COPD: Effectiveness of Therapies (2007-2008)

Walda IC, Tabak C, Smit HA, Rasanen L, Fidanza F, Menotti A, Nissinen A, Feskens EJM, and Kromhout D.  Diet and 20-year chronic obstructive pulmonary disease mortality in middle-aged men from three European countries.  European Journal of Clinical Nutrition 2002; 56(7):638-643. PubMed ID: 12080403
Study Design:
Prospective Cohort Study
B - 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 study the relationship between antioxidant, fruit, vegetable and fish intake in relation to 20 year COPD mortality in middle aged men.
Inclusion Criteria:

Finnish, Dutch and Italian cohorts of the Seven Countries Study (1970)

  • male inhabitants of Homantsi, Poytya and Mellila, Finland born between 1900 to 1919
  • inhabitants of Crevalcore or Montegiorgio, Italy
  • random sample of eligible males in Zutphen, Netherlands



Exclusion Criteria:

Incomplete data for BMI, alcohol consumption, dietary intake.

Description of Study Protocol:


  • invitation to random 4 of 9 male participants of Seven Countries Study in Zutphen, Netherlands
  • unclear - Finland, Italy 


Prospective Cohort.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Not applicable.

Statistical Analysis

SAS statistical package version 6.1

  • Cox Proportional Hazard Model (SAS Procedure PHREG, 1991) for assessment of relationship of dietary variables to 20 year COPD mortality
  • Dietary variable ranked into tertiles and associations with COPD mortality were studied after adjustment for age and cigarette smoking at baseline and for country 
  • Adjustment for country by pooled relative risk
  • Dietary factors showing statistically significant trend in COPD mortality across tertiles ued for further analysis
Data Collection Summary:

Timing of Measurements

Baseline and 10 year follow up of physical exam and dietary survey

  • Examination of Finnish males in 1959 (n=1675) and 10 year follow up exam (n=1306) and dietary follow up (n=1260)
  • Zutphen examination and dietary survey of 872 males and follow up in 1970 by re-exam (n=625) and dietary survey (n=558)
  • Baseline exam and dietary survey:  Italy in 1960 (n=1712), follow up exam 1970 (n=1323) and follow up dietary baseline dietary survey and examination in 1960 (n=872) ; follow up exam (n=872) and dietary survey (n=558) in 1970

Dependent Variables

  • Vital status at 20 year follow-up, primary mortality by International Classification of Diseases  (WHO 1967)

Independent Variables

  • Dietary intake
  • Energy (MJ)
  • Ethanol (g)
  • Vitamin C (mg)
  • Beta carotene (mg)
  • Vitamin E (mg)
  • Fruit (g)
  • Vegetables (g)
  • Fish (g)
  • Measured by cross check dietary history method (Burke, 1947 JADA 23, 1041-1046)

Control Variables

  • Body mass index
  • Smoking status (standardised questionnaire)
  • Country of origin
Description of Actual Data Sample:

Initial N: n= 2953 males

Attrition (final N): n=2917 males


  • Finland (n=1227) 59.1 + 5.5 years
  • Italy (n=1132) 59.3 + 4.9 years
  • Netherlands (n=558) 59.6 + 5.4 years

Ethnicity: Finnish, Italian, Dutch

Other relevant demographics:

21.3% never smoked, 50.9% curent smokers, 27.8% former smokers in 1970


Energy intake (MJ); Finland 15.6 + 4.7; Italy 12.3 + 3.3; Netherlands 11.0 + 2.2e.g., were groups same or different on important measures)

Location:  Italy, Finland, Netherlands

Summary of Results:

Other Findings

Vitamin E intake was not statistically significantly assoicaed with COPD mortality after adjustment for country, age and smoking.  Of the other three potential confounders energy intake had the strongest effect.

An inverse trend of COPD mortality across tertiles (p<0.05) of baseline intake of fruit, vitamin C and vitamin E. 

After adjustmen for country, age and smoking the trend remained statistically significant for fruit and vitamin E intake.  Adjusted RR of the highest vs lowest tertile of intake was 0.49 (95% CI=0.26-0.93) for fruit and 0.54 (95% CI = 0.27 - 1.05) for vitamin E.

After adjustment for country, age and smoking a 100 g increase in fruit intake was associated with a 24% lower COPD mortality risk (RR=0.76 95% CI=0.60-0.92).

No trend was observed for vegetables, fish, vitamin C and beta-carotene.


Author Conclusion:
After adjustment for age, smoking and country, we observed and inverse trend (p<0.05) of 20y COPD mortality across tertiles of baseline habitual intake of fruit and vitamin E.  When modelled continuously, a 100 g increase in fruit intake was associated with a 24% lower COPD mortality risk (RR=0.76, 95% CI = 0.60-0.92).  For vitamin E intake (per 5 mg) the RR was 0.77 (95% CI = 0.55 - 1.06), after adjustment for age, smoking and country.  Additional adjustment for BMI, total energy intake and alcohol consumption reduced the RR to 0.86 (95% CI 0.69 - 1.07, p=0.12) for fruit and 0.93 (95% CI = 0.65 - 1.33) for vitamin E.
Funding Source:
Reviewer Comments:
Data available for different time periods:  the 2 Finnish cohorts in 1969 and for the Italian and Dutch cohorts in 1965.  Cohorts not similarly sized.  Difficult to assume that baseline dietary intake would remain similar over 20 years of follow-up.  Authors note that due to the relatively small number of men dying from COPD in the study, confidence intervals were wide.
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? 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? 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) 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.) No
  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? Yes
  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? 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? 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? No
  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? 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? ???
  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? ???
  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)? 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? 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