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

呼吸系统疾病是唐氏综合症患者最常见的死亡原因。唐氏症儿童 综合症有很高的吸入风险，慢性吸入可导致呼吸道疾病，包括 肺炎、肺炎和支气管扩张。对非唐氏综合症儿童的流行病学研究表明 研究表明，儿童时期的呼吸健康是一生中呼吸健康的有力预测因素， 6岁时建立的肺健康轨迹。然而，人们对中国的肺部健康轨迹知之甚少。 儿童时期的吸入性疾病和肺部疾病如何导致一生中唐氏综合症的发病率。 为了在一生中改善呼吸健康，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反应。这项研究是对儿童的病例对照评价。 唐氏综合征患者有吸气者和不吸气者。这个项目的首要目标是 确定可在临床试验中用作结果测量的肺部发病率的可量化测量 旨在治疗和预防DS儿童的吸入。这将通过目标1进行测试：确定 示波法和肺活量测定法测定吸入对肺功能的影响 通过对唐氏综合征患儿进行6分钟步行试验，目的2：确定吸入疗法对唐氏综合征患儿的影响 DS患儿的炎性血液标记物。目标3：确定吸入对照顾者的影响-报道 呼吸道症状和生活质量。这个假说是吸入会引起肺部可测量的变化。 功能、炎症标志物和照顾者报告的症状和生活质量结果不同于 DS儿童的哮喘。这项研究将包括75名3至18岁患有DS的儿童，他们有 临床吞咽检查诊断误吸或无误吸。肺功能、呼吸道症状和质量 生命评估将在3-12个月后对40名参与者的子集进行重复。拟议的研究将 DS儿童的客观肺功能和呼吸道炎症测量的特征。建立 这些用于确定参与者身份和临床结果的措施将使临床试验的设计成为可能 减少吸入对肺功能和炎症的影响和减少呼吸道疾病的治疗 对于患有DS的儿童，这将改善他们一生中的呼吸健康。

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.