Ovomucoid epitope-specific repertoire of IgE, IgG4 , IgG1 , IgA1 , and IgD antibodies in egg-allergic children.

BACKGROUND: Egg-white ovomucoid, that is, Gal d 1, is associated with IgE-mediated allergic reactions in most egg-allergic children. Epitope-specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG1 , IgG4 , IgA, and IgD) may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied. METHODS: Bead-based epitope assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG1 , and esIgG4 antibodies directed at 58 (15-mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg-allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities. RESULTS: BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE-binding epitopes. Egg-allergic children had lower esIgA1 (P = .010) and esIgG1 (P = .016) and higher esIgE (P < .001) and esIgD (P = .015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P = .038). Network analysis identified most associations between esIgE with either esIgG4 or esIgD; indicating that IgE-secreting plasma cells could originate from either sequential isotype switch from antigen-experienced intermediate isotypes or directly from the IgD+ B cells. CONCLUSIONS: Collectively, these data point toward a contribution of epitope-specific antibody repertoires to the pathogenesis of egg allergy.

Endotoxin, food allergen sensitization, and food allergy: A complementary epidemiologic and experimental study.

BACKGROUND: Household endotoxin levels have been variably associated with risk for asthma and atopy. METHODS: We studied participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES, n = 6963), a large cohort representative of the US population (aged 1-84 years). We built logistic regression models to test for associations between house dust endotoxin and sensitization to specific foods (milk, egg, and peanut). To experimentally explore the detected epidemiologic associations, peripheral blood mononuclear cells (PBMCs) were collected from 21 children (aged 1-19 years) mono-food allergic (ie, sensitized and clinically reactive) to milk, egg, or peanut and nonallergic controls for stimulation with endotoxin and secreted cytokine measurement. For each food allergy, linear mixed-effects models were built to test the association between endotoxin stimulation and cytokine level. RESULTS: Among NHANES subjects, the geometric mean household endotoxin level was 15.5 EU/mg (GSE 0.5). Prevalence of food allergen sensitization (sIgE ≥ 0.35 kUA /L) varied by food: milk 5.7%, egg 4.0%, and peanut 7.9%. In models adjusted for potential confounders (age, race, country of birth, total people per household, US region, and history of wheezing in the past year), household endotoxin level was associated with sensitization to milk (OR 1.7, 95% CI 1.2-2.1) and egg (OR 1.4, 95% CI 1.01-1.9), but not peanut (OR 0.98, 95% CI 0.8-1.2). Interferon-γ levels of endotoxin-stimulated PBMCs from children allergic to milk or egg, but not peanut, were significantly lower compared to controls in linear mixed-effects models adjusted for repeated measures, experimental variables, age, and inter-individual variability (P-values .007, .018, and .058, respectively). CONCLUSION: Higher household endotoxin is associated with increased odds of milk and egg sensitization. Altered cytokine responsiveness to endotoxin is also observed in PBMCs from individuals with milk and egg allergy.

Risk factors for multiple epinephrine doses in food-triggered anaphylaxis in children.

BACKGROUND: Food-related anaphylactic reactions may require treatment with more than 1 dose of epinephrine. Current guidelines advise patients at risk of anaphylaxis to carry 2 epinephrine autoinjectors. OBJECTIVE: The objective of this study was to determine risk factors of multiple-dose epinephrine treatment in pediatric food-related anaphylaxis. METHODS: Parents of children with physician-confirmed diagnosis of food allergy were administered a standardized questionnaire at the time of their clinic visit. These patients were then followed-up prospectively by phone. RESULTS: Six hundred forty-two subjects had allergic reactions. Twenty-six percent of patients reported at least 1 reaction treated with epinephrine, for a total of 221 reactions. Among reactions treated with epinephrine, 24 reactions (11%) received 2 or more doses of epinephrine. The most common triggers were milk (30%) and peanut (18%). Milk-triggered allergic reactions (odds ratio [OR] 3.2; 95% confidence interval [CI] 1.2-8.4) and treatment with oxygen (OR 5.0, 95% CI 2.0-12.4) were significant risk factors for requiring multiple doses of epinephrine to treat an allergic reaction. CONCLUSION: This study demonstrates that treatment of anaphylaxis may require more than 1 epinephrine injection. Reactions triggered by milk or requiring treatment with oxygen are at higher risk for needing more than 1 dose of epinephrine. Families of food-allergic children should be counseled on the importance of carrying 2 epinephrine auto-injectors.

Childcare and School Management Issues in Food Allergy.

PURPOSE OF REVIEW: The goal of this review is to characterize food allergy management and anaphylaxis in schools and assess current policies and level of preparedness of schools to recognize and treat anaphylaxis. RECENT FINDINGS: An increasing number of school-aged children have food allergies, and studies show that a significant number of school children with no known history of allergies will experience their first anaphylactic reaction at school. Stock-unassigned epinephrine auto-injectors are recommended in schools but not mandatory in most states, and therefore, epinephrine is not always available. Non-nursing staff members are sometimes administering epinephrine due to limitations in nurse staffing. Wide variations in staff training and lack of stock epinephrine leave many schools inadequately prepared to manage anaphylactic reactions. Emphasis should be placed not only on ensuring all schools have stock epinephrine but also on training a wider range of school staff members to minimize treatment delay with epinephrine and improve clinical outcomes.

Clinical predictors of sustained intraocular pressure elevation due to intravitreal anti-vascular endothelial growth factor therapy.

PURPOSE: We assess for frequency and predictive factors related to sustained intraocular pressure (IOP) elevation in eyes with neovascular age-related macular degeneration receiving intravitreal injections of ranibizumab and/or bevacizumab. METHODS: A total of 328 patients with neovascular age-related macular degeneration (449 eyes) who presented to a single physician over a 6-month period were retrospectively assessed for baseline demographic/clinical information, total number of bevacizumab and/or ranibizumab injections, and sustained IOP elevation on 2 or more consecutive visits (absolute IOP >25 mmHg, increase above baseline >10 mmHg, or IOP of >21 mmHg and increase of >5 mmHg). Cox regression survival analysis and multivariate logistic regression were performed to assess the influence of intravitreal injections on experiencing sustained IOP elevation. RESULTS: Overall, 32 eyes (7.1%) experienced sustained IOP elevation. Survival analysis showed a significant effect of the number of anti-vascular endothelial growth factor injections on sustained IOP elevation (hazard ratio, 1.085; 95% confidence interval: 1.06-1.11, P < 0.001). Also, there was an increased odds ratio (16.1, P = 0.008) of sustained IOP elevation in eyes receiving ≥29 injections compared with ≤12 injections. After controlling for the confounder (prior intravitreal steroid injection), total number of injections still showed a statistically significant association (P = 0.002). CONCLUSION: A greater number of intravitreal anti-vascular endothelial growth factor injections is associated with an increased risk for sustained IOP elevation in eyes with neovascular age-related macular degeneration receiving intravitreal ranbizumab and/or bevacizumab.

The SunBEAm birth cohort: Protocol design.

Background: Food allergy (FA) and atopic dermatitis (AD) are common conditions that often present in the first year of life. Identification of underlying mechanisms and environmental determinants of FA and AD is essential to develop and implement effective prevention and treatment strategies. Objectives: We sought to describe the design of the Systems Biology of Early Atopy (SunBEAm) birth cohort. Methods: Funded by the National Institute of Allergy and Infectious Diseases (NIAID) and administered through the Consortium for Food Allergy Research (CoFAR), SunBEAm is a US population-based, multicenter birth cohort that enrolls pregnant mothers, fathers, and their newborns and follows them to 3 years. Questionnaire and biosampling strategies were developed to apply a systems biology approach to identify environmental, immunologic, and multiomic determinants of AD, FA, and other allergic outcomes. Results: Enrollment is currently underway. On the basis of an estimated FA prevalence of 6%, the enrollment goal is 2500 infants. AD is defined on the basis of questionnaire and assessment, and FA is defined by an algorithm combining history and testing. Although any FA will be recorded, we focus on the diagnosis of egg, milk, and peanut at 5 months, adding wheat, soy, cashew, hazelnut, walnut, codfish, shrimp, and sesame starting at 12 months. Sampling includes blood, hair, stool, dust, water, tape strips, skin swabs, nasal secretions, nasal swabs, saliva, urine, functional aspects of the skin, and maternal breast milk and vaginal swabs. Conclusions: The SunBEAm birth cohort will provide a rich repository of data and specimens to interrogate mechanisms and determinants of early allergic outcomes, with an emphasis on FA, AD, and systems biology.

Effect on intraocular pressure in patients receiving unilateral intravitreal anti-vascular endothelial growth factor injections.

PURPOSE: We assessed the frequency and predictive factors related to intraocular pressure (IOP) elevation in neovascular age-related macular degeneration (AMD) patients undergoing unilateral intravitreal ranibizumab and/or bevacizumab injections. DESIGN: Retrospective cohort study. PARTICIPANTS: Charts of 207 patients with neovascular AMD who presented to a single physician at a retinal referral practice over a 6-month period were retrospectively reviewed. METHODS: Data recorded included demographic information, clinical findings, total number of bevacizumab and ranibizumab injections received and IOP at each visit. Increases above baseline IOP of >5, >10, or >15 mmHg on ≥2 consecutive visits while under treatment were noted. MAIN OUTCOME MEASURES: The frequency of IOP elevation was compared between treated and untreated eyes. In addition, among treated eyes, frequency and odds ratio of experiencing IOP elevation >5 mmHg above baseline on ≥2 consecutive visits was stratified by number of injections. For the main regression analysis, the outcome variable was IOP elevation >5 mmHg on ≥2 consecutive visits and the main independent variable was total number of injections. RESULTS: On ≥2 consecutive visits, 11.6% of treated versus 5.3% of untreated/control eyes experienced IOP elevation of >5 mmHg. The mean number of injections was higher in those with (24.4; 95% confidence interval [CI], 20.9-28.0; range, 9-39) than without IOP elevation of >5 mmHg (20.4; 95% CI, 18.9-21.8; range, 3-48) on ≥2 consecutive visits. There was an increased odds ratio (5.75; 95% CI, 1.19-27.8; P = 0.03) of experiencing IOP elevation >5 mmHg on ≥2 consecutive visits in patients receiving ≥29 injections compared with ≤12 injections. Of the factors considered, only the total number of injections showed a statistically significant association with IOP elevation >5 mmHg above baseline on ≥2 consecutive visits in treated eyes (P = 0.05). CONCLUSIONS: A greater number of intravitreal anti-vasular endothelial growth factor injections is associated with an increased risk for IOP elevation >5 mmHg on ≥2 consecutive visits in eyes with neovascular AMD receiving intravitreal ranbizumab and/or bevacizumab.

Relevance of Early Introduction of Cow's Milk Proteins for Prevention of Cow's Milk Allergy.

Food allergy incidence has increased worldwide over the last 20 years. For prevention of food allergy, current guidelines do not recommend delaying the introduction of allergenic foods. Several groundbreaking studies, such as the Learning Early About Peanut Allergy study, showed that the relatively early introduction of this allergenic food between 4-6 months of age reduces the risk of peanut allergy. However, less is known about the introduction of cow's milk, as many children already receive cow's-milk-based formula much earlier in life. This can be regular cow's milk formula with intact milk proteins or hydrolyzed formulas. Several recent studies have investigated the effects of early introduction of cow's-milk-based formulas with intact milk proteins on the development of cow's milk allergy while breastfeeding. These studies suggest that depending on the time of introduction and the duration of administration of cow's milk, the risk of cow's milk allergy can be reduced (early introduction) or increased (very early introduction followed by discontinuation). The aim of this narrative review is to summarize these studies and to discuss the impact of early introduction of intact cow's milk protein-as well as hydrolyzed milk protein formulas-and the development of tolerance versus allergy towards cow's milk proteins.

Food-Induced Anaphylaxis in Infants: Can New Evidence Assist with Implementation of Food Allergy Prevention and Treatment?

Previous guidance on infant anaphylaxis largely relied on data from older children and adults. Infants are a unique subgroup, which presents specific challenges because infants are unable to verbalize symptoms, although the magnitude of underrecognition is not well studied. Data show that strict avoidance of allergens is difficult to achieve in the infant age group and a source of stress and anxiety for their caregivers. Recent studies suggest that infant anaphylaxis is less severe than in older children, which could greatly assist with implementation of food allergy prevention and treatment. New evidence from clinical trials and observational and real-world studies show that infant anaphylaxis is rare on first ingestion of a new food and typically not severe when it occurs, which parents may not be aware of when preparing to introduce peanut or other common food allergens to infants for the purpose of prevention. The better safety and efficacy of oral immunotherapy in infants and preschoolers could help prevent undesired psychosocial consequences of longstanding food allergy such as anxiety, bullying, and poor quality of life. Evidence from recent years on the lower risk of infant anaphylaxis and its severity could move allergy practice toward the confidence that regular, long-term ingestion provides.

Which family members use the best nets? An analysis of the condition of mosquito nets and their distribution within households in Tanzania.

BACKGROUND: Household ownership of insecticide-treated mosquito nets (ITNs) is increasing, and coverage targets have been revised to address universal coverage with ITNs. However, many households do not have enough nets to cover everyone, and the nets available vary in physical condition and insecticide treatment status. Since 2004, the Government of Tanzania has been implementing the Tanzania National Voucher Scheme (TNVS), which distributes vouchers for ITNs through antenatal clinics to target pregnant women and their infants. This analysis aimed to determine the following: (1) coverage patterns of bed nets within households according to physical condition and treatment status; (2) who might be at risk if mosquitoes were diverted from occupants of untreated nets to those not using nets? (3) the degree to which those at highest risk of malaria use the most protective nets. METHODS: Data from the 2006 TNVS household survey were analysed to assess within-household distribution of net use. The associations between net characteristics and net user were also evaluated. Multivariate analysis was applied to the relationship between the number of holes per net and user characteristics while adjusting for confounders. RESULTS: In households with a net:person ratio better than 1:4 (one net for every four household members), more than 80% of the people in such households reported using a net the previous night. ITNs were most likely to be used by infants, young children (1-4 y), and women of childbearing age; they were least likely to be used by older women (>or=50 y), older children (5-14 y), and adult men. The nets used by infants and women of childbearing age were in better-than-average physical condition; the nets used by older women and older children were in worse-than-average condition; while young children and adult men used nets in intermediate (average) condition. When adjusted for confounders, the nets used by young and older children had more holes than nets used by infants. CONCLUSIONS: Infants and other vulnerable groups were most likely to sleep under the most protective nets. Nevertheless, more communication efforts are needed to increase use of intact ITNs within households for children. Further research is necessary to fully understand motivations influencing within-household net distribution.

Hemoptysis in a Patient with Elevated Immunoglobulin E.

Recurrent pneumonia with cavitation leading to pneumatoceles, secondary fungal infections, and hemoptysis are major causes of mortality and morbidity in patients with hyper-IgE syndrome. Prevention and aggressive treatment of pneumonia in these patients are essential to prevent further lung damage, but treatment may be delayed because the classic signs/symptoms of infection such as fever, chills, or rigors may be lacking. Early imaging to identify infection is essential for diagnosis and treatment. The mainstay of therapy is continuous, full-dose daily trimethoprim-sulfamethoxazole and commonly fungal coverage. Because hyper-IgE syndrome is a progressive disease, patients' condition may worsen despite compliance with prophylactic therapy.