Prenatal pyrethroid exposure and lung function among school-aged children

Pyrethroids are synthetic insecticides derived from the natural pyrethrins, universally used for controlling insect pests in agriculture and households (Burns and Pastoor. 2018; Saillenfait et al., 2015). Currently, PYRs account for approximately 30% of the worldwide insecticide market with increasing usage since restrictions have been placed on many of the organophosphate insecticides (U.S. EPA. 2017; Hossain et al., 2013). For general population, ingestion of contaminated food, dust, and water are the common routes, followed by skin absorption, air ingestion, and unintentional ingestion (Chrustek et al., 2018). Human exposure to PYRs was primarily assessed by measures of nonspecific urinary metabolites such as 3-phenoxybenzoic acid (3-PBA), and cis- and trans-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-DCCA and trans-DCCA) (Starr et al., 2008; Kim et al., 2021). The accumulation and widespread application lead to environmental contamination and increased human exposure, raising concerns about their potential adverse effects on human health, in particular susceptible pregnant women and children (Ye et al., 2017; Saillenfait et al., 2015; Ding et al., 2015; Viel et al., 2015; Mamane et al., 2015; Buralli et al., 2020; Vrijheid et al., 2016).

In early stages of life, especially during the intrauterine development, immature lungs may be highly vulnerable to harmful effects of environmental factors including PYRs (Miller and Marty, 2010; Raanan et al., 2016; Abellan et al., 2019; Balte et al., 2017). Experimental evidence suggested that insecticide exposures could release proinflammatory mediators in lung cells, enhancing the airway hyper-responsiveness, and leading to abnormal alveolar maturation and reduced surfactant production (Diel et al., 2003; Fryer et al., 2004; Nishino et al., 2013; Pandher et al., 2021; Shaikh and Sethi, 2021). To date, only two epidemiologic studies have assessed the effects of PYRs and lung function in children (Ye et al., 2016a; Hu et al., 2021). Using the Canadian Health Measures Survey (CHMS) from 2007 to 2009, a cross-sectional study of 1997 subjects reported that higher the total PYRs (ΣPYRs) concentrations were associated with reduced forced expiratory volume in 1 s (FEV1) and lower forced vital capacity (FVC) in children aged 6–19 years (Ye et al., 2016a). Another study using data from the US National Health and Nutrition Examination Survey (NHANES) 2007–2012 has provided evidence of a negative association between environmental 3-PBA concentration and lung function among children (Hu et al., 2021). However, these studies were limited by the cross-sectional design, and the indicative causal direction of the association could not be determined. As far as we are aware, no prospective, well-designed study focused on the prenatal exposure window to evaluate the impact of PYRs exposure on lung function.

Investigating the effects of prenatal exposure to PYRs on lung function is particularly important, because the impaired lung function during childhood not only poses a burden of adulthood morbidity but is also a risk factor for the development of chronic lung diseases (Fuchs et al., 2017; Løkke et al., 2006; Grant et al., 2020). Therefore, we explored the associations of prenatal PYRs exposure with lung function among school-aged children from a prospective cohort study conducted in Shandong, China. Because previous studies have found sex-specific effects of PYRs on health outcomes, we interrogated the interaction terms and stratified the analysis to assess whether sex modifies the associations between PYRs and lung function in children (Hwang et al., 2019; Andersen et al., 2021).

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