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Baseline Mechanistic Characteristics of Peanut Allergic Children Undergoing Peanut Immunotherapy
90
Milk Oral Immunotherapy (MOI): Interim Results of the First Hundred Patients. Y. Katz, M. Goldberg, M. Levy, M. Stein, A. Elizur, M. Zimmerman, A. Cohen; Assaf-Harofeh Medical Center, Zerifin, ISRAEL. RATIONALE: Mortalities due to accidental ingestion of cow’s milk protein (CMP)-contaminated products highlights the need for food oral immunotherapy (OIT) programs. METHODS: IgE-mediated cow’s milk allergy (IgE-CMA) patients >age 4 were enrolled in an individualized, escalating four-round OIT protocol. Each round consisted of an initial four days in an ambulatory-care hospital setting to determine the maximal tolerated dose (MTD). This dose was then administered at home twice daily for 24 days. All patients and caregivers were instructed on the use of EpipenÒ, antihistamines and bronchodilators. In addition, each patient was required to report daily. RESULTS: To date, 41/103 patients have completed the treatment program. Their ages range from 4-26 years. Nineteen patients achieved full tolerance (ingestion >7.2gram CMP), 13 achieved partial tolerance (>2.0gram), and 41 patients reached beyond a level protective against incidental exposure (PIE) to contaminated non-dairy products (>150mg). Most of those who didn’t reach a PIE level have not entered their second round. The progress of 11 participants was hindered by non-anaphylactic type reactions, albeit most of them still reached a PIE level. Three patients failed to pass the first induction phase. During the 2,453 induction doses given, adverse reactions required 40 injections of adrenaline (1.6%) and 88 treatments with either antihistamines, bronchodilators or both (3.6%). Most of these adverse reactions occurred during the first day of induction. CONCLUSIONS: Patients with IgE-CMA can reach full tolerance with MOI. While the procedure is not without risk, it can be safely carried out in an equipped environment in the presence of experienced personnel.
91
Tolerance To Extensively Heated Milk (HM) In Children With Cow's Milk Allergy: A Follow Up J. S. Kim, A. Nowak-Wegrzyn, S. R. Noone, R. Bencharitiwong, K. A. Bloom, H. A. Sampson; Mt. Sinai School of Medicine, New York, NY. RATIONALE: The majority (75%) of milk-allergic children tolerate HM. We now report on the development of tolerance to unheated milk (UHM) stratified by initial HM-tolerance status. METHODS: Children who demonstrated tolerance to HM (muffin/waffle) underwent sequential food challenges to pizza, macaroni & cheese, and UHM as tolerated. Immunologic parameters were measured at challenge visits. RESULTS: Ninety-four children (median age 6.7 years; IQR:5.3-8.7 years) were followed for a median of 31 months (IQR:18-47 months). Of 70 initially HM-tolerant children (Group A), 42 (60%) became UHM-tolerant; 18 (26%) regularly tolerated some form of HM/cheese; 9 (13%) later chose to avoid all forms of milk; 1 was lost to follow up. Among 24 HMreactive children (Group B), 2 (8%) tolerated UHM and 3 (13%) tolerated HM/cheese whereas 19 (79%) avoided milk completely. One child in each group developed eosinophilic esophagitis; one developed ulcerative colitis (Group A). A significantly greater proportion of children in Group A developed tolerance to UHM compared to Group B (p<0.001). Median time to UHM-tolerance (n544) was 21 months (IQR:13-32 months). Among the 75 children who incorporated HM into their diets, milk skin-prick-test wheal sizes decreased (mean 8 to 6.7mm, p50.001) while casein IgG4 levels increased (0.6 to 1.5mgA/L, p<0.001); b-lactoglobulin IgG4 levels also increased (0.4 to 0.8mgA/L, p50.004). Milk-specific IgE levels did not change significantly. CONCLUSIONS: HM-tolerance is a favorable prognostic indicator for development of UHM-tolerance whereas HM-reactivity portends a more persistent phenotype of IgE-mediated milk allergy. Studies are ongoing to evaluate whether regular ingestion of HM accelerates development of tolerance to UHM.
92
Baseline Mechanistic Characteristics of Peanut Allergic Children Undergoing Peanut Immunotherapy S. D. Narisety, P. Guerrerio, J. Schroeder, R. Hamilton, R. A. Wood; The Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: The mechanistic predictors of peanut challenge responses are poorly understood. METHODS: Baseline characteristics for children with severe peanut allergy (PA) undergoing peanut immunotherapy were collected, including: total IgE, peanut-IgE (P-IgE), peanut IgG (P-IgG), 5-log peanut endpoint skin-prick titration (PEST), double blind placebo controlled peanut challenge (DBPCPC), and spontaneous and stimulated (three dose titration) basophil histamine release (BHR). RESULTS: 7 subjects aged 9-13 years were included with P-IgE range 104-814 kUa/L (median 412), P-IgG range 6.4-31.2 mgA/L (median 14.6), total IgE range 305-1378 kU/L (median 830), PEST mean wheal size range 1.3-7.2mm (median 4.7). The cumulative dose reached during DBPCPC ranged from 1-71mg (median 21). 6 subjects had high spontaneous BHR (median 35.5%, range 13-81). Median average BHR to peanut was 31.7% (range -1-47.7). P-IgG levels correlated with cumulative DBPCPC dose (r50.89, p5<0.05). P-IgE levels were inversely correlated with average BHR (r5-0.79, p5<0.05). There was a trend toward a relationship between total symptoms experienced during DBPCPC and both total IgE and P-IgE (r50.66, p50.1 and r50.55, p50.2, respectively). CONCLUSIONS: This group of peanut allergic children showed high levels of P-IgE, total IgE and spontaneous BHR with reactivity to low doses of peanut during DBPCPC. Subjects with higher P-IgG levels reached a significantly higher cumulative DBPCPC dose. Those with higher average BHR had significantly lower P-IgE levels.
93
Adverse Reactions During Home Dosing on a Milk Oral Immunotherapy (MOI) Program M. B. Levy, M. R. Goldberg, M. L. Stein, A. Elizur, A. Cohen, M. Zimmerman, Y. Katz; Assaf-Harofeh Medical Center, Zerifin, ISRAEL. RATIONALE: Oral food immunotherapy (OFI) has been shown to be efficacious. Adverse events are a concern during the initial induction and especially during subsequent home maintenance phases of therapy with some practitioners suggesting that a high risk-to-benefit ratio for this treatment of food allergies may be unacceptable. METHODS: The records of 103 patients enrolled in a cow’s milk protein OFI program were reviewed. This individualized escalation protocol includes a 4 day induction phase performed in a hospital based out-patient clinic where a maximum individual tolerated dose (MITD) was determined. This home maintenance MITD was then consumed twice daily for 24 days and the cycle repeated. All patients were instructed on the use of an adrenaline auto-injector, antihistamines, bronchodilators and contact information. Adverse events and treatments during the home maintenance phase were reported by daily e-mails and a written monthly record. RESULTS: 72/103 patients were able to tolerate >150mg of milk protein after 3 escalation sessions. Of 2,453 induction doses, 40 injections of adrenaline (1.6%) and 88 treatments with either anti-histamines, bronchodilators or both (3.6%) were administered. Of 5,003 home doses, 5 injections of adrenaline (0.001%) with subsequent physician evaluation and 46 treatments with either antihistamines or bronchodilators (0.9%) were administered. No late phase reactions or hospitalizations occurred. CONCLUSIONS: A small percentage of patients undergoing MOI may require adrenaline, antihistamines or bronchodilators. No hospitalizations or late phase reactions were observed. This reaction rate may suggest an acceptable risk-to-benefit ratio for this effective potential life-saving treatment of cow’s milk allergy.
SATURDAY
Abstracts AB27
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2
Milk Oral Immunotherapy (MOI): Interim Results of the First Hundred Patients. Y. Katz, M. Goldberg, M. Levy, M. Stein, A. Elizur, M. Zimmerman, A. Cohen; Assaf-Harofeh Medical Center, Zerifin, ISRAEL. RATIONALE: Mortalities due to accidental ingestion of cow’s milk protein (CMP)-contaminated products highlights the need for food oral immunotherapy (OIT) programs. METHODS: IgE-mediated cow’s milk allergy (IgE-CMA) patients >age 4 were enrolled in an individualized, escalating four-round OIT protocol. Each round consisted of an initial four days in an ambulatory-care hospital setting to determine the maximal tolerated dose (MTD). This dose was then administered at home twice daily for 24 days. All patients and caregivers were instructed on the use of EpipenÒ, antihistamines and bronchodilators. In addition, each patient was required to report daily. RESULTS: To date, 41/103 patients have completed the treatment program. Their ages range from 4-26 years. Nineteen patients achieved full tolerance (ingestion >7.2gram CMP), 13 achieved partial tolerance (>2.0gram), and 41 patients reached beyond a level protective against incidental exposure (PIE) to contaminated non-dairy products (>150mg). Most of those who didn’t reach a PIE level have not entered their second round. The progress of 11 participants was hindered by non-anaphylactic type reactions, albeit most of them still reached a PIE level. Three patients failed to pass the first induction phase. During the 2,453 induction doses given, adverse reactions required 40 injections of adrenaline (1.6%) and 88 treatments with either antihistamines, bronchodilators or both (3.6%). Most of these adverse reactions occurred during the first day of induction. CONCLUSIONS: Patients with IgE-CMA can reach full tolerance with MOI. While the procedure is not without risk, it can be safely carried out in an equipped environment in the presence of experienced personnel.
91
Tolerance To Extensively Heated Milk (HM) In Children With Cow's Milk Allergy: A Follow Up J. S. Kim, A. Nowak-Wegrzyn, S. R. Noone, R. Bencharitiwong, K. A. Bloom, H. A. Sampson; Mt. Sinai School of Medicine, New York, NY. RATIONALE: The majority (75%) of milk-allergic children tolerate HM. We now report on the development of tolerance to unheated milk (UHM) stratified by initial HM-tolerance status. METHODS: Children who demonstrated tolerance to HM (muffin/waffle) underwent sequential food challenges to pizza, macaroni & cheese, and UHM as tolerated. Immunologic parameters were measured at challenge visits. RESULTS: Ninety-four children (median age 6.7 years; IQR:5.3-8.7 years) were followed for a median of 31 months (IQR:18-47 months). Of 70 initially HM-tolerant children (Group A), 42 (60%) became UHM-tolerant; 18 (26%) regularly tolerated some form of HM/cheese; 9 (13%) later chose to avoid all forms of milk; 1 was lost to follow up. Among 24 HMreactive children (Group B), 2 (8%) tolerated UHM and 3 (13%) tolerated HM/cheese whereas 19 (79%) avoided milk completely. One child in each group developed eosinophilic esophagitis; one developed ulcerative colitis (Group A). A significantly greater proportion of children in Group A developed tolerance to UHM compared to Group B (p<0.001). Median time to UHM-tolerance (n544) was 21 months (IQR:13-32 months). Among the 75 children who incorporated HM into their diets, milk skin-prick-test wheal sizes decreased (mean 8 to 6.7mm, p50.001) while casein IgG4 levels increased (0.6 to 1.5mgA/L, p<0.001); b-lactoglobulin IgG4 levels also increased (0.4 to 0.8mgA/L, p50.004). Milk-specific IgE levels did not change significantly. CONCLUSIONS: HM-tolerance is a favorable prognostic indicator for development of UHM-tolerance whereas HM-reactivity portends a more persistent phenotype of IgE-mediated milk allergy. Studies are ongoing to evaluate whether regular ingestion of HM accelerates development of tolerance to UHM.
92
Baseline Mechanistic Characteristics of Peanut Allergic Children Undergoing Peanut Immunotherapy S. D. Narisety, P. Guerrerio, J. Schroeder, R. Hamilton, R. A. Wood; The Johns Hopkins University School of Medicine, Baltimore, MD. RATIONALE: The mechanistic predictors of peanut challenge responses are poorly understood. METHODS: Baseline characteristics for children with severe peanut allergy (PA) undergoing peanut immunotherapy were collected, including: total IgE, peanut-IgE (P-IgE), peanut IgG (P-IgG), 5-log peanut endpoint skin-prick titration (PEST), double blind placebo controlled peanut challenge (DBPCPC), and spontaneous and stimulated (three dose titration) basophil histamine release (BHR). RESULTS: 7 subjects aged 9-13 years were included with P-IgE range 104-814 kUa/L (median 412), P-IgG range 6.4-31.2 mgA/L (median 14.6), total IgE range 305-1378 kU/L (median 830), PEST mean wheal size range 1.3-7.2mm (median 4.7). The cumulative dose reached during DBPCPC ranged from 1-71mg (median 21). 6 subjects had high spontaneous BHR (median 35.5%, range 13-81). Median average BHR to peanut was 31.7% (range -1-47.7). P-IgG levels correlated with cumulative DBPCPC dose (r50.89, p5<0.05). P-IgE levels were inversely correlated with average BHR (r5-0.79, p5<0.05). There was a trend toward a relationship between total symptoms experienced during DBPCPC and both total IgE and P-IgE (r50.66, p50.1 and r50.55, p50.2, respectively). CONCLUSIONS: This group of peanut allergic children showed high levels of P-IgE, total IgE and spontaneous BHR with reactivity to low doses of peanut during DBPCPC. Subjects with higher P-IgG levels reached a significantly higher cumulative DBPCPC dose. Those with higher average BHR had significantly lower P-IgE levels.
93
Adverse Reactions During Home Dosing on a Milk Oral Immunotherapy (MOI) Program M. B. Levy, M. R. Goldberg, M. L. Stein, A. Elizur, A. Cohen, M. Zimmerman, Y. Katz; Assaf-Harofeh Medical Center, Zerifin, ISRAEL. RATIONALE: Oral food immunotherapy (OFI) has been shown to be efficacious. Adverse events are a concern during the initial induction and especially during subsequent home maintenance phases of therapy with some practitioners suggesting that a high risk-to-benefit ratio for this treatment of food allergies may be unacceptable. METHODS: The records of 103 patients enrolled in a cow’s milk protein OFI program were reviewed. This individualized escalation protocol includes a 4 day induction phase performed in a hospital based out-patient clinic where a maximum individual tolerated dose (MITD) was determined. This home maintenance MITD was then consumed twice daily for 24 days and the cycle repeated. All patients were instructed on the use of an adrenaline auto-injector, antihistamines, bronchodilators and contact information. Adverse events and treatments during the home maintenance phase were reported by daily e-mails and a written monthly record. RESULTS: 72/103 patients were able to tolerate >150mg of milk protein after 3 escalation sessions. Of 2,453 induction doses, 40 injections of adrenaline (1.6%) and 88 treatments with either anti-histamines, bronchodilators or both (3.6%) were administered. Of 5,003 home doses, 5 injections of adrenaline (0.001%) with subsequent physician evaluation and 46 treatments with either antihistamines or bronchodilators (0.9%) were administered. No late phase reactions or hospitalizations occurred. CONCLUSIONS: A small percentage of patients undergoing MOI may require adrenaline, antihistamines or bronchodilators. No hospitalizations or late phase reactions were observed. This reaction rate may suggest an acceptable risk-to-benefit ratio for this effective potential life-saving treatment of cow’s milk allergy.
SATURDAY
Abstracts AB27
J ALLERGY CLIN IMMUNOL VOLUME 127, NUMBER 2