COPD: Determination of Energy Needs (2007)


Burdet L, de Muralt B, Schutz Y, Fitting JW.  Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease.  Thorax 1997;52(2):130-5.

PubMed ID: 9059472
Study Design:
Randomized Crossover Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To examine whether bronchodilators had a thermogenic effect in patients with stable COPD.  The aim of the study was to determine the effect of salbutamol and ipratropium bromide administration on REE in patients with COPD.
Inclusion Criteria:
  • Patients with stable COPD
  • Ratio of FEV1/FVC <70% predicted value
  • Reversibility of <10% of predicted FEV1 after inhalation of 400 mg salbutamol
  • All patients could tolerate withdrawal of bronchodilators for 16 hours
  • All were apyrexial at time of study
Exclusion Criteria:
  • None specifically mentioned
  • None had evidence of diabetes, cancer, digestive or renal disease
Description of Study Protocol:


Patients studied at the end of a stay in the Pulmonary Rehabilitation Center of the Rolle Hospital.


Randomized Crossover Trial.

Blinding used (if applicable)

Double blind.

Intervention (if applicable)

Random order of salbutamol (5 mg), ipratropium bromide (0.5 mg), or placebo.

Statistical Analysis

Mean baseline REE values during 3 measurement sessions were compared by repeated measures ANOVA.  Post-tests then performed with Bonferroni t test.  Differences between treatments compared using repeated measures ANOVA followed by paired t tests.  Relationship between maximal change in REE after bronchodilator and baseline REE analyzed by linear regression.  Differences between those receiving and not receiving theophylline completed using two-tailed unpaired t tests.

Data Collection Summary:

Timing of Measurements

Subjects studied on 3 consecutive mornings after overnight fast.  REE was measured at 30, 60, 120 and 180 minutes after nebulization.

Dependent Variables

  • Weight, height, BMI
  • Body fat measurements through skinfold measurements at 4 sites:  bicipital, tricipital, subscapular and suprailiac
  • Fat free mass through bioelectrical impedance analysis
  • Forced expiratory flow rates measured by mass flow anemometer
  • Carbon monoxide transfer factor by single breath method
  • Arterial blood gas tensions through blood gas analyzer
  • Resting energy expenditure measured by indirect calorimetry
  • Heart rate and respiratory rate 

Independent Variables

  • Salbutamol, ipratropium bromide, or placebo
  • Theophylline concentration measured with polarization fluorescence system in serum samples

Control Variables


Description of Actual Data Sample:

Initial N: 13 patients, 10 men, 3 women

Attrition (final N):  13

Age:  mean age 68.3 +/- 7.3 years

Ethnicity:  not mentioned

Other relevant demographics:  All patients had been treated with salbutamol on a regular basis.


Location:  Switzerland


Summary of Results:

Other Findings

2 patients were obese and 2 were underweight; mean BMI of all patients was 25.2 +/- 4.8.

FEV1 increased both after salbutamol and after ipratropium.

The difference in mean response between salbutamol and placebo over 180 minutes was +199 ml (95% CI:  +104 to +295, p < 0.001).

The difference in mean response between ipratropium and placebo was +78 ml (95% CI:  +2 to +160, p < 0.05).

There were no differences in baseline REE between treatments.  REE increased after salbutamol but was not changed after ipratropium.

The difference in mean response between salbutamol and placebo was +4.8% of baseline REE (95% CI:  +2.2 to +7.4, p < 0.002).

Heart rate increased after salbutamol but not after ipratropium.

The difference in mean response between salbutamol and placebo was +5.5 beats/minute (95% CI: +2.6 to +8.4, p < 0.002). 

Author Conclusion:
In conclusion, the nebulization of salbutamol, but not ipratropium bromide, induced a sustained increase in the REE of patients with COPD treated with bronchodilators on a chronic basis.  The observed thermogenic effect of beta-2 agonists does not explain the hypermetabolism frequently present in COPD because hypermetabolism has also been reported after withdrawal of beta-2 agonists.  However, when added to other factors, it may further disrupt the energy balance.
Funding Source:
Reviewer Comments:
Small sample size and not homogeneous.  1 day of measurement.  Not sure if 0.5 mg ipratropium would be enough to see the same effect as 5 mg salbutamol.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? ???
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes