COPD: Determination of Energy Needs (2007)


Calikoglu M, Sahin G, Unlu A, Ozturk C, Tamer L, Ercan B, Kanik A, Atik U.  Leptin and TNF-alpha levels in patients with chronic obstructive pulmonary disease and their relationship to nutritional parameters.  Respiration 2004;71:45-50.

PubMed ID: 14872110
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 detect serum leptin and TNF-alpha levels in COPD patients without weight loss during stable disease and acute exacerbation, and investigate the relationships between leptin, TNF-alpha, and nutritional parameters at different stages of the disease.
Inclusion Criteria:


  • COPD according to guidelines of American Thoracic Society and chronic airway obstruction defined as measured FEV1 <70% of reference value
  • Irreversible obstructive airway disease:  < 10% improvement in FEV1 after inhalation of a beta-2 agonist
  • No concomitant confounding disease such as malignancies, GI or severe endocrine disorders, collagen vascular disease, cardiac failure, infections or recent surgery


  • Healthy, normal physical examinations, blood counts and chemistries
Exclusion Criteria:


  • Not receiving nutritional support therapy


  • No medical illness, no signs or symptoms of infection 
Description of Study Protocol:


Patients with COPD were consecutively admitted to the pulmonary center.  Recruitment methods for controls not described.


Case-Control Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Not applicable.

Statistical Analysis

Univariate ANOVA used to compare controls with COPD patients.  In each group, Pearson's correlation coefficient was calculated.  Groups were compared with the Z test.

Data Collection Summary:

Timing of Measurements

Measurements made in all subjects and compared.

Dependent Variables

  • Body height, weight, BMI, % IBW
  • Percent fat mass measured through DEXA 
  • Sum of skinfold thicknesses at 4 sites:  biceps, triceps, subscapular, suprailiac
  • Serum leptin and TNF-alpha levels measured by ELISA
  • Pulmonary function tests measured with spirometry

Independent Variables

  • Stable COPD, acute exacerbation, or healthy

Control Variables


Description of Actual Data Sample:

Initial N: 26 stable COPD patients, 16 COPD patients with acute exacerbation and 15 controls, all males

Attrition (final N):  As above

Age:  See Results

Ethnicity:  not mentioned

Other relevant demographics:

Anthropometrics:  All subjects were male, but controls not matched for anything else

Location:  Turkey


Summary of Results:



Exacerbation (n =16) Stable (n = 26)

Controls (n=15)

Age, years

62.18 +/- 2.50 58.26 +/- 1.70 54.73 +/- 2.23


101.56 +/- 2.68

103.57 +/- 2.69

105.06 +/- 1.90


25.24 +/- 0.64

24.54 +/- 0.60

24.31 +/- 0.45

Fat % 30.15 +/- 1.55 26.65 +/- 0.88 27.26 +/- 1.08
Sum of skinfolds, cm 49.68 +/- 3.08 53.69 +/- 3.82 62.00 +/- 4.88
FVC, % predicted 74.31 +/- 2.87, p < 0.05 75.19 +/- 16, p < 0.05 95.86 +/- 1.60
FEV1, % predicted 51.50 +/- 2.77, p < 0.05 50.92 +/- 2.83, p < 0.05 88.40 +/- 2.36
FEV1/FVC 45.06 +/- 2.26, p < 0.05 62.92 +/- 1.46 92.00 +/- 1.39
PaO2, mmHg 65.45 +/- 2.01, p < 0.05 76.20 +/- 1.51 Not determined
PaCO2, mmHg 49.96 +/- 1.03, p < 0.05 42.58 +/- 0.52 Not determined
Leptin-BMI correlation 0.379 (p = 0.14) 0.454 (p = 0.02) 0.748 (p = 0.001)
Leptin-% IBW correlation 0.400 (p = 0.12) 0.481 (p = 0.01) 0.662 (p = 0.007)
Leptin-% FM correlation 0.045 (p = 0.86) 0.570 (p = 0.002) 0.856 (p = 0.0001)

Other Findings

Serum leptin and TNF-alpha levels were significantly higher in the patients experiencing exacerbation than in the stable patients and controls.

Although leptin levels were lower and TNF-alpha levels were higher in the stable patient group than controls, differences were not statistically significant.

Leptin levels were significantly correlated with the nutritional parameters in both control and stable groups.

However, in patients with acute exacerbation, a correlation between leptin and nutritional parameters was not found.

There was no significant relationship between TNF-alpha and nutritional parameters in the 3 groups.

In addition, while there was no correlation between leptin and TNF-alpha levels in the stable and control groups, a significant positive correlation was observed in patients with exacerbation. 

Author Conclusion:

In conclusion:

1.  During an acute exacerbation of COPD, the involvement of the systemic inflammatory response may be more pronounced than in stable patients, and elevated TNF-alpha levels may be related to increased inflammation in patients

2.  Circulating TNF-alpha levels were associated with increased leptin levels

3.  Although leptin and nutritional parameters were correlated in the stable COPD patients, it was weaker compared to controls and disappeared completely during an exacerbation.

Therefore, inappropriately increased levels of leptin and TNF-alpha during recurrent acute exacerbations in patients with COPD may lead to changes in nutritional parameters and body weight during the course of the disease.

Funding Source:
Reviewer Comments:
Small sized groups, only contained males.  Recruitment for control group not well described and controls were not matched except for sex.  No power calculations done.
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? 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) 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.) 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? 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? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  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? ???
  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? No
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