COPD: Determination of Energy Needs (2007)


Schols AM, Creutzberg EC, Buurman WA, Campfield LA, Saris WH, Wouters EF.  Plasma leptin is related to proinflammatory status and dietary intake in patients with chronic obstructive pulmonary disease.  Am J Respir Crit Care Med 1999;160(4):1220-6.

PubMed ID: 10508810
Study Design:
Cross-Sectional Study
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To investigate cross-sectionally the relationship between plasma leptin concentrations and soluble TNF receptor (sTNF-R) 55 and 75 concentrations, as a reflection of an enhanced inflammatory status.
Inclusion Criteria:
  • COPD according to the American Thoracic Society guidelines and chronic airflow obstruction defined as a measured FEV1 < 70% of the reference value
  • Irreversible obstructive airway disease, <10% improvement in FEV1 expressed as a percentage of predicted after inhalation of a beta-2 agonist
  • Clinically stable condition, not suffering from a respiratory tract infection
  • No concomitant confounding diseases, such as malignant disease, GI disorders, severe endocrine disorders or recent surgery
  • No suspected abnormal fluid balance as manifested by the presence of edema or regular use of diuretics
  • For prospective study, subjects were also suffering from below normal body weight (BMI < 23) and/or depletion of fat free mass (fat free mass index < 16)
Exclusion Criteria:
Excluded if not included above.
Description of Study Protocol:


Random group of patients with COPD were consecutively admitted to a pulmonary rehabilitation center and were included in the study if they met inclusion/exclusion criteria.


Cross-Sectional Study/Nonrandomized Clinical Trial.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Standardized nutritional therapy consisting of 500 - 750 kcal/day given as 3 liquid supplements of 200 ml each, for 8 weeks.

Statistical Analysis

Differences between groups statistically analyzed using unpaired Student's t test.  After curve estimation, linear, exponential or logarithmic Pearson product moment correlation coefficients were calculated.  Relationship between leptin and the sTNF receptors was adjusted for fat mass and oral corticosteroid use during partial correlation analysis.  After simple correlations, regression model was fitted to the data to select variables contributing to the explained variation in plasma leptin concentration.

Data Collection Summary:

Timing of Measurements

All measurements performed during the first 2 weeks after admission to the center, and in the prospective study in addition after 8 weeks of nutritional treatment.

Dependent Variables

  • Body height, weight, BMI
  • Body composition by deuterium dilution
  • Subregional fat mass assessed by DEXA 
  • REE measured by indirect calorimetry
  • Plasma concentrations of leptin and sTNF-R 55 and 75 by ELISA, glucose 
  • Response to nutritional therapy was defined as weight change reached after 8 weeks of treatment
  • Dietary intake assessed using dietary history method with cross-check
  • Lung function measurements included spirometry, thoracic gas volumes, and diffusing capacity for carbon monoxide, blood gases

Independent Variables

  • Standardized nutritional therapy consisting of 500 - 750 kcal/day given as 3 liquid supplements of 200 ml each
  • Evaluation of presence and severity of emphysema performed by high-resolution computed tomography

Control Variables

  • Fat mass
  • Oral corticosteroid use
Description of Actual Data Sample:

Initial N: 27 male patients with emphysema, 15 male patients with chronic bronchitis

Attrition (final N):  27 with emphysema, 15 with chronic bronchitis

Age:  emphysema mean age:  67 +/- 8 years, chronic bronchitis mean age:  67 +/- 5 years

Ethnicity: not mentioned

Other relevant demographics:  see Results 


Location: The Netherlands


Summary of Results:



Emphysema (n=27)

Chronic Bronchitis (n=15)

p Value

BMI 21.6 +/- 3.0 25.1 +/- 3.3 0.001
FFM (kg)

47.0 +/- 6.7

48.7 +/- 7.1


FM (kg)

15.7 +/- 6.4

23.5 +/- 7.6


Dietary intake (kcal/d) 2144 +/- 536 1803 +/- 533 0.055
REE (kcal/d) 1494 +/- 194 1588 +/- 232 0.169
FVC, % predicted 86 +/- 14 83 +/- 15 0.434
FEV1, % predicted 33 +/- 10 43 +/- 14 0.016
TLC, % predicted 120 +/- 19 118 +/- 17 0.663
DLCO, % predicted 45 +/- 17 71 +/- 19 <0.001
PaO2, kPa 9.4 +/- 1.4 10.5 +/- 0.9 0.012
PaCO2, kPa 5.8 +/- 0.7 5.6 +/- 1.0 0.354
sTNF-R55, ng/ml 0.65 +/- 0.32 0.65 +/- 0.30 0.992
sTNF-R75, ng/ml 1.57 +/- 0.39 1.66 +/- 0.46 0.512
Glucose, mmol/L 5.9 +/- 0.9 6.5 +/- 1.5 0.121
Leptin, ng/ml 2.6 +/- 2.7 5.1 +/- 3.0 0.020

Other Findings

Emphysematous patients were characterized by a lower BMI due to a lower fat mass (p = 0.001) and by lower mean (detectable) leptin concentrations (p = 0.020) compared with bronchitic patients.

Leptin was exponentially related to fat mass in emphysema (r = 0.74, p < 0.001) and in chronic bronchitis (r = 0.80, p = 0.001).

Furthermore, a significant partial correlation coefficient between leptin and sTNF-R-55 adjusted for fat mass and oral corticosteroid use was seen in emphysema (r = 0.81, p < 0.001) but not in chronic bronchitis.

In 17 predominantly emphysematous depleted male patients with COPD, baseline plasma leptin divided by fat mass was in addition logarithmically inversely related to baseline dietary intake (r = -0.50, p = 0.047) and to the degree of weight change after 8 weeks of nutritional support (r = -0.60, p = 0.017).  

Author Conclusion:
Based on the present findings, it may be argued whether oral nutritional support alone is an appropriate treatment strategy in depleted patients with COPD suffering from anorexia owing to the presence of a systemic inflammatory response.  In line with this hypothesis we showed in a subgroup of predominantly emphysematous depleted patients with COPD that baseline plasma leptin concentrations were inversely related to baseline dietary intake and to the change in body weight after 8 weeks of nutritional therapy.  Further longitudinal studies are indicated to confirm this proposed cytokine-leptin hypothesis in pulmonary cachexia which may then open a novel approach to combat this significant comorbidity in COPD.
Funding Source:
Reviewer Comments:
Only males studied and small sample sizes.  All measurements performed over span of 2 weeks.  Did not include age-matched healthy control group.
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? ???
  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? ???
  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.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  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? Yes
  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? 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? ???
  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? ???
  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? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
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