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Oral antigen-induced intestinal anaphylaxis requires IgE-dependent mast cell degranulation
J ALLERGY CLIN IMMUNOL VOLUME 111, NUMBER 2
from school occurred related to asthma exacerbations (90 days). The Fitness Evaluation results indicated a mean 12-point increase in peak flow reading. CONCLUSIONS: Incorporating exercise in asthma education projects can dispel myths regarding asthma and exercise. Teaching self-management to children increases compliance, enhances quality of care and reduces cost.
Funding: Self-funded
1084The Histamine-|nduced Wheal and Flare: A Systematic Review of Methodology
A. Daly, T. Systematic Review Group; Healthcare Dimensions, Dublin, IRELAND. RATIONALE: The histamine-induced wheal-and-flare (HIWF) has been used extensively in pharrnacodynamic studies of second-generation antihistamines. We conducted a systematic review of the methodologies of HIWF studies to assess subject criteria, dosing schedules and endpoint criteria. METHODS: A comprehensive literature survey was performed using the Medline, Embase, SciSearch and Biosis databases from 1969-2002. This search targeted studies involving HIWF and the second-generation antihistamines, cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine, mizolastine and ebastine. Studies were retrieved and data were extracted regarding: study duration, subject number, subject characteristics (healthy or patient), drug dosing/duration and timing of HIWF assessments. Data handling was managed descriptively. RESULTS: The literature search identified 490 studies, of which 42 were relevant to the terms of the review. The study duration was from 1-84 days (mean=7.88 days; median=l day), of which the majority (28/42 (66.7%)) were single-dose studies. Most studies (71.4%) were conducted in healthy volunteers, while only 28.6% involved atopic/allergic patients or mixed populations. Few studies (12/42) assessed the effects on HIWF of steadystate levels of the antihistamines in this analysis, and only 7 studies were conducted for periods similar to disease activity in allergic rhinitis/chronic idiopathic urticaria (_>14 days). In 8/28 single-dose studies, the HIWF data were collected <12hr post-dosing. CONCLUSIONS: Pharmacodynamic HIWF studies of second-generation antihistamines are heterogeneous. Most data describe the effects of singledose treatment in healthy patients, often shortly after dosing. Single-dose, short-term data in this simple pharmacologic model may not be reliable for predicting the clinical efficacy of antihistamines in the clinical disease state.
Funding: Schering-Plough Corp
1085
Group Discussions with Parents of Pre-schoo, Children-Positive Effects on the Management of Asthma
C. Hederos j, S. Janson z, G. Hedlin3; IBam-Ungdomsmedicin, Primary Care Research Unit VC Gripen, Karlstad, SWEDEN, 2VC Gripen, Primary Care Research Unit VC Gripen, Karlstad, SWEDEN, 3Astrid Lindgrens Hospital, Karolinska Institutet, Stockholm, SWEDEN. The aim was to evaluate if a program for parent support and information would improve adherence to treatment recommendations and the wellbeing of parents and children. Sixty children 1-6 years old with newly diagnosed asthma entered this study. Parents were randomized to either the intervention consisting of 4 meetings in a group setting during 6 months or to the traditional check-up visits at doctor's office. Follow-up visits were done up to 18 months. Sixty-five percent of the children were classified as moderate/severe asthmatics, 48% were RAST/skin prick test positive. 71% of the group attendants agreed at inclusion that the positive effects of asthma medicines surpassed the negative ones--after 18 months 85% had that opinion. In the control group the proportion was unchanged. The mothers in the intervention group had a significant rise in emotional, activity and over all index evaluated by Junipers PACQLQ (Paediatric Asthma Caregiver's Quality of Life Questionnaire). The adherence was poor in 8% of the children in the intervention group but in 30% in the control group (p=0,015). At 18 months 7% of the intervention group still belonged to the moderate/severe asthmatics (p=0,03) while 29% of the control group were classified as moderate/severe (N.S). The group attendants stayed home to take care of their children due to acute asthma in total 56 days less than the control parents during the last 6 months of the
Abstracts
8339
study. In conclusion the group session method resulted in more adherent. informed and satisfied parents and healthier children.
Funding: Primary Care Research Unit Karlstad
1086 ication Fanlily Recall of Treatment Plans and Its Relation to MedAdherence in Pediatric Asthma C, D. Adams I, K. E. Joseph j, T. Ash 1, C. Dotson l, N. W. Wilson2, M. B. Hogan2; )Department of Psychology, West Virginia University, Morgantown, WV, 2Department of Pediatrics, West Virginia University, Morgantown, WV. RATIONALE: Medication adherence amongst pediatric patients with asthma is known to be poor. We hypothesize that errors in family recall of asthma treatment plans will be associated with lower adherence levels to maintenance medication. METHODS: Participants included 35 patients (ages 5-18) with a new maintenance medication plan at the time of enrollment. Youth participated by completing a treatment plan recall interview after the clinic visit. This interview assessed knowledge regarding maintenance medications, allergies and allergen avoidance measures, and rescue plan for asthma episodes. Parents also participated in a separate recall interview. Adherence to inhaled steroids was measured via a MDILog-II device for several weeks (ie, 4-8) after the recall interviews. RESULTS: Treatment plan recall for rescue medications generally was good. In contrast, substantial recall errors for allergy avoidance measures and maintenance medication were found. These errors were significantly related to lower adherence to inhaled corticosteroids. In general, patient recall yielded more errors than parent recall. Finally, adherence levels overall were poor. CONCLUSIONS: Errors in the patients' and parents' recall of treatment plans may contribute to lower medication adherence in pediatric asthma patients. Common errors in recall should be targeted for improved family education efforts.
Funding: American Lung Association
1087
OratAntigen-inducedt,testina' AnaphytaxisRequirestgZdependent Mast Cell Degranulation
E. B. Brandt I, R. T. Strait 2, Q. Wang 3, D. Hershko 3, E. Muntel 1, F. D. Finkelman2,4, M. E. Rothenberg I; ]Division of Allergy and Immunology, Children's Hospital Medical Center, Cincinnati, OH, :University of Cincinnati, College of Medicine. Cincinnati, OH, 3Shriners Hospitals for Children, Cincinnati, OH, 4Veteran's Administration Medical Center, Cincinnati, OH. RATIONALE: This study investigates the molecular and cellular mechanisms involved in a novel model of oral allergen-induced intestinal anaphylaxis (accompanied by acute diarrhea). METHODS: Balb/c mice were sensitized with OVA/alum and then subjected to intragastric saline or OVA challenges. Mice were treated with either anti-cKit (ACK2) or a control antibody to eliminate mucosal mast cells (MMCs). Blocking antibody for FcgRII/RIII (24G2), anti-IgE antibody (EM95) and FceRl deficient mice were used to dissect the role of mast cells and lg. The molecular mediators of intestinal anaphylaxis were examined by employment of PAF, histamine and serotonin receptor antagonists. Levels of MMCs, MMC Protease I (MMCPI), Ig levels, and intestinal permeability (Ussing chamber) were assessed. RESULTS: Sequential intragastric OVA challenges resulted in dose dependent onset of acute diarrhea, accompanied by increased levels of OVA-specific lgGl/lgE, MMCs, and serum MMCPI. Mice treated with anti--cKit had no identifiable MMCs and serum MMCPI, and importantly were protected from oral antigen-induced intestinal permeability changes and diarrhea. Blocking lgG receptors had no effect, while the anti-IgE antibody eliminated diarrhea. Additionally, FceRl-deficient mice were resistant to diarrhea compared with wild-type mice. Finally, diarrhea was blocked by pre-treatment with a combination of histamine, PAE and serotonin receptor antagonists. CONCLUSIONS: Oral allergen-induced intestinal anaphylaxis, manifested by diarrhea, is mediated by lgE/FceRl-dependent mast cell mediator release. These observations open the way for the identification of the precise mediators, mechanisms, and therapeutics for gastrointestinal allergic disorders.
Funding: AHA, NIH, HFSP, ILSI, BWF
from school occurred related to asthma exacerbations (90 days). The Fitness Evaluation results indicated a mean 12-point increase in peak flow reading. CONCLUSIONS: Incorporating exercise in asthma education projects can dispel myths regarding asthma and exercise. Teaching self-management to children increases compliance, enhances quality of care and reduces cost.
Funding: Self-funded
1084The Histamine-|nduced Wheal and Flare: A Systematic Review of Methodology
A. Daly, T. Systematic Review Group; Healthcare Dimensions, Dublin, IRELAND. RATIONALE: The histamine-induced wheal-and-flare (HIWF) has been used extensively in pharrnacodynamic studies of second-generation antihistamines. We conducted a systematic review of the methodologies of HIWF studies to assess subject criteria, dosing schedules and endpoint criteria. METHODS: A comprehensive literature survey was performed using the Medline, Embase, SciSearch and Biosis databases from 1969-2002. This search targeted studies involving HIWF and the second-generation antihistamines, cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine, mizolastine and ebastine. Studies were retrieved and data were extracted regarding: study duration, subject number, subject characteristics (healthy or patient), drug dosing/duration and timing of HIWF assessments. Data handling was managed descriptively. RESULTS: The literature search identified 490 studies, of which 42 were relevant to the terms of the review. The study duration was from 1-84 days (mean=7.88 days; median=l day), of which the majority (28/42 (66.7%)) were single-dose studies. Most studies (71.4%) were conducted in healthy volunteers, while only 28.6% involved atopic/allergic patients or mixed populations. Few studies (12/42) assessed the effects on HIWF of steadystate levels of the antihistamines in this analysis, and only 7 studies were conducted for periods similar to disease activity in allergic rhinitis/chronic idiopathic urticaria (_>14 days). In 8/28 single-dose studies, the HIWF data were collected <12hr post-dosing. CONCLUSIONS: Pharmacodynamic HIWF studies of second-generation antihistamines are heterogeneous. Most data describe the effects of singledose treatment in healthy patients, often shortly after dosing. Single-dose, short-term data in this simple pharmacologic model may not be reliable for predicting the clinical efficacy of antihistamines in the clinical disease state.
Funding: Schering-Plough Corp
1085
Group Discussions with Parents of Pre-schoo, Children-Positive Effects on the Management of Asthma
C. Hederos j, S. Janson z, G. Hedlin3; IBam-Ungdomsmedicin, Primary Care Research Unit VC Gripen, Karlstad, SWEDEN, 2VC Gripen, Primary Care Research Unit VC Gripen, Karlstad, SWEDEN, 3Astrid Lindgrens Hospital, Karolinska Institutet, Stockholm, SWEDEN. The aim was to evaluate if a program for parent support and information would improve adherence to treatment recommendations and the wellbeing of parents and children. Sixty children 1-6 years old with newly diagnosed asthma entered this study. Parents were randomized to either the intervention consisting of 4 meetings in a group setting during 6 months or to the traditional check-up visits at doctor's office. Follow-up visits were done up to 18 months. Sixty-five percent of the children were classified as moderate/severe asthmatics, 48% were RAST/skin prick test positive. 71% of the group attendants agreed at inclusion that the positive effects of asthma medicines surpassed the negative ones--after 18 months 85% had that opinion. In the control group the proportion was unchanged. The mothers in the intervention group had a significant rise in emotional, activity and over all index evaluated by Junipers PACQLQ (Paediatric Asthma Caregiver's Quality of Life Questionnaire). The adherence was poor in 8% of the children in the intervention group but in 30% in the control group (p=0,015). At 18 months 7% of the intervention group still belonged to the moderate/severe asthmatics (p=0,03) while 29% of the control group were classified as moderate/severe (N.S). The group attendants stayed home to take care of their children due to acute asthma in total 56 days less than the control parents during the last 6 months of the
Abstracts
8339
study. In conclusion the group session method resulted in more adherent. informed and satisfied parents and healthier children.
Funding: Primary Care Research Unit Karlstad
1086 ication Fanlily Recall of Treatment Plans and Its Relation to MedAdherence in Pediatric Asthma C, D. Adams I, K. E. Joseph j, T. Ash 1, C. Dotson l, N. W. Wilson2, M. B. Hogan2; )Department of Psychology, West Virginia University, Morgantown, WV, 2Department of Pediatrics, West Virginia University, Morgantown, WV. RATIONALE: Medication adherence amongst pediatric patients with asthma is known to be poor. We hypothesize that errors in family recall of asthma treatment plans will be associated with lower adherence levels to maintenance medication. METHODS: Participants included 35 patients (ages 5-18) with a new maintenance medication plan at the time of enrollment. Youth participated by completing a treatment plan recall interview after the clinic visit. This interview assessed knowledge regarding maintenance medications, allergies and allergen avoidance measures, and rescue plan for asthma episodes. Parents also participated in a separate recall interview. Adherence to inhaled steroids was measured via a MDILog-II device for several weeks (ie, 4-8) after the recall interviews. RESULTS: Treatment plan recall for rescue medications generally was good. In contrast, substantial recall errors for allergy avoidance measures and maintenance medication were found. These errors were significantly related to lower adherence to inhaled corticosteroids. In general, patient recall yielded more errors than parent recall. Finally, adherence levels overall were poor. CONCLUSIONS: Errors in the patients' and parents' recall of treatment plans may contribute to lower medication adherence in pediatric asthma patients. Common errors in recall should be targeted for improved family education efforts.
Funding: American Lung Association
1087
OratAntigen-inducedt,testina' AnaphytaxisRequirestgZdependent Mast Cell Degranulation
E. B. Brandt I, R. T. Strait 2, Q. Wang 3, D. Hershko 3, E. Muntel 1, F. D. Finkelman2,4, M. E. Rothenberg I; ]Division of Allergy and Immunology, Children's Hospital Medical Center, Cincinnati, OH, :University of Cincinnati, College of Medicine. Cincinnati, OH, 3Shriners Hospitals for Children, Cincinnati, OH, 4Veteran's Administration Medical Center, Cincinnati, OH. RATIONALE: This study investigates the molecular and cellular mechanisms involved in a novel model of oral allergen-induced intestinal anaphylaxis (accompanied by acute diarrhea). METHODS: Balb/c mice were sensitized with OVA/alum and then subjected to intragastric saline or OVA challenges. Mice were treated with either anti-cKit (ACK2) or a control antibody to eliminate mucosal mast cells (MMCs). Blocking antibody for FcgRII/RIII (24G2), anti-IgE antibody (EM95) and FceRl deficient mice were used to dissect the role of mast cells and lg. The molecular mediators of intestinal anaphylaxis were examined by employment of PAF, histamine and serotonin receptor antagonists. Levels of MMCs, MMC Protease I (MMCPI), Ig levels, and intestinal permeability (Ussing chamber) were assessed. RESULTS: Sequential intragastric OVA challenges resulted in dose dependent onset of acute diarrhea, accompanied by increased levels of OVA-specific lgGl/lgE, MMCs, and serum MMCPI. Mice treated with anti--cKit had no identifiable MMCs and serum MMCPI, and importantly were protected from oral antigen-induced intestinal permeability changes and diarrhea. Blocking lgG receptors had no effect, while the anti-IgE antibody eliminated diarrhea. Additionally, FceRl-deficient mice were resistant to diarrhea compared with wild-type mice. Finally, diarrhea was blocked by pre-treatment with a combination of histamine, PAE and serotonin receptor antagonists. CONCLUSIONS: Oral allergen-induced intestinal anaphylaxis, manifested by diarrhea, is mediated by lgE/FceRl-dependent mast cell mediator release. These observations open the way for the identification of the precise mediators, mechanisms, and therapeutics for gastrointestinal allergic disorders.
Funding: AHA, NIH, HFSP, ILSI, BWF