COPD: Effectiveness of Therapies (2007-2008)

Tug T, Karatas F, Terzi SM. Antioxidant vitamins (A, C and E) and malondialdehyde levels in acute exacerbation and stable periods of patients with chronic obstructive pulmonary disease. Clinical and Investigative Medicine 2004; 27:123-128. PubMed ID: 15305803
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 determine concentrations of lipid peroxidation product MDA and antioxidant vitamins in patients with COPD, during periods of exacerbation and stable periods.
Inclusion Criteria:


  • patients of chest clinic of Firat Medical Center
  • patients in acute pulmonary exacerbation as defined by criteria of Global Initiative for Chronic Obstructive Lung Disease (GOLD criteria)
  • no chronic disease other than COPD
  • ongoing administration of one or more; beta 2 agonists, ipratropium bromide or theophylline with no additional medicines


  • healthy
Exclusion Criteria:
  • smoking or alcohol consumption in past 5 years


Description of Study Protocol:


  • informed consent by patients of Firat Medical Center's chest clinic
  • control volunteer patient relatives or medical officials


Case-Control Study.

Blinding used (if applicable):  Not applicable

Intervention (if applicable): Not applicable

Statistical Analysis

Group results were expressed as mean and SD.  Paired t test was used to compare the results obtained during exacerbation and stable periods, and 2-sample independent t test to compare study-patient and control data.  Statistical significance was defined as p<0.05; tests were 2-tailed. 

Data Collection Summary:

Timing of Measurements

Prior to disease treatment (acute COPD exacerbation) and one (1) month after treatment

Dependent Variables

  • Mean serum antioxidant concentrations; vitamin A, vitamin E, vitamin C, measured by high performance liquid chromatography (HPLC)
  • Malondialdehyde (MDA); measured by high performance liquid chromatography

Independent Variables 

  • Forced expiratory volume in 1 second (FEV1); spirometry
  • Forced vital capacity (FVC); spirometry
  • FEV1/FVC; spirometry
  • Partial pressure of arterial oxygen (Pa02); spirometry
  • O2 saturation; spirometry

Control Variables

  •  none

  • Description of Actual Data Sample:

    Initial N: 24 patients with COPD, 23 healthy controls

    Attrition (final N):  as above

    Age: 51.8 + 6.7 

    Ethnicity: not specified

    Other relevant demographics: none

    Anthropometrics:  neither controls or subjects had smoked or consumed alcohol within the past 5 years.  Controls were healthy but not necessarily age or sex matched.

    Location: Elazig, Turkey


    Summary of Results:

    Other Findings

    Serum MDA concentrations were lower during th estable period of COPD patients than during exacerbations (p<0.001).  There were significant differences in levels of both vitamins A and E between exacerbations and stable periods, as well as between exacerbations and controls (p<0.01).

    Healthy control subjects had the lowest serum MDA concentrations. 

    Serum MDA concentrations were higher in patients than in controls during both exacerbation and stable periods.  Similar results were also obtained during acute exacerbation compared with stable periods.  Levels of vitamins A and E were lower during acute exacerbations than in stable periods as well as when compared with controls. 

    Author Conclusion:

    The current study indicates that serum concentrations of vitamin A, E and MDA are altered during exacerbations of COPD.  There may be a role in disease pathophysiology by virtue of the roles of vitamins A and E and MDA in oxidative stress.

    Funding Source:
    Reviewer Comments:
    Controls were not matched.
    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? No
      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.) ???
      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? 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? 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? 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? 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? No
      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)? 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? 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