COPD: Effectiveness of Therapies (2007-2008)


Couillard A, Koechlin C, Cristol JP, Varray A, Prefaut C.  Evidence of local exercise-induced systemic oxidative stress in chronic obstructive pulmonary disease patients. European Respiratory Journal 2002; 20:1123-1129.

PubMed ID: 12449164
Study Design:
Case-control study
C - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
The purpose of the study is to investigate whether localized (quadriceps) exercise would generate oxidative stress and to investigate, in vitro, superoxide anion release as an oxidant marker and blood vitamin E as an antioxidant marker.
Inclusion Criteria:
  • moderate to severe COPD (diagnosis by American Thoracic Society Guidelines)
  • ex-smoker
  • irreversible obstructive airway disease
  • no hypoxemia
  • clinically stable
  • no respiratory tract infection or exacerbation > 4 weeks prior
  • nor oral corticosteroid treatment
  • received anticholinergic or beta 2 agonists as bronchodilator therapy
Exclusion Criteria:
  • known muscle disorders
  • cardiac failure
  • diabetes mellitus
  • alcoholism
  • taking antioxidants or vitamin supplements
Description of Study Protocol:


Control subjects recruited as volunteers from friends of experimental laboratory.

Recruitment for experimental subjects unclear.


Case control study; eleven male COPD patients and 12 healthy age-matched male subjects with similar physical activity levels

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Quadriceps femoris endurance exercise performed by execution of maximal knee extensions against weights corresponding to 40% of Maximum Voluntary Contraction (MVC) until exhaustion. 

Statistical Analysis

Unpaired t-test; two way ANOVA.  Values reported as mean + Standard error of mean.  Mann Whitney U and linear regression; Tukey.

Data Collection Summary:

Timing of Measurements

Blood samples at:   Trest = pre-exercise;  Tend = end of exercise;  T6h = 6 hours after exercise

Dependent Variables

  • oxidative stress by thiobarbituric reactive substances (TBARs), fluorimetric method (Yagi, 1976)
  • in vitro superoxide anion release - luminescence measure (Vachier 1994)
  • blood vitamin E by high performance liquid chromotography (Cachia, 1995)

Independent Variables

  • quadriceps femoris endurance exercise by execution of maximal knee extensions to 40% of maximum voluntary contraction (MVC)
  • subjects instructed to abstain from strenuous physical activity 3 days before and on the day of local muscle exercise 

Control Variables


Description of Actual Data Sample:

Initial N: 23

Attrition (final N): 23 males, 12 controls, 11 COPD

Age: COPD group at 65 + 3.6 years;  Controls at 58 + 1.5 years

Ethnicity: unclear

Other relevant demographics:

Anthropometrics: No statistical difference between groups for age, height, weight, BMI, FEV L, FEV % predicted, physical activity score

Location: Montpellier, France


Summary of Results:

  Vitamin E (mg/L) - Trest Vitamin E (mg/L) - Tend

Vitamin E (mg/L) - T6h


27.7 +/- 1.28 28.9 +/- 1.5 28.5 +/- 1.8


23.3 +/- 1.2, p < 0.05

21.55 +/- 1.09, p < 0.01

20.45 +/- 1.26, p < 0.01

Other Findings

Absolute values of blood vitamin E at rest were significantly lower in COPD patients (p<0.05).

Significant correlation was found at rest between blood vitamin E and markers of oxidative stress (TBARs) in COPD (r=0.69; p<0.05)

Local exercise induced a significant increase in plasma levels of lipid peroxidation products 6 h after the end of exercise in COPD patients (p<0.05).

Significant relationship between triglycerides and cholesterol and vitamin E in healthy subjects but not in COPD patients. 

Contribution to increase in oxidative stress markers by ventilatory response checked by dypnea measure in 5 COPD and 5 healthy subjects and considered to be of small amplitude.

Duration limit threefold lower in COPD vs controls with equal activity. 

Authors suggest contribution to above factors deserves further study.



Author Conclusion:

Present study shoed that local exercise induces oxidative stress in COPD patients and a significant decrease in blood vitamin E.  Further studies based on needle muscle biopsies needed to confirm muscular origin of exercise-induced oxidative stress. 

Funding Source:
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? ???
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? Yes
  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? 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? ???
  10.2. Was the study free from apparent conflict of interest? Yes