte Diagnostik kann die klinische Diagnostik unterstützen. Für einzelne Allergene ermöglicht sie eine Risikoabschätzung für das Auftreten systemischer Reaktionen. Sensibilisierungen müssen insbesondere bei unklarer Anamnese durch orale Provokationstests bestätigt werden. Auch neue, bisher unerkannte Allergene können Kreuzreaktionen hervorrufen. Das therapeutische Potenzial der spezifischen Immuntherapie mit inhalativen Allergenen und deren Wirkung auf die pollenassoziierte Nahrungsmittelallergie ist im klinischen Alltag variabel und letztlich nicht geklärt. Placebokontrollierte Studien sind zukünftig erforderlich. Insgesamt treten allergische Sensibilisierungen gegen Pollen- und kreuzreaktive Nahrungsmittelallergene in unseren Breiten sehr häufig auf. Ihre aktuelle Relevanz ist mit Hilfe der klinischen Angaben individuell zu ermitteln.
    Allergologie 02/2014; 37(05):170-189. DOI:10.5414/ALX01655 · 0.30 Impact Factor
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    ABSTRACT: The gold standard in the diagnosis of food allergy is the double-blind, placebo-controlled oral food challenge (DBPCFC). During this challenge, patients receive the allergenic food and placebo on separate randomized days, while being monitored for clinical reactions. Interestingly, some reactions are assessed as positive although the patients had received placebo. The aim of our study was to analyze incidence and characteristics of positive placebo reactions during DBPCFCs. In food-allergic children, we retrospectively analyzed positive placebo reactions in DBPCFCs in 740 placebo challenges in our department. Individual characteristics were compared, such as age or IgE levels, as well as clinical symptoms. 2.8% (21 out of 740) of all placebo challenges were assessed as positive. Young children (age <= 1.5 yrs) had more (p = .047) positive placebo challenges (4.0%) compared to older children (age > 1.5 yrs; 1.5%). Children with positive placebo challenges had higher levels of total IgE (median 201 kU/l) compared to negatively classified children (median 110 kU/l). In children with positive placebo reactions, skin symptoms were observed significantly more often, with a worsening of atopic eczema (AE) as the most reported symptom. Placebo reactions in DBPCFC are not common. Worsening of AE is the most frequent clinical reaction associated with positive placebo challenges, and young children (age <= 1.5 yrs) seem to be affected more often. Therefore - contrary to current recommendations - DBPCFC tests should be considered in infants and young children, especially those with a history of AE. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 01/2014; DOI:10.1111/cea.12284 · 4.32 Impact Factor
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    ABSTRACT: Background: Anaphylaxis is the most severe manifestation of a mast cell–dependent immediate reaction and may be fatal. According to data from the Berlin region, its inci-dence is 2–3 cases per 100 000 persons per year.
    Deutsches Ärzteblatt International 01/2014; DOI:10.3238/arztebl.2014.0367 · 3.61 Impact Factor
  • 01/2014; 4(Suppl 2):O2. DOI:10.1186/2045-7022-4-S2-O2
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  • Sibylle Koletzko, Bodo Niggemann
    Journal of pediatric gastroenterology and nutrition 11/2013; DOI:10.1097/MPG.0000000000000240 · 2.87 Impact Factor

Publication Stats

13k Citations
1,710.19 Total Impact Points


  • 1999–2015
    • Charité Universitätsmedizin Berlin
      • Department of Pediatrics, Division of Pneumonology and Immunology
      Berlín, Berlin, Germany
  • 2013
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 2009–2013
    • DRK Kliniken Berlin
      Berlín, Berlin, Germany
    • Icahn School of Medicine at Mount Sinai
      • Division of Allergy and Immunology
      Borough of Manhattan, New York, United States
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 2008–2012
    • Red Cross
      Washington, Washington, D.C., United States
    • Friedrich Schiller University Jena
      • Section of Pneumology / Allergology
      Jena, Thuringia, Germany
  • 1996–2012
    • Humboldt-Universität zu Berlin
      • Department of Biology
      Berlín, Berlin, Germany
  • 2011
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2005
    • Munich Re
      München, Bavaria, Germany
  • 1997–2004
    • Humboldt State University
      Arcata, California, United States
  • 2002
    • Children´s Hospital Association
      Overland Park, Kansas, United States
    • Umeå University
      Umeå, Västerbotten, Sweden
  • 1991–2002
    • University of Iowa Children's Hospital
      Iowa City, Iowa, United States
  • 1993
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1992
    • University of Hamburg
      • Department of Paediatrics
      Hamburg, Hamburg, Germany