THE AUTHORS REPLY

We appreciate Alquwayfili’s (1) interest in our article on occupational exposure to diesel exhaust (DE) and amyotrophic lateral sclerosis (ALS) in Denmark (2). First, we thank him for pointing out our error in the last paragraph of the methods (2). We excluded those who were born at least 25 years prior to 1964, the year the registry was established. Thus, the exclusion was birth year before 1939, which is the cutoff that was used throughout the analysis; all the numbers shown in the figure and tables are correct (1).

Alquwayfili raises an interesting point about formaldehyde. As a component of DE, it is possible that formaldehyde exposure could account for our findings for DE given that we have found that formaldehyde exposure is associated with amyotrophic lateral sclerosis (3, 4), including in a study of occupational exposures to formaldehyde in these Danish registries (5). Importantly though, the formaldehyde job-exposure matrix (JEM) does not consider DE-exposed industries as formaldehyde-exposed, and there is no overlap between the exposed jobs in the 2 JEMs. The possibility of confounding by formaldehyde from exposures related to use of cosmetic products (data that is not in the Danish registries) is unlikely—it is not clear why that use would be associated with DE-exposed occupations, which would be needed for confounding. Further, such use would not result in misclassification of DE exposure.

We appreciate the acknowledgement of our consideration of differences by sex in the workplace (1). We stratified the analysis by sex to account for potential differences in job tasks and subsequent exposures, such as those Alquwayfili describes, which would appear as effect measure modification, but the stratification also addresses potential confounding by sex.

The issue of personal protective equipment use is certainly a good one, but that kind of data is very difficult to maintain in very large data sets like those of the Registries, a limitation we noted in the limitations section of our manuscript (1). It is important to note, however, that the JEM we used was developed by a team of exposure experts with information covering over 300 occupational categories (6). DE exposure was characterized by 2 measures: the probability of exposure and the mean level of exposure. Probability measures are based on estimates from survey data assessing risk of DE exposure, including technological advances in machinery and use of personal protective equipment in each industry (6). While we believe the significantly protective association seen among women was the result of chance—there was no consistent pattern to that finding as there was with the results in men—we cannot rule out uncontrolled confounding. But what Alquwayfili describes would not cause a confounded result, because it relates to differences in exposure by sex, while the finding was a comparison among women only.

In conclusion, we appreciate the interest in our manuscript. Certainly there are additional data that could help improve on our findings, which might be relevant to current workers in DE-exposed industries and potentially other populations with high and consistent exposures to DE. The difficulty is that such data are often hard to come by in large enough populations for studies of amyotrophic lateral sclerosis.