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.

项目总结 心肺运动试验(CPET)是一种客观、非侵入性的运动功能测试方法。 肺、心血管和神经肌肉系统。CPET评估次极量和最大运动量 反应，告知呼吸困难和/或疲劳的原因，疾病预后和/或进展，在 手术风险分层，或运动训练处方。据估计，CPET的临床应用有所增加 2005至2015年间增长了81%。CPET解释最常见的问题是区分 心血管疾病和神经肌肉脱条件，如肌肉萎缩、虚弱和/或疲劳性。 我们已经开发了一个解决这个问题的方案，使用了一种改进的CPET与集成等速(IK) 肌肉力量的测量，它独立地评估神经肌肉性能，而不是 影响标准CPET变量的测量。改进后的CPET在标准CPET的基础上增加了10分钟 并使用商业上可用的设备。修改后的CPET产生4个新的IK变量：1)基线峰值 等速肌力：去条件肌较弱；2)耐力指数： V̇O2峰。有氧去条件反射降低了有氧可以支持的可用的峰值IK功率 新陈代谢；3)疲劳指数：在给定的工作速率下的峰值功率损失。好氧脱臭增加 疲劳性；4)功率储备：在V̇O2峰值时的急剧功率增加的能力。动力储备表明 神经肌肉表现并不局限于运动耐力。改进后的CPET具有较好的重复性 老年人、正常受试者、运动员以及心力衰竭或慢性阻塞性肺病患者均可耐受。改进型CPET 可以将神经肌肉去条件反射作为运动受限的原因与心血管疾病或 肺限制(由标准CPET评估)。为了向临床解释提供信息，这个项目将开发 描述18-80岁男性和女性的IK变量正常参考值的预测模型。 神经肌肉功能的阈值(具有相应的敏感性和特异性)将为 发展和优化，以区别对待脱离条件的人口。适中神经肌肉的变量 将确定与解除条件相关的绩效指标(例如，V̇O2峰值、舒张期功能障碍、 血管反应性、腿部瘦肉质量、腿部力量和力量、肌肉氧化能力和肌肉活检 形态)。最后，通过测量来检验IK变量对去条件化的区分能力 运动训练对运动训练敏感性及特异度的研究 有创CPET用于区分外周和中枢血流动力学运动受限的变量 有心力衰竭和完好的射血分数。这项研究将改变实用程序和诊断能力 CPET，改善临床决策和各种慢性病的严重程度分层 解除条件是一种常见特征的州。