Of the 19,704 male farmers included in this analysis, 441 individuals (2.2%) reported adult-onset asthma, with 127 classified as allergic and 314 classified as non-allergic. Men with asthma tended to be older and heavier and slightly more likely to have smoked compared to those without asthma (). Wheeze was reported by 17% of controls and 74% of those with asthma. Allergic symptoms were most common in those with allergic asthma. While use of any PPE for pesticide application was similar for those with and without asthma, individuals with asthma were much more likely to report the use of respiratory protection than those without asthma.
Demographic, Medical and Farming Characteristics by adult-onset asthma status for 19,704 male farmers from the Agricultural Health Study
While overall pesticide use history (e.g., total years applied pesticides) was not related to either type of asthma, a history of HPEE was associated with an almost doubling of asthma risk for both types of asthma (ORallergic=1.98, 95% CI=1.30, 2.99; ORnon-allergic=1.96, 95% CI=1.49, 2.56) (). After adjusting for HPEE and other base model covariates, a history of doctor-diagnosed pesticide poisoning was non-significantly associated with an almost two-fold increased prevalence of allergic asthma (OR=1.95, 95%CI=0.86, 4.39. Due to the strong association of HPEE with asthma, all subsequent analyses controlled for HPEE.
Associations of Overall Pesticide Exposure variables with Allergic and Non-allergic Asthma among 19,704 male farmers from the Agricultural Health Study
We evaluated 48 pesticides for asthma risk among farmers (ziram and trichlorfon had too few exposed cases to be assessed). While a minority of the cases were allergic asthma, more individual pesticides were associated with allergic asthma than non-allergic asthma based on ever use (12 vs. 4, ). For allergic asthma, three herbicides (2,4,5-TP, EPTC, and paraquat), six insecticides (organochlorines: chlordane, heptachlor, and lindane; and organophosphates: diazinon, parathion, and coumaphos), one fungicide (captan), and two fumigants (ethylene dibromide and 80/20 mix – carbon tetrachloride and carbon disulfide) were positively associated. For non-allergic asthma, one herbicide (petroleum oil) and three insecticides (organochlorine: DDT and organophosphates; phorate and malathion) were associated. No chemical was significantly associated with both asthma subgroups, though the odds ratios were almost identical in both groups for DDT and phorate. Four pesticides had odds ratios that were significantly different (coumaphos, paraquat, captan, and lindane) between allergic and non-allergic asthma.
Associations of ever-use of individual pesticides with allergic and non-allergic asthma among 19,704 male farmers in the Agricultural Health Study
We evaluated exposure-response for pesticides and adult asthma using three cumulative pesticide exposure metrics: total years of use, lifetime days of use, and intensity-adjusted lifetime days of use. The results for all metrics were similar and because the intensity-adjusted metric accounts for potential differences in exposure as a result of application practices, we present those results in for those pesticides with significant trend tests for either allergic or non-allergic asthma (the online supplement Table E1
includes the exposure-response models for all 48 pesticides evaluated). Ten of the 12 pesticides associated with allergic-asthma also had significant exposure-response trends, and, with the exception of chlordane and parathion, all had higher odds ratios at the higher exposure levels. The herbicides 2,4-D and 2,4,5-T had significant exposure-response trends for allergic asthma, though the models for ever use were not statistically significant. For non-allergic asthma, DDT and malathion had significant dose-response trends.
Selected Pesticide Exposure-Response Models for Adult Asthma
We were also able to assess the association for two fungicides (captan and metalaxyl) related to use of treated seed. Captan-treated seed was associated with allergic asthma only (OR=2.49, 95% CI=1.42, 4.36). Similarly, users of metalaxyl-treated seed were over 5 times more likely to report allergic asthma (OR=5.18, 95% CI =2.48, 10.8).
We saw some evidence of correlations among specific pesticides and attenuation of some associations, but no strong evidence of confounding for any specific pesticide. The highest observed correlation among the controls was 0.37 for 2,4,5-T and 2,4,5-TP. Below, we present the results for the odds ratios that changed in the multiple chemical models. For allergic asthma, parathion attenuated the association of paraquat (OR from 1.67 to 1.36, 95% CI=0.82, 2.25). For the organochlorine pesticides, there was evidence of confounding for the associations with allergic asthma. Chlordane attenuated the associations with DDT and allergic asthma (OR from 1.42 to 1.17, 95% CI=0.75,1.83) and diazinon (OR from 1.57 to 1.39, 95% CI=0.91,2.12) while heptachlor attenuated the association of chlordane (OR from 1.77 to 1.53, 95%CI=1.02,2.31). In a model containing DDT, heptachlor, and chlordane, the association for DDT was reduced to 1.05 (95%CI=0.67, 1.67), while the ORs for heptachlor and chlordane remained elevated (1.93 and 1.52, respectively). When heptachlor and chlordane were included in a model with diazinon, the ORallergic asthma for diazinon was reduced to 1.25 (95% CI=0.82,1.93) with little change in the estimates for heptachlor and chlordane (1.93 and 1.46, respectively). We saw similar attenuation of the exposure-response models for DDT when chlordane and heptachlor were included in the model. None of the significant associations for non-allergic asthma could be explained by correlations with other pesticides.
We saw little evidence of association between prevalent asthma and current farming activities (data not shown). Allergic asthma was associated with using gasoline as a solvent to clean (OR= 1.48, 95%CI=1.04, 2.13) and with performing veterinary services (OR=1.51, 95%CI=1.03, 2.21). Veterinary services (OR=0.77, 95%CI =0.60,0.97) and driving combines (OR=0.72, 95%CI=0.53,0.97) were inversely associated with non-allergic asthma. There were no positive associations between non-allergic asthma and current farming activities. Current farm activities did not appear to confound the pesticide results.
To determine whether the differential results for allergic and non-allergic asthma were due to allergy alone, we removed allergic individuals from our control group and reran the analysis (Online supplement Table E2
). While some pesticides were associated with allergy alone, the odds ratios were stronger for allergic asthma than for allergy alone for all pesticides associated with allergic asthma in earlier models.
To evaluate whether our results were related to asthma, or to some co-morbid respiratory disease, we excluded all individuals with chronic bronchitis and farmers lung and reran our models (online supplement Table E3
). A larger proportion of asthma cases, both allergic and non-allergic, reported some other respiratory illness compared to controls (35% vs. 5%). With these individuals excluded, the odds ratios for allergic asthma were statistically significant for five pesticides (2,4,5-T, parathion, coumaphos, captan, and 80/20 mix) and similar to the values reported in . For four other pesticides, the resulting odds ratios were attenuated: heptachlor (OR from 2.01 to 1.30), chlordane (OR from 1.77 to 1.27), paraquat (OR=1.67 to 1.36), and 2,4,5-TP (OR from 1.91 to 1.68). Of the four pesticides significantly associated with non-allergic asthma, only phorate remained statistically significant when the individuals with other lung diseases were removed. After removing the other respiratory diseases, the odds ratio for fonofos and non-allergic asthma increased from 1.22 to 1.39 (95% CI=1.00, 1.94) and the association between petroleum oil and non-allergic asthma went away (OR from 1.35 to 1.15).