COPD: Effectiveness of Therapies (2007-2008)


Shahar E, Boland LL, Folsom AR, Tockman MS, McGovern PG, Eckfeldt JH for the Atherosclerosis Risk in Communities Study Investigators.  Docosahexaenoic acid and smoking-related chronic obstructive pulmonary disease.  Am J Respir Crit Care Med 1999;159:1780-1785.

PubMed ID: 10351918
Study Design:
Cross-Sectional Study
D - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To investigate the hypothesis that a smoker's risk of developing COPD is inversely related to physiologic levels of eicosapentaenoic acid and docosahexaenoic acid, fatty acids with anti-inflammatory properties.
Inclusion Criteria:
Current or former smokers from Atherosclerosis Risk in Communities Study living in Minneapolis.
Exclusion Criteria:
  • No data about plasma fatty acids (n=45)
  • Those who reported taking lipid-lowering medications (n=51)
  • Those who had not fasted for 12 hours (n=80)
Description of Study Protocol:


Subject sample was derived from the Atherosclerosis Risk in Communities Study, a population based study of atherosclerosis and cardiovascular disease.  Nearly 16,000 men and women were recruited in 4 communities in the US from 1987 - 1989.  Present analysis restricted to study participants in Minneapolis since plasma fatty acid measurements were only made in that population.


Cross-Sectional Study.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Not applicable.

Statistical Analysis

Participants classified into 4 quartiles on basis of proportion of DHA or EPA in their plasma.  Unconditional relation of possible determinants of COPD to the quartile distribution of DHA was described by mean values, percentiles or proportions.  Univariate and multivariate associations of the DHA quartile with the various COPD case definitions were examined with unconditional logistic regression models and linear trends across the quartiles were tested by modeling a 4-value ordinal variable.

Data Collection Summary:

Timing of Measurements

Measurements made and compared.

Dependent Variables

  • COPD identified and defined by clinical symptoms and/or spirometry 

Independent Variables

  • Fasting blood samples evaluated for plasma fatty acids

Control Variables

  • Smoking exposure
  • Height and weight
Description of Actual Data Sample:

Initial N:   2,525 current or former smokers

Attrition (final N):  2,349 subjects analyzed after application of exclusion criteria

Age:  see Results

Ethnicity:  not mentioned

Other relevant demographics:


Location:   Minneapolis


Summary of Results:



DHA Quartile 1

0.78% - 2.15%

DHA Quartile 2

2.16% - 2.59%

DHA Quartile 3

2.60% - 3.17%

DHA Quartile 4

3.18% - 8.88%

Number of Participants

586 593 582 588

Age (years)

54 +/- 6

54 +/- 6

54 +/- 6

55 +/- 5

Sex, % men





Weight (lbs) 173 +/- 36 176 +/- 39 177 +/- 39 172 +/- 37
Height (cm) 171 +/- 9 170 +/- 9 170 +/- 9 170 +/- 9
Smoking status, % current smokers 48 38 31 25
Smoking pack-year, 10th, 50th, 90th percentile 6, 28, 59 3, 25, 51  3, 22, 48 2, 20, 53
Lifetime number of cigarettes per day 21 +/- 10 21 +/- 12 20 +/- 11 20 +/- 12
Formal education, % beyond high school 52 56 56 64

Other Findings

Prevalence odds of COPD were inversely related to the DHA but not the EPA content of plasma lipid components in most of the models.

For example, as compared with the first quartile of the DHA distribution, the prevalence odds ratios for chronic bronchitis were 0.98, 0.88 and 0.69 for the second, third and fourth quartiles, respectively (p for linear trend = 0.09).

The corresponding odds ratios for COPD as defined spirometrically, were 0.65, 0.51 and 0.48 (p < 0.001).

Among 543 current heavy smokers, adjusted mean values of FEV (lowest to highest DHA quartile) were 2,706, 2,785, 2,801 and 2,854 ml. 

Author Conclusion:
Our findings indicate that n-3 fatty acids might be useful in preventing or treating respiratory diseases in which chronic inflammation plays a significant role.  This avenue of research has not yet been fully explored.  Further testing of this paradigm and of our specific hypothesis in experimental models seem warranted.
Funding Source:
Reviewer Comments:
Only participants from Minneapolis included due to data collection.  Authors note that statistical tests of 6 definitions of COPD were not completely independent because some of the case definitions overlapped and so did the actual case groups.
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? 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? N/A
  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? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? 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? N/A
  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? N/A
  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? N/A
  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? ???
  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? ???
  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