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We appreciate the thoughtful letter from Drs. Kanarek and Anderson. Our study does not address the well-established fact that asbestos exposure is the main causal factor of mesothelioma. The objective of our study was to investigate the risk of mesothelioma (and other asbestos related diseases) in motor vehicle mechanics. The key finding is that Danish motor vehicle mechanics do not on average have an elevated risk of mesothelioma during the studied up to 45 years of follow-up. This does not exclude the possibility that some subpopulations of motor vehicle mechanics with more extreme exposure/latency time are at increased risk – but this occupation as a group is not.
We agree that exposure misclassification is a potential problem in epidemiology studies based on occupation and industry titles. We also agree that lifetime asbestos exposure histories, if they could be obtained, might reduce exposure misclassification. However, asbestos exposure is often not recognized or recalled by workers, and workers often do not recall jobs in the distant past. Also, experts may misclassify self-reported jobs regarding asbestos exposure, particularly with respect to asbestos fiber type. Thus, while Drs. Kanarek and Anderson claim “obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease” they offer no practical advice on how reliable asbestos exposure histories can be obtained. They also...
We agree that exposure misclassification is a potential problem in epidemiology studies based on occupation and industry titles. We also agree that lifetime asbestos exposure histories, if they could be obtained, might reduce exposure misclassification. However, asbestos exposure is often not recognized or recalled by workers, and workers often do not recall jobs in the distant past. Also, experts may misclassify self-reported jobs regarding asbestos exposure, particularly with respect to asbestos fiber type. Thus, while Drs. Kanarek and Anderson claim “obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease” they offer no practical advice on how reliable asbestos exposure histories can be obtained. They also provide no evidence that such histories can differentiate between chrysotile and amphibole fibers, and provide no evidence that exposure misclassification from such histories would be less than from the methods we used.
We note that Dr. Anderson and colleagues recently published a study of mesothelioma incidence and mortality in Wisconsin (1) that identified asbestos-exposed occupations based on the self-reported “longest held job reported at the time of diagnosis” or the “usual industry and occupation” recorded on death certificates for mesothelioma cases. It was noted in that paper, that the authors were unable “to determine occupational exposure to asbestos that may have occurred from other work periods” and could not “identify nonoccupational exposure to asbestos.” Dr. Anderson acknowledged that “we would expect any bias introduced to be toward the null and lead to more conservative estimates of effect.” We believe that occupational histories in our study, which were based on historic, written employment records gathered in independent, population-based registers, were far more reliable than the self-reported usual occupations in Dr. Anderson et al.’s study.
There are now over 30 published studies of mesothelioma risks among automobile mechanics, only one of which found increased risk of mesothelioma in which the 95% confidence interval excluded the null, and which otherwise show no increased risk of mesothelioma among automobile mechanics. The consistency of these results observed by different persons, in different places, circumstances, and times (2) (some of which had lifetime occupational and environmental asbestos exposure histories) is a strong argument against the premise that exposure misclassification substantially biased the results.
Dr. Kanarek recently published a review paper in which he reported “There have not been definitive epidemiology studies of brake mechanics because of the nature of the workforce. It is generally nonunionized and spread out in car repair shops” and “Exposure to asbestos from brakes can occur to automobile or truck mechanics anywhere in a vehicle repair shop and the workers are highly transient and not documented.” Dr. Kanarek also noted there have not been “any prospective cohort studies conducted on a group of automobile mechanics.” (3). We believe our study, which is a prospective cohort study based on documented work in vehicle repair shops, answers many of his concerns.
Drs. Kanarek and Anderson point out that over 70% of our cohort of vehicle mechanics were first enrolled after 1986 when asbestos use in Danish vehicle brakes was disappearing. While this statement is correct, it ignores that 21,102 of our subjects were enrolled as mechanics in the 1970 nationwide census and that they were followed through 2015. Moreover, many of them were mechanics prior to the 1970 census. This is substantial number of people followed for a long time, regardless of whether they made up a small proportion of our entire study population. Selikoff’s landmark study of insulators (4) included only 17,800 workers, the majority of whom had yet to achieve 20 years from first exposure at the start of the study, and who were followed for only 10 years. Our population exceeded all these metrics: it was adequate to detect a substantial risk increase of mesothelioma, had there been one. Kanarek and Anderson recognize that our study was adequate to report a significant excess of asbestosis, even though there were fewer asbestosis deaths (19) than there were mesothelioma deaths (48) and the same numbers of incident cases of asbestosis cases (47) as mesotheliomas (47). This is again evidence that our study was adequate to find excess risks of both asbestosis and mesothelioma when they existed.
Drs. Kanarek and Anderson suggest that observing 313 cases of asbestosis in comparators supports the case for exposure misclassification in the comparison group. While it is possible that a small proportion of the 845,480 comparators (who functioned as 1,385,590 comparators after matching with replacement) may have had asbestos exposure at some point in their lives, the more appropriate conclusion is that the comparators were extremely unlikely to be diagnosed with asbestosis (incidence rate 1.19 per 100,000 person-years) or die of asbestosis (mortality rate 0.42 per 100,000 person years), and that not all cases of asbestosis (or mesothelioma) are caused by known exposure to asbestos. We believe a strength of our study was the choice of comparator occupations: we chose those that would be unlikely to have occupational asbestos exposure and that would have no overlapping skills with typical asbestos exposed jobs (such as in shipyards, construction, insulators, plumbing, etc.)
We acknowledge that asbestos is still used in several countries and that that these exposures should be eliminated. The findings in our paper cannot and should not be taken as an argument not to pursue this goal. We thank Drs. Anderson and Kanarek for facilitating a more thorough discussion of these issues.
1) Tomasallo CD, Christensen KY, Raymond M, Creswell PD, Anderson HA, Meiman JG. An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin. J Occup Environ Med. 2018;60(12):1143-9.
2) Hill AB. The environment and disease: association or causation. Proceedings of the Royal Society of Medicine. 1965;58:295-300.
3) Kanarek MS, Anderson HA. Mesothelioma from Asbestos Exposure in Brake Mechanics: Epidemiology in Context. Epidemiology (Sunnyvale). 2018;8(1):12.
4) Selikoff IJ, Hammond EC, Seidman H. Latency of asbestos disease among insulation workers in the United States and Canada. Cancer. 1980;46:2736-40.
Letter to the editor:
We appreciate the opportunity to comment on the article by Thomsen RW et al. Risk of asbestos, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. We believe there are many problems in methodology and we disagree with author’s interpretations and conclusions especially in relation to asbestos and mesothelioma in vehicle mechanics in this article.
The epidemiology analysis described by Thomsen et al lacks asbestos exposure data and uses cross-sectional occupation data as surrogates for longitudinal use. Occupational categories are not equal to exposure. Especially for asbestos it has been clear that obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease. Without longitudinal individual exposure histories in the Thomson et al study, there is undoubtably significant misclassification of exposure in both the motor vehicle mechanic group (unexposed considered exposed) and even more problematic in the control group (exposed classified as unexposed). This double likelihood of exposure misclassification creates unreliable analytics which result in an epidemiologic bias towards the null. 1
Thomsen et al used cross-sectional data at variable dates to place workers in their two study cohorts based on reported current occupation and industry. The occupation on the 1970 census or when first...
Thomsen et al used cross-sectional data at variable dates to place workers in their two study cohorts based on reported current occupation and industry. The occupation on the 1970 census or when first mentioned for individuals on later registrations was used to assign vehicle mechanic occupation with the assumption that asbestos exposure had occurred. The selected occupation categories for the “comparison” cohort assumed non-asbestos exposed occupations throughout their working lifetime. Other than looking for the vehicle mechanic category, apparently no search was made in subsequent registries to see if they had switched to another occupation with asbestos exposure likelihood. The authors do mention that about one half of the 21,102 1970 census vehicle mechanic individuals were in the same category in the 1996-1999 registry. However, was the work they performed the same? The cohort was very young at entrance at any of the time intervals (median age 25) and the median follow-up was 20 years. The age at which mesothelioma occurs is usually in the 70+ age group. Latency for mesothelioma can be as high as 50 years or more. Over 70% of the cohort were first enrolled after 1986 when asbestos use in Danish vehicle brakes was disappearing, exposure standards in place and the likelihood of high exposure for those just entering the cohort reduced. Only 23% of the cohort was deceased and the vast majority had not reached the age group where mesotheliomas or asbestosis would occur, given their long latent period.
The overall finding of Thomsen et al was that asbestosis was elevated in motor vehicle mechanics, but not mesothelioma. A clinical diagnosis of asbestosis requires a history of asbestos exposure while at autopsy a tissue diagnosis may be made when no exposure history is found. What is striking is that there were 313 comparator cases of asbestosis in the morbidity data and 108 in mortality. This information supports the case for exposure misclassification in the comparison group. Similarly, the occurrence of 553 mesothelioma/pleural cancer mortality cases among the comparators and 628 cases in the morbidity files also suggests misclassification among the “non-asbestos exposed” as an explanation for the lack of statistical differences between the cohorts.
The high number of asbestosis cases and deaths among the comparison group and the statistical excess among the vehicle mechanics but not an excess of mesothelioma/pleural cancer is puzzling as a higher dose of asbestos exposure is needed for asbestosis than for mesothelioma.2 An explanation may be that the years of follow-up in the Thomsen et al study may not have been long enough for the peak mesothelioma risk but sufficient for clinical detection of asbestosis/pleural abnormalities. Supporting this is that Thomsen et al found the highest association with mesothelioma in the 1970 census cohort, which had the longest follow-up.
Thomsen et al. states that asbestos use in brakes is now phased out in most countries. Unfortunately, this is not true. Chrysotile asbestos is currently being widely used in Brazil, Russia, China, India, Thailand, Malaysia and elsewhere and is being used in the manufacture of brakes. (2-5) Since there is potential exposure to toxic chrysotile asbestos fibers of various sizes in the dusty environment of motor vehicle mechanics, which is continuing in several countries around the world, precaution should point to policies that concentrate on industrial hygiene measures that limit worker dust exposure.
Marty S Kanarek, PhD1, Henry A Anderson, MD1
1 Department of Population Health Sciences and in the Nelson Institute for Environmental Studies, University of Wisconsin-Madison, Madison, Wisconsin, USA
Correspondence to Professor Marty Kanarek, Department of Population Health Sciences, School of Medicine and Public Health, 610 N. Walnut Street, University of Wisconsin-Madison, 53726; email@example.com
Contributors MSK was the lead author. HAA was co-author, reviewing the original response and contributing original content in addition to editing. Final version was approved by both authors.
Competing interests Both Kanarek and Anderson have served as consultants to government and international agencies on asbestos health effects, and have been consultants and witnesses on plaintiff’s litigation concerning asbestos and disease.
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