The occupational burden of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) accounts worldwide for considerable and increasing morbidity and mortality 1, 2. COPD is a disease state characterised by the presence of airflow limitation that is typically progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases 3. The term COPD subsumes several different and frequently concomitant clinical conditions, including chronic bronchitis and emphysema.

Cigarette smoking is by far the predominant risk factor for COPD. This has obscured the role of other environmental factors that might account for disease among nonsmokers or magnify the adverse impact of cigarettes among those who smoke. Recognition that the complex particulate and irritant gas constituents of tobacco smoke can cause COPD provides high biological plausibility that other inhaled toxins may also play an aetiological role in this disease process. Owing to the intensity and duration of exposure involved, the most likely candidate exposures contributing to COPD are vapours, gases, dusts or fumes (VGDF) encountered in the workplace.

“Dusty trades” have been linked to chronic bronchitis since the nineteenth century 4. Analysis of epidemiological data from the 1930s and 1940s confirmed the impression of a strong link between occupation and chronic bronchitis 5, 6. Later, in the 1950s and early 1960s, irreversible airflow limitation and emphysema, which are functional and pathological abnormalities linked with chronic bronchitis, were shown to be increased among mineworkers, one of the occupational groups most heavily exposed to dust and fumes 7, 8.

Since the mid-1970s, a number of epidemiological studies have implicated occupational exposures in COPD. These investigations, summarised in the seminal 1989 review of Becklake 9 and, more recently, by Viegi and Di Pede 10, have been carried out within specific industrial cohorts as well as across community-based population samples. Most of these population samples were developed for other research purposes; some of the studies examined only recent occupational exposures 11–13, included primarily younger adults 11–15 or covered a limited geographical area 16–19. As a result, although there has been an accumulation of evidence linking occupational inhalant exposures to COPD, estimates of the proportion of COPD cases attributable to workplace exposures have varied widely from study to study 9, 10. Given the high prevalence of COPD and the preventability of occupation-related disease, establishing the occupational contribution to the burden of COPD could have a major public health impact. In this study, older adults were surveyed regarding their health status, prior cigarette smoking and history of occupational exposures.

Methods

Sampling frames and recruitment

The total sample was constructed from three cohorts based on geography and respiratory condition (fig. 1⇓). The first cohort included 1,001 subjects recruited from a national random sample in the 48 contiguous states of the USA. The second and third cohorts were limited to certain geographical “hot spots”, based on Health Service Areas with the highest COPD mortality rates, derived from the National Institute ofOccupational Safety and Health's Atlas of Respiratory Disease Mortality, United States: 1982–1993 20. The telephone area codes corresponding best to the areas in the top quartile of elevated age-adjusted mortality rates were selected (fig. 2⇓), in order to increase the yield of individuals with COPD. The second cohort included 1,002 participants recruited through random sampling of these hot spot area codes. The third cohort included 110 respondents selected from the hot spot areas and prescreened to include only individuals reporting a physician's diagnosis of either one of the three COPD conditions or asthma. The entire sample consisted of 2,113 individuals, representing a combined response rate of 53% of households with at least one person aged 55–75 yrs, as shown in figure 1⇓. After omitting subjects not responding to key analysis variables, the final sample included 2,061 individuals (98% of original sample).

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Fig. 1.—

Subject recruitment in three sampling frames: a) national random sample; b) “hot spots” random sample; and c) hot spots condition sample.

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Fig. 2.—

Telephone area codes (▓) corresponding to the “hot spot” Health Service Areas with the highest age-adjusted chronic obstructive pulmonary disease mortality rates, 1982–1993 20.

Results

The final study sample included 377 individuals who reported a physician's diagnosis of at least one COPD, of whom 288 reported chronic bronchitis and 144 emphysema (table 1⇓). Altogether, 140 (37%) respondents reporting COPD also reported a diagnosis of asthma; an additional 129 individuals reported a physician's diagnosis of asthma but not COPD. By design, the three sampling frames yielded different disease distributions. In the first cohort, the national random sample, and the second cohort, the hot spots sample with and without respiratory disease, 14 and 17% of respondents, respectively, reported a diagnosis of COPD. Among the three sampling frames, there were no significant differences in the proportion of those with COPD who also reported asthma.

As shown in table 2⇓, the study sample was partitioned into three mutually exclusive groups based on reported diagnoses: COPD (with or without concomitant asthma, n=377); asthma alone (n=129); and no reported diagnosis of a chronic airway disease (n=1,555). The three groups did not differ significantly in age distribution within the 20-yr age span of the sample: the mean age of those reporting COPD was 64±6 yrs, asthma alone 63±6 yrs and no chronic airway disease 64±6 yrs (p=0.2). Females were over-represented among those reporting COPD and asthma (p<0.001). Socioeconomical and smoking status also varied significantly by condition group (p<0.001). Those with COPD had lower levels of education and lower household incomes overall, and, as expected, were much more likely to have ever smoked than those with asthma alone or no chronic airway disease. The distribution of smoking status was similar for those with asthma alone and those with no chronic airway disease.

Consistent with a greater degree of work disability associated with COPD relative to asthma, only 19% of respondents reporting COPD were employed at the time of interview (table 3⇓), compared with 30% of those reporting asthma alone and 31% of those with no chronic airway disease (p<0.001). There were no significant differences by diagnosis group in the proportion who had ever been in the labour force (>90%) or in the distribution of longest-held job among the major occupational categories. The mean duration of employment in the longest-held job was 19±11 yrs among those reporting COPD, 23±12 yrs for asthma alone and 22±12 yrs for no chronic airway disease (p<0.001).

As shown in table 4⇓, half of those with COPD reported exposure to VGDF during their longest-held job, compared to 42% of those with asthma alone and 32% of those with no chronic airway disease (p<0.001). Among the 189 subjects with chronic bronchitis alone, 42% reported VGDF exposure and 57% of the 188 subjects reporting diagnoses of COPD or emphysema reported VGDF exposure. Each subgroup of exposures (combustion byproducts, inorganic dusts or fumes, and organic dusts) was also reported more frequently by those with COPD, although these differences by diagnostic group were significant only for inorganic dusts and fumes. The three diagnostic groups were compared using a job matrix for occupational exposure likelihood, classifying respondents as having low, intermediate or high probability of dust exposure based on the occupation of their longest-held job. Using this measure, exposure also varied significantly (p=0.01). Individuals reporting COPD were the most likely to be employed in either intermediate or high probability exposure occupations.

Comparing respondents who did or did not report any COPD diagnosis (regardless of asthma diagnoses), on the basis of self-reported occupational exposure (table 5⇓), VGDF exposure during the longest-held job was associated with a two-fold increase in risk of COPD (OR 2.0, 95% CI 1.6–2.5). The PAR of COPD for self-reported exposure calculated from the logistic regression model was 20% (95% CI 13–27%). On further analysis, the three exposure categories were evaluated separately (data not shown in table). In adjusted models, exposure to inorganic dusts and fumes had the strongest relationship with COPD (OR 1.6, 95% CI 1.1–2.3), followed by combustion byproducts (OR 1.4, 95% CI 1.01–1.9) and organic dusts (OR 1.3, 95% CI 0.9–1.8).

After controlling for covariates, risk of COPD was elevated for those with intermediate (OR 1.4, 95% CI 1.1–1.9) and high probability of dust exposure (OR 1.6, 95% CI 1.1–2.5), according to the job exposure matrix. The combined PAR for intermediate or high probability of exposure was 9% (95% CI 3–15%) based on the adjusted models.

As expected, current and former smoking were strongly associated with COPD, resulting in a combined PAR of 51% (95% CI 40–59%), after controlling for age, sex, race, ethnicity and self-reported occupational exposure. The association of smoking exposure and COPD was not substantively different in a model including the occupational exposure matrix variables instead of the self-reported measure.

Table 5⇑ also includes estimates of the risk of COPD defined more narrowly, excluding all 189 subjects with chronic bronchitis alone. In these models, the adjusted OR for self-reported occupational exposure rose slightly to 2.6 (95% CI 1.8–3.5). For intermediate probability of dust exposure, the adjusted OR was 1.5 (95% CI 1.04–2.2) and, for high probability of exposure, it was 1.9 (95% CI 1.2–3.2). Using the narrower COPD definition, the PAR associated with self-reported exposure was 31% (95% CI 19–41%); the comparable PAR associated with the job exposure matrix was 13% (95% CI 3–22%). After excluding subjects with bronchitis alone, the PAR for COPD associated with cigarette smoking was much greater, yielding a combined PAR for smoking (current and former) of 76% in this model.

Since occupational exposures may have affected cigarette smokers and nonsmokers differently, the joint associations of cigarette smoking (ever versus never smoked) and self-reported occupational exposure with COPD were examined, using the definitions with and without chronic bronchitis included. As shown in table 6⇓, the joint association of cigarette smoking and occupational exposure appeared to be greater than would be expected with a strictly additive relationship. The unadjusted probability of any COPD among those with neither exposure was 0.08, among those with occupational exposure alone it was 0.10, among those with smoking exposure alone it was 0.19 and among those withboth exposures it was 0.32. In an additive relationship, the excess risk of COPD for the combination of smoking and occupational exposure (compared to neither exposure) would be approximately equal to the sum of the excess risks for smoking alone and occupational exposure alone. The excess risk for those with both smoking and occupational exposure was nearly twice that: 0.23 compared to 0.13 for any COPD and 0.20 compared to 0.11 for the narrower definition of COPD excluding chronic bronchitis.

As a sensitivity analysis, the multivariate logistic regression models were re-estimated, further excluding the 129 subjects reporting asthma alone, because of the clinical overlap between asthma and COPD. The adjusted OR associated with self-reported occupational exposure in this subsample was 2.1 (95% CI 1.6–2.7) and the resulting PAR was 21% (95% CI 14–28%).

Discussion

The present findings support an association between COPD and occupational inhalant exposures. Increases of >100% in the risk of COPD due to workplace factors were observed, even after taking into account the impact of cigarette smoking. Since some degree of exposure was relatively common, the proportion of COPD contributed by occupation was considerable, with an estimated PAR of 20 or 31%, depending upon the definition of COPD used. In other words, elimination of all adverse workplace exposures could prevent more than one in five cases of COPD, all other risk factors (including cigarette smoking) being equal.

The risks estimated in the present study are in the range ofthose reported by other investigators. Viegi and Di Pede 10 concluded from their literature review that ∼15% of all COPD could be attributed to occupational exposures. The studies yielding this estimate were heterogeneous in approach. Furthermore, few were designed a priori to focus on occupation as a risk factor for COPD using a population-based approach and studying older adults at greatest risk of disease. It is also interesting to note that the PAR estimated in the present study is similar to that found for asthma in relation to occupational VGDF exposure 27.

The present survey method, despite the advantages of broad-based recruitment of subjects, has important limitations. The retrospective nature of the study may lead to the introduction of recall bias, to the extent that affected individuals may associate their conditions with exposure. However, the job exposure matrix, which would not be prone to this bias, reaffirmed the association between occupation and disease.

The standard epidemiological approach of self-report of a physician's diagnosis of one of three conditions (chronic bronchitis, emphysema or COPD) to define COPD was used. The National Health and Nutrition Examination Survey (NHANES) found a 12.5% US national prevalence of reported physician diagnosis of emphysema or chronic bronchitis (a “COPD” diagnosis was not queried) among adults aged 55–75 yrs 28, compared to the 13.5% found in the present national sampling frame.

This epidemiological approach, although widely used, can lead to overestimations due to attribution of diagnoses that were not made or were made erroneously. Similarly, this approach to case definition can lead to underestimations due to poor access to medical care or missed diagnoses despite medical evaluation. One recent study documented that only a minority of subjects reporting a physician's diagnosis of chronic bronchitis also meet a symptom-based case definition 29. Another study, however, found that, among those reporting the diagnosis and yet with questionnaire-based symptoms falling short of a probable or definite classification of chronic bronchitis, 79% nonetheless demonstrated airway obstruction 30. In another recent study regarding this question, self-report of a physician's diagnosis of COPD, as defined in the present study, was shown to be a potent predictor of airflow obstruction 31. Thus, although using areported diagnosis without confirmation by pulmonary function testing leads to some overdiagnosis, this case definition appears to be valid for epidemiological purposes and is supported by other studies.

Under-reporting of disease may be a more common problem. A recent analysis of NHANES III data found that only 63% of subjects with low lung function (forced expiratory volume in one second (FEV₁)/forced vital capacity of <0.70 or FEV₁ of <80% of the predicted value) reported aphysician's diagnosis of asthma, chronic bronchitis or emphysema 32. The extent to which COPD is similarly under-reported in the present study, however, is unlikely to be differentially related to exposure and thus would bias results towards the null hypothesis. Such misclassification may account for the relatively low PAR for smoking that was observed on analysis of the entire cohort (51%), although, after excluding those with chronic bronchitis alone, the resulting PAR of 76% is closer to the 80–90% range generally cited 33.

The role of cigarette smoking appears to be complex. In the present analyses, evidence was found for an interaction between smoking and occupational exposures, such that current or former smokers reporting job exposure were at particularly high risk of COPD. Other studies have found similar relationships 10, 11, 34. This is biologically plausible, since irritant gas and particulate exposures could interact in either additive or multiplicative ways in the initiation and progression of chronic bronchitis, emphysema or airflow obstruction. Moreover, the differences in attributable risk to PAR for both occupation and smoking, estimated with or without subjects with chronic bronchitis, are consistent with heterogeneity in the causal pathways of diseases subsumed within the overall category of COPD.

Cigarette smoking remains the predominant aetiological factor in chronic obstructive pulmonary disease and is appropriately at the forefront of public health efforts in lung disease prevention. Nonetheless, the present findings support and extend the observations of other studies, indicating a significant role of some occupations in causing chronic obstructive pulmonary disease. Clinicians and healthcare policy-makers need to take workplace conditions into account, perhaps all the more so among smokers, when targeting prevention strategies.