COPD: Effectiveness of Therapies (2007-2008)

Igishi T, Hitsuda Y, Kato K, Sako T, Burioka N, Yasuda K, Sano H, Shigeoka Y, Nakanishi H, Shimizu E.  Elevated urinary 8-hydroxydeoxyguanosine (8-OHdG) a biomarker of oxidative stress, and lack of association with antioxidant vitamins in chronic obstructive pulmonary disease.  Respirology 2003; 8:455-460. PubMed ID: 14629648
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 investigate whether patients with COPD are under oxidative stress and to elucidate the relationship between level of oxidative stress and serum antioxidant vitamin concentrations.
Inclusion Criteria:


  • COPD diagnosis
  • smoking history
  • airway obstruction


  • normal lung function
  • match experimental group by age, sex and smoking history


Exclusion Criteria:


  • evidence of acute exacerbation in 3 months preceding


  • history of chronic disease or current infection
Description of Study Protocol:


Nineteen male subjects with COPD diagnosis were recruited from outpatient department of Tottori University Hospital, Yonago, Japan.  Healthy male volunteers (13) were recruited as controls.


Case control study of 2 groups of smokers, one with COPD diagnosis

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Not applicable.

Statistical Analysis

Results expressed as median and interquartile range.  Two group comparisons by Mann-Whitney U test.  Kruskal-Wallis test used for > 3 group comparisons.  Correlations by Spearman's.  P<0.05 significance level.  Power analysis showed 30 subjects needed.

Data Collection Summary:

Timing of Measurements

Single fasting urine and serum sample collections.

Dependent Variables

  • urinary 8-OHdG excretion by specific enzyme linked immunosorbent assay (ELISA)
  • serum antioxidant (vitamin C, beta carotene, alpha tocopherol) levels by high performance liquid chromatography (HPLC)

Independent Variables

  • smoking habit (control vs experimental by current vs ex-smoker)
  • physiological COPD parameters; FVC, FEV, PaO2

Control Variables

  • urinary creatinine concentration (8-OHdG/creatinine)


Description of Actual Data Sample:

Initial N: 32, all male 

Attrition (final N): 19 COPD, 13 control

Age: Control 66.8 + 5.8; experimental/COPD 69.3 + 8.1

Ethnicity: locale of study - Japan, ethnicity not stated

Other relevant demographics:  subjects matched for age, sex, smoking history


smoking pack years; control 45.9 + 26.3, experimental 51.1 +22.1

Location:  Yonago, Japan

Summary of Results:

Other Findings

Urinary excretion of 8-OHdG was significantly higher in patients with COPD than in control subjects (p<0.01). 

Urinary 8-OHdG levels varied signficantly by smoking habit.  Ex-smokers in the COPD group demonstrated signficantly higher levels of urinary 8-OHdG than the ex-smokers in the control group (p<0.01). 

Urinary 8-OHdG level was negatively correlated with FVC (r=0.42, p=0.016), FEV (r=-0.49, p=0.0048), and oxygen tension in arterial blood (PaO2) (r=-0.41 p=0.0005).

There were no significant differences between patients with COPD and control subjects for serum levels of antioxidant vitamins - vitamin C, beta-carotene and alpha-tocopherol.

No significant correlations between antioxidant vitamin concentrations and the functional indices of COPD were observed.


Author Conclusion:
An increased burden of oxidant stress was observed in patients with COPD as judged by urinary 8-OHdG excretion.  Depletion of a single antioxidant such as (serum) vitamin C, alpha-tocopherol or beta carotene was not essential for this phenomenon in COPD. 
Funding Source:
Reviewer Comments:
Groups not equally sized.  Recruitment of controls not well described.
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) ???
  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.) 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? 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? 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? No
  6.6. Were extra or unplanned treatments described? No
  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? ???
  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)? ???
  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? ???
  10.1. Were sources of funding and investigators' affiliations described? No
  10.2. Was the study free from apparent conflict of interest? ???