CPET is often discussed in the patient, scientific, and clinical communities. However, I find it that even very informed people may not know very much about the test itself, how the data is collected, and what the data means. Even my own phone autocorrects my speech-to-text dictations of “CPET” to “Sea Pet” and “CPAP.” It must think I own a massive marine aquarium where…I do sleep studies?

The next couple of posts will describe CPET. This first one will discuss the procedure. The next one will describe the data, how we analyze it, and how we interpret it.

Hopefully you will find both posts to be understandable even if you are not involved in research and clinical practice. And if you are, I hope these posts are an accessible reminder and primer to share with your patients.

What’s a “CPET?”

CPET test is a supervised physical stress test.² We use it to evaluate how the body responds to physical exertion as demands increase.² In healthy people and most clinical populations (even very ill ones), CPET results are highly reproducible from one day to the next. ME/CFS stands apart because reproducibility often breaks down after exertion.^3-9 This is finding is often held up as an objective marker of PEM.⁵ More on that in a future post.

How a CPET Looks

The type of CPET set-up we use involves pedaling a stationary bicycle.¹ We use a stationary bike rather than a treadmill to improve safety, and to precisely control and measure workload. This allows us to avoid the risk for falling, stop the test quickly if needed, and to pick important timepoints during the test during later analysis. The stationary bicycle has an automatic brake. This allows us to apply a known amount of resistance to the pedals throughout the test, making it progressively harder. The person just needs to maintain a constant rate of pedaling throughout the test.

We start by placing a lightweight mask over the person’s nose and mouth. The mask is connected to a plastic tube going into a machine that analyzes the gas composition of each breath. The computer uses a sensor to measure how much oxygen is consumed, breath by breath, from exhaled air. We know the content of oxygen in room air and we measure the gases expired each breath for oxygen and carbon dioxide. The balance of oxygen and carbon dioxide that we measure during CPET reflects what we call “gas exchange.”

We also keep track of heart rate, blood pressure, and how hard the person is pushing against the pedals continuously throughout the test. This setup allows us to see how efficiently the body is producing energy, how those systems change as the test becomes more challenging, and how much work all these changes are resulting in.

Typically, each CPET session would begin with unloaded cycling.² This means the person pedals at zero resistance for three minutes while we gather some baseline data. Resistance then increases gradually in a continuous fashion until the individual reaches their limit, typically within eight to twelve minutes. Continuous application of resistance is called a ramping protocol.

However, we do not start our CPETs with three minutes of unloaded cycling.¹ We found even unloaded cycling was too taxing on the patient. People were going through the test and hitting their maximal exertion too quickly to gather enough data to be able to comment on the physiology of what happened. Instead, we have modified the protocol to have a person do a 3-minute seated rest period on the bike before the ramping protocol starts.

We call the test a maximal CPET because, if the person is able, we are trying to achieve a certain set of accepted objective criteria that ensure accurate interpretation.¹ Unlike a lot of so-called submaximal tests that involve a lower amount of physical exertion for a longer period of time, people work only briefly at a maximal level.

If the person needs to stop the CPET at any time and for any reason, we stop immediately. The patient remains in control at all times.

Recovering After CPET

For many patients, the most difficult part of the two-day CPET begins after leaving the laboratory. Symptoms often worsen within hours of the first test and intensify after the second.^10,11 Part of the testing is to follow up with questionnaires to see how the recovery process unfolds. Research consistently documents post-test increases in fatigue, cognitive dysfunction, pain, and autonomic symptoms in people with ME/CFS that we do not see in sedentary people.^10-13

Planning ahead for recovery is essential for CPET.¹ We advise patients to rest aggressively, pace activities carefully, and minimize physical and cognitive strain after testing. We do not allow people to drive themselves to and from CPET appointments. For people traveling to see us from out of town, we always recommend a period of rest after the CPET before their return trip.

We recommend hydration, electrolyte support, and environmental modifications to promote recovery.¹ We are studying different “PEM busting” types of treatments, as well, to reduce symptoms and improve recovery times. More on this in a future post.

Recovery takes as long as it takes. The time it takes to recover after a two-day CPET varies widely. The good news is long-term effects appear to be very rare.¹⁴ Some people return to their self-reported baseline within a few days, while others require two weeks or longer.^13,14 This uncertainty is one of the most important considerations when deciding whether to undergo CPET.

We don’t yet know why some people recovery quickly and some people recover slowly. However, we do know that it doesn’t seem to be a simple matter of severity. We are in the process of looking into the physiological predictors of recovery duration. Hopefully this will improve our ability to predict how long it will take for people to recover after CPET. Stay tuned.

Deciding Whether to Do a CPET

From a patient perspective, the key question is not whether the test can be completed, but whether the information gained justifies the payback associated with PEM. Two-day CPET may be appropriate when objective documentation is needed to confirm a diagnosis,^2,15 to establish objective evidence of disability,¹⁶ or for research purposes.^15,17 Not everyone will benefit from a CPET.¹⁵ It is usually inappropriate for individuals with severe illness or limited recovery capacity.¹⁵

Just because CPET is not for everyone also doesn’t mean it’s for no one. The decision to go forward with CPET always should rest with the individual, balancing one’s own risks and benefits with input from trusted and knowledgeable others. Choosing not to undergo testing is always valid.

Conclusion

For decades, people with ME/CFS were told their symptoms could not be measured. CPET is an accessible way to objectively validate the physiological basis for signs and symptoms.

Next up: what does all the data mean?

References

1. Stevens S, Snell C, Stevens J, Keller B, VanNess JM. Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Pediatr. 2018;6:242. doi:10.3389/fped.2018.00242

2. Balady GJ, Arena R, Sietsema K, et al. Clinician’s Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. Jul 13 2010;122(2):191-225. doi:10.1161/CIR.0b013e3181e52e69

3. Davenport TE, Stevens SR, Stevens J, Snell CR, Van Ness JM. Properties of measurements obtained during cardiopulmonary exercise testing in individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Work. 2020;66(2):247-256. doi:10.3233/WOR-203170

4. Franklin JD, Graham M. Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis. Fatigue: Biomedicine, Health & Behavior. 2022;10(3):119-135.

5. Lim EJ, Kang EB, Jang ES, Son CG. The prospects of the two-day cardiopulmonary exercise test (CPET) in ME/CFS patients: a meta-analysis. J Clin Med. Dec 14 2020;9(12)doi:10.3390/jcm9124040

6. 1. Keller B, Receno CN, Franconi CJ, et al. Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations. J Transl Med. Jul 5 2024;22(1):627. doi:10.1186/s12967-024-05410-5

7. van Campen C, Visser FC. Female patients with myalgic encephalomyelitis/chronic fatigue syndrome or idiopathic chronic fatigue: comparison of responses to a two-day cardiopulmonary exercise testing protocol. Healthcare (Basel). Jun 5 2021;9(6)doi:10.3390/healthcare9060682

8. van Campen CLM, Rowe PC, Visser FC. Two-day cardiopulmonary exercise testing in females with a severe grade of myalgic encephalomyelitis/chronic fatigue syndrome: comparison with patients with mild and moderate disease. Healthcare (Basel). Jun 30 2020;8(3)doi:10.3390/healthcare8030192

9. van Campen CLMC, Rowe PC, Visser FC. Validity of 2-day cardiopulmonary exercise testing in male patients with myalgic encephalomyelitis/chronic fatigue syndrome. Advances in Physical Education. 2020;10(1)doi:10.4236/ape.2020.101007

10. Mateo LJ, Chu L, Stevens S, et al. Post-exertional symptoms distinguish myalgic encephalomyelitis/chronic fatigue syndrome subjects from healthy controls. Work. 2020;66(2):265-275. doi:10.3233/WOR-203168

11. Van Ness JM, Stevens SR, Bateman L, Stiles TL, Snell CR. Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). Feb 2010;19(2):239-44. doi:10.1089/jwh.2009.1507

12. Davenport TE, Chu L, Stevens SR, Stevens J, Snell CR, Van Ness JM. Two symptoms can accurately identify post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome. Work. Mar 13 2023;doi:10.3233/WOR-220554

13. Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011;33(19-20):1768-75. doi:10.3109/09638288.2010.546936

14. Moore GE, Keller BA, Stevens J, et al. Recovery from exercise in persons with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Medicina (Kaunas). Mar 15 2023;59(3)doi:10.3390/medicina59030571

15. Davenport TE, Stevens SR, Van Ness M. Myalgic Encephalomyelitis. In: Ozemek C, American College of Sports Medicine, eds. ACSM’s Guidelines for Exercise Testing and Prescription. 11th ed. Lippincott Williams & Wilkins; 2025.

16. Ciccolella ME, Davenport TE. Disability law and the simplification of science: scientific and legal challenges to the functional capacity evaluation in individuals with chronic fatigue syndrome. Fatigue: Biomedicine, Health & Behavior. 2013;1(4):243-255. doi:10.1080/21641846.2013.828960

17. United States National Academy of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. NAM; 2015 Feb 10. The National Academies Collection: Reports funded by National Institutes of Health. Available from: https://www.ncbi.nlm.nih.gov/books/NBK274235/ doi: 10.17226/19012

In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), however, repeating the CPET became something else entirely. It is one of the first and still few objective measures indicative of post-exertional malaise (PEM); a disruptive and ultimately foundational discovery.

Two-day CPET did not emerge from some large federally funded clinical center or a national research initiative or a complicated machine learning deep dive of a massive data set. It began as a small experiment to understand PEM conducted by a scientist living with ME/CFS. And it’s maybe the first and best example of patient-led science in the field.

Here is the background story of why a patient made two-day CPET.

A Scientific Breakthrough From Lived Experience

The origins of the two-day CPET trace back to Staci Stevens, MA. Staci is a person living with ME/CFS. She came down with mononucleosis, subsequently diagnosed as ME/CFS, and never recovered. PEM compromised her ability to function and exercise only made it worse. Gentle walking around the block landed her in bed for days. Recovery was impaired, delayed, and dysfunctional. She began to wonder, as an athlete before she became ill, if she had overtrained.

Ten years after she first became ill, a clinical trial was using a single CPET as an outcome measure. After talking to patients who all experienced PEM from the testing, she realized the researchers were not measuring the right way. Measurements taken in one single point in time were missing the most important part of the illness: PEM. They were missing the impairment. The symptoms that hit 24 hours and beyond and build in intensity. The symptoms that make no sense and are not believed. PEM is the defining feature of ME/CFS, and yet no one was objectively characterizing it.

She knew she could.

Staci’s central scientific question did not arise from theory or textbooks, but from lived experience. This means, from the very beginning, the two-day CPET line of research was not imposed on patients. It originated from a patient using the scientific process and the tools of her discipline to understand her own reality, which science and medicine still have largely failed to adequately explain.

CPET Should be a Reliable Stand-by

CPET is prized for its high test-retest reliability in healthy people and across disease states. When a someone performs a maximal CPET and repeats it a day or two later, the expectations are straightforward. Oxygen consumption should be reproducible. Anaerobic or ventilatory threshold should remain stable. Maximal workload, cardiovascular, and ventilatory responses should closely overlap. Sure, there is a little variability between tests, but the measurements should be very dependable.

Because this reproducibility is assumed, repeat CPETs are used as baseline laboratory validation just to verify equipment calibration, train personnel, and the consistency of a protocol. These ‘practice runs’ exist behind the scenes as simple confirmation that the lab can get the equipment to work. It is mainly ‘throwaway data’ or something that gets cited only briefly in the paper as mundane preparation for the main event.

However, Staci’s thinking was different in a crucial way. Single CPET was making a physiological change that was not measured in the post-exertional state. If there was something different about the post-exertional state, she hypothesized that people with ME/CFS would not be able to reproduce CPET measurements on a second test in the post-exertional state. This meant what we normally think of as throwaway data should be the main analysis.

The Unexpected Finding

At the Pacific Fatigue Laboratory (PFL), the team began observing what should not have been possible under accepted physiological assumptions. On a second CPET performed 24 hours later, people with ME/CFS showed a whole host of unusual findings that deconditioned people did not. These included reduced volume of oxygen consumed, earlier onset of anaerobic threshold, and lower workloads at submaximal levels of exertion. All this evidence began to point to an aerobic energy system that broke down following the first CPET.

These deficits appeared despite objective evidence of maximal physiological effort on both test days. For the first time, the team showed what patients have known for years. Under rigorous testing conditions, PEM is not a failure of motivation, fear, or deconditioning. Instead, it is a failure of metabolic recovery.

“Well, You Don’t Know How to Use the Equipment”

Like anything new in science, the early response from the scientific community was frequently dismissive and hostile. Critics claimed the findings must reflect user error, improper calibration, misapplication of protocols, or misunderstanding of CPET interpretation.

It was too much to accept that a foundational belief might be wrong. And, in certain circles, that acceptance is still difficult, even in the face of abundant research evidence.

What these critiques have ignored and continue to ignore is the data itself. CPET test-retest reliability should be among the most stable principles in the field. If ME/CFS patients uniquely fail to reproduce performance, the issue is the biology and not the test.

Two-day CPET faced (and arguably continues to face) entrenched resistance within the scientific and medical communities. It is still surprising how much resistance this objective evidence of PEM has received and continues to receive both in the research and clinical community even though there is still no definitive diagnostic test for ME/CFS.

However, despite skepticism and institutional pushback, findings from two-day CPET have endured. Carefully done replication studies largely have confirmed the pattern. Independent analyses have demonstrated the same deterioration at submaximal exertion. In a disease marked by noise, this signal has been robust over time.

Two-Day CPET and the Role for Exertional Testing

Even studies that do not perform a second CPET now routinely employ a single CPET or standardized exertional challenge, followed by post-exertional measurement of symptoms, autonomic changes, metabolic disruption, immune markers, or cognitive impairment. In effect, post-exertional assessment is now standard in ME/CFS research. There is a recognition that cross-sectional measurements involving patients only at rest is no longer sufficient. This shift toward understanding what exertion does to the body traces directly back to the two-day CPET paradigm.

With the emergence of Long COVID, CPET has assumed a new importance. Clinicians and researchers began to encounter the familiar pattern of PEM. Many people living with Long COVID show exertion intolerance, a delayed onset of worsening of severe symptoms and signs, and functional collapse that can not be explained by cardiopulmonary disease or deconditioning alone. For this reason, both single-day and two-day CPET protocols are now used in Long COVID research and clinical practice. While not all people with Long COVID show identical findings, the conceptual framework developed in ME/CFS has profoundly shaped how post-exertional disability is now studied more broadly.

Real-World Impact: Supporting Determination of Disability

Beyond the lab and clinic, CPET has had tangible, life-altering implications. Objective CPET findings, particularly from two-day testing, have helped countless people with ME/CFS and ME-like illnesses secure recognition and validation. This has led to disability benefits, workplace accommodations, and legal recognition of functional impairment for many. In systems that routinely discount subjective symptoms, CPET documents physiological limits, demonstrates loss of capacity rather than lack of effort, and proves disability caused by exertion itself. For many patients, these objective data have meant the difference between being believed and being dismissed.

The Future of Exertional Testing

CPET, in part, is a test of physiological limits. We are also now beginning to explore the earliest physiological signatures of PEM and how soon they appear. The answers to these questions may hold the key for more accessible exertional testing with less payback for the patient.

This new line of research does not mean simplistic “submaximal” testing. In fact, poorly characterized low-intensity or prolonged exertional tasks may be more harmful than a brief, controlled maximal CPET. Despite the public perception, maximal CPET is relatively brief, tightly monitored, and well understood. Light or moderate activity, if misapplied, can impose a greater cumulative physiological load while seeming to be biologically innocuous.

This new frontier of exertional testing focuses on detecting metabolic, autonomic, immune, and neurological changes at the very onset of physiological changes associated with exertion. This work to identify the physiological tipping point at the edges of the energy envelope is happening right now. Two-day CPET has made this new work possible and continues to be the gold standard against which new methodologies must be validated.

More on this in future articles.

The ‘Throwaway Data’ That Began to Uncover the Disease

Reliability testing was never designed to validate ME/CFS. It was designed to answer a mundane laboratory question: “if we test someone twice, do we get the same result?” This question is necessary to answer so we can ensure the equipment is working and we can use it correctly.

But for people with ME/CFS, the answer was consistently “no.” In that failure of reproducibility, an important pattern of the disease emerged. The defining pathology of ME/CFS is not fatigue, but a physiological inability to recover from exertion. That insight now underpins ME/CFS research, informs Long COVID science, supports disability justice.

And this insight continues to shape the field, decades after an exercise scientist living with ME/CFS quietly began to answer a question no one else thought to ask.

The failure of medicine and science to understand ME/CFS has been a shortcoming of theory, not technology. For decades, clinicians have assumed that exertion reveals health. The idea is relatively simple, and it holds up most of the time. If you stress the system and observe the resulting performance of physiological systems under load, then you can infer capacity, and counterfactually, pathology. However, ME/CFS is an important exception to this rule.

Functional capacity in people with ME/CFS may be significantly compromised. But there is often a delay between the exertion and the worsening.³ Clinicians and scientists long have assumed this delay must signal a problem with motivation, beliefs, and fear. However, what ME/CFS research has surfaced slowly over time is something that medicine is still in its infancy in understanding: what happens after exertion, the biology of recovery. And the data in ME/CFS are now too coherent to dismiss.

Failure of Biological Recovery is Unusual and Unique to ME/CFS

The most consistent finding in ME/CFS research is also the most instructive. Patients cannot reproduce energy output on repeat exertion, whether physical, cognitive, emotional, or environmental. I’m an exercise physiologist, so I understand this literature the best and the literature is probably best developed related to physical exertion. Across multiple centers all over the world, two-day cardiopulmonary exercise testing (CPET) demonstrates that people with ME/CFS show objective declines in volume of oxygen consumed and workload at submaximal exertion on the second day, despite showing maximal effort on both days.^4-6 ME/CFS is a crisis of reproducibility in science, just not the way we normally talk about it.

This failure of biological recovery does not occur in healthy controls, deconditioned people, or in other chronic diseases, including heart failure, chronic obstructive pulmonary disease, and multiple sclerosis.⁷ It is not fatigue. Rather, it is failed metabolic recovery. Attempts to dismiss this finding have relied on underpowered null studies or inappropriate analyses that erase stratified effects. (More on how ME/CFS researchers have used and abused CPET studies in future articles.) Larger and more carefully analyzed studies continue to confirm impaired reproducibility as a defining signature of PEM.⁴

If medicine and science treated exertional responses the same way it treats glucose testing, the pathophysiology of ME/CFS would have become obvious decades ago. And we would avoid the constant misapplications of the biopsychosocial approach to ‘treat’ the pathophysiology of ME/CFS that still divert precious attention, time, and resources today.

PEM is a Failure of Bioenergetic Recovery

Exercise physiology tells us the process of exertion is not completed at task termination. Recovery means further exertion. It requires mitochondrial substrate switching, redox normalization, autonomic rebalancing, immune system activation, and tissue repair signaling. However, this sequence breaks in ME/CFS. Multi-omics studies show that after an initial bout of exertion, ME/CFS patients exhibit continued impairment TCA cycle flux and fatty acid β-oxidation, reduced ATP generation and altered AMP/ADP ratios, persistent redox imbalance, complement activation and innate immune amplification, and lipidomic signatures consistent with inflammatory repair failure.^8,9 All of these are worse after effort and correlated with symptom severity.

Simply put, the bodies of people with ME/CFS can not efficiently do the work of recovery. And because these abnormalities are found in people with ME/CFS but not matched deconditioned controls, we can confidently say that PEM is not deconditioning.

The Immune System Signals Persistent Danger in PEM

Normal exercise produces a transient inflammatory response followed by rapid resolution. However, people living with ME/CFS show the opposite pattern. A diverse body of studies demonstrate Exaggerated complement (C4a) activation post-exercise, abnormal toll‑like receptor and IL-10 gene expression, and heightened oxidative stress with delayed antioxidant responses.^8,10 These immune changes align with PEM.

Recent large multi-omics studies have gone further, documenting post-exercise innate immune hyperreactivity alongside metabolic collapse. These findings suggest that exertion re-engages a persistent danger response within the immune system rather than resolving it.⁸ Some people are still tempted to think PEM is just exercise intolerance. These data suggest PEM is also exertion-triggered immune system dysregulation.

Autonomic Control Collapses in PEM

The autonomic nervous system is the conductor of the orchestra of physiological recovery. However, the conductor is drunk and the orchestra has become poorly coordinated in ME/CFS. Large multisite studies show common autonomic symptom burden in ME/CFS, including orthostatic intolerance, impaired heart rate variability, and abnormal blood pressure regulation. Severity of these signs and symptoms are correlated with illness burden.¹¹ Invasive CPET studies demonstrate that exertion decouples neurovascular control, which impairs venous return and cardiac preload.¹² These data indicate exertion destabilizes control systems that normally stabilize the body during recovery.

Exertion and Time Are the Key Variables Science and Medicine Have Ignored

Failing to consider previous exertion destroys the validity of cross-sectional outcomes measurements in ME/CFS.¹³ Taking blood samples, obtaining questionnaires, and collecting other outcomes measures must consider the patients signs, symptoms, and previous exertion. Important physiological differences are apparent in people living with ME/CFS on “good days” versus “bad days.”¹⁴ This understanding needs to be incorporated into research and clinical practice.

One assumption in ME/CFS research has been that recovery physiology happens on “clinic time.” However, PEM commonly unfolds over 24–72 hours, with recovery lasting days to weeks to even months. Recovery-focused studies show ME/CFS patients report return-to-baseline times averaging nearly two weeks after a standardized physical exertion compared with around 48 hours in healthy, deconditioned controls.^3,15,16 This means researchers and clinicians need to plan for extended observation times when PEM is involved.¹³ When variability is a key characteristic of the disease, more measurements are needed to separate signal from noise.

Post-Exertional Physiology is Not Optional Science in ME/CFS

The emergence of post‑exertional physiology forces medicine to confront an inconvenient truth. We have engineered entire research and treatment approaches without verifying that post-stress recovery worked. People with ME/CFS have been harmed because we have ignored the physiology of recovery, leading to misapplications of exercise, cognitive-behavioral therapies, and a piecemeal approach to testing repurposed pharmacological therapies.

Post-exertional physiology now sits at the uncomfortable intersection of metabolism, immunology, and cardiovascular function. Science and medicine must break down the conceptual silos between them, so exertion will not continue to be weaponized.

Key References

1. Carruthers BM, Jain AK, DeMeirleir KL, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols. Journal of Chronic Fatigue Syndrome. 2003;1(1):7-115. doi:10.1300/J092v11n01_02

2. Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. Oct 2011;270(4):327-38. doi:10.1111/j.1365-2796.2011.02428.x

3. Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011;33(19-20):1768-75. doi:10.3109/09638288.2010.546936

4. Keller B, Receno CN, Franconi CJ, et al. Cardiopulmonary and metabolic responses during a 2-day CPET in myalgic encephalomyelitis/chronic fatigue syndrome: translating reduced oxygen consumption to impairment status to treatment considerations. J Transl Med. Jul 5 2024;22(1):627. doi:10.1186/s12967-024-05410-5

5. Lim EJ, Kang EB, Jang ES, Son CG. The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis. J Clin Med. Dec 14 2020;9(12)doi:10.3390/jcm9124040

6. Franklin JD, Graham M. Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis. Fatigue: Biomedicine, Health & Behavior. 2022;10(3):119-135.

7. Larson B, Davenport TE, Stevens SR, Stevens J, Van Ness JM, Snell CR. Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals with Fatiguing Health Conditions: A Case Series. Cardiopulmonary Physical Therapy Journal. 2019;30(4):145-152. doi:10.1097/CPT.0000000000000100

8. Che X, Ranjan A, Guo C, et al. Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS. NPJ Metab Health Dis. Sep 3 2025;3(1):34. doi:10.1038/s44324-025-00079-w

9. Heng B, Gunasegaran B, Krishnamurthy S, et al. Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction. Cell Rep Med. Dec 16 2025;6(12):102514. doi:10.1016/j.xcrm.2025.102514

10. Nijs J, Nees A, Paul L, et al. Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review. Exerc Immunol Rev. 2014;20:94-116.

11. Issa A, Lin JS, Chen Y, et al. Autonomic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Findings from the Multi-Site Clinical Assessment of ME/CFS (MCAM) Study in the USA. J Clin Med. Sep 5 2025;14(17)doi:10.3390/jcm14176269

12. Joseph P, Arevalo C, Oliveira RKF, et al. Insights From Invasive Cardiopulmonary Exercise Testing of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Chest. Aug 2021;160(2):642-651. doi:10.1016/j.chest.2021.01.082

13. Soares L, Davis H, Spier E, et al. Recommended long COVID outcome measures and their implications for clinical trial design, with a focus on post-exertional malaise. EBioMedicine. Dec 19 2025;123:106083. doi:10.1016/j.ebiom.2025.106083

14. Aitken A, Sawyer A, Iwasaki A, et al. Digital physiological biomarkers predict within-person symptom changes in complex chronic illness. NPJ Digit Med. Mar 24 2026;9(1)doi:10.1038/s41746-026-02543-3

15. Moore GE, Keller BA, Stevens J, et al. Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medicina (Kaunas). Mar 15 2023;59(3)doi:10.3390/medicina59030571

16. Mateo LJ, Chu L, Stevens S, et al. Post-exertional symptoms distinguish Myalgic Encephalomyelitis/Chronic Fatigue Syndrome subjects from healthy controls. Work. 2020;66(2):265-275. doi:10.3233/WOR-203168

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