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.

项目摘要/摘要 在儿童中，哮喘是呼吸道症状的主要原因和错过上学的原因。通过机制 尚不清楚，哮喘儿童的肥胖是哮喘的强大危险因素，这是更有症状的 并且难以管理。在哮喘儿童中，肥胖与对 常规的抗炎哮喘药物。因此，更好地理解了基础 需要儿童与肥胖有关的机制。发现肥胖的机制 哮喘'为了促进更合适的表型特异性疗法是一种紧迫的公共卫生 需要。肥胖，无论潜在哮喘如何，都会损害呼吸系统依从性和 灵感肌肉效率导致呼吸努力的提高。我们的实验室在哮喘中发现 肥胖的孩子与更频繁的哮喘症状有关 患有呼吸困难。灵感训练和其他形式的康复形式在成人中很常见，但 在儿科研究。吸气性“康复”训练（IT）最近在 儿童和成人减少呼吸困难和哮喘症状。我们的研究团队发现了6周 耐受性良好，并提高了灵感功能，并持续改善临床趋势 措施，哮喘儿童。我们提议的云母的核心目标（机械研究 童年哮喘的灵感训练）研究是测量其8周的影响 灵感功能（强度和耐力）和小型气道功能障碍通过振荡测量 6-17岁的患有哮喘 - 有和没有肥胖症。我们的中心假设是肥胖促进 鼓舞性的肌肉疲劳和小气道功能障碍，它将减轻这些机制。 在一项蒙面的平行手臂试验中，有75名患有哮喘的年轻人（一半的肥胖症）将被随机分配给 （低剂量或高剂量）或8周的假控制。灵感强度和耐力，小气道 功能障碍（SAD）和运动能力将在基线和之后进行评估。目标1将描述 吸气疲劳和对与肥胖有关的哮喘的贡献。 AIM 2将确定 它对吸气肌肉疲劳的影响。 AIM 3将确定其对小气道的影响 功能障碍。云母研究将提供有关小儿“肥胖哮喘”的机械知识 比较肥胖状态的治疗反应。测量灵感肌肉功能的变化 与肥胖有关 哮喘将为肥胖如何恶化的基础机制提供急需的理解 儿童哮喘；并将发现与安全非 - 药物干预将为大型III期试验铺平道路。