COPD: Effectiveness of Therapies (2007-2008)


Agacdiken A, Basyigit I, Ozden M, Yildiz F, Ural D, Maral H, Boyaci H, Ilgazli A, Komsuoglu B. The effects of antioxidants on exercise-induced lipid peroxidation in patients with COPD. Respirology 2004;9:38-42.

PubMed ID: 14982600
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 compare the effects of exercise-induced oxidative stress on lipid peroxidation in COPD patients and healthy controls and to investigate the effect of antioxidant therapy on these parameters.
Inclusion Criteria:

Experimental: stable, COPD diagnosis

Control: age, gender matched, healthy

Exclusion Criteria:
  • Acute admission secondary to exacerbation in last 3 months
  • Reversible airflow obstruction
  • Insufficient mobility to perform exercise test
  • Significant ST/T wave abnormalities secondary to exercise test
  • Positive cardiological test response
  • CVD other than secondary to COPD
Description of Study Protocol:


Methods unclear.


Case-Control Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable) 

Treadmill exercise test using Bruce protocol; symptom-limited exercise test with Quinton 710 machine.  Vitamin E (200 IU/day) and vitamin C (500 mg/day)treatments added to regular bronchodilator therapy in 10 COPD patients for 1 month.

Statistical Analysis  

Data expressed as mean + or - SEM. Student's t-test for comparison between COPD and control; p< 0.05 significant
Data Collection Summary:

Timing of Measurements

Blood sample collection prior to and 1 h post exercise for control and prior, at 1 and 3 h post exercise in experimental.  

Dependent Variables

  • Malondialdehyde (MDA), reduced glutathione (GSH) and vitamin E (VE) levels; fasting sample with am collection from antecubital vein to disodium EDTA for GSH (whole blood) and MDA (plasma)
  • lipid peroxidation by MDA; thiobarbituric acid method
  • GSH assays by Beutler method 
  • 2 mL aliquot, centrifuged samples used for vitamin E measurements 

Independent Variables

  • exercise
  • Vitamin C and E supplementation for 1 month in 10 patients  

Control Variables


Description of Actual Data Sample:

Initial N: 21 stable COPD, 10 healthy controls, all male 

Attrition (final N):  31

Age: experimental group 62.7 +/- 9 years; control group mean age 49.5 +_6 years

Ethnicity: not mentioned

Other relevant demographics:

Experimental group; smoking (pack-years) 49 + 24 / disease duration 6.5 + 6.4  / FEV (% predicted) 49.8 + 22 vs 82.6 + 16.4 in control group / PaO2 = 77 + 15.5 mmHg / Pa CO2  = 42.9 + 7.5 mm Hg / SaO2 = 94.9+2.5.

Anthropometrics: age and gender-matched controls.  Baseline GSH and VE levels lower in COPD group, no significant difference between MDA levels in the 2 groups.


Department of Cardiology, Pulmonary Disease and Biochemistry, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
Summary of Results:

Other Findings

In COPD patients, both MDA and VE levels increased significantly with exercise.  MDA levels at 3 h after exercise cessation were significantly higher than baseline values.  VE levels 1 h after ceasing exercise were significantly higher than baseline.  No statistically significant  difference in GSH levels after exercise.

In controls, there were no significant differences in MDA, VE and GSH levels after exercise.

Exercise time and metabolic equivalent (MET) increased significantly in 10 COPD patients who were treated with Vitamin E (200 IUs) and Vitamin C (500 mg) for 1 month (exercise time 6.4 + 1.8 vs 8.7 + 2.1 min, p=0.01, MET 7.8 + 3.3 vs 9.8 + 1.8, p< 0.05)

Author Conclusion:

Exercise results in significant increase in lipid peroxidation and oxidative stress as evidenced by subsequent changes in MDA levels of COPD patients.  There was no significant change in MDA levels in healthy controls.  Exercise altered the oxidant antioxidant balance in favor of oxidants in COPD patients.  Vitamin E levels increased secondary to exercise in patients with COPD.  Exercise time and metabolic equivalent increased in 10 COPD patients treated with Vitamin E and Vitamin C for one month.


Funding Source:
University/Hospital: Kocaeli University Faculty of Medicine
Reviewer Comments:
Recruitment methods unclear.  Small numbers in groups and groups not equally sized.  Antioxidant therapy only provided for 10 COPD patients.
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? 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.) ???
  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? No
  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? 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? 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)? 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? 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