We had complete information on all base model covariates for 2,245 commercial applicators. Commercial applicators in the AHS are predominantly white males with a median age of 39 years at enrollment (range 16 to 83) (). A total of 1664 individuals (74%) reported at least one episode of current rhinitis in the past year. Individuals with current rhinitis were younger and more educated than those without current rhinitis. As anticipated, individuals with rhinitis were also more likely to report increased asthma, conjunctivitis, and sinusitis. Growing up on a farm was inversely associated with current rhinitis after adjusting for the base model covariates (Odds Ratio (OR) = 0.79, 95% confidence interval (CI): 0.64, 0.97). Applicators in this cohort reported median use of three pesticides in the past year and the number of years of pesticide application did not differ between those with and without rhinitis. There was also no significant difference in reported use of personal protective equipment in those individuals with and without current rhinitis (data not shown). Although never smokers were more likely to report rhinitis, there was no association between smoking status and rhinitis after adjusting for base model covariates.
Characteristics of 2245 Iowa commercial pesticide applicators in the Agricultural Health Study by rhinitis status, 1993-7.
Current use of five of 34 pesticides was positively associated with current rhinitis (). Three herbicides (2,4-D, glyphosate, and petroleum oil), one organophosphate insecticide (diazinon), and one fungicide (benomyl) were significantly associated with current rhinitis. Applicators using benomyl in the past year had the highest odds of current rhinitis (OR= 2.35, 95% CI: 1.11, 4.98). Current use of carbofuran was inversely associated with current rhinitis (OR=0.65, 95% CI: 0.43, 0.98).
Odds of current rhinitis associated with use of 34 pesticides among 2245 commercial pesticide applicators in the Agricultural Health Study.
We evaluated exposure-response trends for 25 of the 34 pesticides. presents results for the pesticides that were significantly associated with rhinitis in in current-use models, as well as other chemicals previously reported to be associated with wheeze (chlorimuron-ethyl)8
or rhinitis (paraquat)3
, and chemicals with a p
-trend value of ~0.1 (carbaryl and dicamba) in the present analysis. While we observed significant exposure-response trends for four pesticides in current use models (petroleum oil, diazinon, and use of both glyphosate and 2,4-D), few exposure-response trends were monotonic (). For example, the OR associated with 20–39 days of use of petroleum oil herbicide was 2.31 (95% CI: 1.1, 4.59), but use for 40 or more days per year had an odds ratio of 1.28 (95% CI: 0.73, 2.24). Use of carbofuran for less than five days of use in the past year (OR1–4 days
= 0.33, 95% CI: 0.15, 0.72) was inversely associated with rhinitis, however there were relatively few applicators in this category (1% of cases and 2% of controls). Increased use of carbofuran was positively associated with rhinitis (OR20 or more days
= 1.50), though the association was not significant. The association with 2,4-D and glyphosate was limited to those who used both in the past year; individuals who were in the highest category of 2,4-D and glyphosate had the highest OR (1.55, 95% CI: 1.08, 2.24) of all 2,4-D and glyphosate users.
Exposure-response models for selected pesticides used in the past year among commercial pesticide applicators in the Agricultural Health Study, 1993-7.
We conducted a number of sensitivity analyses to assess the robustness of our findings. First, we evaluated the role of correlated pesticides as an explanation for our findings. For the pesticides that were significant in either the current use () or exposure-response models (), we evaluated the correlation between pesticides to address potential confounding. Seven pairs of pesticides had Spearman correlation coefficients greater than 0.3. There was some evidence of attenuation of the associations, especially between the herbicides. However, the odds ratio for petroleum did not change significantly in pairwise models with correlated herbicides. Further exploration of the correlation between glyphosate and 2,4-D (r = 0.7) demonstrated that rhinitis was associated only with current use of both chemicals (ORboth = 1.42, 95% CI: 1.14, 1.77) whereas current use of either glyphosate alone (ORglyphosate = 1.07, 95% CI: 0.78, 1.48) or 2,4-D alone (OR2,4-D = 0.99, 95% CI: 0.63, 1.54) was not significantly associated with rhinitis when both were modeled together. Furthermore, a significant exposure-response trend was observed only when the model was restricted to users of both glyphosate and 2,4-D ().
Next, we assessed whether the choice of comparison group influenced results. When we limited the comparison group to never users of a particular pesticide (thereby excluding former users who may have removed themselves from pesticide exposure after experiencing nasal symptoms as well as those who no longer used the chemical for other reasons), the OR increased but exposure-outcome relation became stronger. For example, the OR for diazinon increased from 1.84 to 1.91 (95% CI: 1.27, 2.88). Alachlor (OR = 1.36, 95% CI: 1.02, 1.80), malathion (OR = 1.49, 95% CI: 1.10, 2.00) and the fumigant aluminum phosphide (OR = 1.66, 95% CI: 1.03, 2.67) were the only pesticides that reached statistical significance using this more restricted comparison group. We repeated analyses excluding those individuals with only one or two episodes of rhinitis in the past year. For most pesticides, the odds ratios were similar to those with the broader outcome definition, but associations for two pesticides became statistically significant. The OR for pendimethalin increased from 1.25 to 1.31 (95% CI: 1.01, 1.69) and the OR for phorate increased from 1.74 to 1.98 (95% CI: 1.04, 3.78). When we excluded asthmatic subjects (6% of cases and 3% of controls) we saw no difference in the overall pesticide results (data not shown). When we stratified our results based on hay fever or eczema status, significant pesticide associations were almost exclusively in the group never diagnosed with either condition; however we had limited power to assess rhinitis among those with hay fever or eczema (data not shown).
As some of the commercial pesticide applicators also participated in a variety of farm-related activities, we investigated other agricultural and animal exposures as potential confounders of pesticide exposure and current rhinitis associations. As shown in , activities that were significantly associated with current rhinitis were butchering animals, repairing engines, welding, and painting. Neither handling stored hay (OR=1.18, 95% CI: 0.92, 1.51) nor handling stored grain (OR=1.19, 95% CI: 0.97, 1.47) was associated with rhinitis. When the farming tasks that were significantly associated with rhinitis were included in pairwise models with significant pesticides, there was no attenuation of either the farming or pesticide associations (data not shown).
Odds ratios for current rhinitis and current farm-related exposures among 2245 commercial pesticide applicators in the Agricultural Health Study.