- Click here for explanation of classification scheme.

• To determine if REE measurements are reproducible in stable COPD patients
• To determine the influence of physical activity on the REE measurement
• To determine if there is a difference in REE measurements using a ventilated hood or a mouthpiece.

• COPD patients in stable condition admitted to a pulmonary rehabilitation center
• Maintenance medications were allowed
• Healthy volunteers.

None specified.

Recruitment

• COPD patients in stable clinical condition admitted to a pulmonary rehabilitation center were included as subjects
• Healthy volunteers consisted of hospital staff members.

Design

Five different sub-studies were reported:

• Study 1: Cross-sectional
• Study 2: Time series
• Study 3: Cross-sectional
• Study 4: Time series
• Study 5: Randomized controlled crossover trial.

Statistical Analysis

• Comparisons between measurements under different circumstances were made using the statistical analysis of Bland and Altman
• The differences in REE under different circumstances were plotted against the means of the two methods, which was then used to calculate
  • The overall mean bias (mean difference) between the two methods
  • The associated limits of agreement (+2 standard deviations of the differences between methods)
  • The extent to which the mean bias changes with an increase in the mean of two measurements.

Timing of Measurements

• Measurements were performed in the early morning after a 10-plus-hour fast, approximately two hours after patients had received maintenance medication
• Study 2: Effect of light activities of daily living before the measurement was tested on two consecutive days
• Study 3: REE calculated after five, 10, 15, 20 and 25 minutes
• Study 4: Reproducibility of REE measurements during two-month interval was established.

Dependent Variables

• Measured REE [(VO₂, L per minute), VCO₂ (L per minute; ml per kg per minute), RQ, ventilation (L per minute)]:
  • IC type: Computerized open circuit ventilated hood
  • Equipment of calibration: Extensive description; completed at the beginning and at the end of each test
  • Coefficient of variation using std gases: Yes
  • Rest before measure (state length of time rested if available): Lying in semi-recumbent position; taken at 8:30 to 9:30 A.M.
  • Measurement length: Measurements of different duration were compared: five, 10, 15, 20, 25 and 30 minutes
  • Steady state: Investigators ensured that the subjects did not move or sleep; after initiating the measurements, time was allowed (±7 minutes) to adjust to the hood and to stabilize energy expenditure
  • Fasting length: Yes, 10 hours; two hours after maintenance medications
  • Exercise restrictions XX hours prior to test? As part of study question, activities of daily living were evaluated in Study 2.
  • Room temperature: Not specified
  • Number of measures within the measurement period: Was part of Study 4
  • Were some measures eliminated?
  • Were sets of measurements averaged? No
  • If average, identify length of each measure and number of measurements?
  • Coefficient of variation in subjects’ measures? Not specified
  • Training of measurer? Given the equipment specifications, yes
  • Subject training of measuring process? Subjects allowed initial time to acclimatize to IC
  • Monitored heart rate? Unknown
  • Body temperature? Unknown
  • Medications administered? Mention of broncho-dilators and theophylline
  • Inspiratory vital capacity; forced expiratory volume in one second (FEV1); arterial oxygen (carbon dioxide) tension (i.e., PaO₂ (kPa) and PaCO₂ (kPa)
• Study outcomes: 
  • Study 1 outcome: Variability and accuracy of measurement
  • Study 2 outcome: Differences in measurements after no activity and light activity
  • Study 3 outcome: Calculated REE
  • Study 4 outcome: Reproducibility of the measurement
  • Study 5 outcome: Difference between measurements with mouthpiece vs. hood.

Independent Variables

• Study 1: Ethanol combustion
• Study 2: Activities of daily living vs. rest:
  • One day one, patients were allowed to dress, wash and walk to the metabolic ward. After lying down for 20 minutes, energy expenditure was measured over a 30-minute period.
  • On the next day, the patients stayed in their beds until the investigator took them in a wheelchair to the metabolic ward. Both measurements completed in the same position.
• Study 3: Length of measurement
• Study 4: Measurement one vs. measurement two (two months later)
• Study 5: Ventilated hood vs. mouthpiece.

 

• Final N: See below  (gender not specified)
• Age: See below
• Ethnicity: Unknown; probably Dutch as study was done in the Netherlands.

Anthropometrics

• Study 1: Variability and accuracy of the method (12 stable COPD patients)
• Study 2: Effect of activities of daily living
• Study 3: Length of measurement
  • N=12 patients aged mean 66±6 years
  • Gender unknown.

Patients Controls

	N=12 Mean±SD	N=14 Mean±SD
Age	66±6	31±8
Weight	65.7±11.0	65.5±10
Height	170.0±7.0	172.0±8.1
IVC, percent	61±16
FEV1, percent	29±10
PaO2 (kPa), percent	8.2±1.5
PaCO2 (kPa), percent	5.5±0.6

 

• Study 4: Reproducibility of the method
  • N=12 patients aged mean 66±6 years
  • Gender unknown.

Patients

N=12	Mean±SD
Age	65±9
Weight	64.7±14.3
Height	168.0±7.8
IVC, percent	70±20
FEV1, percent	34±16
PaO2 (kPa), percent	8.1±1.4
PaCO2 (kPa), percent	5.8±0.9

• Study 5: Ventilated hood or mouthpiece
  • N=12 patients aged mean 66±6 years
  • Gender unknown.

Patients Controls

	N=12 Mean±SD	N=6 Mean±SD
Age	63±7	31±16
Weight	61.7±8.8	73.0±10.4
Height	170.0±7.0	177.3±8.2
IVC, percent	61±16
FEV1, percent	29±10
PaO2 (kPa), percent	8.2±1.5
PaCO2 (kPa), percent	5.5±0.6

 

Location

Netherlands.

 

Study 1: Variability and Accuracy of the Method

• Variability and Method Accuracy: Ethanol combustion tests revealed that the gain during the calibration was slight to high (2.2%) and that the deviation of measurements was 2.7% for O₂, 2.1% for CO₂, and 1.7% for RQ
• Study 1, after 12 patients (mean age 66±6 years) were awakened and lying in a semi-recumbent position, a 7-minute acclimatization period to the hood was allowed to stabilize energy expenditure
• [Analyst note: Measurement length was not stated but due to association with Study 2, most likely 30 minutes; one dropout due to claustrophobia.]

Study 2: Effect of Activities of Daily Living

• The same 11 patients from Study 1 were allowed to awaken, dress, wash and walk to the metabolic ward. Once they arrived, they were asked to lie down and for a 20-minute rest period; then, a 30-minute RMR was taken. On a separate day, the patients did not get out of bed and were wheeled down to the metabolic ward for a RMR measure. No significant group mean RMR differences were established between measurements performed after awakening, being wheeled down to the measurement lab and allowing a seven-minute acclimatization period compared to a RMR measure taken after light physical activities and allowing a 20-minute rest (1,406±238kcal vs. 1,431±259kcal per day).
• [Analyst note: Results section for this study reference Figure 2 that reports data for 11 individuals and discussed in text as one patient being claustrophobic in Study 1. In Figure 2, individual RMR kcal per day difference expressed relative to the mean RMR (RMR rest plus RMR activity for Group 2) ranges from resting RMR being approximately 30 to 70kcal greater to activity RMR (after a 20-minute rest) being 5 to 70kcals greater.]

Study 3: Length of Measurement

• N=12 patients aged mean 66±6 years
• Gender unknown.

	Patients	Controls
	N=12	N=14
	Mean±SD	Mean±SD
Age	66±6	31±8
Weight	65.7±11.0	65.5±10
Height	170.0±7.	172.0±8.1
IVC, percent	61±16
FEV1, percent	29±10
PaO2 (kPa), percent	8.2±1.5
PaCO2 (kPa), percent	5.5±0.6

Measured REE did not differ significantly between measurements of five, 10, 15, 20, 25 and 30 minutes’ duration. (no P-value given). 

Time, Minutes	Patients	Control
Five	1,420±242	1,510±227
10	1,410±226	1,505±224
15	1,410±237	1,514±225
20	1,414±239	1,521±229
25	1,428±243	1,531±229
30	1,436±245	1,535±231

• In Study 3, the same group of patients and an additional 14 healthy controls (mean age 31±8 years), group mean RMR not differ between a five-, 10-, 15-, 20-, 25- and 30-minute measurement duration
• [Analyst note: There is no rest time described for Study 3; therefore, healthy adults either slept overnight in facility and were wheeled down and given a seven-minute acclimatization period after awakening or allowed to complete daily living activities and given a 20-minute rest period]
• Group mean RMR in healthy adults ranged from the lowest at 1,505±224kcal per day after a 10-minute measurement interval (plus rest time) to 1,535±231kcal per day at a 30-minute measurement interval (plus rest time)
• Group mean RMR in patients ranged from the lowest at 140±267kcal per day after a 10-minute measurement interval (plus rest time) to 1,436±245kcal per day at a 30-minute measurement interval (plus rest time).

Study 4: Reproducibility of the Method

• N=12 patients aged mean 66±6 years
• Gender unknown.

	Patients
	N=12
	Mean±SD
Age	65±9
Weight	64.7±14.3
Height	168.0±7.8
IVC, percent	70±20
FEV1, percent	34±16
PaO2 (kPa), percent	8.1±1.4
PaCO2 (kPa), percent	5.8±0.9

Average REE in the 12 weight-stable patients after two months was not significantly different from the baseline value at admission to the center (198±138kcal per day).

Study 5: Ventilated Hood or Mouthpiece

• N= 12 patients aged mean 66±6 years
• Gender unknown.

	Patients	Controls
	N=12	N=6
	Mean±SD	Mean±SD
Age	63±7	31±16
Weight	61.7±8.8	73.0±10.4
Height	170.0±7.0	177.3±8.2
IVC, percent	61±16
FEV1, percent	29±10
PaO2 (kPa), percent	8.2±1.5
PaCO2 (kPa), percent	5.5±0.6

The difference between measurements with mouthpiece and ventilated hood was larger in patients than in control subjects, but no systematic difference could be established between both devices in either group. The difference between measured REE (using only O₂) or VO₂ and VCO₂ measurements amounted to 16kcal per day, or -1.9% (range, -3% to 0.3%).

 

As stated by the author in body of report:

• The ethanol combustion tests revealed that when properly maintained, calibrated and interfaced to the patient, the device is very accurate
• A considerable number of patients were dyspneic at rest or suffered from severe exercise impairment... in agreement with finding in patients not suffering from COPD, we found that limited physical activity had no measurable effect on REE when a short rest was taken before the assessment
• Based on the experiments and to obtain an optimum between sample frequency and acceptability of the measurements, we changed the duration of our standard REE experiments from 30 minutes to 15 minutes. Reproducibility of two measurements with the ventilated hood performed under the same standard conditions with an interval of two months was excellent and comparable with findings in healthy subjects…
• Although in some patients measurements with a mouthpiece and a ventilated hood indeed varied substantially, no systematic difference was established in patients or control subjects
• The following implications for the clinical measurement of REE can be drawn from these results: REE measurements using a ventilated hood are highly reproducible, suggesting that one measurement will suffice to characterize resting metabolic rate at a certain time point in patients with stable COPD.... REE in patients with severe COPD can be measured on an outpatient basis providing a rest is taken before the measurement.

University/Hospital:

University of Limbourg

Strengths

• Comprehensive, and detailed description of the indirect calorimeter used, with attention to gas pressure and flow, humidity and calibration
• Use of the Bland-Altman technique to establish limits of agreement between two measurements two months apart and in comparing differences between measurement type
• Did a nice job describing the medication intervening possibilities of increasing or decreasing REE.

Generalizability/Weaknesses

• Generalizability to pulmonary rehab settings and due to small sample size, unable to apply to general outpatient clinic settings
• Very small convenience patient samples; not many specifics about inclusion and exclusion criteria
• Healthy ‘control’ sample is also open to bias as it is a convenience sample of hospital staff members. Since no blinding is possible, staff members more trained than patients. Also, control sample is younger and heavier than patient sample, weakening statements of comparison based on tolerance to machine type tolerance and age.
• Intervening factors: As discussed by the researchers, the precise influence of B2 agonists and theophylline was not measured because withdrawing treatment might exacerbate the condition. [In contrast], bronchodilating treatment itself may reduce the work of breathing.

Analyst Note

Little information was available about the statistical analysis and which sample was used for each of the five studies included.