Factors Affecting Adherence in Allergic Disorders and Strategies for Improvement.

Addressing patient adherence is a key element in ensuring positive health outcomes and improving health-related quality of life for patients with atopic and immunologic disorders. Understanding the complex etiologies of patient non-adherence and identifying real-world solutions is important for clinicians, patients, and systems to design and effect change. This review serves as a key resource for defining key issues related to patient non-adherence and outlines solutions, resources, knowledge gaps, and advocacy areas across five domains: healthcare access, financial considerations, socio-environmental factors, health literacy, and psychosocial factors. To allow for more easily digestible and usable content, we describe solutions based on three macro-levels of focus: patient, clinician, and system. This review and interactive toolkit serve as an educational resource and call to action to improve equitable distribution of resources, institutional policies, patient-centered care, and practice guidelines for improving health outcomes for all patients with atopic and immunologic disorders.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis.

BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Challenging assumptions about the demographics of eosinophilic gastrointestinal diseases: A systematic review.

Background: The demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis. Objectives: We aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics. Methods: We conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index, insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed by chi-square tests. Demographic reporting was compared to recent guidelines. Results: Among 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race = 4, ethnicity = 1, insurance = 1) or were not described (body mass index, urban/rural residence). A higher proportion of male subjects was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. "Sex" and "gender" were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines. Conclusion: Current data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic, or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs.

Volunteerism Addressing Environmental Disparities in Allergy (VAEDIA): The presidential initiative to combat environmental injustice in allergy and immunology-a Work Group Report of the AAAAI VAEDIA task force.

Many vulnerable people lose their health or lives each year as a result of unhealthy environmental conditions that perpetuate medical conditions within the scope of allergy and immunology specialists' expertise. While detrimental environmental factors impact all humans globally, the effect is disproportionately more profound in impoverished neighborhoods. Environmental injustice is the inequitable exposure of disadvantaged populations to environmental hazards. Professional medical organizations such as the American Academy of Allergy, Asthma & Immunology (AAAAI) are well positioned to engage and encourage community outreach volunteer programs to combat environmental justice. Here we discuss how environmental injustices and climate change impacts allergic diseases among vulnerable populations. We discuss pathways allergists/immunologists can use to contribute to addressing environmental determinants by providing volunteer clinical service, education, and advocacy. Furthermore, allergists/immunologists can play a role in building trust within these communities, partnering with other patient advocacy nonprofit stakeholders, and engaging with local, state, national, and international nongovernmental organizations, faith-based organizations, and governments. The AAAAI's Volunteerism Addressing Environmental Disparities in Allergy (VAEDIA) is the presidential task force aiming to promote volunteer initiatives by creating platforms for discussion and collaboration and by funding community-based projects to address environmental injustice.

Tolerance development in cow's milk-allergic children receiving amino acid-based formula with synbiotics: 36-Months follow-up of a randomized controlled trial (PRESTO Study).

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.

Development of a mini pig model of peanut allergy.

Introduction: The prevalence of peanut allergies is increasing, emphasizing the need for an animal model to enhance our understanding of peanut allergy pathogenesis and to advance diagnostic tools and therapeutic interventions. While mice are frequently used as model organisms, their allergic responses do not fully mirror those observed in humans, warranting the exploration of a higher animal model. The porcine gastrointestinal system closely resembles that of humans, and exhibits allergy symptoms akin to human responses, making pigs a promising model for peanut allergy research. Methods: In this study we compared two allergen sensitization protocols involving either topical allergen application after repeated tape stripping (TS) or intraperitoneal (IP) injections to induce peanut-specific allergy and anaphylaxis reactions in mini pigs. Mini pigs sensitized with a combination of peanut protein extract (PE) and cholera toxin (CT) through either the IP or the TS route. Results: Sensitized pigs via both methods developed systemic PE-specific IgG and IgE responses. Following peanut challenge via the IP route, both TS- and IP-sensitized pigs displayed allergy symptoms, including lethargy, skin rashes, vomiting, and a drop in body temperature. However, respiratory distress was observed exclusively in pigs sensitized through the TS route and not in those sensitized through the IP route. However, it is noteworthy that both groups of sensitized pigs maintained peanut hypersensitivity for up to two months post-sensitization, albeit with a reduction in the severity of allergy symptoms. Importantly, both groups exhibited sustained levels of PE-specific IgG, IgE, and elevated concentrations of mast cell protease in their blood following the IP challenges. Discussion: Overall, this study reports TS and IP as two different modes of sensitization leading to onset of peanut specific allergic reactions in mini pigs, but only the TS-sensitization led to systemic anaphylaxis (simultaneous presence of symptoms: breathing difficulty, intense skin rash, and impaired mobility). A distinctive feature of these sensitization protocols is the 100% success rate (N = 4 pigs per group) in sensitizing the subjects.

Heterozygous mutations in the C-terminal domain of COPA underlie a complex autoinflammatory syndrome.

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.

Health disparities in allergic diseases.

PURPOSE OF REVIEW: Healthcare disparities impact prevalence, diagnosis, and management of allergic disease. The purpose of this review is to highlight the most recent evidence of healthcare disparities in allergic conditions to provide healthcare providers with better understanding of the factors contributing to disparities and to provide potential management approaches to address them. This review comes at a time in medicine where it is well documented that disparities exist, but we seek to answer the Why , How and What to do next? RECENT FINDINGS: The literature highlights the socioeconomic factors at play including race/ ethnicity, neighborhood, insurance status and income. Management strategies have been implemented with the hopes of mitigating the disparate health outcomes including utilization of school-based health, distribution of educational tools and more inclusive research recruitment. SUMMARY: The studies included describe the associations between upstream structural and social factors with downstream outcomes and provide ideas that can be recreated at other institutions of how to address them. Focus on research and strategies to mitigate healthcare disparities and improve diverse research participant pools are necessary to improve patient outcomes in the future.

Addressing Health Equity in Food Allergy.

Social determinants of health can lead to poor health outcomes for food-allergic patients, including limited access to allergen-free foods and specialty care. Housing and transportation limitations can worsen social factors including food insecurity, poor early food introduction, increased reactivity to foods, lower tertiary/allergy care utilization, and increased emergency department utilization. A key component of addressing health equity involves valuing all people with sustained, focused efforts to address social determinants of health. In this clinical commentary, we discuss the current state of heath equity for food-allergic patients, highlighting the disparities in emergency care, food allergy prevention, and food insecurity. Solutions to improve health equity through clinical practice are proposed. Currently available funding opportunities through the National Institutes of Health for health equity initiatives are outlined. Gaps in health equity for food-allergic patients include the lack of documented successful implementation of effective solutions to food insecurity, poor early food introduction uptake, poor access to specialist care, and unequal distribution of educational resources. The availability of research funding and legislative policies supporting access to food and education bolster the impetus to move toward health equity for 20 million people in the United States with food allergy.

Reaching Communities Through Food Allergy Advocacy, Research, and Education: A Comprehensive Analysis.

This article explores the multifaceted approach of food allergy (FA) advocacy, research, and education to address the diverse challenges associated with FA, such as disparities in socioeconomic status, food security, quality of life, and the overall burden of the disease. Advocacy initiatives are instrumental in driving policy changes, raising public awareness, and directing substantial research funding, with a focus on reducing disparities. They have influenced allergen labeling regulations and improved access to epinephrine, emphasizing the importance of school-based management plans, especially in underserved communities. Research in FA informs medical practices and offers them hope for improved treatments. Recent breakthroughs in peanut allergy prevention and oral immunotherapy trials exemplify the potential for advancements while highlighting the need to address disparities in health care access. Education is a critical tool for prevention, raising awareness, and reducing the risk of allergic reactions. Efforts should be tailored to reach marginalized communities, particularly in schools where education on FA management is essential. Collaborating directly with communities is imperative to ensure inclusivity and address disparities. Barriers such as mistrust, language and cultural differences, and lack of diversity among researchers must be overcome to encourage diverse participation in research studies. This article concludes by emphasizing the significance of a comprehensive approach to FA research that prioritizes equity and inclusivity. The call to action highlights the need for global initiatives to reshape the landscape of FA care and address disparities in health care access and outcomes.

Quality of life is lower in food allergic adolescents compared to young children at a community educational symposium.

INTRODUCTION: Food allergies (FA) can detrimentally impact physical, emotional, and psychological quality of life (QoL) among pediatric patients. Given the changes from childhood into adolescence, the impact of FA on QoL likely evolves with age. The purpose of this study was to determine whether QoL differed between adolescents and children with FA who participated in a Food Allergy Symposium (FAS). METHODS: Patients with confirmed FA were recruited at an educational community symposium in September 2018 and September 2019. Patients and/or their parents were invited to complete the Food Allergy Quality of Life Questionnaires (FAQLQ). The Food Allergy Independent Measure (FAIM) reflects concerns about accidental food exposure and disease severity. Higher FAIM and FAQLQ scores reflect worse QoL. Summary scores were compared using the Wilcoxon rank sum test, Fisher's exact test, or the Chi-square test. RESULTS: Seventy-four surveys (82% children, 18% adolescents) were included. The FAQLQ total score was higher among adolescents than children (median 5.2 vs 4.2; p = 0.045), and the FAIM was lower in adolescents (median 2.2 vs 2.8; p = 0.037). More adolescents reported previous anaphylaxis than children (91.7% vs 51.8%; p = 0.011). The percentage reassured by having epinephrine was higher in adolescents (81.8% vs 45.8%; p = 0.046). No other QoL scores and survey responses were significantly different. DISCUSSION: In this study, adolescents were more concerned about their disease and more reassured by epinephrine carriage than younger children, which may reflect increased autonomy and responsibility. Community events are an important way to assess QoL and provide FA-related education to pediatric patients.

Efficacy and safety of peanut epicutaneous immunotherapy in patients with atopic comorbidities.

Background: Co-occurring atopic conditions are common in children with peanut allergy. As such, it is important to examine the safety and efficacy of epicutaneous immunotherapy with Viaskin Peanut 250 µg patch (VP250) in peanut-allergic children with these conditions. Objective: We sought to compare efficacy and safety of VP250 versus placebo in peanut-allergic children with/without ongoing atopic conditions at baseline, including asthma, atopic dermatitis/eczema, or concomitant food allergy. Methods: A subgroup analysis of peanut-allergic children aged 4 to 11 years enrolled in PEPITES (12 months) and REALISE (6 months) randomized, placebo-controlled, phase 3 trials was conducted. The efficacy outcome measure was the difference in prespecified responder rate between placebo and VP250 groups at month 12 based on eliciting dose of peanut protein using double-blind, placebo-controlled food challenge in PEPITES. Safety profiles were evaluated by baseline concomitant disease subgroup in all randomized subjects who received 1 or more dose of the study drug in PEPITES and REALISE pooled data. Results: Responder rates were significantly (P < .05, all comparisons) greater with VP250 compared with placebo treatment regardless of whether subjects had other atopic conditions. Safety and tolerability profiles were generally similar across subgroups, with no new safety concerns detected. A trend for both higher responder rates and rates of local reactions was observed in subjects with baseline atopic dermatitis versus those without. In subjects with concomitant food allergy at baseline, higher rates of treatment-emergent adverse events, but not study discontinuations or overall rates of anaphylaxis, were observed. Conclusions: The results support the safety and efficacy of VP250 for treating peanut-allergic children with or without concomitant atopic conditions.

Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma & Immunology Meeting.

The Consortium of Eosinophilic Gastrointestinal Diseases and The International Gastrointestinal Eosinophil Researchers organized a day-long symposium at the 2022 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured a review of recent discoveries in the basic biology and pathogenesis of eosinophilic gastrointestinal diseases (EGIDs) in addition to advances in our understanding of the clinical features of EGIDs. Diagnostic and management approaches were reviewed and debated, and clinical trials of emerging therapies were highlighted. Herein, we briefly summarize the breakthrough discoveries in EGIDs.

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.

Managing Atopic Dermatitis in Patients With Skin of Color.

Managing atopic dermatitis (AD) in patients with skin of color presents unique challenges for the clinician. There is increasing evidence that AD has higher prevalence, persistence, and severity among skin of color populations. This is likely to be partly related to differences in living conditions and exposure to irritants and allergens, among other factors. Assessment of AD severity in patients with darker skin can be challenging, in particular the assessment of erythema, leading to the potential for underscoring AD severity. Variations in disease have also been described, with the potential for a greater risk of inflammation-induced nodularity and hyper- or hypopigmentation. Management challenges include variable adherence to treatment, potential disparities in access to health care, and differences in the metabolism of cyclosporine. Optimal management of AD in patients with skin of color requires a tailored approach. Here, we review approaches to diagnosing AD, evaluating extent and severity with subjective and objective measures, considering treatment options for patients with skin of color, and highlighting areas for improvement in AD care for skin of color populations.

Esophageal Epithelium and Lamina Propria Are Unevenly Involved in Eosinophilic Esophagitis.

BACKGROUND & AIMS: The nature of the involvement of esophageal tissue in eosinophilic esophagitis (EoE) is unclear. We estimated the intrabiopsy site agreements of the EoE Histologic Scoring System (EoEHSS) scores for the grade (degree) and stage (extent) of involvement of the esophageal epithelial and lamina propria and examined if the EoE activity status influenced the intrabiopsy site agreement. METHODS: Demographic, clinical, and EoEHSS scores collected as part of the prospective Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages study were analyzed. A weighted Cohen's kappa agreement coefficient (k) was used to calculate the pairwise agreements for proximal:distal, proximal:middle, and middle:distal esophageal biopsy sites, separately for grade and stage scores, for each of the 8 components of EoEHSS. A k > 0.75 was considered uniform involvement. Inactive EoE was defined as fewer than 15 eosinophils per high-powered field. RESULTS: EoEHSS scores from 1263 esophageal biopsy specimens were analyzed. The k for the stage of involvement of the dilated intercellular spaces across all 3 sites in inactive EoE was consistently greater than 0.75 (range, 0.87-0.99). The k for lamina propria fibrosis was greater than 0.75 across some of the biopsy sites but not across all 3. Otherwise, the k for all other features, for both grade and stage, irrespective of the disease activity status, was 0.75 or less (range, 0.00-0.74). CONCLUSIONS: Except for the extent of involvement of dilated intercellular spaces in inactive EoE, the remaining epithelial features and lamina propria are involved unevenly across biopsy sites in EoE, irrespective of the disease activity status. This study enhances our understanding of the effects of EoE on esophageal tissue pathology.

Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.

BACKGROUND: Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 µg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response. METHODS: Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge. RESULTS: Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p < 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg). CONCLUSIONS: Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.