COPD: Determination of Energy Needs (2007)


Creutzberg EC, Wouters EF, Vanderhoven-Augustin IM, Dentener MA, Schols AM.  Disturbances in leptin metabolism are related to energy imbalance during acute exacerbations of chronic obstructive pulmonary disease.  Am J Respir Crit Care Med 2000; 162(4 Pt 1):1239-45.

PubMed ID: 11029324
Study Design:
Case-Control Study
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To investigate the course of the energy balance in relation to leptin and glucose metabolism and the systemic inflammatory response in patients with COPD hospitalized for an acute exacerbation of their lung failure.
Inclusion Criteria:
  • Acute exacerbation defined as a recent increase in dyspnea, cough, and sputum production of sufficient severity to warrant hospital admission; presence of exacerbation determined by independent chest physician
  • COPD defined according to American Thoracic Society criteria
Exclusion Criteria:


  • Suffering from concomitant diseases
  • Stay in hospital less than 7 days


  • Not exhibiting any acute or chronic disease
  • Not taking medication influencing energy or glucose metabolism
Description of Study Protocol:


Subjects consecutively admitted to the hospital suffering from an acute exacerbation of COPD.


Case-Control Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Patients received bronchodilating medication 2-3 hours before measurements started.

Statistical Analysis

Paired t test used for comparisons across days with Bonferroni correction.  Differences between cases and controls on Days 1 and 7 compared using Student's t test for independent samples and Mann-Whitney U test.  Plasma leptin was logarithmically transformed.  Pearson's product-moment correlation coefficients calculated on Days 1 and 7.  Linear stepwise regression performed to investigate which factor could explain variation in dietary intake/REE ratio.

Data Collection Summary:

Timing of Measurements

Measurements performed in early morning after 10 hour fast.  Measurements done at Days 1, 3, 5 and 7 after hospitalization.

Dependent Variables

  • FEV1, inspiratory vital capacity and peak expiratory flow calculated from flow-volume curve using spirometry
  • Arterial oxygen and carbon dioxide tension analyzed on blood gas analyzer
  • Body height, weight
  • Body composition measured through bioelectrical impedance analysis
  • Habitual dietary intake evaluated using diet history method with cross check
  • Resting energy expenditure measured by indirect calorimetry
  • Blood samples analyzed for glucose, insulin, inflammatory parameters, leptin

Independent Variables

  • COPD or healthy

Control Variables

  • Sex
  • Age
  • Percentage fat mass
Description of Actual Data Sample:

Initial N: 17 subjects, 11 men, 6 women.  23 healthy controls, 16 men, 7 women

Attrition (final N):  17 cases, 23 controls

Age: mean age 66 +/- 10 years

Ethnicity:  not mentioned

Other relevant demographics:

Anthropometrics:  Healthy elderly control subjects not well described.

Location:  The Netherlands


Summary of Results:

Correlation Analysis - Leptin and Glucose Metabolism on Day 7 of COPD Acute Exacerbation


Natural Logarithm of Leptin Glucose


Fat Mass, % Body Weight

r = 0.73, p = 0.10

r = 0.71, p = 0.022






Insulin NS NS --
Soluble TNF receptor 55 r = 0.65, p = 0.041 r = 0.81. p = 0.015 NS

Soluble TNF receptor 75




Other Findings

On admission, the dietary intake/REE ratio was severely depressed (1.28 +/- 0.57) but gradually restored until Day 7 (1.65 +/- 0.45, p = 0.005 versus Day 1).

Glucose and insulin concentrations were elevated on admission, but on Day 7 only plasma glucose was decreased.

The sTNF-Rs were not different from healthy subjects and did not change.

Plasma leptin, adjusted for fat mass expressed as percentage of body weight, was elevated on Day 1 compared with healthy subjects (1.82 +/- 3.85 versus 0.32 +/- 0.72 ng%/ml, p = 0.008), but decreased significantly until Day 7 (1.46 +/- 3.77 ng%/ml, p = 0.015 versus Day 1).

On Day 7, sTNF-R55 was, independently of % fat mass, correlated with the natural logarithm of leptin (r = 0.65, p = 0.041) and with plasma glucose (r = 0.81, p = 0.015).

In addition, the dietary intake/REE ratio was not only inversely related with the natural log of leptin (-0.74, p = 0.037), but also with sTNF-R55 (r = -0.93, p = 0.001) on Day 7. 

Author Conclusion:
In conclusion, temporary disturbances in the energy balance were seen during an acute exacerbation of COPD, related to increased leptin concentrations as well as to the systemic inflammatory response.  Evidence was found that the elevated leptin concentrations were in turn under control of the systemic inflammatory response, and, presumably, the high-dose systemic glucocorticosteroid treatment.
Funding Source:
Reviewer Comments:
Recruitment and descriptions of controls not well described.  Small sample sizes.
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) N/A
  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) N/A
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? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  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.) ???
  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? N/A
  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.) N/A
  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? Yes
  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? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  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? Yes
  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