The association between organophosphate insecticide metabolites (DAPs) and COPD: multi model epidemiological analysis and network toxicology analysis

Background and Aims

In the general population, there is little epidemiological evidence linking exposure to organophosphate pesticides (OPs) to lung function. The aim of this study is to explore the relationship between urinary OP metabolites and chronic obstructive pulmonary disease (COPD).

Material and method

A total of 9291 participants (including 2598 patients with chronic obstructive pulmonary disease) were included in the National Health and Nutrition Examination Survey from 1999 to 2012 and from 2015 to 2017. We used weighted logistic regression, combined with quantile g calculation (Qg) and weighted quantile sum (WQS) regression to evaluate the relationship between individual or mixed exposure to OP and COPD, and further explored the molecular mechanism of increased COPD risk caused by OP exposure through bioinformatics analysis, providing ideas for the prevention and treatment of COPD.

Result

Dimethyl phosphate (DMPT) (OR=1.15, 95% CI: 1.01, 1.22), diethyl thiophosphate (DEPT) (OR=1.29, 95% CI: 1.21, 1.38), dimethyl dithiophosphate diester (DMDTP) (OR=1.25, 95% CI -1.20, 1.29), and diethyl dithiophosphate (DEDTP) (OR=1.54, 95% CI: 1.40, 1.70) are significantly associated with an increased risk of COPD. The QG results showed that mixed OP exposure significantly increased the risk of COPD (OR=1.58, 95% CI: 1.47, 1.70, P<0.001), and the weights of DMPT, DEPT, DMDTP, and DEDTP were relatively high. In the WQS model, co exposure to the OP mixture is significantly associated with an increased risk of COPD (OR=1.8; 95% CI: 1.67, 1.94). The COPD target genes associated with OP exposure are mainly enriched in pathways related to inflammation, infection, metabolism, and hormone regulation.

Conclusion

Exposure to OPs increases the risk of COPD through a mixed effect, emphasizing the significant impact of OPs and the need to prioritize the regulation of high-risk components such as DMPT, DEPT, DMDTP, and DEDTP.