Journal of IiME Volume 2 Issue 1 R Reevviieeww ooff tthhee ““TTwwoo--ddaayy EExxeerrcciissee TTeesstt”” U U Literature Review Review of the “Two-day Exercise Test” In the most recent Journal of Chronic Fatigue Syndrome (Vol 14, Number 2, 2007) there are two articles which may be the first to offer an objective proof of disability in ME/CFS. More importantly, if shown to be correct, they may give us an avenue to test and measure the biochemical abnormality which causes the symptom pattern. In this short review I would like to review these two papers and present a case of pediatric CFS which demonstrates the same abnormalities. In the first of these papers, Margaret Ciccolella, a lawyer, teams up with Staci Stevens, Chris Snell, and Mark Van Ness of the University of the Pacific to review the legal issues surrounding exercise testing and disability (1). As everyone familiar with CFS well knows, insurance companies require proof of disability, which a standard exercise test may or may not demonstrate. However, even if disability is present, insurance companies have been quick to say that the patient was not trying hard enough, or that the patient is deconditioned. The second paper of this series by VanNess, Snell and Stevens explain the two-day exercise test and presents results for six patients with ME/CFS (2). As clinicians have observed, the symptom of “postexertional malaise” is one of the most distinguishing features of CFS. This symptom is listed as one of the eight in the criteria of the Centers for Disease Control (3), and is central to the diagnosis in the recent Canadian Case Definition (4) and the proposed pediatric case definition (5). It is beginning to look like the symptom of postexertional malaise is at the root of disability, and may be central to the pathophysiology of this complex illness spectrum. A person with ME/CFS may be at home for several days doing little except basic activities of daily living. When this patient decides to go shopping, he or she will drive to the mall and shop for one or two hours. During this time, observers would say that the person looks entirely well, not appearing disabled. However, following this activity the patient will experience an exacerbation of pain and other symptoms of ME/CFS. This exacerbation may last one, two or three days, and, in my opinion, the more severe the illness, the longer and more severe the exacerbation. This phenomenon is known as postexertional malaise. The symptoms of the illness (malaise) are exacerbated by mental, physical or emotional activities (post-exertional). In an employment environment, the patient may be able to do a job well for one or even several days. However disability lies in the inability to sustain this normal ! level of activity. The two-day exercise test is the first to begin to explain this phenomenon. The exercise test is no different from what has been used Invest in ME (Charity Nr. 1114035) for years. The patient exercises on a stationary bicycle (bicycle ergometry) and breathes through plastic tubing to measure the concentration of oxygen and carbon dioxide as well as the total amount of air. The six female patients and six sedentary matched control subjects of the study were all able to achieve maximal exertion. The ME/CFS patients had a slightly lower V02max (maximal oxygen utilization) than controls (28.4 ml/kg/min vs. 26.2 ml/kg/min) and lower VO2 at anaerobic threshold (15.01 ml/kg/min vs. 17.55 mg/kg/min) on the first day of exercise testing. These values are not dramatic nor are they statistically significant. It is on the second day that interesting results are seen. The same test was repeated the following day for all twelve subjects. As is often the case, sedentary controls improved slightly in their ability to utilize oxygen, going from 28.4 to 28.9 ml/kg/min for VO2max and from 17.55 to 18.00 ml/kg/min for oxygen utilization at anaerobic threshold. The CFS patients however worsened in both categories: VO2max fell 22% from 26.23 to 20.47 ml/kg/min, and oxygen utilization at anaerobic threshold fell 27%, from 15.01 to 11.01 ml/kg/min. To put this into perspective, these values are in the severe disability range on the AMA guidelines, and the decline in function from day one to day two cannot be explained by inactivity. Sedentary or de-conditioned persons do not change their oxygen utilization because of an exercise test. Even patients with heart disease, cystic fibrosis or other diseases do not vary more than 7% from one day to the next. However, the patients with ME/CFS in this study had a significant drop; something occurred because of the test on the first day interfered with their ability to utilize oxygen on the next day. And this is exactly what patients with ME/CFS have been describing with the symptom of post-exertional malaise. As the authors state, “The fall in oxygen consumption among the CFS patients on the second test appears to suggest metabolic dysfunction rather than a sedentary lifestyle as the cause of diminished exercise capacity in CFS.” Conclusions: The results of the two-day exercise testing are objective and not dependent upon subjective symptoms. Moreover hypochondriasis, intentional falsification, and/or poor effort can be detected by the physiologic parameters. Therefore the two-day exercise test, if confirmed in a larger trial, could become a clinical trial end point. More importantly, evaluations could be designed which would demonstrate the specific metabolic abnormality generated by the exercise of day one and demonstrated on the second day exercise test. It would be my hope that these findings be explored without delay. 1. Ciccolella M, Stevens S, Snell C, VanNess J: Legal and Scientific Considerations of the Exercise Stress Test. JCFS 2008, 14(2):61-75. (Continued on page 23) Page 22/34 www.investinme.org
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