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J Food Allergy
J Food Allergy
Journal of Food Allergy
2689-0267
2689-0275
OceanSide Publications, Inc. Providence, RIUSA

JFA963-24
10.2500/jfa.2024.6.240060
Abstract
Abstracts presented at the Eastern Food Allergy & Comorbidity Conference, January 4–7, 2024, Palm Beach, FL
1 7 2024
7 2024
6 1 5254
Copyright © 2024, The Author(s). Published by OceanSide Publications, Inc., U.S.A.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This article is distributed under the terms of the Creative Commons Attribution License-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits reproduction and redistribution in any medium or format according to the license terms, provided the work is not used for commercial purposes and provided the original authors and source are properly credited and a link is provided to the Creative Commons license. For commercial permissions, visit https://oceansidepubl.com/permission-to-use-content/
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pmc Pharmacokinetic and Pharmacodynamic Effects of 13.2 mg Intranasal Epinephrine Treatment in Congestion

Karen Rance, DNP, Allen Hunt, M.D., Mike Di Spirito, MSc, Mary Lor, BSc, GrDip, David A. Dworaczyk, Ph.D.

Introduction: Nasal congestion could affect the absorption of an epinephrine nasal spray (ENS). The objective of this study was to compare the pharmacokinetics (PK) of 13.2 mg ENS with and without nasal congestion to intramuscular (IM) treatments.

Methods: This Phase I, open-label, 4-period study enrolled 51 healthy adults with seasonal allergies into 2 cohorts that received 13.2 mg ENS (NDS1C) administered as 2 consecutive sprays in either opposite nostrils or the same nostril. Both cohorts received 13.2 mg ENS with and without nasal allergen challenge (NAC), 0.3 mg IM epinephrine autoinjector, and 0.5 mg IM manual syringe (MS).

Results: Administration of 13.2 mg ENS under NAC resulted in higher exposures and more rapid time to reach maximum concentration (Tmax) versus 13.2 mg ENS without NAC and IM treatments. In Cohort 1, maximum observed epinephrine concentration (Cmax, pg/mL) with 13.2 mg ENS with NAC, IM autoinjector, IM MS, or 13.2 mg ENS without NAC was 458.0, 279.0, 364.2, and 270.1, respectively, and in Cohort 2 was 436.3, 228.2, 322.3, and 250.8, respectively. In Cohort 1, Tmax for the respective groups was 15, 21, 45, and 25 minutes and in Cohort 2 was 18, 20, 45, and 20 minutes. The geometric mean ratio (90% CI) for Cmax with 13.2 mg ENS with NAC versus without NAC in Cohort 1 was 170% (123%-234%) and in Cohort 2 was 174% (115%-263%). Postdose heart rate and blood pressure remained stable and relatively similar to predose values regardless of plasma epinephrine concentration. Mild nausea and headache were the most common adverse events with 13.2 mg ENS.

Conclusions: 13.2 mg ENS with congestion demonstrated enhanced absorption versus IM treatments and 13.2 mg ENS without congestion and appeared well tolerated. Pharmacodynamic effects were minimal with no PK correlation.

Funded by Bryn Pharma

13.2 mg Intranasal Epinephrine Spray Demonstrates Comparable PK/PK and Safety to 0.3 mg Epinephrine Autoinjector

Karen Rance, DNP, Allen Hunt, M.D., David A. Dworaczyk, Ph.D.

Introduction: NDS1C 13.2 mg is a self-administered, intranasal dosage form of epinephrine intended for the treatment of type 1 allergic reactions, including anaphylaxis. The present study compares the PK/PD and safety profiles of intranasal epinephrine with epinephrine administered intramuscularly.

Methods: An open-label, 3-period, crossover study was conducted in 100 healthy adult volunteers to assess the relative bioavailability of a single intranasal dose of epinephrine, 13.2 mg, consisting of 2 consecutive 6.6 mg sprays (opposite and single nostril dosing) compared to an intramuscular 0.3 mg autoinjector and 0.5 mg manual syringe. Unadjusted and baseline-adjusted epinephrine concentrations of 50, 100, and 200 pg/mL at 10, 20, 30, and 60-minutes postdose were evaluated.

Results: PK parameters for the 13.2 mg intranasal dose exceeded those of the 0.3 mg intramuscular autoinjector with a rapid and higher Cmax, (intranasal 429.4, autoinjector 328.6), and greater systemic exposure; AUC0–360 intranasal = 39,060 g*min/mL and autoinjector = 17,440 g*min/mL. Similar results were observed compared to the 0.5 mg manual syringe. PK parameters for opposite and same nostril dosing were higher than both intramuscular doses, except Tmax, which was bracketed between the two intramuscular doses; intranasal opposite and same nostril = 20 minutes, autoinjector = 14.9 minutes, manual syringe = 45 minutes. Similar effects on blood pressure and heart rate were observed for intranasal and autoinjector administration. Intranasal epinephrine was safe and well-tolerated, with no serious or unexpected AEs reported.

Conclusions: NDS1C addresses the unmet need for a needle-free, convenient, and effective dose delivery system for self-administration of epinephrine. These data support NDS1C as an alternative to 0.3 mg intramuscular autoinjector for acute anaphylaxis management.

Funded by Bryn Pharma

Impact of food exposure on the pharmacokinetics of epinephrine sublingual film

John Oppenheimer M.D., David Golden M.D., Carlos A. Camargo, Jr., M.D., DrPH, Matthew Greenhawt, M.D., MBA, MSc, David Fleisher M.D., David Bernstein M.D., Gary Slatko M.D.

Introduction: AQST-109 is the first and only sublingual film using a novel prodrug of epinephrine being developed for the same target indication as epinephrine injection in the emergency treatment of Type 1 allergic reactions. A study was conducted to test if consumption of food immediately prior to administration of DESF affects the pharmacokinetic profile of epinephrine.

Methods: Twenty-four healthy adult volunteers each received DESF 12 mg in the fasted state and immediately after eating a peanut butter sandwich. Following DESF administration, blood samples were obtained and pharmacokinetic and pharmacodynamic parameters were compared.

Results: After food, median Tmax was unchanged at 12 minutes. The mean Cmax was slightly lower after food consumption compared to no food, 350 vs 286 pg/ml, respectively. Early exposure, characterized by AUC0-10 and AUC0-30 were unchanged by the presence of food residue compared to no food, 15.0 hr*pg/ml vs 12.8 hours*pg/ml and 73.2 hours*pg/ml vs 79.1 hour*pg/ml respectively. Pharmacodynamic responses did not differ between the two arms.

Conclusion: These results suggest that the presence of food residue from a sticky substance such as peanut butter, has no relevant impact on the pharmacokinetics or pharmacodynamics of DESF. Tmax, Cmax, early partial AUCs, and pharmacodynamic responses were consistent regardless of the presence of food residue. This provides reassurance that the product absorption would not be impaired in “real-world” situations if used to treat a food allergy with very recent ingestion.

Funded by Aquestive Therapeutics

A rare case of isolated chicken meat allergy in a pediatric patient

Nikhil Chowdary Peddi, M.D., Eryn Fox, M.D., Jenny Shliozberg, M.D.

Introduction: Isolated chicken allergy without concomitant sensitization to egg or feathers is quite rare. We describe a case of a pediatric patient who developed rather significant respiratory symptoms after consumption of chicken in the absence of allergy to eggs or feathers.

Case description: A 7-year-old male with a history of asthma was evaluated in our clinic initially for concerns of allergic rhinitis. Respiratory IgE panel revealed sensitization to dust mite, dog, cat, and trees and he was begun on appropriate anti-histamine therapy. At a follow-up visit, mom expressed concern that the patient complained of shortness of breath and chest tightness shortly after ingesting chicken. At first she felt the patient may have been exaggerating his symptoms, however, she gave him a broth that the patient was not aware contained chicken, and he complained of similar chest tightness and mom could see he had objective increased work of breathing. She denies other symptoms such as hives, vomiting, or diarrhea. sIgE testing to feathers on previous respiratory panel was negative, the patient tolerates eggs without issue, and he denies symptoms after ingestion of other types of meat. We performed skin testing to chicken meat extract which was quite positive (7x7mm). We confirmed this finding with sIgE testing which was elevated at 39kU/L. He was advised to avoid chicken meat and an epinephrine auto-injector was prescribed.

Discussion: While chicken allergy in the setting of bird-egg syndrome due to cross sensitization of serum albumins is rather well described, isolated allergy to chicken meat is very rare. Per literature review, it was found that only three cases of isolated chicken allergy have been reported in the past—and all prior to 2006. If clinical history is suggestive, it is important to consider workup of chicken allergy even in the absence of concomitant feather or egg allergy.

Home-based milk OIT using microspoons

Sarah W. Hughes, MPAS, PA-C; Rachel Witsel MSN, APRN, FNP-C.; Jaclyn Bjelac, M.D.; Alexandra E. Conway, BA; Marcus S. Shaker, M.D., MS

Introduction: Food oral immunotherapy (OIT) is a patient preference sensitive treatment option for food allergy. Home-based OIT is an emerging option for patients with food allergies who live in rural settings and wish to pursue desensitization.

Methods: A 14-year-old male with multiple food allergies completed OIT for milk and sesame using Dartmouth’s home-based OIT protocol with microspoons. Comorbid diagnoses included environmental allergies, asthma, allergic rhinitis and atopic dermatitis. Index reactions to milk included vomiting with cow’s milk formula during infancy, rhinorrhea during a baked milk challenge at age 23 months and throat symptoms during a baked milk challenge at age 7 years. He had 1+ positive milk skin-prick test (SPT) and 12.8 kU/L milk sIgE at 2 years, 20 millimeter milk SPT and 20.6 kU/L milk sIgE at 5 years, 4 millimeter milk SPT and 46.9 kU/L milk sIgE at 7 years, and 10 millimeter milk SPT at 10 years.

Results: The OIT protocol included daily micro dose increases (approximating < 1mg protein or < 10% total tolerated dose) at home rather than larger dose increases typically completed under supervision in the allergy clinic. This telehealth model of OIT was preceded by an initial in-person teaching visit for a first subthreshold dose. He tolerated maintenance doses of 405 mg milk protein and 524 mg sesame protein after 12 months. He experienced chest tightness and throat clearing early in the desensitization, confounded by a concurrent upper respiratory infection, and tolerated the remaining buildup without adverse symptoms or reactions. After 4 months of maintenance dosing, milk SPT was negative (0 millimeter). He tolerated a baked milk challenge after 7 months of maintenance dosing.

Conclusion: Home-based OIT using Dartmouth’s home-based microspoons protocol is safe and effective. Home-based OIT provides an opportunity for expanded access to OIT for individuals with food allergies who reside in rural locations.

Food Allergy Prevention Through the Decades: An Ounce of Humility is Worth a Pound of Cure

Alexandra E Conway BA; Matthew Greenhawt, M.D., MBA, MSc; Elissa M Abrams, M.D., MPH; Marcus S Shaker M.D., MS

Introduction: An estimated 18% increase in reported childhood food allergy incidence from 1997 to 2007 has rendered food allergy prevention and treatment an area of high impact, active research, with the last several decades producing an evolving understanding of the pathophysiology and natural course of food allergy. We aim to provide an overview of food allergy prevention guidelines over recent decades while also describing advances in treatment, cost effectiveness, and the role of shared decision making.

Methods: A narrative review of relevant literature was conducted, with attention paid to major changes in national guidelines and the underlying evidence driving those changes.

Results: Changes to food allergy prevention over recent decades can be conceptualized into five epochs, which have followed a general trend of loosening restrictions on the allergen introduction timeline. These epochs are characterized by significant maternal and infant dietary restrictions in a ‘universal avoidance epoch’ (-1990), loosened maternal diet restrictions in an ‘infant avoidance epoch’ (1990–2000), a time-bound allergen introduction schedule in a ‘stratified avoidance epoch’ (2000–2010), retraction of recommendations in a ‘corrective retraction epoch’ (2010–2015), and endorsement of early allergen introduction in the current, ‘early introduction epoch’ (2015-present). The start of the current epoch is notably marked by the 2015 Learning Early About Peanut (LEAP) study and has been accompanied by advances in allergy treatment (including the rise of oral immunotherapy) and increasing recognition of the importance of shared decision-making.

Conclusions: In hindsight, it is clear that certain recommendations from prior decades were not the best course of action. The current no-screening, early introduction approach to food allergy prevention is both cost effective and beneficial to patient quality of life. Our narrative review provides an overview of the evolution of food allergy prevention, highlighting changes in guidance, the emergence of oral immunotherapy, cost effectiveness of prevention, and the role of shared decision making.

Compassionate Care For Patients With Food Allergy and Frustrating Conditions

Marylee Verdi APRN, MSN; Alexandra E Conway BA; Claire C. Beamish M.D.; Marcus S Shaker M.D., MS; Jonathan Bernstein, Michael W. Lee, Ph.D.; Gordon Sussman, M.D.; Daniel Albert M.D.

Introduction: Patients with suspected food allergies may present with a variety of symptoms that may be consistent with mast cell activation syndrome (MCAS). Comorbidities may include cholinergic urticaria or other inducible hives, chronic pain syndrome, hypermobile Ehlers Danlos syndrome (hEDS), postural orthostatic tachycardic syndrome (POTS) associated with dizziness, palpitations and flushing, irritable bowel syndrome with bloating and diarrhea or constipation, headaches, and environmental and medication intolerances.

Methods: A 21 year-old woman with multiple food allergies has experienced anaphylaxis four times over as many years, and each time therapy has been refractory to epinephrine. Her baseline serum tryptase is 12.4 mcg/L, she has a single TPSAB1 copy number variation, and during her last episode of anaphylaxis, which presented with acute hypotension, diffuse urticaria, vomiting, and hoarseness, acute tryptase was 21.2 mcg/L. She has used a β-blocker for 12 months for POTS, carries additional diagnoses of asthma, urticaria, atopic dermatitis, ADHD, and hypermobility syndrome, and has developed significant depression.

Results: This case illustrates the importance of a holistic approach to management of patients presenting with suspected food allergies and complex medical conditions. In this patient and many others, food allergy management is intertwined with the management of comorbid conditions. Appropriate confirmation of comorbid diagnoses is important. Clinicians must address management of these conditions, which includes a balance of trade-offs (e.g., β-blockers for POTS in the setting of recurrent anaphylaxis). Key components of management include the patient-clinician therapeutic alliance and team-based care based in the primary care home, often with involvement of appropriate specialists.

Conclusions: As Sir William Osler said, “The good physician treats the disease, the great physician treats the patient who has the disease.” This case illustrates the importance of team-based management and of a whole-patient care approach to provide the right care, at the right time, every time for patients with food allergy and complex comorbidities.

OIT for a low threshold peanut allergic patient using microspoons

Jaclyn Bjelac, M.D.; Rachel Whitsel, MSN, APRN, FNP-C; Sarah W. Hughes, MPAS, PA-C; Alexandra E. Conway, BA; Marcus S. Shaker, M.D., MS

Introduction: Food oral immunotherapy (OIT) is a treatment option for food allergy. For patients with a very low threshold for anaphylaxis, traditional OIT dosing may incur unacceptable risk despite excellent reported outcomes in preschool age children. Dosing with micro spoons is an emerging option for such patients who wish to pursue desensitization.

Methods: A 2-year-old female with atopic dermatitis presented to allergy clinic with a history of systemic reaction to trace amounts of peanut after consumption of a jelly sandwich; the jar was later determined to have been contaminated with peanut butter from a knife used to prepare a peanut butter sandwich the day prior. Within 30 minutes the patient developed diffuse urticaria, vomiting, and audible wheeze with increased work of breathing requiring home administration of epinephrine. Despite prompt administration, biphasic reaction occurred with diffuse hives 3 hours later. Index reaction at one year of age was diffuse hives to a fingertip amount of peanut butter. Specific IgE to peanut at 2 years of age was >100 kU/L with an Arah2 of 68.7kU/L.

Results: The OIT protocol was modified from Dartmouth’s microspoon protocol, allowing for a starting dose lower than typical protocols and incremental dose increases. Dose increases were performed under observation in clinic given the severity of previous reactions with known low threshold. The patient experienced one episode of diffuse urticaria after a dose at home augmented by physical activity in the setting of mild viral illness. She otherwise tolerated all doses without reaction. After 8 months of buildup, her maintenance of 500mg protein was reached. Laboratory evaluation after 10 months of maintenance dosing demonstrated peanut IgE of 22 ku/L, with Arah2 of 8.14 kU/L.

Conclusions: OIT with modification of Dartmouth’s microspoons protocol allows for very low initial doses and incremental increases and is safe and effective for patients with even very low threshold for reaction.

A Toddler with Baseline Elevated Tryptase and Anaphylaxis to Plant-Based Tube Feeding Formula Due to Suspected Unlabeled Annatto Seed

Travis Satnarine M.D., Jennifer Gebbia APRN, Gary Kleiner M.D. Ph.D., Melissa Gans M.D.

Introduction: Annatto seed, primarily used as a food coloring, is a rare cause of IgE mediated hypersensitivity (1). Several published cases document annatto anaphylaxis (2)(3). The US Food and Drug Administration labeling law (21 CFR 70.25) does not require the listing of natural flavoring or artificial color in food products (4).

Case Description: An 18-month-old female presented for food allergy evaluation after two separate reactions to Kate Farms Formula. She developed whole body urticaria within minutes of ingesting ∼1 ounce of formula. Symptoms resolved quickly with oral diphenhydramine. The patient previously tolerated all the formula's listed ingredients in addition to tree nuts, beans, green peas, chickpeas, sesame seed, flaxseed, and sunflower seed. Patient had never tried peanuts and has a history of immediate urticaria multiple times previously to lentils. IgE blood work to formula's listed ingredients, all common tree nuts, sesame seed, mustard, soybean, and potential hidden allergens (latex, gelatin bovine, gelatin porcine, guar bean gum, carmine, lupine seed, psyllium seed) showed undetectable specific IgE. Positive IgE testing included: lentil IgE 0.32 IU/ml, peanut 0.76 IU/mL, and annatto seed IgE 0.46 IU/ml with total IgE 9 IU/mL. Baseline tryptase level was elevated at 17.7 ng/mL. She was advised to avoid lentil, peanut, and annatto seed, autoinjectable epinephrine was prescribed, and testing for hereditary α tryptasemia was advised.

Discussion: The patient's recurrent reactions to the formula align with a suspected annatto seed allergy, despite its omission from the ingredient list. This case underscores the complexity of diagnosing hidden allergens in food products, necessitating heightened vigilance in managing allergies, especially in pediatric patients reliant on specialized nutrition formulas. Additionally, this patient has an elevated baseline tryptase level, suspected due to hereditary α tryptasemia. This likely worsens her reaction and may make her more susceptible to reactions at low threshold levels of protein.
