New paper: Inability of ME patients to reproduce VO2 max indicates functional impairment

Dolphin

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(Small point on discussion earlier in the thread)
It would be good if people specified which specific currency they are referring to i.e. there are US dollars, Canadian dollars, Australian dollars, etc.
 

Dolphin

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I keep coming back to CPET and severe patients. One hypothesis I have that will not go away, it seems solid to me, is that severe patients exceed their aerobic threshold just with basic survival. I think gas analysis might show this without any exercise. After I have thought about this some more I hope to bring this to the attention of the Workwell researchers.
Betsy Keller presented research at the 2011 IACFS/ME conference making this very point although not just about severe patients:

Abbreviations:
ADL=Activities of Daily Living

IADL=Instrumental Activities of Daily Living

(for more see http://en.wikipedia.org/wiki/Activities_of_daily_living)

Exercise Testing to Quantify Effects of Fatigue on Functional Capacity in Patients With CFS

Betsy A. Keller, B.A. Micale, FG

Ithaca College

Objective:

The purpose of this study was to assess the effects of post-exertional malaise (PEM) on functionalcapacity and anaerobic threshold in subjects diagnosed with chronic fatigue syndrome (CFS).

Methods:

Subjects were 10 females and 2 males (41.3+1.11 yrs) diagnosed with CFS by a physician experienced in the diagnosis of CFS.

To induce PEM, each subject completed a maximum exercise test ona cycle ergometer.

A second maximum exercise test was performed 24 hrs later to assess the effects of exercise-induced PEM on functional capacity.

Maximum oxygen consumption (VO2max), maximum heart rate (HRmax), anaerobic threshold (AT), maximum workload (Wmax), workload at AT (ATwork), and respiratory exchange ratio (RER) were measured.

RER is an objective indicator of substrate utilization and subject effort during exercise.

Results:

Significant decreases from test 1 to test 2 were 13.5% for VO2max (21.5 to 18.6 ml . kg -1. min -1 ; p<0.01), 8 bpm for HRmax (p<0.01), 18.8% for AT (12.0 to 9.7 ml . kg -1. min -1 ; p<0.05), 9.4% for Wmax (121 to 109 W, p<0.05), and 17.3% for ATwork (58.3 to 48.2 W; p<0.05).

However, there was no change in maximum RER indicating that subject effort was maximum and also comparable during both tests.

Conclusion:

Results indicate that PEM decreased maximum functional capacity by more than 13% to below 5 METS; a level at or below that which is required by many job-related activities and IADLs.

To compare, VO2max in healthy individuals is highly reproducible over days and even months (r>.95) 1 , with a SEM of < 6% 1,2 .

Thus, for subjects in this study, an expected variation between tests would be +/- 1.29 ml . kg -1. min -1 in contrast to the observed decrease of 2.9 ml . kg -1. min -1 .

Furthermore, PEM decreased AT to below 3 METS (e.g., light-moderate speed walking), which is a level of many activities considered to be sedentary in nature.

Thus, completion of sedentary ADLs and IADLs for those with CFS requires production of energy via anaerobic processes that will further contribute to PEM and exacerbate symptoms of CFS.

Since many daily activities fall into the 3-5 MET range, individuals with CFS will exacerbate symptoms associated with PEM simply by completing normal daily activities.


1 Taylor, HL, Buskirk, E & Henschel, A. (1955). Maximal oxygen intake as an objective measure of cardiorespiratory performance. J Appl Physiol, 8, 73-80.

2 Katch, VL, Sady, SS & Freedson, P. (1982). Biological variability in maximum aerobic power. Med Sci Sports & Ex, 14(1), 21-25.

Betsy A. Keller, PhD, Professor, Exercise & Sport Sciences, Ithaca College, 318 Center for Health Sciences, Ithaca, NY 14850 keller@ithaca.edu

Frank G. Micale, M.S., Clinical Associate Professor, Exercise & Sport Sciences, Ithaca College, 317 Center for Health Sciences, Ithaca, NY 14850 fmicale@ithaca.edu
 

Dolphin

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James Baraniuk presented on 2-day exercise testing at the 2011 IACFS/ME conference

An Hybrid 70% Plus 85% Predicted Heart Rate Bicycle Stress Test Performed on Two Consecutive Days

James N. Baraniuk, M.D. Christian R. Timbol, Yin Zheng, Amber Surian, Rania Esteitie, Murugan Ravindran, Samantha J. Merck, Rakib Rayhan, Oluwatoyin Adewuyi, and Sharon O’Brien

Pain and Fatigue Research Alliance, Georgetown University

Objective:

Determine the merits of submaximal and maximal bicycle stress tests for Gulf War Illness (GWI), CFS and healthy veterans and controls (HC) for tandem, 2 day testing.

Methods:

Subjects exercised on a Schwinn bicycle ergometer.

Cardiopulmonary function was measured using mouthpieces and Vmax software.

27 GWI and 8 HC participated in 3 bicycle exercise stress test protocols:

#1. 13 GWI and 2 HC had standardized ramped VO2max tests with exercise until physical limitations caused the test to end (85%HR).

#2. 6 GWI and 4 HC cycled at 70% of maximum predicted heart rate for 25 min then accelerated to 85% without cardiopulmonary testing (70%+85%).

#3. 11 GWI and 5 HC had VO2max tests that began with 25 min at 70% maximum heart rate that was followed by acceleration to 85% (70%+85% plus VO2max).

Symptomatic Responses:
Borg Dyspnea Scores were significantly higher for GWI subjects on DAY 1 (3.9; 2.8 to 4.9 [mean; 95% C.I.]; n=25) and DAY 2 (4.1; 3.1 to 5.0) than HC (1.4; 0.1 to 2.6; n=9; p=0.016 by t-test; and 1.3; -0.1 to 2.6; p=0.0053; n=8; respectively).
On DAY 1, whole body pain and fatigue scores at rest and after exercise were in the 3 to 15 range on the 20 point anchored ordinal Gracely Scale for GWI (n=15) compared to 0 to 3 for HC (0.032≥p≥0.00005; n=8).

DAY 2 results were marginally higher at 6 to 16 for GWI and 0 to 5 for HC (0.043≥p≥0.0000004).

None of the HC subjects complained of pain or fatigue on either day.

Adverse Events:

Protocol #1.

Three GWI had to stop because of fatigue and dyspnea with VO2max at 25%, 32% and 50% of predicted.

A fourth had dyspnea and oxygen desaturation (88% by pulse oximetry).

A fifth GWI subject stopped because their systolic blood pressure dropped by 22% as they neared 70% HR.

Protocol #2.

Two GWI had to stop after 25 min at 70% of maximum HR because of fatigue or muscle pain.

A third GWI subject increased their HR by only 29% before stopping.

Protocol #3.

One GWI became so exhausted after 70% HR that within 15 minutes he had fallen asleepfor 1 hour.

One veteran who was otherwise healthy on examination could only exercise to VO2max of 48% of predicted before stopping because of dyspnea on both DAYs.

This subject and another otherwise healthy appearing veteran both demonstrated orthostatic tachycardia (ΔHR>30 bpm).

Energy Expenditures:

In the two 70%+85% protocols, HC expended more METs to reach 85%HR (7.95; 7.08 to 8.82) thanGWI (4.94; 4.16 to 5.72; p=0.0015).

On DAY 2, this significant difference was found for 70% HR in HC(5.00; 4.26 to 5.74; n=4 vs. 3.17; 2.54 to 3.80; n=6; p=0.0064).

At 85% HR the variance of the GWI data was too large for a significant difference to be detected.

Expenditures by GWI subjects were different on DAY 2 from DAY 1. Watts needed to reach 85% HR inramped exercise for GWI were higher on DAY 1 (202; 160 to 245; n=13) than DAY 2 (170; 138 to 202; n=12; p=0.015 by paired t-test).

In contrast, the 70%+85% protocol required more calories on DAY 2 (179; 155 to 203; n=12) than DAY 1 (162; 132 to 191; p=0.033) in a different group of GWI subjects.

HC had no differences in energy requirements between DAY 1 and DAY 2.

Conclusion:

The 70%+85% VO2max test was the optimal provocation.

James N. Baraniuk, M.D. gwiresearch@georgetown.edu Room 3004F3-PHC Building, 3800 Reservoir Road, N.W., Washington DC 20007-2197 USA

Supported by NIEHS RO1 ES015382 and DoD W81XWH-07-1-0618 and W81XWH-09-1-0526.
 

Dolphin

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I vaguely recall talk of 3 exercise tests, possibly over five days, being presented at a previous IACFS/ME conference (i.e. not 2014 nor 2011) i.e. 2007 or 2009 I think. I don't have the abstracts for the 2007 or 2009 conferences.
 

Valentijn

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I wonder why he didn't report the CFS results?
There was probably 100% overlap between the CFS and GWS groups. The symptoms are pretty much identical, hence many GWS studies will mention that the patients also fulfill all of the criteria for Fukuda CFS.

So there might not have been any CFS patients, just CFS/GWS patients.
 

MeSci

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There was probably 100% overlap between the CFS and GWS groups. The symptoms are pretty much identical, hence many GWS studies will mention that the patients also fulfill all of the criteria for Fukuda CFS.

So there might not have been any CFS patients, just CFS/GWS patients.
But he says:

Objective:

Determine the merits of submaximal and maximal bicycle stress tests for Gulf War Illness (GWI), CFS and healthy veterans and controls (HC) for tandem, 2 day testing.
 
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Betsy Keller presented research at the 2011 IACFS/ME conference making this very point although not just about severe patients:
Furthermore, PEM decreased AT to below 3 METS (e.g., light-moderate speed walking), which is a level of many activities considered to be sedentary in nature.

Thus, completion of sedentary ADLs and IADLs for those with CFS requires production of energy via anaerobic processes that will further contribute to PEM and exacerbate symptoms of CFS.

Since many daily activities fall into the 3-5 MET range, individuals with CFS will exacerbate symptoms associated with PEM simply by completing normal daily activities
I'm not sure I quite buy the logic of this point. Certainly the effect of a 2-day CPET in reducing performance is striking, and the day-2 AT levels are at the levels where normal daily activities are likely to go beyond anaerobic limits. However, I don't think you can say that normal PEM will have the same effect on AT (anaerobic threshold) as cycling to exhaustion. Most patients get PEM way below pushing to total exhaustion, one reason the illness is so hard to manage. The Light's gene expression study using moderate exercise provoked PEM, but would moderate physical exercise - or even cognitive exertion provoking PEM - also cause AT to fall in the same way as a maximal cycling test? I don't think we can say from the evidence in this paper.

I think what would be needed would be:
- initial test to establish AT; you can't measure AT on the fly so this might need to be the full max test
- at a later date retesting patients on a day they have PEM not brought on by a max test
One possibility (not sure it would work) would be say, a 70% max heart-rate CPET (ie sub-maximal) to provoke PEM and measure AT, followed by a maximal CPET next day: would the results be the same on day 2 after a sub-maximal test on day 1?

It's also worth bearing in mind that not all patients were effected - in fact, fewer than half showed a drop in day-2 AT, with the rest basically the same on both days, or even increasing slightly (most of these instead showed a drop in day-2 VO2.max). See panel A in the figure from the published paper:
http://www.translational-medicine.com/content/12/1/104/figure/F4

I think the 2-day CPETs give us some of the most striking results seen in studying mecfs to date and need to be pursued in much bigger studies (as Betsy Keller argues in her paper), but I also think we need to be careful in interpreting the data. Particularly as to whether 2-day CPET tests reflect what happens in 'normal' PEM brought on by more typical activities.
 

MeSci

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I'm not sure I quite buy the logic of this point. Certainly the effect of a 2-day CPET in reducing performance is striking, and the day-2 AT levels are at the levels where normal daily activities are likely to go beyond anaerobic limits. However, I don't think you can say that normal PEM will have the same effect on AT (anaerobic threshold) as cycling to exhaustion. Most patients get PEM way below pushing to total exhaustion, one reason the illness is so hard to manage. The Light's gene expression study using moderate exercise provoked PEM, but would moderate physical exercise - or even cognitive exertion provoking PEM - also cause AT to fall in the same way as a maximal cycling test? I don't think we can say from the evidence in this paper.

I think what would be needed would be:
- initial test to establish AT; you can't measure AT on the fly so this might need to be the full max test
- at a later date retesting patients on a day they have PEM not brought on by a max test
One possibility (not sure it would work) would be say, a 70% max heart-rate CPET (ie sub-maximal) to provoke PEM and measure AT, followed by a maximal CPET next day: would the results be the same on day 2 after a sub-maximal test on day 1?

It's also worth bearing in mind that not all patients were effected - in fact, fewer than half showed a drop in day-2 AT, with the rest basically the same on both days, or even increasing slightly (most of these instead showed a drop in day-2 VO2.max). See panel A in the figure from the published paper:
http://www.translational-medicine.com/content/12/1/104/figure/F4
Is that the same study? The one in @Dolphin's info says that VO2 peak/max decreased by 13.5%, whereas the published study says 13.8%, HRmax/peak decreased by 8 bpm vs. 9 bpm, and Wmax/peak by 9.4% vs. 12.5%, if I have read/understood right (brain a bit sub-optimal at moment).
 

Tom Kindlon

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IACFS/ME Conference 2014 abstract

Reproducibility of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With and Without Fatiguing Health Conditions: A Case Series

Benjamin M. Larson 1 , Todd E. Davenport 1,2 , Staci R. Stevens 2 , J. Mark Van Ness 1,2 , Christopher R. Snell 1,2,

1 University of the Pacific, Stockton, CA, USA
2 Workwell Foundation, Ripon, CA, USA

Purpose:

The reproducibility of measurements obtained during cardiopulmonary exercise testing (CPET) is a longstanding tenet of exercise physiology.

However, test-retest variation in CPET measures may be higher for individuals with chronic fatigue syndrome (CFS), which could explain the characteristic functional deficits of post-exertional malaise.

The purpose of this case series was to demonstrate the potential variability of test-retest CPET measurements in individuals with and without fatiguing health conditions.

Case Descriptions:

Subjects (n=7) who were matched to age, body mass index, and gender received 2 maximal CPETs 24 hours apart.

Cardiovascular, respiratory, and metabolic measurements were taken at both peak exertion and ventilatory threshold (VT).

Standard criteria were used to verify a maximal test took place.

Diagnoses included sedentary but non-disabled individuals (n=2), an active and non-disabled individual (n=1), multiple sclerosis (MS; n=1), human immunodeficiency virus (HIV; n=1), an individual with CFS who was low-functioning (n=1; Test 1 peak volume of oxygen [VO2]: 17.2 mL/kg/min), and an individual with CFS who was high-functioning (n=1; Test 1 peak VO2: 33.9 mL/kg/min).

Outcomes:

Subjects ranged in age from 33-46 years, and BMI ranged from 21.1-25.7.

Test-retest CPET measurement variability for most peak variables including oxygen consumption (VO2), workload (WL), heart rate (HR), and ventilation (VE) largely were reproduced, or even increased, between Test 1 and Test 2. However, both individuals with CFS showed significant decreases.

The low-functioning individual with CFS demonstrated decreases of 16%, 67%, and 9%, and 19% in VO2, WL, HR, and VE at VT, respectively.

The high-functioning individual with CFS showed decreases of 30%, 33%, and 14%, and 9% in VO2, WL, HR, and VE at VT, respectively.

Conclusions:

Variability in submaximal cardiac, pulmonary, and metabolic performance may be responsible for the waxing and waning symptoms and activity limitations in individuals with CFS.

The findings of this case study merit further verification in the context of adequately-powered measurement validation studies that compare test-retest CPET measurement characteristics across fatiguing health conditions.

Benjamin M. Larson is doctoral student in physical therapy, University of the Pacific, Department of Physical Therapy, 3601 Pacific Avenue, Stockton, California. Email address: b_larson2@u.pacific.edu.