Journal of IiME Volume 5 Issue 1 (May 2011) Using Cardiopulmonary Exercise Testing to Evaluate Fatigue and Post-Exertional Malaise in ME/CFS continued only modest increases in work rate per stage should be used and tailored to yield a fatiguelimited exercise duration of 8 to 12 minutes. Longer durations may result in patients terminating exercise because of specific muscle fatigue or orthopedic factors rather than cardiopulmonary end points. An important consideration for ME/CFS is to begin the test at a very low workload. Starting at too high a level will make for a very short test with results that are difficult to interpret. Test durations of less than 6 minutes may not show a linear relationship between oxygen consumption and work-rate. [1] Some of the key measures available from CPET include: maximal aerobic capacity (Peak VO2 or VO2 max ); ventilatory or anaerobic threshold (VT); and peak respiratory exchange ratio (RER). In addition to these gas exchange variables, workload at any given point and, with the integration of electrocardiography, key indicators of cardiovascular dynamics can also be measured. Often synonymous with functional capacity or exercise tolerance, Peak VO2 defines the physiological limits of an individual. However it is important to note that when such terms are used to describe performance on activities like timed-walk tests, or the commercial functional capacity assessments often used to evaluate disability, these are only estimates of aerobic capacity which tend to overpredict VO2 .[1] CPET is required for precise measurement of functional capacity. Most activities of daily living (ADL) are performed at levels below peak. VT is an important index of submaximal exercise capacity. It denotes the point at which energy production transitions from primarily aerobic to increasingly anaerobic glycolosis and is a crucial measure in CPET as it represents the onset of fatigue. Due to a lack of oxygen in the working muscle cells, work intensity cannot be maintained resulting in the reduction or cessation of activity. It may also be central to Invest in ME (Charity Nr. 1114035) understanding the activity limitations in ME/CFS. If VT occurs at very low levels of oxygen consumption and/or at very low workloads, then even normal ADL may exceed the VT threshold. It is possible therefore that in ME/CFS the increased stress of requiring a greater anaerobic energy contribution even for normal ADL precipitates the symptom exacerbation seen in PEM. CPET provides the only way to noninvasively assess this significant transition point in energy metabolism. Assessment of subject effort might be considered essential to interpreting any measure of physiological function. Exclusive to expired gas analysis, RER is defined as the ratio between inspired O2 and expired CO2. As exercise intensity increases the volume of CO2 begins to exceed that of O2. A ratio of CO2 to O2 greater than 1.10 is considered an indicator of excellent effort during an exercise test .[1] As an accurate and reliable indication of subject effort, RER substitutes for age-predicted maximal heart-rate values in this respect. Variability of 10-15 beats per minute can be expected within an age group which complicates interpretation of results where percentage of predicted maximal heart rate is the exercise endpoint.[4] There are also difficulties posed by use of pharmacological agents [1] and the cardiovascular abnormalities seen in ME/CFS.[5] Problems of response bias in self-report indictors of effort are also averted. Because RER permits accurate comparison of subject effort across serial exercise tests, it should be of prime consideration for any clinical intervention trial with functional endpoints.[1] CPET data including RER also allow for the more reliable interpretation of results when an exercise challenge is used to elicit symptoms as part of ME/CFS research studies. As a quantifiable measure of both physiological stress and effort, CPET enables direct comparison between patients and controls on these critical measures. This may be particularly Continued page 12 www.investinme.org Page 11/58

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