Time-dependent confounding in the study of the effects of regular physical activity in chronic obstructive pulmonary disease: an application of the marginal structural model

Ann Epidemiol. 2008 Oct;18(10):775-83. doi: 10.1016/j.annepidem.2008.05.003. Epub 2008 Aug 16.


Purpose: Results from longitudinal studies about the association between physical activity and chronic obstructive pulmonary disease (COPD) may have been biased because they did not properly adjust for time-dependent confounders. Marginal structural models (MSMs) have been proposed to address this type of confounding. We sought to assess the presence of time-dependent confounding in the association between physical activity and COPD development and course by comparing risk estimates between standard statistical methods and MSMs.

Methods: By using the population-based cohort Copenhagen City Heart Study, 6,568 subjects selected from the general population in 1976 were followed up until 2004 with three repeated examinations.

Results: Moderate to high compared with low physical activity was associated with a reduced risk of developing COPD both in the standard analysis (odds ratio [OR] 0.76, p = 0.007) and in the MSM analysis (OR 0.79, p = 0.025). In the subgroup with COPD (n = 2,226), high physical activity was associated with a reduced risk of COPD admissions during follow-up (standard, incidence rate ratio, 0.74; p = 0.096; MSM, 0.68, p = 0.044), and with a reduced risk of mortality (standard, hazard ratio 0.80, p = 0.001; MSM, 0.81, p = 0.008).

Conclusion: These results support the previously reported associations between physical activity and reduced risk of COPD development, hospitalizations, and mortality, thereby suggesting they were not due to time-dependent confounding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Confounding Factors, Epidemiologic
  • Exercise*
  • Follow-Up Studies
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Models, Statistical
  • Models, Structural*
  • Motor Activity*
  • Netherlands / epidemiology
  • Pulmonary Disease, Chronic Obstructive / mortality*
  • Pulmonary Disease, Chronic Obstructive / prevention & control
  • Surveys and Questionnaires
  • Survival Analysis