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Purpose Numerous studies have demonstrated effectiveness for acupuncture in the treatment of seasonal allergic rhinitis (SAR). However, the underlying mechanism remains still unclear. Methods 29 SAR patients were recruited from a large randomized, controlled trial investigating the efficacy of acupuncture in SAR. 16 patients were treated by acupuncture plus rescue medication (RM, cetirizine), 6 patients received sham acupuncture plus RM and 8 patients RM alone over 8 weeks. Patients were blinded to the allocation to real or sham acupuncture. At baseline and different time-points during intervention, plasma and nasal concentration of mediators of various biological functions were determined in addition to validated disease-specific questionnaires. Results The concentration of biomarkers related to the Th1-, Th2-, and Treg-cluster was not changed in patients who received acupuncture, in neither plasma nor nasal fluid. However, with respect to eotaxin and some unspecific pro-inflammatory cytokines (IL-1b, IL-8, IP-10, MIP-1b, MCP-1), acupuncture led to a, partially significantly, lower nasal concentration than sham acupuncture or RM. Furthermore, the nasal symptom score was significantly reduced in patients only after real acupuncture. Conclusion In SAR, acupuncture reduces the intranasal unspecific inflammation, but does not seem to act immunologically on the Th1–Th2-imbalance.

Catalina Högerle, Marion San Nicolo, Donata Gellrich, Katharina Eder, Moritz Gröger Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University Munich, München, GermanyCorrespondence: Catalina Högerle, Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maiximilians-Universität München, Marchioninistr. 15, München, D- 81377, Germany, Tel +49 89 4400 73892, Fax +49 89 4400 76892, Email catalina.hoegerle@med.uni-muenchen.dePurpose: Many plant food allergens contain homologs to the major birch allergen Bet v 1; therefore, the majority of patients with birch pollen allergy suffer from oral allergy syndrome. We studied the relevance of sensitization of Bet v 1 and co-sensitization with profilin concerning the clinical manifestations of an oral allergy syndrome.Patients and Methods: A total of 1119 patients with a positive skin prick test to birch and diagnostic for specific IgE to the allergen components Bet v 1 and profilin were analyzed retrospectively regarding complaints in the upper and lower airways, with demographic data as well as oral and gastrointestinal allergy symptoms.Results: Patients with simultaneous specific IgE to the allergen components Bet v 1 and profilin have to deal more often with an oral allergy syndrome and intestinal reactions. They also suffer more frequently and severely from rhinitis symptoms and show a higher tendency for asthma. No increased number of systemic reactions was seen.Conclusion: Patients with birch allergy recognizing both allergens have more probabilities of suffering from an oral allergy syndrome, and allergologists should be aware of this in order to give better advice to their patients.Keywords: oral allergy syndrome, clinical relevance of allergens, birch pollen sensitization, profilin co-sensitization, component resolved diagnostic

ACE inhibitor (ACEi) induced angioedema predominantly affects the upper aerodigestive tract. As ACEi induced angioedema is mediated by bradykinin, therapeutic response to antihistamines and glucocorticoids remains unsatisfactory. In bradykinin mediated hereditary angioedema, C1-esterase inhibitor (C1INH) is an effective and approved treatment since many years. Our aim was to evaluate the therapeutic effect of C1INH in ACEi induced angioedema.We performed a double-blind, parallel-group, multicentre randomised placebo-controlled trial between December 2013 and September 2018. Eligible were adults with ACEi induced angioedema with airway obstruction. Participants were randomised 1:1 to single doses of either C1INH (20 IU/kg) or placebo (0.9% NaCl) i.v in addition to standard care (i.v. 500 mg prednisolone and 2.68 mg clemastine) i.v. Composite symptom scores were assessed at baseline and up to 48 h, at discharge and 1 week after discharge. Physician assessed time to complete oedema resolution (TCER) and time to onset of relief (TOR).30 patients (16 C1INH, 14 placebo) were randomised and dosed. 25 (9 C1INH, 12 placebo) completed the study. TCER was 29.63 h ± 15.56 h in the C1INH and 17.29 h ± 10.40 h in the placebo arm (p = 0.0457). TORs were 4.13 h ± 3.38 h and 2.86 h ± 1.29 h for C1INH and placebo, respectively (p = 0.4443). There were no adverse events related to study medication.In the context of baseline application of steroids and antihistamines C1INH was inferior in the treatment of ACEi induced angioedema when compared to placebo with respect to time to complete resolution of symptoms. Eudra-CT Number: 2012-001670-28.

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Introduction: Sensitization to Aspergillus fumigatus is a risk factor for severe asthma. However, little is known about its presence, appearance, and impact on allergic rhinitis. Herein, we investigated the usefulness of component resolved diagnostics in patients sensitized to Aspergillus fumigatus protein extract. Methods: Seventy-eight patients with suspected allergic rhinitis and elevated IgE levels toward Aspergillus fumigatus protein extract were retrospectively evaluated regarding their total and Aspergillus-specific IgE levels and their skin prick test. Furthermore, they were tested for specific IgE antibodies against Asp f 1, 2, 3, 4, and 6. Results: Skin prick test missed 6 patients (7.7%) with elevated IgE toward Aspergillus fumigatus protein extract. Fifty percent of patients (n = 39) were sensitized to at least one component. Even though monosensitization affected all components, all patients with positivity toward more than one component were sensitized to Asp f 1. There was a statistically significant increase of Aspergillus-specific IgE with increasing number of components affected by sensitization. Many patients were oligo- (34.6%) or polysensitized (51.3%). There was a high prevalence of sinusitis (61.8%). Conclusions: Component resolved diagnostic testing toward the major allergen Asp f 1 was less sensitive than skin prick test and serology to Aspergillus fumigatus protein extract. However, sensitivity of component resolved diagnostics might be underestimated. Diagnostics of the species-specific allergens Asp f 1, 2, and 4 might allow to differentiate between genuine and cross-reactive sensitization. In the clinical routine, skin prick test and serology to crude extract remain the methods of choice.

Regulatory and economic conditions drive the application of the concept of homologous groups on therapeutic and diagnostic formulations. In this context, a possible reduction of allergens in the skin prick test panel in the clinical routine should be investigated for the grass, birch and Dermatophagoides homologous group. Grass and cultivated rye skin prick test results of 1101 patients, birch/hazel/alder skin prick test results of 1131 patients and 1068 Dermatophagoides pteronyssinus and farinae skin prick tests were retrospectively evaluated with regard to sensitivity and false-negative rate detecting sensitization against cultivated rye with grass skin prick test, sensitization against hazel and/or alder with birch skin prick test and sensitization towards Dermatophagoides farinae with Dermatophagoides pteronyssinus skin prick test. Skin prick test results in all groups highly correlated in Spearman Rank Order correlation. Sensitivity of grass skin prick test detecting sensitization against cultivated rye was highest with 98.9%, sensitivity of birch skin prick test detecting sensitization toward hazel and alder was 95.6 and 90.0%, respectively. Sensitivity of skin prick test with Dermatophagoides pteronyssinus detecting sensitization towards Dermatophagoides farinae was 93.6%. Only 26 patients with positive rye, hazel, alder or Dermatophagoides farinae skin prick test that were overlooked by grass, birch or Dermatophagoides pteronyssinus skin prick test reported allergic symptoms. In routine clinical practice, sensitization against cultivated rye can safely be detected by skin prick test with grass allergen. In addition, the sensitivity of birch skin prick test is high in terms of sensitization towards hazel, but lower for alder. Sensitivity of Dermatophagoides pteronyssinus skin prick test also is high to detect sensitization towards Dermatophagoides farinae. Further research will indicate if several skin prick test allergens will disappear and be completely replaced by a single skin prick test based on the principle of homologous groups.

Bei rund einem Drittel der Patienten mit Polyposis nasi ist die Erkrankung mit den bisher zur Verfugung stehenden Therapien nur unzureichend zu kontrollieren. Patienten mit schwerer Rezidiv-Polyposis konnten moglicherweise aber schon bald von einer Therapie mit Biologika profitieren. Um welche Praparate es sich handelt, welche Studienergebnisse vorliegen und wie sich die Indikationsstellung und Therapiekontrolle gestalten durfte, erlautert der folgende Beitrag

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but "social support." Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.

Aspirin-exacerbated respiratory disease (AERD) is a severe form of chronic rhinosinusitis with nasal polyps (CRSwNP) accompanied by asthma and an aspirin intolerance. The underlying pathomechanism of AERD still remains unclear, recent data suggest a complex inflammatory imbalance. In the present study, we investigated the cytokine patterns in AERD, CRSwNP and healthy control patients. Furthermore, we describe the change in cytokine level in the course of aspirin desensitization (AD) with continuous intake of aspirin. The study included a total of 104 participants, 48 healthy controls, 45 patients with nasal polyps and 11 patients with AERD undergoing AD. Nasal secretions were analyzed for IL-1β, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, THF-α, IFN-γ, eotaxin and ECP using Bio-Plex Human Cytokine Assay and Uni-CAP FEIA. Baseline measurements of cytokine levels were performed in all 104 patients; in patients with AERD, follow-up was performed 1–6 and 6–24 months after the initiation of AD. Our preliminary results show a TH2 dominated, eosinophilic milieu in AERD patients, which decreased in the first weeks of AD. However, after 6 months of AD, proinflammatory cytokines show a tendency to increase again. Also, TH1 as well as Treg associated cytokine seem to increase over time. For the first time, the present work shows the cytokine pattern in nasal secretions of AERD patients before and during AD. Further investigation of the complex interaction of inflammatory cytokines during AD might reveal important insights into the disease entity of AERD and open up new horizons for a targeted therapy.

Samter triad is a chronic condition where patients suffer from intolerance to aspirin, recurring nasal polyposis and bronchial asthma. Causative treatment is often hard. Potential approaches are the daily intake of acetylsalicylic acid (ASA), shunting arachidonic acid into the lipoxygenase pathway, and a subsequent habituation to this constant inflammatory stimulus. Alternatively, the paramount interleukins 4 and 13 may be antagonized by the monoclonal antibody dupilumab. Hence, we evaluated the daily intake of 100 mg ASA and systemic dupilumab (300 mg s.c. every 2 weeks) therapy in refractory patients for its efficacy and compliance. We conducted a retrospective chart review for the efficacy and compliance of both continuous ASA desensitization and systemic dupilumab therapy for refractory patients. Thirty-one patients were included in this retrospective chart review, mean follow-up was 20.4 ± 15.7 months. All patients underwent ASA desensitization. Twenty-one patients had eventually discontinued therapy after 5.8 ± 4.5 months; 11 for its side effects, 12 for its inefficacy. Twenty patients developed sinunasal complaints soon thereafter. Ten patients were still undergoing desensitization (mean duration 15.3 ± 15.7 months). These patients had a higher prevalence of concomitant anti-asthmatic medication. Seventeen refractory patients underwent systemic dupilumab therapy. After 6.4 ± 2.7 months of treatment, sinunasal outcome test (68.1 ± 13.9 vs 20.1 ± 13.9) and visual analogue scales of overall complaints (8.7 ± 0.9 vs 2.2 ± 1.5) as well as endoscopic findings and olfactory function (brief smell identification test; 3.5 ± 2.6 vs 8.6 ± 2.4) all improved significantly. A considerable number of patients with Samter triad discontinued ASA desensitization, equally for ineffectiveness or side effects. If desensitization is to be effective, special care needs to be taken in respect to concomitant anti-asthmatic medication. Dupilumab is highly effective and safe in treating refractory patients.

Introduction: Weed pollen allergy is an important and in prevalence increasing cause of pollinosis in Europe and across the world. In this study we focus on the value of common diagnostic tools for detection of a sensitization to mugwort and English plantain, especially with regard to the clinical relevance of the sensitization. Methods: Eighty weed pollen sensitized patients (41 to mugwort and 39 to English plantain) were assessed retrospectively regarding their clinical anamnesis, in-vivo tests (skin prick test [SPT] and allergen specific provocation) and in-vitro tests (immunoglobulin E [IgE] reactivity to purified natural allergen extract and specific allergen components in serum). Results: 85% of mugwort and 83% of English plantain sensitizations could be diagnosed by SPT alone. Distinction between allergic and non-allergic patients could be made with clinical challenges solely. IgE serology revealed IgE antibodies against the native pollen extracts for mugwort in 98% and for English plantain in 90% of patients. Detection of major allergens nArt v 1, nArt v 3 and Pla l 1 did not add accuracy to the diagnosis. A vast majority of the weed pollen allergic patients was sensitized to >1 allergen. Minor allergens were found to be of less importance. Conclusion: The exact diagnosis of weed pollen allergy can be challenging due to confounding components in anamnesis and diagnostic tests. IgE-serology does not delineate allergic from sensitized patients. Component resolved diagnostics (CRD) can confirm, but not replace, extract based diagnostic methods, such as SPT, provocation tests or serology to native extracts. Hence, these are the gold standard diagnostic tools in weed pollen allergy up to now.

Purpose For perennial inhalant allergens such as house dust mite (HDM), the German guideline on allergen-specific immunotherapy explicitly recommends provocation testing. This procedure is time-consuming, expensive, and potentially dangerous for the patient. Recently it has been discussed whether provocation tests are really necessary for diagnosing allergy to Dermatophagoides species. Thus, our study aimed to analyze the concordance between nasal provocation tests with Dermatophagoides species and anamnestic data. Methods We retrospectively analyzed the concordance between patients’ histories including self-reported symptom scores and the results of provocation testing in 471 individuals with proven sensitization to Dermatophagoides species. Results 248 patients had a positive nasal provocation test (NPT) result to Dermatophagoides species and 223 individuals a negative NPT result. Patients allergic to HSM suffered significantly more often from atopic dermatitis (14% vs. 7%, p = 0.046) and more from asthma (20% vs. 19%, p = 0.851). Moreover, individuals with clinically silent sensitization complained less about nasal secretion (37% vs. 45%, p = 0.244) but significantly more about nasal dryness (46% vs. 34%, p = 0.046) whereas rates of nasal airway obstruction, ocular complaints and sleep quality were comparable in both groups. Allergic patients reported more often perennial (34% vs. 30%, p = 0.374) and location-dependent (39% vs. 31%, p = 0.090) symptoms. However, the discrepant prevalence of atopic dermatitis was the only statistically significant difference between both groups. Conclusion Despite slight differences between both patient groups, clinical data are not sufficient to distinguish between silent sensitization and clinically relevant allergic rhinitis to HDM. Therefore, nasal provocation testing remains the gold standard for assessing clinical relevance in patients sensitized to Dermatophagoides species.

Background: Recently, population-based birth-cohort studies provided an insight into the allergic march during childhood.Aims: Our study aimed to investigate sensitization pattern until advanced ag...

Background Allergic rhinitis (AR) continues to increase in incidence and is the most common allergic disease. If abstention of the allergen triggering substances is not possible, allergen-specific immunotherapy (AIT) as causal treatment or a drug therapy with mast cell stabilizers, antihistamines (AHs), glucocorticoids (GCs), leukotriene (LT) receptor antagonists and decongestants is indicated. Despite these diverse therapeutic options, studies on the real-life care situation of patients with AR regularly show that a considerable proportion of patients do not feel adequately treated with monotherapy of the usual drugs and therefore use several preparations with different active ingredients simultaneously and in various combinations. However, such parallel applications of several active ingredients are normally not tested in approval studies and therefore carry a potential risk of side effects or lack of efficacy. Methods For the present publication, a focused literature search in PubMed, Livivo and on the World Wide Web for the previous 20 years (period 01/1999 to 01/2020) was carried out. This literature search included original and review articles in German or English. A further analysis of current publications was also conducted for German-language journals that are not available in international literature databases. Results AHs and nasal GCs represent the therapeutic standard in AR. Their efficacy is well documented for several preparations. The evidence for combination therapies is documented very well for a fixed combination of azelastine and fluticasone (MP29-02). For the simultaneous use of non-fixed combined monopreparations, only a few efficacy and safety studies based on modern evidence criteria exist. Conclusion The free combination therapies of mast cell stabilizers, decongestants, AHs and nasal GCs, frequently used in the routine care of patients with AR, cannot be recommended because they are not evidence-based. Due to the fact that over-the-counter antiallergic drugs are not reimbursable in Germany, there is no medical supervision of the therapy. In addition, there are doubts about appropriate treatment, especially of patients with persistent rhinitis with severe symptoms, as these patients often use several preparations at the same time to alleviate their symptoms.

Die molekulare Komponentendiagnostik hat sich in den letzten Jahrzehnten als ein fester Bestandteil der Routinediagnostik der allergischen Rhinitis etabliert. Systematische Literaturrecherche. Durch einen sinnvollen Einsatz verschiedener Allergenkomponenten konnen die der Allergie zugrundeliegenden Proteine identifiziert, Kreuzreaktionen aufgedeckt und damit Polysensibilisierungen in der Diagnostik mit Extrakten erklart werden. Die Aufdeckung individueller molekularer Sensibilisierungsmuster ermoglicht eine bessere Einordnung der klinischen Symptome und verbessert hierdurch die Moglichkeit einer individuellen, personalisierten Therapieplanung. Fur die spezifische Immuntherapie ergibt sich daraus eine hohere diagnostische Sicherheit, welche auch zu einem besseren Therapieansprechen fuhren sollte — auch wenn hierfur bisher noch die wissenschaftlichen Belege fehlen. Trotz des immensen Wissenszuwachses auf dem Gebiet der Komponentendiagnostik muss die klinische Relevanz der molekularen Befunde nach wie vor konsequent anhand der individuellen Symptome des jeweiligen Patienten bewertet werden. Die vorliegende Arbeit soll beim sinnvollen Einsatz von Einzelkomponenten in der Diagnostik der allergischen Rhinitis Hilfestellung leisten und mogliche Handlungsoptionen aufzeigen.

Molecular component-resolved diagnostics has established itself in recent years as an integral part of the routine diagnosis of allergic rhinitis. A systematic literature review was performed. By using allergen components appropriately, it is possible to identify IgE sensitizations to specific marker allergens and to crossreactive allergens and this way explain polysensitizations obtained in extract-based diagnostics. The detection of individual molecular sensitization patterns enables better classification of the clinical symptoms, thus enhancing the possibility of individual, personalized treatment planning. This implies greater diagnostic reliability for specific immunotherapy, which should in turn result in a better treatment response—despite there being no scientific evidence of this as yet. In spite of the immense expansion of our knowledge in the field of component-resolved diagnostics, the clinical relevance of molecular findings still needs to be consistently assessed on the basis of the individual patient’s symptoms. This paper is intended to provide a guide to—and highlight possible courses of action when—making appropriate use of individual components in the diagnosis of allergic rhinitis.

Background: Bet v 6, a minor birch pollen allergen, is commercially available for allergen-specific IgE antibody testing. However, there is hardly any literature on the clinical impact of Bet v 6. The aim of the present study was to analyze if testing specific IgE against Bet v 6 can add valuable benefit to the standard diagnostics of birch pollen-sensitized patients, especially in patients with unknown sensitization-eliciting allergens. Methods: Birch pollen-sensitized patients with missing IgE reactivity against Bet v 1, 2, and 4 were tested for specific IgE antibodies against Bet v 6. For comparison, an equal number of randomly selected patients with birch pollen sensitization, regardless of their individual sensitization patterns, were tested for specific anti-Bet v 6. Results: Of 57 cases with missing reactivity against the standard birch pollen allergens, 2 patients were positive for Bet v 6. In the representative sample, 3 patients showed specific IgE against Bet v 6 - resulting in a total prevalence of 5%. None of the Bet v 6-positive patients showed allergic symptoms after exposure to birch pollen or an oral allergy syndrome. An increased prevalence of asthma and a higher degree of sensitization were the only distinctive clinical features in Bet v 6-positive patients. Conclusions: Among birch pollen-sensitized patients, the prevalence of specific IgE against Bet v 6 is low. Further, sensitization to Bet v 6, which shows characteristics of a panallergen, remains clinically silent. Therefore, determination of anti-Bet v 6 is not considered useful in the clinical routine.

Introduction: House dust mite contains several allergen components and causes perennial allergy. Lately, a new major allergen, Der p 23, was described with relatively high sensitization rates in different European Countries. In addition, Der p 23 is supposed to cause asthmatic disease. Objective: We would like to question the prevalence and clinical impact of specific immunoglobulin E to Der p 23 in a large patient sample in southern Bavaria, Germany. Methods: 474 patients from southern Bavaria, who visited the allergy department within the Department of Oto-Rhino-Laryngology of a university hospital, with sensitization to Dermatophagoides pteronyssinus were retrospectively compared regarding their sensitization profile to Der p 1, Der p 2, and Der p 23 and their clinical characteristics. Results: Among D. pteronyssinus-sensitized patients, the overall sensitization rate to Der p 23 was 42% in southern Bavaria. Most likely, patients were simultaneously sensitized to Der p 1, Der p 2, and Der p 23. Der p 23-sensitized patients reported more frequently asthma and showed higher prevalence of poly-sensitization towards 3 additional allergen groups and higher prevalence of double-sensitization to Der p 1 and Der p 2 compared to patients with missing sensitization to Der p 23. Considering the results of allergen provocation tests, neither IgE sensitization against Der p 23 nor levels of specific immunoglobulin E to Der p 23 allow a clear prediction of the clinical relevance of the sensitization. Conclusion: With a sensitization rate of 42%, Der p 23 closely misses the criterion of a major allergen in our southern Bavarian patient collective. A higher prevalence of polysensitization and self-reported asthma was the only clinical feature found in Der p 23-sensitized patients.

Since the beneficial implementation of allergen specific subcutaneous immunotherapy (SCIT), there are only a few studies on the risk of SCIT-induced neosensitizations. In 51 patients, we retrospectively analyzed sIgE and sIgG patterns by a multiplex ELISA as well as demographic and clinical features before and after SCIT. 33 allergic patients, who only received symptomatic treatment, served as controls. In 12 of 51 SCIT-treated patients (24%), we found new sIgE against allergen components of the allergen source treated by SCIT; eight of them were adults. Among controls, no adult patient showed neosensitization to components of the primarily affected allergen source. Only two children of the control group were affected by neosensitization, which was limited to major allergen components and rarely accompanied by sIgG. In the SCIT-treated group, neosensitization affected major and minor allergen components, and was accompanied by a strong induction of sIgG against major components. A clear clinical predictor of neosensitization during SCIT was not found. Comparing symptom scores, patients seem to profit more from SCIT, if neosensitization remained absent. Patients undergoing SCIT might carry an enhanced risk of neosensitization towards formerly unrecognized allergen components. According to anamnestic data, these neosensitizations might be of clinical relevance - supporting attempts towards personalized recombinant vaccines.

BACKGROUND AND OBJECTIVE An increasing number of studies have recently discussed whether provocation tests might be replaced by specific IgE serology in patients sensitized to airborne allergens. Objective: Our study aimed to analyze the concordance between a nasal provocation test with Dermatophagoides pteronyssinus and specific IgE measurements based on real-life data. METHODS We retrospectively analyzed concordance between the result of the provocation test and the IgE titer for house dust mite components and extracts in 223 patients with proven sensitization to D pteronyssinus. RESULTS In contrast to findings from other studies, the anti-Der p 1 level alone was not sufficient to distinguish between silent sensitization and allergy to D pteronyssinus. ROC curve analysis revealed that the sum of sIgE against Der p 1 and Der p 2 is-after adjustment for total serum IgE-the best parameter for discriminating between clinically silent and relevant sensitization. However, it does not have sufficient validity to confirm a diagnosis. CONCLUSIONS Despite the high correlation between sIgE levels and symptoms, no serologic parameter is sufficiently accurate to distinguish between silent sensitization and clinically relevant allergy. Therefore, nasal provocation tests remain the gold standard for assessing clinical relevance in sensitization to D pteronyssinus.

Eine 39-jahrige Patientin, Frau A., kommt zur Erstvorstellung in die allergologische Spezialsprechstunde. Sie leidet seit ihrer Jugend — hauptsachlich in den Monaten April bis Juli — unter starken rhinokonjunktivitischen Beschwerden, vor allem mit Niesreiz, Rhinorrhoe und nasaler Obstruktion sowie Juckreiz der Augen. Wie kann ihr geholfen werden?

In den letzten Jahren haben nationale und europaische Fachgesellschaften und Behorden sowie die Hersteller von Therapieextrakten erhebliche Anstrengungen unternommen, Methoden zur allergen-spezifischen Immuntherapie (AIT) zu harmonisieren sowie Wirksamkeit und Sicherheit von Produkten zur AIT zu belegen und somit diese Therapieform mit mehr Evidenz auszustatten.

Non-allergic rhinitis with eosinophilia syndrome (NARES) is an eosinophilic inflammation of the nasal mucosa without evidence of an allergy or other nasal pathologies. Patients complain about perennial symptoms like nasal obstruction, rhinorrhea, itchiness and sneezing of the nose sometimes accompanied by hyposmia. The aim of the study was to better characterize NARES patients using immunoassay-biochip technology to examine serum and nasal secretion. Sera and nasal secretion of patients with NARES (perennial nasal symptoms, no evidence of acute or chronic rhinosinusitis with or without polyps, negative SX1-Screening test and/or negative skin prick test, eosinophilic cationic protein in nasal secretion >200 ng/ml) were tested by immunoassay-biochip technology (ImmunoCAP(®) ISAC, Phadia). 112 different allergen components from 51 allergen sources were tested on the chip. Furthermore, serum and nasal secretion were tested for specific IgE to Staphylococcus aureus enterotoxin TSST-1 by fluorescence-enzyme-immunoassay (UniCAP(®), Phadia). Unrecognized systemic sensitization could be ruled out by negative ISAC results in sera of all patients. Testing of nasal secretion for allergen-specific IgE by ISAC chip technology was negative as well in all cases. In one patient, a systemic sensitization to Staphylococcus aureus superantigen TSST-1 was detectable but no allergen-specific IgE to TSST-1 was measurable in nasal secretion of any patient. The results demonstrate that NARES is not associated with local allergy (entopy) nor with a local inflammation driven by Staphylococcus aureus enterotoxin TSST-1. Further studies are necessary to better understand the underlying mechanisms of NARES.

Introduction 17β-Estradiol ( E 2 ) is neuroprotective in experimental models of stroke. While some postulate a mainly antioxidative action due to E 2 ׳s free C3 hydroxyl group at its A-ring, others suggest that neuroprotection is mediated by a hormonal, receptor mediated effect. The aim of the current study was to clarify this issue by testing whether E 2 analogues lacking hormonal activity are also neuroprotective following cerebral ischemia. Material & Methods Focal cerebral ischemia was induced in male C57/BL6 mice by laser-Doppler-controlled endovascular occlusion of the middle cerebral artery for 40 min. Mice received either 1) memantine, a NMDA-receptor antagonist, as a positive control, 2) E 2 (1400 µg/kg b.w.), or 3) 2,4,6-trimethylphenol (TMP), an E 2 analogue without hormonal activity (1400, 140, or 14 µg/kg b.w.). Motor function was tested 3 h and 24 h after ischemia. Thereafter mice were sacrificed and brain damage was quantified by histomorphometry. Results Treatment with memantine or E 2 significantly reduced infarct volume by >40% and significantly improved neurological function while treatment with TMP had no effect. Conclusion E 2 is equally neuroprotective as antagonization of NMDA receptors while E 2 analogues without hormonal activity are not neuroprotective. Therefore the current data suggest that the neuroprotection activity of E 2 is independent of its free-radical scavenging properties.

Recombinant allergen diagnostics have become increasingly important in daily allergological routine, made possible by inroads into the understanding of major and minor allergens accomplished within the last decade. Recombinant allergen diagnostics will, however, only provide correct diagnoses when sufficient knowledge of the regional IgE reactivity profile to a specific allergen source is available. A variety of studies in different European countries revealed reactivity profiles, where a sensitization to house dust mite could be recognized in more than 97 % of cases in which Der p1 and Der p2 were measured. The aim of this study was to investigate the IgE reactivity profiles of house dust mite allergic patients in southern Germany. Sera of house dust mite allergic patients (positive intranasal provocation) were screened for IgE antibodies against commercially available D pter., nDer p1, rDer p2 and rDer p10. IgE antibodies against D pter. could be found in 98 out of 98 sera (100 %). Seventy-five patients (76.5 %) reacted to nDer p1. In 72 patients (73.4 %), IgE antibodies against rDer p2 could be found, while IgE antibodies against rDer p10 were present in only 4 patients (4.1 %). Seventeen patients (17.3 %) had no IgE antibodies against nDer p1, rDer p2 and nDer p10, but displayed reactions to D pter. Knowledge of IgE regional reactivity profiles is necessary when using recombinant allergen diagnostics. In the case of our house dust mite allergic patients 17 would have remained undiagnosed based on a diagnostic method utilizing only the two major allergens nDerp1 and rDerp2.

Background:Dermatophagoides pteronyssinus is one of the most important perennial allergen sources worldwide. Molecular diagnostics using the commercially available major allergens (Der p 1 and Der p 2) in combination with Der p 10 do not detect house dust mite (HDM) sensitization in a number of cases when used alone. The objective was to evaluate the IgE reactivity profiles of these patients using an experimental immunoassay biochip. Methods: Sera of HDM-allergic patients (positive skin prick test, CAP class ≥1 for allergen extract, and positive intranasal provocation) were tested for IgE antibodies against Der p 1, Der p 2, and Der p 10 by ImmunoCAP fluorescence enzyme immunoassay. Negatively tested sera were examined by an experimental chip containing 13 microarrayed HDM allergens. Results: Of 97 patients tested, 16 showed negative results to Der p 1, Der p 2, and Der p 10. MeDALL chip evaluation revealed 5 patients monosensitized to Der p 23, and 11 patients were negative for all HDM MeDALL chip components. Seven sera were available for further testing, and 3 of them showed IgE reactivity to dot-blotted nDer p 1, and 2 reacted with high-molecular weight components (>100 kDa) in nitrocellulose-blotted HDM extract when tested with 125I-labeled anti-IgE in a RAST-based assay. The HDM extract-specific IgE levels of the 11 patients were Conclusions: Recombinant allergen-based IgE serology is of great value when conventional IgE diagnostics fails. Der p 23 is an important HDM allergen, especially when major allergens are negative. Therefore, it would be desirable to have Der p 23 commercially available. Further research concerning the prevalence and clinical significance of different HDM allergens is needed.

The limitation in olfactory function in patients with seasonal allergic rhinitis (AR) can be ascribed to an increase in eosinophilic and mast cell activity in the olfactory cleft. Therefore, the decrease in olfactory functions seems to be predominantly caused by the inflammation of the epithelium and not by the obstruction of the nose caused by the inflammation.Olfactory dysfunction is frequently seen in patients with AR; however, little is known about the underlying pathophysiological mechanisms. Therefore, the aim of the present study was to examine the olfactory function in patients with seasonal or perennial AR, and to correlate the results with data obtained by analysis of nasal secretion and obstruction.Olfactory function was tested using the Sniffin´Sticks test in patients with seasonal or perennial AR and in a control group. Nasal secretion analysis included eosinophilic cationic protein (ECP) and tryptase testing. Nasal obstruction was evaluated by rhinomanometry.Patients with AR (seasonal and perennial) showed impaired olfactory functions in comparison with the control group. Nasal secretion analysis showed increased values of ECP and tryptase in the seasonal group in comparison with controls. Rhinomanometry showed no differences in nasal flow between the three groups.

The growing popularity and frequency of consumption of seafood is accompanied by an increasing number of adverse reactions reported in literature. Allergic reactions to seafood can generate a variety of symptoms ranging from a mild oral allergy syndrome to keen anaphylactic reactions. Tropomyosin, the major shellfish allergen is regarded to be responsible for clinical cross-reactivity to inhaled house dust mites. The aim of the study was to investigate the prevalence of sensitization to tropomyosin in house dust mite allergic patients in southern Bavaria and to compare the results with allergic symptoms. Sera of house dust mite allergic patients (positive skin prick test, allergen-specific IgE and intranasal provocation) were screened for IgE antibodies to tropomyosin (Der p 10). Patients were contacted by phone to evaluate allergic symptoms when consuming seafood. IgE antibodies to house dust mite tropomyosin (Der p 10) could be found in 4 out of 93 sera (4.3%). Two of these four patients (50%) showed itching and swelling of oral mucosa accompanied by bronchial obstruction after consumption of shrimp. Two patients had no problems when eating seafood. None of the seronegative patients complained about any health problems during or after consumption of seafood. In conclusion, cross-reactivity to tropomyosin in house dust mite allergic patients in southern Bavaria, Germany is rarer than suspected. Beside the direct allergic reactions, a further part of reactions to seafood must therefore be ascribed to other mechanisms such as intoxication or intolerance to, e.g. additives in the food product.

Background Being one of the most common nasal diseases, chronic rhinosinusitis (CRS) is subdivided into CRS with nasal polyps (NP) and CRS without nasal polyps (CRSsNP). CRSsNP presents itself with a TH1 milieu and neutrophil infiltration, while NP is characterised by a mixed TH1/TH2 profile and an influx of predominantly eosinophils, plasma cells and mast cells. For the purpose of discovering disease-specific cytokine profiles, the present study compares levels of mediators and cytokines in nasal secretions between CRSsNP, NP, and healthy controls. Methods The study included 45 participants suffering from NP, 48 suffering from CRSsNP and 48 healthy controls. Allergic rhinitis constituted an exclusion criterion. Nasal secretions, sampled using the cotton wool method, were analysed for IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, IL-8, GM-CSF, G-CSF, IFN-γ, MCP-1, MIP-1α, MIP-1β, eotaxin, and RANTES, and for ECP and tryptase, using Bio-Plex Cytokine assay or ELISA, respectively. Results Elevated levels of IL-5, IL-17, G-CSF, MCP-1, MIP-1α, MIP-1β, ECP, and tryptase, as well as decreased levels of IL-10, IL-12, IL-13, and IFN-γ were detected in NP. CRSsNP presented increased levels of RANTES and MIP-1β while IL-13 was decreased. No differences between the three groups were found for IL-4, IL-8, GM-CSF, and eotaxin. Conclusions The present work suggests a disequilibrium of TH1 and TH2, together with a down-regulation of regulatory T lymphocytes and up-regulated TH17 in NP. Moreover, elevated levels of diverse mediators represent the activation of various inflammatory cells in this disease entity. The inflammation in CRSsNP, however, is only weakly depicted in nasal secretions. Therefore, cytokines in nasal secretions may provide helpful information for differential diagnosis.

Background: Component-resolved diagnostics is gaining importance in allergy diagnostics. Allergen extracts contain components with different rates of prevalence and clinical relevance, which can be subdivided at molecular level into major and minor allergens. Clinical complaints are usually triggered by major allergens, while the role of sensitization to the panallergens profilin and polcalcin still remains unclear. Methods: Eighty-six patients from southern Bavaria with sensitization to the panallergens profilin (Bet v 2/Phl p 12) and/or polcalcin (Bet v 4/Phl p 7) were examined in regard to their sensitization to the 4 main botanic denominations Betulaceae, Oleaceae, Poaceae and Asteraceae by skin prick test and measurement of specific immunoglobulin E antibodies to natural allergen extracts as well as major allergen components rPhl p 1/5, rBet v 1, rOle e 1 and nArt v 1. Sensitization was rated as clinically relevant or irrelevant depending on anamnesis or intranasal allergen challenge. Results: Regarding the 4 botanic denominations, there was no significant difference in the incidence of sensitization to the panallergens profilin, polcalcin or both. The sensitization pattern does not alter when subdividing the cohort into clinically relevant and silent sensitization. We did not find clinically symptomatic sensitization to panallergens without cosensitization to a major allergen. Conclusions: Our results suggest that sole sensitization to panallergens seems to have no clinical relevance in allergic rhinoconjunctivitis. Clinical complaints seem to be triggered manly by major allergens. Thus, component-resolved allergy diagnostics is crucial in the diagnosis and treatment of polysensitized patients.

„Unzumutbare Vorgange wahrend des Speisens“ hatten Herrn N. zum Arzt gefuhrt. Dieser sollte ihn „von der taglichen Leidensgeschichte erlosen“. Das zugrundeliegende Ubel, ein Zenker-Divertikel, konnte durch endoskopischen Einsatz eines CO2-Lasers restlos beseitigt werden. Der 80-Jahrige ist seitdem beschwerdefrei.

Allergic rhinitis (AR), nasal polyps (NP) as well as chronic rhinosinusitis (CRS) are all known to be associated with eosinophilic infiltration and elevated numbers of mast cells (MC) within the mucosa. Both cell types and their markers eosinophilic cationic protein (ECP) and tryptase are utilized in the diagnosis and management of chronic sino-nasal diseases. Mucosal cytology samples were gathered by cytobrush, histological samples were obtained from the inferior turbinate. In both sample sets, the number of eosinophils and MC was determined. Their corresponding markers ECP and tryptase were quantified from nasal discharge. Patients were grouped with reference to their main diagnosis: AR (n = 34), NP (n = 25), CRS (n = 27) and controls (n = 34). Eosinophil counts from cytobrush and ECP levels were significantly elevated in NP compared to all other groups-31- and 13-fold over control, respectively. However, histologic review did not reveal any difference in eosinophil count among groups. Tryptase was significantly elevated threefold in AR versus CRS and controls. No correlation to cytological and histological MC counts could be found. ECP levels in nasal discharge as well as eosinophil counts can provide useful information with regard to the diagnosis. Likewise, tryptase concentrations can do. The presented data show that the measurement of markers in nasal discharge is superior in differentiating among diagnosis groups. Given that the collection of nasal secretions is more comfortable for patients than the more invasive techniques, we recommend first line ECP and tryptase testing performed on nasal secretions.

Background Differential diagnosis between ragweed and mugwort pollen allergy represents a large clinical problem in areas where both plants are present. The aim of this study was to investigate ragweed- and mugwort-sensitized patients to identify specific IgE reactivity profiles. Results were correlated to clinical findings such as medical history and health-related quality of life (HRQL). Methods Seventy-four patients with allergic rhinoconjunctivitis between July and October were examined and underwent in vivo tests (skin-prick test [SPT] and nasal provocation). Sera were evaluated for IgE reactivity to mugwort and ragweed pollen extracts, major (Art v 1; Amb a 1) and minor (profilin and calcium-binding protein) allergens. HRQL was evaluated using a standardized questionnaire. Results Seventy-one patients revealed positive SPT reactivity against mugwort and 60 patients against ragweed extracts. Of these patients, 74 revealed IgE antibodies against mugwort extracts, whereas anti–Art v 1 antibodies were detectable in 50 individuals. Fifty-five patients showed IgE antibodies against natural ragweed extracts; anti–Amb v 1 antibodies were detected in six cases only. Using standardized clinical history and HRQL questionnaires we were not able to detect any differences within different reactivity patterns. Conclusion Within the investigated population of 74 weed-allergic patients the prevalence of true mugwort and ragweed sensitization can be calculated as 68 and 8%. High prevalence of ragweed sensitization when testing with full extracts can be explained by cross-reactivity between other weeds, e.g., mugwort rather than cosensitization. Differences in medical history and HRQL between different reactivity patterns were not detectable.

Background: Patients with nonallergic rhinitis with eosinophilia syndrome (NARES) show typical symptoms of persistent allergic rhinitis (PAR). The aim of the present study was to compare nasal cytokine patterns between NARES and PAR. Methods: Nasal secretions of 31 patients suffering from NARES, 20 patients with PAR to house dust mite and 21 healthy controls were collected using the cotton wool method and analyzed for interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1β (MIP-1β) by Bio-Plex Cytokine Assay as well as eosinophil cationic protein (ECP) and tryptase by UniCAP-FEIA. Results: NARES and PAR presented elevated levels of tryptase, while ECP was markedly increased solely in NARES compared to both the controls and PAR. Elevated levels of IL-1β, IL-17, IFN-γ, TNF-α and MCP-1 were found in NARES compared to the controls as well as PAR. MIP-1β was elevated in NARES and PAR, while IL-4, IL-6 and G-CSF showed increased levels in NARES, and IL- 5 was elevated in PAR only. Conclusions: In patients with NARES and PAR, eosinophils and mast cells appear to be the pivotal cells of inflammation, reflected by high levels of tryptase and ECP as well as IL-5 and GM-CSF as factors for eosinophil migration and survival. The elevated levels of proinflammatory cytokines in NARES may indicate the chronic, self-perpetuating process of inflammation in NARES which seems to be more pronounced than in PAR. IL-17 might be a factor for neutrophilic infiltration or be responsible for remodeling processes in NARES.

Background The aim of this study was to investigate recombinant marker allergens in patients with allergic rhinoconjunctivitis to tree and grass pollens. Methods Sera of 260 tree pollen– and 282 grass pollen–allergic patients were analyzed. Bet v 1 and Phl p 1/p 5 were used as marker allergens for allergies to pollen from birch and grasses. Profilin (Bet v 2 and Phl p 12) and calcium-binding protein (Bet v 4 and Phl p 7) were used as markers for polysensitization. Results Two hundred thirty-nine (92%) patients tested positive for IgE anti–Bet v 1. All of them were positive for IgE antibodies against natural birch extract (t3), hazel (t4), and alder (t2). Bet v 1 in combination with t3 identified allergies from related trees with a sensitivity of 99.2%. Two hundred fifty-six patients (91%) tested positive for IgE anti–Phl p 1 and/or anti–Phl p 5. All of them were positive for IgE antibodies against natural timothy (g6) and rye (g12) extract. Phl p 1/p 5 and natural timothy extract identified allergies from grasses and rye with a sensitivity of 99.3%. All Patients reacting to the cross-reactive allergens Bet v 2, Phl p 12, Bet v 4, and Phl p 7 were polysensitized. Conclusion Bet v 1 in combination with natural birch pollen extract identifies allergies from related trees with a sensitivity of 99.2%. Phl p 1, Phl p 5, and natural timothy extract identifies allergies from grasses and rye in 99.3%. Reactivity to the allergens Bet v 2, Phl p 12, Bet v 4, and Phl p 7 identifies polysensitization and cross-reactivity.

We evaluated birch- and timothy-allergic patients for allergen-specific IgE profiles and health-related quality of life (HRQL). We examined 395 patients with seasonal allergic rhinitis against birch or timothy pollen. Sera were analyzed for IgE reactivity to recombinant allergens (Bet v 1, Bet v 2, Bet v 4; Phl p 1/p 5b, Phl p 7, and Phl p 12) and to native pollen extracts (t3 and g6). Subgroup-specific analyses were performed. Patients with cosensitization against structurally unrelated allergens were termed polysensitized. Patients allergic solely to birch or timothy were labeled monosensitized. HRQL was evaluated using an established questionnaire. In patients polysensitized against native birch pollen (n = 233) the prevalence of allergens was 86% for Bet v 1, 15% for Bet v 2, and 5% for Bet v 4. Similar for timothy (n = 256), the prevalence of allergens was 87% rPhl p 1/p 5b, 5% for rPhl p 7, and 14% for rPhl p 12. Values for birch-monosensitized patients (n = 42) were Bet v 1, 100%, and Bet v 2 and Bet v 4, 0%. Values for timothy-monosensitized patients (n = 35) were Phl p 1/p 5b, 100%; rPhl p 7, 0%; and rPhl p 12, 3%. No difference in HRQL existed between patients sensitized solely against major versus minor allergens in birch-allergic patients. Polysensitized cohorts showed sensitization profiles comparable with published data. Monosensitized patients showed IgE against major allergens in 100% of cases. Patients sensitized solely against major or minor allergens showed no differences in HRQL.

Focal cerebral ischemia is responsible for alterations of vascular permeability, and the loss of microvascular integrity is a primary source of subsequent hemorrhages. We evaluated the influence of different durations of ischemia and reperfusion on infarction size and microvascular damage after focal cerebral ischemia in the mouse.C57BL/6 mice (n=39) were subjected to focal cerebral ischemia (I) and reperfusion (R). Consecutive brain sections were analysed for infarction volumes (Nissl-staining) and for collagen type IV (immunohistochemistry and western blot).Infarction size (percentage of the infarction volume versus ipsilateral hemisphere) increased with total time of ischemia and reperfusion: 19+/-2% (I3R0), 30+/-2% (I3R3), 36+/-4% (I3R12), 41+/-4% (I1R24), 45+/-6% (I2R24) and 58+/-2% (I3R24). The ischemic hemispheres showed a significant progressive reduction of collagen type IV positive vessels (ischemic versus non-ischemic contralateral area): 90+/-3% (I3R0), 88+/-1% (I3R3), 82+/-3% (I3R12), 85+/-3% (I1R24), 79+/-3% (I2R24), 72+/-2% (I3R24).Both prolonged ischemia and reperfusion lead to an increased infarction volume, as well as progressive microvascular damage.

Pharmacological studies using bradykinin B2receptor antagonists suggest that bradykinin, an early mediator of inflammation and the main metabolite of the kallikrein-kinin system, is involved in secondary brain damage after cerebral ischemia. However, the time-course of bradykinin production and kinin receptor expression as well as the conclusive role of bradykinin B2receptors for brain damage after experimental stroke have not been elucidated so far. C57/Bl6 mice were subjected to 45 mins of middle cerebral artery occlusion (MCAO) and 2, 4, 8, 24, and 48 h later brains were removed for the analysis of tissue bradykinin concentration and kinin B2receptor mRNA and protein expression. Brain edema, infarct volume, functional outcome, and long-term survival were assessed in WT and B2−/−mice 24 h or 7 days after MCAO. Tissue bradykinin was maximally increased 12 h after ischemia (three-fold), while kinin B2receptor mRNA upregulation peaked 24 to 48 h after MCAO (10- to 12-fold versus naïve brain tissue). Immunohistochemistry revealed that kinin B2receptors were constitutively and widely expressed in mouse brain, were upregulated 2 h after ischemia in cells showing signs of ischemic damage, and remained upregulated in the penumbra up to 24 h after ischemia. B2−/−mice had improved motor function ( P2receptors are upregulated on dying cells, and B2receptors are involved in cell death and brain edema formation after experimental stroke.

Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore, addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus 1 hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke.