AUTHOR=He Ji , Fu Jiayu , Zhao Wei , Ren Chuan , Liu Ping , Chen Lu , Li Dan , Zhou Lequn , Tang Lu , Liu Xiangyi , Ye Shan , Liu Xiaolu , Ma Yan , Zhang Yixuan , Ma Xinran , Zhang Linjing , Zhang Gaoqi , Li Nan , Fan Dongsheng 

TITLE=Exercise Physiology Impairments of Patients With Amyotrophic Lateral Sclerosis: Cardiopulmonary Exercise Testing Findings

JOURNAL=Frontiers in Physiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.792660

DOI=10.3389/fphys.2022.792660

ISSN=1664-042X

ABSTRACT=Background and Objective: In amyotrophic lateral sclerosis (ALS), progressive weakness significantly limits the exercise ability. However, measurements of the impaired exercise function and their practical value to assess disease progression in ALS is scarce. Cardiopulmonary exercise testing (CPET) is a non-invasive accurate method to comprehensively quantify the exercise physiology in a variety of diseases. This study aims to evaluate the clinical value of CPET, and to explore its association with disease severity and prognosis prediction in ALS.
Methods: A 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 (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-month. 
Results: Decreased exercise capacity (VO2 peak < 16 ml/kg/min) occurred more frequently in ALS patients than in controls (44.95% vs. 9.33%, p < 0.01). In ALS patients, 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, VO2 peak and HR peak were significantly correlated with disease severity and progression scores (p<0.05). Survival analyses revealed VO2 peak and HR peak as protective indicators, while 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). 
Conclusion: Our prospective study quantified the significantly decreased exercise capacity in ALS through non-invasive CPET. 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 objective indicators of disease progression in ALS.