Do human rhinovirus infections and food allergy modify grass pollen-induced asthma hospital admissions in children?

Asthma prevalence in children has remained relatively constant in many Western countries, but hospital admissions for younger age groups have increased over time.1 Although the role of outdoor aeroallergens as triggers for asthma exacerbations requiring hospitalization in children and adolescents is complex, there is evidence that increasing concentrations of grass pollen are associated with an increased risk of asthma exacerbations in children.2 Human rhinovirus (HRV) infections are implicated in most of the serious asthma exacerbations in school-age children.3 In previous research, HRV infections and aeroallergen exposure have usually been studied independently. To our knowledge, only 1 study has examined interactions between these 2 factors,4 but lack of power prevented any meaningful interpretation...

Condition-specific associations of symptoms of depression and anxiety in adolescents and young adults with asthma and food allergy

Objective: This study examined associations of asthma and food allergy with symptoms of depression and anxiety at 14 and 21 years of age to determine whether condition-specific associations exist. Methods: Data come from 4972 adolescents in the Mater University Study of Pregnancy. Symptoms of depression and anxiety were assessed using the Youth Self-Report and Young Adult Self-Report. Results: Condition-specific associations between asthma and depression, OR=1.37 [1.12, 1.67] and between food allergy and anxiety, OR=1.26 [1.04, 1.76] were found during adolescence, but not in young adulthood. Whereas asthma was associated with resolved depression, OR=1.70 [1.13, 2.55], food allergy was associated with persistent anxiety, OR=1.26 [1.01, 1.59]. Conclusions: In adolescents, asthma is associated with an increased risk of clinically relevant symptoms of depression and food allergy with and increased risk of clinically relevant symptoms of anxiety. Future research is needed to clarify directionality and mechanisms explaining these relationships. Health professionals should be aware of the increased risk of mental health problems in adolescents with asthma or food allergy.

Digital signal processing and artificial intelligence for the automated classification of food allergy

As a by-product of the ‘information revolution’ which is currently unfolding, lifetimes of man (and indeed computer) hours are being allocated for the automated and intelligent interpretation of data. This is particularly true in medical and clinical settings, where research into machine-assisted diagnosis of physiological conditions gains momentum daily. Of the conditions which have been addressed, however, automated classification of allergy has not been investigated, even though the numbers of allergic persons are rising, and undiagnosed allergies are most likely to elicit fatal consequences. On the basis of the observations of allergists who conduct oral food challenges (OFCs), activity-based analyses of allergy tests were performed. Algorithms were investigated and validated by a pilot study which verified that accelerometer-based inquiry of human movements is particularly well-suited for objective appraisal of activity. However, when these analyses were applied to OFCs, accelerometer-based investigations were found to provide very poor separation between allergic and non-allergic persons, and it was concluded that the avenues explored in this thesis are inadequate for the classification of allergy. Heart rate variability (HRV) analysis is known to provide very significant diagnostic information for many conditions. Owing to this, electrocardiograms (ECGs) were recorded during OFCs for the purpose of assessing the effect that allergy induces on HRV features. It was found that with appropriate analysis, excellent separation between allergic and nonallergic subjects can be obtained. These results were, however, obtained with manual QRS annotations, and these are not a viable methodology for real-time diagnostic applications. Even so, this was the first work which has categorically correlated changes in HRV features to the onset of allergic events, and manual annotations yield undeniable affirmation of this. Fostered by the successful results which were obtained with manual classifications, automatic QRS detection algorithms were investigated to facilitate the fully automated classification of allergy. The results which were obtained by this process are very promising. Most importantly, the work that is presented in this thesis did not obtain any false positive classifications. This is a most desirable result for OFC classification, as it allows complete confidence to be attributed to classifications of allergy. Furthermore, these results could be particularly advantageous in clinical settings, as machine-based classification can detect the onset of allergy which can allow for early termination of OFCs. Consequently, machine-based monitoring of OFCs has in this work been shown to possess the capacity to significantly and safely advance the current state of clinical art of allergy diagnosis

Hypoallergenic legume crops and food allergy: factors affecting feasibility and risk.

Currently, the sole strategy for managing food hypersensitivity involves strict avoidance of the trigger. Several alternate strategies for the treatment of food allergies are currently under study. Also being explored is the process of eliminating allergenic proteins from crop plants. Legumes are a rich source of protein and are an essential component of the human diet. Unfortunately, legumes, including soybean and peanut, are also common sources of food allergens. Four protein families and superfamilies account for the majority of legume allergens, which include storage proteins of seeds (cupins and prolamins), profilins, and the larger group of pathogenesis-related proteins. Two strategies have been used to produce hypoallergenic legume crops: (1) germplasm lines are screened for the absence or reduced content of specific allergenic proteins and (2) genetic transformation is used to silence native genes encoding allergenic proteins. Both approaches have been successful in producing cultivars of soybeans and peanuts with reduced allergenic proteins. However, it is unknown whether the cultivars are actually hypoallergenic to those with sensitivity. This review describes efforts to produce hypoallergenic cultivars of soybean and peanut and discusses the challenges that need to be overcome before such products could be available in the marketplace.

Basophil activation tests for the diagnosis of food allergy in children.

BACKGROUND: Positive skin prick tests (SPT) for food allergens and specific IgE (sIgE) in serum indicate sensitization but do not enable distinction between sensitized but tolerant and clinically allergic patients. OBJECTIVE: Herein, we evaluate the clinical relevance of basophil activation tests (BATs) for peanut or egg allergy diagnosis. METHODS: Thirty-two peanut-allergic, 14 peanut-sensitized (sIgE(+) and/or SPT(+) to peanuts) but tolerant children and 29 controls with no history of an adverse reaction to peanuts were included. Similarly, 31 egg-allergic, 14 egg-sensitized children (sIgE(+) and/or SPT(+) to egg white) and 22 controls were studied. Flow cytometric analysis of CD63 expression or CD203c upregulation on basophils and the production of leukotrienes (LT) were performed in response to an in vitro crude peanut extract or ovalbumin (OVA) challenge. RESULTS: After in vitro peanut challenge, the basophils from peanut-allergic children showed significantly higher levels of activation than those from controls (P<0.001). After OVA challenge, a similar distinction (P<0.001) was observed between egg-allergics and controls. Interestingly, the majority of egg- or peanut-sensitized children failed to activate basophils, respectively, in response to OVA and peanut challenge. The sensitivity of the CD63, CD203c and LT assay was 86.7%, 89.5% and 76.0% with a specificity of 94.1%, 97.1% and 94.6% for peanut allergy diagnosis. The corresponding performances of BATs applied to egg allergy diagnosis were 88.9%, 62.5% and 77.8% for the sensitivity and 100%, 96.4% and 96.4% for the specificity. CONCLUSION: Neither conventional tests nor BATs are sensitive and specific enough to predict food allergy accurately. However, BATs may helpfully complete conventional tests, especially SPT, allowing improved discrimination between allergic and non-allergic individuals.

Parent perceived quality of life is age-dependent in children with food allergy.

Food allergy in children significantly affects their quality of life. Its impact can be analyzed by quality of life questionnaires. The aim of our study was to validate the French version of disease-specific questionnaires and to evaluate the quality of life in children with IgE-mediated food allergy. Two validated food allergy-specific questionnaires for quality of life, the parent's and children's forms (FAQLQ-PF and FAQLQ-CF), were translated from English to French and submitted to children with food allergy and their parents. Questionnaires were analyzed in terms of emotional impact, food anxiety, and social and food limitations. NCT 01480427. Sixty-two parents of children aged 0-12 yrs answered the FAQLQ-PF, and 32 children aged 8-12 yrs the FAQLQ-CF. Construct validity of both questionnaires was assessed by correlation between the FAQLQs and FAIM (r = 0.85 and 0.84, respectively). Both FAQLQs had good internal consistency (Cronbach's α = 0.748 and 0.67, respectively). Young children (0-3 yrs old) showed better quality of life scores than older children (FAQLQ-PF global score: p = 0.02). Worse scores were also shown among children with previous severe systemic reactions (FAQLQ-PF global score: p = 0.039), the ones with an allergic mother (FAQLQ-PF global score: p = 0.002), or allergic siblings (FAQLQ-PF emotional impact score: p = 0.034), the ones with multiple food allergy (more than 1 food) (FAQLQ-PF anxiety score: p = 0.04) and among the girls (FAQLQ-CF global score: p = 0.031). Older children, the ones with severe systemic reactions, or with mothers or siblings also affected by allergies, as well as girls, and children with multiple food allergies show worse quality of life scores.

Potential links between the emerging risk factors for food allergy and vitamin D status

A variety of hypotheses have been proposed to explain the recently described increase in food allergy among children living in developed countries. In this study, we summarize the emerging risk factors for IgE-mediated food allergy in early life, and then review the evidence for and against an association between low vitamin status (VDS) and food allergy.

We consider whether each of the epidemiological variables that have been associated with food allergy may also be associated with VDS; and argue that future studies must adequately account for the potential relationships between risk factors for food allergy and VDS, and must also discriminate between vitamin D derived by sun exposure, diet and oral supplementation.

The potential link between gut microbiota and IgE-mediated food allergy in early life

There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field.

Are vitamins A and D important in the development of food allergy and how are they best measured?

Food allergy has a dramatic impact on a child's (and their family's) quality of life and places a major financial burden on the community. It has been hypothesized that the increase in food allergy may relate to the concordant rise in prevalence of vitamin D insufficiency. More recently a second hypothesis has implicated vitamin A sufficiency in the development of immune tolerance. Together, these hypotheses have prompted investigation into the circulating levels of vitamins A and D in relation to food allergy prevalence. This review aims to examine the relationship between vitamins A and D and food allergy. The first part of this review presents the available epidemiological data which proposes a dramatic increase of food allergy and related anaphylaxis during the last two decades. There is some indirect evidence that variation in food allergy prevalence within countries might be linked with ambient ultra violet radiation exposure and thus potentially with vitamin D levels. Only a few studies to date have directly examined the relationship between measured serum vitamin D levels and either food sensitization or allergy. The significance of vitamin A in food allergy prevalence is only provided through a hypothetical association due to its role in the immune system. The second part of this review discusses the relevant aspects of the analytical methods to assess vitamin A and D levels in children. The primary methods utilized relate to measuring the main circulating forms of vitamins A and D in blood i.e. retinol and 25-hydroxy-vitamin-D3 respectively. Chromatographic separation coupled with mass spectrometric detection is considered the gold standard method for both vitamins. These analytical methods should be fully validated for the use in pediatric populations to ensure they are fit for their clinical purpose.

Which infants with eczema are at risk of food allergy? Results from a population-based cohort

BACKGROUND: The relationship between early onset eczema and food allergy among infants has never been examined in a population-based sample using the gold standard for diagnosis, oral food challenge. OBJECTIVE: We characterised the risk of challenge-proven food allergy among infants with eczema in the general population. METHODS: One-year-old infants (n = 4453 meeting criteria for this analysis) were assessed for history of eczema, received a nurse-administered eczema examination and underwent skin prick testing to peanut, egg and sesame. Those with a detectable wheal to one of the test foods underwent an oral food challenge irrespective of wheal size. The risk of food allergy, stratified by eczema severity and age of onset, was estimated using multivariate logistic regression with population sampling weights. RESULTS: One in five infants with eczema were allergic to peanut, egg white or sesame, compared to one in twenty-five infants without eczema (OR 6.2, 95% CI 4.9, 7.9, P < 0.001). The prevalence of peanut allergy was low in the absence of eczema (0.7% 95% CI 0.4, 1.1). Infants with eczema were 11.0 times more likely to develop peanut allergy (95% CI 6.6, 18.6) and 5.8 times more likely to develop egg allergy (95% CI 4.6, 7.4) by 12 months than infants without eczema. 50.8% of infants (95% CI 42.8, 58.9) with early eczema onset (<3 months) who required doctor-prescribed topical corticosteroid treatment developed challenge-proven food allergy. CONCLUSION AND CLINICAL RELEVANCE: Eczema, across the clinical severity spectrum in infancy, is a strong risk factor for IgE-mediated food allergy. Infants with eczema were six times more likely to have egg allergy and 11 times more likely to have peanut allergy by 12 months than infants without eczema. Our data suggest that a heightened awareness of food allergy risk among healthcare practitioners treating infants with eczema, especially if early onset and severe, is warranted.

Is low vitamin D status a risk factor for food allergy? Current evidence and future directions

Studies from several countries have reported an association between latitudes further from the equator and proxy markers of food allergy prevalence. As latitudes further from the equator are associated with lower sun exposure and vitamin D status (VDS), it has been proposed that low VDS may be a risk factor for food allergy. A range of basic science evidence supports the biological plausibility of this hypothesis; and recent work has identified a cross sectional association between low VDS and challenge proven food allergy in infants. Overall, however, the evidence regarding the relationship between VDS and food allergy remains controversial and the limited longitudinal data are discouraging. In this review we consider the evidence for and against low VDS as a risk factor for food allergy and discuss the possibility that other factors (including genetic variables) may contribute to the inconsistent nature of the available observational evidence. We then discuss whether genetic and/or environmental factors may modify the potential influence of VDS on food allergy risk. Finally, we argue that given the rising burden of food allergy, the balance of available evidence regarding the potential relevance of VDS to this phenomenon, and the inherent limitations of the existing observational data, there is a compelling case for conducting randomised clinical trials of vitamin D supplementation for the prevention of food allergy during early life.

Novel insights into mechanisms of food allergy and allergic airway inflammation using experimental mouse models

Over the last decades, considerable efforts have been undertaken in the development of animal models mimicking the pathogenesis of allergic diseases occurring in humans. The mouse has rapidly emerged as the animal model of choice, due to considerations of handling and costs and, importantly, due to the availability of a large and increasing arsenal of genetically modified mouse strains and molecular tools facilitating the analysis of complex disease models. Here, we review latest developments in allergy research that have arisen from in vivo experimentation in the mouse, with a focus on models of food allergy and allergic asthma, which constitute major health problems with increasing incidence in industrialized countries. We highlight recent novel findings and controversies in the field, most of which were obtained through the use of gene-deficient or germ-free mice, and discuss new potential therapeutic approaches that have emerged from animal studies and that aim at attenuating allergic reactions in human patients.