Methodological problems in a case-referent study based on a register of occupational asthma

• asthma
• case-referent study

Meredith et al,¹ performed a case-referent study to investigate asthma caused by isocyanates. They claimed that the results indicated that isocyanate asthma occurs at low 8 hour average exposure (around 1.5 ppb); for exposures above 1.125 ppb there was about a threefold increased risk, however, this was of limited significance (odds ratio (OR)=3.2, 95% confidence interval (95% CI) 0.96 to 10.6; p=0.06). They also concluded that their study, by contrast with other studies, had a higher risk of isocyanate asthma in smokers and people with atopy.

The study design is original as cases were recruited from a register of occupational asthma. A case-referent study based on a register of cases with both the disease and the exposure of interest is new. I think the design requires some discussion as it may introduce severe bias.

A typical case-referent study selects cases with a certain disease—for example, asthma—from a hospital register or in a population survey.² The referents should be selected to give an unbiased estimate of frequency of exposure in the study base.³ The study base of a register, including cases of occupational asthma, is the population that if the case had asthma would be reported to the register. Therefore, the authors of this study matched the referents to the cases by reporting doctor and factory or production area. Then they measured or estimated the exposure level for both cases and referents and found that the average 8 hour exposure was higher among cases. This design has certain weaknesses illustrated by the following hypothetical situations:

(1) Assume that the exposure in the production area is homogenous. Then both cases and …