Exploratory immunogenicity outcomes of peanut oral immunotherapy: Findings from the PALISADE trial.

BACKGROUND: Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen-specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters. METHODS: Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) and placebo in the double-blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut-specific and peanut component-specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes. RESULTS: A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double-blind placebo-controlled food challenge (DBPCFC). In PTAH-treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components. CONCLUSIONS: Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder-dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02635776.

Sesame allergy in children: New insights into diagnosis and management.

Sesame is a potentially potent allergen that can trigger skin, gastrointestinal, and respiratory tract symptoms, and anaphylaxis. Only 20% to 30% of sesame-allergic children develop tolerance. The prevalence of sesame allergy depends on local diets and ranges from 0.1% to 0.9%. A high risk of accidental exposure to sesame has resulted in mandatory food labeling in many countries. More than half of patients with sesame allergy are also allergic to peanut/tree nuts. Serum-specific IgE testing with a quantitative Ses i 1 component can be performed safely and has higher clinical specificity and better positive predictive value for oral food challenge (OFC) than whole sesame extract or skin prick testing (SPT). Compared with SPT or OFC, in vitro Ses i 1 testing requires no special techniques and carries no risk of reactions. Diagnosis of suspected sesame allergy begins with a thorough history and physical examination. A positive sesame extract test (≥0.1 kUA /L) should prompt further testing. In patients with a high probability of reacting, results of component testing may facilitate a decision about performing an OFC. In a Japanese study of OFC and Ses i 1, there was a 5% probability of a positive OFC with Ses i 1 sIgE levels <0.13 kUA /L, and a 50% probability of a positive OFC with levels >32.0 kUA /L. Most patients could safely consume sesame if sIgE levels were <0.13 kUA /L. Ses i 1 testing can be used to guide appropriate management (avoidance, emergency medication, and oral immunotherapy).

Asthma and Allergy: Unravelling a Tangled Relationship with a Focus on New Biomarkers and Treatment.

Asthma is a major driver of health care costs across ages. Despite widely disseminated asthma-treatment guidelines and a growing variety of effective therapeutic options, most patients still experience symptoms and/or refractoriness to standard of care treatments. As a result, most patients undergo a further intensification of therapy to optimize symptom control with a subsequent increased risk of side effects. Raising awareness about the relevance of evaluating aeroallergen sensitizations in asthmatic patients is a key step in better informing clinical practice while new molecular tools, such as the component resolved diagnosis, may be of help in refining the relationship between sensitization and therapeutic recommendations. In addition, patient care should benefit from reliable, easy-to-measure and clinically accessible biomarkers that are able to predict outcome and disease monitoring. To attain a personalized asthma management and to guide adequate treatment decisions, it is of paramount importance to expand clinicians' knowledge about the tangled relationship between asthma and allergy from a molecular perspective. Our review explores the relevance of allergen testing along the asthma patient's journey, with a special focus on recurrent wheezing children. Here, we also discuss the unresolved issues regarding currently available biomarkers and summarize the evidence supporting the eosinophil-derived neurotoxin as promising biomarker.

Peanut Can Be Used as a Reference Allergen for Hazard Characterization in Food Allergen Risk Management: A Rapid Evidence Assessment and Meta-Analysis.

Regional and national legislation mandates the disclosure of "priority" allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen ("may contain") labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed "reference doses," below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure.

New visions for food allergy: an iPAC summary and future trends.

The spectrum of food allergy consists of a variety of different clinical pictures including immunoglobulin (Ig)E, and non-IgE food allergy as well as mixed, IgE and non-IgE disorders. In addition, eosinophilic diseases of the gastrointestinal (GI) tract with occasional IgE-type sensitization are increasingly recognized. As a consequence, the clinical picture of food allergy is pleomorphic and can range from chronic GI symptoms to severe anaphylaxis. The diagnosis of food allergy is mostly hampered by the lack of reliable in vitro tests for non-IgE-mediated diseases, and in most cases relies on a reoccurrence of symptoms upon re-exposure to the antigen; in general during a standardized food challenge. Currently, there is no safe and efficient treatment for food allergy and the treatment relies on avoidance diets. Priorities for research have been identified by iPAC (international Pediatric Allergy and Asthma Consortium) and outlined in this review. They include studies to better identify the pathogenesis of food allergy, including genetic aspects; studies to develop diagnostic and follow-up tests; studies for standardization of food challenges; as well as studies addressing a safe and efficient treatment of food allergy.

The prevalence of plant food allergies: a systematic review.

BACKGROUND: There is uncertainty regarding the prevalence of allergies to plant food. OBJECTIVE: To assess the prevalence of allergies to plant food according to the different subjective and objective assessment methods. METHODS: Our systematic search of population-based studies (since 1990) in the literature database MEDLINE focused on fruits, vegetables/legumes, tree nuts, wheat, soy, cereals, and seeds. Prevalence estimates were categorized by food item and method used (food challenges, skin prick test, serum IgE, parent/self-reported symptoms), complemented by appropriate meta-analyses. RESULTS: We included 36 studies with data from a total of over 250,000 children and adults. Only 6 studies included food challenge tests with prevalences ranging from 0.1% to 4.3% each for fruits and tree nuts, 0.1% to 1.4% for vegetables, and < 1% each for wheat, soy, and sesame. The prevalence of sensitization against any specific plant food item assessed by skin prick test was usually < 1%, whereas sensitization assessed by IgE against wheat ranged as high as 3.6% and against soy as high as 2.9%. For fruit and vegetables, prevalences based on perception were generally higher than those based on sensitization, but for wheat and soy in adults, sensitization was higher. Meta-analyses showed significant heterogeneity between studies regardless of food item or age group. CONCLUSION: Population-based prevalence estimates for allergies to plant products determined by the diagnostic gold standard are scarce. There was considerable heterogeneity in the prevalence estimates of sensitization or perceived allergic reactions to plant food.

The prevalence of food allergy: a meta-analysis.

BACKGROUND: There is uncertainty about the prevalence of food allergy in communities. OBJECTIVE: To assess the prevalence of food allergy by performing a meta-analysis according to the method of assessment used. METHODS: The foods assessed were cow's milk, hen's egg, peanut, fish, shellfish, and an overall estimate of food allergy. We summarized the information in 5 categories: self-reported symptoms, specific IgE positive, specific skin prick test positive, symptoms combined with sensitization, and food challenge studies. We systematically searched MEDLINE and EMBASE for publications since 1990. The meta-analysis included only original studies. They were stratified by age groups: infant/preschool, school children, and adults. RESULTS: A total of 934 articles were identified, but only 51 were considered appropriate for inclusion. The prevalence of self-reported food allergy was very high compared with objective measures. There was marked heterogeneity between studies regardless of type of assessment or food item considered, and in most analyses this persisted after age stratification. Self-reported prevalence of food allergy varied from 1.2% to 17% for milk, 0.2% to 7% for egg, 0% to 2% for peanuts and fish, 0% to 10% for shellfish, and 3% to 35% for any food. CONCLUSION: There is a marked heterogeneity in the prevalence of food allergy that could be a result of differences in study design or methodology, or differences between populations. CLINICAL IMPLICATIONS: We recommend that measurements be made by using standardized methods, if possible food challenge. We need to be cautious in estimates of prevalence based only on self-reported food allergy.

The types of circulating fatty acids influence vascular reactivity.

The objective of this study was to investigate the relationship between the composition of FA in serum lipids, a marker of dietary fat intake, and vascular reactivity using a combination of cross-sectional and intervention approaches. Fifty-six middle-aged subjects were evaluated in a cross-sectional protocol regarding the relationship between the proportion of FA in serum cholesterol esters and vascular reactivity using measurements of forearm blood flow (FBF) with venous occlusion plethysmography during hyperemia. Another 19 middle-aged subjects were given a rapeseed oil-based diet rich in mono- and polyunsaturated FA or a control diet rich in saturated FA during two consecutive 4-wk periods separated by a 4-wk washout period. In the cross-sectional protocol, the FA 18:0 and 20:3 were positively related to resting FBF, whereas an inverse relationship was seen for the FA 20:5 and 22:6 (P < 0.05-0.01). Opposite relationships were seen between these four FA and the relative increase in maximal FBF during hyperemia (P < 0.05-0.01). In the intervention protocol, the saturated diet increased resting FBF, as well as the relative increase in maximal FBF during reactive hyperemia, compared to the diet rich in unsaturated FA (P < 0.05). Both the cross-sectional and intervention data support the view that the composition of serum FA, which at least partly reflects the quality of dietary fat, plays a role in determinations of vascular reactivity.