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Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures.

Although specific pesticides have been associated with wheeze in farmers, little is known about pesticides and asthma. Data from 19,704 male farmers in the Agricultural Health Study were used to evaluate lifetime use of 48 pesticides and prevalent adult-onset asthma, defined as doctor-diagnosed asthma after the age of 20 yrs. Asthma cases were categorised as allergic (n = 127) and nonallergic (n = 314) based on their history of eczema or hay fever. Polytomous logistic regression, controlling for age, state, smoking and body mass, was used to assess pesticide associations. High pesticide exposure events were associated with a doubling of both allergic and nonallergic asthma. For ever-use, 12 individual pesticides were associated with allergic asthma and four with nonallergic asthma. For allergic asthma, coumaphos (OR 2.34; 95% CI 1.49-3.70), heptachlor (OR 2.01; 95% CI 1.30-3.11), parathion (OR 2.05; 95% CI 1.21-3.46), 80/20 mix (carbon tetrachloride/carbon disulfide) (OR 2.15; 95% CI 1.23-3.76) and ethylene dibromide (OR 2.07; 95% CI 1.02-4.20) all showed ORs of >2.0 and significant exposure-response trends. For nonallergic asthma, DDT (dichlorodiphenyltrichloroethane) showed the strongest association (OR 1.41; 95% CI 1.09-1.84), but with little evidence of increasing asthma with increasing use. Current animal handling and farm activities did not confound these results. There was little evidence that allergy alone was driving these associations. In conclusion, pesticides may be an overlooked contributor to asthma risk among farmers.

Exposure to certain environmental toxicants may be associated with increased risk of developing diabetes. The authors' aim was to investigate the relation between lifetime exposure to specific agricultural pesticides and diabetes incidence among pesticide applicators. The study included 33,457 licensed applicators, predominantly non-Hispanic White males, enrolled in the Agricultural Health Study. Incident diabetes was self-reported in a 5-year follow-up interview (1999-2003), giving 1,176 diabetics and 30,611 nondiabetics for analysis. Lifetime exposure to pesticides and covariate information were reported by participants at enrollment (1993-1997). Using logistic regression, the authors considered two primary measures of pesticide exposure: ever use and cumulative lifetime days of use. They found seven specific pesticides (aldrin, chlordane, heptachlor, dichlorvos, trichlorfon, alachlor, and cyanazine) for which the odds of diabetes incidence increased with both ever use and cumulative days of use. Applicators who had used the organochlorine insecticides aldrin, chlordane, and heptachlor more than 100 lifetime days had 51%, 63%, and 94% increased odds of diabetes, respectively. The observed association of organochlorine and organophosphate insecticides with diabetes is consistent with results from previous human and animal studies. Long-term exposure from handling certain pesticides, in particular, organochlorine and organophosphate insecticides, may be associated with increased risk of diabetes.

Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate pesticide levels. We analysed cross-sectional data from 18 782 Caucasian, male, licensed pesticide applicators, enrolled in the Agricultural Health Study from 1993 to 1997. Applicators provided information on lifetime pesticide use, and 23 neurologic symptoms typically associated with pesticide intoxication. Increased risk of experiencing ≥10 symptoms during the year before enrollment was associated with cumulative pesticide use, personally mixing or applying pesticides, pesticide-related medical care, diagnosed pesticide poisoning, and events involving high personal pesticide exposure. Greatest risk was associated with use of organophosphate and organochlorine insecticides. Results were similar after stratification by pesticide use during the year before enrollment, or exclusion of applicators with a history of pesticide poisoning, or high-exposure events. Use of pesticide application methods likely to involve high personal exposure was associated with greater risk. Groups of symptoms reflecting several neurologic domains, including affect, cognition, autonomic and motor function, and vision, were also associated with pesticide exposure. These results suggest that neurologic symptoms are associated with cumulative exposure to moderate levels of organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.

Previous studies based on limited exposure assessment have suggested that Parkinson's disease (PD) is associated with pesticide exposure. The authors used data obtained from licensed private pesticide applicators and spouses participating in the Agricultural Health Study to evaluate the relation of self-reported PD to pesticide exposure. Cohort members, who were enrolled in 1993-1997, provided detailed information on lifetime pesticide use. At follow-up in 1999-2003, 68% of the cohort was interviewed. Cases were defined as participants who reported physician-diagnosed PD at enrollment (prevalent cases, n = 83) or follow-up (incident cases, n = 78). Cases were compared with cohort members who did not report PD (n = 79,557 at enrollment and n = 55,931 at follow-up). Incident PD was associated with cumulative days of pesticide use at enrollment (for highest quartile vs. lowest, odds ratio (OR) = 2.3, 95% confidence interval: 1.2, 4.5; p-trend = 0.009), with personally applying pesticides more than half the time (OR = 1.9, 95% confidence interval: 0.7, 4.7), and with some specific pesticides (ORs > or = 1.4). Prevalent PD was not associated with overall pesticide use. This study suggests that exposure to certain pesticides may increase PD risk. Findings for specific chemicals may provide fruitful leads for further investigation.

Background Retinal degeneration is the leading cause of visual impairment in older adults, but little is known about its relationship to neurotoxic exposures. Methods The Agricultural Health Study is a cohort study of licensed pesticide applicators from Iowa and North Carolina. We used cross-sectional data from self-administered questionnaires given at enrollment in 1994–1996 to compare pesticide use in 154 applicators who reported retinal degeneration and 17,804 controls. Results Retinal degeneration was associated with fungicide use (odds ratio = 1.8, 95% confidence interval = 1.3–2.6). This relationship was seen in subgroups defined by state, demographic characteristics, or medical history, as well as in the entire group. Risk increased with cumulative days of fungicide use (P for trend = 0.011) and was greater when application methods involving greater personal exposure were used. Retinal degeneration was also related to use of organochlorine or carbamate insecticides, but these associations were less consistent. Since nearly all applicators used organophosphate insecticides and herbicides, these exposures could not be effectively evaluated. Conclusions These results suggest that exposure to some fungicides and insecticides may increase risk of retinal degeneration. Am. J. Ind. Med. 37:618–628, 2000. © Published 2000 Wiley-Liss, Inc.

PURPOSE: Information on agricultural practices has been obtained by questionnaire in several epidemiologic investigations. This project evaluated the reliability of self-reported information on pesticide use and various demographic and lifestyle factors among a group of farmers from Iowa. METHODS: 2,921 Iowa farmers participating in the Agricultural Health Study completed enrollment questionnaires approximately one year apart. Responses on the two questionnaires were compared for percent agreement and by Kappa statistics to evaluate reliability. RESULTS: Percent agreement for ever/never use of specific pesticides and application practices was quite high and generally ranged from 70% to over 90% and did not vary by age or educational level. Kappas were typically in the 0.50 to 0.60 range. Agreement was lower (typically 50% to 60%) for duration or frequency of use of specific pesticides. Agreement on lifestyle and non-agricultural factors was comparable to that reported in other studies. CONCLUSIONS: Level of agreement regarding pesticide use in this population is similar to that found for diet, physical activity, and medical conditions, which have been successfully evaluated in many epidemiologic studies. Information on agricultural practices from self-completed questionnaires has sufficient reliability for use in epidemiologic investigations.

Objectives We evaluated the cancer incidence among over 49,000 pesticide applicators with exposure to either alachlor or atrazine in the Agricultural Health Study (AHS), a prospective cohort study of over 89,000 restricted use pesticide applicators and spouses of farmer applicators in Iowa and North Carolina, USA. Methods Comprehensive questionnaire data concerning lifestyle, occupations, personal and family medical history and use of 50 important agricultural pesticides, were collected prior to cancer incidence. Standardized incidence ratios (SIR) were estimated for those exposed and those not exposed to alachlor and for those exposed and those not exposed to atrazine, two important agricultural herbicides. Comparing the cancer experience of pesticide applicators from each state with that expected based on state specific incidence rates. Poisson regression was used to controlling for the effects of potential confounders (including age, sex, smoking, alcohol, education, state of residence, enrollment year, family history of cancer and the 5 [in the case of alachlor] or [10 in the case of atrazine] other pesticides most correlated with either alachlor or atrazine). Results A total of 1,466 incident malignant neoplasms occurred during the study period, 1993–2000. The SIR analysis showed a moderate deficit for all malignant neoplasm combined among both users and non-users of these herbicides. In Poisson regression analysis of alachlor, we found a significant increasing trend for the incidence of all lymphohematopoietic cancer and cumulative alachlor exposure (p for trend = 0.02). Incidence of leukemia and multiple myeloma was markedly increased among applicators in the highest exposure category. Similar analyses for other cancers did not suggest any association. For atrazine, no significant exposure-response trends were observed for any cancers or for all cancers combined, but non-significant positive trends were observed for cumulative atrazine exposures cancers of the rectum, bladder, and testicles. Conclusion Our findings suggests an association between alachlor exposure and increased incidence of lymphohematopoietic cancer in the Agricultural Health Study. Findings for atrazine are inconclusive at this time. Although the statistical power of the AHS is still low for some cancer evaluations after only 5.3 years of cohort follow-up, the comprehensive prospectively collected data, especially concerning pesticide exposures is an important strength of the study. Further details of the study are provided at our website: www.aghealth.org. Words = 415

Exposure to animals, their feeds, and by-products contribute to respiratory symptoms among farmers.To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers.Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994-97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers.Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (OR(dairy) = 1.26; OR(eggs) = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OR(eggs) was 2.88 among past smokers but only 1.46 for never smokers. The OR(eggs) for current smokers of 0.80 might reflect self selection of exposure among smokers.Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure.