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

• Published in: Annals of epidemiology Vol. 18; no. 10; pp. 775 - 783
• Main Authors: Garcia-Aymerich, Judith, Lange, Peter, Serra, Ignasi, Schnohr, Peter, Antó, Josep M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2008
• Subjects: Activities of Daily Living; Confounding Factors (Epidemiology); Epidemiologic Methods; Epidemiology; Exercise; Follow-Up Studies; Hospitalization - statistics & numerical data; Humans; Internal Medicine; Male; Middle Aged; Models, Statistical; Models, Structural; Motor Activity; Netherlands - epidemiology; Pulmonary Disease, Chronic Obstructive; Pulmonary Disease, Chronic Obstructive - mortality; Pulmonary Disease, Chronic Obstructive - prevention & control; Surveys and Questionnaires; Survival Analysis; Netherlands; Denmark, Copenhagen; OR; Pulmonary Disease, Chronic Obstructive; CI; MSM; IRR; HR; Models, Statistical; ICD; IQR; Motor Activity; Epidemiology; m; n; SD; FVC; Confounding Factors (Epidemiology); Exercise; FEV 1; CCHS; Epidemiologic Methods; BMI; COPD; forced vital capacity; incidence rate ratio; interquartile range; odds ratio; forced expiratory volume in 1 second; International Classification of Diseases; body mass index; marginal structural model; mean; number of cases; hazard ratio; confidence interval; Copenhagen City Heart Study; chronic obstructive pulmonary disease; standard deviation
• ISSN: 1047-2797; 1873-2585; 1873-2585
• DOI: 10.1016/j.annepidem.2008.05.003

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. 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. 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). 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.