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.

项目概要/摘要 对于儿童来说，哮喘是导致呼吸道症状和缺课的主要原因。通过机制 目前尚不清楚，哮喘儿童的肥胖是哮喘症状的一个强烈危险因素 并且难以管理。在哮喘儿童中，肥胖与对哮喘的反应降低有关 常规抗炎哮喘药物。因此，更好地了解底层 需要了解儿童肥胖相关哮喘的机制。发现“肥胖”的机制 哮喘”以促进更合适的表型特异性治疗是一个紧迫的公共卫生问题 需要。众所周知，肥胖，无论是否有潜在的哮喘，都会损害呼吸系统的顺应性和 吸气肌效率导致呼吸努力增加。我们的实验室发现哮喘 儿童肥胖与更频繁的哮喘症状和更高的可能性相关 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，但 儿科本科生。吸气“康复”训练（IT）最近已在 儿童和成人可减轻呼吸困难和哮喘症状。我们的研究团队在 6 周内发现了 IT 耐受性良好，并导致吸气功能改善和临床趋势持续改善 哮喘儿童的措施。我们提出的 MICA（机制研究）的中心目标 儿童哮喘吸气训练）研究旨在衡量 8 周的 IT 对呼吸训练的影响 通过示波法测量吸气功能（力量和耐力）和小气道功能障碍 患有哮喘的 6-17 岁儿童 - 有或没有肥胖。我们的中心假设是肥胖会促进 吸气肌疲劳和小气道功能障碍，IT 将减轻这些机制。 在一项匿名平行试验中，75 名患有哮喘的青少年（一半患有肥胖症）将被随机分配到任一 IT 组 （低剂量或高剂量）或 SHAM 对照 8 周。吸气强度和耐力，小气道 功能障碍 (SAD) 和运动能力将在基线时和 IT 后进行评估。目标 1 将描述 吸气疲劳和 SAD 对肥胖相关哮喘的影响。目标 2 将确定 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。 MICA 研究将提供有关儿科“肥胖哮喘”的机制知识 根据肥胖状况比较治疗反应。测量吸气肌功能的变化 与肥胖相关症状的儿童接受短期 IT 治疗后出现的小气道功能障碍 哮喘将提供人们急需的关于肥胖恶化机制的理解 儿童哮喘；并将揭示安全非相关机制和最佳剂量强度 药物干预将为更大规模的 III 期试验铺平道路。