Alan B. Goldsobel

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,

Cough in the Pediatric Population

C ough is the most common presenting symptom for medical office visits in the United States. Cough in children is usually related to viral respiratory tract infection and typically resolves spontaneously. Between 35% and 40% of school-age children still cough 10 days after the onset of a common cold, and 10% of preschool children have cough 25 days after respiratory tract infection. In children, cough has been associated with environmental factors, such as outdoor and indoor air pollution, including particulate matter, irritant gases, environmental tobacco smoke exposure, and dampness in the home. The frequent presentation of cough in children is further complicated by studies documenting that parental reporting of cough in children correlates poorly with objective measurement of frequency, duration, or intensity of cough. Cough in children disrupts both the parent’s and the child’s daily activities and can be associated with impaired quality of life in the child and significant stress in parents that improves with cough resolution. It is extremely common for parents to treat children with over-the-counter (OTC) cough and cold medications (CCMs) before seeing a health care provider. In a recent survey, approximately 10% of US children were found to be receiving an OTC CCM in any given week. Although OTC CCMs receive Food and Drug Administration (FDA) approval for adults, testing for efficacy and safety in young children has not been adequate, and inappropriate use of CCMs in children has been documented. Adverse events associated with use of OTC CCMs do occur and rare infant deaths have been reported. In January 2008, the FDA issued a public health advisory regarding OTC CCM use in children questioning safety and efficacy and whether the clinical benefits justify potential risks; it now recommends avoiding these medications in children under age 2 years. The FDA also has supported the recent recommendation by the Consumer Health Product Association to avoid OTC CCM use in children under age 4 years. An American Academy of Pediatrics

H1-Antihistamine Treatment in Young Atopic Children: Effect on Urticaria

Simons FE; Early Prevention of Asthma in Atopic Children Study Group. Ann Allergy Asthma Immunol. 2007;99(3):261–266 PURPOSE OF THE STUDY. To evaluate the effect of long-term treatment with levocetirizine on urticaria in young children with atopic dermatitis (AD). STUDY POPULATION. The group studied 510 children with severe AD disease (mean Scoring Atopic Dermatitis [SCORAD] index: 30) aged 12 to 24 months at enrollment. This study is from the Early Prevention of Asthma in Atopic Children (EPAAC) study. METHODS. This was a multicenter, randomized, double-masked, parallel-group, placebo-controlled study. Enrolled children were followed for 18 months on treatment with levocetirizine 0.125 mg/kg or placebo twice daily. The occurrence of urticaria was recorded on diary cards by parents or caregivers and “validated” by study investigators (validation was not explained). RESULTS. During the 18 months of treatment, 27.5% (70 of 255) of the children receiving levocetirizine experienced urticaria in contrast to 41.6% (106 of 255) of the children receiving placebo (P < .001). The mean number of episodes of urticaria was 0.71 ± 0.11 and 1.71 ± 0.25 in the levocetirizine and control groups, respectively (P < .001). Urticaria was noted on a mean of 4.43 days in levocetirizine-treated patients and 5.36 days in placebo-treated patients (P < .001). For 85% of the children, the urticaria lasted ≤7 days. In 77% of the children with urticaria, the outbreak was associated with food ingestion. No significant adverse effects or long-term adverse effects were noted with active treatment. CONCLUSIONS. Forty-two percent of highly atopic young children in the EPAAC study had acute urticaria, predominantly associated with food ingestion. Levocetirizine was effective at preventing urticarial outbreaks and had a modest effect treating urticaria, as demonstrated by the decrease in the duration of the episodes. REVIEWER COMMENTS. In a previous, similar trial (Early Treatment of the Atopic Child [ETAC]) in young children with AD treated with cetirizine, acute urticaria was reported in 16% of the patients treated with placebo and 6% of the patients treated with the antihistamine (Simons FE. J Allergy Clin Immunol. 2001;107[4]:703–706). These patients were less highly atopic than the present study. The current EPAAC study is hindered by the lack of explanation of validation of urticarial episodes. This study has extended knowledge on the safety of cetirizine/levocetirizine for young children with AD and their efficacy in preventing acute urticaria resulting from food allergy.

Differences in Race, Ethnicity, and Socioeconomic Status in Schoolchildren Dispensed Injectable Epinephrine in 3 Massachusetts School Districts

Purpose of the Study. To analyze the demographic characteristics of schoolchildren dispensed injectable epinephrine in 3 school districts with widely diverse socioeconomic, racial, and ethnic populations. Study Population. Students (prekindergarten to grade 12) from 3 school districts in Massachusetts (n = 21 875) were evaluated. Two of the school districts were affluent, suburban towns outside of Boston (5855 students). The third district (16 020 students) was also a Boston suburb but with a very low per-capita income, with 23% of the school-age population living below the poverty line. The 2 suburban districts were 92% and 95% white, respectively, and the third district was 60% nonwhite. Methods. All school districts in Massachusetts are required to report the number of students using daily or as-needed prescription medications to the Department of Public Health. Data were taken from reports filed by school nurses monthly for all students from the 2003–2004 school year for these 3 school districts. Results. A total of 181 schoolchildren (0.83%) in the 3 districts were dispensed injectable epinephrine during the school year studied. Diagnoses listed for the prescription of epinephrine included peanut ree nut allergy (65%), stinging-insect allergy (19%), seafood allergy (6%), and egg or dairy allergy (3%). A miscellaneous group (7%) included diagnoses for latex, chocolate, pollen, fruit, cold air, and ibuprofen allergy. Males were more likely to be dispensed epinephrine than females (odds ratio [OR]: 1.44; P < .02). White students were nearly 5 times more likely to have been dispensed epinephrine for peanut and tree nut allergy (OR: 4.5; P < .001) and almost 9 times more likely for stinging-insect allergy (OR: 8.7; P < .001). Seventy-five percent of students dispensed epinephrine for peanut or tree nut allergy were enrolled in prekindergarten through grade 5. Conclusions. Significant racial and socioeconomic differences for prescribing self-injectable epinephrine was seen in 3 school districts in Massachusetts. Reviewer Comments. This study describes the racial and socioeconomic demographics of children prescribed injectable epinephrine but does not address the reasons for the disparity between affluent and nonaffluent or white and nonwhite populations. This study suggests that minority, socioeconomically disadvantaged students are being either underdiagnosed or undertreated for potential anaphylactic reactions that require epinephrine. Other studies have not shown racial differences in the incidence of food allergies, suggesting that other factors are involved in the lower rate of epinephrine dispensed to disadvantaged minority students.

Risk of Celiac Disease Autoimmunity and Timing of Gluten Introduction in the Diet of Infants at Increased Risk of Disease

Purpose of the Study. Patients with HLA-DR3 or DR4 alleles are at increased risk for the development of celiac disease. However, not all genetically susceptible individuals develop celiac disease. The objective of this study was to investigate whether there was an association between the timing of exposure to gluten and subsequent development of celiac disease autoimmunity (CDA) in children with a genetic predisposition for celiac disease. Study Population. Children (n = 1560) were identified in the Denver, Colorado, metropolitan area with an increased risk for celiac disease (or type 1 diabetes), defined as having either a first-degree relative with type 1 diabetes or positive cord blood screening for HLA-DR3 or DR4 alleles. This study was conducted over 10 years with a mean follow-up of 4.8 years. Methods. This was a prospective, observational study. Infant diet data were collected during telephone or face-to-face interviews at 3, 6, 9, 12, and 15 months of age. No dietary advice was given to the families. Children had blood drawn at 9, 15, and 24 months and annually thereafter for the measurement of the celiac disease autoantigen, and tissue transglutaminase (tTG). After 1 or 2 positive tTG autoantibody results, small-bowel biopsy was offered to the families, although not all had this procedure performed. The primary outcome of the study was the time to development of CDA defined as the presence of tTG autoantibodies on 2 consecutive results or a positive small-bowel biopsy after a single tTG-positive test. Results. Fifty-one children developed CDA. Children exposed to foods containing wheat, barley, or rye in the first 3 months of life had a 5 times increased odds ratio (P = .02) of CDA as compared with children first exposed to gluten at 4 to 6 months of age. Twenty-five of the CDA-positive children had biopsy-proven celiac disease. In these children, exposure to gluten in the first 3 months of life had a 23 times increased risk (P = .001) of CDA. In the biopsy-proven cohort, children not exposed to gluten until >7 months of age also had a significantly increased risk of CDA (odds ratio: 4; P = .04). There was no association between the development of CDA and the timing of introduction of oats or rice. No protective effect of breastfeeding was found with the development of CDA. Although all children in the cohort were exposed to gluten by 12 months of age, the first positive tTG autoantibody test did not occur until 2 years of age, with a mean age of positive conversion of 4.7 years. Conclusions. In children at increased risk of developing celiac disease, timing of gluten exposure in the diet is associated with the appearance of CDA. Exposure to gluten in the first 3 months of life is thought to be associated with increased risk because of immature or incomplete intestinal barrier function. The authors speculate that late gluten exposure may have been associated with CDA because of greater amounts introduced in the older infants. Reviewer Comments. It is important to understand that this study population was specific children with genetic and family history characteristics at increased risk for the development of celiac disease and may not be generalizable to the entire population. Mean follow-up of this population was just under 5 years, and long-term follow-up of these patients is needed to determine if earlier exposure to gluten simply leads to earlier appearance of CDA and that many (if not all) exposed at-risk children would eventually develop CDA. This study also does not address the relationship between CDA and celiac disease.

Efficacy and Safety of Echinacea in Treating Upper Respiratory Tract Infections in Children: A Randomized Controlled Trial

Taylor J, Weber W, Standish L, et al. JAMA . 2003;290:2824–2830 To determine if echinacea is effective in reducing the duration and/or severity of upper respiratory infection (URI) symptoms in children and assess its safety in this age group. Five hundred twenty-four healthy children, aged 2 to 11 years, were enrolled from a practice-based pediatric research network and an alternative-medicine institution in the Seattle, Washington, area. Each child was enrolled in the project for a 4-month period in 2 consecutive years during the peak rhinovirus season. Data were collected on up to …

Association of Changes in Air Quality With Bronchitic Symptoms in Children in California, 1993-2012

K Berhane, ML Chang, R McConnell. JAMA. 2017;315(14):1491–1501 Exposure to elevated concentrations of ambient air pollutants is associated with increases in the prevalence of bronchitic symptoms in children. The authors hypothesized that reductions in measured air pollutants over the periods studied would be associated with an improvement in respiratory symptoms in children with or without asthma. Data were collected from 3 successively recruited cohorts involving 4602 children (48% female subjects, age range of 5–18 years, mean age of 8 years, 45% Hispanic) from 8 Southern California communities during the years 1993 to 2001, 1996 to 2004, and 2003 to 2012. This was a longitudinal study with data from the 3 separate …

Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma: A Systematic Review

SY Lin, N Erekosima, JM Kim. JAMA. 2013;309(12):1278–1288 This was a systematic review of the clinical efficacy and safety of sublingual immunotherapy (SLIT) delivered via an aqueous solution. This publication was derived from a Comparative Effectiveness Review by the same authors, commissioned by the U.S. Agency for Healthcare Research and Quality. Sixty-three randomized controlled trials (RCTs) involving 5131 participants met the inclusion criteria and were included in this systematic review. Ages ranged from 4 to 74 years. Most of the studies were trials of grass and dust mite SLIT. Also included were trials of tree, ragweed, cat, and Alternaria SLIT. All but one of the trials in this report used a single allergen extract for treatment. All of the included studies were required to …

Association of Early Life Wheeze and Lung Function

Wegienka G, Havstad S, Zoratti EM, Ownby DR, Johnson CC. Ann Allergy Asthma Immunol. 2009;102(1):29–34 PURPOSE OF THE STUDY. To calculate the age-specific incidence of wheeze and to determine whether wheezing at particular ages in early life is predictive of abnormal pulmonary function (airway hyperreactivity [AHR] and percentage of predicted forced expiratory volume in 1 second [FEV1]) and current asthma at age 6 to 7 years. STUDY POPULATION. The Childhood Allergy Study is an ongoing study evaluating environmental determinants of childhood allergies and asthma. An unselected birth cohort consisting of 835 term infants born to women >18 years of age belonging to a health maintenance organization in the suburban Detroit, Michigan, area between 1987 and 1989 was …

Relationship of Body Mass Index With Asthma Indicators in Head Start Children

Vargas P, Perry T, Robles E, et al. Ann Allergy Asthma Immunol. 2007;99(1):22–28 PURPOSE OF THE STUDY. To examine the relationship of BMI and asthma in children in the Head Start program in Arkansas. STUDY POPULATION. A group of 213 children aged 3 to 5 years with physician-diagnosed asthma were compared with 816 age-matched peer control subjects from the sample of the National Health and Nutrition Examination Survey (NHANES) and with 1024 children in prekindergarten in Arkansas public schools. METHODS. Caregivers of the children with asthma from the Head Start program were interviewed with a structured questionnaire including the Juniper Asthma Quality of Life Survey, and the childrens medical charts were reviewed. One hundred forty-one of the 213 children underwent skin-prick testing. One hundred forty-five of the children had urine cotinine levels measured to determine exposure to environmental tobacco smoke. These data were compared with the 2 reference groups in a cross-sectional analysis. RESULTS. The prevalence of obesity (BMI > 95th percentile) was significantly higher in the Head Start children with asthma compared with the NHANES children (P < .001) and the prekindergarten children (P < .05). Compared with Head Start children with a BMI at <85th percentile, Head Start asthmatic patients with a BMI at >85th percentile reported significantly more school days missed, lifetime hospitalizations, emergency department visits, activity limitations, and oral corticosteroid bursts. No significant differences were observed in rescue and controller medications, environmental tobacco smoke exposure, prick-puncture allergy testing, quality of life, or nighttime symptoms. CONCLUSIONS. Obesity (BMI > 95th percentile) was associated with increased asthma prevalence and morbidity. There was no association with the number or type of asthma medications or atopic status. REVIEWER COMMENTS. This is another study showing the association of obesity and asthma. In this study, 18.8% of the Head Start children with asthma had a BMI at >95th percentile, compared with 10.8% of the NHANES and 14.4% of the prekindergarten general-population children. The mechanisms of association have not been clearly established. Both conditions are characterized by chronic inflammation.