Elizabeth C. Matsui

A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy.

BACKGROUND Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals. OBJECTIVE We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cows milk allergy. METHODS Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT. RESULTS Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86-314 kUa/L) versus 14.6 kUa/L (range, 0.93-133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase. CONCLUSIONS Milk OIT appears to be efficacious in the treatment of cows milk allergy. The side-effect profile appears acceptable but requires further study.

Open-label maintenance after milk oral immunotherapy for IgE-mediated cow's milk allergy.

Maria D. Rivas, PhD Javier Molina-Infante, MD Maria A. Gonzalez-Nuñez, MD Moises Perez-G, BSc Juan F. Masa, MD Juan F. Sanchez, MD Jose Zamorano, PhD From Unidad de Investigación, Servicio de Digestivo, Servicio de Anatomia Patologica, Servicio de Neumologia-Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CiberRes), and Servicio de Medicina Interna, Hospital San Pedro de Alcantara, Caceres, Spain. E-mail: jose.zamorano@ses.juntaextremadura.net. Supported by Fondo Europeo Desarrollo Regional (FEDER) Funds, Spanish public funds Fondo de Investigacion Sanitaria 06/1431, and Junta de Extremadura PRI06A035 and SCSS0744. M.D.R. was supported by Subdireccion General de Investigacion Sanitaria CA06/0110. Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

Asthma control, adiposity, and adipokines among inner-city adolescents.

BACKGROUND There is an association between adiposity and asthma prevalence, but the relationship to asthma control is unclear. OBJECTIVES We sought to understand the relationships among adiposity, sex, and asthma control in inner-city adolescents with asthma. METHODS We prospectively followed 368 adolescents with moderate-to-severe asthma (ages 12-20 years) living in 10 urban areas for 1 year. Asthma symptoms and exacerbations were recorded, and pulmonary function and exhaled nitric oxide levels were measured every 6 weeks. Adiposity measures (body mass index [BMI] and dual-energy X-ray absorptiometric scans) were made, and blood was collected for measurement of allergy markers, adiponectin, leptin, TNF-alpha, IL-6, and C-reactive protein levels. RESULTS More than 60% of female subjects and 50% of male subjects were above the 85th percentile of BMI for age. Higher BMI was associated with more symptom days (R = 0.18, P = .02) and exacerbations (R = 0.18, P = .06) among female subjects only. Adiponectin was inversely related to asthma symptoms (R = -0.18, P < .05) and exacerbations (R = -0.20, P < .05) and positively with FEV(1)/forced vital capacity ratio (R = 0.15, P < .05) in male subjects only independent of body size. There was no relationship between adiposity or adipokines and total IgE levels, blood eosinophil counts, and exhaled nitric oxide levels. Dual-energy X-ray absorptiometry provided little additional value in relating adiposity to asthma outcome in this population of adolescents. CONCLUSION Adiposity is associated with poorer asthma control in female subjects. Adiponectin is associated with improved asthma control in male subjects.

The natural history of wheat allergy

BACKGROUND Wheat allergy is 1 of the most common food allergies in children, yet few data are available regarding its natural history. OBJECTIVES To define the natural course of wheat allergy and identify factors that help predict outcome in a large referral population of children with wheat allergy. METHODS Patients were included in the study if they had a history of a symptomatic reaction to wheat and a positive wheat IgE test result. Clinical history, laboratory results, and final outcome were recorded for 103 patients who met the inclusion criteria. Resolution of wheat allergy was determined based on food challenge results. Kaplan-Meier survival curves were generated to depict resolution of wheat allergy. RESULTS Rates of resolution were 29% by 4 years, 56% by 8 years, and 65% by 12 years. Higher wheat IgE levels were associated with poorer outcomes. The peak wheat IgE level recorded was a useful predictor of persistent allergy (P < .001), although many children outgrew wheat allergy with even the highest levels of wheat IgE. CONCLUSION The median age of resolution of wheat allergy is approximately 6 1/2 years in this population. In a significant minority of patients, wheat allergy persists into adolescence.

The natural history of soy allergy

BACKGROUND Soy allergy is very common, affecting approximately 0.4% of children. It is generally thought that the majority of children with soy allergy develop tolerance in early childhood; however, this has not been examined in a large cohort with soy allergy. OBJECTIVE We sought to describe the natural history of soy allergy and identify predictors of oral tolerance/outgrowing soy allergy. METHODS The records of patients with soy allergy seen in a tertiary referral clinic were reviewed. Data collected included soy allergy-related symptoms, history of other food allergies and atopic diseases, soy-specific IgE levels, peanut-specific IgE levels, and food challenge results. RESULTS One hundred thirty-three patients were studied (96 male and 37 female patients). Eighty-five (64%) had asthma, 95 (71%) had allergic rhinitis, and 108 (85%) had atopic dermatitis. Eighty-eight percent had concomitant peanut allergy. The median age at the initial visit was 1 year (range, 2 months to 17.5 years); the median duration of follow-up was 5 years (range, 1-19 years). Kaplan-Meier analysis predicted resolution of soy allergy in 25% by age 4 years, 45% by age 6 years, and 69% by age 10 years. By age 6 years, 59% of children with a peak soy IgE level of less than 5 kU/L, 53% of children with a peak s-IgE level of 5 to 9.9 kU/L, 45% of children with a peak s-IgE level of 10 to 49.9 kU/L, and 18% of children with a peak s-IgE level of greater than 50 kU/L had outgrown soy allergy (P < .01 for trend). CONCLUSIONS In this referral population approximately 50% of children with soy allergy outgrew their allergy by age 7 years. Absolute soy IgE levels were useful predictors of outgrowing soy allergy.

Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization

BACKGROUND Endocrine-disrupting compounds (EDCs) have immune-modulating effects. We were interested in determining their association with allergic sensitization. OBJECTIVE We sought to determine the association between EDCs and allergic sensitization and whether this relationship depends on the antimicrobial properties of the EDCs, sex, or both. METHODS Data were obtained from the 2005-2006 National Health and Nutrition Examination Survey in which urinary bisphenol A; triclosan; benzophenone-3; propyl, methyl, butyl, and ethyl parabens; and specific IgE levels were available for 860 children. Aeroallergen and food sensitizations were defined as having at least 1 positive (≥ 0.35 kU/L) specific IgE level to an aeroallergen or a food. Logistic regression was used to determine the association of EDCs and sensitization. Analyses were adjusted for urinary creatinine level, age, sex, ethnicity, and poverty index ratio. RESULTS The odds of aeroallergen sensitization significantly increased with the level of the antimicrobial EDCs triclosan and propyl and butyl parabens (P ≤ .04). The odds of food sensitization significantly increased with the level of urinary triclosan among male subjects (odds ratio for third vs first tertiles, 3.9; P= .02 for trend). There was a significant interaction between sex and triclosan level, with male subjects being more likely to be food sensitized with exposure (P= .03). Similar associations were not identified for the nonantimicrobial EDCs bisphenol A and benzophenone-3 (P > .2). CONCLUSIONS As a group, EDCs are not associated with allergen sensitization. However, levels of the antimicrobial EDCs triclosan and parabens were significantly associated with allergic sensitization. The potential role of antimicrobial EDCs in allergic disease warrants further study because they are commonly used in Western society.

Household mouse allergen exposure and asthma morbidity in inner-city preschool children

BACKGROUND Inner-city children experience disproportionate asthma morbidity, and suspected reasons include indoor environmental exposures. OBJECTIVE To determine if mouse allergen exposure is a risk factor for asthma morbidity. METHODS Preschool children with asthma were recruited from inner-city Baltimore, MD. Skin testing was performed and blood was collected at the baseline visit for quantification of mouse allergen specific IgE. A questionnaire evaluated symptoms, medication, and health care use at baseline, 3 months, and 6 months. A trained technician collected dust samples from the childs home for analysis of Mus m 1 at baseline, 3 months, and 6 months. Outcomes were compared between mouse-sensitized, highly exposed children and all other children. RESULTS A total of 127 children had complete data for mouse sensitization status and bedroom settled dust mouse allergen levels at baseline. The mean age of the children was 4.4 years, 92% were African American, and 26% were sensitized to mouse. Mouse-sensitized children exposed to higher levels of Mus m 1 (>0.5 microg/g) had 50% more days of symptoms (incidence rate ratio [IRR], 1.5; 95% confidence interval [CI], 1.1-2.1) and 80% more days of beta-agonist use than other children (IRR, 1.8; 95% CI, 1.3-2.5). Children in the sensitized and highly exposed group were also more likely to have an unscheduled physician visit (odds ratio [OR], 3.1; 95% CI, 1.6-6.3), emergency department visit (OR, 2.1; 95% CI, 1.1-4.1), and hospitalization (OR, 36.6; 95% CI, 4.1-327.3) than other children. These associations between mouse allergen exposure and asthma symptoms and morbidity remained statistically significant after adjusting for potential confounders, including atopy and cockroach sensitization and exposure. CONCLUSIONS In mouse-sensitized inner-city children, exposure to mouse allergen may be an important cause of asthma morbidity.

Section on allergy and immunology

Founded in 1948, the Section on Allergy and Immunology is dedicated to ensuring that children receive the highest quality of allergy and immunology care. To accomplish its mission, the Section provides a number of educational, training, and research programs and continually advocates for improved allergy and immunology care and services. The Section sponsors educational programs for both pediatric generalists and subspecialists at the American Academy of Pediatrics (AAP) National Conference and Exhibition (NCE) each fall and at the American Academy of Allergy Asthma & Immunology annual meeting each spring. The Section’s other educational endeavors include this annual “Best Articles Relevant to Pediatric Allergy and Immunology” supplement to Pediatrics, Visiting Professor Program, Pediatric Asthma Speaker’s Kit, online continuing medical education course on “asthma gadgets,” electronic quality improvement in practice program on asthma diagnosis and management (Education in Quality Improvement for Pediatric Practice [eQIPP], which meets the American Board of Pediatrics maintenance-ofcertification criteria), school nurse allergy tool kit, and a number of public education materials. The Section is also active in contributing to educational programs and resources such as AAP News, educational brochures, clinical reports, and many other endeavors. To support training and promote research in pediatric allergy and immunology, the Section awards travel grants to residents and training fellows to participate and present cases at the AAP NCE and provides outstanding abstract awards for training fellows and junior faculty for presentation at the American Academy of Allergy Asthma & Immunology annual meeting. In close collaboration with other subspecialty societies, the Section is actively involved with initiatives to improve subspecialty education such as the American Board of Allergy and Immunology maintenance-of-certification requirements. Section members represent the AAP in national and government conferences and provide input on federal legislation on behalf of the AAP. For more information on all AAP allergy and immunology resources and initiatives, visit www.aap.org/sections/allergy. The reviews contained in the 2011 synopsis were written by Fellows of the AAP Section on Allergy and Immunology and fellows in allergy and immunology training programs who contributed reviews with their mentors. The editor selected the journals to be reviewed on the basis of the likelihood that they would contain articles on allergy and immunology that would be of value and interest to the pediatrician. Each journal was assigned to a voluntary reviewer who was responsible for selecting articles and writing reviews of their articles. Only articles of original research were selected for review. Final selection of the articles to be included was made by the editor. The 2010–2011 journals chosen for review were Allergy, American Journal of Asthma & Allergy for Pediatricians, Archives of Pediatric and Adolescent Medicine, American Journal of Medicine, American Journal of Respiratory and Critical Care Medicine, Annals of Allergy, Asthma, and Immunology, Annals of Internal Medicine, Archives of Disease in Childhood, Archives of Internal Medicine, Blood, British Journal of Dermatology, British Medical Journal, Chest, Clinical and Experimental Allergy, Clinical Pharmacology and Therapeutics, Critical Care Medicine, European Journal of Pediatrics, European Respiratory Journal, Immunology, Journal of Allergy and Clinical Immunology, Journal of the American Academy of Dermatology, Journal of the American Medical Association, Journal of Applied Physiology, Journal of Experimental Medicine, Journal of Immunology, Journal of Infectious Diseases, Journal of Pediatric Gastroenterology and Nutrition, Journal of Pediatrics, Journal of Pharmacology and Experimental Therapeutics, Lancet, Nature, New England Journal of Medicine, Pediatrics, Medicine, Pediatric Allergy and Immunology, Pediatric Asthma, Allergy & Immunology, Pediatric Dermatology, Pediatric Infectious Disease Journal, and Science. The editor and the Section on Allergy and Immunology gratefully acknowledge the work of the reviewers and their trainees who assisted. The reviewers were Stuart L. Abramson, MD, PhD, Sugar Land, TX; James R. Banks, MD, Arnold, MD; Theresa A. Bingemann, MD, Rochester,

A Longitudinal Study of Indoor Nitrogen Dioxide Levels and Respiratory Symptoms in Inner-City Children with Asthma

Background The effect of indoor nitrogen dioxide concentrations on asthma morbidity among inner-city preschool children is uncertain. Objectives Our goal was to estimate the effect of indoor NO2 concentrations on asthma morbidity in an inner-city population while adjusting for other indoor pollutants. Methods We recruited 150 children (2–6 years of age) with physician-diagnosed asthma from inner-city Baltimore, Maryland. Indoor air was monitored over a 72-hr period in the children’s bedrooms at baseline and 3 and 6 months. At each visit, the child’s caregiver completed a questionnaire assessing asthma symptoms over the previous 2 weeks and recent health care utilization. Results Children were 58% male, 91% African American, and 42% from households with annual income <

In-Home Particle Concentrations and Childhood Asthma Morbidity

25,000; 63% had persistent asthma symptoms. The mean (± SD) in-home NO2 concentration was 30.0 ± 33.7 (range, 2.9–394.0) ppb. The presence of a gas stove and the use of a space heater or oven/stove for heat were independently associated with higher NO2 concentrations. Each 20-ppb increase in NO2 exposure was associated significantly with an increase in the number of days with limited speech [incidence rate ratio (IRR) = 1.15; 95% confidence interval (CI), 1.05–1.25], cough (IRR = 1.10; 95% CI, 1.02–1.18), and nocturnal symptoms (IRR = 1.09; 95% CI, 1.02–1.16), after adjustment for potential confounders. NO2 concentrations were not associated with increased health care utilization. Conclusions Higher indoor NO2 concentrations were associated with increased asthma symptoms in preschool inner-city children. Interventions aimed at lowering NO2 concentrations in inner-city homes may reduce asthma morbidity in this vulnerable population.