Omalizumab for the Treatment of Multiple Food Allergies.

BACKGROUND: Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. METHODS: In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension. RESULTS: Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group. CONCLUSIONS: In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).

Prescription fill patterns in underserved children with asthma receiving subspecialty care.

BACKGROUND: Children with asthma receiving specialty care have been found to have improved asthma outcomes. However, these outcomes can be adversely affected by poor adherence with controller medications. OBJECTIVE: To analyze pharmacy fill patterns as a measure of primary adherence in a group of underserved minority children receiving allergy subspecialty care. METHODS: As part of a larger 18-month nebulizer use study in underserved children (ages 2-8 years) with persistent asthma, 53 children were recruited from an urban allergy practice. Pharmacy records were compared with prescribing records for all asthma medications. RESULTS: Allergist controller prescriptions were written in 30-day quantities with refills and short-acting ß-agonists (SABAs) with no refills. Only 49.1% of inhaled corticosteroid (ICS), 49.5% of combination ICS and long-acting ß-agonist, and 64.5% of leukotriene modifier (LTM) initial and refill prescriptions were ever filled during the 18-month period. A mean of 5.1 refills (range, 0-14) for SABAs were obtained during 18 months, although only 1.28 SABA prescriptions were prescribed by the allergist. Mean times between first asthma prescription and actual filling were 30 days (range, 0-177 days) for ICSs, 26.6 days (range, 0-156 days) for LTMs, and 16.8 days (range, 0-139 days) for SABAs. CONCLUSION: Underserved children with asthma receiving allergy subspecialty care suboptimally filled controller prescriptions, yet filled abundant rescue medications from other prescribers. Limiting albuterol prescriptions to one canister without additional refills may provide an opportunity to monitor fill rates of both rescue and controller medications and provide education to patients about appropriate use of medications to improve adherence.

Retail Food Equivalents for Post-Oral Immunotherapy Dosing in the Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults (OUtMATCH) Clinical Trial.

BACKGROUND: Patients with food allergy may be advised to introduce specific foods into their diets, both to increase tolerance gradually and as next steps after completing oral immunotherapy or other therapeutic interventions. However, the safe use of retail foods depends on the ability to establish the specific allergen protein content of these foods. OBJECTIVE: To develop a systematic approach to estimate the protein content of peanut, milk, egg, wheat, cashew, hazelnut, and walnut in a variety of retail food equivalents for each allergen and associated patient education materials. METHOD: We created an algorithm that used a multistep process with information from product food labels, nutrient databases, independent weighing and measuring of foods, and information provided by manufacturers, including certificates of analysis, and e-mail communication to estimate the allergen protein content of multiple retail foods for each of seven allergens. Once a variety of retail food equivalents for each allergen and allergen serving size was determined, we developed participant education handouts, which were reviewed by study teams at 10 food allergy centers, the National Institute of Allergy and Infectious Diseases, and the Consortium for Food Allergy Research coordinating center. After 1 year of use, multiple queries were addressed and the retail food equivalents and educational materials were reviewed and edited. RESULTS: We identified a variety of retail food equivalents for seven allergens at six serving sizes, and created 48 unique patient education materials. CONCLUSION: Our results provide extensive guidance on a variety of retail equivalents for seven foods, and a method to estimate retail food protein equivalents systematically with ongoing reassessment.

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.

Food Insecurity in the Food Allergic Population: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Food allergies affect 32 million Americans. Restricted diets due to food allergies can be difficult to maintain especially when the household is food insecure. Food insecurity is defined as the inability to acquire food for household members due to insufficient money or resources for food. The COVID-19 pandemic has caused many people to face food insecurity for the first time with Latinx, Native American, and Black communities disproportionately affected. Because of the increase in food insecurity, this work group developed a survey regarding food insecurity screening. This survey was sent out to a random sample of American Academy of Allergy Asthma & Immunology members to assess food insecurity knowledge and practices. The majority of survey participants did not routinely screen their patients for food insecurity. The biggest barrier identified to screening was lack of knowledge of how to perform a screen and resources available when a patient screened positive. This work group report provides guidance on how to implement and perform a food insecurity screen, including federal resources and assistance programs.

Protocol design and synopsis: Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults with Food Allergy (OUtMATCH).

Background: Food allergy is common and causes substantial morbidity and even mortality. Safe and effective treatments for food allergy would therefore be highly desirable, especially for individuals with multiple food allergies. Objectives: Our aim was to describe a phase 3 study on treatment of patients with multiple food allergies with omalizumab. Methods: The study was developed as a collaboration between the Consortium for Food Allergy Research, the National Institute of Allergy and Infectious Diseases, and 2 industry sponsors (Genentech and Novartis). Results: The study is currently under way, enrolling participants from age 1 year to age 55 years who are allergic to peanut and at least 2 other foods (including milk, egg, wheat, cashew, hazelnut, and walnut). The study is designed to address 3 major questions. First, stage 1 will study the potential value of omalizumab for the treatment of patients with peanut allergy and at least 2 other common food allergens. Second, stage 2 will directly compare treatment of patients with multifood allergies using omalizumab as monotherapy versus treatment with omalizumab-facilitated multiallergen oral immunotherapy in which omalizumab is used as an adjunctive treatment. Third, stage 3 will address the longer-term outcomes following these treatment approaches, including the introduction of dietary forms of the study foods to induce or maintain desensitization. Conclusions: This phase 3 study will provide important information on the potential of omalizumab to treat patients with multiple food allergies.

Extension of food allergen specific IgE ranges from the ImmunoCAP to the IMMULITE systems.

BACKGROUND: Quantitative measures of food specific IgE antibody using the Phadia ImmunoCAP method have documented value in the diagnosis of food allergy. OBJECTIVE: To define factors that could be used to relate IMMULITE-measured IgE antibody levels for chicken egg white, cow's milk, and peanut into ImmunoCAP-comparable quantities that could then be correlated with published levels that have been generated with the ImmunoCAP system. METHODS: Serum samples from 328 patients (median age, 5.4 years; age range, 1-18 years; 32% female) who were known to be IgE positive (>0.1 kU/L) to chicken egg white (n = 120), cow's milk (n = 135), and/or peanut (n = 304) were analyzed in both the ImmunoCAP and IMMULITE autoanalyzers. RESULTS: IgE antibody levels from both assays for each of the 3 food specificities were highly correlated: r(2)= 0.95 for egg white, r(2) = 0.93 for milk, and r(2) = 0.95 for peanut (P < .001). Empirically determined IMMULITE/ImmunoCAP ratios (mean ± 1 SD) were 4.85 ± 1.79 kU/L (egg), 2.33 ± 1.0 kU/L (milk), and 1.86 ± 0.98 kU/L (peanut). For milk and peanut, the IgE antibody levels for individuals who either passed or failed a food challenge were not significantly different between the assay methods. Because of the small sample size of egg white challenged patients, no statistical analysis was performed. CONCLUSION: These data indicate that specific IgE levels to egg white, milk, and peanut measured by the IMMULITE and ImmunoCAP systems are highly correlated and that differences between the systems are circumscribed and modest (IMMULITE was a mean of 2- to 5-fold higher than ImmunoCAP).

Concordance of Medicaid and pharmacy record data in inner-city children with asthma.

BACKGROUND: Management of asthma involves adherence to medication regimens. Assessing adherence is difficult for health care providers and researchers. Self-reported medication use is subjective, so objective methods of data collection for medication use are frequently used in asthma research. The aim of this project is to examine the concordance between asthma medication pharmacy data culled from Medicaid claims data ("Medicaid pharmacy data") and patient pharmacy record data obtained from individual pharmacies ("pharmacy record data"). METHODS: Medicaid pharmacy data and pharmacy record data were obtained from inner-city children enrolled in a prospective study of children with persistent asthma. A subject level comparison of pharmacy records and Medicaid pharmacy data pharmacy records was done to determine concordance between the 2 data collection methods. RESULTS: Of 513 children recruited for inclusion, 221 were consented and randomized. Medicaid claims data were collected on 72.8% (n=161) of the 221 enrolled subjects. Pharmacy record data were available on 96.8% (n=214) of the 221 subjects. Data presented represent the 159 subjects who had both Medicaid claims data and pharmacy records data available throughout the study period. There was complete agreement between Medicaid pharmacy data and pharmacy record for 26% (n=42) of subjects. A total of 1858 asthma medication claims were captured by the Medicaid pharmacy data. Medicaid pharmacy data missed 149 claims that were capture by the pharmacy record data. Medicaid pharmacy data failed to capture a single claim on 4.4% (n=7) of subjects. The pharmacy record data captured a total of 1627 asthma medication claims and missed 371 claims that were captured by the Medicaid pharmacy data. Pharmacy record data failed to capture a single claim in 1.9% (n=3) of subjects. CONCLUSIONS: There was overlap between the pharmacy data captured by the Medicaid pharmacy dataset and pharmacy record dataset, but the overall concordance between the two data collection methods was low. Pharmacy records collected directly from the pharmacy included data on more subjects and pharmacy data culled from Medicaid claims captured more total number of claims. In spite of the differences in the methods used to collect data, pharmacy fill records are a rich source of data with both clinical and research applications. Clinicians and researchers must weigh the benefits and limitations of each method used to collect pharmacy data.

Seasonal patterns of controller and rescue medication dispensed in underserved children with asthma.

OBJECTIVE: To determine whether temporal trends exist for short-acting beta agonist (SABA), oral corticosteroid (OCS), and anti-inflammatory prescription fills in children with persistent asthma. METHOD: This was a longitudinal analysis of pharmacy record data and health information data obtained by parent report over 12 months for children with persistent asthma 2 to 9 years of age. Eligible children had to report current nebulizer use and one or more emergency department visits or hospitalizations within the past 12 months. RESULTS: Children were primarily African-American (89%), male (64%), received Medicaid health insurance (82%), and were a mean age of 4.5 years (SD 2.1). Few families (11%) reported any problems paying for their child's asthma medications at baseline or at the 12-month follow-up. There was a high degree of association between filling a rescue (SABA or OCS) and controller (leukotriene modifier, inhaled corticosteroid, cromolyn) medication during the same month for all months with Pearson's correlation coefficients ranging from a low of 0.28 for October to a high of 0.53 in September. Short-acting beta agonist fills were significantly more likely to be filled concurrently with inhaled corticosteroid fills. However, significantly fewer prescription fills were obtained in the summer months with an acceleration of medication fills in September through December and an increase in early spring. CONCLUSIONS: There was a summer decline in both inhaled corticosteroid and SABA fills. Timing of asthma monitoring visits to occur before peak prescription fill months, i.e., August and December for an asthma "tune-up," theoretically could improve asthma control. During these primary care visits children could benefit from more intensive monitoring of medication use including monitoring lung function, frequency of prescription refills, and assessment of medication device technique to ensure that an effective dose of medication is adequately delivered to the respiratory tract. Additionally, scheduling non-urgent asthma care visits at pre-peak prescription fill months can take advantage of "step down" during decreased symptom periods and when appropriate restart daily controller medications to "step up" prior to peak asthma periods.

The natural history of IgE-mediated cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is the most common food allergy in infants and young children, affecting 2% to 3% of the general population. Most studies have shown the prognosis of developing tolerance to cow's milk to be good, with most outgrowing their allergy by age 3 years. OBJECTIVE: To define the natural course of CMA and identify the factors that best predict outcome in a large referral population of children with CMA. METHODS: Clinical history, test results, and final outcome were collected on 807 patients with IgE-mediated CMA. Patients were considered tolerant after they passed a challenge or experienced no reactions in the past 12 months and had a cow's milk IgE (cm-IgE) level <3 kU/L. RESULTS: Rates of resolution were 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Patients with persistent allergy had higher cm-IgE levels at all ages to age 16 years. The highest cm-IgE for each patient, defined as peak cm-IgE, was found to be highly predictive of outcome (P < .001). Coexisting asthma (P < .001) and allergic rhinitis (P < .001) were also significant predictors of outcome. CONCLUSION: The prognosis for CMA in this population is worse than previously reported. However, some patients developed tolerance during adolescence, indicating that follow-up and re-evaluation of CMA patients is important in their care. cm-IgE level is highly predictive of outcome. CLINICAL IMPLICATIONS: The increasing potential for persistence of CMA, along with cm-IgE level's effect on prognosis, should be considered when counseling families regarding expected clinical course.

Long-Term Follow-Up After Baked Milk Introduction.

BACKGROUND: Clinical trials of baked milk (BM) introduction have demonstrated accelerated resolution of milk allergy. OBJECTIVE: Long-term data regarding real-world introduction of BM are lacking. We sought to characterize our experience of BM introduction. METHODS: We performed a retrospective chart review of consecutive BM oral food challenges performed in our clinic from 2009 to 2014, with a minimum follow-up of 24 months. RESULTS: Of the 206 patients challenged, 99 (48%) passed and 187 were sent home with detailed instructions to incorporate BM into their diets. After a median of 49 months of follow-up, 43% of the 187 had progressed to direct milk, 20% to less-cooked forms of milk, 10% remained ingesting BM, and 28% were strictly avoiding milk. Higher milk IgE levels were associated with decreased odds of passing a BM challenge and advancing to less-cooked forms of milk. Predictors of progressing to less-cooked forms of milk were passing the challenge and younger age. There were 79 reported milk reactions involving 68 patients (33% of total) during follow-up. Of these, 78% were classified as mild, 14% severe, and 6 patients developed eosinophilic esophagitis. Of 11 severe reactions, 4 were accidental exposures, 3 were planned escalations, and 4 occurred with previously tolerated doses. CONCLUSIONS: The majority of patients who underwent a BM challenge, including those who failed their challenge, were able to progress to direct or less-cooked forms of milk. However, adverse reactions were common, and even a successful BM challenge does not guarantee future tolerance of BM or preclude later reactions, even to previously tolerated doses.

Effectiveness of nebulizer use-targeted asthma education on underserved children with asthma.

OBJECTIVE: To determine the effectiveness of a home-based asthma education intervention in increasing appropriate nebulizer use and reducing symptom frequency, emergency department (ED) visits, and hospitalizations over 12 months. DESIGN: A randomized clinical trial. Settings Pediatric primary care, pulmonary/allergy, and ED practices associated with the University of Maryland Medical System and The Johns Hopkins Hospital, Baltimore. PARTICIPANTS: Children with persistent asthma, aged 2 to 9 years, with regular nebulizer use and an ED visit or hospitalization within the past 12 months. Children were randomized into the intervention (n = 110) or control (n = 111) group. Follow-up data were available for 95 intervention and 86 control children. INTERVENTION: Home-based asthma education, including symptom recognition, home treatment of acute symptoms, appropriate asthma medication, and nebulizer practice. MAIN OUTCOME MEASURES: Estimates of mean differences in asthma symptom frequency, number of ED visits and hospitalizations and appropriate quick relief, controller medication, and nebulizer practice over 12 months. RESULTS: Of the 221 children, 181 (81.9%) completed the study. There were no significant differences in home nebulizer practice, asthma morbidity, ED visits, or hospitalizations between groups (P range, .11-.79). Although most children received appropriate nonurgent asthma care (mean, 2 visits per 6 months), more than one third of all children received at least 6 quick-relief medication prescriptions during 12 months, with no difference by group. CONCLUSIONS: A nebulizer education intervention had no effect on asthma severity or health care use. Of concern is the high quick-relief and low controller medication use in young children with asthma seen nearly every 3 months for nonurgent care.

Conversion to low-protein, powder-free surgical gloves: is it worth the cost?

This study was conducted to determine changes in overall costs associated with conversion to powder-free gloves including cost of workers' compensation cases for natural rubber latex (NRL)-related symptoms and health care workers' glove satisfaction. The study, a 2-year, longitudinal design with retrospective and prospective aspects, was developed to determine health care worker use of powder-free, low-protein NRL gloves, sensitization, cost, and glove satisfaction. Informed consent was obtained from 103 health care workers. Prior to glove conversion, nearly one-half (44%, 36 of 82) of the operating room staff reported symptoms related to NRL exposure. At the end of the 14-month data collection period, only 27% (22 of 82, McNemar test = .007) reported symptoms related to NRL exposure. Additionally, a cost savings of 10,000 dollars per year for gloves was evident with reports of increased user satisfaction. This study demonstrated that conversion to the use of powder-free, low-protein NRL gloves not only reduces health care worker NRL symptoms, but also positively affects the costs of glove purchases and workers' compensation.

Impact of converting to powder-free gloves. Decreasing the symptoms of latex exposure in operating room personnel.

This study examined health care worker satisfaction with the use of non-powdered natural rubber latex (NRL) surgical gloves to determine the impact of non-powdered NRL gloves on the NRL sensitization of operating room personnel. The study used a 1-year longitudinal design to obtain recall information from employees about their NRL exposure. Additionally, a survey was completed by participants related to their satisfaction with non-powdered NRL gloves. Informed consent was obtained from 103 employees. After conversion to an operating room using non-powdered NRL, there was a significant decrease in reported symptoms with NRL exposure (42% pre- and 29% post-conversion, Fisher's exact, two-tailed, p = .0001). This study demonstrated that the conversion to non-powdered low-protein NRL gloves resulted in decreased symptoms because of NRL exposure.

Managing food allergies in schools and camps.

Managing food allergy in school and camp environments involves creating an individualized plan that addresses safety, and supports growth and development of the food-allergic child. The result is a dynamic strategy that meets the needs of a food-allergic child and promotes the development of a food-allergic adolescent.

The impact of food allergy on the daily activities of children and their families.

BACKGROUND: Food allergy affects a significant number of children, and its management requires considerable time and vigilance. OBJECTIVE: To determine the impact of food allergy on the daily activities of food allergic children and their families. METHODS: Caregivers of food allergic children from a university-based allergy practice completed a questionnaire that evaluated their perception of the impact of their child's food allergy on family activities. RESULTS: Of the 87 families who completed the study, more than 60% of caregivers reported that food allergy significantly affected meal preparation and 49% or more indicated that food allergy affected family social activities. Forty-one percent of parents reported a significant impact on their stress levels and 34% reported that food allergy had an impact on school attendance, with 10% choosing to home school their children because of food allergy. The number of food allergies had a significant impact on activity scores, but the existence of comorbid conditions such as asthma and atopic dermatitis did not significantly affect the results. CONCLUSIONS: Food allergy has a significant effect on activities of families of food allergic children. Further study is needed to determine more detailed effects of food allergy on parent-child interactions and development.

Pharmacy fill patterns in young urban children with persistent asthma.

BACKGROUND: Medication adherence impacts healthcare utilization. Pharmacy records are useful to establish fill patterns. OBJECTIVE: Use pharmacy records to establish medication patterns fill patterns for comparison to healthcare utilization. Methods. Pharmacy records of 175 children with persistent asthma were collected and compared to healthcare utilization. RESULTS: Majority of subjects had significant healthcare utilization, low numbers of rescue medications, and poor controller medication fill rates. Those with more rescue medications had more healthcare utilization and more controller medications. CONCLUSIONS: Pharmacy fill patterns demonstrate few rescue and/or controller medication fills. Those with more rescue medications reported increased healthcare utilization despite controller medications.

Patterns of inhaled antiinflammatory medication use in young underserved children with asthma.

BACKGROUND: Asthma guidelines advocate inhaled corticosteroids as the cornerstone treatment of persistent asthma, yet several studies report underuse of inhaled corticosteroids in children with persistent asthma. Moreover, few studies use objective pharmacy data as a measure of drug availability of asthma medications. We examined factors associated with the use of inhaled corticosteroids in young underserved children with persistent asthma using pharmacy records as their source of asthma medications. METHODS: This was a cross-sectional analysis of questionnaire and pharmacy record data over a 12-month period from participants enrolled in a randomized clinical trial of a nebulizer educational intervention. RESULTS: Although exposure to > or = 1 inhaled corticosteroids refill was high at 72%, 1 of 5 children with persistent asthma had either no medication or only short-acting beta agonist fills for 12 months. Only 20% of children obtained > or = 6 inhaled corticosteroids fills over 12 months. Obtaining > or = 3 inhaled corticosteroids fills over 12 months was significantly associated with an increase in short-acting beta agonist fills and receiving specialty care in the regression models while controlling for child age, asthma severity, number of emergency department visits, having an asthma action plan, and seeking preventive care for the child's asthma. CONCLUSIONS: Overreliance on short-acting beta agonist and underuse of inhaled corticosteroid medications was common in this group of young children with persistent asthma. Only one fifth of children obtained sufficient controller medication fills.