Lung Health Study in the Agricultural Health Study

National Institute Of Environmental Health Sciences

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Abstract

To investigate the relationship between farming exposures and asthma, allergies and related phenotypes, we carried out a nested case control study of asthma within a large cohort of farmers -- the Agricultural Health Study. This study follows up findings regarding the association between correlates of microbial exposures and various questionnaire-based asthma and atopy phenotypes. It was also designed to follow-up findings based on questionnaire data of positive associations between pesticide exposures and questionnaire-based asthma phenotypes. To confirm and better understand these associations, objective measures of asthma and atopy phenotypes were made along with more detailed exposure assessment. This study builds upon the Agricultural Health Study, a large cohort of farmers and their spouses in Iowa and North Carolina. We identified presumptive cases of asthma and a random sample of non-cases from the third phase of cohort follow-up and made home visits on eligible subjects. The Lung Health Study was launched on Feb 4, 2009. Field work ended September 30, 2013 and telephone interviews ended on November 15, 2013. We completed home visits on over 3,200 individuals. Pulmonary function was measure at home visit along with exhaled nitric oxide and blood was analyzed for immunoglobulin E (IgE) to a panel of 10 common allergens. Endotoxin was measured in house dust on over 2500 subjects. The house dust microbiome was measured on a random sample of 1000 individuals. Genome wide single nucleotide polymorphism data and genome methylation data were generated. Plasma proteomic data was generated on 2,000 participants. We have used state of the art techniques to assess the microbiome of house dust in this population and identified some unique microbial signatures of farm exposures. In two publications, we have examined associations between the dust microbiota measured using 16s sequencing and the various health outcomes measured in this study. We added metagenomics to better understand our 16s findings. We made the novel observation that early consumption of raw milk is related to better lung function. While there are many studies showing that early exposure to the farm environment is protective for allergies, we found that this association holds also in adults. We have extended this finding to eczema (Wyss et al, in press). Using the genome wide methylation data that we have generated (Illumina EPIC array) we published one of the few epigenome wide association study of adult asthma and we were additional able to consider asthma and atopic status together (PMID: 32381493) . In the past year we published on associations of pesticide exposures with methylation (PMID: 34516295). With our genome wide genotype and epigenetic data we are also contributing to as well as leading international meta-analyses of health outcomes available in this study. For example, we led a epigenome-wide meta-analysis of pulmonary function within the CHARGE consortium (PMID: 35536696).