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1.  Egg-white-specific IgA and IgA2 antibodies in egg-allergic children: is there a role in tolerance induction? 
Background
Decreased serum food-specific-IgA antibodies have been associated with allergic disease in cross-sectional, case-control studies. The purpose of this study was to prospectively compare egg-white-(EW)-specific-IgA and IgA2 levels between egg-allergic children and children tolerating egg.
Methods
Seventeen egg allergic children were followed prospectively. Total IgA, EW-specific-IgA and EW-specific-IgA2 levels were measured in their sera with a sensitive ELISA. As negative controls were used children with no previous history of egg allergy. Egg-allergic children with or without concomitant milk allergy were evaluated as additional controls with measurement of casein-specific-IgA.
Results
After 2.5±0.9 years, 9 out of 17 allergic children became tolerant and 8 remained allergic to baked egg. Baseline EW-specific-IgA2 levels were significantly lower in the egg-allergic subjects (median 23.9ng/ml) compared with the negative control subjects (99.4ng/ml) and increased significantly by 28% over the study time period in 8 out of the 9 allergic children that became tolerant to baked egg. There was no significant change over time in EW-specific-IgA in any of the study groups. Non-milk-allergic subjects with concomitant egg allergy had almost 3-fold higher casein-specific-IgA levels than the milk- and egg-allergic subjects (P=0.025).
Conclusions
These results suggest a potential role for allergen-specific-IgA2 antibodies in the induction of food tolerance. Furthermore, they support the hypothesis that immature or impaired production of allergen-specific-IgA2 may be associated with the pathophysiology of food allergy, a defect that seems to be selective for the culprit allergen.
doi:10.1111/pai.12143
PMCID: PMC4134474  PMID: 24118158
food allergy; egg white; immunoglobulin A; neutralizing antibodies; tolerance induction
3.  Development and validation of educational materials for food allergy 
The Journal of Pediatrics  2011;160(4):651-656.
Objective
To develop and validate a food allergy educational program.
Study design
Materials developed through focus groups, parental and expert review were submitted to 60 parents of newly referred children having a prior food allergy diagnosis and an epinephrine autoinjector. The main outcome was correct demonstration of an autoinjector.
Results
The correct number of autoinjector activation steps increased from 3.4 to 5.95 (of 6) after training (p<.001) and was 5.47 at 1 year (p<.05). The mean score for comfort with using the autoinjector (7 point Likert scale) before the curriculum was 4.63 (somewhat comfortable) and increased to 6.23 after the intervention (p<.05) and remained elevated at 1 year (6.03). Knowledge tests (maximum 15) increased from a mean score of 9.2 to 12.4 (p<.001) at the initial visit and remained at 12.7 at 1 year. The annualized rate of allergic reactions fell from 1.77 (historical) the year prior, to 0.42 (p<.001) after the program. On a 7 point Likert-scale, all satisfaction categories remained above a favorable mean score of 6: straight-forward, organized, interesting, relevant, and recommend to others.
Conclusions
This food allergy educational curriculum for parents, now available online at no cost, showed high levels of satisfaction and efficacy.
doi:10.1016/j.jpeds.2011.09.056
PMCID: PMC3307837  PMID: 22082955
food allergy; anaphylaxis; education
4.  A Phase 1 Study of Heat/Phenol Killed, E. coli-Encapsulated, Recombinant Modified Peanut Proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the Treatment of Peanut Allergy 
Allergy  2013;68(6):803-808.
Background
Immunotherapy for peanut allergy may be limited by the risk of adverse reactions.
Objective
To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins.
Methods
This was a Phase 1 trial of EMP-123, a rectally administered suspension of recombinant Ara h 1, Ara h 2 and Ara h 3, modified by amino acid substitutions at major IgE binding epitopes, encapsulated in heat/phenol killed E. coli. Five healthy adults were treated with 4 weekly escalating doses after which 10 peanut allergic adults received weekly dose escalations over 10 weeks from 10mcg to 3063mcg, followed by 3 biweekly doses of 3063 mcg.
Results
There were no significant adverse effects in the healthy volunteers. Of the 10 peanut allergic subjects [4 with intermittent asthma, median peanut-IgE 33.3kUA/L (7.2–120.2), median peanutskin prick test wheal 11.3mm (6.5–18)], 4 experienced no symptoms, one had mild rectal symptoms, and the remaining 5 experienced adverse reactions preventing completion of dosing. Two were categorized as mild but the remaining three were more severe, including one moderate reaction and two anaphylactic reactions. Baseline peanut IgE was significantly higher in the 5 reactive subjects (median 82.4 versus 17.2kUA/L, p=0.032), as was baseline anti-Ara h 2 IgE (43.3 versus 8.3, p=0.036). Peanut skin test titration and basophil activation (at a single dilution) were significantly reduced after treatment but no significant changes were detected for total IgE, peanut IgE, or peanut IgG4.
Conclusions
Rectal administration of EMP-123 resulted in frequent adverse reactions, including severe allergic reactions in 20%.
doi:10.1111/all.12158
PMCID: PMC3663889  PMID: 23621498
5.  Developing A Food Allergy Curriculum for Parents 
Food allergy (FA) is potentially severe and requires intensive education to master allergen avoidance and emergency care. There is evidence suggesting the need for a comprehensive curriculum for food allergic families. This paper describes the results of focus groups conducted to guide the development of a curriculum for parents of food allergic children. The focus groups were conducted using standard methodology with experienced parents of food allergic children. Participants were parents (n=36) with experience managing FA recruited from allergy clinics at two academic centers.
Topics identified by parents as key for successful management included as expected: 1) early signs/symptoms, 2) “cross-contamination”, 3) label-reading, 4) self-injectable epinephrine; and 5) becoming a teacher and advocate. Participants also recommended developing a “one pageroad map” to the information, and to provide the information early and be timed according to developmental stages/needs. Suggested first points for curriculum dissemination were emergency rooms, obstetrician and pediatrician offices. Participants also recommended targeting pediatricians, emergency physicians, school personnel, and the community-at-large in educational efforts. Parents often sought FA information from non-medical sources such as the Internet and support groups. These resources were also accessed to find ways to cope with stress. Paradoxically, difficulties gaining access to resources and uncertainty regarding reliability of the information added to the stress experience. Based on reports from experienced parents of food allergic children, newly diagnosed parents could benefit from a comprehensive FA management curriculum. Improving access to clear and concise educational materials would likely reduce stress/anxiety and improve quality of life.
doi:10.1111/j.1399-3038.2011.01152.x
PMCID: PMC3977654  PMID: 21332804
children; food hypersensitivity; qualitative; education; quality of life
6.  The natural history of milk allergy in an observational cohort 
Objective
There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes.
Methods
Children aged 3 to 15 months were enrolled in an observational study with either (1) a convincing history of egg allergy, milk allergy, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis (AD) and a positive SPT response to milk or egg. Children enrolled with a clinical history of milk allergy were followed longitudinally, and resolution was established by means of successful ingestion.
Results
The cohort consists of 293 children, of whom 244 were given a diagnosis of milk allergy at baseline. Milk allergy has resolved in 154 (52.6%) subjects at a median age of 63 months and a median age at last follow-up of 66 months. Baseline characteristics that were most predictive of resolution included milk-specific IgE level, milk SPT wheal size, and AD severity (all P < .001). Baseline milk-specific IgG4 level and milk IgE/IgG4 ratio were not predictive of resolution and neither was expression of cytokine-inducible SH2-containing protein, forkhead box protein 3, GATA3, IL-10, IL-4, IFN-γ, or T-bet by using real-time PCR in CD25-selected, casein-stimulated mononuclear cells. A calculator to estimate resolution probabilities using baseline milk IgE level, SPT response, and AD severity was devised for use in the clinical setting. Conclusions: In this cohort of infants with milk allergy, approximately one half had resolved over 66 months of follow-up. Baseline milk-specific IgE level, SPT wheal size, and AD severity were all important predictors of the likelihood of resolution.
doi:10.1016/j.jaci.2012.10.060
PMCID: PMC3691063  PMID: 23273958
Milk allergy; natural history; food allergy; IgE
7.  Food Allergy Education for School Nurses: A Needs Assessment Survey by the Consortium of Food Allergy Research 
Food allergy is increasing in school-age children. School nurses are a primary health care resource for children with food allergy and must be prepared to manage allergen avoidance and respond in the event of an allergic reaction. An anonymous survey was administered to school nurses attending their association meetings to determine their educational needs regarding children with food allergy. With 199 school nurses responding, their self-reported proficiency for critical areas of food allergy knowledge and management varied, with weaknesses identified particularly for emergency plan development, staff education, delegation, developing guidelines for banning foods and planning school trips. Nurses reported a high interest in obtaining educational materials in these areas and prefer video and Internet resources that could be promoted through professional organizations.
doi:10.1177/1059840510369482
PMCID: PMC3888215  PMID: 20404357
school nurses; food allergy; education; emergency plan
8.  Child and Parental Reports of Bullying in a Consecutive Sample of Children With Food Allergy 
Pediatrics  2013;131(1):e10-e17.
OBJECTIVE:
The social vulnerability that is associated with food allergy (FA) might predispose children with FA to bullying and harassment. This study sought to quantify the extent, methods, and correlates of bullying in a cohort of food-allergic children.
METHODS:
Patient and parent (83.6% mothers) pairs were consecutively recruited during allergy clinic visits to independently answer questionnaires. Bullying due to FA or for any cause, quality of life (QoL), and distress in both the child and parent were evaluated via questionnaires.
RESULTS:
Of 251 families who completed the surveys, 45.4% of the children and 36.3% of their parents indicated that the child had been bullied or harassed for any reason, and 31.5% of the children and 24.7% of the parents reported bullying specifically due to FA, frequently including threats with foods, primarily by classmates. Bullying was significantly associated with decreased QoL and increased distress in parents and children, independent of the reported severity of the allergy. A greater frequency of bullying was related to poorer QoL. Parents knew about the child-reported bullying in only 52.1% of the cases. Parental knowledge of bullying was associated with better QoL and less distress in the bullied children.
CONCLUSIONS:
Bullying is common in food-allergic children. It is associated with lower QoL and distress in children and their parents. Half of the bullying cases remain unknown to parents. When parents are aware of the bullying, the child’s QoL is better. It is important to proactively identify and address cases in this population.
doi:10.1542/peds.2012-1180
PMCID: PMC3529950  PMID: 23266926
food allergy; anxiety; bullying; health-related quality of life; quality of life
9.  Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial 
Background
There are presently no available therapeutic options for peanut-allergic patients.
Objective
To investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT).
Methods
After a baseline oral food challenge (OFC) of up to 2g of peanut powder (~50% protein) (median successfully consumed dose [SCD] 46mg), 40 subjects, aged 12–37 (median 15) years, were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5g OFC was performed after 44 weeks followed by unblinding; placebo subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5g OFC. Week 44 OFCs from both groups were compared to baseline OFCs; subjects successfully consuming 5g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders.
Results
After 44 weeks of SLIT, 14/20 (70%) subjects receiving peanut SLIT were responders compared to 3/20 (15%) subjects receiving placebo (p<0.001). In peanut-SLIT responders, median SCD increased from 3.5mg to 496mg. After 68 weeks of SLIT, median SCD significantly increased to 996mg (compared to week 44, p=0.05). The median SCD at the Week 44 crossover OFC was significantly higher than baseline (603mg vs 71mg; p=0.02). 7/16 (44%) crossover subjects were responders; median SCD increased from 21mg to 496mg among responders. Of 10,855 peanut doses through Week 44 OFCs, 63.1% were symptom-free; excluding oral/pharyngeal symptoms, 95.2% were symptom-free.
Conclusions
Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared to placebo. Longer duration of therapy showed statistically significant increases in the SCD.
doi:10.1016/j.jaci.2012.11.011
PMCID: PMC3550002  PMID: 23265698
peanut allergy; sublingual immunotherapy; desensitization; food allergy
10.  Maternal Consumption of Peanut during Pregnancy is Associated with Peanut Sensitization in Atopic Infants 
Background
Peanut allergy is typically severe, life-long and prevalent.
Objective
To identify factors associated with peanut sensitization.
Methods
We evaluated 503 infants 3–15 months of age (mean, 9.4 months) with likely milk or egg allergy but no previous diagnosis of peanut allergy. A total of 308 had experienced an immediate allergic reaction to cow’s milk and/or egg and 204 had moderate to severe atopic dermatitis and a positive allergy test to milk and/or egg. A peanut IgE level of ≥ 5 kUA/L was considered likely indicative of peanut allergy.
Results
A total of 140 (27.8%) infants had PN-IgE levels ≥5 kUA/L. Multivariate analysis including clinical, laboratory and demographic variables showed frequent peanut consumption during pregnancy (OR 2.9, 95% CI 1.7–4.9, p < 0.001), IgE levels to milk (p = 0.001) and egg (p < 0.001), male sex (p = 0.02) and non-white race (p = 0.02) to be the primary factors associated with peanut IgE ≥5 kUA/L. Frequency of peanut consumption during pregnancy and breast feeding showed a dose-response association with peanut IgE ≥ 5 kUA/L, but only consumption during pregnancy was a significant predictor. Among 71 infants never breastfed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE ≥ 5 kUA/L (OR-4.99, 95% CI-1.69–14.74, p < 0.004).
Conclusions
In this cohort of infants with likely milk or egg allergy, maternal ingestion of peanut during pregnancy was strongly associated with a high level of peanut sensitization.
doi:10.1016/j.jaci.2010.08.036
PMCID: PMC3018157  PMID: 21035177
food allergy; sensitization; atopy; peanut allergy
11.  Immunologic Features of Infants with Milk or Egg Allergy Enrolled in an Observational Study (CoFAR) of Food Allergy 
Background
Immune features of infants with food allergy have not been delineated.
Objectives
To explore basic mechanisms responsible for food allergy and identify biomarkers, e.g. prick skin tests (PST), food-specific IgE, and mononuclear cell responses in a cohort of infants with likely milk/egg allergy at increased risk of developing peanut allergy.
Methods
Infants aged 3–15 months were enrolled with a positive PST to milk or egg and either a corresponding convincing clinical history of allergy to milk or egg, or with moderate to severe atopic dermatitis (AD). Infants with known peanut allergy were excluded.
Results
Overall, 512 infants (67% males) were studied with 308 (60%) having a history of a clinical reaction. Skin tests and/or detectable food-specific IgE revealed sensitization as follows: milk-78%, egg-89% and peanut-69%. PST and food-specific IgE levels were discrepant for peanut: 15% IgE ≥ 0.35 kUA/L/PST- versus 8% PST+/IgE < 0.35, p = 0.001. Mononuclear cell allergen stimulation screening for CD25, CISH, FOXP3, GATA3, IL-10, IL-4, IFN-gamma and TBET expression using casein, egg white and peanut revealed that only allergen-induced IL-4 expression was significantly increased in those with clinical allergy to milk (compared to non-allergic) and in those sensitized to peanut, despite the absence of an increase in GATA-3 mRNA expression.
Conclusions
Infants with likely milk/egg allergy are at considerably high risk of having elevated peanut-specific IgE (potential allergy). Peanut-specific serum IgE was a more sensitive indicator of sensitization than PST. Allergen-specific IL-4 expression may be a marker of allergic risk. Absence of an increase in GATA-3 mRNA expression suggests that allergen-specific IL-4 may not be of T cell origin.
doi:10.1016/j.jaci.2010.02.038
PMCID: PMC2868273  PMID: 20451041
food allergy; sensitization; atopy
12.  DIETARY BAKED EGG ACCELERATES RESOLUTION OF EGG ALLERGY IN CHILDREN 
Background
Baked egg is tolerated by a majority of egg-allergic children.
Objective
To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets plays in the development of tolerance to regular egg.
Methods
Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance.
Results
Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initial baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kUA/L) than those who subsequently tolerated baked egg (4.4 kUA/L; P=0.04) and regular egg (3.1 kUA/L, P=0.05). In subjects ingesting baked egg, EW-induced SPT wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG4 levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely to develop regular egg tolerance than subjects in the comparison group (P < 0.0001), and they developed tolerance earlier (median 50.0 versus 78.7 months; P<0.0001).
Conclusion
Initiation of a baked egg diet accelerates the development of regular egg tolerance compared to strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not.
doi:10.1016/j.jaci.2012.06.006
PMCID: PMC3428057  PMID: 22846751
egg allergy; hen’s egg allergy; baked egg; heated egg; food allergy; egg tolerance; oral food challenge; egg allergy immunotherapy
13.  Allergic Reactions to Foods in Preschool-Aged Children in a Prospective Observational Food Allergy Study 
Pediatrics  2012;130(1):e25-e32.
OBJECTIVE:
To examine circumstances of allergic reactions to foods in a cohort of preschool-aged children.
METHODS:
We conducted a prospective, 5-site observational study of 512 infants aged 3 to 15 months with documented or likely allergy to milk or egg, and collected data prospectively examining allergic reactions.
RESULTS:
Over a median follow-up of 36 months (range: 0–48.4), the annualized reaction rate was 0.81 per year (367/512 subjects reporting 1171 reactions [95% confidence interval: 0.76–0.85]). Overall, 269/512 (52.5%) reported >1 reaction. The majority of reactions (71.2%) were triggered by milk (495 [42.3%]), egg (246 [21.0%]), and peanut (93 [7.9%]), with accidental exposures attributed to unintentional ingestion, label-reading errors, and cross-contact. Foods were provided by persons other than parents in 50.6% of reactions. Of 834 reactions to milk, egg, or peanut, 93 (11.2%) were attributed to purposeful exposures to these avoided foods. A higher number of food allergies (P < .0001) and higher food-specific immunoglobulin E (P < .0001) were associated with reactions. Of the 11.4% of reactions (n = 134) that were severe, 29.9% were treated with epinephrine. Factors resulting in undertreatment included lack of recognition of severity, epinephrine being unavailable, and fears about epinephrine administration.
CONCLUSIONS:
There was a high frequency of reactions caused by accidental and nonaccidental exposures. Undertreatment of severe reactions with epinephrine was a substantial problem. Areas for improved education include the need for constant vigilance, accurate label reading, avoidance of nonaccidental exposure, prevention of cross-contamination, appropriate epinephrine administration, and education of all caretakers.
doi:10.1542/peds.2011-1762
PMCID: PMC3382915  PMID: 22732173
food allergy; IgE-mediated allergic reaction; epinephrine
14.  Oral Immunotherapy for Treatment of Egg Allergy in Children 
The New England journal of medicine  2012;367(3):233-243.
BACKGROUND
For egg allergy, dietary avoidance is the only currently approved treatment. We evaluated oral immunotherapy using egg-white powder for the treatment of children with egg allergy.
METHODS
In this double-blind, randomized, placebo-controlled study, 55 children, 5 to 11 years of age, with egg allergy received oral immunotherapy (40 children) or placebo (15). Initial dose-escalation, build-up, and maintenance phases were followed by an oral food challenge with egg-white powder at 10 months and at 22 months. Children who successfully passed the challenge at 22 months discontinued oral immunotherapy and avoided all egg consumption for 4 to 6 weeks. At 24 months, these children underwent an oral food challenge with egg-white powder and a cooked egg to test for sustained unresponsiveness. Children who passed this challenge at 24 months were placed on a diet with ad libitum egg consumption and were evaluated for continuation of sustained unresponsiveness at 30 months and 36 months.
RESULTS
After 10 months of therapy, none of the children who received placebo and 55% of those who received oral immunotherapy passed the oral food challenge and were considered to be desensitized; after 22 months, 75% of children in the oral-immunotherapy group were desensitized. In the oral-immunotherapy group, 28% (11 of 40 children) passed the oral food challenge at 24 months and were considered to have sustained unresponsiveness. At 30 months and 36 months, all children who had passed the oral food challenge at 24 months were consuming egg. Of the immune markers measured, small wheal diameters on skin-prick testing and increases in egg-specific IgG4 antibody levels were associated with passing the oral food challenge at 24 months.
CONCLUSIONS
These results show that oral immunotherapy can desensitize a high proportion of children with egg allergy and induce sustained unresponsiveness in a clinically significant subset. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00461097.)
doi:10.1056/NEJMoa1200435
PMCID: PMC3424505  PMID: 22808958
15.  NIAID-Sponsored 2010 Guidelines for Managing Food Allergy: Applications in the Pediatric Population 
Pediatrics  2011;128(5):955-965.
Data from many studies have suggested a rise in the prevalence of food allergies during the past 10 to 20 years. Currently, no curative treatments for food allergy exist, and there are no effective means of preventing the disease. Management of food allergy involves strict avoidance of the allergen in the patient's diet and treatment of symptoms as they arise. Because diagnosis and management of the disease can vary between clinical practice settings, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored development of clinical guidelines for the diagnosis and management of food allergy. The guidelines establish consensus and consistency in definitions, diagnostic criteria, and management practices. They also provide concise recommendations on how to diagnose and manage food allergy and treat acute food allergy reactions. The original guidelines encompass practices relevant to patients of all ages, but food allergy presents unique and specific concerns for infants, children, and teenagers. To focus on those concerns, we describe here the guidelines most pertinent to the pediatric population.
doi:10.1542/peds.2011-0539
PMCID: PMC3208961  PMID: 21987705
food allergy; food hypersensitivity; infants; children; guidelines; anaphylaxis
16.  Dietary baked-milk accelerates resolution of cow's milk allergy in children 
Background
The majority (∼75%) of cow's milk-allergic children tolerate extensively heated-(baked-) milk products. Long-term effects of inclusion of dietary baked-milk have not been reported.
Objective
We report on the outcomes of children who incorporated baked-milk products into their diets.
Methods
Children evaluated for tolerance to baked-milk (muffin) underwent sequential food challenges to baked-cheese (pizza) followed by unheated-milk. Immunologic parameters were measured at challenge visits. The comparison group were matched to active subjects (using age, sex, and baseline milk-specific IgE) to evaluate the natural history of tolerance development.
Results
Over a median of 37 months (range 8-75 months), 88 children underwent challenges at varying intervals (range 6-54 months). Among 65 subjects initially tolerant to baked-milk, 39 (60%) now tolerate unheated-milk, 18 (28%) tolerate baked-milk/baked-cheese and 8 (12%) chose to avoid milk strictly. Among the baked-milk-reactive subgroup (n=23), 2 (9%) tolerate unheated-milk, 3 (13%) tolerate baked-milk/baked-cheese, while the majority (78%) avoid milk strictly. Subjects who were initially tolerant to baked-milk were 28 times more likely to become unheated-milk-tolerant compared to baked-milk-reactive subjects (P<.001). Subjects who incorporated dietary baked-milk were 16 times more likely than the comparison group to become unheated-milk-tolerant (P<.001). Median casein IgG4 levels in the baked-milk-tolerant group increased significantly (P<.001); median milk IgE values did not change significantly.
Conclusions
Tolerance of baked-milk is a marker of transient IgE-mediated cow's milk allergy whereas reactivity to baked-milk portends a more persistent phenotype. The addition of baked-milk to the diet of children tolerating such foods appears to accelerate development of unheated-milk tolerance compared to strict avoidance.
Clinical implications
Addition of dietary baked-milk is safe, convenient, and well-accepted by patients. Prescribing baked-milk products to milk-allergic children represents an important shift in the treatment paradigm for milk allergy.
Capsule summary
The majority of cow's milk-allergic children tolerate extensively baked-milk products, which is a marker of transient IgE-mediated cow's milk allergy. Dietary baked-milk appears to accelerate development of unheated-milk tolerance compared to strict avoidance.
doi:10.1016/j.jaci.2011.04.036
PMCID: PMC3151608  PMID: 21601913
cow's milk allergy; milk allergy; tolerance; extensively heated; baked; immunotherapy; immunomodulation
17.  Epinephrine Treatment is Infrequent and Biphasic Reactions Are Rare in Food-Induced Reactions During Oral Food Challenges in Children 
Background
Data about epinephrine utilization and biphasic reactions in childhood food-induced anaphylaxis during oral food challenges are scarce.
Objective
To determine the prevalence and risk factors of reactions requiring epinephrine and the rate of biphasic reactions during oral food challenges (OFCs) in children.
Methods
Reaction details of positive OFCs in children between 1999 and 2007 were collected using a computerized database. Selection of patients for OFCs was generally predicated on ≤50% likelihood of a positive challenge and a low likelihood of a severe reaction based on the clinical history, specific IgE levels, and skin prick tests (SPTs).
Results
A total of 436 of 1273 OFCs resulted in a reaction (34%). Epinephrine was administered in 50 challenges (11% of positive challenges, 3.9% overall); for egg (n=15, 16% of positive OFCs to egg), milk (n=14, 12%), peanut (n=10, 26%), tree nuts (n=4, 33%), soy (n=3, 7%), wheat (n=3, 9%), and fish (n=1, 9%). Reactions requiring epinephrine occurred in older children (median 7.9 vs. 5.8 years, P<0.001), and were more often caused by peanuts (P=0.006) when compared to reactions not treated with epinephrine. There was no difference in the gender, prevalence of asthma, history of anaphylaxis, specific IgE level, SPTs, or amount of food administered. Two doses of epinephrine were required in 3/50 patients (6%) reacting to wheat, cow’s milk, and pistachio. There was one (2%) biphasic reaction. No reaction resulted in life-threatening respiratory or cardiovascular compromise.
Conclusion
Older age and reactions to peanuts were risk factors for anaphylaxis during oral food challenges. Reactions requiring multiple doses of epinephrine and biphasic reactions were infrequent.
doi:10.1016/j.jaci.2009.10.006
PMCID: PMC2798852  PMID: 20004784
food allergy; autoinjector; self-injectable; epinephrine; children; anaphylaxis; oral food challenge; food-induced anaphylaxis; peanut allergy; tree nut allergy; cow’s milk allergy; milk allergy; egg allergy; allergic reaction
18.  National Prevalence and Risk Factors for Food Allergy and Relationship to Asthma: Results from the National Health and Nutrition Examination Survey 2005-2006 
Background
The national prevalence and patterns of food allergy (FA) in the United States (US) are not well understood.
Objective
We developed nationally representative estimates of the prevalence of and demographic risk factors for FA, and investigated associations of FA with asthma, hay fever, and eczema.
Methods
8,203 participants in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 had food-specific serum IgE measured to peanut, cow's milk, egg white, and shrimp. Food-specific IgE and age-based criteria were used to define Likely FA (LFA), Possible FA (PFA), and Unlikely FA (UFA), and to develop estimates of clinical FA. Self-reported data were used to evaluate demographic risk factors and associations with asthma and related conditions.
Results
In the US, the estimated prevalence of clinical FA was 2.5% (peanut 1.3%, milk 0.4%, egg 0.2%, shrimp 1.0%, not mutually exclusive). Risk of PFA/LFA was increased in non-Hispanic blacks (odds ratio (OR) 3.06; 95% confidence interval (CI) 2.14-4.36), males (1.87; 1.32-2.66), and children (2.04; 1.42-2.93). Study participants with doctor-diagnosed asthma (vs. no asthma) exhibited increased risk of all measures of food sensitization. Moreover, in those with LFA, the adjusted OR for current asthma (3.8; 1.5-10.7) and an emergency room (ER) visit for asthma in the past year (6.9; 2.4-19.7) were both notably increased.
Conclusion
Population-based serologic data on 4 foods indicate an estimated 2.5% of the US population has FA, and increased risk was found for blacks, males, and children. Additionally, FA could be an under-recognized risk factor for problematic asthma.
doi:10.1016/j.jaci.2010.07.026
PMCID: PMC2990684  PMID: 20920770
asthma; eczema; egg; food allergy; food sensitization; food-specific serum IgE; peanut; hay fever; milk; prevalence; risk; shrimp
19.  Development of a food allergy education resource for primary care physicians 
Background
Food allergy is estimated to affect 3–4% of adults in the US, but there are limited educational resources for primary care physicians. The goal of this study was to develop and pilot a food allergy educational resource based upon a needs survey of non-allergist healthcare providers.
Methods
A survey was undertaken to identify educational needs and preferences for providers, with a focus on physicians caring for adults and teenagers, including emergency medicine providers. The results of the survey were used to develop a teaching program that was subsequently piloted on primary care and emergency medicine physicians. Knowledge base tests and satisfaction surveys were administered to determine the effectiveness of the educational program.
Results
Eighty-two physicians (response rate, 65%) completed the needs assessment survey. Areas of deficiency and educational needs identified included: identification of potentially life-threatening food allergies, food allergy diagnosis, and education of patients about treatment (food avoidance and epinephrine use). Small group, on-site training was the most requested mode of education. A slide set and narrative were developed to address the identified needs. Twenty-six separately enrolled participants were administered the teaching set. Pre-post knowledge base scores increased from a mean of 38% correct to 64% correct (p < 0.001). Ability to correctly demonstrate the use of epinephrine self injectors increased significantly. Nearly all participants (>95%) indicated that the teaching module increased their comfort with recognition and management of food allergy.
Conclusion
Our pilot food allergy program, developed based upon needs assessments, showed strong participant satisfaction and educational value.
doi:10.1186/1472-6920-8-45
PMCID: PMC2569928  PMID: 18826650

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