Repeated maximal exercise tests of peak oxygen consumption in people with myalgic encephalomyelitis/chronic fatigue syndrome: a systematic review and meta-analysis

Figures & data

Table 1. Correlation coefficients used to calculate change SDs.

Variable	ME/CFS correlation coefficient	Control correlation coefficient
VO2peak	0.975	0.96
VO2 at AT	0.927	0.858
Peak WR	0.984	0.996
WR at AT	0.916	0.979

Calculated using data from Nelson et al. [13].

Table 2. Data inputted into meta-analysis for difference in change VO_2peak and WR at peak between people with ME/CFS and controls.

			Change in VO2peak (ml kg^−1 min^−1)		Change in work rate (W)
Study	Sample size ME/CFS	Sample size control	Mean difference (SD) ME/CFS	Mean difference (SD) control	Mean difference (SD) ME/CFS	Mean difference (SD) control
Vermeulen et al. [7]	15	15	−1.33 (1.68)	0.73 (1.39)	−6.3 (11.5)	11.1 (18.3)
Hodges et al. [14]	10	10	1.32 (3.04)	1.08 (1.25)	−9 (8.08)*	3 (3.86)*
VanNess et al. [8]	6	6	−5.76 (3.19)*	0.47 (2.3)*	–	–
Snell et al. [12]	51	10	−1.07 (1.04)*	−1.08 (1.23)*	−7.94 (5.59)*	2.8 (2.84)*
Nelson et al. [13]	16	10	0.1 (2.07)	0.38 (1.74)	−1.9 (10.5)	2 (3.5)
Lien et al. [23]	18	15	−1.44 (1.04)	−0.93 (1.68)	−6.97 (7.18)	−4.27 (6)

Data for VO_2peak and work rate reported as the change in mean difference (test 2 minus test 1) and standard deviation of the change. *Change SD has been estimated. – data not available in study.

Table 3. Data inputted into meta-analysis for difference in change VO₂ and WR at AT between people with ME/CFS and controls.

			Change in VO2 (ml kg^−1 min^−1)		Change in work rate (W)
Study	Sample size CFS/ME	Sample size control	Mean difference (SD) ME/CFS	Mean difference (SD) control	Mean difference (SD) ME/CFS	Mean difference (SD) control
Vermeulen et al. [7]	15	15	−0.87 (1.77)	1.07 (2.63)	−4.4 (9.66)	7.67 (19.5)
Hodges et al. [14]	10	10	1.27 (2.72)*	4.9 (6.65)*	−12 (15.36)*	13 (15.68)*
VanNess et al. [8]	6	6	−4 (2.15)*	0.45 (2.72)*	–	–
Snell et al. [12]	51	10	−1.38 (1.1)*	0.29 (1.67)*	−27.31 (8.22)*	5.5 (4.67)*
Nelson et al. [13]	16	10	−0.51 (1.59)	−0.64 (1.05)	−15.3 (11.9)	−2.5 (3.5)
Lien et al. [23]	18	15	–	–	−7 (9.96)	Query

Data for VO_2peak and work rate reported as the change in mean difference (test 2 minus test 1) and standard deviation of the change. *Change SD is estimated. Query – there appeared to be some anomalies in the data that we were unable to clarify. – data not available in study.

Table 4. Anomalies and decision making during data extraction.

Study	Anomaly	Action	Decision
Lien et al. [23]	Figure 5(D) in the published manuscript relating to WR at AT in the control group did not appear to be correct	The research team was contacted however unable to verify data	These data were not included in the meta-analysis
Snell et al. [12]/Davenport et al. [11]	Appeared to be the same data set presented in both papers	The research team was contacted and Davenport et al. [11] confirmed that the study involved analysis of the same dataset as Snell et al. [11]	The original data from Snell et al. [12] were included
Snell et al. [12]/Davenport et al. [11]	Data for the WR at AT for the ME/CFS group differed greatly	The research team was contacted however unable to clarify	The original data from Snell et al. [12] were included, however, this included a mean difference of −27.31 W compared with −5.4 W in Davenport et al. [11]

Figure 1. PRISMA flow chart. From: Page et al. [17].

Table 5. Summary of included papers.

Study	ME/CFS diagnostic criteria	ME/CFS: Control sample size %Female	Controls defined as	ME/CFS and controls matched for	Description of VO2peak test	Results of study VO2peak (ml kg^−1 ml^−1) Mean ± SD Change data is included if reported in study
Vermeulen et al. [7]	Fukuda	15:15 100%	Healthy sedentary	–	Performed on cycle ergometer 3 min without activity, 3 min of unloaded pedalling, followed by pedalling against increasing resistance until exhaustion Criteria used to assess if maximum effort was achieved is not described	CFS/ME Test 1: 22.3 ± 5.7 Test 2: 20.9 ± 5.5 Change: −1.33 ± 1.68 Controls Test 1: 31.2 ± 7.0 Test 2: 31.9 ± 7.4 Change: 0.73 ± 1.39
Hodges et al. [14]	Fukuda and Canadian and ICC	10:10 82%	Gender and age match healthy controls	Age and gender	Cycled on a cycle ergometer at between 50 and 80 rpm. Starting at 15 W load increased by 15 W/min Criteria for maximum effort was voluntarily termination by the participant or when they were unable to maintain a pedal rate of 50 rpm, or the ACSM termination criteria were met	CFS/ME Test 1: 24.95 ± 8.9 Test 2: 26.27 ± 7.78 Controls Test 1: 31.99 ± 10.88 Test 2: 33.06 ± 12.5
VanNess et al. [8]	Fukuda	6:6 100%	Sedentary female controls	Sex	People with ME/CFS performed either a modified Bruce treadmill protocol or a 10 W/min ramping protocol on a cycle ergometer. Controls completed a 20 W/min ramping protocol on a cycle ergometer Criteria used to assess if maximum effort was achieved is not described	CFS/ME Test 1: 26.23 ± 4.92 Test 2: 20.47 ± 1.80 Controls Test 1: 28.43 ± 7.27 Test 2: 28.90 ± 8.06
Snell et al. [12]	Fukuda	51:10 100%	Sedentary controls	Age and BMI	3 min rest followed by 1 min unloaded cycling. Participants were required to maintain 60–80 rpm. Workload increased by 5 W/s (15 W/min) Criteria for maximum effort: RER≥1.1 as well as one of the following; (1) plateau in oxygen consumption (2) rating perceived exertion >17 (3) heart rate >85% age predicted max. Reported that all participants achieved RER ≥1.1; however, data are not provided	CFS/ME Test 1: 21.51 ± 4.09 Test 2: 20.44 ± 4.47 Controls Test 1: 25.04 ± 4.41 Test 2: 23.96 ± 4.30
Nelson et al. [13]	Fukuda and Canadian and ICC	16:10 53.85%	Healthy participants	Age, BMI, physical activity status	Seated rest for 4–6 min. Commence cycling a self-selected cadence for 5 min at 40 W for males and 30 W for females. Workload increased by 5 W/20 s until exhaustion Criteria for maximum effort: required to meet at least two of the following (1) achieve at least 90% age predicted max HR (2) RER >1.1 (3) RPE ≥ 17	CFS/ME Test 1: 27.3 ± 9.2 Test 2: 27.4 ± 8.8 Controls Test 1: 29.9 ± 6.1 Test 2: 30.3 ± 6.2
Lien et al. [23]	Carruthers et al. (2003)	18:15 100%	Healthy control participants	–	Designed for test to last between 8 and 12 min. Rate varied based on demographics. Protocol – 2 min rest, 2 min unloaded pedalling at 60–75 rpm. Linear increase in power till exhaustion or couldn’t maintain 45 rpm Criteria used to assess if maximum effort was achieved is not described	Change data were extracted using digitising software. Test 1 and test 2 data reported in figures only

W – Watts. Rpm – revolutions per minute. RER – respiratory exchange ratio. ACSM – American College of Sports Medicine.

Table 6. Summary of the assessment of methodological quality.

Question	Vermeulen et al. [7]	Hodges et al. [14]	VanNess et al. [8]	Snell et al. [12]	Nelson et al. [13]	Lien et al. [23]
Source of sample is clear	Good	Not reported	Adequate	Adequate	Adequate	Adequate
Sampling method is described	Not reported	Not reported	Adequate	Not reported	Not reported	Not reported
Power analysis conducted	Not reported	Not reported	Not reported	Not reported	Not reported	Good
Entry criteria justified	Good	Good	Good	Good	Good	Good
Control group included	Good	Good	Good	Good	Good	Good
Control group identifiable	Good	Good	Good	Good	Good	Good
Source of controls explained	Not reported	Not reported	Not reported	Not reported	Good	Adequate
Controls are matched	Not reported	Good	Good	Good	Good	Not reported
Stat. sig, cases vs. controls	Good	Not reported	Not reported	Good	Good	Good
Overview of exposure	Good	Good	Good	Good	Good	Good
Adequate measure of outcome(s)	Adequate	Good	Poor	Good	Good	Good
Description of exercise test	Adequate	Good	Adequate	Good	Good	Adequate
Criteria for max effort	Not reported	Adequate	Poor	Adequate	Adequate	Not reported
Control of extraneous variables	Not reported	Good	Good	Not reported	Good	Adequate
Explanation of missing data	Not reported	Not reported	Not reported	Not reported	Not reported	Adequate
Accuracy of results	Adequate	Adequate	Adequate	Adequate	Adequate	Poor
Total score	15	18	14	20	24	19

Scoring: ‘Not reported/ Poor’ resulted in a score of 0, ‘Adequate’ resulted in a score of 1, ‘Good’ resulted in a score of 2. Maximum score 32.

Table 7. Individual study level differences for changes in WR at AT (W).

Study	Mean difference (95% CI)
Nelson et al. [13]	−12.8 (−19.02 to −6.58)
Vermeulen et al. [7]	−12.07 (−23.03 to −1.06)
Hodges et al. [14]	−25 (−38.6 to −11.4)
Snell et al. [12]	−32.8 (−36.48 to −29.14)

Minus values favour control group (i.e. WR at AT reduced in ME/CFS).

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Data availability statement

All data that has been collated in the development of this review is presented in this manuscript.