Blood VOCs mixture, biological aging, with preserved ratio impaired spirometry and pulmonary dysfunction: Unraveling impact, mediation, and latent mechanism.

VOCs mixture was associated with significantly reduced pulmonary function measures across multiple spirometric parameters.

• VOCs mixture was related to reduced FVC (β=-94.03, 95% CI: -135.03~-53.04) and FEV1 (β=-80.27, 95% CI: -114.42~-46.11)
• VOCs mixture was also associated with reduced FEV1/FVC (β=-0.76, 95% CI: -1.25~-0.27), PEF (β=-178.90, 95% CI: -272.80~-84.94), and MMEF (β=-130.30, 95% CI: -197.61~-62.91)
• Analysis was conducted using weighted quantile sum (WQS) models among 2421 adults from NHANES 2007-2012
• The four VOCs examined were bromodichloromethane, chloroform, nitromethane, and m-/p-xylene measured in blood

VOCs mixture was associated with increased prevalence of obstructive, restrictive, and preserved ratio impaired spirometry lung function patterns.

• VOCs mixture was associated with increased prevalent risk of obstructive lung function (OLF) with odds ratio=1.36 (95% CI: 1.02-1.80)
• VOCs mixture was associated with increased prevalent risk of restricted lung function (RLF) with odds ratio=1.28 (95% CI: 1.02-1.68)
• VOCs mixture was associated with increased prevalent risk of PRISm with odds ratio=1.42 (95% CI: 1.08-1.86)
• PRISm is described as 'an emerging pattern of pulmonary dysfunction predictive of multiple clinical events'

Individual VOCs were negatively associated with multiple spirometric measures and positively associated with pulmonary dysfunction categories.

• Individually, VOCs were negatively related to FVC, FEV1, FEV1/FVC, PEF, and/or MMEF
• Individually, VOCs were positively related to prevalent obstructive lung function (OLF), restricted lung function (RLF), and/or PRISm
• Analysis was conducted using weighted generalized linear models
• The four individual VOCs analyzed were bromodichloromethane, chloroform, nitromethane, and m-/p-xylene

Biological aging indicators phenotypic age and homeostatic dysregulation mediated the associations between VOCs and pulmonary dysfunction including PRISm.

• Phenotypic age and homeostatic dysregulation mediated the associations of nitromethane and VOCs mixture with pulmonary dysfunction including PRISm
• The mediating proportion ranged from 0.17% to 40.78%
• The role of biological aging was assessed by mediation analysis
• Both individual VOC (nitromethane) and VOCs mixture associations with pulmonary dysfunction were mediated by these biological aging indicators

Network pharmacology analysis identified the PI3K-Akt signaling pathway as enriched in linking VOCs with pulmonary dysfunction.

• Phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway was enriched in linking VOCs with pulmonary dysfunction
• The latent mechanism was probed by network pharmacology
• PI3K-Akt signaling pathway is proposed as the underlying mechanism connecting VOC exposure to pulmonary dysfunction

The study population consisted of 2421 adults drawn from the National Health and Nutrition Examination Survey 2007-2012.

• Study sample: 2421 adults from NHANES 2007-2012
• Blood VOC concentrations were measured for bromodichloromethane, chloroform, nitromethane, and m-/p-xylene
• Statistical methods included weighted generalized linear models for individual effects and weighted quantile sum (WQS) models for mixture effects
• Mediation analysis was used to assess the role of biological aging indicators