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A Histamine Pharmacodynamic Biomarker to Guide Treatment in Pediatric Asthma

指导小儿哮喘治疗的组胺药效生物标志物

基本信息

批准号：
10624863
负责人：
BRIDGETTE L. JONES
金额：
$ 51.17万
依托单位：
CHILDREN'S MERCY HOSP (KANSAS CITY, MO)
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-05 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10624863
关键词：
Adrenal Glands Adverse effects African American Allergens Allergic Antibody Therapy Antihistamines Asthma Biological Markers Biological Response Modifiers Blood Bronchoconstriction Caucasians Cell Adhesion Molecules Cessation of life Chemotaxis Child Childhood Childhood Asthma Chronic Disease Clinical Clinical Markers Data Decision Making Disease Effectiveness Emergency department visit Enzymes Exhalation Exhibits Exposure to Extrinsic asthma Functional disorder Generations Genes Genetic Genetic Polymorphism Genotype Goals Guidelines Histamine Histamine Receptor Hypersensitivity IgE Immunologic Markers Immunologics Individual Inhalation Iontophoresis Knowledge Lasers Leukotrienes Link Literature Modeling Monitor Monoclonal Antibodies Moods Morbidity - disease rate Mucous body substance Nitric Oxide Nucleotides Outcome Pathway interactions Patient Selection Patients Pharmaceutical Preparations Pharmacodynamics Phenotype Prediction of Response to Therapy Production Race Regimen Reproducibility Research Safety Single Nucleotide Polymorphism Steroids Techniques Testing Therapeutic Therapeutic Intervention Treatment Efficacy United States Weight Gain Work biomarker validation chemokine clinical biomarkers cost cytokine disease phenotype eosinophil experience immunoregulation improved innovation mortality risk neutrophil novel omalizumab pediatric patients pharmacodynamic biomarker predicting response predictive marker predictive modeling pulmonary function racial population response side effect skin prick test success therapy outcome treatment response

项目摘要

Abstract There is a critical need for validated objective biomarkers that predict therapeutic response for asthma therapies in children. Children who require daily asthma treatment with a controller medication such as an inhaled steroid are defined to have persistent asthma. Approximately 60% of children with asthma in the United States have persistent disease. Variability in treatment response to standard guideline supported medications (e.g. inhaled steroids, leukotriene modifiers, mono-clonal antibodies) exist among children with persistent asthma. Clinical markers such as IgE level, exhaled nitric oxide level, eosinophil and neutrophil counts have not been validated to predict treatment response to asthma medications in children. It is not possible to optimize currently available treatments for asthma in achieving therapeutic efficacy and limiting exposure to adverse effects from non-efficacious medications without robust non-invasive biomarkers that can drive therapeutic decision making. The long-term goal is to advances and improve therapeutic intervention for pediatric patients with asthma. The objective in this particular application is to establish the utility of Histamine Iontophoresis with Laser Doppler monitoring (HILD) as biomarker for accurate prediction of therapeutic response to low cost and low side-effect antihistamine treatment in children with allergic asthma. The central hypothesis is that “HILD is predictive of treatment response to an antihistamine in children with asthma”. This hypothesis has been formulated by the applicant's strong preliminary data and supporting literature. The rationale for the proposed research is that HILD is able to identify distinct histamine pharmacodynamic response types that predict treatment response to antihistamine medications in asthma. Guided by strong preliminary data, this hypothesis will be tested by two specific aims: 1) to determine HILD prediction of therapeutic response to an antihistamine among children with allergic asthma; 2) to develop a robust predictive model of therapeutic response to an antihistamine among children with allergic asthma. The first aim will compare change in Asthma Control Test (ACT®) scores by histamine response type in a six week, 2x2 cross-over, add-on trial of Levocetirizine (LTZ) among children with uncontrolled allergic asthma. The second aim will determine the best predictive model (incorporating HILD and clinical variables) for change in ACT® scores after LTZ treatment among children with allergic asthma. The proposed research is significant because it has the potential to alter the current treatment paradigms for children with asthma where response to treatment is predicted a priori; and is innovative in testing and validating a first biomarker accurately predicting response to an asthma treatment in children. The knowledge gained will make available the first validated biomarker to predict treatment response in children with asthma and will improve therapeutic efficacy and outcomes in these children.

摘要