RESULTS

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Characteristics of the 6,790 included subjects are shown in Table 1. At baseline (second CCHS examination), 43% were men, the mean age was 52 years, and the mean body mass index (BMI) was 25.1 kg/m²; 23, 22, and 55% were never-, former, and active smokers, respectively. Twelve percent suffered from COPD according to the spirometric definition, and levels of regular physical activity were as follows: 12% low, 50% moderate, and 38% high. At the third CCHS examination, a mean of 11 years later, most variables remained relatively similar, with the exception of an increase in the prevalence of ischemic heart disease, asthma, diabetes, and COPD. Mean measure of physical activity provided 15.6% of subjects in the low, 36.6% in the moderate, and 47.8% in the high physical activity group. These groups corresponded to a mean expenditure of 82, 99, and 123 kcalories per day in physical activity, respectively. Smoking status during the study period did not change for 86% of subjects, although 10% quit, 2% started, and 2% resumed smoking.

In the bivariate analysis, FEV₁ decline (mean [SD] 18.0 [41.6] ml/yr) was higher in men; older subjects; those with low income and education, high BMI, cardiac comorbidity, or respiratory symptoms (dyspnea, sputum); active and former smokers; and those with very high and very low alcohol consumption, lower FEV₁ levels at baseline, and lower physical activity level; but no difference was found with respect to asthma, diabetes, or COPD at baseline. After including all the relevant covariates in a multivariate linear regression model (Table 2), the rate of FEV₁ decline was lower for the moderate and high physical activity group as compared with the low physical activity group, but only among the active smokers.

FVC decline (7.0 [52.1] ml/yr) was higher in older subjects; those with low income and education, high BMI, cardiac comorbidity, dyspnea, or sputum; active and former smokers; and those with very high and very low alcohol consumption, baseline COPD, lower FVC level at baseline, and lower physical activity level; but no difference was found according to sex, asthma, or diabetes. In the multivariate linear regression model (Table 3), the rate of FVC decline was lower for the moderate and high physical activity group as compared with the low physical activity group, but again, only among the active smokers.

After excluding subjects with COPD at baseline, a total of 928 subjects developed COPD during follow-up, corresponding to 15 new cases per 100 subjects during 11 years. As expected, in the multivariate logistic regression model with COPD incidence as the outcome, the risk of COPD was higher for active smokers than for non- or former smokers. In addition, those with moderate to high levels of physical activity had a reduced risk of COPD as compared with the low physical activity group (odds ratio [OR], 0.80; 95% confidence interval [95% CI], 0.65–0.98; P = 0.03) (Table 4). In the stratified models, similar odds ratios were found both for non- and active smoker groups, but only the latter reached statistical significance. The prevented fraction of COPD among smokers attributable to moderate to high levels of physical activity was 21%.

Results for FEV₁ decline, FVC decline, and COPD risk remained very similar after stratification according to sex, baseline chronic mucus hypersecretion, and baseline BMI. Physical activity was not associated with lung function decline in young adults (< 40 yr) or in subjects with mild COPD. The effect of physical activity on FEV₁ and FVC decline was higher in individuals with asthma than in those without asthma. In individuals with asthma, moderate to high physical activity improved lung function decline by gaining 10 ml/yr of FEV₁ and 7 ml/yr of FVC, as compared with the low physical activity group. Among those without asthma, the corresponding figures were 1 ml/yr in FEV₁ decline and 2 ml/yr in FVC decline.

The sensitivity analysis restricted to subjects who after follow-up remained in the same category of physical activity, or in the same category of smoking, or excluding subjects with COPD or asthma at baseline, provided very similar estimates with larger confidence intervals in all described associations.

After adjusting for baseline physical activity and other covariates, subjects who decreased their physical activity during follow-up had an increased lung function decline (−7; 95%CI, −9 to −4 ml/yr of FEV₁ and −9; −12 to −6 ml/yr of FVC) and COPD risk (OR, 1.20, 0.98–1.46), while subjects who increased showed a reduction in lung function decline (+2, −1 to +4 ml/yr of FEV₁ and +3, −1 to +6 ml/yr of FVC) and COPD risk (OR, 0.81, 0.65–1.02), as compared with subjects with unchanged physical activity levels, although some of these associations were not statistically significant.

DISCUSSION

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The present study shows that moderate to high levels of regular physical activity are associated with a lower lung function decline and risk of COPD in active smokers after adjusting for other risk factors and confounders. Three previous epidemiologic studies in selected or restricted samples found inconsistent results regarding the association between some physical activity variables and changes in some lung function parameters. In our study, the use of a population-based sample with information for most known potential confounders and other risk factors of lung function decline is an improvement with respect to previous studies, making unlikely selection bias and confounding factors potential explanations for the present results.

As expected (18, 19), FEV₁ and FVC declines and the risk for COPD were higher in active versus nonsmokers. Former smokers showed intermediate values. Among active smokers, we observed a dose–response relationship: the higher the level of physical activity, the lower the lung function decline or COPD incidence. The observation that the effect of physical activity was restricted to a subgroup of smoking status may represent a biological antagonistic interaction (20). Under the Rothman model of causality, both factors (active smoking and physical activity) are considered to be component causes of the same sufficient cause of disease and, as a result, are involved in the same causal mechanism.

We suggest that the biological mechanism on which both physical activity and smoking interact antagonistically is an exaggerated inflammatory response in the lungs. Inflammation relates smoking with lung function decline and pathogenesis of COPD (21). Regular physical activity suppresses the production of inflammatory markers IL-6, TNF-α, CRP, and intracellular adhesion mollecule-1; enhances the anti-inflammatory markers TGF-β, ILO-4, IL-10, and adiponectin; and stimulates the synthesis of eNO, prostacyclin from the vascular endothelial cells, and tissue Mn-SOD (9, 22). Although most of these effects have been demonstrated in experimental studies or healthy subjects, some indirect evidence is also available from studies in patients with advanced COPD, in whom long-term respiratory rehabilitation may reduce exercise-induced oxidative stress (23). It is plausible that regular physical activity could counteract the smoking effects through an anti-inflammatory and antioxidant mechanism. Effects on obesity and fat distribution, or on respiratory muscle strength, have been previously proposed as mechanisms of the effect of physical activity on lung function (5, 7). In our cohort, physical activity was surprisingly associated with weight gain, which in turn was related to a higher lung function decline as previously reported (24, 25). Despite all the possible mechanisms mentioned here, a great uncertainty still exists on the mechanisms of action of physical activity for respiratory diseases. Present epidemiologic findings should encourage further research on this topic.

The effect of physical activity was higher in individuals with asthma than in those without asthma, which when considering the inflammatory nature of asthma (26) could be in favor of the proposed mechanism of action between physical activity and COPD. However, this result needs to be interpreted with caution due to the small number of subjects with asthma in our sample. The lack of an association between physical activity and lung function decline or COPD risk in the group of former smokers is somewhat surprising. If an anti-inflammatory action of physical activity is the main mechanism for lung function decline, an effect would be expected in former smokers, who still suffer an important inflammatory burden. A stratified analysis showed a not statistically significant association between physical activity and lung function decline in former smokers who had quit more recently (in the previous 5 yr), which would agree with this possibility. Unfortunately, sample size does not allow for a more detailed analysis. It may also be that there is a need of an inflammatory threshold for having the anti-inflammatory action of physical activity, which should be tested in further studies.

It has been well known for decades that poor lung function, apart from its respiratory effects, predicts all-cause and cause-specific mortality (19, 27, 28). With the exception of tobacco smoking and some occupational exposures, the factors related to lung function decline cannot be modified at the individual level, which raises the importance of our results given the possibility of modifying physical activity level with physician advice or specific health promotion programs (29). In our cohort, the practice of moderate to high levels of physical activity in smokers avoided 21% of the potentially new COPD cases. The interaction between physical activity and smoking should be taken into account when projecting the future burden of respiratory diseases. The increase in smoking and sedentary lifestyle in developing countries is likely to have an important impact with respect to COPD, which already has a leading position both for mortality and disability throughout the world (30).

Although there is compelling evidence that regular physical activity is a beneficial factor improving and/or preventing multiple chronic diseases, the effects on respiratory morbidity have not been appropriately assessed (29). Our results suggest that respiratory outcomes should be considered when studying the effects of physical activity and/or the effectiveness of physical activity promotion programs.

Potential limitations of the present analysis are a misclassification of the exposure, survival bias, and residual confounding factors. The measure of physical activity using a questionnaire involves some degree of misclassification that is likely nondifferential and therefore would lead to an underestimation of the effects of physical activity (31). Subjects who were alive at the end of follow-up had higher baseline physical activity and lung function levels than those who were lost or dead during follow-up, which cannot be avoided in longitudinal studies and could bias the estimates of the association in this study. With regard to the possibility of residual confounding factors, our results have been adjusted for all known risk factors of lung function decline (2), with the exception of diet, which, unfortunately, was not included in the CCHS data. Reverse causation is also possible even in a longitudinal study. Repeated measures of lung function and physical activity would be needed to discard it. Unfortunately this data is not available in the present study.

In conclusion, the present prospective study shows that moderate to high levels of regular physical activity are associated with an attenuation of lung function decline and a lower risk of COPD at the population level. The prospective design and consistency of these findings with previous studies strongly suggest a causal nature of the reported association. Beyond the importance of reinforcing antismoking initiatives at all levels of the health care process, the recommendation of increasing the level of physical activity may be especially important in active smokers, which is supported by the finding of a reduced lung function decline and COPD among those who increased the physical activity during follow-up.