Mechanistic Study of Inspiratory Training in Childhood Asthma

儿童哮喘吸气训练机制研究

• 批准号: 10637048
• 负责人: Jason E. Lang
• 金额: $ 37.77万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10637048
• 关键词: 17 year old; Address; Adherence; Adult; Anti-Inflammatory Agents; Asthma; Automobile Driving; Cardiopulmonary; Chest; Child; Childhood; Childhood Asthma; Chronic; Clinical; Communities; Coughing; Data; Doctor of Philosophy; Dose; Dyspnea; Esthesia; Fatigue; Fostering; Functional disorder; Impairment; Inhalation; Intervention; Knowledge; Laboratory Finding; Link; Lung; Masks; Measures; Mechanics; Morbidity - disease rate; Muscle; Muscle Fatigue; Muscle function; Non obese; Obesity; Oscillometry; Participant; Pediatrics; Pharmaceutical Preparations; Phase II/III Trial; Phenotype; Play; Plethysmography; Prevalence; Public Health; Qualifying; Randomized; Regimen; Rehabilitation therapy; Reporting; Research; Research Personnel; Residual volume; Resistance; Respiration; Respiratory Mechanics; Respiratory Signs and Symptoms; Respiratory System; Rest; Risk Factors; Role; Sampling; Schools; Symptoms; Techniques; Testing; Thinness; Training; Training Programs; Wheezing; Work; Youth; airway inflammation; arm; asthmatic; conventional therapy; design; exercise capacity; exercise physiologist; experience; improved; multidisciplinary; muscle strength; non-drug; novel; obesity in children; obesity-associated asthma; phase III trial; pressure; recruit; rehabilitation science; response; stem; treatment comparison; treatment response; trend; trial design

PROJECT SUMMARY/ABSTRACT In children, asthma is a leading cause of respiratory symptoms and missed school. By mechanisms that are unclear, obesity in children with asthma is a strong risk factor for asthma that is more symptomatic and difficult to manage. Among asthmatic children, obesity is associated with a reduced response to conventional anti-inflammatory asthma drugs. Therefore, a better understanding of the underlying mechanisms of obesity-related asthma in children is needed. Discovering the mechanisms of `obese asthma' in order to foster more appropriate phenotype-specific therapies is a pressing public health need. Obesity, regardless of underlying asthma, is known to impair respiratory system compliance and inspiratory muscle efficiency leading to increases in the effort of respiration. Our lab found in asthmatic children that obesity is associated with more frequent asthma symptoms and a higher likelihood of having dyspnea. Inspiratory training and other forms of rehabilitation are common in adults but is understudied in pediatrics. Inspiratory `rehabilitation' training (IT) recently has been shown in both children and adults to reduce dyspnea and asthma symptoms. Our research team found IT over 6 weeks was well-tolerated, and led to improved inspiratory function and consistently improved trends in clinical measures, among children with asthma. The central objective of our proposed MICA (Mechanistic Study of Inspiratory Training in Childhood Asthma) study is to measure the effects of 8-weeks of IT on inspiratory function (strength and endurance) and small airway dysfunction measured by oscillometry in 6-17 year olds with asthma - with and without obesity. Our central hypothesis is that obesity promotes inspiratory muscle fatigue and small airway dysfunction, and that IT will mitigate these mechanisms. In a masked parallel arm trial, 75 youths with asthma (half with obesity) will be randomized to either IT (low or high dose) or SHAM control for 8-weeks. Inspiratory strength and endurance, small airway dysfunction (SAD), and exercise capacity will be assessed at baseline and after IT. Aim 1 will describe the contributions of inspiratory fatigue and SAD to obesity-related asthma. Aim 2 will determine the effects of IT on inspiratory muscle fatigue. Aim 3 will determine the effects of IT on small airway dysfunction. The MICA study will provide mechanistic knowledge about pediatric `obese asthma' by comparing treatment responses by obesity status. Measuring the changes in inspiratory muscle function and small airways dysfunction following a short regimen IT in children with symptomatic obesity-related asthma will provide much needed understanding about mechanisms underlying how obesity worsens asthma in children; and will uncover mechanisms and optimal dosing intensity involved in a safe non- drug intervention that will pave the way for larger phase III trials.

项目总结/摘要 在儿童中，哮喘是呼吸道症状和失学的主要原因。通过机制， 目前尚不清楚，哮喘儿童的肥胖是哮喘的一个强有力的危险因素， 并且难以管理。在哮喘儿童中，肥胖与对 常规的抗炎哮喘药。因此，更好地了解潜在的 儿童肥胖相关性哮喘的发病机制。发现“肥胖”的机制 为了促进更合适的表型特异性治疗，哮喘是一个紧迫的公共卫生 需要的肥胖，不管潜在的哮喘，已知会损害呼吸系统的顺应性， 吸气肌肉效率导致呼吸努力的增加。我们的实验室在哮喘患者中发现 儿童肥胖与更频繁的哮喘症状和更高的可能性有关， 有呼吸困难。吸气训练和其他形式的康复在成年人中很常见， 在儿科学中是替补最近，在两个地区都显示了吸气式“康复”训练（IT）。 儿童和成人，以减少呼吸困难和哮喘症状。我们的研究团队发现， 耐受性良好，导致吸气功能改善，临床趋势持续改善 在哮喘儿童中采取措施。我们提出的云母（机械研究）的中心目标 儿童哮喘吸气训练）研究的目的是测量8周IT对 吸气功能（力量和耐力）和小气道功能障碍， 6-17患有哮喘的10岁奥尔兹-有和没有肥胖。我们的中心假设是肥胖促进 吸气肌疲劳和小气道功能障碍，IT将减轻这些机制。 在一项设盲的平行组试验中，75名患有哮喘的年轻人（其中一半患有肥胖症）将被随机分为两组， (low或高剂量）或SHAM对照持续8周。吸气强度和耐力，小气道 将在基线和IT后评估功能障碍（SAD）和运动能力。目标1将描述 吸气性疲劳和SAD对肥胖相关性哮喘的影响。目标2将决定 IT对吸气肌疲劳的影响。目标3将确定IT对小气道的影响 功能障碍云母研究将通过以下方式提供关于儿童“肥胖性哮喘”的机制知识： 通过肥胖状态比较治疗反应。测量吸气肌功能的变化 在症状性肥胖相关的儿童中接受短期IT方案后， 哮喘将提供关于肥胖是如何引起哮喘的机制的迫切需要的理解。 儿童哮喘;并将揭示机制和最佳剂量强度参与安全的非 这将为更大规模的III期临床试验铺平道路。