Showing papers by "Stacie M. Jones published in 2013"

The natural history of egg allergy in an observational cohort.

Abstract: Background There are few studies on the natural history of egg allergy, and most are single-site and nonlongitudinal and have not identified early predictors of outcomes. Objective We sought to describe the natural course of egg allergy and to identify early prognostic markers. Methods Children age 3 to 15 months were enrolled in a multicenter observational study with either (1) a convincing history of an immediate allergic reaction to egg, milk, or both with a positive skin prick test (SPT) response to the trigger food and/or (2) moderate-to-severe atopic dermatitis and a positive SPT response to egg or milk. Children enrolled with a clinical history of egg allergy were followed longitudinally, and resolution was established based on successful ingestion. Results The cohort with egg allergy consists of 213 children followed to a median age of 74 months. Egg allergy resolved in 105 (49.3%) children at a median age of 72 months. Factors that were most predictive of resolution included the following: initial reaction characteristics (isolated urticaria/angioedema vs other presentations), baseline egg-specific IgE level, egg SPT wheal size, atopic dermatitis severity, IgG 4 level, and IL-4 response (all P Conclusions In this cohort of infants with egg allergy, approximately one half had resolved over 74 months of follow-up. Baseline egg-specific IgE levels and initial reaction characteristics were important predictors of the likelihood of resolution.

Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens.

Abstract: Background Patients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3. Objective We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. Methods Measurements of total peanut-specific IgE (psIgE) and peanut-specific IgG 4 (psIgG 4 ) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG 4 binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described. Results At baseline, psIgE and psIgG 4 diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG 4 levels increased from a median of 0.3 μg/mL (interquartile range [25% to 75%], 0.1-0.43 μg/mL) at baseline to 10.5 μg/mL (interquartile range [25% to 75%], 3.95-45.48 μg/mL; P de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kU A /L (23.05-101.0 kU A /L) to 7.75 kU A /L (2.58-30.55 kU A /L, P 4 binding occurred, including at an informative epitope of Ara h 2. Conclusion OIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG 4 levels, with concurrent reduction in IgE amount and diversity.

Sublingual versus oral immunotherapy for peanut-allergic children: A retrospective comparison

Abstract: To the Editor: There has been considerable recent interest in developing therapies for food allergy, an increasingly common and highly morbid disorder for which strict dietary elimination and ready access to epinephrine remain the standard of care.(1) While both oral immunotherapy (OIT)(2-4) and sublingual immunotherapy (SLIT)(5) have been shown to induce clinical desensitization to foods (reviewed in 6), no head-to-head comparative analysis of the two treatments has been published. We conducted a retrospective study of two previously published protocols for peanut allergy(2,3). This new analysis includes additional subjects, compares the 12-month oral food challenge outcomes, and extends analysis of immunologic parameters out to 24 months. Eligible peanut-allergic subjects were recruited into one of two concurrent clinical trials: OIT (maintenance dose of 4000 mg/day and cumulative double-blind, placebo-controlled challenge (DBPCFC) dose of 5000 mg); or SLIT, (2 mg/day, and 2500 mg, respectively) [all quantities refer to peanut protein]. Although the optimal immunotherapy dose remains unknown, the doses chosen in these trials were based on preliminary data from pilot studies. Of note, unique properties of the oral mucosal immune response are hypothesized to account for SLIT’s efficacy at log-fold lower doses (reviewed in 7). Both trials utilized randomized, double-blind, placebo-controlled designs. Mechanistic studies were performed longitudinally as previously described using blood drawn from subjects within 24 hours of their last immunotherapy dose.(2, 3) At 12 months, subjects underwent DBPCFC to assess clinical desensitization; OIT subjects received a maximal 5000 mg cumulative protein dose, and for safety reasons SLIT challenges were limited to 2500 mg (Online Repository Tables E1/E2). We compared laboratory data between OIT and SLIT at baseline, 12 months, and 24 months, as well as DBPCFC pass/fail outcomes, using the Wilcoxon signed rank test (STATA 12; College Station, TX) and Mann-Whitney U test (GraphPad Prism; La Jolla, CA). Twenty-three subjects on OIT and 27 subjects on SLIT were evaluated after receiving 2 years of treatment (Table 1). We did not undertake a formal comparison of safety parameters between the two studies, and upcoming interval reports of each study will include these data. However, there were no serious adverse events reported in either study. No SLIT and two OIT subjects (one active, one placebo) required four total doses of epinephrine for dose-related reactions. At baseline, the peanut-specific IgE was similar between OIT and SLIT subjects (Fig 1A). Twelve months of treatment led to higher median peanut-specific IgE levels in the OIT group compared to the SLIT group (204.5 kU/L versus 66.7 kU/L, p=0.0382); however, levels were not significantly different between the groups at 24 months (Fig 1A). While peanut-specific IgG4 increased over time in both groups (Fig 1B), the effect was greater with OIT at 12 (20.1 mg/L versus 3.1 mg/L) and 24 months (20.3 mg/L versus 7.9 mg/L, p<0.001). Although decreased in both groups, median peanut-specific IgE/IgG4 ratios were significantly lower at 12 and 24 months for subjects receiving OIT (Fig 1C). Thirty-four subjects (14 OIT, 20 SLIT) had basophil activation assessed by CD63 up-regulation at baseline and 12 months. After 12 months, a significantly lower percentage of CD63+ basophils was found in the OIT group compared with the SLIT group when stimulated with 100 (median 5.90% versus 21.50%) and 10−1 μg/mL (median 6.34% versus 30.75%) crude peanut extract (p<0.01). No between-group difference was seen after stimulation with weaker dilutions of 10−2 and 10−3 μg/mL crude peanut extract. Too few samples were obtained at 24 months to perform an analysis. FIG 1 A and B, Change in serum peanut-IgE and peanut-IgG4 (SLIT/OIT). C, IgE/IgG4 ratio to peanut (SLIT/OIT). D, Cumulative amount tolerated during DBPCFC (SLIT/OIT). E, Serum peanut-IgE (Pass/Fail). F, Fold change in serum peanut-IgG4 from baseline to 12 months ... Table 1 Baseline subject characteristics Eighteen subjects on OIT and 27 subjects on SLIT underwent 12 month desensitization DBPCFCs, results of which are shown in Figure 1D. Despite differences in DBPCFC protocols, SLIT subjects reacted at lower eliciting dose thresholds. A Fisher’s exact test was used to calculate the difference in proportions and relative risk for passing or failing the DBPCFC according to treatment group. The difference in proportions was statistically significant (p=0.002), with OIT-treated subjects 3 times more likely to pass the 12 month desensitization DBPCFC than SLIT-treated subjects (RR=3.00, 95% CI 1.64-5.49). In an attempt to identify candidate biomarkers, we combined all SLIT and OIT subjects and then categorized them by “pass” or “fail” based upon their ability to complete the DBPCFC without symptoms. Consistent with other studies, subjects passing the 12 month desensitization DBPCFC tended to have lower baseline peanut-specific IgE levels (34.6 kU/L versus 167 kU/L, p=0.0575) (Fig 1E). Peanut-specific IgG4 was increased by 27-fold in the “pass” group compared to a 6.5-fold increase in the “fail” group (p=0.01; Fig 1F). Interestingly, the percentage of CD63+ basophils was significantly lower at 12 months in the “pass” group compared with the “fail” group when stimulated with 100 (median 5.90% versus 21.50%) and 10−1 μg/mL (median 6.34% versus 34.75%) crude peanut extract (p<0.01). Again no differences were seen between groups after stimulation with weaker dilutions. Skin prick tests decreased over time in all subjects. Wheal size, serum peanut-specific IgA and peanut-specific IgG, and CD4+CD25+FoxP3+ T-regulatory cells were not significantly different between the OIT and SLIT groups or the “pass” and “fail” groups. In summary, our results suggest that after two years of treatment, OIT produces greater immunologic changes than SLIT in peanut-allergic children. Specifically, peanut OIT resulted in greater changes in peanut-specific IgE, IgG4, and IgE/IgG4 ratio as well as basophil activation. In addition, eliciting dose thresholds were lower and more variable during DBPCFC at 12 months in SLIT-treated subjects, compared to OIT-treated subjects. Subjects who passed the DBPCFC tended to have lower baseline peanut-IgE levels, in addition to a larger fold change in peanut-IgG4 and less basophil activation at 12 months. The major limitation of this study is that it was not a randomized prospective study designed to directly compare the two modalities with a uniform protocol and consecutive enrollment. It is important to also note that interim clinical endpoints measured after only 12 months of immunotherapy likely do not provide a full assessment of the efficacy of either method. Further research is needed to determine the optimal length of treatment, dose, and ideal immunotherapy candidate for each modality.

The changing CARE for patients with food allergy

Abstract: The field of food allergy is continually changing, with advances in clinical care to better understand the mechanisms of disease and in possible new diagnostics and treatment models. The development of several new guidelines that focus on improving the standardization of the diagnosis and management of food allergy has helped to further guide clinicians in providing optimized care for children and adults with food allergy around the world. Much of this work has been made possible through the collaborative efforts of advocacy organizations, industry, and government with clinicians and researchers in the fields of allergy and immunology. We have been able to advance our understanding of disease mechanisms and to help close gaps in knowledge and resolve misconceptions in the treatment of food allergy. This review will focus on the concepts of a holistic approach to food allergy that is working to improve CARE for subjects with food allergy, including new advances in clinical care, advocacy, research, and education.

Sublingual Immunotherapy for Peanut Allergy: A Randomized, Double-Blind, Placebo-Controlled Multicenter Trial

Abstract: DM Fleischer, WA Burks, BP Vickery; Consortium of Food Allergy Research (CoFAR). J Allergy Clin Immunol . 2013;131(1):119–127 To determine the safety and efficacy of sublingual immunotherapy (SLIT) for inducing desensitization in subjects with peanut allergy. The study population consisted of 40 subjects (ages 12–37 years) from 5 US sites with peanut allergy defined by clinical history or physician diagnosis, positive skin-prick test or peanut-specific immunoglobulin E (Pn-IgE; ≥0.35 kU/L), and a positive double-blind, placebo-controlled oral food challenge (OFC) to ≤2 g of peanut powder. Patients with a history of severe anaphylaxis to peanut were excluded. Subjects were randomly assigned 1:1 to peanut (Pn) or placebo (Pb) SLIT groups. Subjects started with an initial …

Mental Health Comorbidity in Patients With Atopic Dermatitis

Abstract: P Yaghmaie, CW Koudelka, EL Simpson. J Allergy Clin Immunol. 2013;131(2):428–433 To quantify the mental health burden associated with pediatric atopic dermatitis (AD) in the United States. Recent data suggest that children with AD might be at an increased risk of mental health disorders. Data were analyzed from the 2007 National Survey of Children’s Health, a survey reporting on the health status of 91 642 children aged 0 to 17 years. The analysis was limited to those children who had seen a health care provider in the past year ( n = 79 667). Data were used from the 2007 …

Reply: To PMID 23265692.

Abstract: would be is not easy to answer. Oral corticosteroids are no longterm option for CRSwNP, because they will cause thewell-known systemic side effects, and provide only a rather short-lived therapeutic answer. Also, repeated surgeries carry a risk for complications, which should be taken into consideration. Although it might be interesting to compare an innovative treatment to oral corticosteroids, the standard treatment could only be topical steroids in the recommended dosage, but not leukotriene inhibitors or antibiotics. However, our study cannot answer the question whether omalizumab may be a long-term solution for patients with CRSwNP, the performance of trials investigating this aspect of treating a severe persistent airway disease would need consideration. It is our hope that omalizumab and other innovative treatments would provide a long-term answer for those patients better than the ‘‘arsenal’’ of therapies currently available. Lien Calus, MD Peter Hellings, MD, PhD Guy Brusselle, MD, PhD Claus Bachert, MD, PhD Philippe Gevaert, MD, PhD