Health Effects Of Exposures In Agriculture

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

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 IA and NC, as well as 4900 commercial applicators from Iowa. The enrollment questionnaire collected data on 50 specific pesticides, and baseline health conditions. About 44% of private applicators subsequently completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of private applicators were also enrolled and provided data on pesticides and health (including reproductive health) and children under age 21 at time of enrollment. Participants have completed up to three follow-up surveys in 1999-2003, 2005-2010, and 2013-2015, updating data on farming and lifestyle exposures and health outcomes. A fourth cohort-wide survey started in 2019, with nearly 31,000 completed surveys as of 8/2021. This latest survey includes new questions on agricultural stressors, such as loss of crops due to weather, as well as injury, chronic pain, and pain medication use, of particular importance in older farmers. The cohort is routinely linked to cancer registries in IA and NC and vital statistics to identify cancer cases and deaths. Nearly 47,000 participants ages 65 and older were linked to Medicare data from 1999-2016, reducing participant burden while enabling researchers to confirm diagnoses and identify cases among those lost to follow-up or for outcomes not included on survey questionnaires. In 2020, the cohort was also linked to the U.S. Renal Data System to identify cases of end stage renal disease. We also collected buccal-cell samples for genetic research from 40% of participants and from those with specific incident cancers and other conditions. A dietary survey was conducted in 1999-2003. We conducted in-depth pesticide exposure assessments for selected chemicals in sub-samples of the cohort, and results have been used to validate study questionnaires and inform exposure classification. NIEHS leads AHS research on diverse non-cancer outcomes, including neurologic conditions. We recently described case-validation for Parkinsons disease in the AHS (Shrestha 2021) and reported associations between some pesticides and Parkinsons disease risk in a prospective study (Shrestha, 2020). We also reported associations between self-reported olfactory impairment, a pre-clinical marker associated with PD risk (Shrestha, 2020) and pesticides. New research is underway in a nested sample of 2538 AHS participants, in collaboration with Michigan State University investigators, collecting additional data and validating olfactory impairment for further 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% of these were identified as possible AD or other forms of dementia. Home visits, blood collection, and case validation efforts are complete, and initial findings on pesticides, cognitive function and dementia have been presented at national meetings. Analyses are ongoing. New research is planned to investigate dementia using Medicare-based diagnoses, including among cohort participants lost to follow-up. NIEHS research on respiratory outcomes includes findings on pesticides, wheeze and asthma, and an in-depth study of respiratory diseases involving a sub-cohort of applicators and spouses (The Lung Health Study; report by S London). Recent papers describe associations of house dust endotoxin levels and diversity of the microbiome with asthma phenotypes (Lee 2020), an epigenome wide association study of DNA methylation and adult asthma (Hoang 2020), and the interaction between genetic risk scores for reduced pulmonary function and smoking, asthma, and endotoxin (Sikdar 2021). Our research on rheumatoid arthritis (RA) in AHS has identified associations with pesticides and other exposures, including chemical fertilizers and solvent use, in farmers and spouses. We have also identified associations of lifetime pesticide use with prevalence of anti-nuclear autoantibodies (ANA) in a sub-study of 700 male farmers. Ongoing work is examining ANA in relation to recent pesticide use and other exposures, as well associations of pesticides and other agricultural exposures with systemic lupus erythematosus and Sjogrens disease. We recently reported between pesticide use and incidence of shingles, the clinical reactivation of the herpes zoster virus, a marker of potential immune dysfunction (Parks 2021). New research using Medicare data is underway, identifying 14 systemic autoimmune diagnoses, immunosuppressive medication use, and new shingles cases. In the AHS Growth and Puberty Study, we explored the feasibility of measuring early puberty markers (hormones in urine and saliva, height velocity, Tanner staging) in 60 children and reported 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 pooling projects evaluating 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), and we are collaborators on recently published research describing rates of asthma in males and females (Fix, 2020), as well as ongoing work studying neurologic outcomes. In the future, this collaboration will enhance our ability to assess rare exposures and outcomes, such as autoimmune diseases. Through linkage to the U.S. Renal Data System (USRDS), we previously identified associations of pesticides with end-stage renal disease in farmers and spouses. With NCI collaborators we found associations between some of the same pesticides and biomarkers of kidney dysfunction (Shearer 2021). The recently updated linkage of the cohort to the USRDS adds new end stage renal disease cases in the past decade provides, allowing us to reconsider the role of pesticides and other agricultural exposures in risk of renal failure in the AHS. In collaboration with Johns Hopkins University investigators, research is underway characterizing heat stress in relation to kidney disease 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.