Stefan Zielen

Elevated Oxidative Stress in Patients with Ataxia Telangiectasia

Ataxia telangiectasia (AT) is a pleiotropic genetic disorder characterized by progressive neurodegeneration, especially of cerebellar Purkinje cells, immunodeficiency, increased incidence of cancer, and premature aging. The disease is caused by functional inactivation of the ATM (AT-mutated) gene product, which is thought to act as a sensor of reactive oxygen species and oxidative damage of cellular macromolecules and DNA. The compound phenotype of AT might thus be linked to a continuous state of oxidative stress leading to an increase of programmed cell death (apoptosis). To assess this hypothesis, we analyzed lipid peroxidation products and the oxidative stress associated DNA base damage 8-hydroxy-2-deoxyguanosine in patients with AT. Oxidative damage to lipids and DNA was found to be markedly increased in AT patients. These results indicate that ATM might play an important role in the maintenance of cell homeostasis in response to oxidative damage. In this context, a better control of levels of reactive oxygen species could be a rational foundation of therapeutic intervention to help alleviate some of the symptoms associated with AT.

Lipid-laden alveolar macrophages (LLAM): A useful marker of silent aspiration in children

At present there is no test available which identifies children suffering from silent aspiration due to gastroesophageal reflux (GER). The purpose of this study was to determine whether lipid‐laden alveolar macrophage (LLAM) scoring is a useful method to arrive at the diagnosis. We evaluated bronchoalveolar lavage fluid (BALF) from 68 children aged 6 months to 14 years (median 3.75 years) for the presence of lipid‐laden alveolar macrophages. We compared children with chronic chest disease (CCD) and GER to healthy surgical controls without known lung disease, and to children with recurrent pneumonia without GER. By grading the amount of intracellular Sudan Red‐positive material, we determined a semiquantitative lipid‐laden macrophage (LLAM) score for each patient.

The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children

Background: Specific immunotherapy (SIT) and treatment with anti‐immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment.

Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: a randomized controlled trial.

BACKGROUND Asthma control is now recognized as the main goal of asthma therapy. Guidelines recommend finding the lowest effective dose of inhaled corticosteroids in children with persistent asthma. OBJECTIVE The aim of this study was to investigate the efficacy of an allergen-specific immunotherapy with a high-dose hypoallergenic mite preparation (allergoid) as steroid-sparing agent in children with allergic asthma. METHODS Sixty-five children with asthma (Global Initiative for Asthma treatment levels II and III; 6-17 years old), after reaching asthma control with inhaled steroids during a 5-month baseline period, were randomized for subcutaneous mite allergoid immunotherapy (SCIT) plus fluticasone propionate (FP) or FP therapy alone for 2 years. During 2 subsequent 5-month winter periods, steroid therapy was adjusted according to predefined dose steps, determining and comparing the changes in FP dosages and the lowest FP dose sufficient to maintain asthma control. Immunologic and functional investigations were also carried out. RESULTS Children treated with house dust mite SCIT plus FP were able to significantly reduce the FP dose by more steps (P < .05), compared with the control group on FP alone. The mean daily dose in the immunotherapy group decreased from 330.3 μg in the baseline period to 151.5 μg after 2 treatment years, whereas in the control group the dose decreased from 290.6 μg to 206.3 μg. Compared with the control group, significant improvement was also observed in morning peak expiratory flow (P = .0315). Significantly increased levels of specific IgG(1) (P = .0001) and IgG(4) (P < .0001) were also observed. CONCLUSION Adding a mite allergoid SCIT to pharmacologic treatment is an effective and safe strategy to reduce corticosteroid doses while maintaining disease control in children with mite-induced allergic asthma.

Efficacy of probiotic Lactobacillus GG on allergic sensitization and asthma in infants at risk

Background Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases.

Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) and association between pulmonary function.

Lung diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are associated with chronic airway inflammation. The aim of our study was to compare a complex biomarker profile in order to characterize specific inflammatory patterns in sputum of patients with CF and COPD. Induced sputum samples of 19 CF-, 26 COPD patients and 21 healthy controls were analyzed for concentrations of IL-1beta, IL-2, IL-6, IL-8, IL-13, IP-10, MCP-1, IFN-gamma and TNF-alpha using the new cytometric bead array (CBA) technology. Significant differences in airway biomarker profiles of CF and COPD were detected. Patients with CF showed a significant increase in IL-1beta, IL-6, IL-8, IL-13, TNF-alpha, IFN-gamma and MCP-1. COPD patients showed an increase in IL-6, IL-8, IL-13 and MCP-1 compared to healthy controls. CF and COPD compared to each other exhibited differences in IL-1beta, IL-2, IL-8, TNF-alpha, IFN-gamma and MCP-1 levels. Significant correlations between the parameters of lung function and sputum biomarker levels were found. Analyzing induced sputum allows characterization of specific airway biomarker profiles in CF and COPD and can be related to the clinical status of the patient. CBA of induced sputum seems to be a pivotal tool to characterize pulmonary inflammation.

Beekeepers anaphylaxis: successful immunotherapy covered by omalizumab

been reported as an allergen up till now. To our knowledge, there have only been six studies in which cases of allergy to lychee were reported. In one of these (1) a 16 kDa profilin (Lit c 1) was identified, which cross-react with that of Compositae plants, including sunflower seed. Niggemann et al. (2) described a case of cross-reactivity between lychee and latex by CAP inhibition but without identifying the responsible allergen. In the other four cases published (3–6) only a description of the reactions which occurred after lychee ingestion was given but no mention was made of the allergenic proteins responsible for these.

Lung clearance index: Evidence for use in clinical trials in cystic fibrosis

The ECFS-CTN Standardisation Committee has undertaken this review of lung clearance index as part of the groups work on evaluation of clinical endpoints with regard to their use in multicentre clinical trials in CF. The aims were 1) to review the literature on reliability, validity and responsiveness of LCI in patients with CF, 2) to gain consensus of the group on feasibility of LCI and 3) to gain consensus on answers to key questions regarding the promotion of LCI to surrogate endpoint status. It was concluded that LCI has an attractive feasibility and clinimetric properties profile and is particularly indicated for multicentre trials in young children with CF and patients with early or mild CF lung disease. This is the first article to collate the literature in this manner and support the use of LCI in clinical trials in CF.

Mucosal immunity and nasal influenza vaccination

Influenza remains a threat to public health, with immunization being a suitable method of infection prevention and control. Our understanding of the immunological regulations at the mucosa, antigen processing and presentation, and B-cell activation has improved, enabling research and targeted induction of immune responses at the site of antigen delivery. Nasal influenza immunization has distinct features compared with intramuscular vaccines, providing protection at the pathogen’s entry site, higher levels of mucosal antibodies, cross-protection and needle-free application. This review summarizes our knowledge about mucosal immunity and the experience from clinical trials on the impact and safety of nasal influenza vaccination.

Comprehensive Phenotypic Characterization of Human Adipose-Derived Stromal/Stem Cells and Their Subsets by a High Throughput Technology

The characterization of adipose-derived stromal/stem cells (ASCs) remains difficult due to the lack of a definitive and unique cellular marker. Therefore, a combination of markers is necessary to identify the cells. No comprehensive analysis of the immunophenotype of expanded plastic adherent ASCs has been published. Therefore, the aim of this study was to characterize the general phenotype of cultured ASCs and to further analyze cellular subsets. ASCs were isolated from lipoaspirates from patients undergoing cosmetic liposuction and cultured in standard cell culture. A comprehensive phenotype characterization was done with the BD Lyoplate™ Human Cell Surface Marker Screening Panel containing 242 antibodies and isotype controls. Cultured ASCs not only showed the characteristic expression profile of mesenchymal stem cells (MSCs), but also revealed donor-specific variability in the expression of 49 other markers. We further detected markers with a scattering in the fluorescence intensity, indicating subpopulations with different expression profiles. Therefore, a multi-color flow cytometric analysis was done after staining the cells with direct-labeled antibodies against CD73, CD90, CD105, and either CD34, CD140b, CD200, CD201, or CD36 to verify the selected subpopulations of ASCs. We detected no CD34-CD36 double-positive population, but CD34(+)-CD36(-) and CD34(-)CD36(+) subpopulations, both of which are positive for the 3 main MSC markers, CD73, CD90, and CD105. All other detected subpopulations also co-expressed the 3 main MSC markers, and therefore fulfill the minimal phenotypic criteria for the definition of cultured MSCs. Our study demonstrates the first comprehensive phenotypic characterization of ASCs and clearly highlights donor-specific variability in ASC preparations.