Independent and joint effects of volatile organic compounds on pulmonary function in U.S. adults from NHANES: the mediating role of platelet-to-lymphocyte ratio

Environ Pollut. 2025 Jul 15:377:126473. doi: 10.1016/j.envpol.2025.126473. Epub 2025 May 16.

Abstract

Volatile organic compounds (VOCs) are known to impair pulmonary function. However, the specific VOC with the main significant impact on pulmonary function and the joint effect of combined VOC exposure on pulmonary health, and the underlying mechanisms remain unclear. We used the of data 1,697 participants aged ≥18 years old from the National Health and Nutrition Examination Survey 2007-2012. Forced expiratory volume in the first 1.0 s (FEV1), pre-bronchodilator forced vital capacity (FVC), peak expiratory flow rate (PEF) and FEV1/FVC % were used to evaluate pulmonary function. A covariate-adjusted multiple linear regression model evaluated associations between pulmonary function and blood concentrations of seven selected VOCs. Additionally, Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression were employed to assess combined VOC effects, interactions, and nonlinear dose-response relationships. Parallel mediation analyses explored the mediating role of platelet-to-lymphocyte ratio (PLR) in the associations between VOC mixtures and pulmonary function, utilizing a WQS-derived VOC index. In an analytical sample of 1,697 general adults, the concentrations of blood 1,4-dichlorobenzene, m-/p-xylene, bromodichloromethane, and nitromethane were significantly negatively correlated with pulmonary function, whilst dibromochloromethane was significantly positively correlated with pulmonary function. The joint effect of the seven blood VOCs was also negatively associated with pulmonary function. Particularly, 1,4-dichlorobenzene (PIP = 0.992 for FEV1; 0.998 for FVC) and nitromethane (PIP = 0.990 for FEV1; 1.000 for FVC; 0.845 for PEF) as the most influential VOCs contributing to the overall mixture effect. PLR partially mediated the association between VOC mixtures and pulmonary function, particularly impacting FEV1, FVC, and PEF. This study demonstrated that in addition to chloroform, dibromochloromethane and toluene, the other four blood VOCs were associated with pulmonary function impairment. Their combined exposure effects reflect realistic environmental scenarios. Further research is needed to elucidate the underlying biological mechanisms of these associations.

Keywords: Joint effect; Pulmonary function; Volatile organic compounds.

MeSH terms

  • Adult
  • Aged
  • Air Pollutants*
  • Blood Platelets*
  • Environmental Exposure* / statistics & numerical data
  • Female
  • Humans
  • Lung* / drug effects
  • Lung* / physiology
  • Lymphocytes*
  • Male
  • Middle Aged
  • Nutrition Surveys
  • Respiratory Function Tests
  • United States
  • Volatile Organic Compounds* / blood
  • Volatile Organic Compounds* / toxicity
  • Young Adult

Substances

  • Volatile Organic Compounds
  • Air Pollutants