Thesis (doctoral)--Köln, 1988.

Yes / Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. Methods: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication,and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. Results: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63,-0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores.Conclusions: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy. / EAACI and BM4SIT project (grant number601763) in the European Union’s Seventh Framework Programme FP7.

Asthma is .a respiratory.,disease.that affects over 300 million people world-wide and is involved in over 250000 deaths annually. Asthma is classically thought of as an allergic disease with variable airflow obstruction and airway hyperresponsiveness (AHR) associated with airway remodeling, although phenotype variations are observed in the population. Due to multiple factors including genes, gender, exposure to pathogens, environmental pollutants, diets, and obesity, a clear picture of the complex interactions between an individual's genes, the environment which they live in, and the development of an asthmatic phenotype remains elusive. Despite the availability of treatment strategies for asthma, varying degrees of airway inflammation, remodeling, and AHR remain present in an asthmatic patient. Our general hypothesis that was the basis for all studies was the following: "Airway remodeling in response to allergen exposure is a major contributing factor to AHR observed in asthmatics. Understanding the mechanisms behind the different components of airway remodeling will provide new avenues for therapeutic development aimed at improving lung function above and beyond current treatment strategies." The currently available therapeutics and management strategies for asthma are unable to prevent or reverse components of airway remodeling. It is possible that with greater understanding of the processes involved in the various indices of airway remodeling new classes of therapeutics could be developed to selectively target this broad, ill-managed aspect of asthma. Collectively the studies contained in this thesis have been linked by the general themes of greater characterization of in vivo mouse models of allergen exposure, the application of these models to mechanistically explore the biological pathways involved in the different components of airway remodeling, and the testing of novel therapeutic strategies targeting these pathways of interest. / Thesis / Doctor of Philosophy (PhD)

Among the environmental airborne fungi one of the most common is <i>Alternaria alternata</i>. From a clinical perspective Alternaria has long been associated with IgE-mediated, histamine-dependent mold allergy, allergic rhinitis, chronic rhinosinusitis (CRS) and asthma. Recently it has been proven that an abnormal immunological response to Alternaria most likely contributes to the pathogenesis of upper respiratory airway disorders. In this body of work, we present for the first time results of several sets of experiments including, 1) the analysis of A. alternata spore germination expressed sequence tags (ESTs), 2) the survey of global allergen homologues in fungal genomes, and 3) the first microarray experiment investigating airway epithelial cell responses to this fungus. In the first project, the analyses of the EST dataset offered a first look into the gene content of A. alternata and represents the beginning of future research of this ubiquitous fungus. Annotation and classification of ESTs revealed a number of genes that could be involved in the immunomodulation process of the human immune response toward fungi. We also discovered that the majority of known allergens are expressed during the spore germination phase of A. alternata. For investigating the allergenic potential of fungi we developed a whole genome approach by querying fungal genome sequences (<i>A. alternata, A. brassicicola,</i> and <i>Aspergillus fumigatus</i>) with a database of all known allergenic proteins from a taxonomically diverse group of organisms. Interestingly, we identified homologues of diverse types of allergens in these fungal genomes and also many homologues of allergens from other organisms including those from pollen, insects, and venoms. Finally, we investigated global gene expression changes of human airway cells in response to <i>A. alternata</i> and an ∆alt a 1 deletion mutant. We found that wild type Alternaria spores induced significant changes in gene expression patterns in human airway epithelial cells, especially known immune response genes. Furthermore, results of these analyses revealed that Alt a 1 is a major factor in inducing epithelial inflammatory responses. / Ph. D.

No description available.

The purpose of this manuscript was to present a brief history, the current status, and a prospectus of allergen and allergic reactions. Research on allergic reactions, particularly as viewed from the psychogenic position, was presented. The review strongly suggests that the psychogenic orientation has been frought with contradictions, unnecessarily complex interpretations, and an over-abundance of subjective, dynamic, and analytic redundancies which have done little more than perpetuate the stagnation of a rather important subdomain of the "mental" health professions.

Techn. Universiẗat, Diss., 2006--München.

Univ., Diss., 2006--Giessen

Introduction: Wheat is one of the most cultivated cereal grains in the world and is used for the manufacture of a wide range of food products; however its consumption has been linked to several health issues. Food products containing wheat flour commonly elicit a high glycaemic response (GR) through rapid breakdown of starch and absorption of the resulting glucose. Regular over-consumption of such foods has been linked to obesity and development of type 2 diabetes. Dietary fibre may alter GR after meal consumption indirectly through modification of chyme viscosity. Wheat can also elicit immune-mediated adverse reactions, such as immunoglobulin E(IgE)-mediated wheat allergy and coeliac disease (CD), which are most often associated with gluten proteins consisting of gliadins and glutenins. Resistance to digestion may impact the allergenicity of such protein components. Digestion of gluten and its epitopes important for CD have been enhanced in vitro and in vivo using a prolyl endopeptidase from Aspergillus niger (AnPEP) however the impact on IgE-mediated allergy has yet to be considered. Additional information is needed about the digestion of wheat. Specifically the impact of food matrix, digestion conditions and effect of AnPEP require further investigation. Methods: First, the effect of food matrix on proteolysis was tested by in vitro batch oral-gastric digestion of a purified total gliadin fraction (TGF), flour and bread. As the most physiologically relevant material, bread was also processed through the duodenal/intestinal phase in varying conditions to assess the impact of enzyme inclusions on macronutrient breakdown. Second, results from the batch digestions were compared to bread digestion in dynamic models, where the effect of natural variations in soluble fibre was also tested. Increasing levels of AnPEP were used in two in vitro batch oral-gastric models. Protein breakdown in digestions was assessed using a combination of 1D PAGE, immunoblots with a variety of wheat-specific antibodies, kinetic analysis and inhibition ELISA. Immunoassays were performed with sera from 23 wheat-allergic patients and some digestions were analysed in terms of starch digestion. Finally, LC-MS/MS was used to obtain specific sequence information and relative intensity of peptides from in vitro batch model digestions. Thus, digestion of selected allergens and key epitopes was monitored. Results and Discussion: Wheat proteins were very resistant to in vitro batch gastric digestion in bread compared to the TGF, with flour proteins somewhat intermediate. Thus, studies digesting purified proteins are not always indicative of protein digestion in a processed food matrix. Digestion of bread protein was enhanced by starch digestion and vice versa. This has implications for patients with deficiency in pancreatic amylase, which is often observed in childhood, so may play a role in food allergy development by influencing polypeptides reaching the gut mucosa. Digestion model conditions also had a large impact on wheat protein digestibility with differences observed between batch and dynamic models, and the two batch models used. This may reflect biological variations observed in vivo. Unexpectedly, the wheat cultivar with higher soluble fibre digested slightly more quickly which may be due to alterations in other macronutrients present. In most cases patient sera were poly-sensitized to a number of wheat proteins and IgE-binding was mostly unaffected by baking. Gastric digestion reduced IgE-reactivity of bread but large polypeptides of high relative intensity remained. Addition of AnPEP further reduced IgE-reactivity of digestion samples by digesting gluten proteins into smaller peptides of lower relative intensity. This reduced the presence of epitopes important for IgE-mediated allergy and CD. Therefore, AnPEP may have an application for treatment of accidental wheat consumption for patients with IgE-mediated wheat allergy.

Airway hyperresponsivness (AHR) is one of most prominent pathophysiological features of asthma. Increasing evidence suggests that vagal bronchopulmonary afferents may be involved in the development of AHR. However, the underlying mechanisms are not clear. Therefore, the purpose of this dissertation was to investigate the effect of chronic airway inflammation induced by allergen sensitization on vagal bronchopulmonary afferents. The study was carried out in an animal model of allergic asthma. Brown-Norway rats were sensitized by intraperitoneal Ovalbumin (Ova) and exposed to aerosolized Ova 3 times/week for three weeks. Control rats received the vehicle. In vivo single-fiber recording technique was applied in this study. Our results showed that chronic Ova exposure caused an elevated baseline activity of pulmonary Cfibers, and a distinctly higher sensitivity of these afferents to chemical stimulants and lung inflation. After an acute Ova inhalation challenge, the increase in baseline activity and the excitability of pulmonary C-fibers were further augmented in sensitized rats, but not in control rats. In addition, sensitivity of pulmonary myelinated afferents to capsaicin was significantly elevated after chronic airway inflammation was induced by allergen. Furthermore, immunohistochemsitry data showed that, in nodose ganglia the proportion of transient receptor potential vanilloids type 1 channels (TRPV1)-expressing bronchopulmonary neurons was significantly higher in sensitized rats than in controls. This increase of TRPV1 expression was found mainly in neurofilament-positive neurons (myelinated neurons), but this effect was absent in jugular ganglia. In conclusion, allergen-induced airway inflammation caused a pronounced sensitizing effect on vagal pulmonary non-myelinated (C-fiber) afferents and elevated the sensitivity of vagal pulmonary myelinated afferents to capsaicin. The latter was accompanied by the upregulation of TRPV1 expression in these myelinated neurons.