European legislators and wine producers still debate on the requirement for labeling of wines fined with potentially allergenic food proteins (casein, egg white or fish-derived isinglass). We investigated whether wines fined with known concentrations of these proteins have the potential to provoke clinical allergic reactions in relevant patients.|In-house wines were produced for the study, fined with different concentrations of casein (n = 7), egg albumin (n = 1) and isinglass (n = 3). ELISA and PCR kits specific for the respective proteins were used to identify the fining agents. Skin prick tests and basophil activation tests were performed in patients with confirmed IgE-mediated relevant food allergies (n = 24). A wine consumption questionnaire and detailed history on possible reactions to wine was obtained in a multinational cohort of milk, egg or fish allergic patients (n = 53) and patients allergic to irrelevant foods as controls (n = 13).|Fining agents were not detectable in wines with the available laboratory methods. Nevertheless, positive skin prick test reactions and basophil activation to the relevant wines were observed in the majority of patients with allergy to milk, egg or fish, correlating with the concentration of the fining agent. Among patients consuming wine, reported reactions were few and mild and similar with the ones reported from the control group.|Casein, isinglass or egg, remaining in traces in wine after fining, present a very low risk for the respective food allergic consumers. Physician and patient awareness campaigns may be more suitable than generalized labeling to address this issue, as the latter may have negative impact on both non-allergic and allergic consumers.

A prospective epidemiologic surveillance of hospitalizations associated with influenza was conducted in order to calculate population-based hospitalization rates. Eligible children were 6 months to 13 years of age and were admitted to one of the two large children's hospitals in the Athens area during two influenza seasons. Nasopharyngeal aspirates were tested for influenza by a polymerase reaction assay. Influenza accounted for 9.9-11.8% of all admissions during the influenza season and the overall annual rate of hospitalizations was 13.6-16.8 cases per 10,000 children being highest for children under 5 years of age (26-31.2/10,000 children). Febrile seizures and acute otitis media were the two most common complications associated with influenza and antibiotics were administered to 61% of flu positive patients. Influenza is associated with high hospitalization rates among young children and these may be substantially reduced with the introduction of routine immunization.

Allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) are highly burdensome diseases, which are increasing in prevalence, especially in the paediatric population. Despite the availability of a large number of medications for treatment of AR and CIU, their use in children has primarily been based on data obtained from a limited number of clinical trials in children and/or testing in adults. The H(1)-antihistamines have traditionally been used as first-line treatment for the relief of both AR and CIU symptoms in children. The first-generation H(1)-antihistamines are associated with marked adverse effects such as sedation, sleepiness/drowsiness as well as difficulties in learning and cognitive processing; thus, they are recommended for limited or discontinued use in children with AR or CIU. In contrast, second-generation H(1)-antihistamines are more adapted for the use in children with AR and CIU due to better safety profiles. However, only a limited number of trials with these agents have been conducted and generally, data from well-designed trials in children are lacking. Levocetirizine is one of the most extensively investigated H(1)-antihistamines for its pharmacologic properties, safety, efficacy as well as overall global satisfaction in children aged 2-12 years. Levocetirizine is the only H(1)-antihistamine launched in the 21st century shown to lack clinically relevant adverse effects on physical and psychomotor development or routine laboratory tests over a long-term period of 18 months in 1- to 3-year-old children predisposed to development of allergic disease. Available data suggest that levocetirizine is a suitable treatment option for AR and CIU in children aged 6 months to 12 years.

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

The mechanisms governing the induction of peripheral tolerance as a result of specific immunotherapy are far from being clearly characterized. In the last 15 years, a number of studies have highlighted the tolerogenic role of regulatory T cells, blocking antibodies and anti-inflammatory cytokines such as IL-10 and TGF-β; however, the best part of our knowledge is mostly limited to mechanisms underlying the maintenance phase. By contrast, little is known regarding the very early effects seen in rush and ultrarush immunotherapy protocols. In this article, Bussmann et al. provide evidence on the possible role, first, of inhibitory receptors of the leukocyte immunoglobulin-like receptor family and, second, of the upregulation of indoleamine 2,3-dioxygenase and subsequent tryptophan starvation on the induction of specific tolerance within a few hours after the initial doses. They also suggest that the observed changes reflect the activation of protective mechanisms, which we are just beginning to understand.

Venom immunotherapy (VIT) has been shown to be an effective and safe treatment for preventing sting-induced anaphylaxis in patients with systemic reactions to hymenoptera stings. A remaining problem is the relative effectiveness and safety of different immunotherapy protocols used with respect to maintenance dose, injection interval, and duration.|We aimed to describe a modified cluster VIT protocol with a maintenance dose of 50 μg lasting 5 yr and to evaluate retrospectively its safety and efficacy in children.|Fifty four children 9.5±3.2 yr old with a history of at least one anaphylactic reaction to hymenoptera stings underwent VIT between 1995 and 2006. The identification of the offending insect(s) was based on patient's report and documented with in-vivo (SPTs and IDs) and in-vitro (RAST/CAP) test results. A modified cluster outpatient protocol lasting 5 wks, reaching a maintenance dose of 50 μg was followed according to clinical history and test results. After the maintenance dose was achieved, the followed injection-intervals were 4 wks for the first year, 5 wks for the 2nd year and 3rd year, and 6 wks for the last 2 yr.|Of the 54 children, 52 tolerated the 50 μg VIT protocol without side effects. Twenty one of them reported at least one field sting from at least one of the culprit, for their allergy, insects, 6±3.5 yr after they have started VIT treatment. In 11 of them, sting occurred 3.5±2.9 yr after the VIT was completed, whereas the other 10 of them during immunotherapy, 3.2±1.4 yr after they have started VIT. In the remaining two children, the maintenance dose was increased to 100 μg due to systemic reactions from the VIT. The data reflect outcomes 6-16 yr after the patients' initial allergic reaction.|VIT with 50 μg maintenance dose lasting 5 yr appears to be safe and effective enough to induce tolerance in children with hymenoptera venom hypersensitivity.

Acute urticaria (AU) is a common condition that often presents in childhood. Although there is a general perception of cyclic annual trends in AU, no one has tried to identify any seasonal variation on its prevalence and incidence, associate environmental influences and impute geographic, ethnic, or even genetic features that may contribute to its onset. We aimed to analyze the influence of climate and geographic parameters on annual fluctuation of AU cases referred to the Emergency Departments (EDs) of Norwich (UK) and Heraklion (Crete, Greece), compare all identifiable potential triggers and severity, and calculate the prevalence and incidence of AU. Record-based data of all children up to 14 yr of age referred to both EDs between June 2005 and May 2007 were examined retrospectively. Demographic characteristics and any potential identifiable triggers of AU were recorded and compared. Poisson's regression was utilized to examine any influence of meteorological parameters on AU incidence. Edwards' test for seasonality was applied to identify any significant seasonal trend of the AU incidence within each city. Seven hundred and twenty-nine AU cases were identified (324 in Norwich and 405 in Heraklion), among 56,624 total referrals (28,931 and 27,693 cases, respectively). Respiratory infections were found to be the most commonly associated potential triggers of AU and food allergens the least. AU cases and incidence rates in both cities were equally distributed during the study period. A non-significant seasonal trend in AU incidence (October, April-May) was observed in Norwich, in contrast to a significant seasonal pattern (December, February-May) of AU in Heraklion. Temperature was inversely associated with AU incidence, while the statistically significant effect of relative humidity varied. Acute childhood urticaria shows a similar epidemiological pattern in northern and southern Europe regardless of the expected differences in genetic, geographic, and environmental background. Temperature and humidity are correlated with AU incidence. Seasonality of several acute respiratory viral infections, the most prominent associated trigger of AU, coincides with the observed AU seasonality, suggesting a potential linkage. However, this needs to be elucidated from larger epidemiological studies.

{Cow's milk is one of the most common causes of food allergy. In two-thirds of patients, adverse symptoms following milk ingestion are caused by IgE-mediated allergic reactions, whereas for one-third, the mechanisms are unknown. Aim of this study was to investigate whether patients suffering from non-IgE-mediated cow's milk protein intolerance can be distinguished from persons without cow's milk protein intolerance based on serological measurement of IgG and IgA specific for purified cow's milk antigens.|We determined IgG(1-4) subclass and IgA antibody levels to purified recombinant αS1-casein, αS2-casein, β-casein, κ-casein, α-lactalbumin, and β-lactoglobulin in four patient groups by ELISA: Patients with IgE-mediated cow's milk allergy (CMA

Comparable international data on food and nutrient intake is often hindered by the lack of a common instrument to assess food intake. The objective of this study was within the Global Allergy and Asthma European Network of Excellence (GA(2)LEN), we developed and piloted a food frequency questionnaire (FFQ) to assess its validity in Europe.|Five countries participating in GA(2)LEN took part in the pilot study. A total of 200 adults aged 31-75 years were invited to complete a FFQ in two occasions and to give a blood sample. The intra-class correlation coefficient (ICC) was used to assess repeatability of the FFQ. Plasma phospholipid fatty acids (FAs) were analysed by gas chromatography. Pearson correlation was used to analyse the correlation between estimated dietary FA intake and plasma phospholipid FA levels.|A total of 177 participants (89%) had complete data on FFQ(1) and plasma phospholipid FAs. In all, 152 participants (76%) completed both FFQs. ICCs between macronutrients ranged from 0.70 (saturated FAs) to 0.78 (proteins) and between 0.70 (retinol) and 0.81 (vitamin D) for micronutrients. Dietary n-3 FAs showed a good correlation with total plasma phospholipid n-3 FAs and with docosahexaenoic acid in the whole sample (0.40) and in individual countries. Poor correlations were observed for other FAs.|The GA(2)LEN FFQ is an appropriate tool to estimate dietary intake for a range of nutrients across Europe regardless of cultural and linguistic differences. The FFQ seems to be useful to estimate the intake of n-3 FAs but not other FAs.

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.

Cow's milk (CM) allergy affects about 2% of infants. The allergenicity of dietary proteins, including those from CM, has been related to their digestibility although the generality of the link and its causality remains to be demonstrated. In this study we use an in vitro digestion system, to investigate the digestibility of β-lactoglobulin (blg) during gastrointestinal transit and to assess the impact of this process on blg allergenic reactivity in CM allergic children.|Blg digesta were prepared using an in vitro digestion protocol simulating either gastric digestion alone or followed by duodenal digestion with or without phosphatidylcholine (PC). Biochemical analysis of blg digesta was performed by SDS-PAGE and their concentration was measured by a sandwich ELISA. Assessment of their allergenic reactivity was done in vitro by EAST inhibition, specific basophil activation (basotest) and lymphocyte proliferation (PCNA-flow cytometry) assays using sera and cells from patients allergic to blg and in vivo by skin prick testing (SPT) of these patients.|Blg was only broken down to smaller peptides after gastro-duodenal digestion although a sizeable amount of intact protein still remained. Digestion did not modify the IgE binding capacity of blg except for gastro-duodenal digestion performed in the absence of PC. These results are consistent with the quantity of intact blg remaining in the digesta. Overall both gastric and gastroduodenal digestion enhanced activation of sensitized basophils and proliferation of sensitized lymphocytes by blg. However, there was a tendency towards reduction in mean diameter of SPT following digestion, the PC alone during phase 1 digestion causing a significant increase in mean diameter.|Digestion did not reduce the allergenic reactivity of blg to a clinically insignificant extent, PC inhibiting digestion and thereby protecting blg allergenic reactivity. SPT reactivity was reduced compared to blg immunoreactivity in in vitro tests.