Novel cardiopulmonary exercise testing variables to differentiate neuromuscular deconditioning from disease

新型心肺运动测试变量可区分神经肌肉功能失调与疾病

• 批准号: 10736044
• 负责人: Harry B Rossiter
• 金额: $ 75.74万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736044
• 关键词: Abdomen; Acute; Aerobic; Affect; Biopsy; Blood Pressure; Blood Vessels; Cardiopulmonary; Cardiopulmonary Physiology; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Caring; Cell Respiration; Chest; Chronic Disease; Chronic Obstructive Pulmonary Disease; Clinical; Clinical assessments; Data; Diagnosis; Diagnostic; Disease; Disease Progression; Dual-Energy X-Ray Absorptiometry; Dyspnea; EFRAC; Echocardiography; Education; Elderly; Electrocardiogram; Enrollment; Equation; Equipment; Exercise; Exercise Test; Exercise Tolerance; Fatigue; Functional disorder; Gases; Guidelines; Health system; Heart Diseases; Heart Transplantation; Heart failure; Individual; Interruption; Intervention; Isotonic Exercise; Leg; Life Expectancy; Lung; Measurement; Measures; Monitor; Morphology; Muscle; Muscle Weakness; Muscular Atrophy; Neuromuscular Diseases; Normal Range; Normalcy; Operative Surgical Procedures; Outcome; Participant; Patients; Performance; Peripheral; Population; Postoperative Period; Prognosis; Property; Protocols documentation; Publishing; Pulmonary Gas Exchange; Pulse Oximetry; Race; Reference Values; Rehabilitation therapy; Reproducibility; Rest; Sampling; Sensitivity and Specificity; Severities; Skeletal Muscle; Specificity; Speed; Stratification; Stress; System; Technology; Testing; Therapeutic; Thinness; Training; Training Programs; Translating; Triage; Woman; Work; age stratification; aged; clinical decision-making; clinical practice; clinical prognostic; deconditioning; demographics; diagnostic value; disease prognosis; exercise intolerance; exercise training; experience; heart preservation; hemodynamics; improved; indexing; laboratory experiment; male; manufacturing test; men; muscle form; neuromuscular; neuromuscular function; neuromuscular system; novel; predictive modeling; preservation; pulmonary function; reduced muscle mass; response; risk stratification; sex

PROJECT SUMMARY Cardiopulmonary exercise testing (CPET) is an objective, non-invasive, measure of the integrated function of the pulmonary, cardiovascular and neuromuscular systems. CPET evaluates submaximal and peak exercise responses, informing on causes of dyspnea and/or fatigue, disease prognosis and/or progression, pre- or post- surgical risk stratification, or exercise training prescription. Clinical use of CPET is estimated to have increased by 81% between 2005 and 2015. The most common problem for CPET interpretation is discriminating between cardiovascular disease and neuromuscular deconditioning e.g., low muscle mass, weakness and/or fatigability. We have developed a solution to this problem, using a modified CPET with integrated isokinetic (IK) measurements of muscle power, which independently assesses neuromuscular performance without affecting measurement of standard CPET variables. The modified CPET adds <10min to the standard CPET and uses commercially available equipment. The modified CPET produces 4 new IK variables: 1) Baseline peak isokinetic power: deconditioned muscles are weak; 2) Tolerance index: the fraction of peak IK power at V̇O2peak. Aerobic deconditioning reduces the available peak IK power that can be supported by aerobic metabolism; 3) Fatigue index: The loss of peak IK power for a given work rate. Aerobic deconditioning increases fatigability; 4) Power reserve: The capacity for acute power increase at V̇O2peak. A power reserve indicates that neuromuscular performance is not limiting to exercise tolerance. The modified CPET is reproducible and well tolerated by elderly, normal subjects and athletes, and those with heart failure or COPD. The modified CPET can differentiate neuromuscular deconditioning as a cause of exercise limitation from cardiovascular or pulmonary limitations (assessed by standard CPET). To inform clinical interpretation, this project will develop predictive models describing normal reference values for IK variables in men and women aged 18-80yr. Threshold values of neuromuscular performance (with corresponding sensitivity and specificity) will be developed and optimized to discriminate a deconditioned population. Variables that moderate neuromuscular performance measures associated with deconditioning will be identified (e.g. V̇O2peak, diastolic dysfunction, vascular reactivity, leg lean mass, leg strength and power, muscle oxidative capacity and muscle biopsy morphology). Finally, the discriminative ability of IK variables for deconditioning will be tested by measuring sensitivity of IK variables in response to exercise training in deconditioned individuals and the specificity of IK variables to discriminate peripheral vs. central hemodynamic exercise limitations using invasive CPET in patients with heart failure and preserved ejection fraction. This study will transform the utility and diagnostic capabilities of CPET and improve clinical decision-making and severity stratification across a wide range of chronic disease states where deconditioning is a common feature.

项目摘要 心肺运动测试（CPET）是客观的，无创的，衡量的综合功能 肺，心血管和神经肌肉系统。 CPET评估次最大和高峰锻炼 回答，了解呼吸困难和/或疲劳的原因，疾病进展和/或进展，前或之后 手术风险分层或运动训练处方。估计CPET的临床用途已增加 在2005年至2015年之间，达到81％。CPET解释的最常见问题是区分 心血管疾病和神经肌肉衰减，例如低肌肉质量，无力和/或疲劳性。 我们使用具有集成的同动剂（IK）的修改后的CPET开发了解决此问题的解决方案。 肌肉力量的测量，可独立评估神经肌肉性能 影响标准CPET变量的测量。修改后的CPET向标准CPET添加了<10分钟 并使用市售的设备。修改后的CPET产生4个新的IK变量：1）基线峰 同动力：肌肉弯曲的肌肉很弱； 2）公差指数：峰值IK功率的比例 vïo2peak。有氧运动降低了可用的峰值IK功率，该功率可以由有氧运动支持 代谢; 3）疲劳指数：给定工作率的IK峰值功率损失。有氧运动增加 疲劳； 4）动力储备：VİO2PEAK时急性功率增加的能力。动力储备表明 神经肌肉性能并非限制运动耐受性。修改后的CPET可再现且很好 由老年人，正常的受试者和运动员以及心力衰竭或COPD的运动员容忍。修改后的CPET 可以区分神经肌肉缩减作为导致运动限制的原因与心血管或 肺部局限性（通过标准CPET评估）。为了告知临床解释，该项目将开发 描述18-80岁男性和女性IK变量正常参考值的预测模型。 神经肌肉性能的阈值（具有相应的灵敏度和特异性）将是 开发和优化以区分被污染的人群。现代化神经肌肉的变量 将确定与调节性相关的性能指标（例如，vïo2peak，舒张功能障碍， 血管反应性，腿部质量，腿部强度和力量，肌肉氧化能力和肌肉活检 形态学）。最后，将测量IK变量对结论的判别能力进行测试 IK变量响应于decondientition的个体的运动训练和IK的特异性的敏感性 使用患者使用侵入性CPET区分外围与中央血液动力学局限性的变量 具有心力衰竭和保留的射血分数。这项研究将改变效用和诊断功能 CPET并改善各种慢性疾病的临床决策和严重性分层 调节是一个共同特征的状态。