Implementing Food Oral Immunotherapy Into Clinical Practice: Quality and Safety Perspectives From a US Academic Center.

Oral immunotherapy (OIT) is an accessible procedure for practicing allergy/immunology providers, yet rigorous safety standards are limited in the clinical setting. By exploring the transition from research to clinical practice OIT, we review relevant safety considerations necessary for the clinical provider. We offer a perspective on clinical benefits and considerations at the individual, collaboration, and policy levels from the vantage of a large academic OIT program, and we propose several practical start-up checklists and clerical considerations for practicing providers. Awareness of the local population and front-end planning is necessary to improve the accessibility of this procedure in clinical practice among racial and socioeconomic minority populations. Sharing and merging OIT protocols, procedural methods, and electronic medical record order sets may increase harmonization among OIT-providing institutions and further our abilities to pool safety and outcomes data, ultimately enhancing the safety and efficacy of clinical OIT.

Indonesia-Based Study of the Clinical and Cost-Saving Benefits of Subcutaneous Allergen Immunotherapy for Children with Allergic Rhinitis in Private Practice.

BACKGROUND: Until now, the cost of allergy treatment in the insured public health care system and the non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. OBJECTIVE: To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in a non-insured self-financing private health care system. METHODS: A retrospective cohort study conducted from 2015 until 2020 that compared the clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1098 subjects. RESULTS: A decrease in sp-HDM-IgE level (kU/mL) from 20.5 + 8.75 kU/mL to 12.1 + 3.07 kU/mL was observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT, it costs IDR 21,753,062.7 per child, and for non-SCIT, it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT, it costs IDR 17,024,138.8, while with non-SCIT, it costs IDR 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT, it costs IDR 9,550,126.6, while with non-SCIT, it costs IDR 52,073,938.9. CONCLUSIONS: In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

Assessment of Lung Eosinophils In Situ Using Immunohistological Staining.

Eosinophils are rare white blood cells that are recruited from circulation to accumulate in the lung in mouse models of allergic respiratory inflammation. In hematoxylin-eosin (HE) stained lungs, eosinophils may be difficult to detect despite their bright eosin staining in the secondary granules. For this reason, antibody-mediated detection of eosinophils is preferable for specific and clearer identification of these cells. Moreover, eosinophils may degranulate, releasing their granule proteins into surrounding tissue, and remnants of cytolysed cells cannot be detected by HE staining. The methods here demonstrate the use of eosinophil-specific anti-mouse antibodies to detect eosinophil granule proteins in formalin-fixed cells both in situ in paraffin-embedded lungs, as well as in cytospin preparations from the lung. These antibody staining techniques enable either colorimetric or fluorescence imaging of eosinophils or their granule proteins with the potential for additional antibodies to be added for detection of multiple molecules.

Biologics for the Treatment of Food Allergies.

Food allergy is increasingly prevalent and poses a life-threatening risk to those afflicted. The health care costs associated with food allergies are also increasing. Current and emerging treatments for food allergies aim at protecting against reactions caused by accidental ingestion and increasing the food allergen reaction threshold, although this protection is often temporary. In the future, ideal biologic therapies would target key mediators of the type II immune pathway, essential in development of the atopic march to prevent development of food allergies. Biologics offering long-term protection against allergic reactions to food are needed, and several agents are already in development.

Biologic Agents for the Treatment of Anaphylaxis.

Several biologic therapies and new devices are emerging as potential preventive treatment of anaphylaxis. However, adrenaline (epinephrine) is still the first-line treatment of any type of anaphylaxis. Biologic drugs, such as omalizumab, although not US Food and Drug Administration approved for anaphylaxis, have been used as therapeutic adjuvants in the preventive treatment of anaphylaxis, but cost-effectiveness should be considered individually.

Biologics and Allergy Immunotherapy in the Treatment of Allergic Diseases.

Allergic diseases represent some of the most chronic and costly chronic conditions. Medical management may require long-term pharmacotherapy, which is often associated with poor adherence. Although medications provide symptomatic control, they do not modify the allergic disease. Patients may prefer disease-modifying treatments that provide lasting benefits after discontinuation. To date, allergy immunotherapy is the only proved disease modification therapy associated with lasting benefits after discontinuation. However, allergy immunotherapy safety and efficacy has only been established in allergic rhinitis, mild to moderate asthma, and some patients with atopic dermatitis.

Hymenoptera venom allergy among children in Italy: time for pediatricians to take action.

Hymenoptera venom allergy (HVA) is one of the most frequent causes of anaphylaxis following a bee, vespid or ant sting. Real-life data regarding the management of HVA in children are lacking. To address this unmet need, we carried out a survey defining the current management of HVA in children among pediatric allergists in Italy. Educational investments on the improvement of the management of pediatric patients with HVA are urgently needed, and our analysis represents a relevant instrument in targeting a roadmap with this aim. The time for pediatric allergists to take action has come, and a task force from the Rare Allergic Diseases Commission of the Italian Society of Pediatric Allergy and Immunology is working on the topic to improve pediatricians' knowledge and optimize the care of these patients.

Updated population minimal eliciting dose distributions for use in risk assessment of 14 priority food allergens.

Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset were published for 11 allergenic foods in 2014. Systematic data collection has continued (2011-2018) and the dataset now contains over 3400 data points. The current study provides new and updated EDp values for 14 allergenic foods and incorporates a newly developed Stacked Model Averaging statistical method for interval-censored data. ED01 and ED05 values, the doses at which 1%, and respectively 5%, of the respective allergic population would be predicted to experience any objective allergic reaction were determined. The 14 allergenic foods were cashew, celery, egg, fish, hazelnut, lupine, milk, mustard, peanut, sesame, shrimp (for crustacean shellfish), soy, walnut, and wheat. Updated ED01 estimates ranged between 0.03 mg for walnut protein and 26.2 mg for shrimp protein. ED05 estimates ranged between 0.4 mg for mustard protein and 280 mg for shrimp protein. The ED01 and ED05 values presented here are valuable in the risk assessment and subsequent risk management of allergenic foods.

Clinical aspects of sublingual immunotherapy tablets and drops.

BACKGROUND: Sublingual immunotherapy (SLIT) is administered via tablets (SLIT-T) or liquid drops (SLIT-D). In North America, currently 4 SLIT-T formulations are approved by the US Food and Drug Administration for allergy immunotherapy, and SLIT-D is an off-label use of subcutaneous immunotherapy (SCIT) extracts. OBJECTIVE: To compare and contrast aspects of SLIT-T and SLIT-D, including physical characteristics, mechanism of action, dosing, efficacy, safety, adherence, and cost. DATA SOURCES: PubMed literature review (no limits), product prescribing information, and manufacturer websites. STUDY SELECTIONS: Publications related to physical characteristics, mechanism of action, dosing, efficacy, safety, and adherence. RESULTS: Published evidence indicates that tablet and drop formulations differ in regard to physical characteristics, dosing, and strength of evidence for efficacy. Whether there are any differences in absorption and mechanism of action between the 2 formulations is currently unknown. Optimal dosing, efficacy, and safety have been established for SLIT-T. In contrast, in North America there is little support for efficacy of SLIT-D from randomized double-blind, placebo-controlled trials, and dose ranges have not been appropriately evaluated. SLIT-T treats a single allergen, whereas in the United States SLIT-D often contains multiple allergens to treat polysensitization. The safety profiles of SLIT-T and SLIT-D appear similar, and both formulations are considered safer than SCIT. CONCLUSION: Professional guidelines should make a clear distinction between SLIT-T and SLIT-D in their recommendations to minimize confusion with the umbrella term SLIT.

Clinical Efficacy of Allergen-Specific Immunotherapy from Patient and Physician Perspectives.

PURPOSE: Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic diseases, but a few allergic patients receive AIT. In this multicenter cross-sectional study, we aimed to explore patient and physician perspectives on AIT through a questionnaire survey. MATERIALS AND METHODS: Allergic patients who received subcutaneous immunotherapy for at least 1 year were asked to answer a questionnaire developed by an expert panel of allergen and immunotherapy workgroup in Korea. RESULTS: A total of 267 patients (adults, 60.3%) with allergic rhinitis (91.4%), asthma (42.7%), or atopic dermatitis (20.2%) from referred hospitals completed the survey. Among patients and physicians, respectively, the overall rates of satisfaction with AIT for allergic rhinitis were 86.4% and 83.3% (kappa agreement=0.234, p<0.001), and those for asthma were 85.3% and 72.9% (kappa agreement=0.373, p<0.001). Moreover, pediatric asthmatic patients reported a significantly higher satisfaction rate than adult asthmatic patients after AIT (p=0.040). Symptom severity (p<0.001, respectively) and drug use for allergic rhinitis and asthma decreased after AIT. However, there was no significant difference in satisfaction rates between children and adults in allergic rhinitis (p=0.736). Interestingly, 35.7% and 35% of allergic rhinitis and asthma patients, respectively, reported experiencing improvement in their symptoms within 6 months of starting AIT. CONCLUSION: In this study evaluating the perspectives of patients and physicians on AIT, the majority of patients were satisfied with the efficacy and safety of AIT, but not its cost. AIT should be recommended for AR and allergic patients.

2019 ARIA Care pathways for allergen immunotherapy.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.

Retrospective review of insurance coverage for patch testing.

BACKGROUND: There is a paucity of data on the burden of insurance limitations for patients undergoing patch testing. OBJECTIVE: To characterize the burden of insurance limitations and its impact on differences in management and execution of patch testing. METHODS: A retrospective chart review was performed on patients with a diagnosis of contact dermatitis (International Classification of Disease [ICD], Ninth Edition, code ICD 692) who received patch testing (Current Procedural Terminology code 95044) at the George Washington Medical Faculty Associates Dermatology Clinic between January 1, 2015 and June 30, 2017. Variables including allergen limitations were compared between government-sponsored insurance and private insurance providers (eg, Insurers A, B, C, and D). RESULTS: A total of 371 records were identified. Government-sponsored insurance patients encountered allergen limitations more frequently than private insurance patients (86.8% vs 14.2%, P < .0001). Insurer C and D patients were least likely to encounter allergen limitations (1.2% vs 0%, P < .0001) and were tested to the most allergens (mean = 146 vs 152, P < .0001). Insurer A patients had the least allergens tested among those privately insured. CONCLUSION: Considering modification of insurance policies to allow patch testing with a larger number of allergens without restrictions is needed, with the goal of improving quality of life of these patients while saving costs from chronic use of topical corticosteroids.

Adherence to Subcutaneous Allergen Immunotherapy in Southeast Turkey: A Real-Life Study.

BACKGROUND Subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR) and asthma is a very effective treatment, but adherence is still a serious problem. Studies addressing real-life adherence to SCIT are rare in the literature. The aim of this study was to evaluate the adherence to SCIT in AR and asthma. MATERIAL AND METHODS The medical records of patients prescribed SCIT for treatment of AR and/or asthma were evaluated. Patients who continued the SCIT treatment as prescribed were defined as adherent, patients who stopped the treatment before the recommended period were defined as nonpersistent, and those who never started the treatment were defined as primary poor adherence. Age, gender, residence, type of SCIT, comorbidities, occupation, income, and adverse reactions were evaluated between these groups. RESULTS Ninety-five patients prescribed SCIT for the treatment of AR and/or asthma formed our cohort (female/male: 51/44). The mean (SD) age and duration of SCIT were 32.2±10.0 (range, 17-63) years, 14.4±12.7 (1.0-58.5) months, respectively. Sixty-two (65.3%) patients were adherent, (28.4%) patients were nonpersistent, and 6 (6.3%) patients were primary poor adherent. Nineteen (21.4%) patients had local adverse reactions and one (1.1%) had anaphylaxis. There were no differences between groups for age, gender, residence, type of SCIT, comorbidities, income, or occupation. The most frequent reason of nonpersistence was the cost of treatment. CONCLUSIONS Our study found that adherence to SCIT is low in a real-life setting in southeast Turkey, similar to most previous adherence studies.

Assessment of Th1/Th2 Bias of STING Agonists Coated on Microneedles for Possible Use in Skin Allergen Immunotherapy.

Microneedle-based skin allergen-specific immunotherapy (AIT) can benefit from adjuvants that can stimulate a stronger Th1 response against the allergen. We evaluated two stimulator of interferon genes (STING) agonists, namely, cyclic diguanylate monophosphate (c-di-GMP) and cyclic diadenylate monophosphate (c-di-AMP), as skin adjuvants using coated microneedles (MNs). For comparison, the approved subcutaneous (SC) hypodermic injection containing alum was used. Ovalbumin (Ova) was used as a model allergen. Ova-specific IgG2a antibody in serum, which is a surrogate marker for Th1 type immune response was significantly higher when STING agonists were used with coated MNs as compared to SC injection of Ova+alum in mice. In contrast, IgG1 antibody, a surrogate marker for Th2 type immune response, was at comparable levels in the MN and SC groups. Restimulation of splenocytes with Ova produced higher levels of Th1 cytokines (IFN-γ and IL-2) in the STING agonists MN groups as compared to the SC group. In conclusion, delivery of STING agonists into the skin using coated MNs activated the Th1 pathway better than SC- and MN-based delivery of alum. Thus, STING agonists could fulfill the role of adjuvants for skin AIT and even for infectious disease vaccines, where stimulation of the Th1 pathway is of interest.

Allergenicity assessment of Buchanania lanzan protein extract in Balb/c mice.

Tree nuts are among "Big Eight" and have been reported globally for causing allergy. Buchanania lanzan (Bl) is one of the major tree nuts consumed by Indian population. However, very little is known about B. lanzan's induced allergic manifestation. Therefore, evaluation of it's allergenic potential was undertaken. Bl-crude protein extract sensitized BALB/c mice sera were used to identify the allergic proteins by it's IgE binding capability. The major IgE binding proteins found with molecular weight of 11, 20, 23, 25, 48, 54, and 65 kDa. Specific IgE, specific IgG1, MCPT-1, PGD2 and histamine were assessed in mice sera. Enormous amount of mast cell infiltration was noted in different organs. The levels of Th1/Th2 transcription factors GATA-3, SOCS3 and STAT-6 were found upregulated, whereas T-bet was downregulated. Furthermore, elevated Th1/Th2 cytokine responses were observed in mice sera. All together, these reactions developed systemic anaphylaxis upon Bl-CPE challenge in sensitized BALB/c mice. In order to confirm the evidences obtained from the studies carried out in BALB/c, the investigation was extended to human subjects as well. Control subjects and allergic patients were subjected to skin prick test (SPT). Later sera collected from those positive to SPT along with controls were used for IgE immunoblotting. The study evaluated the allergic manifestation associated with Bl, and identified it's proteins attributing Bl-mediated allergy. This work may help in managing tree nuts mediated allergies especially due to Buchanania lanzan sensitization.

Does evidence support the use of cat allergen immunotherapy?

PURPOSE OF REVIEW: Cat allergy can manifest as allergic rhinitis, conjunctivitis and/or asthma. With widespread cat ownership and exposure, cat allergy has emerged as a major cause of morbidity. Cat allergen immunotherapy is a potential disease modifying treatment for patients with cat allergy. We examine evidence on the effectiveness, cost-effectiveness and safety of cat allergen immunotherapy and consider the clinical contexts in which it should be prescribed. RECENT FINDINGS: The European Association of Allergy and Clinical Immunology systematic reviews on allergic rhinitis and asthma along with the accompanying guidelines on allergic rhinitis were used as primary sources of evidence. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are most common routes of administration for allergen immunotherapy (AIT). A limited number of high-quality studies related to cat dander have shown mixed results in improvements in ocular and nasal symptoms, asthma symptoms, peak expiratory flow rate and medication use scores with subcutaneous immunotherapy. Two studies examining cat dander and cat-related allergy response with sublingual immunotherapy have shown mixed results in terms of symptomatic response. One randomized trial examining intralymphatic immunotherapy has shown a positive symptom response and a favourable safety profile. Although studies have reported mixed results regarding safety of SCIT, adverse events have been reported more commonly with SCIT than SLIT. SUMMARY: There is a limited body of high-quality evidence on the effectiveness and safety of cat AIT and no high-quality data on its cost-effectiveness. The available evidence on effectiveness is mixed based on studying a limited array of immunological, physiological and patient-reported outcome measures. Based on this evidence and extrapolating on the wider evidence base in AIT, it is likely that some patients may benefit from this modality of treatment, particularly those with moderate-to-severe disease who are inadequately controlled on allergen avoidance measures and pharmacotherapy and those who are monosensitized to Felix Domesticus 1. Further evidence is, however, required from larger trials before more definitive advice can be offered.