Table_1_Exercise Physiology Impairments of Patients With Amyotrophic Lateral Sclerosis: Cardiopulmonary Exercise Testing Findings.DOCX

Background and ObjectiveIn amyotrophic lateral sclerosis (ALS), progressive weakness significantly limits the ability to exercise. However, measurements of the impaired exercise function and their practical value to assess disease progression in ALS are scarce. Cardiopulmonary exercise testing (CPET) is a non-invasive accurate method used to comprehensively quantify exercise physiology in a variety of diseases. This study aimed to evaluate the clinical value of CPET and to explore its association with disease severity and prognosis prediction in ALS.
MethodsA total of 319 participants were enrolled in this 3-year prospective study. After strict quality control, 109 patients with ALS and 150 age- and sex-matched healthy controls were included with comprehensive clinical assessment and follow-ups. The incremental ramp protocol for symptom-limited CPET was applied in both groups. The exercise physiology during peak effort exercise was systematically measured, including the overall aerobic capacity of exercise (VO2 peak) and the respective capacity of the exercise-involved organs [cardiac response (heart rate peak—HR peak), ventilatory efficiency (VE/VCO2 slope), breathing economy (VE/VO2 peak), and other relevant parameters]. Disease severity and progression were evaluated using recognized scales. Survival was monitored with regular follow-ups every 6 months.
ResultsDecreased exercise capacity (VO2 peak < 16 ml/kg/min) occurred more frequently in patients with ALS than in controls (44.95% vs. 9.33%, p < 0.01). In patients with ALS, the average VO2 peak (16.16 ± 5.43 ml/kg/min) and HR peak [135 (112–153) bpm] were significantly lower (p < 0.01) than in controls [22.26 ± 7.09 ml/kg/min; 148 (135–164) bpm], but the VE/VCO2 slope was significantly higher [28.05 (25.03–32.16) vs. 26.72 (24.37–29.58); p = 0.03]. In patients with ALS, the VO2 peak and HR peak were significantly correlated with disease severity and progression scores (p < 0.05). Survival analyses revealed the VO2 peak and HR peak as protective indicators while the VE/VO2 peak as a detrimental indicator for the prognostic prediction in ALS (HR = 0.839, p = 0.001; HR = 0.967, p < 0.001; HR = 1.137, p = 0.028, respectively).
ConclusionOur prospective study quantified the significantly decreased exercise capacity in ALS through non-invasive CPET. The impaired VO2 peak and HR peak closely correlated with disease severity and independently predicted a worse prognosis. Our findings identified the clinical value of CPET as an objective indicator of disease progression in ALS.

背景与目的：肌萎缩侧索硬化（amyotrophic lateral sclerosis, ALS）患者会出现进行性肌无力，显著限制其运动能力，但目前针对ALS受损运动功能的评估指标，及其用于评估疾病进展的临床价值相关研究仍较为匮乏。心肺运动试验（cardiopulmonary exercise testing, CPET）是一种无创且精准的方法，可全面量化多种疾病状态下的运动生理学特征。本研究旨在评估CPET的临床应用价值，并探讨其与ALS患者疾病严重程度及预后预测的相关性。
方法：本项为期3年的前瞻性研究共纳入319名受试者。经过严格质量控制后，最终纳入109例ALS患者与150例年龄、性别匹配的健康对照者，所有受试者均接受全面临床评估与随访。两组均采用症状限制性递增斜坡方案进行CPET检测，系统测量极量运动时的运动生理学参数，包括整体有氧运动能力（峰值摄氧量，VO2 peak）、运动相关器官的功能储备[心脏反应（峰值心率，HR peak）、通气效率（VE/VCO2斜率）、呼吸经济性（VE/VO2 peak）及其他相关指标]。采用公认量表评估疾病严重程度与进展情况，每6个月定期随访以监测生存状态。
结果：ALS患者的运动能力下降（VO2 peak < 16 ml/kg/min）发生率显著高于对照组（44.95% vs. 9.33%，p < 0.01）。ALS患者的平均VO2 peak（16.16 ± 5.43 ml/kg/min）与HR peak[135（112–153）次/分]均显著低于对照组[22.26 ± 7.09 ml/kg/min；148（135–164）次/分]（均p < 0.01），但VE/VCO2斜率显著更高[28.05（25.03–32.16）vs. 26.72（24.37–29.58）；p = 0.03]。在ALS患者中，VO2 peak与HR peak与疾病严重程度及进展评分显著相关（p < 0.05）。生存分析显示，VO2 peak与HR peak为ALS预后预测的保护性指标，而VE/VO2 peak为有害性指标（风险比分别为0.839，p = 0.001；0.967，p < 0.001；1.137，p = 0.028）。
结论：本项前瞻性研究通过无创CPET量化证实，ALS患者的运动能力显著下降。受损的VO2 peak与HR peak与疾病严重程度密切相关，且可独立预测不良预后。本研究结果明确了CPET作为ALS疾病进展客观评估指标的临床应用价值。