COPD: Effectiveness of Therapies (2007-2008)


Tabak C, Feskens EJ, Heederik D, Kromhout D, Menotti A, Blackburn HW.  Fruit and fish consumption:  a possible explanation for population differences in COPD mortality (The Seven Countries Study).  Eur J Clin Nutr 1998;52(11):819-25. 

PubMed ID: 9846595
Study Design:
Cohort Study
B - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To investigate whether average intake of antioxidants, fruits, vegetables and fish may help to explain international differences in chronic obstructive pulmonary disease mortality.
Inclusion Criteria:
  • Men aged 40 - 59 years at baseline
Exclusion Criteria:
  • None specifically mentioned
Description of Study Protocol:


16 cohorts of the Seven Countries Study.


Cohort Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Not applicable.

Statistical Analysis

All analyses concern inter-cohort comparisons.  Poisson regression was carried out.  The proportion of explained variance in the final model could not be derived directly from the Poisson regression analyses.  Therefore, the Pearson's product-moment correlation coefficient was determined.  A square root transformation was performed on both observed and expected COPD mortality.  All presented correlation coefficients are Spearman correlation coefficients. 

Data Collection Summary:

Timing of Measurements

Analysis using information on baseline diet and the 25 year COPD mortality rate.

Dependent Variables

  • Underlying cause of death after 25 years used to calculate COPD mortality rate ratios 

Independent Variables

  • Dietary information collected at baseline in small random samples of each cohort between 1959 and 1964 for 14 cohorts and in 1970 for other cohorts 
  • In 1987 the foods were bought locally and analyzed chemically

Control Variables

  • Age
  • Smoking
  • Height, weight, BMI
  • Total energy intake
  • Work-related physical activity
Description of Actual Data Sample:

Initial N: 12,763 men enrolled in Seven Countries Study

Attrition (final N):  Only 56 men lost to follow-up

Age:  aged 40 - 59 years at baseline 

Ethnicity:  not mentioned

Other relevant demographics:


Location: Finland, Italy, Greece, former Yugoslavia, Japan, US, the Netherlands


Summary of Results:



10% of mean intake

Crude COPD mortality rate ratio (95% CI)

COPD mortality rate ratio adjusted for BMI (95% CI)

n-6 Fatty Acids

1.5 g 1.04 (0.91, 1.18) 1.12 (0.97, 1.29)
n-3 Fatty Acids 0.3 g 1.00 (0.90, 1.11) 0.96 (0.86, 1.08)


0.1 g

0.97 (0.89, 1.05)

0.92 (0.84, 0.99)


4.4 g

0.98 (0.93, 1.02)

0.96 (0.92, 1.00)

Other Findings

During 25 years of follow-up, 273 men died with COPD as the underlying cause of death, resulting in an overall age-adjusted COPD mortality rate of 2.1%. 

Independent inverse associations were observed between 25-year COPD mortality and baseline consumption of fruits (rate ratio 0.49, 95% confidence interval:  0.36 to 0.67) and fish (rate ratio 0.97, 95% confidence interval 0.93 to 1.00), after adjustment for potential confounders.

COPD mortality showed no statistically significant association with intake of antioxidants or vegetables.

Fruit and fish consumption together explained about 67% of the variance in the COPD mortality rates of the cohorts. 

Author Conclusion:
We conclude that fruit and fish consumption may partly explain international differences in COPD mortality.  This is in accordance with suggestions of a relationship between fruit and fish consumption and COPD observed in individual-level studies.
Funding Source:
Reviewer Comments:
Inclusion/exclusion criteria not well defined.  Dietary intake only measured at baseline and measured at different times for the cohorts, difficult to assume that dietary intake would remain similar over 25 years of follow-up.
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) N/A
  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) N/A
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? 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? No
  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? Yes
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) N/A
  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? ???
  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? ???
  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? Yes
  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? Yes
  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? Yes
  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? ???
  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? ???
  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)? Yes
  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? N/A
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