These data are consistent with a previous analysis we carried out using interview data from the same referent population use in a study with an entirely different group of COPD cases whose occupational exposures had been similarly characterized. In that previous investigation, VGDF was associated with a doubling of the odds of COPD (OR = 2.0) and a PAF of 20%.6
The current analysis also complements the results we reported from another, clinically- and spirometrically-defined COPD cohort in which the VGDF-related risk also was doubled (OR= 2.1) and the PAF was 31%.7
Moreover, the current study fits in well with summary data generated through systematic reviews of multiple studies of occupational exposures in COPD; two such reviews have both concluded that approximately 15% of COPD is attributed to workplace factors.3,4
In both of the previous studies alluded to above, however, there was evidence that combined occupational exposure and smoking manifest an effect that was more than additive6,7
whereas we observed a somewhat less than additive effect. The current analysis, however, differs methodologically from those studies by combining never smokers with light smokers (<10 pack-years) as the referent category. This was necessitated by limited numbers of never-smokers with disease. This is a relatively small study, with a further reduction in study numbers for the subset with spirometry that was obtained through home visits. The limited number of cases limits study power to examine certain questions, especially disease among non-smokers, as noted, or the ability to reliably carry out analyses stratified by sex or age groups. Although the small study numbers contribute to the wide confidence intervals for certain estimates, this should not have led to the positive findings that were observed in terms of statistical significance (alpha error).
Another limitation is the national sampling basis of the referents compared to the regional (northern California) derivation of the cases, along with the temporal lag in sampling of more than five years. This may have accounted for the relatively weak JEM-based associations that we observed, given the narrower range and different distribution of occupations likely on a regional compared to national basis (although migration to California after a longest-held job would have blunted this effect). Certainly, the geographic factor may limit the ability to generalize these findings to other locations. Moreover, since the referents were interviewed earlier in time and were somewhat younger, (although like the cases, the referents were approaching or past the age typical of retirement), they might have gone on to receive a COPD diagnosis after the date at which they were studied. This could have led to systematic misclassification of cases as referents, biasing our findings toward the null. We do not have follow-up data that would allow us to analyze this further. In addition, we did not analyze years of employment at the longest held job as a modifying factor or separately analyze broad classes of occupation (for example blue collar trades) of industry of employment.
Reporting bias is another consideration when using subject-reported VGDF exposure. We have previously analyzed this question in depth, using data from a different cohort study of adults with asthma.18
We found that self-reported VGDF was fairly sensitive measured against JEM-defined exposure as the gold standard. More importantly, compared to asthma, rhinitis (a less severe condition) was more likely to lead to over-reporting of VGDF, arguing against reporting bias driven by disease severity. In a previous analysis of data from the COPD cohort, based on the original baseline survey, we showed that the single VGDF item performs well (sensitivity 69%; specificity 88%) against a checklist of 16 specific exposures including subsets of irritant exposures, and organic and inorganic dusts and fumes.10
We did not have medical records from which to verify the reported physician diagnosis. We addressed this limitation, in part, through our analysis of the subset of cases defined either by airflow obstruction by spirometry or the standard questionnaire criterion for chronic bronchitis.
In summary, these findings add yet another positive study to a growing body of evidence indicating that occupational exposures are indeed a risk factor for COPD. A number of questions arise out of this central observation, including whether or not there is a different pattern of risk for chronic bronchitis as compared to airflow obstruction and the role that sex, duration and type of exposure and other co-factors may play in modifying occupational risks. In particular, the potential interplay between active smoking, which is by far the dominant risk factor in COPD causation, and occupational exposure remains to be more fully explored. This is important for improved prevention efforts, clinical diagnosis, management, and, from a societal point of view, attribution of cause and apportionment of the costs of preventing and treating illness.