Using data from food challenges to inform management of consumers with food allergy: A systematic review with individual participant data meta-analysis.

BACKGROUND: Eliciting doses (EDs) (eg, ED01 or ED05 values, which are the amounts of allergen expected to cause objective symptoms in 1% and 5% of the population with an allergy, respectively) are increasingly being used to inform allergen labeling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis in response to these low levels of allergen exposure and their reproducibility are unknown. OBJECTIVE: Our aim was to determine (1) the rate of anaphylaxis in response to low-level peanut exposure and (2) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge. METHODS: We conducted a systematic review and individual participant data meta-analysis of studies that reported at least 50 individuals with peanut allergy reacting to peanut at double-blind, placebo-controlled food challenge (DBPCFC) and were published between January 2010 and September 2020. Risk of bias was assessed by using National Institute for Clinical Excellence methodologic checklists. RESULTS: A total of 19 studies were included (covering a total of 3151 participants, 534 of whom subsequently underwent further peanut challenge). At individual participant data meta-analysis, 4.5% (95% CI, 1.9% to 10.1%) of individuals reacted to 5 mg or less of peanut protein with anaphylaxis (moderate heterogeneity [I2 = 57%]). Intraindividual thresholds varied by up to 3 logs, although this variation was limited to a half-log change in 71.2% (95% CI, 56.2% to 82.6%) of individuals. In all, 2.4% (95% CI, 1.1% to 5.0%) of patients initially tolerated 5 mg of peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity [I2 = 16%]); none developed anaphylaxis. CONCLUSION: Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might develop anaphylaxis in response to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose, respectively, in the broader population of individuals with peanut allergy.

Oral Immunotherapy for Peanut Allergy.

Peanut allergy is a common disease and the cause of severe, life-threatening allergic reactions and death. It is rarely outgrown; most pediatric patients carry the disease into adulthood. Peanut allergy poses a significant burden on the quality of life of sufferers and their families, which results mainly from the fear of accidental peanut ingestion but is also due to dietary and social restrictions. Current standard management involves avoidance advice, patient education, and provision of emergency rescue medication. Immunotherapy, commonly used to treat other allergic diseases, has shown promise as a disease-modifying therapy for peanut allergy. Results from studies of oral immunotherapy show high efficacy rates, improvement in quality of life, and a good safety profile. Treatment may result in sustained unresponsiveness in a proportion of patients, whereas others require ongoing treatment.

Food immunotherapy for children with food allergies: state of the art and science.

PURPOSE OF REVIEW: This review examines the current literature and provides insight into the role of food immunotherapy in the management of food-allergic children. Key food immunotherapy trials, benefits, and risks of the intervention, as well as areas requiring further study are all discussed. RECENT FINDINGS: Research studies have reported encouraging results regarding the efficacy of food immunotherapy in desensitizing food-allergic patients with an acceptable safety profile and a documented improvement in quality of life. The role of biologics and long-term effects of food immunotherapy are still under investigation. SUMMARY: The burden of food allergy is significant, multifaceted, and well documented. Food immunotherapy is a novel treatment option and an exciting area of research that has seen tremendous progress over the last decade, presenting encouraging results for the treatment of children with food allergies.

Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial.

BACKGROUND: Small studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts. METHODS: We did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2-800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7-16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244. FINDINGS: The primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45-78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0-9; p<0·001). 84% (95% CI 70-93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45-1400; p<0·001) or 25·5 times (range 1·82-280; p<0·001). After the second phase, 54% (95% CI 35-72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79-98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change -1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant). INTERPRETATION: OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group. FUNDING: MRC-NIHR partnership.

Optimising treatment of allergic rhinitis in children.

Acute and chronic symptoms of allergic rhinitis (AR) can disrupt school and leisure activities, significantly reducing quality of life. Symptoms often impair sleep, resulting in tiredness and poor concentration. Children with seasonal AR perform significantly worse in summer exams, relative to their mock exam results, when compared with their peers. Those individuals showing most symptoms are also likely to be affected by other allergic diseases, magnifying the detrimental impact on quality of life. Nasal blockage is the most common complaint associated with chronic AR, with acute exacerbations causing sneezing, clear nasal discharge and itchy eyes following exposure to the relevant airborne triggers. Allergen avoidance measures should be instituted according to seasonal or perennial symptomatology guided by allergy testing, alongside nonsedating antihistamines such as cetirizine or loratadine. Continued symptoms should be treated with regular intranasal steroid spray. Anti-leukotrienes should be considered early in children presenting with multi-trigger wheeze. Temporal patterns of exacerbation give clues as to the most important aeroallergens implicated. In the UK, tree pollen allergy predominates throughout the spring, whereas those affected by grass pollen allergy may find their symptoms increasing over the summer months. Perennial AR symptoms are the result of exposure to house dust mites, animals and moulds. Children who are allergic to these often find the winter more troublesome as they spend more time indoors and the central heating disperses these household allergens. Where continuing deterioration presents a challenge and allergic symptoms remain uncontrolled, patients should be referred to a specialist allergy service to be considered for immunotherapy.

Risk factors for childhood asthma deaths from the UK Eastern Region Confidential Enquiry 2001-2006.

BACKGROUND: Confidential enquiries into asthma deaths can identify inadequacies in medical management and factors which contribute to patients' death. AIMS: To identify risk factors for paediatric asthma deaths over a 6-year period. METHODS: Observational case-series study of paediatric asthma deaths between 2001-2006 in the UK Eastern Region. Hospital, primary care and post-mortem data were obtained for every child (≤17 yrs) with asthma recorded on the death certificate, and a detailed questionnaire was completed. Information was obtained on asthma severity, medications, hospital admissions, GP and hospital follow-up, adherence, psychosocial / behavioural factors, allergies, details of the terminal attack and precipitating factors. RESULTS: 20 children (10 male; 8-17 yrs; median: 11.5 yrs) died of asthma between 2001-2006. 9/20 had mild to moderate asthma (BTS/ SIGN criteria), 10/20 had severe asthma and 1 child was not known to have asthma. 13/20 were clinically atopic. Only 3 had undergone allergy assessment. 10/20 died between June and August. 12/20 children had adverse psychosocial and behavioural factors. 7/20 children were on non-combination long-acting ß2-agonist (LABA) treatment without inhaled corticosteroids (ICS). CONCLUSIONS: Almost half the deaths occurred in children with mild/moderate asthma. We recommend that allergic factors and seasonal allergy should be identified early, non-combination LABAs avoided, and speculate that overuse of short-acting ß2-agonists (SABAs) may indicate non-adherence with ICS. Asthma deaths in children can be avoided if risk factors are identified early.

Myths, facts and controversies in the diagnosis and management of anaphylaxis.

Anaphylaxis is a serious systemic allergic reaction that is rapid in onset and may cause death. Despite numerous national and international guidelines and consensus statements, common misconceptions still persist in terms of diagnosis and appropriate management, both among healthcare professionals and patient/carers. We address some of these misconceptions and highlight the optimal approach for patients who experience potentially life-threatening allergic reactions.

The Role of Probiotics in Preventing Allergic Disease.

The prevalence of allergic disorders has been increasing worldwide and significantly impacts the quality of life of the atopic individual. There has been an increased interest in the role of probiotics for the prevention and treatment of allergic disorders, given the recent evidence that atopy risk may be associated with a dysbiosis of the gut microbiome. Research in this area is ongoing with some studies showing possible benefits of probiotics, with seemingly little to no risk. While these studies suggest that there may be a promise in probiotic use for the prevention or treatment of allergy, further evidence is needed to determine its efficacy, optimal dosing, and strains needed for treatment. In this review, we discuss recently published studies examining the benefits, risks, and role of probiotics in preventing atopic dermatitis, asthma, allergic rhinitis, and food allergy.

Epidemiology of Anaphylaxis in Critically Ill Children in the United States and Canada.

BACKGROUND: Anaphylaxis is a rapid-onset, multisystem, and potentially fatal hypersensitivity reaction with varied reports of prevalence, incidence, and mortality. There are limited cases reported of severe and/or fatal pediatric anaphylaxis. OBJECTIVE: This study describes the largest cohort of intensive care unit pediatric anaphylaxis admissions with a comprehensive analysis of identified triggers, clinical and demographic information, and probability of death. METHODS: We describe the epidemiology of pediatric anaphylaxis admissions to North American pediatric intensive care units (PICUs) that were prospectively enrolled in the Virtual Pediatric Systems database from 2010 to 2015. One hundred thirty-one PICUs in North America (United States and Canada) were queried for anaphylaxis International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision codes from the Virtual Pediatric Systems database from 2010 to 2015 in the United States and Canada. One thousand nine hundred eighty-nine patients younger than 18 years were identified out of 604,279 total number of patients admitted to a PICU in the database during this time frame. RESULTS: The primary outcome was mortality, which was compared with patient and admission data using Fisher exact test. Secondary outcomes (intubation, length of stay, mortality risk scores, systolic blood pressure, and pupillary reflex) were analyzed using the Kruskal-Wallis test or Wilcoxon rank-sum test, as appropriate. One thousand nine hundred eighty-nine patients with an anaphylaxis International Classification of Diseases code were identified in the database. One percent of patients died because of critical anaphylaxis. Identified triggers for fatal cases were peanuts, milk, and blood products. Peanuts were the most common trigger. Children were mostly male when younger than 13 years, and mostly female when 13 years and older. Average length of stay was 2 days. There was a higher proportion of Asian patients younger than 2 years or when the trigger was food. CONCLUSIONS: This is the largest study to describe pediatric critical anaphylaxis cases in North America and identifies food as the most common trigger. Death occurs in 1% of cases, with intubation occurring most commonly in the first hour. The risk for intensive care unit admission in children underscores the serious nature of anaphylaxis in this population.

Anaphylaxis in Children: Epidemiology, Risk Factors and Management.

BACKGROUND: Anaphylaxis is defined as a serious, generalized or systemic allergic reaction that is rapid in onset and may cause death. It is unpredictable and can be the result of various allergic triggers including food, insect venom and medication. The European Anaphylaxis Registry confirmed food as the major elicitor of anaphylaxis in children, specifically hen's egg, cow's milk and nuts. OBJECTIVES: It has been reported that the incidence of anaphylaxis is on the rise. In the US, there is a continued trend of increasing food-induced anaphylaxis hospitalizations among children, which is supported by nationally representative data. METHODS: Anaphylaxis can occur both in the home and outdoors and can be life-threatening, however, fatalities are a rare occurrence. A recent systematic review and meta-analysis reported that fatal food anaphylaxis is rarer than accidental death in the general population. Studies of fatal and near-fatal allergic reactions have identified potential risk factors for fatalities and have provided important information that may help minimize future risk. Following confirmation of the relevant allergen trigger, prevention of anaphylaxis is through strict avoidance of the allergen and optimal management of existing co-morbidities. The cornerstone in the successful management of anaphylaxis is early recognition of signs and symptoms and the prompt administration of intramuscular adrenaline. RESULT AND CONCLUSION: Patients and their families need to be well educated on how to manage potential anaphylactic reactions with training in the use of adrenaline auto-injectors and personalized emergency management plans. Healthcare professionals must be familiar with this clinical emergency and able to respond to anaphylaxis in a timely and appropriate manner.

Safety of Oral Food Challenges in Early Life.

Oral food challenges are becoming more frequent in the allergy clinic due to an increased demand related to early food introduction in infants. We examined the safety of oral food challenges in 18 high-risk infants with prior allergic reactions, as well as infants with no known exposure to the food, presenting consecutively in a dedicated food allergy clinic for an oral food challenge. Foods challenged included peanut, tree nuts, sesame, baked egg, baked milk, and soy. A total of 17/18 (94%) infants had a negative challenge. Only 1/18 (6%) had a positive challenge, and in this case, symptoms were mild and limited to the skin. Our results suggest that food challenges in infants and young children up to the age of 2 years are safe with symptoms limited to the skin when reactions occur. In our cohort, the large majority of food challenges were negative, with most infants being sensitized rather than allergic to the food. Larger studies are needed to confirm this finding.

The Nuts and Bolts of Food Immunotherapy: The Future of Food Allergy.

Food allergies are on the rise and have a major impact on the quality of life of the food allergic child and their family. Currently, the mainstream treatment for food allergies is strict avoidance and elimination of the allergenic food(s) from the patient's diet in order to prevent an allergic reaction. However, recent advances in research have presented new therapeutic options for food allergic patients that are potentially becoming promising alternatives to traditional treatment. Food immunotherapy is the most popular of these new emerging interventions and has been studied intensively over the last decade for various foods. In this review, we discuss this exciting new development that is aspiring to become part of the mainstream therapy for food allergy.

The Value of Food Allergy Prevention in Clinical Practice in Pediatrics: Targeting Early Life.

Food allergies are common and increasing in prevalence, representing a major health concern in many countries around the world. In an effort to diminish the burden of food allergy, many research studies have focused on prevention, and recent findings have revolutionized the way we introduce allergenic foods in early life. We discuss the role of early allergenic food introduction and the value of food allergy prevention in this manuscript.

Coconut Allergy Revisited.

Despite concerns voiced often by food-allergic patients, allergy to coconut is rare, not directly associated with nut allergy and few cases are reported so far in the literature. We present an interesting case of coconut allergy in a child that was previously tolerant to coconut and regularly exposed via both the skin and gastrointestinal route.

Recent advances in immunotherapy and vaccine development for peanut allergy.

Peanut allergy is a common problem and can be the cause of severe, life-threatening allergic reactions. It rarely resolves, with the majority of patients carrying the disease onto adulthood. Peanut allergy poses a significant burden on the quality of life of sufferers and their families, which results mainly from the fear of accidental peanut ingestion, but is also due to dietary and social restrictions. Current standard management involves avoidance, patient education and provision of emergency medication, for use in allergic reactions, when they occur. Efforts have been made to develop a vaccine for peanut allergy. Recent developments have also highlighted the use of immunotherapy, which has shown promise as an active form of treatment and may present a disease-modifying therapy for peanut allergy. So far, results, especially from oral immunotherapy studies, have shown good efficacy in achieving desensitization to peanut with a good safety profile. However, the capacity to induce long-term tolerance has not been demonstrated conclusively yet and larger, phase III studies are required to further investigate safety and efficacy of this intervention. Peanut immunotherapy is not currently recommended for routine clinical use or outside specialist allergy units.

The management of peanut allergy.

Peanut allergy is common and can be a cause of severe, life-threatening reactions. It is rarely outgrown like other food allergies such as egg and milk. Measures aiming to reduce its prevalence via maternal avoidance during pregnancy and lactation, or delayed introduction into the diet, have failed to show any benefit. Peanut allergy has a significant effect on the quality of life of sufferers and their families due to dietary and social restrictions, but mainly stemming from fear of accidental peanut ingestion. The current management consists of strict avoidance, education and provision of emergency medication. Families find avoidance challenging as peanut is hidden in various food products. Despite the fact that food labelling has improved, with a legal obligation to declare certain food allergens (including nuts) in prepacked products, it still causes confusion and does not extend to cross-contamination. In an effort to address issues of safety at school, a lot of work has been undertaken to better care for peanut-allergic children in that environment. This includes training of school staff on how to recognise and treat allergic reactions promptly. Recent developments in the management of peanut allergy, such as immunotherapy, have shown some promise as an active form of treatment, but larger studies are required to further investigate safety and efficacy.

The rapidly changing world of food allergy in children.

Food allergy is a common problem in childhood. The term is used to include both immunoglobulin E (IgE)-mediated and non-IgE-mediated food allergies, which have a significant effect on the quality of life of patients and their families. In this report, we aim to discuss recent advances in the diagnosis, management, and treatment modalities of food allergy in children.