Publications (12)38.21 Total impact
-
Article: Omalizumab: Anti-IgE therapy in allergy.
[show abstract] [hide abstract]
ABSTRACT: Omalizumab is a humanized, monoclonal anti-IgE antibody that binds specifically to circulating IgE molecules, thus interrupting the allergic cascade. Omalizumab has been shown to be highly effective in treating children and adults with moderate to severe allergic asthma. Beyond this indication, the mode of action itself suggests that omalizumab is not only an antiasthmatic drug but also a promising therapeutic option for various allergic conditions, including allergic rhinitis, food allergy, urticaria, allergic bronchopulmonary aspergillosis, insect hypersensitivity, and atopic dermatitis. However, data from double-blind, placebo-controlled clinical trials are only available for allergic rhinitis and moderate to severe bronchial asthma. The aim of this review is to discuss the current clinical data as well as possible further indications of omalizumab treatment.Current Allergy and Asthma Reports 01/2011; 11(2):101-6. · 2.50 Impact Factor -
Article: Haplotypes covering the TNFSF10 gene are associated with bronchial asthma.
[show abstract] [hide abstract]
ABSTRACT: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is elevated in the airways of subjects with asthma and has been linked to the development of allergic airway disease by promoting STAT6-dependent T helper 2 cell (T(H) 2) effector functions. To determine whether single nucleotide polymorphisms (SNPs) in the TNFSF10 gene are associated with bronchial asthma we genotyped 498 Caucasian subjects living in Southern Germany for eight SNPs in the TNFSF10 by restriction fragment length polymorphism analysis. In contrast to single SNPs, haplotypes constructed from eight SNPs were robustly associated with asthma (p=0.00012). A small haplotype approach returned four alleles consisting of two (rs3136586/ rs3136598), three (rs12488654/rs3136586/rs3136598 and rs3136586/rs3136598/rs3136604), and four SNPs (rs12488654/ rs3136586/ rs3136598/ rs3136604) that were highly associated with asthma (p=0.00005, p=0.00008, p=0.00017 and p=0.00038). Combinations of SNPs in the TNFSF10 allele were strongly associated with asthma supporting the concept that TRAIL is important in the development of hallmark features of this disease.Pediatric Allergy and Immunology 10/2010; 22(1 Pt 1):25-30. · 2.46 Impact Factor -
Article: Safety of anti-IgE treatment with omalizumab in children with seasonal allergic rhinitis undergoing specific immunotherapy simultaneously.
[show abstract] [hide abstract]
ABSTRACT: Seasonal allergic rhinitis (SAR) affects at least 10-25% of the Caucasian race and about 40% of patients are children. Standard treatment of SAR is specific immunotherapy (SIT), but anti-allergic drugs can significantly enhance efficacy of SIT. One candidate is the humanized monoclonal anti-IgE antibody omalizumab. Randomized, double-blind, placebo-controlled, multi-centre trial in Germany. A total of 221 children were randomly assigned to four different groups and treated with SIT (either grass or birch pollen), starting at least 14 wk before the local birch pollen season. After the 12-wk SIT titration phase, either anti-IgE (omalizumab) or placebo (NaCl 0.9%) therapy was added. This combination therapy with SIT and anti-IgE or placebo lasted 24 wk. To record local reactions and adverse events (AE), the injection site was examined by a clinician 20 min after application of study medication. Further, patients stated any AE and the use of rescue medication by means of a diary 3 days after every injection. Finally, any AE or serious adverse event (SAE) reported by the patients was specified on a standard form by clinicians. Overall tolerance was judged by the doctors according to the patient's diaries. To test differences between the groups, we used either the two-sided Wilcoxon rank-sum test or the two-sided chi-square test. Tolerability of SIT and omalizumab treatment was good (82% of patients). Only some AE with possible causal relationship to treatment occurred slightly more often in the verum groups, i.e. local reactions (16.8 vs. 12.3%) and gastrointestinal (2.7 vs. 0.9%) and ear symptoms (1.8 vs. 0%). Most AE (93.4% in omalizumab and 87.2% in placebo group) were judged by the patients as mild to moderate. SAE were restricted to four patients with asthma in the placebo group, two subjects with headache in the verum group and three patients with infections (two in verum and one in placebo group). Only the cases of asthma were judged to be possibly related to study medication. Further, redness and swelling at the SIT injection site appeared significantly more often in the placebo group which suggests a positive effect of omalizumab on local reaction induced by SIT. Omalizumab represents an important clinical advance in the management of allergic diseases and can be considered to be safe in children.Pediatric Allergy and Immunology 10/2009; 21(1 Pt 2):e160-5. · 2.46 Impact Factor -
Article: Treatment with a combination of anti-IgE and specific immunotherapy for allergic rhinitis and asthma.
[show abstract] [hide abstract]
ABSTRACT: Novel therapies that interfere specifically with immunological mechanisms underlying allergen-induced pathology are currently in clinical evaluation. Among these is anti-IgE, which directly targets IgE serum antibodies, thus inhibiting the central mechanism of immediate type hypersensitivity reactions. Application of anti-IgE antibodies effectively reduces IgE serum levels regardless of allergen specificity. It has been successfully tested in patients with allergic rhinitis, asthma and food allergy, showing significant efficacy in reducing symptom scores and use of rescue medications. Anti-IgE therapy is limited by high costs and the requirements for permanent or every-season treatment. The advantage of specific immune therapy (SIT) is the potential to alter the course of the disease, which has been demonstrated in patients with allergic rhinitis, insect venom allergy and, to a lesser degree, with asthma. The broader application of SIT is restricted by sometimes life-threatening side-effects. Here, we summarize the results of clinical trials investigating the effects of combination therapy with anti-IgE and SIT in patients with rhinitis and asthma. These studies show that combination of anti-IgE plus SIT may be beneficial for the treatment of allergic diseases by improving efficacy and limiting side effects.Arbeiten aus dem Paul-Ehrlich-Institut (Bundesamt für Sera und Impfstoffe) zu Frankfurt a.M 01/2009; 96:303-13; discussion 313-5. -
Article: Randomized, double-blind, placebo-controlled trial of probiotics for primary prevention: no clinical effects of Lactobacillus GG supplementation.
[show abstract] [hide abstract]
ABSTRACT: The value of probiotics for primary prevention is controversial. Published trials vary considerably in study design and the applied probiotics, thereby limiting comparability of the results. The purpose of this trial was to study the preventive effect of the probiotic Lactobacillus GG on the development of atopic dermatitis. In a double-blind, placebo-controlled prospective trial, 105 pregnant women from families with > or = 1 member (mother, father, or child) with an atopic disease were randomly assigned to receive either the probiotic Lactobacillus GG (American Type Culture Collection 53103; 5 x 10(9) colony-forming units of Lactobacillus GG twice daily) or placebo. Ninety-four families (89.5%) completed the trial. The supplementation period started 4 to 6 weeks before expected delivery, followed by a postnatal period of 6 months. The primary end point was the occurrence of atopic dermatitis at the age of 2 years. Secondary outcomes were severity of atopic dermatitis, recurrent episodes of wheezing bronchitis, and allergic sensitization at the age of 2 years. Atopic dermatitis was diagnosed in 14 (28%) of 50 in the Lactobacillus GG group and in 12 (27.3%) of 44 in the placebo group. The risk of atopic dermatitis in children on probiotics relative to placebo was 0.96 (confidence interval 0.38-2.33). Severity of atopic dermatitis was comparable between the 2 groups. Notably, children with recurrent (> or = 5) episodes of wheezing bronchitis were more frequent in the Lactobacillus GG group (26%; n = 13), as compared with the placebo group (9.1%; n = 4). No difference was observed between both groups in total immunoglobulin E concentrations or numbers of specific sensitization to inhalant allergens. Supplementation with Lactobacillus GG during pregnancy and early infancy neither reduced the incidence of atopic dermatitis nor altered the severity of atopic dermatitis in affected children but was associated with an increased rate of recurrent episodes of wheezing bronchitis. Therefore, Lactobacillus GG cannot be generally recommended for primary prevention.PEDIATRICS 05/2008; 121(4):e850-6. · 4.47 Impact Factor -
Article: Cytokine levels in supernatants of whole blood and mononuclear cell cultures in adults and neonates reveal significant differences with respect to interleukin-13 and interferon-gamma.
[show abstract] [hide abstract]
ABSTRACT: Findings regarding cytokine levels in neonates and their impact on the development of allergic diseases are controversial. This might be attributed to different laboratory approaches. To compare cytokine levels in supernatants of whole blood (WB) and mononuclear cell (MC) cultures in response to unspecific and allergen specific stimuli. A total population of n = 25 healthy full-term neonates and n = 25 adults was recruited. WB was diluted 1 in 5 and incubated with phytohaemagglutinine (PHA; 20 mug/ml) and the cows' milk protein betalactoglobulin (BLG) for 24 and 120 h. In parallel, cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) were isolated, and cells were cultured with PHA and BLG in the same concentrations in a medium supplemented with fetal calf serum (FCS) and in a serum- free medium (only PBMC from adults). The cytokines interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and IL-13 in the cell culture supernatants were measured using the ELISA technique. IFN-gamma and IL-10 levels in response to PHA in supernatants of MC of neonates were significantly lower compared to that in adults (p < 0.05, Wilcoxon two-sample test). IL-13 levels were significantly higher in response to PHA in neonates. In adults, only levels of IL-10 were significantly correlated in WB and PBMC cultures (PHA: r(S) 0.6; p = 0.002; BLG: r(S) 0.54; p = 0.005). In neonates, IL-10 (PHA: r(S) 0.77; p < 0.001; BLG: r(S) 0.63; p < 0.001) and IFN-gamma (PHA: r(S) 0.48; p = 0.02; BLG: r(S) 0.4; p < 0.047) were significantly correlated. Supernatants of PBMC cultured with an FCS-supplemented medium showed a significant lower IFN-gamma release (PHA 1297 pg/ml; BLG 2762 pg/ml) compared to serum-free cell cultures (PHA 6592.5 pg/ml, p < 0.0001; BLG 14228 pg/ml, p = 0.04). IFN-gamma and IL-13 levels in WB and MC supernatants revealed significant differences. Our data indicate the need for thoroughly defined and standardized culture conditions for the detection of in vitro cytokine levels.Pediatric Allergy and Immunology 03/2008; 19(2):140-7. · 2.46 Impact Factor -
Article: Omalizumab (Xolair) in children with seasonal allergic rhinitis: leukotriene release as a potential in vitro parameter to monitor therapeutic effects.
[show abstract] [hide abstract]
ABSTRACT: To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3-17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC-Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT-grass [median SLT-release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT-birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT-grass [2231 and 2490 ng/ml] or placebo + SIT-birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT-grass: 2855; SIT-grass + placebo: 2543; omalizumab + SIT-birch: 2417; SIT-birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy.Pediatric Allergy and Immunology 09/2007; 18(6):523-7. · 2.46 Impact Factor -
Article: Hospital admission with neonatal sepsis and development of atopic disease: Is there a link?
[show abstract] [hide abstract]
ABSTRACT: The role of suspected or confirmed neonatal sepsis in modifying the risk of atopic disease during childhood was assessed. Children with early-onset neonatal sepsis were identified from a cohort of neonates, hospitalized between 1990 and 1995. Of 196 individuals, 140 were recruited (71.4%). Pre- and postnatal history was ascertained from neonatal medical records. Based on clinical symptoms and a positive blood culture or at least three of initially defined laboratory or bacteriological criteria, they were stratified in either confirmed neonatal sepsis (CS) or suspected sepsis (SS) group. A control group (C) comprised children who were never hospitalized during infancy (n = 696). Primary end-point was the development of atopic dermatitis, bronchial asthma or allergic rhinitis during childhood (mean age 8.4 yr, range 5.7-12.4). CS and SS children had a higher prevalence of atopic dermatitis (CS 15.7%, SS 21.4%) compared with controls (C 5.2%, p < 0.001). Similarly, children with SS (7.1%), but not with CS (4.3%) had significantly more often a doctor's diagnosis of bronchial asthma compared to controls (1.9%, p = 0.02). No difference in the prevalence of allergic rhinitis was observed (CS 4.3%, SS 10%, C 8.3%). After adjusting for parental history of atopic disease and demographic factors, no significant difference for the risk to develop atopic dermatitis, asthma or allergic rhinitis among the groups was calculated in children with normal birth weight (>2500 g). Our data failed to show a possible link between hospital admission with SS and development of atopic disease.Pediatric Allergy and Immunology 12/2005; 16(8):630-6. · 2.46 Impact Factor -
Article: Interleukin-18 enhances the production of interferon-gamma (IFN-gamma) by allergen-specific and unspecific stimulated cord blood mononuclear cells.
[show abstract] [hide abstract]
ABSTRACT: IL-18 is a pleiotropic cytokine involved in the polarisation of T-cell response. This study was performed to determine whether or not IL-18 is detectable in phytohemagglutinin (PHA) or betalactoglobulin (BLG) stimulated supernatants of cord blood mononuclear cells (CBMC) and to study the in vitro effect of IL-18 on the interferon (IFN)-gaamma and IL-13 release of CBMC of healthy neonates. CBMC of neonates were isolated by Ficoll density centrifugation. The cytokines IFN-gamma, IL-13 and IL-18 in the cell culture supernatants were measured using the ELISA technique following stimulation with a unspecific (PHA 20 microg/ml) and an allergen-specific stimulus (BLG 25 microg/ml). In order to study the in vitro effect of IL-18, CBMC were stimulated either with medium alone or with IL-18, IL-18 + PHA and IL-18 + BLG. IL-18 levels in supernatants of CBMC were low and did not vary significantly between unstimulated and PHA or BLG stimulated cell cultures (median 21.4; 23.5 and 15.5 pg/ml, respectively). IFN-gamma and IL-13 levels were significantly higher in response to PHA and BLG (PHA: IFN-gamma, 6154; IL-13, 4357; BLG: IFN-gamma, 801; IL-13, 249 pg/ml) compared to unstimulated cell cultures. The addition of IL-18 to PHA or BLG stimulated CBMC significantly enhanced the IFN-gamma release (PHA: 6154; PHA + IL-18: 13474, p = 0.0001; BLG: 801; BLG + IL-18: 1077, p = 0.008). In comparison to incubation without IL-18, the release of IL-13 was invariable or even reduced, when CBMC were stimulated with PHA + IL-18 (4026, p = 0.16) or BLG + IL-18 (124, p = 0.0001) compared to stimulation of CBMC with PHA (4357 pg/ml) or BLG (249 pg/ml) alone. IL-18 is detectable in supernatants of CBMC. We observed a significant effect of IL-18 + PHA as well as IL-18 + BLG on IFN-gamma release in vitro. Based on our findings we conclude that IL-18 could act as a strong TH1-inducing factor on stimulated CBMC also in vivo.Cytokine 03/2004; 25(4):172-8. · 3.02 Impact Factor -
Article: Urinary leukotriene E4 levels in children with allergic rhinitis treated with specific immunotherapy and anti-IgE (Omalizumab).
[show abstract] [hide abstract]
ABSTRACT: Recently, we were able to demonstrate that Omalizumab, a humanized monoclonal anti-IgE antibody, reduces in vitro leukotriene (LT) release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy. The aim of this study was to investigate the effect of anti-IgE in combination with specific immunotherapy (SIT) on urinary leukotriene E4 (LTE4) levels. Children and adolescents with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomized to receive SIT for either birch or grass pollen and to receive either subcutaneous anti-IgE or placebo for 24 weeks during the pollen season. From a total population of 225 children, we collected three urine samples in a subgroup of 19 children [n = 12 boys (63%); mean age 11.8 years; range 7.2-17.5 years; Group A (n = 10): SIT (grass or birch) + anti-IgE; Group B (n = 9): SIT (grass or birch) + placebo]. Urine samples were collected before, during and at the end of treatment. Endogenous urinary LTE4 was separated by high-performance liquid chromatography (HPLC) and determined by enzyme immunoassay with a specific antibody. No differences in urinary LTE4 concentrations were observed between the anti-IgE and the placebo groups before (A: 35.2; B: 36.5 nmol/mol creatinine), during (A: 27.0; B: 29.3) and after treatment (A: 28.9; B: 26.5 nmol/mol creatinine). We conclude that urinary LTE4 levels are not helpful in monitoring patients treated with anti-IgE and SIT.Pediatric Allergy and Immunology 11/2003; 14(5):401-4. · 2.46 Impact Factor -
Article: Urinary leukotriene E4 levels in children with allergic rhinitis treated with specific immunotherapy and anti‐IgE (Omalizumab)
[show abstract] [hide abstract]
ABSTRACT: Recently, we were able to demonstrate that Omalizumab, a humanized monoclonal anti-IgE antibody, reduces in vitro leukotriene (LT) release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy. The aim of this study was to investigate the effect of anti-IgE in combination with specific immunotherapy (SIT) on urinary leukotriene E4 (LTE4) levels. Children and adolescents with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomized to receive SIT for either birch or grass pollen and to receive either subcutaneous anti-IgE or placebo for 24 weeks during the pollen season. From a total population of 225 children, we collected three urine samples in a subgroup of 19 children [n = 12 boys (63%); mean age 11.8 years; range 7.2–17.5 years; Group A (n = 10): SIT (grass or birch) + anti-IgE; Group B (n = 9): SIT (grass or birch) + placebo]. Urine samples were collected before, during and at the end of treatment. Endogenous urinary LTE4 was separated by high-performance liquid chromatography (HPLC) and determined by enzyme immunoassay with a specific antibody. No differences in urinary LTE4 concentrations were observed between the anti-IgE and the placebo groups before (A: 35.2; B: 36.5 nmol/mol creatinine), during (A: 27.0; B: 29.3) and after treatment (A: 28.9; B: 26.5 nmol/mol creatinine). We conclude that urinary LTE4 levels are not helpful in monitoring patients treated with anti-IgE and SIT.Pediatric Allergy and Immunology 10/2003; 14(5):401 - 404. · 2.46 Impact Factor -
Article: The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis.
[show abstract] [hide abstract]
ABSTRACT: Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587 ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition, treatment with anti-IgE was also followed by significantly lower SLT releases to the allergens unrelated to SIT (grass SIT: 300 ng/L [1-2432 ng/L] in response to birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch SIT: 2792 ng/L [154-5839 ng/L], P =.04]. Anti-IgE therapy reduces leukotriene release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy independent of the type of SIT allergen used.Journal of Allergy and Clinical Immunology 12/2002; 110(5):728-35. · 11.00 Impact Factor
Top co-authors
Top Journals
Institutions
-
2011
-
Universität zu Lübeck
- Klinik für Kinder- und Jugendmedizin
Lübeck, Schleswig-Holstein, Germany
-
-
2009
-
Ruhr-Universität Bochum
Bochum, North Rhine-Westphalia, Germany
-
-
2002–2008
-
Universitätsklinikum Freiburg
Freiburg, Lower Saxony, Germany
-
-
2003
-
Universität Freiburg
Freiburg, Lower Saxony, Germany
-
