Fatigue is one of the most pervasive and sometimes debilitating symptoms experienced by patients with systemic lupus erythematosus (SLE), with some studies noting prevalence in up to 90% of patients. Evaluating patients with SLE and associated fatigue can be challenging, as this symptom is often not responsive to immunosuppressive medications. Previous data have shown dysregulated mitochondrial function to be associated with SLE fatigue. Thus, the authors of an exploratory study sought to examine changes in objective measures of cardiorespiratory function and patient-reported outcomes (PROs) following an exercise training program in women with SLE and explore the association with measures of mitochondrial function.1
The primary outcome was time to attain the anaerobic threshold (AT-Time) during cardiopulmonary exercise testing, with secondary outcomes of peak exercise capacity during the testing and a 10-minute walk test (10MWT). Mitochondrial function was assessed by the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) metabolic potential ratio.
The study enrolled 16 patients with SLE who had a Safety of Estrogen in Lupus Erythematosus National Assessment modification of the Systemic Lupus Erythematosus Disease Activity Index score ≤4 and a Fatigue Severity Scale (FSS) score ≥3. The patients were 18.8% Black, 18.8% Asian, 50% Hispanic, and 12.5% White. All were female.
Patients performed a cardiopulmonary exercise test by walking on a treadmill with an increase in work rate, with a target end point of volitional exhaustion by the subject. Researchers verified the anaerobic threshold and determined peak oxygen consumption and respiratory exchange ratio. The supervised aerobic exercise training involved treadmill walking 3 times per week over a period of 12 weeks, with at least 30 continuous minutes of vigorous intensity exercise (70%-80% of heart rate reserve). Patients also performed a 10MWT so researchers could determine walking capacity and obtain fatigability indices. Researchers used the FSS (impact on fatigue) and the Patient-Reported Outcomes Measurement Information System to define PROs.
After the 12 weeks of exercise training, there was a significant improvement in the primary outcome of AT-Time (P<.001) as well as other outcomes (10MWT and peak oxygen uptake), which indicated improved cardiorespiratory function. The average postexercise training distance walked during the 10MWT increased by 84 meters (P<.001). There were also significant improvements in performance fatigability index. The composite FSS score was reduced after exercise training (−1.3; P<.0001), and each of the individual FSS domains significantly improved. Interestingly, a decrease in FSS score correlated with an increase in the mitochondrial function test (the OCR/ECAR ratio).
This exploratory study demonstrated improvements in cardiorespiratory function and patient-reported fatigue in women with SLE following a vigorous treadmill walking-based exercise program. The data suggested possible inverse correlation between fatigue and mitochondrial function. The program was well tolerated with no serious adverse effects. The authors noted some limitations, including the absence of a control group with or without SLE; the study also included a small number of subjects.
Mitochondrial dysfunction may be a biological mechanism that contributes to chronic fatigue, and this study offered an intriguing preliminary observation regarding the potential benefits of exercise training in improving mitochondrial dysfunction and associated fatigue in patients with SLE. Mitochondrial dysfunction is a potential future therapeutic target for SLE-associated fatigue. In the meantime, physicians can counsel patients with SLE, especially those with ongoing fatigue, on the benefits of cardiovascular exercise training.
- 1. Hasni S, Feng LR, Chapman M, et al. Changes in cardiorespiratory function and fatigue following 12 weeks of exercise training in women with systemic lupus erythematosus: a pilot study. Lupus Sci Med. doi:10.1136/lupus-2022-000778