Health Effects Of Exposures In Agriculture

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. Four follow-up surveys in 1999-2003, 2005-2010, 2013-2015, and 2019-2022 have updated data on farming, health covariates and outcomes. 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 cohort and Black farmers study samples 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. We recently reported that pyrethroid insecticide use was associated with death from some neurological, respiratory, and genitourinary diseases (Shrestha, 2022). Nearly 47,000 cohort participants were linked to Medicare data from 1999-2016 to help 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). We collected buccal-cell samples for genetic research on 40% of cohort participants and those with specific cancers and other conditions. A dietary survey was conducted in 1999-2003. We conducted pesticide exposure assessments in sub-samples of the cohort and were used to validate questionnaires and inform exposure classification. In 2022, to enable research on racial health disparities and health impacts of climate change, we have used participants' residential addresses to capture geographically patterned risk factors, 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, focused on date-specific county-level losses to crops, property, and life.

NIEHS leads AHS research on neurologic conditions. We recently described case-validation for Parkinson's disease (PD) (Shrestha, 2021), and new PD cases were identified through Medicare claims data, enabling further research on pesticides and PD. The cohort supports research on pre-clinical symptoms associated with PD, with recent findings showing high pesticide exposure events are associated with dream enacting behaviors (Yuan, 2022). Research is underway in a sub-study of 2538 participants, in collaboration with Michigan State University investigators, validating olfactory impairment for analyses of pesticide exposures and neurologic health. A collaboration with Duke University investigators is studying risk factors for dementia and Alzheimer's disease (AD); nearly 2500 elderly participants were screened for cognitive function and 16% were identified as possible AD or other forms of dementia; findings on pesticides, cognitive function and dementia have been presented at national meetings with manuscripts in preparation.

NIEHS research includes findings on pesticides, wheeze, and asthma, including an in-depth study of respiratory and lung function in a sub-sample of applicators and spouses (The Lung Health Study; report by S London). Recent papers describe an epigenome wide association study of DNA methylation and adult asthma (Hoang, 2021), and an interaction of genetic risk scores for pulmonary function, smoking, asthma, and endotoxin (Sikdar, 2021). Frequent residential wood burning was associated with decreased lung function in those with asthma and with markers of lung inflammation (White, 2022). Extending prior findings in male farmers of pesticides associated with wheeze, we recently showed that current pesticide use and moldy hay exposure were associated with wheeze in female spouses (Islam, 2022).

We previously identified associations of pesticides and other occupational exposures with rheumatoid arthritis (RA), with recent findings for Systemic Lupus Erythematosus (SLE) and Sjogren's Syndrome (SS) in farmers and spouses (Parks, 2022), and we are revisiting this question in older adults, using Medicare claims data to identify 14 autoimmune rheumatic diseases. Anti-nuclear autoantibodies (ANA) were also 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. Susceptibility to infections may indicate immune dysfunction, which is related to both autoimmune diseases and lymphoid cancer risk. We found associations of some pesticides with shingles, the clinical reactivation of the herpes zoster virus (Parks, 2021), and are now replicating these analyses using Medicare claims data to identify shingles diagnoses, also considering changes in vaccination and other medical risk factors.

In the AHS Growth and Puberty Study, we examined early puberty markers (hormones in urine and saliva, height velocity, Tanner staging) in 60 children, finding that urinary and salivary hormones are elevated before physical signs of puberty are apparent and that hormone patterns can be used as an adjunct to Tanner staging to identify puberty onset (Goldberg, 2021).

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). 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 (Shearer, 2021). We've also linked participant residence and water source to estimate drinking water nitrates (Manley, 2022), which impact diverse physiologic pathways and possibly kidney cancer. New NIEHS research will investigate nitrates and kidney disease, and with increased ESRD cases in the past decade, we are reconsidering the role of pesticides. In collaboration with Johns Hopkins University investigators, research is underway on 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.

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 explore differences in mortality, cancer, and kidney disease, and 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.