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

Little is known about the effect of mixed volatile organic compounds (VOCs), a class of omnipresent hazardous pollutants receiving considerable attention, on pulmonary function particularly preserved ratio impaired spirometry (PRISm), an emerging pattern of pulmonary dysfunction predictive of multiple clinical events, as well as the underlying role of biological aging and latent mechanism, which warrant urgent illustration. Among 2421 adults from National Health and Nutrition Examination Survey 2007-2012, the individual- and mixture-effects of blood VOCs (bromodichloromethane, chloroform, nitromethane, and m-/p-xylene) on pulmonary function were examined by weighted generalized linear models and weighted quantile sum (WQS) models, respectively. Role of biological aging was assessed by mediation analysis. Latent mechanism was probed by network pharmacology. Individually, VOCs were negatively related to FVC, FEV₁, FEV₁/FVC, PEF, and/or MMEF while positively related to prevalent obstructive lung function (OLF), restricted lung function (RLF), and/or PRISm. VOCs mixture was related to reduced FVC (β=-94.03, 95 % CI: -135.03∼-53.04), FEV₁ (-80.27, -114.42∼-46.11), FEV₁/FVC (-0.76, -1.25∼-0.27), PEF (-178.90, -272.80∼-84.94), and MMEF (-130.30, -197.61∼-62.91), and increased prevalent risks of OLF (odds ratio=1.36, 95 % CI: 1.02-1.80), RLF (1.28, 1.02-1.68), and PRISm (1.42, 1.08-1.86). Biological aging indicators phenotypic age and homeostatic dysregulation mediated the associations of nitromethane and VOCs mixture with pulmonary dysfunction including PRISm (mediating proportion: 0.17∼40.78 %). Phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway was enriched in linking VOCs with pulmonary dysfunction. Conclusively, individual and particularly mixed VOCs exposure were associated with pulmonary dysfunction including PRISm, which were mediated by biological aging, and PI3K-Akt signaling pathway may be the underlying mechanism.