COPD: Effectiveness of Therapies (2007-2008)

Gosker HR, Bast A, Haenen G, Fischer M, van der Vusse GJ, Wouters E, Schols A.  Altered antioxidant status in peripheral skeletal muscle of patients with COPD. Respiratory Medicine 2005; 99:118-125. PubMed ID: 15672860
Study Design:
Case Control
C - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
The purpose of the current study was to assess the antioxidant status in skeletal muscle of patients with COPD compared to healthy controls at rest. 
Inclusion Criteria:


  • COPD by ATS guidelines
  • irreversible obstructive airway disease
  • clinically stable condition
  • no respiratory tract infection
  • no exacerbation of COPD > 4 weeks prior to the study


  • healthy
  • age matched
Exclusion Criteria:


  • malignancy
  • cardiac failure
  • distal arteriopathy
  • recent surgery severe endocrine, hepatic or renal disorders
  • use of anticoagulant medication



Description of Study Protocol:


  • controls by volunteer recruitment through local newspaper advertisement
  • recruitment for patients unclear

Design:  Case Control study 

Blinding used (if applicable):  Not applicable

Intervention (if applicable) Not applicable

Statistical Analysis

Unpaired Student's t-test or Pearson correlation; group differences by chi square test, two tailed probability

Data Collection Summary:

Timing of Measurements

Muscle biopsies analyzed and compared.

Dependent Variables

  • total antioxidant capacity by Trolox equivalent antioxidant capacity (TEA) assay (van den Berg et al 1999)
  • vitamin E levels by hexane extraction and high performance liquid chromatography (HPLC) analysis
  • glutathione levels by enzymatic reduction absorption level
  • uric acid levels
  • superoxide dismutase activity
  • glutathione reductase activity by absorbence increase
  • glutathione peroxidase activity
  • glutathione-S-transferase activity
  • MDA by HPLC

Independent Variables

  • COPD or control

Control Variables


Description of Actual Data Sample:

Initial N: 21 patients (3 female, 18 males), 12 controls (4 female, 8 males)

Attrition (final N): 21 patients, 12 controls

Age: controls = 65 + 7; COPD = 65 + 8

Ethnicity: unclear

Other relevant demographics: smoking history (pack years): controls 15 + 5; patients 51+ 7

Anthropometrics:  age-matched controls.  There were no statistically significant differences in age and gender between groups.  Lung function was impaired in patients with COPD, and patients had a lower BMI, reduced peripheral muscle strength, and decreased exercise capacity compared to controls.

Location: Maastricht, The Netherlands


Summary of Results:

Total antioxidant capacity (TEAC) was significantly increased in COPD, being 25% higher than in healthy controls.  Muscle tissue uric acid levels were signficantly higher (24%) in patients compared to control subjects.  Secondary to comparison of antioxidant capacities of TEAC and uric acid, it was calculated that the difference in the uric acid level accounted for 2% of the difference in TEAC. 

Table 2  Muscle biopsy data





SOD (U/mg protein)

6.9 + 5.0 9.5 + 4.0

GR (U/mg protein)

 12.8 + 2.5

13.3 + 3.6

GST (U/mg protein)

0.17  + 0.07

0.23 + 0.08*

GPX (nmol NADPH/min/mg protein

20.7 + 6.7

 23.1 + 6.4
Glutathione (nmol/mg protein) 18.5 + 4.9 19.6  + 5.2
TEAC (nmol Trolox Eq/mg protein)  46 + 8.8  58 + 12.7**
Uric acid (nmol/mg protein)  1.04 + 0.21  1.29 + 0.31*
Vitamin E (ug/mg tissue)  21.6 + 0.5 17.3 + 0.5*
MDA (nmol/mg protein)  0.69 + 0.17  0.77 + 0.37

 Values are mean + SD; Significance of difference copared to controls:*P<0.05; **P<0.01.  GPX: glutathione peroxidase; GR; glutathione reductase; GST: gltathiione S-transferase; SOD: superoxide dismutase; TEAC: Trolox equivalent antioxidant capacity; MDA: malondialdehyde

Other Findings

GST activity was signficantly higher (35%) in COPD patients.  The level of vitamin E was reduced in patients at 66% of control values.  Lipid peroxidation (MD) was not different between patients and controls.  

Muscle antioxidant status was not related to desease severity.  Increased antioxidant capacity could not be explained by differences in smoking history.  There were no relations between antioxidant status and muscle strength or exercise capacity. 

Author Conclusion:
Overall antioxidant capacity of peripheral skeletal muscle in rest was higher in patients with COPD compared to healthy age-matched control subjects, whereas the vitamin E level was reduced.  Findings indicate that the muscular antioxidant status is chronically altered in COPD patients.  Antioxidant capacity is likely a compensatory adaptation to elevated reactive oxygen species formation in skeletal muscle of patients with COPD.
Funding Source:
Foundation associated with industry:
Reviewer Comments:
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? Yes
  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) N/A
  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.) Yes
  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? Yes
  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? N/A
  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? N/A
  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? N/A
  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? N/A
  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? N/A
  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)? N/A
  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? Yes
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