Rachel G. Robison

Omalizumab facilitates rapid oral desensitization for peanut allergy

Background: Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti‐IgE medication omalizumab (Xolair; Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. Objective: We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods: Thirty‐seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1‐day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results: The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab‐treated subjects versus 22.5 mg for placebo‐treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo (P < .01). Twenty‐three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000‐mg food challenge. Overall reaction rates were not significantly lower in omalizumab‐treated versus placebo‐treated subjects (odds ratio, 0.57; P = .15), although omalizumab‐treated subjects were exposed to much higher peanut doses. Conclusion: Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

BACKGROUND Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. METHODS In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. RESULTS Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. CONCLUSIONS Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

Maternal smoking during pregnancy, prematurity and recurrent wheezing in early childhood†

Prenatal maternal smoking and prematurity independently affect wheezing and asthma in childhood.

The effect of prenatal and postnatal dietary exposures on childhood development of atopic disease.

Purpose of reviewPrenatal and early life dietary factors may influence asthma and allergic disease development. We review recent studies and consensus statements regarding the effects of prenatal/early life dietary exposures on atopic disease. Recent findingsThe American Academy of Pediatrics consensus statement highlighted the inadequacy of evidence for pregnancy antigen avoidance diets or delay of infant complementary foods beyond 4–6 months. Recent studies raise the question of whether early food introduction may promote tolerance, though controlled trials are pending. A recent meta-analysis suggested that antioxidants may protect against the development of atopy. Furthermore, some of the conflicting results on the effects of vitamin E may be related to variability in the isoforms prevalent in local diet. Recent studies of vitamin D similarly suggest that it may be protective, though this remains controversial. Finally, prenatal methyl donor exposure promoted the development of allergy in an animal model. SummaryThere are conflicting data on the effects of most prenatal and early childhood dietary exposures on childhood atopic disease. Longitudinal prenatal/birth cohort studies with prospective measurements and clinical supplementation trials of promising dietary factors will be needed to make reliable recommendations in this vulnerable population of pregnant women and their infants.

Natural History of Food-Triggered Atopic Dermatitis and Development of Immediate Reactions in Children

BACKGROUND Case reports suggest that children with food-triggered atopic dermatitis (AD) on elimination diets may develop immediate reactions on accidental ingestion or reintroduction of an avoided food. OBJECTIVE The objective of this study was to systematically study the incidence and risk factors associated with these immediate reactions. METHODS A retrospective chart review of 298 patients presenting to a tertiary-care allergy-immunology clinic based on concern for food-triggered AD was performed. Data regarding triggering foods, laboratory testing, and clinical reactions were collected prospectively from the initial visit. Food-triggered AD was diagnosed by an allergist-immunologist with clinical evaluation and laboratory testing. We identified immediate reactions as any reaction to a food for which there was evidence of sIgE and for which patients developed timely allergic signs and symptoms. Differences between children with and without new immediate reactions were determined by a Mann-Whitney, χ(2), or Fishers exact test as appropriate. RESULTS A total of 19% of patients with food-triggered AD and no previous history of immediate reactions developed new immediate food reactions after initiation of an elimination diet. Seventy percent of reactions were cutaneous but 30% were anaphylaxis. Cows milk and egg were the most common foods causing immediate-type reactions. Avoidance of a food was associated with increased risk of developing immediate reactions to that food (P < .01). Risk was not related to specific IgE level nor a specific food. CONCLUSION A significant number of patients with food-triggered AD may develop immediate-type reactions. Strict elimination diets need to be thoughtfully prescribed as they may lead to decreased oral tolerance.

Patterns of allergen sensitization and self-reported allergic disease in parents of food allergic children

BACKGROUND Sensitization in adults has not been extensively studied. OBJECTIVE To investigate patterns of allergen sensitization in parents of food allergic children and to compare self-report of allergic disease with specific IgE (sIgE) measurements. METHODS A total of 1,252 mothers and 1,225 fathers of food allergic children answered standardized questionnaires about demographics, home environment, history of atopic diseases, and food allergy. Skin prick testing and sIgE serum tests were performed to 9 foods and 5 aeroallergens. RESULTS A total of 66.1% of parents were sensitized to either a food or aeroallergen. Mean sIgE levels were low for all foods tested. A total of 14.5% of mothers and 12.7% of fathers reported current food allergy. Only 28.4% had sensitization to their reported allergen. Fathers had significantly higher rates of sensitization to both foods and aeroallergens (P < .01) than mothers. Logistic regression evaluating predictors of self-reported food allergy revealed statistically significant positive associations in fathers with self-reported asthma, environmental allergy, and eczema. For mothers, significant positive associations were found with environmental allergy and having more than 1 food allergic child. CONCLUSION This cohort of parents of food allergic children found higher rates of sensitization to foods and aeroallergens compared with the general population. However, food sIgE levels were low and correlated poorly with self-reported food allergy. Sex differences in sensitization to foods and aeroallergens were seen.

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations

BACKGROUND Asthma exacerbations occur frequently despite the regular use of asthma‐controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS We studied 254 children, 5 to 11 years of age, who had mild‐to‐moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low‐dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low‐dose group) or use a quintupled dose (high‐dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control (“yellow zone”). Treatment was provided in a double‐blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high‐dose group and 0.37 exacerbations per year in the low‐dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow‐zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high‐dose group than in the low‐dose group. The difference in linear growth between the high‐dose group and the low‐dose group was ‐0.23 cm per year (P=0.06). CONCLUSIONS In children with mild‐to‐moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129.)

Chapter 23: Food allergy.

The onset of IgE-mediated food allergy is usually within minutes to 2 hours of food ingestion. Risk factors for fatal food-induced anaphylaxis include presence of asthma (which is a risk factor for anaphylaxis in general), failure to use epinephrine autoinjectors promptly, history of prior severe reactions, known food allergy, denial of symptoms, and adolescent/young adult age. The most commonly implicated foods are cows milk, eggs, peanuts, soy, tree nuts, fish, shellfish, and wheat. Allergies to peanut, tree nuts, and seafood are the most common food allergens in adults. The major food allergens are glycoproteins that are generally water soluble and stable to the effects of heat, proteases, and acids. Food proteins that escape proteolysis are taken up by intestinal epithelial cells and presented to primed T cells. This process leads to the generation of T-helper type 2 (Th2) cells that produce IL-4, IL-5, and IL-13. Recent studies have found that tolerance can be acquired with >70% of children becoming tolerant to cows milk and eggs by age 16 years. Allergies to peanuts, tree nuts, and seafood are frequently lifelong. Food-allergic patients or their care givers should be taught when and how to administer injectable epinephrine. In terms of prevention, the American Academy of Pediatrics concluded that there is no convincing evidence that delaying the introduction of solid foods, including common allergens, beyond 4-6 months of age has a protective effect on the development of atopic disease.

A computable phenotype for asthma case identification in adult and pediatric patients: External validation in the Chicago Area Patient-Outcomes Research Network (CAPriCORN)

ABSTRACT Objective: Comprehensive, rapid, and accurate identification of patients with asthma for clinical care and engagement in research efforts is needed. The original development and validation of a computable phenotype for asthma case identification occurred at a single institution in Chicago and demonstrated excellent test characteristics. However, its application in a diverse payer mix, across different health systems and multiple electronic health record vendors, and in both children and adults was not examined. The objective of this study is to externally validate the computable phenotype across diverse Chicago institutions to accurately identify pediatric and adult patients with asthma. Methods: A cohort of 900 asthma and control patients was identified from the electronic health record between January 1, 2012 and November 30, 2014. Two physicians at each site independently reviewed the patient chart to annotate cases. Results: The inter-observer reliability between the physician reviewers had a κ-coefficient of 0.95 (95% CI 0.93–0.97). The accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of the computable phenotype were all above 94% in the full cohort. Conclusions: The excellent positive and negative predictive values in this multi-center external validation study establish a useful tool to identify asthma cases in in the electronic health record for research and care. This computable phenotype could be used in large-scale comparative-effectiveness trials.