Fractional exhaled nitric oxide (FeNO) is elevated in asthma and reflects eosinophilic airway inflammation. The aim of this prospective, randomized, single-blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome. Forty-seven children with mild to moderate asthma were allocated to a FeNO group (n = 22) and to a control group (n = 25). In the FeNO group therapy was based on symptoms, beta-agonist use, lung function, and FeNO whereas in the control group therapy was based on symptoms, beta-agonist use and lung function only. Patients performed five visits in 6 weeks intervals. Frequency of respiratory symptoms, beta-agonist use, FEV(1)% predicted and the frequency of exacerbations were similar between groups. Patients in the FeNO group received higher doses of inhaled corticosteroids (ICS) (control group: median (interquartile range): 241 microg (26-607 microg); FeNo group: 316 microg (200-500 microg) and had significantly higher MEF(50)% predicted (control group: median (interquartile range): 68.5% (55.8-83.1%); FeNO group: 83.2% (62.9%-98.3%). At a cut-off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80% and specificity of 60% was found. Significant relationships were observed between FeNO and dose of ICS (beta = -8.77; P < 0.002), beta-agonist use 2 weeks prior to a visit (beta = 0.11; P < 0.05), asthma symptoms (beta = 0.02; P < 0.0001), and bronchial hyperresponsiveness (beta = 0.04; P = 0.02). In conclusion, FeNO was related to important markers of asthma control. A therapy regimen aimed at lowering FeNO in children with asthma improved parameters of small airway function, but was not able to improve clinical markers of asthma control.

We propose a role for Th17 and Th2 T cells in chronic inflammation in lungs of patients with CF. High concentrations of these cytokines/chemokines in CF airways precede infection with P. aeruginosa.

Prebiotic oligosaccharides are present in breast milk and evidence is pointing toward immunomodulatory properties of the acidic fraction. Recently, prebiotic supplements of infant formula [short-chain galacto (scGOS)-, long-chain fructo (lcFOS)-oligosaccharides] showed preventive effects on atopic disease development. We aimed to define the direct immunologic effects of these oligosaccharides and of human (aHMOS) and cows' milk (aCMOS) acidic oligosaccharides and to investigate the systemic uptake of prebiotic supplements of infant formula and a specific pectin-derived acidic oligosaccharide hydrolysate (pAOS) in vitro. After assurance of LPS-free conditions (limulus assay, toll like receptor-2, -4 transfected human embryonic kidney-cells), in vitro-transfer through a CaCo-2 cell monolayer was measured using high-pH anion exchange chromatography with pulsed amperometric detection. Direct effects on proliferation, cytokine-induction of cord blood mononuclear cells and modulation of allergen-specific CD4+ T-cell cytokine profiles from allergic and non-allergic individuals were investigated. Transfer of scGOS/lcFOS and pAOS in-vitro was detected with a rate of transfer of 4-14%, depending on the molecular size and structure. AHMOS induced IFN-γ and IL-10 but not the Th-2 cytokine IL-13 at physiologic concentrations (10-100 μg/ml) in cord blood, whereas aCMOS did not induce any of these cytokines. AHMOS significantly suppressed Th-2 type cytokine-production by Ara h1-specific CD4+ T cells (CFSE(low) CD3(+) CD4(+) cells) from peanut allergic patients. In conclusion, human milk-derived acidic oligosaccharides may modulate postnatal allergen-specific immune responses by the suppression of Th-2-type responses in atopy-prone individuals. Moreover, there is in vitro evidence for epithelial transport of prebiotic oligosaccharides.

Anaphylaxis is the most severe reaction of an IgE-mediated hypersensitivity. Data about affected patients may help to improve our knowledge of anaphylaxis and its medical care. We analysed data from the anaphylaxis registry of German speaking countries with regard to the provoking allergens and treatment modalities of anaphylaxis in children and adolescents. Inclusion criteria were severe systemic allergic reactions with concomitant pulmonary and/or cardiovascular symptoms. The data are collected by a password-controlled online-questionnaire. For this analysis, data of 197 reported anaphylactic reactions from children and adolescents registered between 2006 and 2009 were included. The data show that within the registered cases the most frequently affected organ systems for children and adolescents were the skin (89%) and the respiratory tract (87%) followed by symptoms of the cardiovascular system (47%) and the gastrointestinal tract (43%). The most frequent elicitors were food allergens accounting for 58% of cases, followed by insect venom (24%) and drugs (8%). The most frequent food allergens were peanuts followed by tree nuts and animal related food products. In 18% aggravating factors such as physical exercise were noted by the clinicians. 26% of the analysed patients had experienced more than one reaction. The data regarding the emergency treatment show that antihistamines (87%) and corticosteroids (85%) were often used but that adrenaline was rarely used (22% of the registered cases). Taken together these data show that the analysis of anaphylaxis by registration of affected individuals can provide data about provoking allergens and treatment measures but also suggest the impact of aggravating factors on anaphylactic reactions. The under-represented usage of adrenaline indicates the need of educational measures for patients and their physicians.

The recognition of allergen by cord blood cells indicates that allergen priming must occur prenatally. The relevance for subsequent sensitization is unclear.

This birth cohort provides unique data on prevalence, risk factors, quality-of-life, and costs of food allergies in Europe, leading to the development of more informed and integrated preventative and treatment strategies for children with food allergies.

Twenty-five T cell clones specific for Bet v I were established from the peripheral blood of two birch pollen-allergic patients. The T cell epitopes of these clones were mapped using dodecapeptides overlapping for 2 amino acids (neighbors share 10 residues) spanning the whole amino acid sequence of the protein (159 amino acids). In total, 7 epitopes could be detected. One donor displayed 6 distinct T cell specificities for the Bet v I molecule in 14 T cell clones; for the other donor, 4 stimulating peptides for 11 clones could be identified. Two T cell epitopes were recognized by both subjects. One of these might represent an immunodominant epitope located at amino acid position 77-92 of the Bet v I molecule, as in 13/25 T cell clones activation could be induced by this amino acid sequence. One T cell clone reacted with purified pollen-derived Bet v I, but neither with any peptide synthesized according to a Bet v I-encoding cDNA nor with the respective recombinant protein. Upon stimulation with allergen, the majority of the clones (21/24) revealed the TH0 or TH2 type of cytokine production (interleukin-4 production), indicating their importance in the pathogenesis of the allergic disease.

Human milk contains large amounts of free oligosaccharides (HMOs). HMOs have been shown to exert antiinflammatory properties, and evidence for their immunomodulatory effects is increasing. The purpose of this study was to evaluate influences of two human breast milk-derived oligosaccharide samples (neutral and acidic oligosaccharides), and of a low-molecularweight fucoidan on cytokine production and activation of cord blood mononuclear cells. Cord blood mononuclear cells from randomly chosen healthy newborns were co-cultured with the oligosaccharide samples. By means of flow cytometry, intracellular cytokine production (d 20) and surface marker expression of T cells (d 5) were measured. In vitro-induced Ig levels were quantified nephelometrically (total IgG1) and by ELISA (total IgE) in the supernatant of cell cultures. The acidic oligosaccharide fraction increased the percentage of interferon-␥ producing CD3ϩCD4ϩ and CD3ϩCD8ϩ cells (p Ͻ 0.05) and the IL-13 production in CD3ϩCD8ϩ cells (p Ͻ 0.05). In acidic oligosaccharide cultures, CD25ϩ expression on CD3ϩCD4ϩ cells was significantly elevated (p Ͻ 0.05). Low-molecular-weight fucoidan induced IL-4 production in CD3ϩCD4ϩ T cells (p Ͻ 0.05) and IL-13 production in CD3ϩCD8ϩ T cells (p Ͻ 0.05), whereas interferon-␥ production remained unaffected in both T-cell populations. Ig production (total IgE and total IgG1) remained unaffected. Human milk-derived oligosaccharides and plant-derived oligosaccharides affect the cytokine production and activation of cord blood derived T cells in vitro. Therefore, oligosaccharides and, in particular, acidic oligosaccharides may influence lymphocyte maturation in breast-fed newborns. The postnatal period is a crucial time for the maturation of the immune system. At birth, T-lymphocytes exhibit a Th2-profile, characterized by a limited ability to produce cytokines. Throughout the first months after birth these Th2-skewed responses are modified into low-level immunity, predominantly expressing Th1-cytokines and IgG-antibodies, particularly of the IgG1 subclass (1,2).Human milk is a biologic fluid containing large amounts of free oligosaccharides. HMOs represent the third largest solid component (after lactose and lipids) in breast milk, occurring at a concentration of 20 -23 g/L in colostrum and 12-14 g/L in mature milk (3). HMOs are very resistant to enzymatic hydrolysis (4,5), indicating that these oligosaccharides must display essential nonnutritive functions.Throughout the last decade, numerous studies demonstrated the ability of HMOs to inhibit pathogens acting as receptors for microbes (6,7). Only a few reports on direct effects on immune function have been published so far. Human milk oligosaccharide structures like lacto-N-fucopentaose III (LNFPIII) and lacto-N-neotetraose (LNneoT) showed an effect on murine IL-10 production (8). It is further discussed that human milk is involved in the generation of antiinflammatory mediators that suppress Th1-type and inflammatory responses in mice (9). 0031-3998/04/5604-0536 PEDIATRIC RES...