Phenotypes and Endotypes of Preschool Wheeze

学龄前喘息的表型和内型

• 批准号: 10092222
• 负责人: Anne Mentro Fitzpatrick
• 金额: $ 49.33万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-03 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092222
• 关键词: 6 year old; Address; Adrenal Cortex Hormones; Adult; Affect; Age; Allergic; Area; Asthma; Basic Science; Biological; Biological Markers; Biological Products; Biology; Caregivers; Cells; Characteristics; Child; Childhood; Childhood Asthma; Clinical; Clinical Trials; Cohort Studies; Collaborations; Disease; Disease Outcome; Economic Burden; Emergency department visit; Future; Goals; IgE; Immune; Immunologics; Impairment; Inflammation; Inflammatory; Interleukin-5; Intervention Studies; Knowledge; Life; Link; Molecular; Morbidity - disease rate; Nursery Schools; Outcome; Outpatients; Pathway interactions; Pharmacotherapy; Phenotype; Plasma; Preschool Child; Prevalence; Probability; Public Health; Recording of previous events; Recurrence; Research; Respiration Disorders; Schools; Strategic Planning; Symptoms; Syndrome; Testing; Time; Viral; Virus; Wheezing; Work; age group; airway obstruction; anti-IgE; base; cost; cytokine; eosinophil; experience; functional status; hospitalization rates; improved; metabolomics; multidisciplinary; neutrophil; personalized approach; personalized intervention; personalized medicine; predictive modeling; primary outcome; response; secondary outcome; study population; symptom science; treatment response

PROJECT SUMMARY/ABSTRACT The prevalence of wheezing in preschool children has increased dramatically over the past three decades, resulting in a public health crisis. Nearly 50% of all preschool children experience at least one episode of wheezing before 6 years of age and up to 20% of all preschool children have recurrent wheezing episodes in early life associated with significant morbidity. Compared to older children, preschool children have twice the rate of emergency department visits, five times the rate of hospitalizations, and higher costs. Although preschool children with recurrent wheezing are a heterogeneous group with differing disease outcomes, there is a paucity of research in this age group and the associated biology of exacerbation and related outcomes in these children is not understood. Segmentation of preschool children with recurrent wheezing for the purpose of basic research is therefore one of the main research challenges in pediatric airway research today, since at present, the clinical course of preschool children with recurrent wheezing remains an enigma that is impossible to predict. Given our broad goal to advance personalized medicine for all children with respiratory disorders, we propose a 50-week phenotype-stratified cohort study (N=145) to determine whether phenotypic (i.e., clinical) and associated endotypic (i.e., biological) features predict wheeze exacerbation and related outcomes in preschool children age 12-59 months with a history of recurrent wheezing. We will pursue three aims: 1) determine whether wheezing phenotype predicts exacerbation occurrence (primary outcome), 2) determine whether wheezing phenotype predicts episode-free days (EFDs) and response to treatment with systemic corticosteroids (secondary outcomes), and 3) refine the prediction model for wheeze exacerbation with endotyping approaches (cytokines, metabolomics and immune cell studies). We hypothesize that a higher proportion of children with Type-2 (i.e., eosinophilic) inflammatory features will experience an exacerbation irrespective of viral status, and that these same children will have fewer EFDs, a higher proportion of virus- associated exacerbations, a greater response to treatment with systemic corticosteroids, and distinguishing cytokine profiles, plasma metabolomic biomarkers and markers of neutrophil and eosinophil activation and function. This project involves a multidisciplinary team with a history of collaboration and addresses a key area in the NINR Strategic Plan: to explore mechanisms underlying symptoms of illness and develop personalized treatments that address these mechanisms through symptom science research. The study population, preschool children with recurrent wheezing, is understudied and the knowledge gap is quite large. This project is ultimately expected to lay groundwork to: 1) refine knowledge of wheeze exacerbation and associated mechanisms, 2) improve clinical prediction of exacerbation and related outcomes, and 3) identify biomarkers of exacerbation that can be targeted in the future with personalized approaches, to reduce the high morbidity.

项目摘要/摘要 在过去的三十年中 导致公共卫生危机。在所有学龄前儿童中，近50％至少经历了一集 在6岁之前喘息，最多20％的学龄前儿童会在 早期生活与明显的发病率有关。与大孩子相比，学龄前儿童有两倍 急诊务访问率，住院率的五倍，成本更高。虽然 复发性喘息的学龄前儿童是一个异质群体，有不同的疾病结果， 是该年龄段的研究很少，并且与加剧和相关结果的相关生物学相关的生物学 这些孩子不理解。针对此目的的复发性喘息的学龄前儿童的细分 因此，基础研究是今天儿科气道研究的主要研究挑战之一，因为 目前，复发性喘息的学龄前儿童的临床课程仍然是不可能的 预测。鉴于我们为所有呼吸系统疾病儿童推进个性化医学的广泛目标， 我们提出了一项为期50周的表型分层研究（n = 145），以确定是否表型（即 临床）和相关的内型（即生物学）特征预测喘息的恶化和相关结果 在学龄前儿童中，有12-59个月的喘息病史。我们将追求三个目标：1） 确定喘息的表型是否预测了加剧的发生（主要结果），2）确定 喘息的表型是否预测无情节日（EFD）和对全身治疗的反应 皮质类固醇（次要结果）和3）完善喘息的预测模型 内型方法（细胞因子，代谢组学和免疫细胞研究）。我们假设更高 2型儿童（即嗜酸性粒细胞）炎症特征的比例会遭受恶化 不论病毒地位如何，这些相同的孩子的EFD较少，病毒的比例较高 相关的加剧，对全身性皮质类固醇治疗的反应更大，并区分 细胞因子谱，血浆代谢组生物标志物以及嗜中性粒细胞和嗜酸性粒细胞活化的标志物以及 功能。该项目涉及一个具有协作历史的多学科团队，并解决了关键领域 在NINR战略计划中：探索疾病症状潜在的机制并发展个性化的机制 通过症状科学研究来解决这些机制的治疗方法。研究人群， 复发性喘息的学龄前儿童被研究了，知识差距很大。这个项目 最终期望为：1）提高喘息的知识和相关性 机制，2）改善加重和相关结果的临床预测，3）确定生物标志物 将来可以通过个性化方法来降低发病率高的方法。