ETS exposure, both at home and work, was associated with a greater risk of COPD in this population-based study of older adults, even after taking personal smoking history into account. On a population level, approximately 1 in 11 cases of COPD may be attributed, at least in part, to home ETS exposure; 1 in 15 cases may be attributable to workplace ETS exposure.
The previous epidemiologic literature, albeit limited, supports an association between ETS exposure and COPD. A cross-sectional population-based study from Switzerland found a relationship between self-reported ETS exposure during the past 12 months and a higher risk of chronic bronchitis symptoms [26
]. A case-control study demonstrated that self-reported ETS exposure was associated with obstructive respiratory disease, defined as asthma, chronic bronchitis, or emphysema [27
]. Reports from the Adventist Health Study of Smog (AHSMOG) indicated a relationship between self-reported ETS exposure and a greater risk of "airway obstructive disease" (asthma, chronic bronchitis, or emphysema), chronic bronchitis symptoms, and airway obstruction by pulmonary function testing [28
]. These studies are limited by the lack of a comprehensive and specific definition of COPD (i.e., includes chronic bronchitis, emphysema, and COPD but not asthma), the absence of cumulative lifetime ETS exposure data, and the omission of other occupational exposures that could be correlated with ETS exposure.
The results suggest that home ETS exposure and personal smoking may act synergistically to increase the risk of COPD. There are several possible biological mechanisms that could account for this synergistic action. ETS contains potent respiratory irritants, such as formaldehyde and acrolein, which could directly irritate the airways and exacerbate smoking-related airflow obstruction. Both ETS and direct smoking may increase airway permeability, causing increased IgE levels and enhanced allergic sensitization to airborne antigens [30
]. By this and other mechanisms, ETS and cigarette smoking could act to increase airway inflammation. Other possible mechanisms are combined effects of smoking and ETS on bronchial hyperresponsiveness [32
]. Further experimental work will be necessary to elucidate the apparent synergy between ETS exposure and direct smoking.
Our results suggest that the highest quartiles of home and work ETS exposure were associated with a greater risk of COPD. Is it therefore possible to conclude that lower levels of ETS exposure are "safe" in terms of obstructive lung disease? We believe that our data do not suggest a "safe" level of ETS exposure. Based on our results, the 95% confidence intervals for the lower exposure quartiles are compatible with a substantially increased risk of COPD. Moreover, we have previously shown that very low levels of ETS exposure can exacerbate adult asthma [33
]. We have also shown that moderate levels of ETS exposure are associated with impaired pulmonary function [34
]. Taken together, these results indicate that even low-to-moderate levels of ETS exposure may have deleterious effects on airway function and obstructive lung disease.
We used the standard epidemiologic definition of COPD, based on a self-reported physician diagnosis of chronic bronchitis, emphysema, or COPD [1
]. This survey-based approach enabled us to evaluate a population-based sample of adults who resided throughout the continental United States, which ensured generalizable results. On logistical grounds, conducting spirometry among subjects who reside thousands of miles apart would be highly difficult, if not impossible. The use of self-reported physician-diagnosis, however, may have resulted in some misclassification of disease status. Previous work indicated that a similar survey-based definition of COPD had a high positive predictive value (78%) when validated using a blinded medical record review that included spirometry and radiographic studies [35
]. Other work confirmed that a self-reported history of COPD is a strong predictor of airflow obstruction [36
]. In the subset of our participants with COPD who had available spirometry data, the prevalence of airflow obstruction was very high (89%). In addition, the high prevalence of lifetime smoking in our study, which was more than 80%, supports the diagnosis of COPD. The prevalence of COPD in our sample (18%) was also similar to that reported in two other population-based studies conducted in the United States [1
]. Furthermore, reanalysis of our data using a more restrictive definition of COPD that excluded chronic bronchitis did not appreciably affect the results. In sum, misclassification of COPD is not likely to bias our results; if present, such bias would likely be non-differential with respect to ETS exposure and reduce effect estimates towards the null value.
Lifetime cumulative ETS exposure was ascertained by self-report, which could have resulted in exposure misclassification. Previous studies have found moderate correlations between self-reported ETS exposure and biomarker levels (e.g., cotinine) or direct personal exposure monitoring (e.g., nicotine) [33
]. We cannot, however, exclude some systematic misclassification of ETS exposure. For example, persons with COPD, because they have respiratory symptoms, could be more likely to remember and report ETS exposure, upwardly biasing the effect estimates. Because our focus was on lifetime ETS exposure, there is no other available ETS exposure methodology. Cotinine level, the most widely used biomarker for ETS exposure, reflects exposure during the past 1–2 days [42
]. Direct exposure monitoring, such as the personal nicotine badge, can only be used for brief periods of up to several weeks [33
]. Consequently, the only feasible method for lifetime ETS exposure is survey-based.
Because smoking is the dominant risk factor for COPD, we cannot completely exclude some residual confounding by smoking. There were too few never smokers with COPD (n = 75) to restrict the overall analysis to never smokers. To address this issue, we controlled for personal smoking history in multivariate analysis, defined as ever smoking or current / past smoking. The multivariate analysis was also restricted to non-current smokers, yielding essentially the same results. We also controlled for cumulative lifetime pack-years of smoking in additional analyses, which continued to show highly significant results for home ETS exposure, but slightly attenuated findings for workplace ETS after VGDF exposure was also controlled. The interaction analysis also supported the elevated risk for home ETS exposure among never smokers. In sum, the results do not indicate that the results can be explained by residual confounding by direct personal smoking history.