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.

项目概要 心肺运动测试（CPET）是一种客观、非侵入性的综合功能测量方法 CPET 评估肺、心血管和神经肌肉系统。 反应，告知呼吸困难和/或疲劳的原因、疾病预后和/或进展、治疗前或治疗后 手术风险分层或运动训练处方估计会增加。 2005 年至 2015 年间增加了 81%。CPET 解释最常见的问题是区分 心血管疾病和神经肌肉失调，例如肌肉质量低、虚弱和/或易疲劳。 我们开发了一个解决方案来解决这个问题，使用带有集成等速 (IK) 的改良 CPET 肌肉力量测量，独立评估神经肌肉表现，无需 影响标准 CPET 变量的测量 修改后的 CPET 比标准 CPET 增加了 <10 分钟。 并使用改进的 CPET 产生 4 个新的 IK 变量：1) 基线峰值。 等速功率：失调的肌肉较弱；2）耐受指数：峰值 IK 功率的分数 V̇O2peak 有氧运动失调会降低有氧运动可支持的可用峰值 IK 功率。 新陈代谢；3) 疲劳指数：在给定的工作速率下，峰值 IK 功率的损失增加。 疲劳性； 4) 功率储备：在 V̇O2peak 时急剧增加功率的能力。 改进的 CPET 的神经肌肉性能不仅限于运动耐量，具有良好的可重复性。 老年人、正常人和运动员以及患有心力衰竭或慢性阻塞性肺病的人可以耐受改良的 CPET。 可以区分作为运动限制原因的神经肌肉失调与心血管或 肺部限制（通过标准 CPET 评估） 为了为临床解释提供信息，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（具有相应的敏感性和特异性）将为 开发和优化以区分调节神经肌肉的变量。 将确定与失调相关的表现测量（例如 V̇O2peak、舒张功能障碍、 血管反应性、腿部肌肉质量、腿部力量和力量、肌肉氧化能力和肌肉活检 最后，将通过测量来测试 IK 变量对去适应的辨别能力。 IK 变量对身体状况不佳的个体运动训练的敏感性以及 IK 的特异性 使用侵入性 CPET 区分患者外周血流动力学运动限制与中枢血流动力学运动限制的变量 这项研究将改变心力衰竭和保留射血分数的实用性和诊断能力。 CPET 并改善各种慢性疾病的临床决策和严重程度分层 状态失调是一个共同特征的州。