COPD: Effectiveness of Therapies (2007-2008)

Calikoglu M, Unlu A, Tamer L, Ercan B, Bugdayci R, Atik U.  The levels of serum vitamin C, malonyldialdehyde and erythrocyte reduced glutathione in chronic obstructive pulmonary disease and in healthy smokers.  Clinical Chemistry and Laboratory Medicine 2002; 40, 1028-1031. PubMed ID: 12476943
Study Design:
Case-Control Study
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
The purpose of the current study was to test the systemic oxidant/antioxidant balance in the acute exacerbation or stable form of COPD, and to test the effect of smoking on systemic oxidant/antioxidant balance both in patients and in the controls.
Inclusion Criteria:
  • patients with COPD, diagnosed according to the British Thoracic Society guidelines
  • age- and sex- matched controls
Exclusion Criteria:
  • history of evidence of atopy on skin prick tests for common inhaled allergens
  • history of asthma or inhaled glucocorticoids or antibiotics usage during 3 months before the study
Description of Study Protocol:


Methods not described.


Case-Control Study.

Blinding used (if applicable): not applicable

Intervention (if applicable):  not applicable

Statistical Analysis

Arithmetic means + standard deviation; students t test and pearson's correlation coefficients.


Data Collection Summary:

Timing of Measurements

Single measurement compared between patients with COPD and healthy controls.

Dependent Variables

  • serum malonyldialdehyde (MDA) (nmol/l); by spectrophotometry, Yagi K. 1994, Plenum Pres.
  • reduced glutathione (GSH) (micromoles per g HB); venous blood samples measured by sulfhydryl reduction
  • vitamin C (mg/dl) in venous blood measured by 2,6 dichlorophenol-indophenol reduction

Independent Variables

  • COPD diagnosis vs healthy controls
  • COPD status; stable vs acute exacerbation
  • smoking status during acute COPD exacerbation (nonsmokers for period of 1 year or more before study)
  • smoking status during stable COPD
  • smoking status of control subjects 

Control Variables:  none


Description of Actual Data Sample:

Initial N: 62 patients (31 males, 31 females) and 30 age- and sex-matched controls (15 males, 15 females)                

Attrition (final N): as above

Age:  COPD patients 60.06 + 9.90; Controls  62.56 + 10.24

Ethnicity: not specified

Other relevant demographics



  • all COPD                   59.24 +19.5
  • acute exacerbation  53.04 +15.76
  • stable COPD             65.71 +20.32
  • controls                    97.81 + 13.45 

Location: Turkey


Summary of Results:

Other Findings

Levels of erythrocyte GSH and serum vitamin C were significantly decreased in patients compared to controls.  Decreased levels of the two antioxidants were accompanied by an increase in MDA levels.  The decreased antioxidant levels were paralleled by the increase in MDA levels.

GSH and vitamin C were lower during acute exacerbation of COPD, while MDA levels were higher when compared to the stable phase.  Smoking had no effect on GSH, vitamin C and MDA levels in patients with acute exacerbation of COPD.  Levels of GSH and vitamin C were lower in control smokers in comparison to control non-smokers.

Author Conclusion:
Results demonstrate that oxidant/antioxidant imbalance is more obvious in patients with acute exacerbation of COPD and smoking has no signficant effect on the circulating antioxidants during acute exacerbation of the disease.
Funding Source:
University/Hospital: Mersin University
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? No
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? Yes
  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.) N/A
  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? 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? 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? No
  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? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? No
  7.7. Were the measurements conducted consistently across groups? ???
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? No
  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? ???
  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)? No
  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? No
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? No
  10.2. Was the study free from apparent conflict of interest? ???