Health Effects Of Exposures In Agriculture

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Between 1993 and 1997, the Agricultural Health Study (AHS) enrolled more than 57,000 licensed private applicators, 82% of eligible licensed private pesticide applicators (largely farmers) in Iowa (IA) and North Carolina (NC), as well as 4900 commercial applicators from IA. The enrollment questionnaire collected data on 50 specific pesticides, and health conditions; 44% of private applicators completed a more detailed take-home questionnaire on farming practices and health, and 32,000 spouses were enrolled and provided data on pesticides, health, and children under age 21. In 1995-1996, we enrolled a supplemental sample of Black farmers (N=1181, 66% female) in central and eastern NC, where most of Black cohort participants also reside. Four follow-up surveys in 1999-2003, 2005-2010, 2013-2015, and 2019-2022 have updated data on farming, health covariates and outcomes. In 1999-2003, we collected diet questionnaires as well as buccal cell DNA from 40% of the cohort; over time, additional participants with cancer and health conditions of interest also provided buccal samples. The fourth survey included new questions on stressors, such as crop loss due to weather, injury, pain, and disability. In 1995-1996, we enrolled a supplemental sample of Black farmers (N=1181, 66% female) in central and eastern NC, where most of Black cohort participants also reside. The overall cohort and Black farmer have been linked to NC and IA cancer registries and vital statistics to identify cancers and deaths, for comparisons with the general population and research on associations with specific pesticides. For example, we reported that pyrethroid insecticides were associated with death from some neurological, respiratory, and genitourinary diseases (Shrestha, 2022). Nearly 47,000 eligible cohort participants were linked to Medicare data from 1999-2016 to identify health outcomes in older participants (Parks, 2022). In 2020, the cohort was linked to the U.S. Renal Data System to identify cases of end stage renal disease (ESRD). To enable research on racial health disparities and health impacts of climate change, we are using data on participants' residential addresses to capture geographically patterned exposures, linking to data from the Social Vulnerability Index (SVI), the FEMA National Risk Index (NRI), and the Spatial Hazard Events and Losses in the US (SHELDUS) database. For research on racial health disparities in North Carolina, in 2023 we also linked participants to county-level US Census of Agriculture data to identify factors such as average farm income and assets. NIEHS leads AHS research on neurologic conditions, including Parkinsons Disease (PD). We have performed PD case-validation and new cases were identified through Medicare claims data, enabling ongoing research on pesticides and PD. The cohort supports research on pre-clinical symptoms associated with PD, such as dream enacting behaviors (Yuan, 2022) and olfactory impairment. Research is underway in a sub-study of 2538 participants, in collaboration with Michigan State University investigators, characterizing and validating olfactory impairment for analyses of pesticide exposures and neurologic health. In a collaboration with Duke University investigators nearly 2500 elderly participants were screened for cognitive function and 16% were identified as possible Alzheimers diseases or other forms of dementia; findings on pesticides, cognitive function and dementia have been presented at national meetings with manuscripts in preparation. NIEHS-led research includes studies of wheeze, and asthma, including an in-depth study of respiratory and lung function in a sub-sample of farmers/applicators and spouses (The Agricultural Lung Health Study; report by S London). Extending prior findings in male farmers, we recently showed that current pesticide use and moldy hay exposure were associated with wheeze in female spouses (Islam, 2022). Previous results showed inverse associations of early life farming activities and adult atopy; recent results also show protective associations of childhood farming exposures with adult eczema among those with atopy (Wyss, 2022). Following-up on prior results showing microbial composition of house-dust (measured using 16s ribosomal sequencing) associations with various farm exposures, the application of newer methods (whole genome shotgun sequencing) identified both greater diversity and new associations (Wang, 2023). NIEHS has also led AHS research on systemic autoimmune diseases. In past studies, we identified associations of some specific pesticides and other occupational exposures with rheumatoid arthritis (RA), i Systemic Lupus Erythematosus (SLE), and Sjogren's Syndrome (SS) in farmers and spouses. We are revisiting this question in older adults for 14 autoimmune rheumatic diseases identified using disease algorithms applied to Medicare claims data. Another line of research addresses the question of whether pesticides are associated with immune dysfunction, which may lie on the pathway to autoimmune diseases and lymphoid cancer risk. We previously found associations of some pesticides and high pesticide-exposure events with shingles, the clinical reactivation of the herpes zoster virus, and are now replicating these analyses using Medicare claims data to identify shingles diagnoses, also considering changes in vaccination and other medical risk factors. NIEHS-AHS research also includes research on biomarkers (e.g., immune biomarkers or oxidative stress). Anti-nuclear autoantibodies (ANA) were associated with baseline use of some pesticides in a sub-study of 700 male farmers, and we are currently examining recent pesticide use and other exposures. In collaboration with the NCI, i we identified oxidative stress biomarkers associated with use of the herbicide glyphosate (Chang, 2023). The AHS has participated in large data pooling projects through the NCI-sponsored Cohort Consortium, contributing to large-scale studies of genetic and lifestyle or environmental risks for several cancers (e.g., breast, thyroid, ovarian cancers). AHS data have also contributed to large genetic consortia studies on pulmonary function (from the Lung Health Study, report by S London). The AHS is a founding member of the Agricultural Cohort Consortium (AGRICOH), with NIEHS collaborations on respiratory health and neurologic outcomes. We previously identified associations of some pesticides with ESRD, and with NCI collaborators we found associations of some of the same pesticides with biomarkers of kidney dysfunction. With increased ESRD cases in the past decade, we are reconsidering the role of pesticides. In collaboration with Johns Hopkins University investigators, we are investigating heat stress, ESRD risk and interactions with pesticides, a concern given rising temperatures due to climate change and the global epidemic of unexplained kidney disease in tropical locales. We have also linked participant residence and water source to estimate drinking water nitrates, supporting analyses of water and dietary nitrates and nitrites in kidney disease. NIEHS is leading research on climate-related exposures, e.g., disaster risk and crop loss due to flooding, to better understand racial disparities in NC participants. We are comparing Black to White participants to examine differences in mortality, cancer, and kidney disease, and explore the role of personal characteristics, pesticide use, and community-level factors. Comparisons with the Black Farmers study sample and Black population of central and eastern NC will help to identify risk and resiliency factors, informing future research mitigating the impacts of climate change.