Oral Food Immunotherapy in Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is one of the main risk factors for infants in the development of food allergy. Oral immunotherapy therapy (OIT) in early childhood has been demonstrated to be highly effective and safe in preschoolers with and without AD, especially in young infants. Delays in initiation of OIT in infants and children due to uncontrolled AD risks expansion of the number of foods children develop allergy to via unnecessary avoidance of multiple foods. Parents and caregivers may attribute eczema flares to OIT doses, which physicians usually ascribe to non-food triggers such as weather changes, psychological stress, and infection. There is a lack of published literature confirming OIT as a trigger of AD flares, and the degree to which OIT may be associated with AD flares needs to be further studied. We describe eight case scenarios with varying degrees of AD flare before and during OIT. We propose management algorithms for children with pre-existing concurrent AD and food allergy who are being considered for starting OIT, and children with AD flares during OIT. Optimizing AD control strategies and providing adequate AD care education prior to starting OIT can reduce confusion for both parents and allergists if rashes arise during OIT, thus improving adherence to OIT.

Decisions with patients, not for patients: Shared decision-making in allergy and immunology.

Shared Decision-Making (SDM) is an increasingly implemented patient-centred approach to navigating patient preferences regarding diagnostic and treatment options and supported decision-making. This therapeutic approach prioritizes the patient's perspectives, considering current medical evidence to provide a balanced approach to clinical scenarios. In light of numerous recent guideline recommendations that are conditional in nature, and are clinical scenarios defined by preference-sensitive care options, there is a tremendous opportunity for SDM and validated decision aids. Despite the expansion of the literature on SDM, formal acceptance among clinicians remains inconsistent. Surprisingly, a significant disparity exists between clinicians' self-reported adherence to SDM principles and patients' perceptions of its implementation during clinical encounters. This discrepancy underscores a fundamental issue in the delivery of healthcare, where clinicians may overestimate their integration of SDM, while patients' experiences suggest otherwise. This review critically examines the factors contributing to this inconsistency, including barriers within the healthcare system, clinician attitudes and behaviours, and patient expectations and preferences. By elucidating these factors in the fields of food allergy, asthma, eosinophilic esophagitis, and other allergic diseases, this review aims to provide insights into bridging the gap between clinician perception and patient experience in SDM. Addressing this discordance is crucial for advancing patient-centred care and ensuring that SDM is not merely a theoretical concept but a tangible reality in the practice of Allergy and Immunology.

The Safety and Efficacy of Baked Egg and Milk Dietary Advancement Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: Cow's milk and egg allergy affect approximately 1.9% and 0.9% of children, respectively. Dietary advancement therapies (DAT), including milk (ML) and egg (EL) ladders, baked milk (BM-OIT) and baked egg (BE-OIT) oral immunotherapy are potential therapeutic options for these patients. OBJECTIVE: To perform systematic review and meta-analysis of the safety and efficacy of DAT in children with IgE-mediated milk or egg allergy. METHODS: A systematic literature review was conducted, exploring 22 potential outcomes, with meta-analysis performed where >3 studies reported data. The GRADE approach was used to determine the certainty of evidence for each outcome, and the Johanna Briggs Institute tools for determining risk of bias. RESULTS: Twenty-nine studies met inclusion criteria among 9946 titles screened. Tolerance occurred in 69% of EL, 58% of ML, 49% of BE-OIT and 29% of BM-OIT patients. All-severity allergic reactions occurred in 21% of EL, 25% of ML, 20% of BE-OIT and 61% of BM-OIT patients, with epinephrine use in 3% of EL, 2% of ML, and 9% of BM-OIT patients. At-home reactions occurred in 19% of BE-OIT and 10% of BM-OIT patients. Discontinuation occurred in 14% of EL, 17% of ML, 17% of BE-OIT and 20% of BM-OIT patients. Mean time to BE egg and BE-OIT tolerance was 13.25 months (4 studies) and 19.1 months (3 studies). Certainty of evidence was very low, and risk of bias high. Study heterogeneity was high, attributable to multiple factors. CONCLUSIONS: There is very low certainty of evidence supporting DAT safety and efficacy. We cannot conclude DAT accelerates tolerance development.

Incidence of Surgically Managed Post-Tonsillectomy Hemorrhage Associated With NSAID Prescribing for Postoperative Pain Management.

INTRODUCTION: Tonsillectomy ranks high among the most common pediatric surgical procedures in the United States. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as ibuprofen, are routinely prescribed to manage post-tonsillectomy pain, but may carry the risk of hemorrhage. MATERIALS AND METHODS: This retrospective, longitudinal, secondary-data analysis study compared the incidence of surgically managed post-tonsillectomy hemorrhage (sPTH) in pediatric patients prescribed ibuprofen at Brooke Army Medical Center (BAMC) after tonsillectomy compared to a similar cohort of pediatric patients at the Children's Hospital of Philadelphia (CHOP) not prescribed ibuprofen. Additional regression analysis examined predictors of sPTH at BAMC. RESULTS: The odds of sPTH was lower in patients who were prescribed ibuprofen at BAMC, relative to patients who were not at CHOP (OR 0.57, 95% CI, 0.37, 0.87; P < 0.01). In a generalized linear model evaluating BAMC patient data, there was a lack of a relationship between reason for tonsillectomy (tonsillitis versus tonsillar obstruction), primary procedure (tonsillectomy-only versus tonsillectomy with adenoidectomy), and presence of a co-occurring procedure. CONCLUSIONS: Post-tonsillectomy ibuprofen prescribing practices were not associated with an elevated risk of sPTH, relative to patients at CHOP not exposed to ibuprofen.

Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent.

BACKGROUND: Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process. OBJECTIVE: We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form. METHODS: We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed. RESULTS: The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form. CONCLUSION: We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

Core Outcome Set for IgE-mediated food allergy clinical trials and observational studies of interventions: International Delphi consensus study 'COMFA'.

BACKGROUND: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions. METHODS: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS. RESULTS: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes. CONCLUSION: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes.

Age-Related Food Aversion and Anxiety Represent Primary Patient Barriers to Food Oral Immunotherapy.

BACKGROUND: Although oral immunotherapy (OIT) for food allergy is a reasonable treatment option, barriers to this procedure's implementation have not been extensively evaluated from a patient perspective. OBJECTIVE: We evaluated the barriers patients face during OIT administration, including anxiety and taste aversion, and the role of health care professionals, especially dietitians. METHODS: A survey in Canada and the United States involved families currently enrolled in food OIT programs. RESULTS: Of responses from 379 participants, fear of reaction was the most common barrier to OIT initiation, with 45.6% reporting it being a "very significant" barrier with other fears reported. However, taste aversion represented the prominent obstacle to continuation. Taste aversion was associated with a slower buildup (P = .02) and a reduction in dose (P = .002). Taste aversion was a strongly age-dependent barrier for initiation (P < .001) and continuation (P < .002), with older children over 6 years of age reporting it as a very significant barrier (P < .001). Boredom was reported as a concern for specific allergens such as peanut, egg, sesame, and hazelnuts (P < .05), emphasizing the need for diverse food options. Notably, 59.9% of respondents mixed OIT foods with sweet items. Despite these dietary concerns, dietitians were underutilized, with only 9.5% of respondents having seen a dietitian and the majority finding dietitian support helpful with greater certainty about the exact dose (P < .001). CONCLUSIONS: Taste aversion and anxiety represent primary patient-related barriers to OIT. Taste aversion was highly age dependent, with older patients being more affected. Dietitians and psychology support were underutilized, representing a critical target to improve adherence and OIT success.

SQ sublingual immunotherapy tablets for children with allergic rhinitis: A review of phase three trials.

AIM: To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebo-controlled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. METHODS: PubMed searches were conducted and unpublished data were included if necessary. RESULTS: Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials. CONCLUSION: Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease-modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course.

Flex-IT! Applying "Platform Trials" Methodology to Immunotherapy for Food Allergy in Research and Clinical Practice.

There is an increasing trend in the management of food allergy toward active treatment using allergen immunotherapy (AIT). Although AIT is efficacious, treatment-related adverse events are common, particularly with oral immunotherapy in those with high levels of allergen-specific IgE sensitization. In clinical practice, these adverse events inevitably create challenges: clinicians and patients routinely face decisions whether to alter the dose itself, the frequency of dosing, and the pace of escalation, or indeed discontinue AIT altogether. Flexibility is therefore needed to adapt treatment, particularly in clinical practice, so that participants are "treated-to-target." For example, this may entail a significant change in the dosing protocol or even switching from one route of administration to another in response to frequent adverse events. We refer to this approach as flexible immunotherapy. However, there is little evidence to inform clinicians as to what changes to treatment are most likely to result in treatment success. Classical clinical trials rely, by necessity, on relatively rigid updosing protocols. To provide an evidence base to optimize AIT, the food allergy community should adopt adaptive platform trials, where a "master protocol" facilitates more efficient evaluation, including longer-term outcomes of multiple interventions. Within a single clinical trial, participants are able to switch between different treatment arms; interventions can be added or dropped without compromising the integrity of the trial. Developing platform trials for food AIT may initially be costly, but they represent a significant opportunity to grow the evidence base (with respect to both treatment outcomes and biomarker discovery) at scale. In addition, they could help understand longitudinal disease trajectories that are difficult to study in clinical trials for food allergy due to the time needed to demonstrate changes in efficacy. Finally, their adoption would achieve greater collaboration and consistency in approaches to proactive management of food allergy in routine clinical practice. As a community, we need to actively pursue this with funders and established research collaborations to deliver the very best outcomes for our patients and their families.

Hypoglossal Nerve Stimulator in the Active Duty Population: Military Readiness and Satisfaction.

INTRODUCTION: Because inadequate sleep impairs mission performance, the U.S. Army regards sleep as a core pillar of soldier readiness. There is an increasing incidence of obstructive sleep apnea (OSA) among active duty (AD) service members, which is a disqualifying condition for initial enlistment. Moreover, a new diagnosis of OSA in the AD population often prompts a medical evaluation board, and if symptomatic OSA proves refractory to treatment, this may result in medical retirement. Hypoglossal nerve stimulator implantation (HNSI) is a newer implantable treatment option, which requires minimal ancillary equipment to function and may provide a useful treatment modality to support AD service members while maintaining readiness in appropriate candidates. Because of a perception among AD service members that HNSI results in mandatory medical discharge, we aimed to evaluate the impact of HNSI on military career progression, maintenance of deployment readiness, and patient satisfaction. METHODS: The Department of Research Programs at the Walter Reed National Military Medical Center provided institutional review board approval for this project. This is a retrospective, observational study and telephonic survey of AD HNSI recipients. Military service information, demographics, surgical data, and postoperative sleep study results were collected from each patient.Additional survey questions assessed each service member's experience with the device. RESULTS: Fifteen AD service members who underwent HNSI between 2016 and 2021 were identified. Thirteen subjects completed the survey. The mean age was 44.8 years (range 33-61), and all were men. Six subjects (46%) were officers. All subjects maintained AD status following HNSI yielding 14.5 person-years of continued AD service with the implant. One subject underwent formal assessment for medical retention. One subject transferred from a combat role to a support role. Six subjects have since voluntarily separated from AD service following HNSI. These subjects spent an average of 360 (37-1,039) days on AD service. Seven subjects currently remain on AD and have served for an average of 441 (243-882) days. Two subjects deployed following HNSI. Two subjects felt that HSNI negatively affected their career. Ten subjects would recommend HSNI to other AD personnel. Following HNSI, of the eight subjects with postoperative sleep study data, five achieved surgical success defined as >50% reduction of apnea-hypopnea index and absolute apnea-hypopnea index value of <20. CONCLUSIONS: Hypoglossal nerve stimulator implantation for AD service members offers an effective treatment modality for OSA, which generally allows for the ability to maintain AD status, however: The impact on deployment readiness should be seriously considered and tailored to each service member based on their unique duties before implantation. Seventy-seven percent of HNSI patients would recommend it to other AD service members suffering from OSA.

Epicutaneous immunotherapy with Viaskin™ Peanut in toddlers: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article published in The New England Journal of Medicine about the EPITOPE clinical study, which tested a skin patch called ViaskinTM Peanut 250 µg (micrograms) as a treatment option for peanut allergy in children aged 1 through 3 years. The patch is a form of epicutaneous immunotherapy (EPIT), which is a new approach to allergen immunotherapy that delivers a small amount of peanut protein to the immune system through the skin. Viaskin Peanut is an investigational therapy, meaning it has not yet been approved by the United States Food and Drug Administration (FDA), that has been studied before in young children aged 4 through 11 years. In those studies, the children who received the patch were desensitized and were less likely to experience anaphylaxis when they ate peanut at the end of the study. The EPITOPE study included children aged 1 through 3 years with peanut allergy and looked at how well the peanut patch worked and how safe it was compared to a patch with no medicine (placebo, no medicine) after 12 months. WHAT WERE THE KEY TAKEAWAYS?: The study showed that the peanut patch was better in desensitizing children to peanuts than the placebo patch. Most of the children in the study who received the peanut patch for 12 months (the treatment group) were able to eat and tolerate more peanut at the end of the study than those who received only the placebo patch (the control group). This demonstrates that the children in the treatment group were less likely to have an allergic reaction if they ate peanut by accident at the end of the study. The children in the treatment group also had less severe symptoms when they were given peanut during the oral food challenges at the end of the study. Most children in both groups experienced side effects. Mild to moderate local skin reactions where the patch was applied were most common. These side effects happened less often and were less serious over the 12-month treatment period. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Overall, these results show the peanut patch may be a possible treatment option to help desensitize young children with peanut allergy to peanut.

Updates in Food Allergy Prevention in Children.

Although significant evidence exists that feeding early has a role in the prevention of food allergy, this intervention in isolation may not be sufficient. Recent evidence highlights that early introduction of peanut specifically has had no significant impact on the populational prevalence of peanut allergy. Other factors that may contribute to food allergy prevention include regularity of ingestion once an allergen is introduced and consideration to the form in which the allergen is introduced (such as baked versus cooked egg). There are also many practicalities to early feeding and some discrepant viewpoints on these practicalities, which has led to poor implementation of early feeding strategies. In general, preemptive screening before food introduction is not recommended by most international allergy societies. Although there is little guidance to inform early introduction of allergens other than milk, egg, and peanut, the mechanism of sensitization is thought to be similar and there is no harm to early introduction. In terms of frequency and duration of feeding, there is little evidence to inform any concrete recommendations.

The future of food allergy: Challenging existing paradigms of clinical practice.

The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into clinical practice with the goal to reduce the need for food challenges and assist physicians in the-often complex-diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.

Varying Approaches to Management of IgE-Mediated Food Allergy in Children Around the World.

Food allergy is a chronic disease that affects individuals of all ages and is a significant public health problem globally. This narrative overview examines clinical management strategies for IgE-mediated food allergy in children around the world to understand variations in practice. Information was drawn from clinical practice guidelines, recent research, the websites of professional and governmental bodies with expertise in food allergy, and clinical experts from a broad cross-section of geographical regions. The structure and delivery of clinical services, allergen avoidance and food labeling, and resources to support the management of allergic reactions in the community are discussed in detail. The adoption of emerging food immunotherapies is also explored. Wide variations in clinical management of food allergy were apparent across the different countries. Common themes were continuing issues with access to specialist care and recognition of the need to balance risk reduction with dietary and social restrictions to avoid unnecessary detrimental impacts on the quality of life of food allergy sufferers. Findings highlight the need for standardized presentation of practice and priorities, and may assist clinicians and researchers when engaging with government and funding agencies to address gaps.

Minimization of ragweed allergy immunotherapy costs through use of the sublingual immunotherapy tablet in Canadian children with allergic rhinoconjunctivitis.

BACKGROUND: Allergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC. METHODS: A cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes. RESULTS: Over the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios. CONCLUSIONS: In this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA.

Are There Hidden Dangers Associated With Milk and Egg Dietary Advancement Therapy?

Dietary advancement therapies (DATs) constitute a continuum spanning extensively heated item ingestion, progressive milk or egg ladders, and oral immunotherapy (OIT). These represent an evolution in food allergy management from strict avoidance to an active therapy that may modulate the immune system to develop tolerance to particular forms of the allergen. Many egg or milk individuals are tolerant to baked egg or milk at baseline, and regular consumption (at home ingestion) of baked milk or egg is a safe process with potential quality of life and immunologic benefit. Milk and egg ladders, developed for non-IgE mediated allergy, are increasingly being adapted to IgE-mediated allergy as a potentially safe at-home option for gradual dietary advancement. However, data are limited regarding how safe and effective these approaches are or what patient is best suited for which DAT. It is also unclear whether extensively heated allergen consumption and ladders are susceptible to the same patient-specific factors that affect day-to-day tolerance and safety in OIT. Several recent events involving near-fatal or fatal reactions to milk or egg products (all among patients with asthma) have highlighted that DATs are not risk-free, and that physician guidance in these therapies is essential. Such guidance may include obtaining informed consent before starting any DAT and instituting the same safe dosing rules for OIT across any form of DAT. This rostrum discusses practical concerns about the safety of DAT, and considerations regarding how clinicians can maximize patient protection while defining the safety and efficacy of real-world implementation of these concepts.