Showing papers by "Stacie M. Jones published in 2009"

Clinical efficacy and immune regulation with peanut oral immunotherapy.

Abstract: Background Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. Objective The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Methods Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Results Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12 to 18 months, whereas IgG 4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over a period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter. In addition, T-cell microarrays showed downregulation of genes in apoptotic pathways. Conclusion Oral immunotherapy induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT.

Safety of a peanut oral immunotherapy protocol in children with peanut allergy.

Abstract: Background Oral immunotherapy (OIT) offers a promising therapeutic option for peanut allergy. Given that during OIT an allergic patient ingests an allergen that could potentially cause a serious reaction, the safety of OIT is of particular concern. Objective The purpose of this study was to examine safety during the initial escalation day, buildup phase, and home dosing phase in subjects enrolled in a peanut OIT study. Methods Skin, upper respiratory tract, chest, and abdominal symptoms were recorded with initial escalation day and buildup phase dosings. Subjects also maintained daily diaries detailing symptoms after each home dosing. A statistical analysis of these data was performed. Results Twenty of 28 patients completed all phases of the study. During the initial escalation day, upper respiratory tract (79%) and abdominal (68%) symptoms were the most likely symptoms experienced. The risk of mild wheezing during the initial escalation day was 18%. The probability of having any symptoms after a buildup phase dose was 46%, with a risk of 29% for upper respiratory tract symptoms and 24% for skin symptoms. The risk of reaction with any home dose was 3.5%. Upper respiratory tract (1.2%) and skin (1.1%) symptoms were the most likely after home doses. Treatment was given with 0.7% of home doses. Two subjects received epinephrine after 1 home dose each. Conclusions Subjects were more likely to have significant allergic symptoms during the initial escalation day when they were in a closely monitored setting than during other phases of the study. Allergic reactions with home doses were rare.

Adverse reactions during peanut oral immunotherapy home dosing

Abstract: To The Editor: Oral immunotherapy (OIT) is increasingly being investigated as a potential treatment for peanut and other food allergies, with a recent study demonstrating evidence of clinical desensitization and immunologic changes suggesting the development of long-term tolerance1 Unlike traditional subcutaneous immunotherapy for inhalant allergens, peanut OIT is administered daily, with the vast majority of doses given at home In our peanut OIT protocols, subjects are seen in the research unit for observed dose escalations every two weeks, and subsequent doses are given at home In the open-label study of peanut OIT, home doses were generally well-tolerated2 The incidence of allergic reactions with any home dose was 35%, with mild upper respiratory and skin symptoms being the most common complaints Despite the infrequent incidence of symptoms with peanut OIT home dosing, certain patterns of reactions have surfaced during this phase Characterizing these reactions and identifying potential triggers or factors which predispose to reactions may improve the safety of home dosing Reactions occurring during investigational OIT or any immunotherapy protocol are challenging to study prospectively, due to ongoing modifications in the protocol and recommendations that are instituted to prevent further reactions In subcutaneous aeroallergen immunotherapy, asthma has been identified as a risk factor for systemic reactions, prompting recommendations to evaluate respiratory symptoms and consider objective measures of airway function during administration3 Researchers studying milk and egg OIT noted certain “augmentation factors” that lowered threshold doses – namely, infection, exercise, pollen allergy, and irregular intake4 – and identifying these factors and reducing the immunotherapy dose prevented further allergic reactions We have noted five patterns associated with a propensity to react to a previously tolerated dose of peanut OIT, including several not previously described It is interesting that these factors would provoke symptoms after a given OIT dose when, in many of the examples noted, the dose had been tolerated for weeks to months without symptoms Table I lists selected examples illustrating the observed patterns – (1) concurrent illness, (2) suboptimally-controlled asthma, (3) timing of dose administration after food ingestion, (4) physical exertion after dosing, and (5) dosing during menses Addressing these factors (see Table II) has improved the safety profile of our peanut OIT protocol While some of our recommendations mirror those instituted in subcutaneous immunotherapy protocols, most are unique to OIT administration We expand on reports from other research centers4, 5, which have described triggers such as infection, exercise, pollen allergy, and irregular intake, and this is the first report involving protocols for peanut allergy Table I Examples of Reactions during Peanut OIT Home Dosing Table II Recommendations for Future OIT Investigations We have observed that dosing during febrile illnesses has been associated with systemic reactions to previously tolerated peanut OIT doses We recommend withholding OIT during acute illnesses and advise subjects to resume dosing at home if fewer than three doses are missed If three to five doses are missed, subjects return to the research unit for observed dosing Those who miss more than five days of dosing may require significant dose reduction or repeat desensitization In our open-label study2, asthma was associated with a higher rate of chest symptoms during OIT Of the subjects reporting chest symptoms during home dosing, 82% had co-existing asthma Several subjects receiving peanut OIT noted cough and wheezing after doses Some also had chronic cough or exercise-induced respiratory symptoms Although we did not observe changes in pulmonary function in these subjects, their symptoms improved with the initiation of asthma controller medications (see Table I), highlighting the importance of diagnosing and treating co-morbid atopic conditions Regular peak flow measurements and pulmonary function testing has been implemented to optimize asthma control It has not been uncommon for a subject taking a daily OIT dose without eating a meal or snack in the two hours before dosing to have symptoms with a dose that has been previously tolerated; taking the same dose with food the next day and thereafter prevents further reactions Additionally, several subjects have experienced allergic symptoms with exercise after OIT dosing, and we advise these individuals to avoid exertion for two hours after dosing Finally, one subject had several systemic reactions when menses was coupled with exercise despite no symptoms with daily dosing in the interval between episodes and was eventually withdrawn from the study She was not taking other medications (eg non-steroidal anti-inflammatory drugs) Of note, she did not have systemic reactions each time she exercised during menses At this time, the role of menses is unclear, and further study is needed In the studies to date, peanut and food OIT have a good safety profile, and home dosing is infrequently associated with adverse reactions2, 6 However, allergic symptoms should be expected, and subjects and their families should be counseled about circumstances associated with an increased possibility of reacting to previously tolerated OIT doses As OIT for food allergy becomes increasingly studied in research settings, implementing these recommendations and modifications can improve the safety of these experimental protocols

Oral immunotherapy for food allergy

Abstract: Food allergy is an increasingly prevalent disorder with potentially life-threatening complications that requires life-altering changes in dietary habits and psychosocial interactions. The standard of care presently includes strict dietary elimination of the implicated allergen and ready access to injectable epinephrine; however, no active, definitive therapeutic options exist for food-allergic patients. Although the detailed immunologic mechanisms underlying the development of food allergy are still being fully defined, food allergy appears to be the direct result of a breakdown in oral tolerance. Thus, current therapeutic approaches to food allergy are focused on modulating the immunologic response to food proteins to promote induction of oral tolerance. In this review, we examine gastrointestinal mucosal immunity and the mechanisms of oral tolerance, as well as the breakdown in oral tolerance that promotes food allergy, and we also explore novel therapeutic interventions for treatment of food allergy.

Episodic Use of an Inhaled Corticosteroid or Leukotriene Receptor Antagonist in Preschool Children With Moderate-To-Severe Intermittent Wheezing

Abstract: Bacharier LB, Phillips BR, Zeiger RS, et al. J Allergy Clin Immunol. 2008;122(6):1127–1135 PURPOSE OF THE STUDY. To examine the effectiveness of episodic use of an inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA) in preschool-aged children with moderate-to-severe intermittent wheezing associated with respiratory tract illness (RTI). STUDY POPULATION. Children 12 to 59 months of age with ≥2 episodes of wheezing with RTI in the previous year and either 2 urgent care visits for wheezing, 2 wheezing episodes requiring oral steroid treatment (<6 courses), or 1 episode requiring urgent care and oral steroid treatment. METHODS. The study design was a randomized, double-blind, placebo-controlled trial, with children assigned randomly to 1 …

Efficacy and Safety of 5–Grass-Pollen Sublingual Immunotherapy Tablets in Pediatric Allergic Rhinoconjunctivitis

Abstract: Wahn U, Tabar A, Kuna P, et al. J Allergy Clin Immunol. 2009;123(1):160–166 PURPOSE OF THE STUDY. To determine the efficacy and safety of a 300-index of reactivity sublingual immunotherapy (SLIT) tablet for children with allergic rhinoconjunctivitis. STUDY POPULATION. Subjects were 278 children (age: 5–14 years) with seasonal grass pollen-induced allergic rhinoconjunctivitis for ≥2 years. Allergy was confirmed by a timothy grass-specific immunoglobulin E (IgE) level of at least class 2 and a wheal diameter of >3 mm in a skin-prick test containing 5 grass pollens included in the SLIT tablet (orchard, meadow, perennial rye, sweet vernal, and timothy grasses). Patients who were sensitized …

A Randomized, Double-Blind, Placebo-Controlled Study of Milk Oral Immunotherapy for Cow's Milk Allergy

Abstract: Skripak J, Nash S, Rowley H, et al. J Allergy Clin Immunol. 2008;122(6):1154–1160 PURPOSE OF THE STUDY. To determine the safety and efficacy of milk oral immunotherapy (OIT) in desensitizing children with cow's milk allergy. STUDY POPULATION. Twenty children, 6 and 21 years of age, with an immunoglobulin E (IgE)-mediated cow's milk allergy. METHODS. This study was a randomized, placebo-controlled trial with subjects randomly assigned to milk or placebo OIT. OIT was administered in 3 phases: (1) initial build-up day; (2) daily home dosing with 8 weekly, in-office, dose increases; and …