Identifying Measures of Pulmonary Morbidity for Clinical Trials in Children with Down Syndrome and Aspiration

唐氏综合症和误吸儿童临床试验中确定肺部发病率的指标

• 批准号: 9894579
• 负责人: Emily M DeBoer
• 金额: $ 18.61万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9894579
• 关键词: 6 year old; Affect; Airway Resistance; Allergic inflammation; Aspirate substance; Asthma; Blood; Breathing; Bronchiectasis; Bronchodilator Agents; C-reactive protein; Caregivers; Case-Control Studies; Cause of Death; Characteristics; Child; Childhood; Childhood Asthma; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Collaborations; Colorado; Conduct Clinical Trials; Data; Deglutition; Diagnosis; Down Syndrome; Evaluation; Exercise Tolerance; Future; General Population; Goals; Gold; Health; IgE; Individual; Inflammation; Inflammatory; Institutes; Institution; Intellectual functioning disability; Lead; Liquid substance; Longevity; Lung; Lung Inflammation; Lung diseases; Measurable; Measurement; Measures; Morbidity - disease rate; Muscle hypotonia; Oscillometry; Outcome; Outcome Measure; Participant; Patients; Pediatric Hospitals; Phenotype; Physician Executives; Pneumonia; Population; Positioning Attribute; Prevalence; Prevention; Principal Investigator; Pulmonary Inflammation; Quality of life; Quality-of-Life Assessment; Questionnaires; Readiness; Reporting; Research Personnel; Respiratory Signs and Symptoms; Respiratory physiology; Spirometry; Structural defect; Symptoms; Testing; Walking; Work; airway inflammation; case control; clinical care; eosinophil; epidemiology study; high risk; immune function; improved; inflammatory marker; mortality; multidisciplinary; neutrophil; prevent; pulmonary function; respiratory health; response; vocal cord

Respiratory disease is the most common cause of death in people with Down syndrome. Children with Down syndrome have a high risk of aspiration, and chronic aspiration can lead to respiratory diseases including pneumonitis, pneumonia, and bronchiectasis. Epidemiological studies in children without Down syndrome have shown that respiratory health in childhood is a strong predictor of respiratory health across the lifespan, with trajectories of lung health established by age 6 years. However, little is known about lung health trajectories in DS or how aspiration and lung disease in childhood leads to morbidity in Down syndrome across the lifespan. To improve respiratory health over the lifespan, this study aims to determine the effect of aspiration on lung function and inflammation in children with Down syndrome. This study is a case-control evaluation of children with Down syndrome who aspirate and those who do not aspirate. The overarching goal of this project is to identify quantifiable measures of pulmonary morbidity that can be used as outcome measures in clinical trials designed to treat and prevent aspiration in children with DS. This will be tested through AIM 1: Determine the effect of aspiration on lung function measured by oscillometry and spirometry with bronchodilator response and by six-minute walk in children with Down syndrome, and AIM 2: Determine the effect of aspiration on inflammatory blood markers in children with DS. AIM 3: Determine the effect of aspiration on caregiver-reported respiratory symptoms and quality of life. The hypothesis is that aspiration causes measurable changes in lung function, inflammatory markers, and caregiver-reported symptom and quality of life outcomes distinct from asthma in children with DS. The study will include 75 children between 3 and 18 years with DS who have had a clinical swallow study diagnosing aspiration or no aspiration. The lung function, respiratory symptom, and quality of life assessments will be repeated after 3-12 months for a subset of 40 participants. The proposed study will characterize objective lung function and airway inflammation measurements in children with DS. Establishing these measures for participant identification and clinical outcomes will enable the design of clinical trials that test treatments to diminish the effects of aspiration on lung function and inflammation and reduce respiratory disease in children with DS, which will improve respiratory health across their lifespan.

呼吸系统疾病是唐氏综合症患者最常见的死亡原因。儿童Down 综合征有很高吸入风险，长期吸入可导致呼吸系统疾病，包括 肺炎、肺炎和支气管扩张。对非唐氏综合征儿童的流行病学研究表明， 儿童期的呼吸健康是整个生命周期呼吸健康的强有力预测因素， 6岁时建立的肺部健康轨迹。然而，对肺健康轨迹知之甚少， DS或儿童期的吸入和肺部疾病如何导致唐氏综合征在整个生命周期中的发病率。 为了改善生命周期中的呼吸健康，本研究旨在确定吸入对肺的影响 唐氏综合征患儿的功能和炎症。本研究是一项儿童病例对照研究 患有唐氏综合症的人吸气和不吸气。该项目的总体目标是 确定可用作临床试验结局指标的肺部发病率的可量化指标 旨在治疗和预防DS儿童的误吸。这将通过AIM 1进行测试：确定 吸入对肺功能的影响，通过肺功能测定法和肺功能测定法测量， 目的2：确定吸入对唐氏综合征儿童的影响， DS患儿的炎症性血液标志物。目的3：确定误吸对护理人员报告的影响 呼吸道症状和生活质量。假设是误吸导致肺部可测量的变化 功能，炎症标志物，以及患者报告的症状和生活质量结果， DS患儿的哮喘这项研究将包括75名3至18岁的DS儿童，他们有一个 临床吞咽研究，诊断是否有吸入。肺功能、呼吸道症状和质量 将在3-12个月后对40名受试者的子集重复进行生命评估。拟定的研究将 描述DS儿童的客观肺功能和气道炎症测量。建立 这些用于参与者识别和临床结果的措施将使临床试验的设计能够测试 减少吸入对肺功能和炎症的影响并减少呼吸系统疾病的治疗 在患有DS的儿童中，这将改善他们一生的呼吸健康。