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1. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XII – Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA

Author

Antonio Bognanni, MD, PhD (c), Alessandro Fiocchi, MD, Stefania Arasi, MD, MSc, PhD, Derek K. Chu, MD, PhD, Ignacio Ansotegui, MD, PhD, Amal H. Assa'ad, MD, Sami L. Bahna, MD, DrPH, Roberto Berni Canani, MD, PhD, Martin Bozzola, MD, Lamia Dahdah, MD, Christophe Dupont, MD, PhD, Piotr Dziechciarz, MD, PhD, Motohiro Ebisawa, MD, PhD, Ramon T. Firmino, MD, Alexandro Chu, BHSc(Hons), Elena Galli, MD, PhD, Andrea Horvath, MD, PhD, Rose Kamenwa, MD, Gideon Lack, MBBCh, Haiqi Li, MD, Alberto Martelli, MD, Anna Nowak-Węgrzyn, MD, PhD, Nikolaos G. Papadopoulos, MD, PhD, Ruby Pawankar, MD, PhD, Yetiani Roldan, MD, Maria Said, RN, Mario Sánchez-Borges, MD, Raanan Shamir, MD, PhD, Jonathan M. Spergel, MD, PhD, Hania Szajewska, MD, Luigi Terracciano, MD, Yvan Vandenplas, MD, PhD, Carina Venter, PhD, RD, Siw Waffenschmidt, PhD, Susan Waserman, MD, MSc, Amena Warner, RN, SN (PG Dip), Gary W.K. Wong, MD, Holger J. Schünemann, MD, MSc, PhD, and Jan L. Brozek, MD, PhD

Subjects
Milk allergy, Milk replacement formulas, Probiotics, Clinical practice guidelines, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as “conditional” following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers’ values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Published
2024
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2. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update – X – Breastfeeding a baby with cow's milk allergy

Author

Vicki McWilliam, PhD, AdvAPD, Merryn J. Netting, PhD, BSc, BND, Evelyn Volders, PhD, AdvAPD, Debra J. Palmer, PhD, BSc, BND, Ignacio Ansotegui, Stefania Arasi, Amal H. Assa'ad, Sami L. Bahna, Roberto Berni Canani, Antonio Bognanni, Martin Bozzola, Jan Brozek, Derek Chu, Lamia Dahdah, Christophe Dupont, Piotr Dziechciarz, Motohiro Ebisawa, Ramon T. Firmino, Alessandro Fiocchi, Elena Galli, Rose Kamenwa, Gideon Lack, Haiqi Li, Alberto Martelli, Anna Nowak-Węgrzyn, Nikolas G. Papadopoulos, Ruby Pawankar, Maria Said, Mario Sánchez-Borges, Holger Schunemann, Raanan Shamir, Jonathan Spergel, Hania Szajewska, Luigi Terracciano, Yvan Vandenplas, Susan Waserman, Carina Venter, Amena Warner, and Gary W.K. Wong

Subjects
Breastfeeding, Infant, IgE-mediated cow's milk allergy, Non-IgE-mediated cow's milk allergy, Maternal nutrition, Immunologic diseases. Allergy, RC581-607
Abstract

Cow's milk allergy is rare in exclusively breastfed infants. To support the continuation of breastfeeding an infant after diagnosis with a cow's milk allergy, it is critical to examine the evidence for and against any form of cow's milk elimination diet for lactating mothers. In this narrative review, we highlight the lack of high-quality evidence, hence subsequent controversy, regarding whether the minuscule quantities of cow's milk proteins detectable in human milk cause infant cow's milk allergy symptoms. Current clinical practice recommendations advise a 2–4 week trial of maternal cow's milk dietary elimination for: a) IgE-mediated cow's milk allergy only if the infant is symptomatic on breastfeeding alone; b) non-IgE-mediated associated symptoms only if the history and examination strongly suggest cow's milk allergy; and c) infants with moderate to severe eczema/atopic dermatitis, unresponsive to topical steroids and sensitized to cow's milk protein. There should be a clear plan for home reintroduction of cow's milk into the maternal diet for a period of 1 week to determine that the cow's milk elimination is responsible for resolution of symptoms, and then subsequent reoccurrence of infant symptoms upon maternal cow's milk reintroduction. The evidence base to support the use of maternal cow's milk avoidance for the treatment of a breastfed infant with cow's milk allergy is of limited strength due to a lack of high-quality, adequately powered, randomised controlled trials. It is important to consider the consequences of maternal cow's milk avoidance on reducing immune enhancing factors in breast milk, as well as the potential nutritional and quality of life impacts on the mother. Referral to a dietitian is advised for dietary education, along with calcium and vitamin D supplementation according to local recommendations, and a maternal substitute milk should be advised. However, for most breastfed infants with cow's milk allergy maternal cow's milk dietary elimination will not be required, and active support of the mother to continue breastfeeding is essential.

Published
2023
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3. Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

Author

Sebastian A. Jensen, MD, Alessandro Fiocchi, MD, Ton Baars, PhD, Galateja Jordakieva, PhD, Anna Nowak-Wegrzyn, MD, PhD, Isabella Pali-Schöll, MD, PhD, Stefano Passanisi, MD, Christina L. Pranger, MSc, Franziska Roth-Walter, PhD, Kristiina Takkinen, PhD, Amal H. Assa'ad, MD, Carina Venter, PhD, RD, and Erika Jensen-Jarolim, MD

Subjects
Allergy, Cow's milk, Beta-lactoglobulin, Food allergy, Pasteurization, Immunologic diseases. Allergy, RC581-607
Abstract

Background: The immunopathogenesis of cow's milk protein allergy (CMPA) is based on different mechanisms related to immune recognition of protein epitopes, which are affected by industrial processing. Purpose: The purpose of this WAO DRACMA paper is to: (i) give a comprehensive overview of milk protein allergens, (ii) to review their immunogenicity and allergenicity in the context of industrial processing, and (iii) to review the milk-related immune mechanisms triggering IgE-mediated immediate type hypersensitivity reactions, mixed reactions and non-IgE mediated hypersensitivities. Results: The main cow’s milk allergens – α-lactalbumin, β-lactoglobulin, serum albumin, caseins, bovine serum albumins, and others – may determine allergic reactions through a range of mechanisms. All marketed milk and milk products have undergone industrial processing that involves heating, filtration, and defatting. Milk processing results in structural changes of immunomodulatory proteins, leads to a loss of lipophilic compounds in the matrix, and hence to a higher allergenicity of industrially processed milk products. Thereby, the tolerogenic capacity of raw farm milk, associated with the whey proteins α-lactalbumin and β-lactoglobulin and their lipophilic ligands, is lost. Conclusion: The spectrum of immunopathogenic mechanisms underlying cow's milk allergy (CMA) is wide. Unprocessed, fresh cow's milk, like human breast milk, contains various tolerogenic factors that are impaired by industrial processing. Further studies focusing on the immunological consequences of milk processing are warranted to understand on a molecular basis to what extent processing procedures make single milk compounds into allergens.

Published
2022
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4. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XIII – Oral immunotherapy for CMA – Systematic review

Author

Antonio Bognanni, MD, Derek K. Chu, MD, Ramon T. Firmino, DDS, PhD, Stefania Arasi, PhD, MSc, Siw Waffenschmidt, Arnav Agarwal, MD, Piotr Dziechciarz, MD, PhD, Andrea Horvath, MD, PhD, Rime Jebai, MSc, MPH, Hanako Mihara, MD, MPH, Yetiani Roldan, MD, Maria Said, RN, Raanan Shamir, MD, PhD, Martin Bozzola, MD, Sami Bahna, MD, DrPH, Alessandro Fiocchi, MD, Susan Waserman, MD, MSc, Holger J. Schünemann, MD, MSc, PhD, Jan L. Brożek, MD, PhD, Ignacio J. Ansotegui, MD, PhD, Stefania Arasi, MD, PhD, Amal H. Assa'ad, MD, Sami L. Bahna, MD, DrPH, Roberto Berni Canani, MD, PhD, Jan Brozek, MD, PhD, Derek K. Chu, MD, PhD, Lamia Dahdah, MD, Christophe Dupont, MD, PhD, Motohiro Ebisawa, MD, PhD, Ramon Targino Firmino, MD, Elena Galli, MD, PhD, Rose Kamenwa, MD, Gideon Lack, MBBCh, Haiqi Li, MD, Alberto Martelli, MD, Anna H. Nowak-Wegrzyn, MD, PhD, Nikolaos G. Papadopoulos, MD, PhD, Ruby Pawankar, MD, PhD, Mario Sánchez-Borges, MD, Jonathan M. Spergel, MD, PhD, Hania Szajewska, MD, Luigi Terracciano, MD, Yvan Vandenplas, MD, PhD, Carina Venter, PhD, RD, Amena Warner, RN, SN (PG Dip), and GaryW.K. Wong, MD

Subjects
Milk allergy, Oral immunotherapy, Systematic review, Meta-analysis, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's milk allergy. We previously published the systematic review of OIT for cow's milk allergy (CMA) in 2010 as part of the World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Objective: To systematically synthesize the currently available evidence about OIT for IgE-mediated CMA and to inform the updated 2022 WAO guidelines. Methods: We searched the electronic databases including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations. We included all studies irrespective of the language of the original publication. The last search was conducted in February 2021. We registered the protocol on Open Science Framework (10.17605/OSF.IO/AH2DT). Results: We identified 2147 unique records published between 2010 and 2021, including 13 randomized trials and 109 observational studies addressing cow's milk OIT. We found low-certainty evidence that OIT with unheated cow's milk, compared to elimination diet alone, increased the likelihood of being able to consume ≥150 ml of cow's milk in controlled settings (risk ratio (RR): 12.3, 95% CI: 5.9 to 26.0; risk difference (RD): 25 more per 100, 95% CI 11 to 56) as well as accidently ingest a small amount (≥5 ml) of cow's milk (RR: 8.7, 95% CI: 4.7 to 16.1; RD: 25 more per 100, 95% CI 12 to 50). However, 2–8 weeks after discontinuation of a successful OIT, tolerance of cow's milk persisted in only 36% (range: 20%–91%) of patients. OIT increased the frequency of anaphylaxis (rate ratio: 60.0, 95% CI 15 to 244; rate difference 5 more anaphylactic reactions per 1 person per year, 95% CI: 4 to 6; moderate evidence) and the frequency of epinephrine use (rate ratio: 35.2, 95% CI: 9 to 136.5; rate difference 268 more events per 100 person-years, 95% CI: 203 to 333; high certainty). OIT also increased the risk of gastrointestinal symptoms (RR 6.9, 95% CI 1.6–30.9; RD 28 more per 100, CI 3 to 100) and respiratory symptoms (RR 49.0, 95% CI 3.12–770.6; RD 77 more per 100, CI 62 to 92), compared with avoidance diet alone. Single-arm observational studies showed that on average 6.9% of OIT patients (95% CI: 3.8%–10%) developed eosinophilic esophagitis (very low certainty evidence). We found 1 trial and 2 small case series of OIT with baked milk. Conclusions: Moderate certainty evidence shows that OIT with unheated cow's milk in patients with IgE-mediated CMA is associated with an increased probability of being able to drink milk and, at the same time, an increased risk of serious adverse effects.

Published
2022
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5. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guideline update – XIV – Recommendations on CMA immunotherapy

Author

Jan L. Brozek, Ramon T. Firmino, Antonio Bognanni, Stefania Arasi, Ignacio Ansotegui, Amal H. Assa'ad, Sami L. Bahna, Roberto Berni Canani, Martin Bozzola, Derek K. Chu, Lamia Dahdah, Christophe Dupont, Piotr Dziechciarz, Motohiro Ebisawa, Elena Galli, Andrea Horvath, Rose Kamenwa, Gideon Lack, Haiqi Li, Alberto Martelli, Anna Nowak-Węgrzyn, Nikolaos G. Papadopoulos, Ruby Pawankar, Yetiani Roldan, Maria Said, Mario Sánchez-Borges, Raanan Shamir, Jonathan M. Spergel, Hania Szajewska, Luigi Terracciano, Yvan Vandenplas, Carina Venter, Siw Waffenschmidt, Susan Waserman, Amena Warner, Gary W.K. Wong, Alessandro Fiocchi, and Holger J. Schünemann

Subjects
Milk allergy, Immunotherapy, Practice guidelines, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Background: The prevalence of cow's milk allergy (CMA) is approximately 2–4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the benefits must be balanced with the adverse effects. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of oral and epicutaneous immunotherapy for the treatment of IgE-mediated CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to public comment. Results: After a careful review of the summarized evidence and thorough discussions the WAO guideline panel suggests: a) using oral immunotherapy with unheated cow's milk in those individuals with confirmed IgE-mediated CMA who value the ability to consume controlled quantities of milk more than avoiding the large adverse effects of therapy, b) not using oral immunotherapy with unheated cow's milk in those who value avoiding large adverse effects of therapy more than the ability to consume controlled quantities of milk, c) using omalizumab in those starting oral immunotherapy with unheated cow's milk, d) not using oral immunotherapy with baked cow's milk in those who do not tolerate both unheated and baked milk, and e) not using epicutaneous immunotherapy outside of a research setting. The recommendations are labeled “conditional” due to the low certainty about the health effects based on the available evidence. Conclusions: Clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable effects of oral immunotherapy for IgE-mediated CMA and integrate them with the patients' values and preferences before deciding on a treatment option. More robust research is needed to determine with greater certainty which interventions are likely to be the most beneficial with the least harms, and to develop safer, low-cost, and equitable treatments.

Published
2022
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6. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update – I – Plan and definitions

Author

Alessandro Fiocchi, MD, Antonio Bognanni, MD, Jan Brożek, MD, PhD, Motohiro Ebisawa, MD, PhD, Holger Schünemann, MD, Ignacio J. Ansotegui, MD, PhD, Stefania Arasi, MD, Amal H. Assa'ad, MD, Sami L. Bahna, MD, DrPH, Roberto Berni Canani, MD, PhD, Martin Bozzola, MD, Derek Chu, Lamia Dahdah, MD, Christophe Dupont, MD, PhD, Ramon Targino Firmino, Elena Galli, MD, PhD, Rose Kamenwa, MD, Gideon Lack, MD, Haiqi Li, MD, Alberto Martelli, MD, Anna Nowak-Węgrzyn, MD, Nikolas G. Papadopoulos, MD, PhD, Ruby Pawankar, MD, PhD, Maria Said, RN, Mario Sánchez-Borges, Raanan Shamir, PhD, Jonathan M. Spergel, MD, PhD, Hania Szajewska, MD, Luigi Terracciano, MD, Yvan Vandenplas, MD, PhD, Carina Venter, PhD, RD, Amena Warner, Susan Waserman, MD, MSc, and Gary W.K. Wong, MD

Subjects
Food allergy, Cow's milk allergy, Oral immunotherapy, GRADE, Immunologic diseases. Allergy, RC581-607
Abstract

Since the World Allergy Organization (WAO) Diagnosis and Rationale against Cow's Milk Allergy (DRACMA) Guidelines were published 10 years ago, new evidence has accumulated about the diagnosis, therapy, and specific immunotherapy for cow's milk allergy (CMA). For this reason, WAO has felt the need to update the guidelines.We introduce here this update. The new DRACMA guidelines aim to comprehensively address the guidance on diagnosis and therapy of both IgE non-IgE-mediated forms of cow's milk allergy in children and adults. They will be divided into 18 chapters, each of which will be dedicated to an aspect. The focus will be on the meta-analyzes and recommendations that will be expressed for the 3 most relevant clinical aspects: (a) the diagnostic identification of the condition; (b) the choice of the replacement formula in case of CMA in infancy when the mother is not able to breastfeed, and (c) the use of specific immunotherapy for cow's milk protein allergy.

Published
2022
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7. The effect of age, sex, race/ethnicity, health insurance, and food specific serum immunoglobulin E on outcomes of oral food challenges

Author

Andrew T. Dang, Pavan K. Chundi, Nadeem A. Mousa, Amanda I. Beyer, Somboon Chansakulporn, Carina Venter, Tesfaye B. Mersha, and Amal H. Assa'ad

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Background: Although oral food challenge (OFC) is an important clinical procedure for diagnosing food allergy, there is a paucity of literature on the outcome of the procedure and specifically the patients on whom the procedure is performed from the aspects of their age, sex, race/ethnicity, health insurance status, and serum specific IgE to the food tested. Objective: We aimed to review results of OFC and determine the impact of patient age, sex, race/ethnicity, insurance status, private or public, and food specific serum IgE on the outcome of OFC. Methods: A retrospective chart review was performed of patients undergoing OFCs at a children's hospital outpatient allergy clinic over a two-year period. The outcome of OFC was allergic or non-allergic based on determination and documentation by the treating physician. A logistic regression model was built to determine the association between the OFC outcomes, age, and symptoms at the time of OFC. A Chi-square analysis was performed to check for any significant relationship between the OFC outcome and age when stratified by insurance status. Results: Five hundred and eight children underwent 641 OFCs. Twenty nine percent of OFCs had an allergic outcome with the most commonly challenged foods being peanuts, eggs, and milk. Patient age and gender, when stratified by insurance status, did not have a significant effect on OFC outcomes. Serum IgE to peanuts and egg was significantly different between allergic OFC and non-allergic outcome. Vomiting and urticaria/angioedema correlated with an allergic OFC outcome. Conclusion: OFCs confirm the food allergy diagnosis in about one-third of patients tested, and they should continue to be used when possible for an accurate diagnosis. Age, sex, and insurance status do not have a significant association with the outcome of OFC and cannot be added as predictive factors.

Published
2020
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8. Associations of Food Allergy-Related Dietary Knowledge, Attitudes, and Behaviors Among Caregivers of Black and White Children With Food Allergy

Author

Eileen Vincent, Lucy A. Bilaver, Jamie L. Fierstein, Neil Thivalapill, Andrea A. Pappalardo, Amaziah Coleman, Adam Robinson, Hemant P. Sharma, Audrey Brewer, Amal H. Assa’ad, Jialing Jiang, Haley W. Hultquist, Ashwin J. Kulkarni, Johnathan Choi, Mahboobeh Mahdavinia, Jacqueline Pongracic, Mary C. Tobin, Christopher Warren, and Ruchi S. Gupta

Subjects
Health Knowledge, Attitudes, Practice, Cross-Sectional Studies, Nutrition and Dietetics, Adolescent, Caregivers, Humans, General Medicine, Child, Food Hypersensitivity, United States, Article, Diet, Food Science
Abstract

BACKGROUND: The increasing prevalence of pediatric food allergy (FA) in the US has disproportionately affected non-Hispanic Black youth. However, racial and other socioeconomic disparities in FA management among caregivers of children with FA remain unclear. OBJECTIVE: To determine associations between socioeconomic, clinical, and healthcare factors and FA-related knowledge, attitudes and behaviors (KAB) among caregivers of Black and White children with FA. DESIGN: Cross-sectional survey analysis from the Food Allergy Outcomes Related to White and African American Racial Differences (FORWARD) Study. PARTICIPANTS/SETTINGS: Longitudinal cohort of caregivers of 385 Black and White children with FA ages birth-12 years of age residing in Chicago, IL, Cincinnati, OH and Washington, D.C. from 2017- March 2021. MAIN OUTCOME MEASURES: There were three primary outcomes of interest: 1) FA knowledge assessed by scores from the Knowledge Survey, 2) FA-related attitudes assessed by newly developed survey and 3) food- related behaviors assessed by the FORWARD Diet and Purchasing Habit Surveys completed six months post-enrollment. ANALYSES: Multivariable linear and logistic regression. RESULTS: The overall response rate to the six months post-enrollment survey was 51.3% (385 of 751). White caregivers represented 69.4% of the participants. Black race was associated with a 1.5-point lower FA knowledge score (95% Confidence Interval (CI):: −2.2, −0.7) while earning a graduate degree or bachelor’s degree was associated with associated with a 1.7-point increase (95% CI: 0.8, 2.7) and 1.1-point increase (95% CI: 0.2, 2.0) in overall FA knowledge score, respectively, compared with caregivers earning less than a bachelor’s degree. Having multiple food allergies and having ever visited the ED for a food-related allergic reaction were also associated with higher levels of FA knowledge. Having visited the ED for FA was also associated with higher odds of two measures of FA attitudes reflecting parental anxiety. Greater FA knowledge scores were consistently associated with lower odds of several FA related food purchasing and eating behaviors assumed to have elevated risk. Eating food prepared at school was the only FA behavior associated with race. Compared to White children, Black children were 2.5 times more likely to eat school-prepared foods (95% CI: 1.2 – 5.6). CONCLUSIONS: Findings from this study identified socioeconomic, racial, and clinical factors associated with caregivers’ FA-related KAB, but further research is warranted to better understand these relationships.

Published
2022
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9. B cell repertoire in children with skin barrier dysfunction supports altered IgE maturation associated with allergic food sensitization

Author

Kirandeep Gill, Carolina Moore, Onyekachi Nwogu, John W. Kroner, Wan-Chi Chang, Mariana L. Stevens, Asel Baatyrbek kyzy, Jocelyn M. Biagini, Ashley L. Devonshire, Leah Kottyan, Justin T. Schwartz, Amal H. Assa’ad, Lisa J. Martin, Sandra Andorf, Gurjit K. Khurana Hershey, and Krishna M. Roskin

Subjects
Article
Abstract

The skin is a major immune organ and skin barrier dysfunction is a major risk factor for the development of the inappropriate immune response seen in allergic disease. Skin barrier disruption alters the landscape of antigens experienced by the immune system and the downstream impacts on the antibody repertoire remain poorly characterized, particularly for the IgE isotype responsible for allergic specificity and in early life, when allergic disease is developing. In this study, we sequenced antibody gene repertoires from a large and well-characterized cohort of children with atopic dermatitis and found that food sensitization was associated with lower mutation frequencies in the IgE compartment. This trend was abrogated in children living with pets during the first year of life. These results elucidate potential molecular mechanisms underlying the protective effects of pet ownership and non-antiseptic environs reported for allergic disease, and the hygiene hypothesis more broadly. We also observed increased IgE diversity and increased isotype-switching to the IgE isotype, suggesting that B cell development, particularly isotype-switching, is heavily altered in the those with food allergen sensitizations relative to those without food allergen sensitizations. Unlike for food antigens, aeroallergen sensitization exhibited no effect on IgE mutation or diversity. Consistent patterns of antibody rearrangement were associated with food allergen sensitization in subjects with atopic dermatitis. Thus, we propose the Immune Repertoire in Atopic Disease (IRAD) score, to quantify this repertoire shift and to aid clinically in patient diagnosis and risk stratification.One Sentence SummaryFood allergic sensitization is associated with altered B cell development in children with skin barrier dysfunction.

Published
2023

10. Oral food challenges

Author

Amal H. Assa’ad

Subjects
digestive, oral, and skin physiology
Abstract

Oral food challenge (OFC) is a procedure that is conducted most commonly by allergist/immunologists in their office or in food allergy centers to confirm a food allergy or to confirm tolerance to the food. The procedure as conducted in clinical practice is mostly open food challenge and, in research, a double-blind, placebo controlled food challenge. OFC has associated risks that can be minimized by having the challenges conducted by trained personnel who are prepared to treat allergic reactions and who have rescue medications available. However, OFCs have tremendous benefits to the patients and their families, including the potential to determine that a food is no longer an allergen and can be introduced into the diet. Even OFCs that result in clinical reactions have the benefit of confirming the food allergy and demonstrating the therapeutic effect of the rescue medications. The study of the outcomes of OFC has shed light on food allergy reactions and characteristics of the patients with food allergy as well as on the value of other diagnostic tests compared with OFC. OFCs have helped establish food allergy thresholds, confirm that subjects enrolled in research studies have the allergy, and demonstrate the response to the therapies tested in terms of ameliorating the allergic response or raising the reaction threshold. OFCs have also been used to promote the recent guidelines for the prevention of peanut allergy by identifying the infants at risk for peanut allergy but who are not allergic yet.

Published
2020
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11. Participant characteristics and safety outcomes of peanut oral immunotherapy in the RAMSES and ARC011 trials

Author

Christina Ciaccio, Alan B. Goldsobel, Aikaterini Anagnostou, Kirsten Beyer, Thomas B. Casale, Antoine Deschildre, Montserrat Fernández-Rivas, Jonathan O'B. Hourihane, Marta Krawiec, Jay Lieberman, Amy M. Scurlock, Brian P. Vickery, Alex Smith, Stephen A. Tilles, Daniel C. Adelman, Kari R. Brown, Amal H. Assa'ad, David I. Bernstein, J. Andrew Bird, Tara F. Carr, Warner W. Carr, Amarjit S. Cheema, Jonathan Corren, Amy Liebl Darter, Morna J. Dorsey, Stanley M. Fineman, David M. Fleischer, Stephen B. Fritz, Shaila U. Gogate, Alexander N. Greiner, Frank C. Hampel, Joshua S. Jacobs, Sanjeev Jain, Kirsi Jarvinen-Seppo, David K. Jeong, Douglas T. Johnston, Rita Kachru, Edwin H. Kim, Majed Koleilat, Bruce J. Lanser, Stephanie A. Leonard, Mary C. Maier, Michael E. Manning, Lyndon E. Mansfield, Jonathan Matz, Kari Nadeau, Jason A. Ohayon, Elena Perez, Daniel H. Petroni, Stephen J. Pollard, Punita Ponda, Jay M. Portnoy, Rima Rachid, Paul H. Ratner, Rachel Robison, Ned T. Rupp, Georgiana M. Sanders, Hemant P. Sharma, Ellen R. Sher, Lawrence D. Sher, Mandel Sher, Wayne G. Shreffler, Dareen D. Siri, Helen S. Skolnick, Weily Soong, Daniel F. Soteres, Jonathan M. Spergel, Allan Stillerman, Gordon L. Sussman, Jonathan Tam, Pooja Varshney, Susan Waserman, Hugh H. Windom, Robert Wood, and William H. Yang

Subjects
Pulmonary and Respiratory Medicine, Immunology, Immunology and Allergy
Published
2022
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12. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation

Author

Sebastian A. Jensen, Alessandro Fiocchi, Ton Baars, Galateja Jordakieva, Anna Nowak-Wegrzyn, Isabella Pali-Schöll, Stefano Passanisi, Christina L. Pranger, Franziska Roth-Walter, Kristiina Takkinen, Amal H. Assa'ad, Carina Venter, and Erika Jensen-Jarolim

Subjects
Pulmonary and Respiratory Medicine, Immunology, Immunology and Allergy
Published
2022
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13. Continuous and Daily Oral Immunotherapy for Peanut Allergy: Results from a 2-Year Open-Label Follow-On Study

Author

Brian P. Vickery, Andrea Vereda, Caroline Nilsson, George du Toit, Wayne G. Shreffler, A. Wesley Burks, Stacie M. Jones, Montserrat Fernández-Rivas, Katharina Blümchen, Jonathan O’B. Hourihane, Kirsten Beyer, Aikaterini Anagnostou, Amal H. Assa’ad, Moshe Ben-Shoshan, J. Andrew Bird, Tara F. Carr, Warner W. Carr, Thomas B. Casale, Hey Jin Chong, Christina E. Ciaccio, Morna J. Dorsey, Stanley M. Fineman, Stephen B. Fritz, Alexander N. Greiner, Leon S. Greos, Frank C. Hampel, Maria Dolores Ibáñez, David K. Jeong, Douglas T. Johnston, Rita Kachru, Edwin H. Kim, Bruce J. Lanser, Stephanie A. Leonard, Mary C. Maier, Lyndon E. Mansfield, Antonella Muraro, Jason A. Ohayon, Joanna N.G. Oude Elberink, Daniel H. Petroni, Jacqueline A. Pongracic, Jay M. Portnoy, Rima Rachid, Ned T. Rupp, Georgiana M. Sanders, Hemant P. Sharma, Vibha Sharma, Ellen R. Sher, Lawrence Sher, Sayantani B. Sindher, Dareen Siri, Jonathan M. Spergel, Aline B. Sprikkelman, Gordon L. Sussman, Marina Tsoumani, Pooja Varshney, Girish Vitalpur, Julie Wang, William H. Yang, José Manuel Zubeldia, Alex Smith, Robert Ryan, and Daniel C. Adelman

Subjects
medicine.medical_specialty, Adolescent, Arachis, Oral immunotherapy, medicine.medical_treatment, Peanut allergy, Administration, Oral, Placebo, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Humans, Immunology and Allergy, Peanut Hypersensitivity, 030212 general & internal medicine, Dosing, Child, Adverse effect, Desensitization (medicine), business.industry, Allergens, medicine.disease, 030228 respiratory system, Desensitization, Immunologic, Cohort, Open label, business
Abstract

Background The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. Objective ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. Methods Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non–daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. Results Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non–daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non–daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. Conclusions Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Published
2021
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14. CLINICAL, PATHOLOGICAL AND MOLECULAR CHARACTERIZATION OF FAMILIAL EOSINOPHILIC ESOPHAGITIS COMPARED WITH SPORADIC CASES

Author

Margaret H. Collins, Carine Blanchard, J. Pablo Abonia, Cassie Kirby, Rachel Akers, Ning Wang, Philip E. Putnam, Sean C. Jameson, Amal H. Assa'ad, Michael R. Konikoff, Keith F. Stringer, and Marc E. Rothenberg

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Gastroenterology, White People, Article, Pathogenesis, Atopy, Internal medicine, medicine, Esophagitis, Humans, Eosinophilic esophagitis, Child, High-power field, Asthma, Oligonucleotide Array Sequence Analysis, Family Health, Mucous Membrane, Hepatology, business.industry, Gene Expression Profiling, Infant, Eosinophil, Middle Aged, medicine.disease, Dysphagia, Eosinophils, medicine.anatomical_structure, Child, Preschool, Female, Esophagoscopy, medicine.symptom, business, Deglutition Disorders
Abstract

Eosinophilic esophagitis (EE) occurs in families.Record review confirmed patient kinship and provided clinical information. Slide review confirmed the diagnosis (threshold peak numberor = 24 eosinophils/high-power field).Fifty-nine members (41 males, 18 females) of 26 families were 3 months to 47 years of age (mean age, 10.3 y) at diagnosis. The only recorded race was Caucasian. In 4 families a parent of an affected male had EE. The most common complaint at diagnosis was dysphagia (68% of patients). Endoscopy showed esophageal mucosal furrows (93% of patients) and exudates (44%). Fifty-one percent had asthma. Skin prick tests to food and aeroallergens were positive in 76% and 71%, respectively. Familial EE characteristics (clinical, endoscopic, pathologic, and global esophageal transcript expression profile analysis) were similar to sporadic EE, except among patients with mucosal furrows: familial patients had lower peak eosinophil counts in the distal esophagus (P = .03) compared with sporadic patients. The basic characteristics of EE (eg, eosinophil levels, rate of atopy) did not vary with patient age. By using genome-wide microarray analysis, no significant differences (P.05, false-discovery rate) were observed between familial and sporadic EE. Among all patients, chest pain was more common in females (P = .02), and thickened mucosa was more common in males (P = .006).These data support a familial pattern of inheritance of EE and a pathogenesis shared with sporadic EE. EE should be considered in symptomatic family members of patients who have EE.

Published
2008

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