Pesticide Exposure and Asthma

Pierre Ernst, M.D.

McGill University, Montreal, Quebec, Canada

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Occupational exposures have been recognized as causes of asthma and asthma-like syndromes since the early 18th century (1). Recent estimates suggest that between 5% and 10% of asthma in young adults may be directly attributable to substances encountered at work (2). Among the occupational groups with the highest risk of asthma, one finds farmers and agricultural workers (2). Farmers and agricultural workers are exposed to various allergens of plant, animal, and chemical origin that are associated with classic IgE-mediated allergic asthma; to irritants that might aggravate pre-existent asthma or, at high doses, result in irritant-induced asthma; and to plant dusts (for example, grain and cotton dusts) that cause a nonallergic asthma-like syndrome (3). Although exposure to pesticides is common in both agricultural and nonagricultural settings (4), these have not featured prominently in lists of substances associated with occupational asthma (5).

In the current issue of the AJRCCM, Hoppin and colleagues (pp. 683-689) describe a cohort of ~ 20,000 farmers, certified pesticide applicators, from Iowa and North Carolina, who participated in a study originally designed to look at cancer risk in relation to pesticide exposure (6). Among these mostly white male farmers, those who reported wheeze in the past year were compared with those not reporting this symptom as to the reported use of various pesticides, frequency of their use, and application techniques. Ever use of 11 of 40 pesticides, mostly insecticides and herbicides, was associated with a greater likelihood of reported wheeze, and for most of these, the likelihood of wheeze increased with the frequency of exposure in the last year. Some of the strongest associations were seen with application of insecticides to animals with methods in which the insecticide is aerosolized. We are told by the authors that these associations persisted after adjustment for the extent of exposure to animals by the farmers. It is unclear how this adjustment for possible confounding was done, and therefore, how precise such an adjustment could be.

Overall, possible differences in exposures of farmers, other than to pesticides, are not taken into account. Because such exposures might very well be related to both the occurrence of wheezing and use of pesticides, the associations described may be due to confounding by farming exposures truly related to an excess risk of asthma. The presence of an increasing risk with increasing frequency of exposure to pesticides does not necessarily reduce the likelihood of such confounding.

If pesticide exposure is a risk factor for wheezing, what might such wheezing represent? As mentioned previously, there is scant evidence that pesticides cause occupational asthma through allergic sensitization. Many pesticides cause inhibition of cholinesterase and can provoke bronchospasm through increased cholinergic activity. At high doses, certain pesticides may act as irritants to the airways. One would expect these two later mechanisms to confer an increased susceptibility of subjects with prior asthma to wheezing with pesticide exposure. On the contrary, Hoppin and colleagues found that for five of the chemicals they studied, wheezing was more likely to be reported with exposure only among nonasthmatics (6).

The lack of an effect among subjects reporting a diagnosis of asthma likely reflects health selection; that is, the most susceptible subjects avoid exposure. This leads to an underestimation of the potential adverse effects of the exposure under study. The consequences of pesticide exposure on the airways may also be underestimated in a study of farmers because subjects raised on a farm may be less prone to atopy and asthma (7, 8). Therefore, if the association between wheeze and pesticide exposure is not due to confounding, we may be faced with a causal relationship with a magnitude of effect substantially larger than the odds ratios for the association reported by Hoppin and colleagues (6) (all the odds ratios were less than two).

The possible magnitude of the association is of concern because of the very large amounts of pesticides used domestically and in urban environments as well as the exposure of children who may be more susceptible to the adverse effects of these chemicals and who may sustain higher exposures than adults in the same environment (4, 9). Exposure to pesticides, especially insecticides, has effects of potential relevance to the induction and aggravation of asthma, such as modification of autonomic function and modification of the immune response (4, 10). Exposure to insecticides is particularly high in inner cities in the United States (9), areas where asthma morbidity is also high and where use of insecticides is advocated to control cockroach exposure, itself related to an increase in asthma morbidity (11, 12). One cannot help but wonder whether exposure to insecticides in these areas may be contributing to asthma morbidity.

To progress beyond speculation, we need more convincing evidence that pesticide use does cause asthma de novo, or makes existing asthma worse, at levels of exposure commonly encountered. Such information is most likely to come from astute clinicians who obtain a detailed occupational history in subjects with asthma, especially for those with asthma of recent onset or recent aggravation. Linking asthma to the work environment may be particularly difficult among farmers, however, because of their prolonged work week and residence in the same environment as their work. Confirmation of pesticide exposure as the cause of asthma will require the demonstration of an acute worsening of airway obstruction and an increase in bronchial responsiveness with exposure (1).

	References

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