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We report a multicast switch PIC serving as a transponder aggregator. Successful data transmission through InP multicast switch and reception in a fully packaged coherent receiver demonstrates the drop traffic flow of a ROADM node.

Patients with Oral Allergy Syndrome (OAS) to fresh apple may tolerate low allergenic apple cultivars. We aimed to investigate if the low allergenic properties of Elise and Santana, as previously identified in a Dutch population, could be generalised within North West Europe within the birch pollen region with regard to both the prevalence and degree of sensitization. Prick-to-prick tests (PTP) were performed in eighty-five adult patients with OAS to fresh apple in Great Britain, Switzerland and Northern Italy, before the birch pollen season, using the putatively low allergenic apple cultivars Elise, Santana, Granny Smith, Modi and Mcintosh, as well as the putatively high allergenic apple cultivars Golden Delicious and Kanzi. No significant differences in percentages of negative responses of PTPs were found between the three countries. Negative responses did not differ from negative responses to the different apple cultivars we previously found in 2006/2007 in the Netherlands. The size of the PTPs of all apple cultivars tested were correlated to the size of the skin prick tests with birch pollen. These results add to the indications for the low allergenic properties of the low allergenic apple cultivars Santana and Elise, as the number of negative responses were reproducible in three countries within the birch pollen region and were similar to previous results in the Netherlands. These results justify oral challenge studies with Elise and Santana within the birch pollen region, to establish the low allergenic properties for the benefit for apple allergic consumers for definite conclusions.

Background: Atopic dermatitis (AD) and food allergy frequently co-exist in children. Both immediate and late reactions have been reported after oral food challenge. The aim of this study was to investigate the reactions occurring in children with AD during double blind, placebo-controlled food challenges (DBPCFC). Also, the frequency of positive DBPCFCs in children reporting exacerbations of eczema as their only symptom to foods was studied. Method: Between 2001 and 2011, children underwent DBPCFCs for one or more suspected food allergies as part of regular care. The history relating to the suspected food was obtained. Children and/or parents were questioned about current AD. Immediate symptoms were defined as symptoms occurring during the challenge, or within 2 h after the last dose. Symptoms were considered 'intermediate' when they occurred between 2 and 6 h and 'late' between 6 and 48 h after the last challenge dose. McNemar's test was used to test for statistical differences between frequencies on verum and placebo days. Results: Of the 682 children undergoing DBPCFC, 381 children (55.9%) had a current history of AD, of which 317 had a history of reactions to foods and 64 had no known ingestion of the food previously. Immediate reactions consisting of exacerbations of AD only occurred rarely [two patients out of 326 (0.6%) on verum days vs one patient on a placebo day (0.3%), not significant (n.s.)]. Comparing verum to placebo days, immediate symptoms other than AD were seen more frequently (39.6% vs 8.0% respectively, P

Background Diagnostic and accidental food allergic reactions may be modified by the matrix containing the allergenic food. Previous studies of double-blind, placebo-controlled food challenges (DBPCFCs) with peanut found an effect of the fat content of the challenge matrix on the severity of the challenge reactions.Objective The aim of this study was to examine whether the fat content of the food matrix is related to eliciting dose and reaction severity in DBPCFCs with heated hen's egg.Methods Sensitized egg allergic children (n=59) undergoing DBPCFCs with egg as a routine diagnostic procedure in our tertiary care centre were evaluated retrospectively. Three different recipes were used for the food matrix: vanilla pudding, pancake and minced meat, containing 22.8%, 31.9% and 52.7% fat (weighted average), respectively. The eliciting dose (i.e. the highest cumulative dose to which the child reacted) was analyzed by Kaplan-Meier log-rank statistic and by Cox regression. Reaction severity was quantified by using an index (range 1-12) and was analysed by multiple linear regression analysis.Results The overall influence of type of recipe on eliciting dose was not significant (P=0.12). The rate of response to minced meat (with the highest fat content) was not significantly different from pudding [HR=0.61 (0.26-1.45, P=0.26) or pancake (HR=1.41 (0.50-3.99), P=0.52] after adjustment for confounders. The type of recipe did not influence the severity of the challenge reaction. The severity of the challenge reaction for minced meat compared to pudding and pancake was 1.06 (0.52-2.16), P=0.87 and 0.81 (0.32-2.01), P=0.64, respectively, after correction for confounders.Conclusion and Clinical Relevance In contrast to similar research with peanut, no significant influence of the fat content of the matrix was found on the eliciting dose or severity of the reaction in 59 DBPCFCs with hen's egg. Matrix fat content differences comparable to those reported here may not be an important co-determinant of reaction severity for all allergenic foods.

Risk indicators of indolent systemic mastocytosis (ISM) in adults with clinical suspicion of ISM without accompanying skin lesions [urticaria pigmentosa (UP)] are lacking. This study aimed at creating a decision tree using clinical characteristics, serum tryptase, and the urinary histamine metabolites methylimidazole acetic acid (MIMA) and methylhistamine (MH) to select patients for bone marrow investigations to diagnose ISM.Retrospective data analysis of all adults, in whom bone marrow investigations were performed to diagnose ISM, was carried out.In total, 142 patients were included. SM was absent in all 44 patients with tryptase10 μg/l, in 45 of 98 (46%) patients with tryptase ≥10 μg/l and in 18 of 52 patients (35%) with tryptase20 μg/l. Above 43 μg/l, all patients had ISM (n = 11). Male gender, insect venom anaphylaxis as presenting symptom, tryptase, MIMA, and MH were independent ISM predictors. If tryptase was ≥10 μg/l, the diagnostic accuracy of MIMA and MH was high (areas under the ROC curve 0.92).In suspected patients without UP, the ISM risk is very low (if present at all) if tryptase is10 μg/l. If tryptase is ≥10 μg/l, this risk depends on MIMA and MH, being low if these are normal, but high if these are elevated. Male gender and insect venom anaphylaxis are additional risk indicators. We recommend refraining from bone marrow examinations in suspected patients without UP if tryptase is10 μg/l. Our results question the reliability of the minor diagnostic World Health Organization criterion of tryptase20 μg/l.

To cite this article: Vlieg-Boerstra BJ, Herpertz I, Pasker L, van der Heide S, Kukler J, Jansink C, Vaessen W, Beusekamp BJ, Dubois AEJ. Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults. Allergy 2011; 66: 948–954. Abstract Background: In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume. Methods: Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test. Results: For young children, three recipes with cow’s milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs. Conclusions: All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children.

P>Background: As oral allergy syndrome (OAS) symptoms to apple are frequent, we aimed to identify low allergenic apple cultivars and to validate the prick-to-prick skin prick test (SPT) as a suitable screening method. Methods: Sixty-eight apple cultivars were tested by SPTs in 33 Dutch adults with OAS, before and during the birch pollen season in 2006 and 2007, respectively. Three cultivars yielding the largest number of negative SPTs (Elise, Santana and Pink Lady (R)) and one reference cultivar (Golden Delicious) were subsequently tested by single-blind oral food challenges (SBFC) just after picking in fall 2007 (fresh) and in spring 2008 (stored), outside the birch pollen season and preceded by SPTs. In spring, Santana was replaced by Modi (R). Results: In fresh apples, OAS symptoms of Elise, as measured by cumulative scores on a Visual Analogue Scale VASt, were significantly lower than those of Santana, Pink Lady and Golden Delicious (P = 0.021; 0.040 and 0.005, respectively). VASt scores of Santana were significantly lower than those of Golden Delicious (P = 0.049). In stored apples, VASt scores of Elise were significantly lower than that of Golden Delicious (P = 0.038). VASt scores of fresh apples did not differ significantly from stored apples, except in Golden Delicious (spring

In many European centers insect venom allergic patients with a reaction confined to the skin are only offered an epinephrine auto-injector and not venom immunotherapy (VIT). Previously we showed that VIT improves health-related quality of life (HRQL) of yellow jacket allergic patients with more than dermal reactions.To examine whether HRQL of dermal reactors is impaired and to examine the influence of VIT on HRQL in comparison with the EpiPen((R)).Patients with solely dermal reactions were asked if they were willing to be randomized either to VIT or EpiPen((R)), after receiving patient information. Before and 1 year after enrollment, patients completed the Vespid allergy Quality of Life Questionnaire (VQLQ), Burden of Treatment and Expectation of Outcome.Of 55 patients eligible for the study, 29 consented to randomization: 15 to VIT, 14 to EpiPen((R)). The remaining 26 patients preferred to choose their treatment: 11 VIT and 15 EpiPen((R)). The VQLQ score of patients randomized to VIT improved (mean change 0.83 (SD 0.87), in contrast to patients randomized to the EpiPen((R)) whose scores deteriorated (mean change -0.42 (SD 0.64), P VIT results in a clinically significant improvement of HRQL in most patients with reactions limited to the skin following yellow jacket stings. Prescription of an EpiPen((R)) in patients not choosing this treatment is associated with deterioration in HRQL and should therefore be avoided as definitive treatment in these patients.

Background: The vast majority of children will undergo their first exposure to common allergenic foods at home. However, the first exposure may lead to clinical reactions. It has been proposed to introduce allergenic foods gradually into the diets of children at risk for food allergy, but no practical dietary advice has been devised. Objective: The aim of this study was to devise safe introduction schedules for common allergenic foods for use at home, based on the challenge doses as administered in double-blind, placebo-controlled food challenge (DBPCFCs) in children who were never exposed previously to these foods. Methods: Seventy-two DBPCFCs were performed in 63 children as a first known exposure. The incrementing challenge doses were converted into equivalent portions of these foods in their usual household form and incorporated in introduction schedules. The feasibility of the introduction scales was tested in parents of the children attending our clinic. Results: Based on the results of the positive challenges (37) in which severe reactions did not occur, detailed introduction schedules and a reference photograph of the required increasing amounts of food were devised for use at home. Feasibility testing showed that, when using these introduction schedules, parents portioned the initial doses significantly lower than without detailed instructions. Conclusions: The introduction schedules and reference photograph provide information for parents to introduce the required amounts of allergenic foods in initial low doses at home. This is expected to improve the safety of this procedure.

Het meten van allergeenspecifieke IgE-antistoffen in serum is een belangrijk hulpmiddel in het verzamelen van informatie over de sensibilisatie van een patient voor specifieke allergenen. Hoewel de specifieke IgE-metingen de laatste jaren sterk verbeterd zijn, blijven er discrepanties bestaan tussen de concentratie specifiek IgE tegen een bepaald allergeen en de aan- of afwezigheid van klachten na contact met dit allergeen.Veel van deze discrepanties kunnen verklaard worden uit het feit dat een IgE-test een methode is om allergische sensibilisatie aan te tonen maar dat sensibilisatie niet hetzelfde is als klinische reactiviteit. Daarnaast wordt in een specifieke IgE-bepaling regelmatig IgE aangetoond die niet (of nauwelijks) betrokken is bij een allergische reactie. Dit laatste is vooral het geval bij voedselallergie. Bij een verdenkingvan voedselallergie kan daarom in veel gevallen de specifieke IgEtest een voedselprovocatie nog niet vervangen.

Background: Venom immunotherapy (VIT) is a treatment with established efficacy for the prevention of repeated anaphylactic reactions in patients with Hymenoptera allergy, which also allows patients to discontinue carrying an EpiPen. Despite their merits, both treatments can have negative aspects potentially important to patients.Objective: We examined possible negative aspects of the EpiPen in comparison with VIT as perceived by patients.Methods: Positive and negative aspects of both treatments were measured by using a burden of treatment questionnaire together with statements about the EpiPen.Results: One hundred ninety-three patients were included, of whom 94 consented to randomization: 47 received VIT, and 47 received the EpiPen. Of the remaining 99, 75 chose VIT, and 26 chose the EpiPen. Of the patients receiving VIT, 91.5% were (extremely) positive about their treatment, and 85% would choose VIT again. Of the patients receiving the EpiPen, only 48% were positive about their treatment, and even of these patients, 68% preferred to be treated with VIT after 1 year of carrying the EpiPen. Although most patients indicated that it is reassuring to carry an EpiPen and makes them feel safe, many patients also indicated that it is inconvenient and troublesome. Especially patients who were negative about the EpiPen indicated that they would not dare use the EpiPen if necessary and were afraid at possible side effects.Conclusion: In contrast to VIT, the EpiPen is perceived as burdensome by most patients with venom allergy. For most patients, an EpiPen is an unsuitable definitive treatment.Clinical implications: As VIT enables patients with venom allergy to get rid of the EpiPen, patients should be offered VIT.

After the start of heroin (diacetylmorphine)-assisted treatment to a selected group of chronic treatment-resistant heroin-dependent patients in the Netherlands, we reported about work-related eczema and positive patch tests to heroin in some nurses and nasal and respiratory complaints. To investigate the prevalence of heroin contact allergy, we started a questionnaire-based study with follow-up by allergological examinations. Of 120 questionnaires sent, 101 (84%) was returned: 67 from nurses and 34 from other employees. Of 101 workers, 38 (38%) had reported work-related complaints: 33 of 67 (49%) nurses and 5 of 34 (15%) other employees. Patch tests to heroin were performed in 24 nurses and were positive in 8 (33%). All the 8 had eyelid or facial eczema and, in 6, accompanied by mucosal or respiratory complaints. The prevalence of heroin contact allergy in this study was 8% (8/101) among all employees and 12% (8/67) among nurses. Respiratory and mucosal complaints could not be ascribed to a contact allergy, and in these cases, serum was analysed for specific immunoglobulin E to heroin. A type 1 allergy to heroin could not be shown. These complaints are possibly due to the histamine-liberating effect of heroin, to atopic constitution, to a combination of these factors or - less likely - to other non-allergic factors.

Healthy individuals are continuously exposed to fungal biomass, which includes live and dead spores and fungal debris that is entrapped in the airways. In patients with asthma and/or atopy, exposure to fungal biomass might result in age-dependent sensitization and asthmatic reactions. Interaction with Toll-like receptors (TLRs) of the innate immune defense (alveolar macrophages and epithelial cells) and protease-activated receptors (PARs) determine the effectiveness of elimination of fungal material. The association of sensitization to Alternaria with severe asthma is discussed in relation to the age-dependent sensitization, rate of release of allergens from spores, and activity of its proteases. A model is described concerning the influence of polymorphic genes for airway hyperresponsiveness (AHR) and atopy, showing a cumulating influence on susceptibility for allergen-induced asthma, and explaining that fungus-induced airway obstruction is mainly associated with more severe asthma.

Background Multiple population studies have shown the presence of a sibling effect on atopic disease. However, it is unclear if the sibling effect is also of importance in subjects who are genetically at high risk for the development of atopy. Objective To study the presence of a sibling effect on markers of atopy (serum total IgE, specific IgE, skin tests) and asthma (bronchial hyper-responsiveness to histamine) in families ascertained through a parent with asthma. Methods First-degree offspring in 200 asthma families were studied (n = 541). Mixed effects regression models were used to account for the dependence of the observations within a family, and to adjust for possible confounding variables. Results Multiple regression analysis showed that having older siblings was inversely related to atopy, defined as greater than or equal to 2, greater than or equal to 3, greater than or equal to 4, or greater than or equal to 5 skin tests (P = 0.07-0.009). In addition, family size (number of siblings) had a significant protective effect on the presence of specific IgE to common aeroallergens (P = 0.03). Exposure to cigarette smoke in the first 3 years of life significantly increased the risk of having specific IgE to common aeroallergens (P = 0.04). No sibling effect was detected for serum total IgE or bronchial hyper-responsiveness to histamine. Conclusions This study shows a protective sibling effect on the presence and severity of atopy but not on bronchial hyper-responsiveness in children who are genetically at risk. The identification of the sibling effect in high-risk families stresses the need to understand the basis of this effect, in order to design future prevention programmes.

The mechanism that determines the difference between asymptomatic sensitisation and clinical reactivity to food is as yet unknown. The aim of this study was to determine the effect of loss-of-function variants in the filaggrin gene on clinical reactivity, sensitisation and severity of food allergy.

Background Exposure to house dust mite (HDM) allergens often results in worsening of asthma. Therefore, avoidance of exposure to HDM allergens is often proposed. Unfortunately, the most effective and feasible avoidance strategy is still not completely assessed. Consequently, we investigated the effects of a combined HDM avoidance strategy on HDM allergen concentrations and clinical condition of allergic, mild asthmatic, patients using no inhaled steroids. Methods Asthmatic patients, allergic to HDM, using no inhaled corticosteroids, were randomly allocated to an active (n = 76) or a placebo allergen-avoidance group (n = 81). Avoidance measures consisted of applying Acarosan® (placebo: water) to the living room and bedroom floors, and the use of HDM-impermeable covers for mattresses and bedding (placebo: cotton covers for mattresses only). Effects on allergen concentrations (Der p 1), FEV1, bronchial hyperresponsiveness, peak flow parameters and asthma symptom scores were studied during 20 weeks and controlled for the allergic status of the patients. Results The active covers reduced Der p 1 concentrations to 9.4% (P = 0.0001), and were always significant lower than in the placebo group (P = 0.0002). Acarosan® resulted in slight but significant decreases (twofold, P = 0.0001), both on living room and bedroom floors, but concentrations were never significantly lower than the placebo group. Although the combined avoidance strategy resulted in a considerable reduction in allergen load in the active group, no differences were seen between the two groups in any of the clinical parameters during the follow-up period in this group of allergic asthmatics, using no inhaled corticosteroids. Corrections for the allergic status did not alter these results. Conclusions The combined avoidance strategy was effective in reducing HDM allergen concentration. This was especially achieved by the allergen-impermeable covers, while the effects of Acarosan® were only marginal. However, this allergen reduction was not reflected in a convincing improvement in clinical condition in this group of mild allergic asthmatics, using no inhaled steroids. Perhaps, a longer follow-up period would have resulted in more pronounced effects.

The prevalence of sensitization to the storage mites Acarus siro (AS), Tyrophagus putrescentiae (TP), and Lepidoglyphus destructor (LD) was studied in 250 sera of patients with different degrees of sensitization to the house-dust mite Dermatophagoides pteronyssinus (DP) by measuring IgE binding to extracts of the storage mites. Additionally, allergenic cross-reactivity between DP and the storage mite species was studied by RAST inhibition with five individual sera (and a pool of these sera) with moderate IgE levels to all three storage mites and to DP. Increased serum IgE to storage mites was found in 46% of the 200 patients sensitized to DP. Increased prevalence rates of IgE titers to storage mites were associated with higher IgE levels to DP. In 50 sera without sensitization to DP, only five sera showed increased IgE to one of the storage mites. Extracts of TP almost completely inhibited the IgE binding to AS, and vice versa. DP inhibited IgE binding to all storage mites up to 60%, whereas IgE binding to DP was only minimally inhibited by extracts of storage mites. In conclusion, cosensitization to storage mites is a frequent finding in patients sensitized to DP. Although this is largely the result of cross-reactivity between different mite species, it may nevertheless be of clinical significance in patients exposed to storage mites.

This double-blind, placebo-controlled study investigated whether the application of an acaricide (Acarosan(R)) on mattresses and on textile floor coverings in living rooms and bedrooms can contribute to improvement in lung function and airway hyperresponsiveness in 40 adult asthmatic patients sensitized to house-dust mite. In a second group of 19 patients who refused chemical intervention, the clinical effects of application of allergen-impermeable mattress encasings were studied. In all three treatment groups, Der p 1 levels in mattress dust were statistically significantly decreased after 12 months. However, this decrease was much greater in the group who received mattress encasings (final mean level 430 ng/g) than in groups with acaricide-or placebo-treated mattresses (final mean levels 1730 and 2100 ng/g, respectively). Treatment of textile floors with either Acarosan or placebo chemical caused a statistically significant decrease in the level of the house-dust-mite allergen Der p 1 in floor dust. In the group with mattress encasings, no significant changes of floor dust Der p 1 were found. Airway hyperresponsiveness (as measured by the PC20, histamine) improved significantly in the mattress cover group after 6 months. The Acarosan group also showed a small but statistically significant improvement after 12 months.

Background: There is need for an accurate diagnostic test in mastocytosis patients with wasp venom allergy (WVA) and monitoring of these patients during immunotherapy (IT). In this study, we aimed to evaluate sensitivity and specificity of the Basophil Activation Test (BAT) as a diagnostic and monitoring test in patients with mastocytosis and WVA. Methods: Seventeen patients with mastocytosis and WVA and 6 mastocytosis patients without WVA were included. BAT was performed before the start of IT (1st visit) and at 6 weeks (2nd visit) and 1 year (3rd visit), after reaching the maintenance dose. Of 17 patients included, 11 complerted the 3rd visit.In mastocytosis patients with WVA, dose-dependent wasp-venom induced upregulation of CD63 and CD203c expression on basophils was observed compared to mastocytosis patients without WVA. Serum specific IgE, IgG4 and tryptase levels were measured in all patients. Results: BAT had a sensitivity of 87% and specificity of 100% in diagnosing WVA in mastocytosis patients. Basophil allergen threshold sensitivity with respect to CD63 and CD203c was significantly decreased in the second visit compared to the first visit and increased significantly in the third visit compared to the second visit. Specific IgE levels increased significantly in the 2nd visit compared to first and decreased significantly in the third visti compared to the second. Specific IgG4 levels rose significantly in the 2nd visit compared to the 1st and on the 3rd visit compared to the 2nd . Tryptase levels did not change significantly during the study. Conclusions: BAT can represent a diagnostic test in allergic patients with mastocytosis and these patients are better to be monitored for a longer period during IT. © 2013 Clinical Cytometry Society.

Mal d 1 is not equally distributed over the apple. We aimed to examine the influence of the location of pricking in the apple on prick-to-prick skin prick test (PTP) results. PTPs were performed in autumn 2007 and spring 2008, before the birch pollen season, in 32 Dutch adults with symptoms of oral allergy to fresh apple, using apples harvested in autumn 2007. PTPs with fresh intact and unpeeled Pink Lady, Golden Delicious, Elise, Santana and Modi apples were performed using material obtained from approximately 2cm near the stalk (top), and the middle region. All PTP responses were greater when performed with apple material near the stalk than from the middle region. In 2007, these differences were statistically significant for Pink Lady, Golden Delicious and Elise, and in 2008, for Pink Lady and Modi. When performing PTPs, the apple should be pricked near the stalk rather than in the middle.

The influence of exogenous factors in the home on the circadian variation of airway obstruction has not been fully assessed in children with asthma. The aim of the present study was to investigate the contribution of exogenous stimuli to the degree of peak expiratory flow (PEF) variability during 24 h. Fifty-five children (33 boys and 22 girls; mean age, 9.3 +/- 1.7 yr) with symptoms of asthma, increased bronchial responsiveness, and a solitary allergy to house dust mite (HDM) participated. Their asthma symptoms were well-controlled for at least 4 mo with daily inhaled corticosteroids (ICS) and beta 2-adrenergic drugs if needed. Symptoms, peripheral blood eosinophils, total IgE, and specific IgE to HDM were assessed. Spirometry and PC20 histamine were performed. PEF amplitudes during 24 h (highest minus lowest as a percentage of the day's mean value) were obtained at home during and 6 d after withdrawal of ICS. Dust samples were collected from the total area of the living rooms, bedrooms, mattresses (n = 25), and classrooms to obtain the HDM allergen (HDMA) exposure to Der p I and Der p II. Family smoking habits, presence of pets, and types of floor-covering were recorded on a checklist. Mean PEF amplitude did not increase after withdrawal of ICS, but absolute PEF values were significantly lower (p = 0.05) at midnight and 4:00 A.M. Twenty-six children (47%) were exposed to environmental tobacco smoke (ETS), and 23 (42%) kept pets. Mattresses contained significantly higher amounts of HDMA compared with other locations. PEF amplitude after withdrawal of ICS was significantly higher in children exposed to ETS, a pet, or a high HDMA level in their mattress than in children who were not exposed (ETS: 29.7% [3.9 to 56.6] versus 19.4% [0.0 to 56.6], p

Background: About 25% of greenhouse flower and/or ornamental plant growers sensitised to workplace flowers or moulds have occupational asthma, a disease that is suffered by 8% of the growers who cultivate these crops. Aim: To document a case of occupational asthma due to IgE mediated allergy to the flower Molucella laevis. Methods and Results: There was a history of work related seasonal asthmatic and rhinoconjunctivitis symptoms in a Molucella laevis grower. Bronchial obstruction following exposure to Molucella laevis was documented by a fall in FEV1 from 89% to 73% of predicted during seasonal exposure to Molucella laevis. Daily PEF measurements showed a fall from 500 to 250 l/min during this period following withdrawal of inhaled steroids. Bronchial reactivity to inhaled methacholine was increased ( PC 20 1.45 mg/ml). Confirmation of sensitisation to Molucella laevis flower pollen extract was done using an SPT and by demonstration of Molucella laevis specific serum IgE ( 18 IU/ml; class 4). Specific inhalation challenge with Molucella laevis extract provoked an early and late asthmatic reaction ( EAR and LAR) with a fall in FEV1 compared with control day of 40% and 53% respectively, with associated 5.1-fold increase in absolute sputum eosinophil cell counts and 2.9-fold increase in neutrophil cell counts.

In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume.Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test.For young children, three recipes with cow's milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs.All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children.

As oral allergy syndrome (OAS) symptoms to apple are frequent, we aimed to identify low allergenic apple cultivars and to validate the prick-to-prick skin prick test (SPT) as a suitable screening method.Sixty-eight apple cultivars were tested by SPTs in 33 Dutch adults with OAS, before and during the birch pollen season in 2006 and 2007, respectively. Three cultivars yielding the largest number of negative SPTs (Elise, Santana and Pink Lady®) and one reference cultivar (Golden Delicious) were subsequently tested by single-blind oral food challenges (SBFC) just after picking in fall 2007 (fresh) and in spring 2008 (stored), outside the birch pollen season and preceded by SPTs. In spring, Santana was replaced by Modi®.In fresh apples, OAS symptoms of Elise, as measured by cumulative scores on a Visual Analogue Scale VASt, were significantly lower than those of Santana, Pink Lady and Golden Delicious (P = 0.021; 0.040 and 0.005, respectively). VASt scores of Santana were significantly lower than those of Golden Delicious (P = 0.049). In stored apples, VASt scores of Elise were significantly lower than that of Golden Delicious (P = 0.038). VASt scores of fresh apples did not differ significantly from stored apples, except in Golden Delicious (springfall: P = 0.021). The SPTs did not predict the severity of OAS.SPTs are not useful to assess the allergenicity of apple cultivars. By using SBFC, Elise and Santana were identified as low allergenic apple cultivars in patient with OAS. Our data on the effect of storage are inconclusive.

Data on the frequency of resolution of anaphylaxis to foods are not available, but such resolution is generally assumed to be rare.To determine whether the frequency of negative challenge tests in children with a history of anaphylaxis to foods is frequent enough to warrant challenge testing to re-evaluate the diagnosis of anaphylaxis, and to document the safety of this procedure.All children (n=441) who underwent a double-blind, placebo-controlled food challenge (DBPCFC) between January 2003 and March 2007 were screened for symptoms of anaphylaxis to food by history. Anaphylaxis was defined as symptoms and signs of cardiovascular instability, occurring within 2 h after ingestion of the suspected food.Twenty-one children were enrolled (median age 6.1 years, range 0.8-14.4). The median time interval between the most recent anaphylactic reaction and the DBPCFC was 4.25 years, range 0.3-12.8. Twenty-one DBPCFCs were performed in 21 children. Eighteen of 21 children were sensitized to the food in question. Six DBPCFCs were negative (29%): three for cows milk, one for egg, one for peanut, and one for wheat. In the positive DBPCFCs, no severe reactions occurred, and epinephrine administration was not required.This is the first study using DBPCFCs in a consecutive series of children with a history of anaphylaxis to foods, and no indications in dietary history that the food allergy had been resolved. Our study shows that in such children having specific IgE levels below established cut-off levels reported in other studies predicting positive challenge outcomes, re-evaluation of clinical reactivity to food by DBPCFC should be considered, even when there are no indications in history that anaphylaxis has resolved. DBPCFCs can be performed safely in these children, although there is a potential risk for severe reactions.Cite this as: B. J. Vlieg-Boerstra, E. J. Duiverman, S. van der Heide, C. M. A. Bijleveld, J. Kukler and A. E. J. Dubois, Clinical and Experimental Allergy, 2008 (38) 1935-1942.

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from decreased mast cell activation and impaired intestinal inflammation.Objective: To quantify mast cell activation and inflammation in patients undergoing conventional and minimal invasive surgery.Methods: (1) Mast cell activation (ie, tryptase release) and pro-inflammatory mediator release were determined in peritoneal lavage fluid obtained at consecutive time points during open, laparoscopic and transvaginal gynaecological surgery. (2) Lymphocyte function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) mRNA as well as leucocyte influx were quantified in non-handled and handled jejunal muscle specimens collected during biliary reconstructive surgery. (3) Intestinal leucocyte influx was assessed by 99mTc-labelled leucocyte single photon emission computed tomography (SPECT)-computed tomography (CT) scanning before and after abdominal or vaginal hysterectomy.Results: (1) Intestinal handling during abdominal hysterectomy resulted in an immediate release of tryptase followed by enhanced interleukin 6 (IL6) and IL8 levels. None of the mediators increased during minimal invasive surgery except for a slight increase in IL8 during laparoscopic surgery. (2) Jejunal ICAM-1 and iNOS mRNA transcription as well as leucocyte recruitment were increased after intestinal handling. (3) Leucocyte scanning 24 h after surgery revealed increased intestinal activity after abdominal but not after vaginal hysterectomy.Conclusions: This study demonstrates that intestinal handling triggers mast cell activation and inflammation associated with prolonged postoperative ileus. These results may partly explain the faster recovery after minimal invasive surgery and encourage future clinical trials targeting mast cells to shorten postoperative ileus.

Background: A cardinal feature of the double-blind, placebo-controlled food challenge (DBPCFC) is that placebo administration is included as a control. To date, the occurrence and diagnostic significance of placebo events have not extensively been documented.Objective: To analyse the occurrence and features of placebo events in DBPCFCs and to assess their contribution to the diagnostic accuracy of the DBPCFC in children.Methods: The study population consisted of 132 challenges in 105 sensitized children (age range 0.7-16.6 years, median 5.3 years), who underwent DBPCFCs with cow's milk, egg, peanut, hazelnut and soy. Placebo and active food challenges were performed on different days.Results: A total number of 17 (12.9%) positive placebo events occurred, which could be classified as immediate (9/17), late-onset (8/17), objective (11/17) or subjective (6/17). Four of 74 (5.4%) positive active food challenges were revealed to be false positive by administration of a placebo challenge. This is 3% (4/132) of all challenges. When computed by a statistical model, the false positive rate was 0.129 (12.9% of all challenges).Conclusions: Placebo events with diverse clinical characteristics occur in DBPCFCs in a significant number of children. The diagnostic significance of the administration of a placebo challenge is first, to identify false positive diagnoses in DBPCFCs by refuting false positive tests in individual patients. Secondly, to allow for blinding of the active food challenge. Thirdly, applying a statistical model demonstrates that some positive challenges may be false positive and that the test may need to be repeated in selected cases.

Studies have been performed suggesting that administration of probiotics may have therapeutic and/or preventive benefits in the development of sensitization and atopic disease, particularly in infants with atopic dermatitis (AD).The purpose of this study was to evaluate the clinical and immunological effects of supplementation of a hydrolysed formula with two probiotic strains of bacteria on symptoms of AD in infancy.We conducted a randomized, double-blind, placebo-controlled study. After 4-6 weeks of baseline and double-blind, placebo-controlled challenges for diagnosis of cow's milk allergy (CMA), infants less than 5 months old with AD received a hydrolysed whey-based formula as placebo (n = 17), or supplemented with either Lactobacillus rhamnosus (n = 17) or Lactobacillus GG (n = 16) for 3 months. Before, during and after intervention, the clinical severity of AD was evaluated using SCORing index Atopic Dermatitis (SCORAD). Allergic sensitization was evaluated by measurement of total IgE and a panel of food-specific IgEs as well as skin prick testing for cow's milk. Inflammatory parameters were blood eosinophils, eosinophil protein X in urine, fecal alpha-1-antitrypsin and production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells after polyclonal stimulation.No statistically significant effects of probiotic supplementation on SCORAD, sensitization, inflammatory parameters or cytokine production between groups were found. Only four infants were diagnosed with CMA.We found no clinical or immunological effect of the probiotic bacteria used in infants with AD. Our results indicate that oral supplementation with these probiotic bacterial strains will not have a significant impact on the symptoms of infantile AD.

Objective: The purpose of this investigation was to verify if avoidance of allergenic foods in children adhering to a food allergen avoidance diet from birth was complete and feasible, and whether dietary assessment can be used as a tool in predicting the outcome of double-blind, placebo-controlled food challenges (DBPCFCs).Design: Children adhering to an allergen avoidance diet from birth underwent DBPCFCs. The investigator-dietician verified whether the elimination was complete, using food frequency questionnaires for common allergenic foods.Setting: University Medical Centre Groningen, the Netherlands.Subjects: Thiry-eight children aged 1-13 years, who were consecutively referred to the University Medical Centre Groningen for DBPCFC between January 2002 and February 2004.Results: Among the 38 children undergoing DBPCFCs, there were 15 challenges with egg, 15 with peanut, five with hazelnut and three with soy. Fifteen food challenges (39%) were positive. Small quantities of allergenic foods were inadvertently present in the diets of 13 patients (34%), were possibly present in the diets of 14 patients (37%) and could not be identified in the diets of 11 patients (29%). Seven patients (54%) who had inadvertently ingested small quantities of allergenic foods without sequelae had a positive DBPCFC.Conclusion: Dietary avoidance was incomplete and not feasible in most cases. Tolerance of small amounts of allergenic foods does not preclude positive challenge reactions. Dietary assessment does not seem a useful tool in predicting the outcome of DBPCFC in children adhering to an elimination diet.

In Nederland is blootstelling aan airborne allergenen binnenshuis (huisstofmijten, huisdieren en in mindere mate schimmels) een van de oorzaken van klachten bij allergische en astmatische patienten. Uit verschillende studies blijkt dat een beperking van de blootstelling aan deze allergenen kan bijdragen tot een vermindering van klachten of tot een afname van de overgevoeligheid van de luchtwegen bij patienten met astma (1). De beste oplossing is de verwijdering van de allergenenbron, wat echter niet altijd kan.

Het vastleggen van de allergische sensibilisatie door huidtests of serum IgE-metingen is een belangrijk hulpmiddel in de diagnostiek van allergische ziekten (1).

Multiple population studies have shown the presence of a sibling effect on atopic disease. However, it is unclear if the sibling effect is also of importance in subjects who are genetically at high risk for the development of atopy.To study the presence of a sibling effect on markers of atopy (serum total IgE, specific IgE, skin tests) and asthma (bronchial hyper-responsiveness to histamine) in families ascertained through a parent with asthma.First-degree offspring in 200 asthma families were studied (n = 541). Mixed effects regression models were used to account for the dependence of the observations within a family, and to adjust for possible confounding variables.Multiple regression analysis showed that having older siblings was inversely related to atopy, defined as/= 2,/= 3,/= 4, or/= 5 skin tests (P = 0.07-0.009). In addition, family size (number of siblings) had a significant protective effect on the presence of specific IgE to common aeroallergens (P = 0.03). Exposure to cigarette smoke in the first 3 years of life significantly increased the risk of having specific IgE to common aeroallergens (P = 0.04). No sibling effect was detected for serum total IgE or bronchial hyper-responsiveness to histamine.This study shows a protective sibling effect on the presence and severity of atopy but not on bronchial hyper-responsiveness in children who are genetically at risk. The identification of the sibling effect in high-risk families stresses the need to understand the basis of this effect, in order to design future prevention programmes.

Since heroin is delivered to a selected group of drug addicts under supervision of nurses in the Netherlands, we reported about several nurses who presented with work-related eczema and positive patch tests to heroin. To investigate the prevalence of heroin contact allergy among all workers in this heroin delivery project, a study was started using questionnaires. Altogether 31 nurses reported work-related complaints out of 100 who returned questionnaires. Besides reports of eczema, mainly of eyelids (probably airborne) and hands, there were mucosal and respiratory complaints. Patch tests were performed in 25 nurses with complaints; in 9 of them a heroin contact allergy could be confirmed. In 6 out of these 9 nurses this was combined with mucosal or respiratory complaints. There were also 6 nurses with mucosal or respiratory complaints without a contact allergy. Contact dermatitis from opioids, such as morphine and codeine, has been documented among opioid industry workers, nurses, doctors, pharmacists, and in patients. In conclusion heroin appears to be a potent contact allergen, causing contact dermatitis. Mucosal and respiratory complaints however, cannot be explained by this contact allergy; they might be caused by a type-1-allergy to heroin, or by a direct histamine liberating effect. Opioids are known histamine liberators causing urticaria, rhinitis and anaphylactoid reactions; therefore intracutaneous tests with heroin are unreliable. In an ongoing research project it will be attempted to detect specific IgE to heroin in the 12 workers with mucosal or respiratory complaints; within the next few months results will be available.

The degree of airway hyperresponsiveness in allergic asthmatic patients may be influenced by changes in environmental exposure to inhalant allergens.This study investigates the relationship between seasonal changes in exposure to house dust mite (HDM) allergens and non-specific airway hyperresponsiveness in asthmatic patients with multiple sensitizations to inhaled allergens.In 43 asthmatic patients sensitized to several inhalant allergens, lung function (FEV1), airway hyperresponsiveness (PC20 histamine), serum total IgE, house dust mite (HDM) specific IgE and number of peripheral blood eosinophils were measured during autumn 1990 (September-November) and spring 1991 (March-May). During each season, floor dust samples were collected twice from living- and bedrooms and the concentration of the HDM allergens Der p 1 and Der p 2 determined.More severe airway hyperresponsiveness (lower PC20 histamine) during autumn was only found in patients sensitized to HDM (n = 32; autumn: 2.05 mg/mL, spring: 4.51 mg/mL (geometric means), P0.01), whereas in patients not sensitized to HDM (n = 11) similar values were observed in both seasons (3.44 and 4.52 mg/mL, respectively, P = 0.56). More severe airway hyperresponsiveness of HDM sensitized patients in autumn was significantly associated with higher Der p 1 concentrations in floor dust. Aside from airway hyperresponsiveness, seasonal changes in serum total IgE and number of peripheral blood eosinophils were seen in patients sensitized to HDM.In allergic asthmatic patients, airway hyperresponsiveness may increase during autumn, depending on sensitization to HDM and an increase of exposure to HDM allergen.

Recommendations for allergen avoidance or allergen reduction measures play an important part in the treatment of allergic asthmatic patients. The purpose of this study was to test recently developed air-cleaners with respect to their capacity to capture airborne allergen particles and to improve clinical parameters of asthmatic patients sensitized to aeroallergens.Forty five allergic asthmatic patients were studied in a double-blind procedure for 6 months, The patients were divided into three groups of 15 patients. In Group 1, the intervention consisted of the application of active air-cleaners in living-rooms and bedrooms, In Group 2, placebo air-cleaners were used in combination with allergen-impermeable mattress covers, In Group 3, the same intervention was performed as in Group 2 but with active air-cleaners. Allergen levels in mattress and floor dust were measured before, and 3 and 6 months after the interventions, After 6 months, the air-cleaners were dismantled and the filters were analysed for the amount of dust collected and allergen content, Immunological and lung function parameters were measured before, and 3 and 6 months after the interventions.Considerable amounts of airborne dust and allergenic particles were captured in the filters of the air-cleaners, Up to the 18.9 g of dust, 4,513 ng of house dust mite allergen, Der p 1, and 50,000 mU of cat allergen, Fel d 1, (in houses with cats) were collected by air-cleaners in living-rooms, Only in Group 3 (in which both active air-cleaners and mattress covers were used) was a small (less than 1 doubling dose) but statistically significant improvement of provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20) observed (from 5.96 to 9.02 mg mL(-1)). The amount of dust and house dust mite allergen collected in the filters was significantly correlated with an improvement of peak flow variation.In combination with other allergen avoidance measures, the examined air-cleaners can contribute to diminished allergen exposure and improvement of airway hyperresponsiveness in asthmatic patients.

Background: Asthma caused by allergy to house dust mite is a growing problem. Patients with allergy who do not have asthma (yet) might develop asthma depending on exposure to precipitating factors. Objective: We sought to determine whether house dust mite avoidance measures have an effect on the development of asthma. Methods: Patients with allergy ( n = 29) who had no diagnosis of asthma (FEV1 of 99.1% ± 10.6% of predicted, peak flow variability of 5.21% ± 3.41%, reversibility of FEV1 after 400 μg salbutamol of 3.92% ± 3.75% according to the reference values) were randomly allocated (subjects blinded) to a treatment ( n = 16) and a placebo group ( n = 13). House dust mite avoidance treatment consisted of applying Acarosan (Allergopharma, J. Ganzer KG, Hamburg, Germany) (the placebo group used water) to the floors (living room, bedroom), and the use of covers for mattresses and bedding that were impermeable to house dust mite (the placebo group used cotton covers for mattresses only). We tested whether the intervention had an effect on peak flow parameters and asthma symptom scores during 6 weeks of treatment. Results: Significant improvements were seen in the treatment group in symptom scores (Borg score) for disturbed sleep, breathlessness, wheeze, and overall symptom score. Slight but statistically significant improvements in peak flow (morning, evening, and variability) were seen in the treatment group also. No significant changes were seen in the placebo group. Conclusions: Although this study is not long enough to study the development of asthma, the results indicates that house dust mite avoidance measures had an effect on peak flow parameters and asthma symptoms in patients with allergy but without asthma. These findings might implicate that a shift in developing clinically manifest asthma could be achieved with house dust mite avoidance measures. To give a better answer to whether preventing the development of asthma is possible, larger studies with a longer follow-up period are necessary. (J Allergy Clin Immunol 1997;100:313-9.)

Mal d 1 is not equally distributed over the apple. We aimed to examine the influence of the location of pricking in the apple on prick-to-prick skin prick test (PTP) results. PTPs were performed in autumn 2007 and spring 2008, before the birch pollen season, in 32 Dutch adults with symptoms of oral allergy to fresh apple, using apples harvested in autumn 2007. PTPs with fresh intact and unpeeled Pink Lady, Golden Delicious, Elise, Santana and Modi apples were performed using material obtained from approximately 2 cm near the stalk (top), and the middle region. All PTP responses were greater when performed with apple material near the stalk than from the middle region. In 2007, these differences were statistically significant for Pink Lady, Golden Delicious and Elise, and in 2008, for Pink Lady and Modi. When performing PTPs, the apple should be pricked near the stalk rather than in the middle.

Rationale Infants at high risk for developing food allergy are advised to delay the introduction of highly allergenic foods. The purpose of this study was to verify the complete avoidance of these foods as reported by the parents. Methods In 22 children double blind placebo-controlled food challenges (DBPCFC's) were performed with foods which had been eliminated from the diet from birth. The presence of the eliminated allergenic foods in the diet was ascertained by an experienced dietitian. Specific food frequency questionnaires for foods containing either milk, egg, soy, peanut or nuts were developed (but not validated) and adapted to foods and brands frequently used in the Netherlands. Special attention was paid to the correct reading of labels on commercial products. The composition of manufactured foods was verified by inquiring with the manufacturers or obtaining data available from the Allergen Databank Alba (TNO Nutrition and Food Research, the Netherlands). Results The detailed dietary history was inconclusive in 9 children (41%), revealed no allergenic foods in the diets of 4 children (18%), but showed incidental presence of the allergenic foods in the diets of 9 children (41%). None of these unintentional ingestions resulted in clinical reactions. However, in 4 of the 9 children who inadvertently ingested small amounts of the allergenic food by history, DBPCFC with the same food was positive. Conclusion Complete dietary avoidance of allergenic foods is difficult and often incomplete. Ascertainment of previous asymptomatic ingestion of small amounts of allergenic foods does not preclude positive challenge reactions.

A rapid, quantitative method is described for the analysis of fatty acids from human lipids, namely serum lipids and lipids from adipose tissue biopsies. The method includes extraction of serum lipids with chloroform—methanol, hydrolysis with tetramethylammonium hydroxide, methylation with methyl iodide and N,N-dimethylformamide and gas chromatographic analysis on a Supelcoport SP-2330 column. Fat biopsies are analysed without extraction. Optimal hydrolysis conditions have been investigated.

IgG, IgA and IgM ELISA antibody titers against Aspergillus fumigatus were elevated in sera of patients with aspergilloma and allergic bronchopulmonary aspergillosis (ABPA), showing higher titers for the IgG antibodies compared with the IgA and IgM antibodies. No differences were found between titers of identical antibody classes in the two groups of sera. IgG and IgA ELISA titers were highly specific whereas IgM ELISA showed more unspecific binding of IgM antibodies. Antibodies, as measured by ELISA, studied after fractionation of the antigen into fractions of decreasing molecular weight, showed a preferential binding by the high molecular weight fractions. Precipitating antibodies studied in patient sera did not always correspond with the IgG ELISA titers. IgE antibody binding was observed in all fractions from Sephadex G-100 fractionated components; maximum binding was found with fractions of 28,000–60,000 daltons. The low molecular weight fractions (18,000–

The liberation of polystyrene binding antigenic components (PBC) of Aspergillus fumigatus involved in ELISA IgG measurements was studied during cultivation in the culture filtrates. PBC were rapidly liberated into the culture medium during the logarithmic phase of growth (phase I), were in part degraded or reconsumed during the stationary phase (phase II) and again secreted (other PBC) during the lytic phase (phase III). ELISA IgG titers and numbers of precipitating components are not always related with one another, may show an inverse relationship; maximal ELISA titers are reached during phase I when precipitating components are limited. The striking similarity between the liberation of PBC and IgE-binding components is discussed.

When growing Botrytis cinerea in Sabouraud medium, different phases of growth could be recognized using pH, mycelium yield, and culture filtrate antigens as parameters of growth. Immunological characteristics of the different phases (early, intermediate, and late) of growth were measured using IgE and IgG binding by enzyme allergosorbent test and enzyme-linked immunosorbent assay, respectively, and quantities of precipitating components (double immunodiffusion and rocket immunoelectrophoresis). The number of precipitating components was maximal in culture filtrate extracts during late phase (III) of growth. In contrast, both IgE and IgG binding were already maximal in the early phase of growth (9 days of cultivation). In a group of patients with elevated IgE antibodies against Aspergillus fumigatus, about half of them also showed elevated IgE antibodies against B. cinerea. This indicates that multiple exposition is a cause of multiple sensitization; however, cross-reactivity in some of these sera cannot be excluded.